Say what you want about Chinese papermill fraud, but at least the rodent experiments they describe are entirely fictional. No animals were harmed in the production of those fake biomedical papers from China, but it is quite different with this Sicilian papermill which my colleagues Cheshire (Actinopolyspora biskrensis) and Aneurus Inconstans uncovered. Approved by the University of Messina, many rodents were subjected to cruel experiments, but instead of real scientific results, only Photoshop fraud was published. Virtually every “original research” paper which the sleuths looked at contained fake data. All because there was money to be made: the Fraud Squad patented some flavanol drugs (one later proved to be toxic), and they soon enough moved to experimenting on… children.
This looks like a gigantic research fraud scandal, even for Italian standards. It spans two decades and involves many people, mostly at the University of Messina. At the centre is the pharmacology professor Francesco Squadrito.
And it is not the first Sicilian fraud ring my colleagues uncovered. Here is another gang in Palermo, who managed to forge tobacco research even:
But this flavanol fraud affair in Messina seems to be much, much bigger. Let me introduce you to other key members of Squadrito’s Fraud Squad. First of all, there is the University of Messina pharmacology professor Domenica Altavilla, who also happens to be Squadrito’s wife. I found out these two are married from a Facebook post by the Rotary Club in Messina from 2017, which mentions:
There are more family members in the gang, as co-authors of fraudulent papers. There is another Messina professor named Giovanni Squadrito, presumably the ringleader’s brother. There seems to be other family relations involved, like Rolando Marini (deceased in 2019) and Herbert Ryan Marini (an US-American who possibly married Rolando’s daughter). The Messina professors Giuseppe Vita and Carmelo Romeo are likely the fathers of the Gian Luca Vita (local neurologist), and Sara Romeo (postdoc in UK), respectively.
In Italy, women keep their maiden name when marrying, so it is difficult to establish who is married to whom there. Yet, entire extended families are known to be employed at same Italian university.
The Messina professor Alessandra Bitto is a major figure in the affair, her name is on almost all of the fake papers I will present, but she doesn’t seem to be married to someone else, not a co-author of the fake papers. A younger Messina gang member with a big role is the assistant professor Natasha Irrera, she calls Squadrito her “scientific father“. Another important name is Salvatore Guarini, a Sicilian based at the University of Modena and Reggio Emilia in Northern Italy, Bitto did her PhD there under his supervision.
Finally, for all we know a regular member of the Fraud Squad, the University of Messina professor Letteria Minutoli, might be related to top governmental officials in the commune of Messina (Massimo Minutoli and Caterina Minutoli), which would preclude all attempts of investigation into the affair.
And here is Squadrito himself telling you about the curative magic of the bergamot fruit. The man is obsessed with plant flavanols.
Now, let us finally look at all these fake papers. We shall start with a Squadrito-Altavilla-Bitto-Irrera paper which was recently corrected by the publisher Wiley.
Alessandra Bitto, Domenica Altavilla , Gabriele Pizzino , Natasha Irrera , Giovanni Pallio , Michele R Colonna , Francesco Squadrito Inhibition of inflammasome activation improves the impaired pattern of healing in genetically diabetic mice British journal of pharmacology (2014) doi: 10.1111/bph.12557
This was the correction notice, issued in August 2021:
“Accidental mistakes during article preparation led to duplications in Figures 1b, d, 2a and 3a.
Since substantial time has elapsed since the study was originally conducted, the authors were not able to retrieve the original images. The authors have therefore re-probed the original protein samples and re-run the western blots with the antibodies currently in use.
Images of the re-run analyses are provided below. As per current BJP guidelines, the authors have set a single level of significance as P < 0.05. The statistical analysis shown is one way ANOVA with Tukey’s multiple comparisons post-tests conducted only if F was significant at (P < 0.05).
The authors sincerely apologize for these mistakes and state that these mistakes do not affect the quantification or conclusions of this study.”
Now look at the Figure 2A.
This PubPeer exchange shows that in the Squadrito and Altavilla labs “raw data” is a foreign concept. Anything can be raw data: unrelated gel images, digital fabrications, just label it any way you feel like. The journals approve. Well, anyway, MDPI does.
That corrected paper used diabetic mouse model to have their backs slashed to study wound healing. The team did a lot of animal research of this kind, all of its results were faked in Photoshop.
Squadrito doesn’t reply on PubPeer anymore. Initially, he did, here is one such case (a rare cell culture study without any abused rodents, btw):
Federica Mannino , Giovanni Pallio, Roberta Corsaro , Letteria Minutoli, Domenica Altavilla , Giovanna Vermiglio , Alessandro Allegra , Ali H. Eid , Alessandra Bitto, Francesco Squadrito , Natasha Irrera Beta-Caryophyllene Exhibits Anti-Proliferative Effects through Apoptosis Induction and Cell Cycle Modulation in Multiple Myeloma Cells Cancers (2021) doi: 10.3390/cancers13225741
Squadrito replied on PubPeer:
That supplemental file which MDPI published online was not really raw data. It looked as if someone scanned an empty X-Ray film and digitally pasted a string of gel bands onto it.
This kind of gel image is very similar to what the fraudsters of Cassava Science presented to the journals as “raw data”.
As Cheshire also noted, “The supplemental files provided on the journal site do not appear to include the control bands, although one would expect to see them on the same gel.” So Squadrito send MDPI another gel image and the publisher happily added that.
Yep, because the originally published actin gel obviously never existed as such, they just sent a random picture of some other western blot experiment. Who cares.
Nobody also cares about all that animal abuse which was absolutely unnecessary because the authors faked the results anyway.
In December 2014, someone (possibly a former lab member) shared something on PubPeer regarding a Squadrito gang paper, the posted link is broken by now. But in November 2016, this person returned to share their concerns as an image:
Letteria Minutoli, Alessandra Bitto, Francesco Squadrito, Natasha Irrera , Mariagrazia Rinaldi , Piero Antonio Nicotina , Salvatore Arena , Carlo Magno , Herbert Marini , Luca Spaccapelo , Alessandra Ottani , Daniela Giuliani , Carmelo Romeo , Salvatore Guarini , Pietro Antonuccio, Domenica Altavilla Melanocortin 4 receptor activation protects against testicular ischemia-reperfusion injury by triggering the cholinergic antiinflammatory pathway Endocrinology (2011) doi: 10.1210/en.2011-1016
What’s wrong here? Every one of these four actin western blots is a composite of one single gel band cloned 8 times.
Here, live rats had their testicles torn off:
“Rats were anesthetized with an ip injection of 50 mg/kg of pentobarbital sodium. Testicular ischemia-reperfusion (TI/R) injury was induced by torsion of the left testis, with a 720° twisting of the spermatic cord so as to produce a total occlusion of testis for 1 h. The same testis was then detorted.”
Note that the rats did not receive any anaesthetic after the testicle-twisting operation and suffered in pain for a whole day until they were killed.
More testicular torture on rats:
Pietro Antonuccio , Letteria Minutoli , Carmelo Romeo , Piero Antonio Nicòtina , Alessandra Bitto, Salvatore Arena , Domenica Altavilla, Biagio Zuccarello , Francesca Polito, Francesco Squadrito Lipid peroxidation activates mitogen-activated protein kinases in testicular ischemia-reperfusion injury The Journal of Urology (2006) doi: 10.1016/j.juro.2006.06.086
“All animals were anesthetized with an intraperitoneal injection of 50 mg/kg pentobarbital sodium. TI/R [Testicular Ischemia-Reperfusion Injury,- LS] was induced by torsion of the left testis with 720-degree twisting of the spermatic cord to produce total testicular occlusion for 1 hour. The same testis was then detorsed. Following 0, 10, 15,20, 25 and 30 minutes, and 1, 3 and 24 hours of reperfusion, respectively, rats were sacrificed with an overdose of pentobarbital sodium and bilateral orchiectomy was performed.”
All to produce this fake data:
Also these rats had their testicles ripped off, with these results:
Letteria Minutoli, Pietro Antonuccio, Francesca Polito, Alessandra Bitto , Francesco Squadrito, Natasha Irrera, Piero Antonio Nicotina , Carmine Fazzari , Angela Simona Montalto , Vincenzo Di Stefano , Carmelo Romeo, Domenica Altavilla Peroxisome proliferator activated receptor beta/delta activation prevents extracellular regulated kinase 1/2 phosphorylation and protects the testis from ischemia and reperfusion injury The Journal of Urology (2009) doi: 10.1016/j.juro.2008.11.095
More rats with their testicles torn off:
Letteria Minutoli , Pietro Antonuccio , Carmelo Romeo , Piero Antonio Nicòtina , Alessandra Bitto, Salvatore Arena , Francesca Polito , Domenica Altavilla , Nunzio Turiaco , Antonio Cutrupi , Biagio Zuccarello , Francesco Squadrito Evidence for a role of mitogen-activated protein kinase 3/mitogen-activated protein kinase in the development of testicular ischemia-reperfusion injury Biology of Reproduction (2005) doi: 10.1095/biolreprod.105.040741
Not just rats, also mice were subjected to testicle twisting:
Letteria Minutoli, Pietro Antonuccio , Francesca Polito, Alessandra Bitto, Tiziana Fiumara , Francesco Squadrito, Piero Antonio Nicotina , Salvatore Arena , Herbert Marini, Carmelo Romeo, Domenica Altavilla Involvement of mitogen-activated protein kinases (MAPKs) during testicular ischemia-reperfusion injury in nuclear factor-kappaB knock-out mice Life Sciences (2007) doi: 10.1016/j.lfs.2007.06.016
“Mice were anesthetized with an intraperitoneal injection of 80 mg/kg of pentobarbital sodium. Testis ischemia–reperfusion injury (TI/R) was induced by torsion of the left testis, with a 720° twisting of the spermatic cord so as to produce a total occlusion of testis for one hour. The same testis was then detorted. Following 0, 10, 30 min and 1, 3 and 24 h of reperfusion, the animals were sacrificed with an overdose of pentobarbital sodium and bilateral orchidectomies were performed.”
The Messina professors had their fun:
More testicle torture, mice again:
Letteria Minutoli , Pietro Antonuccio, Francesca Polito, Alessandra Bitto, Francesco Squadrito, Vincenzo Di Stefano , Piero Antonio Nicotina , Carmine Fazzari , Daniele Maisano, Carmelo Romeo, Domenica Altavilla Mitogen-activated protein kinase 3/mitogen-activated protein kinase 1 activates apoptosis during testicular ischemia-reperfusion injury in a nuclear factor-kappaB-independent manner European Journal of Pharmacology (2009) doi: 10.1016/j.ejphar.2008.12.028
“Animals were anesthetized with an intraperitoneal injection of 80 mg\kg of pentobarbital sodium to perform torsion of the left testis and spermatic cord, 720° for 1 h.”
They just kept tearing off rodents’ testicles, but what for? Because the results were always faked in Photoshop.
