Research integrity

Javier suspects everyone!

"If in any case we consider that the problems with the images really affected the validity of the results, we ourselves would ask the corresponding journal to retract the article." - Prof Javier González-Gallego

Meet Javier Gonzalez-Gallego, since 1987 professor of physiology and former director at the Institute of Biomedicine (IBIOMED) of the University of León in Spain. He has published over 300 peer reviewed papers by his own account.

Now the question arises how trustworthy all these biomedical studies are. Dr Gonzalez-Gallego has over 50 papers flagged on PubPeer now and he promised to investigate all his co-authors. Except himself.

Most of the work was done by Aneurus Inconstans (a contributor to For Better Science) and another PubPeer user whose identity is unknown to us, Hydrophis melanocephalus.

Iberian yeast masters do it classic with a flip

“These figures were elaborated by me personally and I remember quite well how I made them. Definitely, the images shown in this figure were cut and pasted from the originals in order to elaborate the figures, the overlapping was done “manually” using GIMP…” – Dr. José R Pérez-Castiñeira

Our hero Gonzalez-Gallego has a great interest in the hormone melatonin and how it can be deployed as medicine. The Leon professor even suggested melatonin as cancer cure, but he apparently failed to convince even himself, so he sticks to pushing it for liver health. Here is one relatively recent study on the topic:

González-Fernández B, Sánchez DI, Crespo I, San-Miguel B, de Urbina JO, González-Gallego J, Tuñón MJ. Melatonin Attenuates Dysregulation of the Circadian Clock Pathway in Mice With CCl4-Induced Fibrosis and Human Hepatic Stellate Cells. Front Pharmacol. (2018) doi: 10.3389/fphar.2018.00556

Figure 2C seems to have two sets of images which overlap, however they are described as having been treated differently
Figure 1A image (a) is the same liver control already used in Figure 2A of Crespo et al. 2015, a paper with its own serious problems too.

More on melatonin, this time in a very dedicated journal, with same author names all over:

San-Miguel B, Crespo I, Sánchez DI, González-Fernández B, Ortiz de Urbina JJ, Tuñón MJ, González-Gallego J. Melatonin inhibits autophagy and endoplasmic reticulum stress in mice with carbon tetrachloride-induced fibrosis. J Pineal Res. (2015) doi: 10.1111/jpi.12247.  

Aided by ImageTwin software.
Each image is supposed to describe a different treatment
Conditions are different: Control and Control + Mel, respectively.

Another study using fake science to prove that melatonin is definitely the drug to take against liver fibrosis:

Bárbara González-Fernández , Diana I. Sánchez , Irene Crespo , Beatriz San-Miguel , Marcelino Álvarez , María J. Tuñón, Javier González-Gallego Inhibition of the SphK1/S1P signaling pathway by melatonin in mice with liver fibrosis and human hepatic stellate cells BioFactors doi: 10.1002/biof.1342 

Figure 1A, three actin bands seems as they were copy/pasted (red boxes). Image analysis below done with enhanced contrast and color map.
Images are rotated 180 deg and the horizontal dimensions have been modified. The melatonin treatments are supposed to be different.
Figure 3A, two more overlaps of micrographs that are supposed to be representative for different treatments.”

And yes, melatonin can cure liver cancer if applied creatively:

Diana I. Sánchez , Bárbara González-Fernández , Beatriz San-Miguel, Juan Ortiz De Urbina, Irene Crespo, Javier González-Gallego, María J. Tuñón Melatonin prevents deregulation of the sphingosine kinase/sphingosine 1-phosphate signaling pathway in a mouse model of diethylnitrosamine-induced hepatocellular carcinoma Journal of Pineal Research (2017) doi: 10.1111/jpi.12369 

Would you like to know where the common author on the above papers and former PhD student of Gonzalez-Gallego, Irene Crespo, is professor now? University of Oviedo. Yes, the Opus Dei-controlled home of Carlos Lopez-Otin, where two of his professor colleagues are now under misconduct investigation, or rather stand a trial for blasphemy (they dared to criticise Lopez-Otin’s research fraud).

Carlos Lopez-Otin and the revoked Nature Mentoring Award

St Carlos of Oviedo almost was canonised as Spain’s first living martyr, but now Nature revoked his mentoring award. Spanish media and science elites are desperate, even the Queen is not amused. The Royal Academy of Sciences insists Lopez-Otin is a victim of journal’s failure.

