Research integrity Smut Clyde

Yogeshwer Shukla’s toxic career of Ayurvedic infusions

Professor Shukla is a bigwig in Indian toxicology because he uses fresh fruit, tea and curry spices to cure cancer. For maximum effect, his lab resorts to fabricating data in Photoshop.

Welcome to another hagiography of an acdemic career built on fabricated research results, brought to you by Smut Clyde. Today’s Photoshop hero is professor Yogeshwer Shukla, a highly distinguished Indian expert of toxicology, cancer research, proteomics and recently also nanotechnology, where he announced to cure cancer with nanoparticles soaked in Ayurvedically-relevant plant extracts. Shukla spent his entire career at the CSIR-Indian Institute of Toxicology Research (IITR) in Lucknow, where he has practised his art for almost 35 years since his early days of PhD in 1984, and where he now made it as Chief Scientist of Food, Drug and Chemical Toxicology.

The man who is not afraid to use a mango or even a pomegranate to kill cancer, received awards from the Indian Society of Health, Environment, Education and Research, for his Photoshop contributions in the field of cancer chemoprevention. Shukla, who probably will proclaim resveratrol’s antioxidative powers even after his 5th bottle of red wine, also used to be the General Secretary of Environmental Mutagen Society of India and the Indian Society of Toxicology. Despite having published oodles of peer-reviewed artworks, Professor Shukla’s due recognition in form of retractions was so far unjustly sparse: just 3, one for plagiarism in 2012 and two for data falsification in 2019.

Screenshot_2019-05-29 Retraction notice to Theaflavins induced apoptosis of LNCaP cells is mediated through induction of p5[...]

Professor Shukla’s visits abroad were rare and brief, like to WHO-IARC in Lyon, maybe his hosts didn’t like the competition.  The great moustache wearer, now aged 55, rather prefers admirers to come to him. He organised the annual meeting of Environmental Mutagen Society of India in 2002 and in 2005, and more recently, was appointed as the Organising Secretary for the next year’s Environmental Mutagen Society of India in 2020. This eulogy is meant to promote Professor Shukla’s academic reputation and national fame to some new heights he might have never expected to reach.

certificate_Yogeshwer_Shukla
Not a fake. Prof Shukla recognised by his friends at OMICS

Another green world, by Smut Clyde

These mice were treated for cancer in 2014, using nano-encapsulated pineapple-squeezed bromelain (VII and VIII are identical twins) [1].

Not only was the treatment successful, but it prolonged their lives long past the usual murine span so they could be treated for cancer again in 2018, this time using nano-encapsulated barberry squeezings [2].

npsSome uncertainly lingered whether the nano-encapsulation involved “Hyaluronic acid-grafted PLGA” or “O-Hexadecyl-Dextran” [3].

The history of “medicinal pineapple” is in fact an interest of mine (I suspect it may be inspired by the verbal resonance between Ananas and Ananias, the patron saint of liars). It began with a German charlatan who reasoned that Bromelain is a meat-softening enzyme. and tumours are made of meat. Anyway, our rodent friends provide a convenient entry point to the cuisine-based corpus of Professor Yogeshwer Shukla at CSIR-Indian Institute of Toxicology Research (Delhi, India). For with the help of his colleagues and students, Dr Shukla has reported diverse botanical treatments for cancer (in mice!) in the course of his illustrious career… with squeezings from garlic, pomegranates, and mangos as well as pineapples. Also grape-skins and tea-leaves; and extracts from cinnamon, ginger and turmeric. Sometimes in isolation, sometimes in synergistic combination. It is as if an unlikely concatenation of events had led to the acceptance of a nouvelle-cuisine cookbook as a grant proposal.