The team was tearing off testicles from live rodents for years, so much fun they had, “authorized by our local institution“:
Letteria Minutoli, Pietro Antonuccio , Natasha Irrera , Mariagrazia Rinaldi , Alessandra Bitto, Herbert Marini , Gabriele Pizzino , Carmelo Romeo , Antonina Pisani , Giuseppe Santoro , Domenico Puzzolo , Carlo Magno , Francesco Squadrito , Antonio Micali , Domenica Altavilla NLRP3 Inflammasome Involvement in the Organ Damage and Impaired Spermatogenesis Induced by Testicular Ischemia and Reperfusion in Mice The Journal of pharmacology and experimental therapeutics (2015) doi: 10.1124/jpet.115.226936
“Both WT and KO mice (total number = 126; each group consisted of seven animals) were anesthetized with an intraperitoneal injection of 80 mg/kg of pentobarbital sodium and torsion of the left testis and spermatic cord was performed as previously described (Minutoli et al., 2009). Then, the same testis was detorted.”
Everything in this paper is fake:
The latter image reuse involved this Frontiers paper with other problems (the editor was Squadrito’s own university rector, Salvatore Cuzzocrea). The mice were injected with the toxic heavy metal cadmium (Cd):
Francesco Squadrito, Antonio Micali , Mariagrazia Rinaldi , Natasha Irrera , Herbert Marini , Domenico Puzzolo , Antonina Pisani , Cesare Lorenzini , Andrea Valenti , Rosaria Laurà , Antonino Germanà , Alessandra Bitto, Gabriele Pizzino , Giovanni Pallio , Domenica Altavilla , Letteria Minutoli Polydeoxyribonucleotide, an Adenosine-A2A Receptor Agonist, Preserves Blood Testis Barrier from Cadmium-Induced Injury Frontiers in Pharmacology (2017) doi: 10.3389/fphar.2016.00537
In this paper, Cheshire noted:
“”The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. […]
However, the paper does not seem to mention that the first author notes on his CV states that he was “Principal Investigator 2007-2010 – Mastelli s.r.l” which seems to have invented and holds the patent on PDRN, which is the subject of this research. Perhaps related to this, the first author may also be a co-inventor [on a patent ](https://patents.google.com/patent/EP3377075A1/en?assignee=Mastelli+S.R.L.)currently assigned to Mastelli related to PDRN (that patent also lists Giulia Cattarini Mastelli and Laura Cattarini Mastelli as inventors).”
We will hear more of Squadrito’s COIs later. But for now you must understand: his own top boss, the University of Messina rector magnificus Cuzzocrea, obviously fully supports all this misconduct, even jumping in as editor when needed. This is Italian academia in all its pride, as we know it from Giorgio Zauli affair.
Anyway, some more testicular damage. Here, male rats received a surgery which caused varicocele (testicle vein enlargement), the “protocol was approved by the Committee of Animal Health and Care of University of Messina“:
Letteria Minutoli, Salvatore Arena , Pietro Antonuccio , Carmelo Romeo , Alessandra Bitto, Carlo Magno , Mariagrazia Rinaldi , Antonio Micali , Natasha Irrera , Gabriele Pizzino , Federica Galfo , Francesco Squadrito, Domenica Altavilla , Herbert Marini Role of Inhibitors of Apoptosis Proteins in Testicular Function and Male Fertility: Effects of Polydeoxyribonucleotide Administration in Experimental Varicocele BioMed research international (2015) doi: 10.1155/2015/248976
Too rpoduce these forgeries as results:
But now let’s see what other creative things Squadrito’s team did to rodents.
Bleed, poison and boil
Here, the mice were merely injected with drugs to cause prostata tumours, and not subjected to “surgeries”:
Letteria Minutoli, Domenica Altavilla , Herbert Marini, Mariagrazia Rinaldi , Natasha Irrera , Gabriele Pizzino , Alessandra Bitto , Salvatore Arena , Sebastiano Cimino , Francesco Squadrito, Giorgio Ivan Russo, Giuseppe Morgia Inhibitors of apoptosis proteins in experimental benign prostatic hyperplasia: effects of serenoa repens, selenium and lycopene Journal of Biomedical Science (2014) doi: 10.1186/1423-0127-21-19
But of course, there was no restraint in fraud. Look what the Figure 1 alone looks like:
All that was just Figure 1, mind you.
In the next study, a number of things was done to live rats, in particular very slowly bleeding them to death:
Salvatore Guarini , Domenica Altavilla, Maria-Michela Cainazzo , Daniela Giuliani , Albertino Bigiani , Herbert Marini , Giovanni Squadrito, Letteria Minutoli, Alfio Bertolini , Rolando Marini , Elena B. Adamo , Francesco S. Venuti , Francesco Squadrito Efferent vagal fibre stimulation blunts nuclear factor-kappaB activation and protects against hypovolemic hemorrhagic shock Circulation (2003) doi: 10.1161/01.cir.0000050627.90734.ed
“Under general anesthesia (urethane, 1.25 g/kg intraperitoneally) and after heparinization (heparin sodium, 600 IU/kg), rats were instrumented with indwelling polyethylene catheters in the left common carotid artery to record arterial blood pressure and into the right iliac vein to inject drugs and to bleed. […]
Acute hypovolemic hemorrhagic shock14–16 was induced by a graded withdrawal of blood (1.8 to 2 mL per 100 g body weight) until the MAP fell and stabilized at levels of 35 to 40 mm Hg. […]
Two minutes before the start of bleeding, rats were subjected to bilateral cervical vagotomy or sham surgical procedures. Direct stimulation of both caudal vagal trunks was carried out by means of bipolar platinum electrodes connected to a stimulator. […] Survival rate and survival time were evaluated for 180 minutes after the bleeding was discontinued.”
This is the kind of fake data these scientists produced, possibly while waiting for the rats to die:
Also in this study rats were slowly bled to death, and its fake data was flagged on PubPeer already in May 2015:
Salvatore Guarini , Maria Michela Cainazzo , Daniela Giuliani , Chiara Mioni , Domenica Altavilla , Herbert Marini , Albertino Bigiani , Valeria Ghiaroni , Maria Passaniti , Sheila Leone , Carla Bazzani , Achille P Caputi , Francesco Squadrito, Alfio Bertolini Adrenocorticotropin reverses hemorrhagic shock in anesthetized rats through the rapid activation of a vagal anti-inflammatory pathway Cardiovascular Research (2004) doi: 10.1016/j.cardiores.2004.03.029
“Acute hemorrhagic shock was induced by a stepwise (within 20–25 min) withdrawal of about 50% of the circulating blood…”
Here, mice were fed alcohol to cause liver damage:
Domenica Altavilla, Herbert Marini, Paolo Seminara , Giovanni Squadrito, Letteria Minutoli, Maria Passaniti , Alessandra Bitto, Gioacchino Calapai , Margherita Calò , Achille P. Caputi , Francesco Squadrito Protective effects of antioxidant raxofelast in alcohol-induced liver disease in mice Pharmacology (2005) doi: 10.1159/000082939
Squadrito’s antioxidants can cure anything, as the Photoshop forgery testifies:
This study was particularly nasty, mice were dumped into 80°C hot water:
Mariarosaria Galeano , Domenica Altavilla, Alessandra Bitto, Letteria Minutoli, Margherita Calò , Patrizia Lo Cascio , Francesca Polito , Giovanni Giugliano , Giovanni Squadrito, Chiara Mioni , Daniela Giuliani , Francesco S. Venuti , Francesco Squadrito Recombinant human erythropoietin improves angiogenesis and wound healing in experimental burn wounds* Critical care medicine (2006) doi: 10.1097/01.ccm.0000206468.18653.ec
“After general anesthesia with sodium pentobarbital (80 mg/kg), hair on the back was shaved […] Mice were inserted headfirst into a burn template so that the dorsum was centered by the 2 3 cm window. The shaved skin on the back was immersed in 80°C water for 10 secs to achieve a second-degree scald burn. We produced a deep-dermal second degree burn.”
The mice were tortured again for further experiments, all to obtain this fake data:
More mouse boiling:
Natasha Irrera , Alessandra Bitto, Gabriele Pizzino , Mario Vaccaro , Francesco Squadrito, Mariarosaria Galeano , Francesco Stagno D’Alcontres , Ferdinando Stagno D’Alcontres , Michele Buemi , Letteria Minutoli , Michele Rosario Colonna , Domenica Altavilla Epoetin Alpha and Epoetin Zeta: A Comparative Study on Stimulation of Angiogenesis and Wound Repair in an Experimental Model of Burn Injury BioMed research international (2015) doi: 10.1155/2015/968927
“The protocol was evaluated and accepted by the Ethics Committee of the University of Messina […] Skin injury was performed on the shaved back of mice: after general anaesthesia with sodium pentobarbital (80 mg/kg/i.p.), hair on the back was shaved using a depilatory cream to reduce any possible injury due to hair removal. Burn injury was produced with 80°C water, and mice were immersed for 10 seconds with a burn template so that the dorsum was exposed to hot water through a 2 × 3 cm window. In this way, we produced a deep-dermal second-degree burn; postburn sedation and analgesia were provided with diazepam (50 mg/L added to drinking water) for 7 days to alleviate pain.”
Do we believe they really gave mice pain medicine after boiling their backs? Because they didn’t do this in earlier study. And anyway, nothing these authors claim can be trusted:
How about stroke?
Francesco Squadrito , Letteria Minutoli, Maria Esposito , Alessandra Bitto, Herbert Marini , Paolo Seminara , Alessandra Crisafulli , Mariolina Passaniti , Elena Bianca Adamo , Rolando Marini , Salvatore Guarini, Domenica Altavilla Lipid peroxidation triggers both c-Jun N-terminal kinase (JNK) and extracellular-regulated kinase (ERK) activation and neointimal hyperplasia induced by cessation of blood flow in the mouse carotid artery Atherosclerosis (2005) doi: 10.1016/j.atherosclerosis.2004.10.013
“Mice were anesthetized by intraperitoneal injection with a solution of xylazine (5 mg/kg) and ketamine (80 mg/kg). The left common carotid artery was exposed through a small mid-line incision in the neck. The artery was completely ligated
just proximal to the carotid bifurcation to disrupt blood flow.”
The results were then fabricated:
More stroke, but this time with Mongolian gerbils!