Spanish elites rally in support of data manipulation

Carlos Lopez-Otin was forced to retract EIGHT papers in the Journal of Biological Chemistry, right after he retracted a very important paper in Nature Cell Biology. Spanish elites cry foul, a letter signed by 50 Spanish researchers was sent to JBC to prevent retractions. The ringleader is Juan Valcarcel of CRG in Barcelona, and I release 3 incompetent investigative reports Valcarcel commissioned in 2015 to whitewash his CRG colleague Maria Pia Cosma.

But many other González-Gallego papers flagged on PubPeer are without Crespo. And look how fraudulent this one is:

Rodriguez-Miguelez P, Lima-Cabello E, Martínez-Flórez S, Almar M, Cuevas MJ, González-Gallego J. Hypoxia-inducible factor-1 modulates the expression of vascular endothelial growth factor and endothelial nitric oxide synthase induced by eccentric exercise. J Appl Physiol (2015) doi: 10.1152/japplphysiol.00780.2014

The cloned lanes in Figure 1A are the same ones used to assamble Figure 4A of Tieppo et al. 2009 (boxes of same color). Of note while 6 years before the signal was supposedly showing NF-kB, in this article is instead supposedly showing HIF-1a.
The cloned lanes in Figure 1A are (again) the same ones used to assamble Figure 3 of Jiménez-Jiménez et al. 2008 (boxes of same color). Again, while 7 years before the signal was supposedly showing NF-kB, in this article is instead supposedly showing HIF-1a.

A very similar situation here, but with different junior authors:

Cristi-Montero C, Sánchez-Collado P, Veneroso C, Cuevas MJ, González-Gallego J. Effect of an acute exercise bout on Toll-like receptor 4 and inflammatory mechanisms in rat heart. Rev Med Chil. (2012) doi: 10.4067/S0034-98872012001000007.

Figure 2, the blot is a patchwork of lanes copy/pasted and sometimes (red boxes) also flipped horizontally. These lanes come from other two papers by the same group, Tieppo et al. 2009 and Jiménez-Jimémez et al. 2008

The Tieppo et al 2009 paper had even more forgeries, required to promote the plant flavonoid quercetin for the liver diseases:

Tieppo J, Cuevas MJ, Vercelino R, Tuñón MJ, Marroni NP, González-Gallego J. Quercetin administration ameliorates pulmonary complications of cirrhosis in rats. J Nutr. (2009) doi: 10.3945/jn.109.105353.

Here a study on the benefits of nitric oxide, done in collaboration with Brazilian colleagues:

Filippin LI, Cuevas MJ, Lima E, Marroni NP, Gonzalez-Gallego J, Xavier RM. Nitric oxide regulates the repair of injured skeletal muscle. Nitric Oxide. (2011) doi: 10.1016/j.niox.2010.11.003.

“…several microscopy images in Figure 1 and Figure 3 have been published also in Figure 1 and Figure 5 of Filippin et al. 2011 Inflamm Res, a paper that has its own serious issues. The two papers have almost identical titles, were submitted on February 11th and February 23rd 2010 respectively, and got both accepted in November 2010.”

Maybe Maria Jose Cuevas, a former PhD student of the Leon professors Gonzalez-Gallego and Maríamar Almar, did this? But there are papers without Cuevas…

Like this one, curing colon inflammation with the useless, but popular amino acid supplement glutamine:

Fillmann H, Kretzmann NA, San-Miguel B, Llesuy S, Marroni N, González-Gallego J, Tuñón MJ. Glutamine inhibits over-expression of pro-inflammatory genes and down-regulates the nuclear factor kappaB pathway in an experimental model of colitis in the rat. Toxicology. (2007) doi: 10.1016/j.tox.2007.04.012

Fig 4A & 6A by Hydrophis melanocephalus

Here a set of papers where Gonzalez-Gallego was apparently undecided about quercetin vs melatonin for liver health, so he decide to push both, thanks to fake science.