As is the custom of my people, I shall draw heavily on comments left at the ‘PubPeer’ website, where 40 threads are currently devoted to discussing specific papers from his oeuvre. Some of those papers have been retracted, but surprisingly few in light of the unabashed data frauds they display. I can promise a promenade of hedgehogs, in illustration of Clyde’s First Law (“Everything is better with googly eyes”) [4].

djco_qaxcaag15o

But gratification deferred is gratification doubled, and to heighten the dramatic tension I’ll begin with a peripheral figure: Sahdeo Prasad, now Instructor at Texas Tech University Health Sciences Center, one shudders to think what he instructs people in, given his own record. The PubPeer archives for Prasad namely show him participating in much of the output from Shukla’s output — perhaps as a grad or post-grad student — around 2007-2009, a notably productive period for the laboratory. After that he ascended to the MD Anderson Cancer Center (University of Texas) to work with Bharat Aggarwal and co-author a string of papers, later retracted because the amount of fabrication in them exceeded editorial tolerance. Prasad now collaborates with the mendacious scoundrels at OMICS, and also edits journal-shaped dumpsters for Longdom Publishing (an OMICS polyp).

dydtvzvuwaam2byNow Aggarwal’s name should be familiar. He was a pioneer in the field of ‘Jurisprudential Science’, which is where you prove the validity of your theories and results by issuing bumptious, censorious legal threats against your critics. If Jurisprudential Science is not yet the title of a parasitical journal from OMICS, it should be. Disgrace as a con-man and departure from the MD Anderson did not greatly discommode Aggarwal’s career. He continued to publish in Frontiers journals (aided by the complaisance of his quondam colleagues as editors and reviewers), and to star as a guest speaker at magical-thinking scamborees on “curing cancer with culturally-significant herbs and spices”.

Many of the Prasad / Aggarwal impostures emerged from a research goal of finding curative benefits from turmeric (more exactly, from the dyestuff / secondary metabolite curcumin extracted from turmeric), obliging them to fake results because in practice curcumin is a shite drug. Aggarwal also played a role in in the Red-Wine bubble… I do not mean the beaded bubbles winking at the brim of a beaker of blushful Hippocrene, but rather, the swell of enthusiasm for the grape-skin component resveratrol which was going to lengthen lifetimes and cure heart disease and cancer by drinking red wine until people collectively tired of faking positive results.

cz1

czThe relevance of this little digression is that Yogeshwer Shukla espouses the same “culturally-significant plant product” ethnocentric-pharmacognosy approach to drug development, attempting to bring his artistic practice under the protective aegis of Ayurveda (like Aggarwal, he plays up the medieval-herbalism aspect of the Ayurvedic scammocopoeia and plays down the arsenic / mercury / lead toxic-metal alchemy). It must be tempting for scientists in India to claim that their work vindicates Ayurvedic Traditional Knowledge, so that as champions of Vedic cultural virtues they can call on the political forces of ethnocentric chauvinism to keep themselves dismissal-proof despite incompetence or corruption. As it happens, herbs like caraway and dill are important in my culture, especially their secondary metabolites infused in alcohol, but I do not pretend that Akvavit botanicals are responsible for my unnaturally-extended life-span.

 

But back to the PubPeer archives. With so many threads, we can only scratch the surface of the iceberg on the seashore and divert ourselves in now and then finding a smoother pebble or a prettier shell than ordinary. Rest assured that curing cancer does not distract Dr Shukla entirely from the ‘Toxicology’ aspect of his institution, and he also studies the carcinogen side of the coin, even if he sometimes confuses Deltamethrin and Benz-α-pyrene, on one hand [5], with Cypermethrin and mezerein on the other [6].

So let’s start with a recent paper (2016) [7], in which the magic of mango squeezings (Lupeol) prevent a fungicide (Mancozeb) from causing cancer. Here are two panels from Figure 2. Now I am not wise in the ways of counting cells by fluorescence and graphing the results as a histogram, but I do know that histograms are supposed to be solid. If they are undercut by erosion or the ravages of termites (marked in red), something is wrong. It is also a problem if fine details are identical in what are purportedly independent experiments (marked in blue).