Unlike with most of Squadrito’s animal studies in Messina, this one was supervised by Guarini and “approved by the Committee on Animal Health and Care of Modena and Reggio Emilia University“
Daniela Giuliani, Alessandra Ottani , Letteria Minutoli, Vincenzo Di Stefano , Maria Galantucci , Alessandra Bitto, Davide Zaffe , Domenica Altavilla, Annibale R. Botticelli , Francesco Squadrito, Salvatore Guarini Functional recovery after delayed treatment of ischemic stroke with melanocortins is associated with overexpression of the activity-dependent gene Zif268 Brain Behavior and Immunity (2009) doi: 10.1016/j.bbi.2009.03.009
“Transient global brain ischemia was induced by occluding with atraumatic clips both common carotid arteries for 10 min”
The gerbils were abused to produce this bizarrely fake data:
More abused gerbils in Modena:
Daniela Giuliani , Chiara Mioni , Domenica Altavilla , Sheila Leone , Carla Bazzani , Letteria Minutoli, Alessandra Bitto , Maria-Michela Cainazzo , Herbert Marini , Davide Zaffe , Annibale R. Botticelli , Roberto Pizzala , Monica Savio , Daniela Necchi , Helgi B. Schiöth , Alfio Bertolini , Francesco Squadrito, Salvatore Guarini Both early and delayed treatment with melanocortin 4 receptor-stimulating melanocortins produces neuroprotection in cerebral ischemia Endocrinology (2006) doi: 10.1210/en.2005-0692
Again stroke was induced:
“Transient global brain ischemia was induced, under general anesthesia with chloral hydrate (400 mg/kg ip; Sigma, St. Louis, MO), by occluding with atraumatic clips both common carotid arteries for 10 min…”
And this is how one fakes the result:
Let me show you one utter insanity of the Squadrito team. This paper should be used as teaching material to educate students of biomedicine of the utter failure of peer review and scholarly publishing in general. It was published by a SAGE journal with an impact factor of 6.7.
Alessandra Ottani, Daniela Giuliani, Chiara Mioni , Maria Galantucci , Letteria Minutoli, Alessandra Bitto, Domenica Altavilla, Davide Zaffe , Annibale R Botticelli , Francesco Squadrito, Salvatore Guarini Vagus nerve mediates the protective effects of melanocortins against cerebral and systemic damage after ischemic stroke Journal of Cerebral Blood Flow & Metabolism (2009) doi: 10.1038/jcbfm.2008.140
Here the authors caused stroke in rats by injecting endothelin-1 into their brains (and removing the vagus nerve). But now observe what the figures of the paper look like:
The rest, Figures 1 and 7, are just bar diagrams. Maybe you noticed that the figures are not just boring repetitions: all gel bands are cloned. Strings of cloned gel bands, in every single western blot panel. As Aneurus Inconstans wrote on PubPeer:
Once, Squadrito and his team decided to prove that abdominal infection from a ripped appendix can be cured with pumping CO2 into the peritoneal cavity.
Angela Simona Montalto , Alessandra Bitto, Letteria Minutoli , Pietro Impellizzeri , Gaetano Costa , Natasha Irrera , Gabriele Pizzino , Francesco Squadrito, Domenica Altavilla , Carmelo Romeo CO2Pneumoperitoneum Preservesβ-Arrestin 2 Content and Reduces High Mobility Group Box-1 (HMGB-1) Expression in an Animal Model of Peritonitis Oxidative Medicine and Cellular Longevity (2015) doi: 10.1155/2015/160568
“…rats were anaesthetized with ether, and a midline incision was made below the diaphragm to expose the cecum. The cecum was ligated at the colon juncture with a 2-0 silk ligature suture without interrupting intestinal continuity. The cecum was punctured twice with an 18-gauge needle. The cecum was returned to the abdomen, and the incision was closed in layers with a 2-0 silk ligature suture. Six hours following CLP, animals were randomly selected to undergo CO2 pneumoperitoneum (LS) at a pressure of 5–7 mmHg or laparotomy…”
The real therapy was Photoshop of course:
There are so many ways to cause intestinal pain to make rodents suffer.
Letteria Minutoli, Domenica Altavilla, Alessandra Bitto, Francesca Polito, Ersilia Bellocco, Giuseppina Laganà, Daniela Giuliani, Tiziana Fiumara , Salvatore Magazù, Pietro Ruggeri , Salvatore Guarini, Francesco Squadrito The disaccharide trehalose inhibits proinflammatory phenotype activation in macrophages and prevents mortality in experimental septic shock Shock (Augusta, Ga.) (2007) doi: 10.1097/01.shk.0000235092.76292.bc
Rats were tortured by inducing inflammation shock:
“Rats were anesthetized with ethyl ether and a cannula (PE 50) was inserted into the right jugular vein to allow intravenous injection and facilitate blood withdraw.
Twenty-four hours after surgery endotoxin shock was induced in animals by a single intravenous injection of S. enteritidis LPS (20 mg/kg; LD90 ).”
The rats had to die in pain so the authors could publish this shocking fraud:
Also here rats were injected with LPS to cause massive inflammation:
Alessandra Bitto, Letteria Minutoli, Maria Rosaria Galeano, Domenica Altavilla, Francesca Polito, Tiziana Fiumara , Margherita Calò, Patrizia Lo Cascio, Lorena Zentilin , Mauro Giacca, Francesco Squadrito Angiopoietin-1 gene transfer improves impaired wound healing in genetically diabetic mice without increasing VEGF expression Clinical Science (2008) doi: 10.1042/cs20070250
The figures showing the desired experimental results were faked. Some of the data was recycled from the Shock paper.
The shocking Shock paper had other uses:
Domenica Altavilla, Francesca Polito, Alessandra Bitto, Letteria Minutoli, Elisabetta Miraldi, Tiziana Fiumara , Marco Biagi, Herbert Marini, Daniela Giachetti, Mario Vaccaro, Francesco Squadrito Anti-Inflammatory Effects of the Methanol Extract of Sedum telephium ssp. maximum in Lipopolysaccharide- Stimulated Rat Peritoneal Macrophages Pharmacology (2008) doi: 10.1159/000157626
For some reason, the authors didn’t torture rats before killing them to obtain macrophages. Or maybe they did? After all, the paper doesn’t say if the rats were killed before “washing the abdominal cavity with RPMI 1640“. Anyway, here is the result:
The Messina slashers
Sometimes the rodents were cut. How about some fake diabetes research:
Mariarosaria Galeano , Domenica Altavilla, Domenico Cucinotta , Giuseppina T. Russo , Margherita Calò , Alessandra Bitto, Herbert Marini, Rolando Marini, Elena B. Adamo , Paolo Seminara , Letteria Minutoli, Valerio Torre , Francesco Squadrito Recombinant human erythropoietin stimulates angiogenesis and wound healing in the genetically diabetic mouse Diabetes (2004) doi: 10.2337/diabetes.53.9.2509
Transgenic models of diabetic mice had their backs slashed:
“After general anesthesia with ketamine hydrochloride (110 mg/kg), the hair on the back was shaved and the skin washed with povidone-iodine solution and wiped with sterile water. Two full-thickness longitudinal incisions (4 cm) were made on the dorsum of the mice, and the wound edges were closed with skin clips placed at 1-cm intervals. Seven animals for each group were killed after 3, 6, and 12 days”
All to produce some fake immunohistochemistry:
Once again, diabetic mice were used and then “Two full-thickness longitudinal incisions (4 cm) were made on the dorsum of the mice“:
Mariarosaria Galeano, Francesca Polito, Alessandra Bitto, Natasha Irrera, Giuseppe M. Campo , Angela Avenoso , Margherita Calò, Patrizia Lo Cascio, Letteria Minutoli, Mauro Barone , Francesco Squadrito, Domenica Altavilla Systemic administration of high-molecular weight hyaluronan stimulates wound healing in genetically diabetic mice Biochimica et Biophysica Acta (2011) doi: 10.1016/j.bbadis.2011.03.012
To produce these completely made-up results:
More back-slashing of mice:
Letteria Minutoli, Domenica Altavilla, Alessandra Bitto, Francesca Polito, Ersilia Bellocco, Giuseppina Laganà, Tiziana Fiumara , Salvatore Magazù, Federica Migliardo , Francesco Saverio Venuti , Francesco Squadrito Trehalose: a biophysics approach to modulate the inflammatory response during endotoxic shock European Journal of Pharmacology (2008) doi: 10.1016/j.ejphar.2008.04.005
And then the results were faked:
That other paper (again with diabetic mice whose backs were slashed) reused immunohistochemistry images in other ways:
Alessandra Bitto, Letteria Minutoli, Domenica Altavilla, Francesca Polito, Tiziana Fiumara , Herbert Marini, Mariarosaria Galeano, Margherita Calò, Patrizia Lo Cascio, Michele Bonaiuto , Alba Migliorato, Achille P Caputi , Francesco Squadrito Simvastatin enhances VEGF production and ameliorates impaired wound healing in experimental diabetes Pharmacological Research (2008) doi: 10.1016/j.phrs.2008.01.005
More diabetic mice slashed:
Alessandra Bitto, Natasha Irrera, Letteria Minutoli, Margherita Calò, Patrizia Lo Cascio, Paolo Caccia, Gabriele Pizzino, Giovanni Pallio, Antonio Micali, Mario Vaccaro, Antonino Saitta, Francesco Squadrito, Domenica Altavilla Relaxin improves multiple markers of wound healing and ameliorates the disturbed healing pattern of genetically diabetic mice Clinical Science (2013) doi: 10.1042/cs20130105
“After general anaesthesia with sodium pentobarbital (80 mg/kg of body weight, intraperitonealy), hair on the back was shaved and two parallel 4-cm incisions were produced with the use of a scalpel (Figure 1A), on the back of all mice as described previously .”
As described previously, the results were fabricated:
More wound healing research, where mouse backs were slashed and the results faked in Photoshop:
Mariarosaria Galeano, Francesca Polito, Alessandra Bitto, Natasha Irrera, Giuseppe M. Campo , Angela Avenoso , Margherita Calò, Patrizia Lo Cascio, Letteria Minutoli, Mauro Barone , Francesco Squadrito, Domenica Altavilla Systemic administration of high-molecular weight hyaluronan stimulates wound healing in genetically diabetic mice Biochimica et Biophysica Acta (2011)
Other creative ways to torture animals while faking the results:
Alessandra Bitto, Francesca Polito, Domenica Altavilla, Letteria Minutoli, Alba Migliorato, Francesco Squadrito Polydeoxyribonucleotide (PDRN) restores blood flow in an experimental model of peripheral artery occlusive disease Journal of Vascular Surgery (2008) doi: 10.1016/j.jvs.2008.06.041
Rats were abused by cutting off blood flow to their hindlimbs:
“The left femoral artery was exposed aseptically through a 2-mm incision and isolated from the femoral vein and nerve, with care taken to avoid damage to vessels or nerve, then was ligated with 7-0 suture just distal to the bifurcation of the anterior epigastric and lateral caudal femoral arteries. Finally, the femoral artery was excised from the ligation to the point distally where it bifurcates into the saphenous and popliteal arteries. As a consequence, blood flow to the ischemic limb becomes completely dependent on the collateral vessels (HLI animals).”
The experimental outcome was forged:
Falsified Laser Doppler perfusion imaging data, one doesn’t see this every day. How exotic! And yes, there were also fake western blots:
Here, the team induced skin and lung fibrosis in mice, because why not.
This paper features a father and son team from Messina, Gianfilippo Bagnato (deceased in 2019) and Gianluca Bagnato, which makes me wonder why Bitto’s old mentor, the Messina professor Antonino Saitta didn’t also invite his son Carlo Saitta to join, as on his other papers with Bitto? Oh, and the Messina rheumatologist Marco Atteritano is quite possibly Bitto’s partner, judging from this photo.