Marcolin E, San-Miguel B, Vallejo D, Tieppo J, Marroni N, González-Gallego J, Tuñón MJ. Quercetin treatment ameliorates inflammation and fibrosis in mice with nonalcoholic steatohepatitis. J Nutr. (2012) doi: 10.3945/jn.112.165274

Hydrophis melanocephalus: “Fig. 3 – more similar than expected.
Aneurus inconstans: “Figure 2, 2 wk CO+Q (C) and 4 wk CO (B) are the same image

Laliena A, San Miguel B, Crespo I, Alvarez M, González-Gallego J, Tuñón MJ. Melatonin attenuates inflammation and promotes regeneration in rabbits with fulminant hepatitis of viral origin. J Pineal Res. (2012) doi: 10.1111/j.1600-079X.2012.00995.x

Figure 1, effects of rabbit hemorrhagic disease virus (RHDV) infection and melatonin treatment on liver tissue from New Zealand white rabbits. The actin control was used in at least two other previous papers by the same group, Kretzmann et al 2008 and Crespo et al 2008 (red boxes), where experiments were on Winstar rats and human umbilical vein endothelial cells, respectively, and on completely unrelated topics.”

de David C, Rodrigues G, Bona S, Meurer L, González-Gallego J, Tuñón MJ, Marroni NP. Role of quercetin in preventing thioacetamide-induced liver injury in rats. Toxicol Pathol. (2011) doi: 10.1177/0192623311418680.

Hydrophis melanocephalus: “Fig. 4: More similar than expected.”
Aneurus: “Sometimes the bands have a different size, but the good resolution of the figure allows to distinguish the pixel-by-pixel details and the internal features of each band.

Carbajo-Pescador S, Martín-Renedo J, García-Palomo A, Tuñón MJ, Mauriz JL, González-Gallego J. Changes in the expression of melatonin receptors induced by melatonin treatment in hepatocarcinoma HepG2 cells. J Pineal Res. (2009) doi: 10.1111/j.1600-079X.2009.00719.x

Why they never made a study combining quercetin and melatonin is puzzling. What is not at all puzzling – why the data had to be forged to prove the efficiency of either drug. Because they just don’t work, at least not as planned. But who did the forgery?

Gonzalez-Gallego replied to me, telling me of his health problems, a recent operation which made him home-bound and on medical leave. He also said:

First of all, I thank you for having detected this series of anomalies in different articles, of which I can assure you that you were not aware, which obviously cannot be an apology at all. Please give me a few days so that I can review, together with those responsible for the different lines of work within the group, each of the comments on pubpeer to be able to give a response. If in any case we consider that the problems with the images really affected the validity of the results, we ourselves would ask the corresponding journal to retract the article. I already anticipate that I must recognize tutoring problems in the group and that perhaps sometimes the work carried out under supervision has not been sufficiently careful….

Fraud Simple

US cancer research professors Paul B Fisher, Paul Dent and Stephen Grant look like the characters of a Joel and Ethan Coen crime movie, unfortunately never filmed. Smut Clyde will give you a peek into their spree of data manipulation

So I would like to help Prof Gonzalez-Gallego with his investigations. Look, a hot lead here, a collaborative study done with US colleagues, led by Paul Dent of Virginia Commonwealth University.

Laurence Booth , Jane L. Roberts , Heath Ecroyd , Sarah R. Tritsch , Sina Bavari , St. Patrick Reid , Stefan Proniuk , Alexander Zukiwski , Abraham Jacob , Claudia S. Sepúlveda , Federico Giovannoni , Cybele C. García , Elsa Damonte , Javier González-Gallego, María J. Tuñón , Paul Dent AR-12 Inhibits Multiple Chaperones Concomitant With Stimulating Autophagosome Formation Collectively Preventing Virus Replication Journal of Cellular Physiology (2016) doi: 10.1002/jcp.25431

Figure 3A and 3B: several images were already published four months before in Booth et al. 2016 Oncotarget 7(11):12975-9 (dashed boxes of same color). Original reserch articles cannot include already published images, and least of all at this large extent.
Another perplexing detail is that the manuscript was submitted on 13th May 2016 and accepted 3 days later.

But the Dent paper is a one-off, and it reuses pics from an older Dent lab papers. It’s just that science cheaters are attracted to each other, even across oceans and continents. To find the fraudster who soiled Prof Gonzalez-Gallego’s papers, we must look close to home.

In this regard, maybe the University of Leon professor María Jesús Tuñón, co-author on the this paper and many melatonin and quercetin studies above, is the perpetrator? But there are papers without Mary Jesus from Tuñón, too. And without Cuevas, or Crespo.