The pixels which were whittled away from the left-hand panel with the Eraser tool show up as black, after black / white reversing the right-hand panel and superimposing it on the former (everything else cancels out). This is MS Paint work, not even Photoshop! This clumsy, lazy falsification is a slap in the face for honest hard-working data forgers who take pride in their workmanship.

Here are earlier examples of white-anted overhanging histograms, from Fig 4A of [8] at left, while the outlined examples at right (from Figure 2 of [9]) are riddled with glitches, like free software:

In fact these are snapshots in the process of carving cell-count histograms from scratch. They are like scenes from the creation of a sculpture or a painting, like watching Giaocometti scraping away the clay or pigment he had added in an earlier stage in the cycle. Now [8] still centred on mango juice, while [9] focused on the cancer-preventing powers of garlic… but an overlay of these supposedly-separate data sets shows the sections of perimeter which were not re-worked, and leaves one to wonder if there were any original data measurements at all.

One last example before we move on. In contrast to the toppling minarets in Fig. 4A of [8], what renders 4B risible are similarities among its panels, where only a few pixels were scraped from one and added to another.

When we turn from to Figure 2 of [10], which at least still hoes the row of mango-juice cancer prevention (even though its protective powers are extended over mouse liver cells, rather than lymph node carcinoma of the prostate), it is not too great a surprise to encounter find cell-count plots that are outlined but superimposable.

In contrast to histogrammed cell counts, flow-cytometry plots (FACS) measure two fluorescent indicators of each cell’s status and use them as coordinates to plot each cell as a point in two dimensions. They feature prominently in this body of work. They display a recurring quality of insufficient difference. Partial replications could arise when someone took a single file of data (recorded for one experimental condition) and ran it twice through different settings of the filter parameters… but also when someone modified a plot in Paint / Photoshop.

A good example is Figure 2 from a 2012 paper on the mutagenic mayhem wrought by Allethrin insecticide in the absence of mango protection. “Boeckella Robusta” wondered “could authors explain how the same dot plots were generated for different treatments in the indicated boxes?”

Indeed, in a superimposition of the Allethrin and Benz-α-pyrene panels, cancellation is complete across three quarters of the plane. There is a patch of white points unique to B-α-P treatment; an exact rectangle of discordant cells; and a zone of black/white pairs where cells were displaced en masse. The forger saw no need for anything sophisticated.

As for the Control panel, res ipsa loquitur.

Paper [1] from 2014 gave us the curative nano-pineapples. As “Notarius Cookei” noted, it also provides examples of FACS fakery. Here I choose Figures 6(G) and 6(H), and 9(F) and 9(H).

“When 99% of cells are identical in both plots, the most parsimonious explanation is that both plots used the same data.”

I skip over other examples in my haste to reach the delirious heights of [12] and [13]. These companion papers from 2007 and 2008 fed ginger and mangos respectively through the juicer, but the authors liked the FACS plots so much that they used them in both.

Then someone customised and enhanced each version, cloning clusters of points with all the enthusiasm of a child who has just been introduced to the artistic possibilities of the potato-stamp medium. Figures 5(B) of [12] and 4(C) of [13] should be enlarged to appreciate their plenitude.

imgur-gwlespa.png

Another spurt of potato-stamp creativity occurred in 2011, in the panels of Figure 6 of [14]. The prospect of inhibiting the growth of skin tumours (in mice) with a synergistic combination of grape-skins and black tea evidently distracted the reviewers’ attentions from the crystalline alignment of the FACS plots.

shukla1

It also emerged that garlic and pomegranates, together, exerted exactly the same inhibition, resulting in a companion paper [15]. I do not rate for this recipe.

A lot of work went into these constructions, possibly more than simply conducting an experiment would require, so one can understand the authors’ decision to repeat them across papers. Suffice to say that the cloning tool contributed to Figure 6 of [15].

Regrettably, [14] was retracted in April for a number of reasons (not just Figure 6). The world of science was thereby deprived of a row of hot-dogs comprising the ERK1/2 band of Figure 2.