Gianluca Bagnato , Alessandra Bitto , Natasha Irrera, Gabriele Pizzino , Donatella Sangari , Maurizio Cinquegrani , William Roberts , Marco Atteritano , Domenica Altavilla, Francesco Squadrito, Gianfilippo Bagnato , Antonino Saitta Propylthiouracil prevents cutaneous and pulmonary fibrosis in the reactive oxygen species murine model of systemic sclerosis Arthritis Research & Therapy (2013) doi: 10.1186/ar4300
“A total of 100 μl of solution containing HOCl was injected s.c. into the back of the mice, by using a 27-gauge needle, every day for 6 weeks. Mice (n = 10) from the HOCl group (n = 20) were randomly chosen to be treated with propylthiouracil
(Sigma-Aldrich, Italy///) at the dose of 12 mg/kg/day.
[…] PTU administration was initiated 30 minutes after the HOCl subcutaneous injection, and continued for 6 weeks.”
To obtain these fake figures:
How about hitting mice on the head with a hammer?
Natasha Irrera , Gabriele Pizzino , Margherita Calò , Giovanni Pallio , Federica Mannino , Fausto Famà , Vincenzo Arcoraci , Vincenzo Fodale , Antonio David , Cosentino Francesca , Letteria Minutoli, Emanuela Mazzon , Placido Bramanti , Francesco Squadrito, Domenica Altavilla , Alessandra Bitto Lack of the Nlrp3 Inflammasome Improves Mice Recovery Following Traumatic Brain Injury Frontiers in pharmacology (2017) doi: 10.3389/fphar.2017.00459
“…animals were anesthetized by intraperitoneal injection of ketamine/xylazine (80 and 10 mg/kg, respectively) and subjected to an impact-acceleration model of diffuse TBI, based on the model described by Marmarou et al. (Marmarou et al., 1994), with some modifications. Briefly, an incision was made along the sagittal midline to expose the skull and a 3 mm thick steel disk was placed on between λ and bregma sutures. Animals were arranged on a 10-cm foam bed to soften the impact. Briefly, a 8 g weight with a 5 mm diameter and 5.5 cm length was dropped from a distance of 1.27 m, to produce TBI. After TBI, the steel disk was removed and the skin immediately sutured; a 2% lidocaine jelly was spread on to the impact site to reduce pain.”
Why yes, the brain injury was real, “approved by the Ethic Committee of the University of Messina“, but the figures in this Frontiers paper fake.
Hammering live rodents on the heads (after scalping!) is a cherished tradition in Messina, in this earlier paper they used rats:
Alessandra Bitto, Francesca Polito , Natasha Irrera , Margherita Calò , Luca Spaccapelo , Herbert R. Marini , Daniela Giuliani , Alessandra Ottani , Mariagrazia Rinaldi , Letteria Minutoli , Salvatore Guarini , Francesco Squadrito, Domenica Altavilla Protective effects of melanocortins on short-term changes in a rat model of traumatic brain injury* Critical Care Medicine (2012) doi: 10.1097/ccm.0b013e318236efde
”After 1 wk of acclimatization, animals were anesthetized by intraperitoneal injection of sodium pentobarbital (50 mg/kg) and subjected to the impact-acceleration model of diffuse TBI, as previously described (12). Briefly, a 450-g weight was dropped from a distance of 2 m onto a 10-mm diameter by 3-mm thick steel disc that had been fixed in place on the exposed dorsal surface of the skull midway between and bregma. The animal was supported on a 10-cm foam bed that provided the deceleration after impact. After injury, the steel disc was removed and the skin sutured before termination of anesthesia. ”
“Again the actin control in 2B and 2D (red box) was used three years before in Bitto et al. 2010 J Vasc Surg […] where the control was for human carotid arteries samples, while here is supposed to be for rat brain tissue. Then bands duplications are present also within blots of TNF-a, Caspase 3 and BAX (green, magenta and turquoise boxes). Finally the same actin control in 3C was reused from Figure 2A of again Bitto et al. 2010 J Vasc Surg, where the control was for human carotid arteries samples, while here is supposed to be for rat brain tissue (yellow boxes).“
These people are trolling, no? But no limits for creative ways of torturing a small animal:
Sonia Messina, Domenica Altavilla, M’hammed Aguennouz , Paolo Seminara , Letteria Minutoli , Maria C. Monici , Alessandra Bitto , Anna Mazzeo, Herbert Marini, Francesco Squadrito, Giuseppe Vita Lipid peroxidation inhibition blunts nuclear factor-kappaB activation, reduces skeletal muscle degeneration, and enhances muscle function in mdx mice The American journal of pathology (2006) doi: 10.2353/ajpath.2006.050673
“Five-week-old mdx and WT mice have been treated for 5 weeks with intraperitoneal injections with either IRFI 042 (n:8; 20 mg/kg three times a week) or vehicle (n:8; dimethyl sulfoxide/NaCl 0.9%; 0.1:1 v/v; 0.2 mg/kg three times a week). At the end of the experiments, animals were anesthetized with an intraperitoneal administration of sodium pentobarbital (80 mg/kg). Then, blood, collected by intracardiac puncture, was drawn to analyze creatine kinase (CK) levels and the biceps, quadriceps, and extensor digitorum longus (EDL) muscles were removed bilaterally”
Let’s hope the injected anaesthetics were not as fake as these gels, because the mice were literally vivisected, alive:
The last author, the University of Messina professor Giuseppe Vita pleaded on PubPeer that some immigrant of Muslim origin (his Messina colleague professor Mhammed Aguennouz) was to blame for this horrid conspiracy against Italian science:
Shall we blame Aguennouz also for papers were he is not even co-author? Those foreigners, eh, Dr Vita?
The tech did it!
Aneurus Inconstans and Cheshire have found fraud in almost every Squadrito paper they screened, and, at press time, they have over a hundred papers more to look at. The Messina lab puts every Chinese papermill to shame, also because Chinese forgeries are of much better quality and not just a string of one gel band cloned 10 times over.
But then again, the Chinese forgers have to work harder, because scientific journals do not offer same trust and service to non-white authors. And especially certain kind of Italian “scientists” knows how to organise a scam ring and publish many papers.
Squadrito replied to me only once, and he blames not his faculty colleague Aguennouz, but a technician. This is what Squadrito wrote to me on 24 April 2022:
“Dear Leonid Schneider,
Thank you for your mail. We are providing explanation for the concerns regarding the western blot analysis of the papers you mentioned, but this is a procedure that need time. We are checking all the records, and I kindly ask you 3 working weeks and I will come back to you and PubPeer with proper explanation. At this time I wish to underline that the scientific meaning of the papers under inquire has been confirmed several times by other authors. The concerns are only related to the the western blot analysis. As you know the majority of the articles date back to 2005 (17 years ago !!!!) and the experiments have been carried out even earlier (18-19 years ago) . At that time a lab technician was in charge for the protein extraction, western blot analysis, calculations and graph preparation based on coded samples prepared by the researchers. She retired 5 years ago and we are not keeping the old files of published papers for longer than 5 years; moreover since 2014 we’ve got a new image acquisition system (the Li-Cor C-Digit), while years ago we used fixer and developer and then the image was acquired and processed. Working on coded samples many times the images needed to be cut to get in the proper order the samples, but as said before it was a specific task of our technician. Following the imput of PubPeer we are searching for the old protein samples and if we find the residual extracts in the -80° freezer we will run again the experiments. Finally I wish to underline tha nobody has been investigated for research misconduct
Again we apologize for this unpleasant situation and remain at your complete disposal for any further clarification
Francesco Squadrito “
It is not clear whom Squadrito and his gang will blame for the papers published in the last 5 years. Maybe another technician. Or Aguennouz.
It is also not clear if Squadrito will ever have to retract a single paper, despite all of them being entirely fictional (expect for the reality of abused animals). His networks involve even the rector of his university, who surely will eagerly attest to every inquiring journal that all results are reproducible and no conclusions were ever affected.
No other member of the Squadrito gang replied to my emails. And neither did his university, but again, what with the rector Cuzzocrea, what can one expect. That’s how it’s usually done in Italian universities.
But now let’s talk about Squadrito’s business activities.
Conflicts of Interest
It is all about plant substances with alleged anti-oxydative properties, specifically the flavanols genistein and flavocoxid (which is a mixture of various flavanols, primarily baicalin and catechin). Flavanols are very popular in certain circles of biomedical scamming, because of the money from wine and chocolate industry, and because the drugs are assumed to be safe because natural and from plants. Yes, there are limits to this logic.
Here one such flavocoxid paper by the Squadrito gang:
Antonio Micali , Giovanni Pallio , Natasha Irrera , Herbert Marini , Vincenzo Trichilo , Domenico Puzzolo , Antonina Pisani , Consuelo Malta , Giuseppe Santoro , Rosalba Laurà , Domenico Santoro , Francesco Squadrito, Domenica Altavilla, Antonino Germanà , Letteria Minutoli Flavocoxid, a Natural Antioxidant, Protects Mouse Kidney from Cadmium-Induced Toxicity Oxidative Medicine and Cellular Longevity (2018) doi: 10.1155/2018/9162946
Mice received heavy metal poisoning:
“The animals were divided into four groups to receive vehicle (0.9% NaCl) alone, flavocoxid alone (20 mg/kg/day i.p.), cadmium chloride (CdCl2, 2 mg/kg/day i.p.) alone , or CdCl2 (2 mg/kg/day i.p.) plus flavocoxid (20 mg/kg/day i.p.), respectively. […] All mice were sacrificed after 14 days of treatment with an i.p. overdose of ketamine and xylazine, and bilateral nephrectomies were performed.”
To obtain this fake microscopy image of a kidney:
But then Cheshire spotted something else:
“I am interested if the authors might address the issue of this or other patents on Flavocoxid, studied in this paper, which is available here. It appears the authors could have a relationship that should be disclosed to readers and peer reviewers.“
Suqadrito remained silent, but he did reply in another case of omitted COI, in Irerra et al Nutrients 2017 where Cheshire commented, referencing Squadrito’s CV:
“This paper’s conflicts of interest disclosure reads, “The authors declare no conﬂict of interest.”
Could the authors please describe the relationship between Dr. Francesco Squadrito and Primus Pharmaceuticals of Scottsdale, AZ, USA? In his CV, it states that he has been a principal investigator for this company since 2005, studying pharmacological potential of genistein aglicone. Is this a paid position? Is that position related to this paper? Does Dr. Squadrito receive royalties on the related patents?“
Squadriot replied on PubPeer:
I disclosed myself to Squadrito, but he didn’t explain me.
It is not just Squadrito who works as principal investigator for Primus. Altavilla does this since 2015, as per her CV. Bitto acts as “consulting researcher” for Primus since 2006 as per her CV, and she even founded her own company to market genistein, SunNutraPharma s.r.l.
If you believe Squadrito that he and his gang don’t receive money into their private pockets from Primus, you might just as well believe that their western blots are not fake.