This one was done in collaboration with colleagues in Madrid, and published in the elite journal Gut (by BMJ) with an impact factor of 31.8:

Miquilena-Colina ME, Lima-Cabello E, Sánchez-Campos S, García-Mediavilla MV, Fernández-Bermejo M, Lozano-Rodríguez T, Vargas-Castrillón J, Buqué X, Ochoa B, Aspichueta P, González-Gallego J, García-Monzón C. Hepatic fatty acid translocase CD36 upregulation is associated with insulin resistance, hyperinsulinaemia and increased steatosis in non-alcoholic steatohepatitis and chronic hepatitis C. Gut. (2011) doi: 10.1136/gut.2010.222844

Figure 2, excess of FAT/CD36 protein is found in the liver of patients with NAFLD and HCV G1. The actin control is the same Western blot (red boxes) used a year before in Figure 3 of Lima-Cabello et al. 2010 J Appl Physiol 108(3):575-83, where Western blot analyses of IkBa and phospho-IkBa (pIkBa) was performed in the cytosolic fraction of deep vastus lateralis skeletal muscle.”

Let’s look at more fake melatonin science, maybe we will find the perpetrator there, what do you say? Did you know melatonin prevents liver ageing?

Molpeceres V, Mauriz JL, García-Mediavilla MV, González P, Barrio JP, González-Gallego J. Melatonin is able to reduce the apoptotic liver changes induced by aging via inhibition of the intrinsic pathway of apoptosis. J Gerontol A Biol Sci Med Sci. (2007) doi: 10.1093/gerona/62.7.687.

Fig 3B and 5B, by Hydrophis melanocephalus

Mauriz JL, Molpeceres V, García-Mediavilla MV, González P, Barrio JP, González-Gallego J. Melatonin prevents oxidative stress and changes in antioxidant enzyme expression and activity in the liver of aging rats. J Pineal Res. (2007) doi: 10.1111/j.1600-079X.2006.00409.x.

Fig 4A

Or how about glycine supplements, they also do wonders for liver health, I am told:

J.L Mauriz , B Matilla , J.M Culebras , P González , J González-Gallego Dietary glycine inhibits activation of nuclear factor kappa B and prevents liver injury in hemorrhagic shock in the rat Free Radical Biology and Medicine (2001) doi: 10.1016/s0891-5849(01)00716-x 

Fig 3
Fig 4

J.L Mauriz , B Matilla , J.M Culebras , P González , J González-Gallego Dietary glycine inhibits activation of nuclear factor kappa B and prevents liver injury in hemorrhagic shock in the rat Free Radical Biology and Medicine (2001) doi: 10.1016/s0891-5849(01)00716-x

Fig 3
Fig 4

Here some pharma industry-sponsored liver research:

Mauriz JL, Gonzalez P, Duran MC, Molpeceres V, Culebras JM, Gonzalez-Gallego J. Cell-cycle inhibition by TNP-470 in an in vivo model of hepatocarcinoma is mediated by a p53 and p21WAF1/CIP1 mechanism. Transl Res. (2007) doi: 10.1016/j.trsl.2006.07.004.

Fig 6B

Maybe Gonzalez-Gallego’ graduate José L Mauriz did it? Let’s see what that rogue PhD student is up to now, let’s catch him and make him talk…. Oops, he rose to the position of the IBIOMED director, succeeding the former IBIOMED director who was, as you might recall, Gonzalez-Gallego. Thus, Prof Mauriz is the bigwig whose job it is to investigate his former mentor and himself. The two men have currently 15 joint papers on PubPeer, with very fake data in those. I’m sorry, it is really a very trashy detective novel script.

Well, it could very well have been a team work, by a whole gang of data forgers in Leon, but there is only one common name on all these 50 fake papers. Here, another melatonin paper, with just 3 authors, and we recognise only one of them.

Alonso M, Collado PS, González-Gallego J. Melatonin inhibits the expression of the inducible isoform of nitric oxide synthase and nuclear factor kappa B activation in rat skeletal muscle. J Pineal Res. (2006) doi: 10.1111/j.1600-079X.2006.00323.x.

Another classic, and whom shall we blame here?

Dias AS, Porawski M, Alonso M, Marroni N, Collado PS, González-Gallego J. Quercetin decreases oxidative stress, NF-kappaB activation, and iNOS overexpression in liver of streptozotocin-induced diabetic rats. J Nutr. (2005) doi: 10.1093/jn/135.10.2299.

Figure 3A, two iNOS bands have been duplicated (red boxes) and roteted by 180 deg. Actin bands are also duplicated (blue boxes).

Gonzalez-Gallego is now in a full investigative modus. He informed me on 20 July 2022:

First, I confirm that the academic authorities of our university (Rector and Vice-Rector for Research) have received your message. I have already let the Vice-Rector know that I am in contact with you and that I will keep him informed.