These provide a segue to the inevitable Western-blot discussion. For this body of work has its fair share of gel bands with acrobatic talents, somersaulting and stretching and reflecting as they re-identify from one Protean protein to another (and from one paper to another). Figures 3, 4 and 6 from [16]:

somersaults

The next somersaults are lane-specific and require more skill. At left, Apaf 1 (from Fig 5B of [4]) becomes Cytochrome C (in Fig 3(d) of [17]). At right, p21/ras (from 2(b) of [18]) becomes AKT (in Fig 5(b) of [17])!

At one end of the spectrum of manipulation, blots might be repeated in successive figures with different labels, relying on the incuriosity of readers and reviewers. At the other extreme, they are cut up and reassembled like letters in a ransom note. Here from [19] to [20].

All this is for substantive protein measurements. The normalising controls fare no better. As interest in Shukla’s productions grew, ‘Orophea Enterocarpa‘ identified a small but hard-working repertoire of loading controls. The ‘bubble and hairline’ control, for instance, first spotted in 2004 with five lanes for five experimental levels of garlic [21], has at least nine recorded sightings, sometimes cut down to four lanes or extended to six with a lane duplication to meet the details of the study design. These lanes corresponded to dosage of tea [22, 24], mango / lupeol [8, 10], grape-skins [4, 17, 23] and pineapple [19]. In its most recent appearance (2010) it widened to an eight-lane Interstate highway.

hairline
The “scrolls” were another hard-worked loading-control panel with five sightings [8, 12, 17, 18, 22]. Sadly, there is not space to show the “inchworm” panel, or the “dotted dashes“, or the “Nike Swoosh“, or even the “dashes-and-dots” in their four- and eight-lane incarnations.

scrolls

My favourite in this little genre began in 2008 as Fig 3(A) of [4], holding sway over six variants of grape-skin therapy. It reappeared as a four-lane version as Fig 1(B) of [20], a pineapple study (other panels of 1(B) also repay attention); and in Fig 3 of [19]. Pay attention to the third (or first) lane: for greater standardisation, it was quadruplicated in another 2009 loading control [23].

hedgehogs

While back where we started, [4] also starred Fig 6(B), the “hedgehog promenade”. This proves to be another version of that single lane lane from 3(A), now multiplied six-fold and stretched vertically.

bandsAdmittedly, not everyone agrees on the necessity for dose-equalising controls. Between publication of [4] in 2008 and an amendment in 2016, it had featured Figs 3(B) and 5, in which five-lane letterbox panels of β-actin sufficed to normalise a series of six-lane blots of interest. Either the readers and reviewers and editors couldn’t count or they didn’t care.

Recall the point of compass-coded blotting methods: to quantify the protein expression within cells under specific conditions, by a circuitous but precise route (extracting cell contents and separating the proteins by racing them along an electrophoresis-gel racetrack or Proteodrome, then labelling them with antibodies so as to measure total antibody density). Now it is always possible that researchers did measure all the numbers they tabulate and analyse, producing blots in the process with which they could have illustrated their reports, and they only decide to fabricate the illustrations (or repurpose old ones) because of the artistic challenge.

After all this, there is a sense of relief to be had from meeting plain microphotographs of vat-grown tumour cells from the A549 cell-line, rendered fluorescent by different treatment with black tea polyphenols [16]. Or perhaps they hailed from the HeLa and SiHa cell-lines [25].

I had originally hoped to show some Northern blots of RNA expression (Caspase-3 becomes iκBα); or perhaps some DNA fragmentation assays, which display a lapidary, mosaic nature when closely examined. But this report is long enough. I must be content with this loading control from [19], which reminds me (when the lightness is turned up) of a row of caddis-fly larvae.

Now I am not alleging retouching or Photoshop manipulations, but there are two images of Dr Yogeshwer Shukla on the Intertubes. The version shown on his staff page at the CSIR-Indian Institute of Toxicology Research website has changed a lot from the version on his ResearchGate account.