Regarding this curative substance genistein from plant extracts, here another such COI-free paper:
Sonia Messina, Alessandra Bitto, M’hammed Aguennouz, Gian Luca Vita , Francesca Polito , Natasha Irrera, Domenica Altavilla, Herbert Marini, Alba Migliorato, Francesco Squadrito, Giuseppe Vita The soy isoflavone genistein blunts nuclear factor kappa-B, MAPKs and TNF-α activation and ameliorates muscle function and morphology in mdx mice Neuromuscular disorders : NMD (2011) doi: 10.1016/j.nmd.2011.04.014
“I am hopeful that the authors in the meantime could help readers understand the relationship between 1) the inventors of the patents, 2) the owners of the patents, 3) the authors, and 4) Primus Pharmaceuticals, who may own or have licensed the patents.
It seems likely that Primus has licensed the patents, but not who from. Nor is it clear whether the authors were compensated for the patents or the research related to the inventions (colloquially, but perhaps not legally, “drugs”) being studied, or whether these were owned by the University. It does appear that Primus was the sponsor of multiple clinical trials for Genistein and Flavocoxid conducted by the authors and that one or more of the authors was the principal investigator for Primus for at least one of these drugs. […]
While Primus is mentioned in many of the authors’ papers about these drugs, this particular paper seems to only mention the company in passing, “Genistein aglycone was a kind gift of Primus Pharmaceuticals Inc., Scottsdale, AZ, USA.” There doesn’t appear to be any other disclosures about whatever relationship might exist.“
Well, actually we do know from whom Primus licensed the patents. All these flavanol patents with Squadrito as inventor have the company Primus Pharmaceuticals as assignee. The only non-Messina inventors are Primus executives James Weir (President & CEO) and Bruce Burnett (left company). Here is a flavocoxid paper by the Squadrito gang with Burnett as coauthor (“approved by the Ethics Committee of the University of Messina“):
D Altavilla, L Minutoli , F Polito, N Irrera, S Arena , C Magno , M Rinaldi , B P Burnett , F Squadrito, A Bitto Effects of flavocoxid, a dual inhibitor of COX and 5-lipoxygenase enzymes, on benign prostatic hyperplasia British Journal of Pharmacology (2012) doi: 10.1111/j.1476-5381.2012.01969.x
Here, the rats “were treated daily with testosterone propionate (3mg·kg−1 s.c.) or its vehicle for 14 days to induce” prostatic hyperplasia and then injected with flavanol and other drugs. The experimental outcome:
Aneurus Inconstans noted:
In this study, transgenic mice were injected with flavocoxid, the results forged as usual:
Sonia Messina, Alessandra Bitto, M’hammed Aguennouz, Anna Mazzeo, Alba Migliorato, Francesca Polito, Natasha Irrera, Domenica Altavilla, Gian Luca Vita, Massimo Russo, Antonino Naro , Maria Grazia De Pasquale, Emanuele Rizzuto, Antonio Musarò, Francesco Squadrito, Giuseppe Vita Flavocoxid counteracts muscle necrosis and improves functional properties in mdx mice: a comparison study with methylprednisolone Experimental Neurology (2009) doi: 10.1016/j.expneurol.2009.09.015
The mice in this flavocoxid study were less lucky, they were made to suffer and die from intestinal sepsis:
Alessandra Bitto, Letteria Minutoli, Antonio David, Natasha Irrera, Mariagrazia Rinaldi , Francesco S Venuti , Francesco Squadrito, Domenica Altavilla Flavocoxid, a dual inhibitor of COX-2 and 5-LOX of natural origin, attenuates the inflammatory response and protects mice from sepsis Critical care (2012) doi: 10.1186/1364-8535-16-r32
“Specifically, mice were anesthetized with ether, and a midline incision was made below the diaphragm to expose the cecum. The cecum was ligated at the colon juncture with a 4-0 silk ligature suture without interrupting intestinal continuity. The cecum was punctured once with a 22-gauge needle. The cecum was returned to the abdomen, and the incision was closed in layers with a 4-0 silk ligature suture. After the procedure, the animals were fluid-resuscitated with sterile saline…”
To produce this fake preclinical data in support of flavocoxid:
Despite the aforementioned patent for flavocoxid and other flavonols, the Squadrito gang wrote:
Let’s have more COI-free flavocoxid!
Here, rats were tortured to prove some curative powers of flavocoxid: kainic acid (KA) was injected into their brains to cause symptoms of epilepsy.
Letteria Minutoli, Herbert Marini, Mariagrazia Rinaldi , Alessandra Bitto, Natasha Irrera , Gabriele Pizzino , Giovanni Pallio , Margherita Calò , Elena Bianca Adamo , Vincenzo Trichilo , Monica Interdonato , Federica Galfo , Francesco Squadrito, Domenica Altavilla A dual inhibitor of cyclooxygenase and 5-lipoxygenase protects against kainic acid-induced brain injury NeuroMolecular Medicine (2015) doi: 10.1007/s12017-015-8351-0
“After general anesthesia with sodium pentobarbital (50 mg/kg i.p.), the animals (n = 96) were divided into the following groups: sham + vehicle (1 ml/kg i.p.); sham + flavocoxid (20 mg/kg i.p.); KA (10 mg/kg i.p.) + vehicle; and KA + flavocoxid (20 mg/kg i.p.). Flavocoxid was administered 30 min after KA injection.”
The result was some fake western blots:
So you see, Squadrito did a great job helping Primus to preclinically verify their drug flavoxid, which the company markets as “medical food” under the tradename Limbrel®.
And then, this happened, an FDA announcement from 2018:
Primus Announces a Voluntary Nationwide Recall of All Lots Within Expiry of Prescription Medical Food Limbrel® Due to Rare But Serious and Reversible Adverse Events While Seeking FDA’s Cooperation to Restore Access for Patients with Medical Necessity
This recall has been completed and FDA has terminated this recall.
“Primus Pharmaceuticals, Inc. of Scottsdale, Arizona is voluntarily recalling all unexpired lots of Limbrel products to the patient (user/consumer) level at FDA’s request. FDA has requested a recall of Limbrel due to rare but serious and reversible side effects associated with Limbrel.
Between January 1, 2007, and November 9, 2017, FDA received 30 adverse event reports of elevated liver function tests or acute hypersensitivity pneumonitis associated with the use of Limbrel products. These conditions present in rare cases with varying degrees of severity in patients taking Limbrel for the first time in the initial weeks of exposure, and may go unnoticed by the patient until they consult with their physician or until symptoms develop that require hospitalization. There have been no deaths reported with the use of Limbrel, and in all reported cases adverse effects resolved without residual effects after discontinuing use of the product. [….]
Limbrel has been marketed since 2004 as a medical food available only by prescription for patients under active and ongoing supervision of a physician for the dietary management of osteoarthritis (OA), a degenerative disease of the joints and the most common form of arthritis. Prior to marketing, Primus conducted clinical studies that support the efficacy and safety of Limbrel and compiled an extensive dossier providing an analysis of published data to support the medical food status of Limbrel and to establish how the product meets the distinctive nutritional requirements of OA. Primus stands by the legal status of Limbrel as a medical food. Limbrel products have been distributed nationwide in the USA to wholesalers, pharmacies, and physicians as medical foods without challenge from FDA for over 13 years, with approximately 2 million prescriptions and physician samples dispensed to an estimated 450,000 patients.”
There are now several law firms inviting those damaged by Limbrel to a class action lawsuit against Primus. Sadly, Squadrito’s rodents were tortured to death and can’t sue.
It wasn’t of course just mice, rats and gerbils which Squadrito and his gang deployed to help Primus market their jointly patented drug. There also was a clinical trial at the University of Messina, to treat Duchenne Muscular Dystrophy with the flavanol quackery.
Gian Luca Vita, Maria Sframeli, Norma Licata, Alessandra Bitto, Sara Romeo, Francesca Frisone, Annamaria Ciranni, Giovanni Pallio, Federica Mannino, M’Hammed Aguennouz , Carmelo Rodolico, Francesco Squadrito, Antonio Toscano , Sonia Messina, Giuseppe Vita A Phase 1/2 Study of Flavocoxid, an Oral NF-κB Inhibitor, in Duchenne Muscular Dystrophy Brain Sciences (2021) doi: 10.3390/brainsci11010115
Of course the authors declared to have no conflicts of interests while being listed as patent inventors. Cheshire noted, among other things:
“The registered clinical trial NCT01335295 does help with the timeline a bit. Looks like trial commenced April 14, 2011 and ended December 2013.
The trial page shows 20 people were enrolled. This paper discusses 17 people were treated with flavocoxid and 17 were not. Could the authors clarify the study cohort sizes?“
The trial NCT01335295 listed our friend Giuseppe Vita as principal investigator (his son Gian Luca is first author). Vita Senior explained on PubPeer:
“Ethical approval was obtained early in 2011. At that time, no specific reports of liver injury due to flavocoxid were available except rare elevations of liver enzymes in some trials. The protocol included serum AST, ALT and LDH determinations.The patients were enrolled and followed in the period 2011-2013. […] The owner of the patent is Primus Pharm. […]
When the trial was registered as NCT01335295, the protocol designed the recruitment of 20 patients, all to be treated. Since it was an open-label study, and also after presentation to TREAT-NMD Advisory Committee for Therapeutics (TACT), we then decided to include an untreated group. The number of 20 treated patients was not reached and we stopped at 17 treated subjects and untreated groups same size.“
The trial’s participants were children suffering from Duchenne Muscular Dystrophy, aged “between 4 -16 years”. Having fabricated a massive amount of papers with fake preclincial data about flavocoxid, this Messina gang thought it was a good time to switch from rodents to children. Who then received a liver-damaging drug.
I am sure the ethics committee of University of Messina finds all this hilarious. As reminder, the university never replied to my emails. They don’t give a flying f***. Patient abuse in bullshit clinical trials? Meh.
Finally a proper reaction from University of Messina. Squadrito now announced that he is suing me in court. Because he obviously disagrees with FDA’s decision that Flavocoxid/Limbrel is toxic. Here his email:
“You sent the below mail on May 2nd 2022 to more than 50 coauthors stating that I also experimented on children with a toxic substance [actually, the email was addressed to 50 recepients including trial’s PIs- LS]. This is a false and serious allegation. It is not a problem of blots. This accusation has penal l implications. You cannot send statements of this kind to everyone. With this crazy allegation of yours you are accusing me unfairly and you have created serious moral and material damage for me that you must compensate. You have to pay for it. My attorney is suing you and will demand appropriate money compensation for all the damage you have done to me with this false allegation without proof. People you emailed will testify against you. I am looking forward to meet you in the court.
Francesco Squadrito “
Money, money, money, that’s all he can think about, this “scientist” without any COI. Go sue FDA then.
As Squadrito kept announcing lawsuits in his follow-up emails, he said this interesting thing:
Domenica Altavilla, wife of Squadrito, has suddenly died.