Within the limitations set by my state of health, I am going to hold a telematic meeting today with those people responsible for the different lines of work in the group, so that all the comments can begin to be reviewed,  the co-authors of the different papers contacted and the original data and images located whenever possible, in order to be able to respond to the criticisms raised. We would contact the corresponding journals in those cases in which a correction or even retraction would be considered necessary.

Here is one way to react: deny everything, like Antoni Camins in Barcelona did.

It was not just preclinical research where animals were injected, sliced up and trashed to create fake results in Photoshop.

There were also clinical trials, with human participants. Remember the Jiminez-Jiminez et al 2008 paper? It had even more problems.

Rodrigo Jiménez-Jiménez , María José Cuevas, Mar Almar , Elena Lima , David García-López , José A. De Paz , Javier González-Gallego Eccentric training impairs NF-kappaB activation and over-expression of inflammation-related genes induced by acute eccentric exercise in the elderly Mechanisms of Ageing and Development (2008) doi: 10.1016/j.mad.2008.02.007 

Exercise physiology is another line of research Gonzalez-Gallego is very interested in, next to melatonin. Here another clinical trial:

Fernandez-Gonzalo R, De Paz JA, Rodriguez-Miguelez P, Cuevas MJ, González-Gallego J. TLR4-mediated blunting of inflammatory responses to eccentric exercise in young women. Mediators Inflamm. (2014) doi: 10.1155/2014/479395.

Same team, another clinical trial:

María J. Cuevas , Mar Almar , Juan C. García-Glez , David García-López , José A. De Paz , Ildefonso Alvear-Órdenes , Javier González-Gallego Changes in oxidative stress markers and NF-kappaB activation induced by sprint exercise Free Radical Research (2005) doi: 10.1080/10715760500072149

One of the bands appears twice and rotated by 180 deg.

The co-author Jose Antonio De Paz was the only collaborator of our protagonist who was shocked about all that massive fraud and wanted to do something. He replied to me:

Of course it worries me!!! although I do not do molecular biology, in those articles I have been involved in the design of the exercise program, in the medical evaluation of the participants, in the blood collection and in the design of the research!!!!

Maybe it will reassure De Paz that Gonzalez-Gallego is an expert on sports doping? Seriously, he is. Knows all about cheating in a competition. Which reminds me of another sports doping expert, Gaetano Cairo in Milan.

Gaetano Cairo’s doped science

Smut Clyde is back to Milan, to show you some more artworks exhibited at the Institute of General Pathology. He will give you a quick run of Gaetano Cairo’s doped science.

Gonzalez-Gallego said at a doping conference in 2017:

The greatest danger of genetic manipulation for sporting purposes is that not enough is known about the effects it can produce […] there are certain sports in which traditional doping is used a lot because the level of demand is excessive; therefore, when it is seen that certain genetic agents work well and the risks are relatively low, they will begin to be used frequently

It is just as true for research doping with Photoshop. And now the cheater got caught. But good news, it’s Spain! Expect nothing but complaints about foreign conspiracies and being a victim of a witch hunt.

Nobody Expects the Spanish Inquisition!

“Recently we realized that some images were used wrongly in the paper, so I want to retract this article.
The key message of the paper is very solid and results have been reproduced independently in many laboratories, but I find unacceptable the wrong use of some images during figure preparation” – Pedro L Rodriguez


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7 comments on “Javier suspects everyone!

  1. Important to say: dozens of other articles by Javier Gonzalez-Gallego do present Western blots with signs of manipulation, but no “smoking gun” was found (at least by me), thus I left them alone.

    Like

  2. I just realized that Javier Gonzalez-Gallego is the perfect impersonation of “Prof. Smith” by PhD Comics:

    Liked by 1 person

  3. Many thanks for covering this, Leonid! (And for sending this tip to other sleuths, like Aneurus, they did an incredible job!). I initially found it by pure luck, since I was actually investigating the papers of a Brazilian group (Norma Marroni). Since Javier was a co-author in some of their articles, I had to check his papers too.

    It’s a shame that this went unnoticed for decades.

    Thanks,
    HM

    Liked by 1 person

  4. JGG and his gang reached the remarkable number of 56 papers flagged in PubPeer.
    It could be possible I missed something and there could be more, but I guess I’ll stop here.

    Liked by 1 person

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