If this is the effect of pineapple or mango or grape-skin treatment, he is his own best advertisement for his discoveries.

[1] Priyanka Bhatnagar, Soma Patnaik, Amit K. Srivastava, Mohan K. R. Mudiam, Yogeshwer Shukla, Amulya K. Panda, Aditya B. Pant, Pradeep Kumar, Kailash C. Gupta

Anti-Cancer Activity of Bromelain Nanoparticles by Oral Administration

Journal of Biomedical Nanotechnology (2014) doi: 10.1166/jbn.2014.1997

https://pubpeer.com/publications/D7569FE3179E5C77F10CD7D0CAFF1C

[2] Priyanka Bhatnagar, Manisha Kumari, Richa Pahuja, A. B. Pant, Y. Shukla, Pradeep Kumar, K. C. Gupta

Hyaluronic acid-grafted PLGA nanoparticles for the sustained delivery of berberine chloride for an efficient suppression of Ehrlich ascites tumors

Drug Delivery and Translational Research (2018) doi: 10.1007/s13346-018-0485-9 

https://pubpeer.com/publications/17D26A485788CD2B46B52781D8DD50

[3] Radhika Kapoor, Shruti Singh, Madhulika Tripathi, Priyanka Bhatnagar, Poonam Kakkar, Kailash Chand Gupta

O-hexadecyl-dextran entrapped berberine nanoparticles abrogate high glucose stress induced apoptosis in primary rat hepatocytes

PLoS ONE (2014)   doi: 10.1371/journal.pone.0089124 

https://pubpeer.com/publications/012D4D634C827AE2183864F22FD1A0

[4] Neetu Kalra, Preeti Roy, Sahdeo Prasad, Yogeshwer Shukla

Resveratrol induces apoptosis involving mitochondrial pathways in mouse skin tumorigenesis

Life Sciences (2008) doi: 10.1016/j.lfs.2007.11.006

https://pubpeer.com/publications/4197501DBC472982247DE0AFA234E3

[5] Jasmine George, Yogeshwer Shukla

Early changes in proteome levels upon acute deltamethrin exposure in mammalian skin system associated with its neoplastic transformation potential

Journal of Toxicological Sciences (2013)

https://pubpeer.com/publications/F65D2C5FFC638303800927B2E28661

[6] Jasmine George, Amit Kumar Srivastava, Richa Singh, Yogeshwer Shukla

Cypermethrin exposure leads to regulation of proteins expression involved in neoplastic transformation in mouse skin

Proteomics (2011) doi: 10.1002/pmic.201100233 

https://pubpeer.com/publications/A384A6D53974AF627FC83477C2D43E

[7] Amit Kumar Srivastava, Sanjay Mishra, Wahid Ali, Yogeshwer Shukla

Protective effects of lupeol against mancozeb-induced genotoxicity in cultured human lymphocytes

Phytomedicine (2016) doi: 10.1016/j.phymed.2016.03.010 

https://pubpeer.com/publications/5AA6712082CCC91EEE90C4C5196BFE

[8] Sahdeo Prasad, Neetu Kalra, Yogeshwer Shukla

Induction of apoptosis by lupeol and mango extract in mouse prostate and LNCaP cells

Nutrition & Cancer (2007) doi: 10.1080/01635580701613772 

https://pubpeer.com/publications/5316531EB262091B243859A00C0137

[9] S Prasad, N Kalra, S Srivastava, Y Shukla

Regulation of oxidative stress–mediated apoptosis by diallyl sulfide in DMBA-exposed Swiss mice

Human & Experimental Toxicology (2008) doi: 10.1177/0960327108088978 

https://pubpeer.com/publications/92E0808D22F88CCD9F6CB46ACC36A8

[10] Sahdeo Prasad, Neetu Kalra, Yogeshwer Shukla

Hepatoprotective effects of lupeol and mango pulp extract of carcinogen induced alteration in Swiss albino mice