University of Messina announced the funeral for 14 May 2022. It is a bizarre obituary. It mentions her h-index, 300 papers, her work for Primus since 2015, a company she founded (“SunNutraPharma S.r.l.”, unmentioned other owners Squadrito, Bitto, Primus Pharmaceuticals, Pizzino & Irrera), other pointless things like curcumin, but the obituary never states any cause of death, or how old Altavilla was when she died (which was 64). Neither is Squadrito mentioned.
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Thank you for exposing the vile animal abuse. I also want to applaud your apt drawings of the perpetrators.
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Its interesting/striking that Schneider draws 1/2 the female protagonists (not just in this picture) wearing boots. Boot fetish I’d say.
I spent four and a half years in an Italian lab.
I have known about these egregious issues for a very long time. Unfortunately, Journals have turned a blind eye to it.
You knew about the Squadrito case? Which journals did you contact?
Well, I was only aware of the 2014 and 2019 Pubpeer posts. I did not mean to imply that I had contacted journals about it specifically (I have not). Back then, I assumed the commenter and/or Pubpeer people did. Even if the journals knew, I doubt they would have acted upon it. In the past, every time I have contacted a journal about integrity issue with very respectul and non-anonymous emails, I never got an answer, so I gave up. That is why your blog is important.
One journal was contacted a year ago. They acknowledged and that was it.
I’m afraid we can brace ourselves for nanoparticle fraud now, because Dr Bitto got a million of Euros to study that.
“Use of Graphene Quantum Dots as carrier of theranostics agents for solid tumours”
Responsible: Prof. Alessandra Bitto”
As in other cases, fraud began decades ago
and academic authorities,local politicians and media outlets colluded.
In the meantime fraudsters achieved wealth, social reputation
and academic prestige with fake papers.
Of more than 30 types of congenital muscular dystrophy,
Duchenne muscular dystrophy -DMD- and Becker muscular dystrophy are the two most common types
Related to most usual Duchenne, DMD sick boys -autosomal recessive,its linked to X chromosome-
stop walking when 12 years old
and need a respirator to breathe.
If they do not receive medical treatment and care,
most die in their teens and few reach their twenties.
In European Union, a rare disease is one that affects no more than 1 person in 2,000.
Prevalence of muscular dystrophy in Italy is about 0.563 per 100,000.
The cause could be identified as genetic in 65.5 % of sick volunteers in study.
So DMD could be labeled as rare disease.
If “fraud squad famiglia” didn’t find enough DMD-sick children in Italy,
were they going to start twisting the testicles of healthy children?
“Strong antioxidant” molecules that cures everything:
senescence, infections, inflammations, any type of cancer, etc.
It looked good because they were found in fruit or berry juices and our ancestors
-ancient wisdom- used them and they are cheap.
To my despair this nightmare of mine from High School days returns everyday.
Some of these molecules are not harmless and it is not the same to buy something for a dietary supplement than to use it as a therapy.
When you take any medication prescribed by your doctor,
it must reach your organism and it depends on various enzymes encoded by genes that are expressed more or less in one or another tissue.
Flavonols inhibit CYP2C9 and CYP3A4
These enzymes are part of the cytochrome P450 “famiglia”
And this other “grande famiglia” is important to you because it depends on how your body metabolizes medications – maybe toxins too by the way – in addition to oxidizing fatty acids and steroids.
In my last pre-college year, my Biology teacher suggested an assignment on aging.
I went to Library of Medicine Faculty and traveled through every crazy idea about this from late 19th century,even from Nazi science.
Torture and mistreatment of mice and rats of this “fraud squad” is nothing compared to what I read in those days.
I’m just a little voice from Sevilla not comparable to tenor voices of titans of Asturian science,
but pay attention to this because I know what I’m writing about:
A single cell of a unicellular organism contains 42 million proteins
-the last census i read- all with three-dimensional structure up to a tertiary level and some reaching the quaternary.
Most are functional -proteome- but even “junk proteins” probably are there for something.
Heh, I would say that it is what in Physics is called a complex system.
“vaya ignorancia tan impresionante del premio nobel en Bioquímica
Alfredo Ballesteros Ainsa! Y ya queda clara otra cosa de la que
no tenía prueba hasta ahora. Cuánto estáis pagando?
— Mireia_Fraser (@MireiaFraser) March 12, 2022”
In Asturias they say that ignorance and envy devours me and such ones rots me to the core.
“Maldad genética” they wrote it.
Well, I read and admire many people, but not pay attention to Spanish “charlatanes”,
able to draw a line with a pencil from a locus in DNA to a human disease,Opus Dei buddies or not.
In June 2019 Michael J. Feigenbaum died
Feigenbaum was a great thinker and for me one of the last great physics-mathematicians
Almost no Spanish media published a simple “in memoriam”
Take some time to read Feigenbaum’s views on science if interested.
You can read:
Overview on “The Nazi War on Cancer” by Robert N. Proctor
Antioxidant therapy: current status and future prospects by O Firuzi, R Miri, M Tavakkoli, L Saso
Curr Med Chem. 2011;18(25):3871-88.
I wrote it wrong:
Mitchell J. Feigenbaum <- good
Yes I’m wrong
Envy and ignorance of mine that devour me to the core and rot my mind.
And “maldad genética” of mine helps too.
Re “Overview on “The Nazi War on Cancer””
For an overview on the current/half century medical allopathy’s “war on cancer” read this well referenced scholarly article’s (“A Mammogram Letter The British Medical Journal Censored”) afterword … https://www.rolf-hefti.com/mammogram.html (scroll down to the afterword that addresses the ‘war on cancer’).
It is not an article as I understand it
(motivation, arguments and final thesis) but a group of pieces.
Discarding botched ones,
a binary test does not have two possible results but four: positive, negative, false positive and false negative.
With these four we calculate sensitivity and specificity of the test
Prevalence of condition tested would be interesting too.
That is why a diagnosis should not be based on a single test, but be formed from the results of several different tests,
which is sometimes not possible and by understanding these maths of the tests.
Evolution of a disease is called prognosis.
There seems to be agreement that the prognosis is more favorable
the earlier the detection of cancer. That is why screenings are done.
The controversy with mammograms and overdiagnosis was published in the Spanish press
but I haven’t seen the numbers so I can’t say anything
but in “Epilogue On My Banned BMJ Letter Pertaining To The Canadian Mammogram Study” section,
second paragraph, I can read that
“(e.g., mammograms cause cancer)”
and this statement is NOT TRUE.
In two cases, friends close to me went to the doctor when they couldn’t stand the pain.
Their cancer was already in final stage and they were terminal patients.
Could their lives have been saved by a screening run seven years earlier
or would it be seven years devoted to fear?
I can only state that prognosis of their cancer would have been more favorable.
In these two cases screening did not happen.
I visited them in San Lázaro Hospital
they were under sedation, one recognized me and the other did not.
There are now over 50 Squadrito papers on PubPeer, while our sleuth team faces the mountain of over 100 more to screen, so far finding fraud in almost every paper.
Here new finds:
Domenica Altavilla , Francesco Squadrito, Francesca Polito , Natasha Irrera , Margherita Calò , Patrizia Lo Cascio , Mariarosaria Galeano , Letizia La Cava , Letteria Minutoli , Herbert Marini , Alessandra Bitto
Activation of adenosine A2A receptors restores the altered cell-cycle machinery during impaired wound healing in genetically diabetic mice Surgery (2011) doi: 10.1016/j.surg.2010.04.024
No need to label anything here, it’s just same band cloned all over:
Letteria Minutoli, Francesco Squadrito, Piero Antonio Nicotina , Daniela Giuliani , Alessandra Ottani , Francesca Polito , Alessandra Bitto , Natasha Irrera , Giuseppe Guzzo , Luca Spaccapelo , Carmine Fazzari , Antonio Macrì , Herbert Marini , Salvatore Guarini , Domenica Altavilla Melanocortin 4 receptor stimulation decreases pancreatitis severity in rats by activation of the cholinergic anti-inflammatory pathway* Critical Care Medicine (2011) doi: 10.1097/ccm.0b013e318207ea80
“Acute pancreatitis was induced in male Sprague-Dawley rats by intraperitoneal injections of cerulein (80 μg/kg, four injections at hourly intervals). Before pancreatitis induction, groups of animals were subjected to bilateral cervical vagotomy…”
And so on.
Well, the sleuth team on the Squadrito case got bigger. Examples:
Rats “were subjected to surgical partial bladder outlet obstruction“, flagged by Tulipa fosteriana:
Giulio Bonvissuto , Letteria Minutoli, Giuseppe Morgia , Alessandra Bitto , Francesca Polito , Natasha Irrera , Herbert Marini , Francesco Squadrito , Domenica Altavilla
Effect of Serenoa repens, lycopene, and selenium on proinflammatory phenotype activation: an in vitro and in vivo comparison study Urology (2011) doi: 10.1016/j.urology.2010.07.514
“In Fig.2 and Fig. 3, all beta-actin in their western blot analysis have unusual similarity within each figure.”
Edentulina martensi chimed in about “Figure 1, Panel B and C“:
Another example, flagged by Orchestes quercus
Here, rats first had their ovaries removed, then injected with flavanols, then they had the skin on their backs pulled off (under anaesthetic). It is not clear if the rats were sacrificed afterwards or just forgotten and let to die from infection.
Francesca Polito, Herbert Marini , Alessandra Bitto, Natasha Irrera , Mario Vaccaro , Elena Bianca Adamo , Antonio Micali , Francesco Squadrito, Letteria Minutoli , Domenica Altavilla Genistein aglycone, a soy-derived isoflavone, improves skin changes induced by ovariectomy in rats British Journal of Pharmacology (2012) doi: 10.1111/j.1476-5381.2011.01619.x
“The collage below shows all the WBs presented in the paper. The ‘control’ ‘bands’ indicated by a green arrow are actually single blots duplicated five times. And yes, this happens for every ‘control’.”
Another example, where rats were bled to death, flagged by Asplenium x:
Domenica Altavilla , Antonino Saitta , Giovanni Squadrito , Mariarosaria Galeano , Saverio F. Venuti , Salvatore Guarini , Carla Bazzani , Alfio Bertolini , Achille P. Caputi , Francesco Squadrito Evidence for a role of nuclear factor-kappaB in acute hypovolemic hemorrhagic shock Surgery (2002) – 1 Comment
“Fig.3 from this publication is identical to Fig. 4 of the publication: Inhibition of nuclear factor-kappaB activation by IRFI 042, protects against endotoxin-induced shock DOI:10.1016/s0008-6363(02)00276-6
I am afraid Prof Squadrito is losing his mind.
I received this confused email, subject: “Request to deny a false allegation”
” To: Leonid Scheineider,
Freelance science journalist and cartoonist known for the blog “For Better Science”.