Molecular Nutrition & Food Research (2007) doi: 10.1002/mnfr.200600113

https://pubpeer.com/publications/76E17585B48AC0B38E498B5EC23054

[11] Amit Kumar Srivastava, Pramod Kumar Srivastava, Abdulaziz A. Al-Khedhairy, Javed Musarrat, Yogeshwer Shukla

Allethrin-induced genotoxicity and oxidative stress in Swiss albino mice

Mutation Res/Fund Mol Mech Mutagenesis (2012) doi: 10.1016/j.mrgentox.2012.03.003

https://pubpeer.com/publications/3D8F9A166D74AE68A779582773B7AD

[12] Yogeshwer Shukla, Sahdeo Prasad, Chitra Tripathi, Madhulika Singh, Jasmine George, Neetu Kalra

In vitro and in vivo modulation of testosterone mediated alterations in apoptosis related proteins by [6]-gingerol

Molecular Nutrition & Food Research (2007) doi: 10.1002/mnfr.200700197

https://pubpeer.com/publications/F9BEECCBE9F74B9796BFA11F079FF9

[13] Sahdeo Prasad, Nidhi Nigam, Neetu Kalra, Yogeshwer Shukla

Regulation of signaling pathways involved in lupeol induced inhibition of proliferation and induction of apoptosis in human prostate cancer cells

Molecular Carcinogenesis (2008)   doi: 10.1002/mc.20442

https://pubpeer.com/publications/977BFB109F38955F21E8259D74F9C0

[14] RETRACTED: Jasmine George, Madhulika Singh, Amit Kumar Srivastava, Kulpreet Bhui, Preeti Roy, Pranav Kumar Chaturvedi, Yogeshwer Shukla

Resveratrol and black tea polyphenol combination synergistically suppress mouse skin tumors growth by inhibition of activated MAPKs and p53

PLoS ONE (2011) doi: 10.1371/journal.pone.0023395

https://pubpeer.com/publications/1ADC5417FEF462F17636A43498D670

[15] Jasmine George, Madhulika Singh, Amit Kumar Srivastava, Kulpreet Bhui, Yogeshwer Shukla

Synergistic growth inhibition of mouse skin tumors by pomegranate fruit extract and diallyl sulfide: evidence for inhibition of activated MAPKs/NF-κB and reduced cell proliferation

Food & Chemical Toxicology (2011) doi: 10.1016/j.fct.2011.03.040

https://pubpeer.com/publications/4A46821594EB7EB392F5A9BB471E5A

[16] Madhulika Singh, Kulpreet Bhui, Richa Singh, Yogeshwer Shukla

Tea polyphenols enhance cisplatin chemosensitivity in cervical cancer cells via induction of apoptosis

Life Sciences (2013) doi: 10.1016/j.lfs.2013.02.001

https://pubpeer.com/publications/8BC7D198B330260105915A17A97BE7

[17] Preeti Roy, Neetu Kalra, Sahdeo Prasad, Jasmine George, Yogeshwer Shukla

Chemopreventive potential of resveratrol in mouse skin tumors through regulation of mitochondrial and PI3K/AKT signaling pathways

Pharmaceutical Research (2009) doi: 10.1007/s11095-008-9723-z

https://pubpeer.com/publications/850796C5228A56DF71E8D4E4601C87

[18] Annu Arora, Neetu Kalra, Yogeshwer Shukla

Regulation of p21/ras protein expression by diallyl sulfide in DMBA induced neoplastic changes in mouse skin

Cancer Letters (2006) doi: 10.1016/j.canlet.2005.10.049 

https://pubpeer.com/publications/A5216BB8F4E05BB3A05E274F56618B

[19] Neetu Kalra, Kulpreet Bhui, Preeti Roy, Smita Srivastava, Jasmine George, Sahdeo Prasad, Yogeshwer Shukla