I come to know that you has frequently been sued over by several scientists haunted by your resentment and bitterness. In this regard I was recently accused by you of having conducted experiments in children with toxic substances, by interpreting my biomonitoring studies in a distorted and biased way. In fact, by contrast, I have shown that children living in a polluted area of Sicily have enhanced urinary levels cadmium that causes a delay in puberty onset and an impairment in glucose metabolism that can predispose to the onset of obesity and metabolic syndrome. More correctly my studies have been used by investigative judges to sue the oil refinery located nearby the children living area on charges of negligent pollution. This means that you may have been paid by someone to block my scientific investigation and to intimidate or blackmail me; alternatively you are unable to correctly interpret the data; rather you misinterprets them in order to slander and blackmail the researchers. For these reasons I formally ask you to deny this specific allegation. Otherwise, I will instruct my lawyer to sue you on false and slanderous charges. and I will ask for the moral and material damages caused by your superficial and acrimonious action.
Francesco Squadrito ”
It’s now 80 papers on PubPeer. Here some new finds:
Letteria Minutoli, Antonio Micali, Antonina Pisani, Domenico Puzzolo, Alessandra Bitto, Mariagrazia Rinaldi , Gabriele Pizzino, Natasha Irrera, Federica Galfo , Salvatore Arena, Giovanni Pallio, Anna Mecchio , Antonino Germanà , Daniele Bruschetta, Rosaria Laurà, Carlo Magno, Herbert Marini, Francesco Squadrito, Domenica Altavilla Flavocoxid Protects Against Cadmium-Induced Disruption of the Blood-Testis Barrier and Improves Testicular Damage and Germ Cell Impairment in Mice Toxicological Sciences (2015) doi: 10.1093/toxsci/kfv185
Mice were poisoned with Cadmium:
Salvatore Arena is paediatric surgeon and associate professor at University of Messina, his brother Francesco Arena used to work there too, but at the Department of Engineering, doing “research in Chemical Engineering, Catalysis and Chemical Kinetics”.
Letteria Minutoli, Salvatore Arena, Giulio Bonvissuto , Alessandra Bitto, Francesca Polito, Natasha Irrera, Francesco Arena, Eugenia Fragalà , Carmelo Romeo, Piero Antonio Nicotina , Carmine Fazzari , Herbert Marini , Alessandra Implatini , Silvia Grimaldi , Noemi Cantone , Vincenzo Di Benedetto , Francesco Squadrito, Domenica Altavilla, Giuseppe Morgia Activation of adenosine A2A receptors by polydeoxyribonucleotide increases vascular endothelial growth factor and protects against testicular damage induced by experimental varicocele in rats Fertility and Sterility (2011) doi: 10.1016/j.fertnstert.2010.07.1047
Again, rat testicle torture, for this:
Meet Salvatore Campo, associate professor at University of Messina and his brother, the full professor there, Giuseppe Campo.
Giuseppe M. Campo, Angela Avenoso, Antonio Micali , Giancarlo Nastasi , Francesco Squadrito, Domenica Altavilla, Alessandra Bitto, Francesca Polito, Maria Grazia Rinaldi , Alberto Calatroni , Angela D’Ascola , Salvatore Campo High-molecular weight hyaluronan reduced renal PKC activation in genetically diabetic mice Biochimica et Biophysica Acta (2010) doi: 10.1016/j.bbadis.2010.08.004
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Not to be the conspiracy-theory nut job, but maybe it’s a conspiracy. From 20 years ago:
“Professors lured into crime by mafia.
Extortion, drug smuggling, gun running and murder were not advertised on the campus syllabus, but that is exactly what Sicily’s University of Messina was teaching, Italian police said yesterday.”
Messina città “babba”
Better to expose everything.
For more than fifty years, students at University of Messina used to pay bribes to professors to pass exams.
Teachers who didn’t want to approve such fools were threatened and visited by thugs.
Cheating students used to go to exams with personal enforcers of theirs.
Although the logical thing would be for this bizz to be controlled by Cosa Nostra – Sicilians-
the truth is that it was the ‘Ndranghetta -Calabrians –
The money was invested in buying drugs and weapons.
But it is curious that some of these drugs were smuggled from labs of University of Messina
After the murder of Matteo Bottari, doctor and teacher, in 1998,
Squadra Mobile of Polizia di Stato and Polizia Criminale raided Messina.
Commissione Antimafia unveiled “rito peloritano” -Cosa Nostra slang-
mafiosi collusion scheme in Messina
Local mobsters colluded with academic authorities and reluctant professors were persuaded
even with death threats
The exam thing is “peccata minuta” because the big deal, the delicious gig big cake, was budget for contracts at University of Messina.
250 (uS) billion -Italian lira because the figure appears in an article from 1998-
“Mafia? Che cos’è? Non ne so niente.”
When Mafia is guilty, nobody is guilty.
Main suspect was never charged for homicide and committed suicide in 2013.
Why did the ‘Ndranghetta end up taking over the Cosa Nostra bizz?
Curious. Two things:
Cosa Nostra has always maintained the figure of the associate
-he is not Sicilian but he’s a good fella and we make profits with him-
‘Ndranghetta set up an effective system for resolving internal conflicts while
in Cosa Nostra they bled to death in internal wars between the different “famiglie” to gain influence and money.
In European Union everybody knows where fraud is and who the crooks are.
The problem isn’t finding them, the problem is who wants to cross the line,
expose liars and big bizz and ruin a life for nothing because nothing changes.
You can read on this
“Dietro l’omicidio Bottari si scopre la città verminaio”
pub at La Repubblica 1998 Junio, 24
“Quando Messina svelò il suo “verminaio”: l’omicidio di Matteo Bottari.”
pub at New Sicilia, 2021 January, 15
“Messina, il silenzio assordante dell’omicidio Bottari”
by Maurizio Zoppi at blog Bernini_52 2022, January,21
Maybe the thugs (whichever group) are also getting a cut of the nutraceutical sales from seemingly legitimate companies?
If some of this is affecting the Fraud Squad papers, it seems very unlikely that anything will happen in Messina. Maybe some papers will get corrected or retracted, or not even that.
Thanks for sharing.
Regarding the threat of lawsuit:
If the Fraud Squad could point to precisely what Leonid has written that is untrue, it would certainly help.
It seems likely that the offending portion of the article is about drug trials in young boys. There was a flavocoxid trial in boys discussed on PubPeer: https://pubpeer.com/publications/AA83B3A2788C6D5784186133F3A0EA. Dr. Squadrito’ co-author replied, but not Dr. Squadrito. In that article, I asked a series of questions, and so far, most remain unanswered.
What was the Squads financial relationship with the manufacturer of flavocoxid?
Were possible conflicts of interest disclosed?
Were participants informed about concerns about possible liver damage of flavocoxid that seem to have been revealed by other researchers during the trial timeframe?
Until Dr. Squadrito answers these questions, readers (like Leonid) are going to form their own opinions. If Dr. Squadrito doesn’t like this, he can easily provide facts that address the concerns.
E-mail you have reproduced tells me that Francesco Squadrito mixes
different things to create confusion as usual.
Limbrel -Flavocoxid- is a preparation that contains two flavonoids:
baicalin -extracted from plants Scutellaria baicalensis-
and catechin -from Senegalia catechu-
you will love this, Leonid because all these plants comes from TCM -Traditional Chinese Medicine- quackery
which are supposedly anti-inflammatory and used for osteoarthritis
Biochemical values in the liver explain that the damage is detectable in liver
one to three months after starting with Limbrel.
The drug began to be marketed in 2004 but Primus Pharmaceuticals and Squadrito were unlucky
because in the US it exists prospective studie based on clinical trials
and Drug Induced Liver Injury Network (DILIN) detected it.
This poison is already in scientific literaturature since 2012 at least.
The thing is serious because in some cases it produces jaundice
-You don’t have to be an expert, you can see at first glance the yellow and know that this shit is screwing up your liver-
Why is Limbrel not withdrawn until February 2018 by the FDA?
Possibly because the mechanism by which it damages the liver is not clear
and they wait until a second adverse effect hypersensitivity pneumonitis is documented.
Francesco Squadrito has published several studies about pollution in thee area of Milazzo-Valle del Mela
-by the way two other ones in Sicily have been flagged-
Squadrito took urine and blood samples from children in that area and from another further away
– so far away that heavy metal dragging by wind, drinking water and contaminated vegetables does not reach the kids, I guess –
and tries to correlate the concentrations of heavy metals in urine samples with markers that indicate overexpression of DNA repair gene and what he calls detoxification gene group.
There is no histological test that measures the concentrations of toxic metals in organs
but he considers that toxic metals would be accumulated in children’s kidneys.
I would have to read the series of articles more carefully but Fraud Squad precents are not good.
Squadrito saves your kidney -WoW!- but fucks up your liver -BuuuH!-
Well, shit happens.
I would not take lawsuits in Court as a joke because unfortunately plaintiff’s lawyers
can lie as much as he wants in the lawsuit and nothing happens to his.
Everything is accepted for legal process and lots of time is wasted.
Good luck anyway.
You can read about this:
Acute liver injury due to flavocoxid (Limbrel), a medical food for osteoarthritis: a case series
by Naga Chalasani et alii
Ann Intern Med. 2012 Jun 19;156(12):857-60, W297-300.
Limbrel Recall Announced in Wake of FDA Side Effects Warning
by Sandy Liebhard pub 2018 February,02
This is why I asked them for more details on their study timeline. Could they have heard about these concerns and still continue to treat the boys?
Well, Squadrito also wrote this to me (added as update above):
Links at the end of this comment.
I don’t have much interest in disputing what Squadrito is telling by email
but before writing my comment I searched “Limbrel” on the FDA page and there is only one thing:
a safety alert issued in 2018 January,29
FDA post such ones after a recall, market withdrawal, or safety alert of the company
as a public service.
Domain http://www.limbrel.com exists, it is up and it gives some information on the affair.
Primus hired Exponent,a independent product safety and regulatory consulting firm
Exponent reviewed all of Limbrel’s adverse events
and the FDA’s Limbrel adverse events analysis Health Hazard Evaluation
Exponent signed a report in 2018 January 16 and then Primus submitted it to FDA,
asked for a meeting to discuss.
Squadrito is M.D. but I don’t think he has a Ph.D.
I guess Dr. Squadrito has seen people with jaundice and knows what happens when there is liver failure
during his only year of residency at School of Specialization in Internal Medicine
at the University of Messina.
I have seen them.
I know what happens.
You can read:
MedWatch: The FDA Safety Information and Adverse Event Reporting Program
COMPANY ANNOUNCEMENT -Primus-
Limbrel 500 webpage
CFSAN HEALTH HAZARD EVALUATION
Adverse Event Reporting Evaluation Exponent Project No. 1107976.000 E0T1
C.V. Prof Francesco Squadrito
“I don’t treat patients.” -wrote Squadrito to me.
He is PI on several clinical trials, mostly genistein, but also the fish sperm one.
This genistein trial is currently recruiting:
This man is incapable of saying anything truthful.
Another example on how the Fraud Squad works
In 2014,Squadrito went involved in a controversy over clinical trial of another miracle drug of his.
Treatment with polydeoxyribonucleotide (PDRN), an adenosine A2A-receptor agonist, on
diabetic foot ulcers in 1 or 2 of Wagner Classification.
Squadrito maintained that with his treatment 85% of amputations would be avoided.
A source told to the journalist that Squadrito tested his miraculous ointment with neuropathic patients
from two centers in southern Italy who had little ability to express the pain caused by ulcers and to use offloading footwear
Squadrito manifests in Eligibility Criteria of the trial that “neurological or psychiatric pathologies” were exclusión criteria
Trials lasted four years as you can read in Clinicaltrials.gov
If problem of nonhealing ulcers was pressure problem, many of these could be granulated but not reepithelialized and Polydeoxyribonucleotide did nothing.
Lastly, the source of Squadrito’s polydeoxyribonucleotide was local fish farms.
It is produced with the sperm of trout raised for food purposes.
I want to to believe in Science but it’s soooooooooooooo hard!
By the way animal or human trials of Polydeoxyribonucleotide by Fraud Squad were published in several journals between 2008 and 2012. Some if these papers have zero citations..
You can read:
New Drug a Possible Breakthrough for Diabetic Foot Ulcers?
by Becky McCall pub at MedScape Medical News 2014 March, 05
Polydeoxyribonucleotide -Placentex Mastelli(Pdrn) for the Treatment of Diabetic Ulcers
submitted to ClinicalTrials.gov by Francesco Squadrito, University of Messina in 2012 September,11
“The effect of PDRN, an adenosine receptor A2A agonist, on the healing of chronic diabetic foot ulcers: results of a clinical trial”
by Francesco Squadrito et alii
J Clin Endocrinol Metab . 2014 May;99(5):E746-53.
doi: 10.1210/jc.2013-3569. Epub 2014 Jan 31.
It seems that the Polydeoxyribonucleotide is marketed as a tissue regenerator
for skin treatment under the seal 100% authentic Italy.
Chinese suppliers sold it with PaYPaL mean of payment.
To the women who are using this,
tell you that it is actually dead trout’ cum and that trout did not enjoy too much
in the process.
You can read:
El 100% Italia auténtica Placentex Mastelli
Squadrito gang can also treat bowel disease with fish sperm. https://patents.google.com/patent/WO2017085670A1/ko
This last paper you cited:
“This work was supported by departmental funding (to F.S.) and the Mastelli s.r.l. (Sanremo, Italy).
Disclosure Summary: None of the authors have conflict of interest to disclose.”
We are to believe he worked as PI for Mastelli unpaid:
“Investigatore principale 2007-2015 – Mastelli s.r.l., Sanremo Italia – Effetti del polideossiribonucleotide (PDRN) nell’infiammazione – Investigatore principale”
The Trout Sperm Squad.
I don’t think Squadrito lied to you in his “I don’t treat patients” statement.
If you examine Squadrito’s resume, after getting his university degree in Medicine,
he only spent 1 year at School of Specialities of Internal Medicine of University of Messina
-maybe it’s an error coz he only wrote his last year-
The rest of the years are stays with scholarships or prizes.
In Spain you get a medical degree after six years at the University,
then you have to pass a MIR exam and spend four or five years training in a public hospital
to become a medical practitioner. It is quite difficult.
Squadrito’s profile is not that of a medical practitioner but that of a researcher except for one thing:
he does NOT have a Ph.D. He has not proved capability to do research.
I doubt that Squadrito has read anything about Ethics, Bioethics or Philosophy of Science.
On the other side, Squadrito doesn’t treat patients as he probably would NOT twist mice’s testicles or throw rats into boiling water.
By the way, having the nerve is needed to accept that studies at the university led you to end up twisting mouse’s bollocks or smearing trout sperm on sores on the feet of psychotics
in an Italian asylum.
After the 2008 crisis, the science and technology system in Spain collapsed.
There were many critical articles and voices about “science-that-is-done-in-Spain”
-not about “Spanish science” because “Spanish science” does NOT exist-
and conclusion is that it relies on a group of local self-proclaimed geniuses entrenched in public universities and public research organizations , whose merits are not known outside of Spain.
Squadrito is Italian but he is a bit of this Spanish profile.
Spain’s problem is not money but ignorance.
Out of ignorance comes this uncivil and shameless behavior that Larra satirized
in “El Castellano Viejo” and that pops up to light when someone from outside the group observes them and writes about this.
You can have all the money in the world, a tenure in this corrupt Spanish system
or raise money writing nosense op-eds in La Nueva España
It’s the same.
When you are ignorant, you die in ignorance.
When you question all this, they refer that you probably are ETA close collaborator
or they sue you in Court.
I prefer higher-end Italian fraudsters.
With Adriano there was more level
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Full professor Sonia Messina, who has 8 entries in PubPeer as of today, is the daughter of late Corrado Messina, emeritus professor in Neurology at University of Messina. (please note the coincidence of the surname and the city name).
From Corrado Messina’s obituary, authored by Giuseppe Vita (another protagonist of The Fraud Squad), we learn that Sonia has two siblings: Maria Francesca Messina, associate professor also at Uni Messina, and Lorenzo Messina, ophtalmologist. The latter seems to not be tenured at the local university, which is surprising.
Sadly, Prof. Domenica Altavilla passed away a few days ago. Her funeral was celebrated on May 14th, 2022.
I offer my condolences.
The university statement includes this: “Since 2015 she has been Scientific Director of a Research Project funded by Primus Pharmaceuticals (Scottsdale, Arizona) for the development of anti-inflammatory drugs and nutraceuticals,” which I don’t remember seeing mentioned in any conflict of interest statement on their studies of flavocoxid.
Her husband last wrote to me on 9 May, threatening lawsuit. No replies since.
The “chemical brothers” Francesco & Giovanni Squadrito are the sons of Giuseppe Squadrito, who was Uni Messina professor (of course!) and boasts about 120 papers in PubMed, from the 1950s up to mid 1990s.
My deepest condolences.
In “True Romance”, don Vincenzo starts his speech with:
“Sicilians are great liars. The best in the world”
Francesco Squadrito’s resume is strange and if I were writing about a dynasty of Sicilian scientists I would understand.
The year (1984-1985) after finishing his degree in medicine and surgery,
Squadrito wrote that he won a scholarship from the Bonino-Puleyo Foundation at Department of Pharmacology
of New Jersey School of Medicine for a work entitled
“The role of cerebral acetylcholine in the control of cardiovascular apparatus during pathological conditions”
A year later(1985-1986), he enjoyed another scholarship -FarmaIndustria I think- at the Institute of Pharmacology of the University of Messina.
And pay attention: with a job with the title:
“The role of neurotransmitters in the control of cardiovascular apparatus during pathological conditions”
Sadly for me I know what acetylcholine is for: it’s a neurotransmitter.
Possibly the same work allowed him to obtain two scholarships.
A third year(1988) is spent at the School of specialization in Internal Medicine of University of Messina.
Next year (1989-1990) he has something he calls “Nominated Assistant Professor” at the University.
Squadrito misspelled the name of the Foundation in his CV.
It’s Fondazione “Bonino-Pulejo”
Uberto Bonino was an Italian banker and right-wing politician but coming from 50s Italian monarchical sectors aka Italian elites displaced by Mussolini’s “camicie nere”
Bonino was in Italian Politics since the Constituent Assembly -1946- after the fall of fascism.
He survived the failure of monarchical restoration in Italy
and stayed in politics for so many years because he was intelligent:
he was rich, his wife was richer and he sets up a publishing group “Società Editrice Siciliana”
that publishes local daily “Gazzetta del Sud” and “Giornale di Sicilia”.
Fondazione Bonino-Pulejo was established in 1972 and Rector of University of Messina has a seat on Board of Directors of Fondazione “Bonino-Pulejo”
Elites and dinasties.
There is also Violetta Squadrito, who is the daughter of Francesco and Domenica Altavilla.
Violetta has published with her parents already 9 papers from 2016 to today, none of them has been flagged on PubPeer, as The Squad became more attentive lately.
Likely she is aiming at a tenured position at Uni Messina too, because a civil servant position in Sicily is gold.
The Squad people with most flagged pappers in PubPeer as of today:
Francesco Squadrito 107, Domenica Altavilla 100, Alessandra Bitto 84, Letteria Minutoli 75, Natasha Irrera 47, Giovanni Squadrito 42, Herbert Marini 42.
For Giovanni Squadrito the total is not definitive.
One of the first journals to take action. https://twitter.com/Thatsregrettab1/status/1562540421305503744?s=20&t=v7fDMZM4wwbyGw39pm5A9A
Two Expressions of Concern for “The Squad”, both issued by the Journal of Vascular Surgery in August 2022 (about two months after the editorial board were notified):
“This is a note of a temporary expression of concern related to the above-mentioned publication.
The editors have been alerted to concerns about apparent figure manipulation in Figures 2, 3, and 4.
Figures 2B and 4A: The first 3 bands in the β-actin row in Figure 2B appear to match the final 3 bands. The 6 bands in 2B also appear to match the 6 bands in Figure 4A.
Figure 3D: The first 3 bands in the β-actin row appear to match the final 3 bands.
Figure 4B: The first 2 bands in the β-actin row appear to match the middle 2 bands.
Figure 4C: The first 2 bands in the β-actin row appear to match the middle 2 and final 2 bands.
Figure 4D: The first 3 bands in the β-actin row appear to match the final 3 bands.
The authors have communicated to the journal that original blots are no longer available, given the amount of time that has elapsed since publication. Additionally, the editors believe that any remaining samples are unlikely to be usable at this point. However, since the concerns cannot be decided with certainty, the validity of the data and the conclusions of the paper must be questioned; therefore, the journal does believe the concerns are sufficiently well-founded to support a formal notice alerting the reader to this situation. The concern and this note will remain appended to the above-mentioned article, unless the authors provide the editors of the Journal of Vascular Surgery evidence adequate to allay the above concerns.”
“This is a note of a temporary expression of concern related to the above-mentioned publication.
The editors have been alerted to the following concerns about apparent figure manipulation in Figures 2 and 3.
Figure 2A: The left panel in the “HLI + PDRN 8mg + DMPX” column appears to duplicate the left panel in the “Sham HLI + vehicle” column.
Figure 2A-B: The right panel in the “HLI + vehicle” column in 2B appears to be a rescaled version of the right panel in the same column in 2A.
Figure 2B-C: The left panel in the “Sham HLI + vehicle” column in 2C appears to duplicate the left panel in the same column in 2B. Additionally, the left panels in the “HLI + PDRN 8mg + DMPX” column in both rows appear to be duplicated.
Figure 3A: Each of the 6 blots for β-actin at both 14 and 21 days appears to be the same band, and the β-actin blots for 21 days appear to be a 180° rotation of the blots at 14 days.
The authors have communicated to the journal that original blots and files are no longer available, given the amount of time that has elapsed since publication. Additionally, the editors believe that any remaining samples are unlikely to be usable at this point. However, since the concerns cannot be decided with certainty, the validity of the data and the conclusions of the paper must be questioned; therefore, the journal does believe the concerns are sufficiently well-founded to support a formal notice alerting the reader to this situation. The concern and this note will remain appended to the above-mentioned article, unless the authors provide the editors of the Journal of Vascular Surgery evidence adequate to allay the above concerns.”