Regulation of p53, nuclear factor kappaB and cyclooxygenase-2 expression by bromelain through targeting mitogen-activated protein kinase pathway in mouse skin

Toxicology and Applied Pharmacology (2008) doi: 10.1016/j.taap.2007.08.012 

https://pubpeer.com/publications/4A3803831AE2603C9276ADB9750A85

[20] Kulpreet Bhui, Sahdeo Prasad, Jasmine George, Yogeshwer Shukla

Bromelain inhibits COX-2 expression by blocking the activation of MAPK regulated NF-kappa B against skin tumor-initiation triggering mitochondrial death pathway

Cancer Letters (2009) doi: 10.1016/j.canlet.2009.03.003 

https://pubpeer.com/publications/19913878F1C75788FE95D3FD1FCADE

[21] Annu Arora, Imtiaz A Siddiqui, Yogeshwer Shukla

Modulation of p53 in 7,12-dimethylbenz[a]anthracene-induced skin tumors by diallyl sulfide in Swiss albino mice

Molecular Cancer Therapeutics (2004)

https://pubpeer.com/publications/2DE54FD49EB1CAE22A11E768845A2C

[22] RETRACTED: Neetu Kalra, Kavita Seth, Sahdeo Prasad, Madhulika Singh, Aditya B. Pant, Yogeshwer Shukla

Theaflavins induced apoptosis of LNCaP cells is mediated through induction of p53, down-regulation of NF-kappa B and mitogen-activated protein kinases pathways

Life Sciences (2007) doi: 10.1016/j.lfs.2007.04.009 

https://pubpeer.com/publications/916B9A4E38D79FAF24E97FFB891AC8

[23] Preeti Roy, Esha Madan, Neetu Kalra, Nidhi Nigam, Jasmine George, Ratan Singh Ray, Rajendra K Hans, Sahdeo Prasad, Yogeshwer Shukla

Resveratrol enhances ultraviolet B-induced cell death through nuclear factor-kappaB pathway in human epidermoid carcinoma A431 cells

Biochem & Biophys Research Comm (2009) doi: 10.1016/j.bbrc.2009.04.100

https://pubpeer.com/publications/D9903CAA6326AC41B3A998B45FDFD7

[24] Preeti Roy, Nidhi Nigam, Madhulika Singh, Jasmine George, Smita Srivastava, Hasnain Naqvi, Yogeshwer Shukla

Tea polyphenols inhibit cyclooxygenase-2 expression and block activation of nuclear factor-kappa B and Akt in diethylnitrosoamine induced lung tumors in Swiss mice

Investigational New Drugs (2010) doi: 10.1007/s10637-009-9274-0 

https://pubpeer.com/publications/202F3FCC1C55B94992B036E1761395

[25] Madhulika Singh, Priyanka Bhatnagar, Sanjay Mishra, Pradeep Kumar, Yogeshwer Shukla, Kailash Chand Gupta

PLGA-encapsulated tea polyphenols enhance the chemotherapeutic efficacy of cisplatin against human cancer cells and mice bearing Ehrlich ascites carcinoma

International Journal of Nanomedicine (2015) doi: 10.2147/ijn.s79489

https://pubpeer.com/publications/90ECC2BE7345B133B7E876E34801FB

shukla-dream.png


 

 

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35 comments on “Yogeshwer Shukla’s toxic career of Ayurvedic infusions

  1. Smut Clyde

    An out-take: “Mancozeb-induced genotoxicity and apoptosis in cultured human lymphocytes”
    Life Sciences (2012) doi: 10.1016/j.lfs.2011.12.013
    https://pubpeer.com/publications/671AA7F0A525DA4151A909C5ED93C1

    Contains lots of FACS goodness, and as noted by ‘Delphinium Cuneatum’, there’s a somersault connection to [20].

    “Figure 6 (caspase 9 blot) is more similar than one would expect with figure 5 (total ERK1/2) of a previous paper from this group. The same blot with two different exposures appears to have been used after changing the orientation as illustrated below.”

    Like

  2. Smut Clyde

    Must credit Didymella Curtisii!
    “Reversal of P-glycoprotein-mediated multidrug resistance by diallyl sulfide in K562 leukemic cells and in mouse liver”.
    Carcinogenesis (2004) – doi: 10.1093/carcin/bgh060
    https://pubpeer.com/publications/ECB93B72B59D541AAD2A7660F2DF7D


    Like

  3. Zebedee

    Could you put me through to Yogeshwer Shukla?
    This is Chitra Mandal, CSIR – Indian Institute of Chemical biology, Kolkata, calling.
    I have some important data to dicuss.

    https://iicb.res.in/faculty/chitra-mandal

    https://pubpeer.com/search?q=chitra+mandal

    Like

  4. Smut Clyde

    The ‘bubble and hairline’ control, for instance, first spotted in 2004 with five lanes for five experimental levels of garlic [21]

    Whoops, up to 11 sightings already!
    Kalra et al (2006) – more garlic: https://pubpeer.com/publications/8123113071476EBDEF55EDEE231182

    Madan et al (2008) – grapeskins again. https://pubpeer.com/publications/15094E64ADDFEDF790E810B4E056EA

    Like

  5. Pingback: With 73 problematic papers listed on Pubpeer, Indian Institute of Toxicology Research has a serious problem – Science Chronicle

  6. Pingback: Topi con il mal di pancia - Ocasapiens - Blog - Repubblica.it

  7. Smut Clyde

    A few more hand-crafted FACS histograms that were left out in the sun and started to melt:

    Figures 2(B, C) from [22].

    Like

  8. Pingback: Weekly Digest, June 1, 2019 – Science Integrity Digest

  9. Zebedee

    “After that he ascended to the MD Anderson Cancer Center (University of Texas) to work with Bharat Aggarwal and co-author a string of papers, later retracted because the amount of fabrication in them exceeded editorial tolerance.”

    Slightly worrying.
    https://nccih.nih.gov/health/ayurveda/introduction.htm#hed4

    “Is Ayurvedic Medicine Safe?
    Some Ayurvedic preparations may contain lead, mercury, or arsenic in amounts that can be toxic.

    Is Ayurvedic Medicine Effective?
    A few studies suggest that Ayurvedic preparations may reduce pain and increase function in people with osteoarthritis and help manage symptoms in people with type 2 diabetes, but most of these trials are small or not well-designed. There is little scientific evidence on Ayurveda’s value for other health issues.

    Yet,
    NCCIH-Funded Research
    NCCIH is funding research that:

    Builds on earlier investigations in breast cancer survivors that found a positive effect of integrated Ayurvedic medicine on improved quality of life; new research will evaluate ways to make this intervention easier to incorporate into peoples’ lives. The proposed Ayurvedic intervention includes diet, lifestyle, yoga, and pressure point treatment.
    Studies the mechanism by which an extract from Butea monosperma (BME) flowers may protect against joint destruction from osteoarthritis (BME is widely used in Ayurveda for arthritis and other inflammatory diseases in India).

    There is no significant regulation of Ayurvedic practice or education in the United States, and no state requires a practitioner to have a license. For more information on credentialing complementary health practitioners, see the NCCIH fact sheet Credentialing, Licensing, and Education.

    Other References

    Darvesh AS, Aggarwal BB, Bishayee A. Curcumin and liver cancer: a review. Current Pharmaceutical Biotechnology. 2012;13(1):218-228.

    This page last modified January 14, 2019”

    Is the NIH gormless, or just behind the times?Ofentimes several blocks behind the perps.

    http://retractiondatabase.org/RetractionSearch.aspx?AspxAutoDetectCookieSupport=1#?AspxAutoDetectCookieSupport%3d1%26auth%3dAggarwal%252c%2bBharat%2bB

    Like

    • Smut Clyde

      Is the NIH gormless, or just behind the times?

      You have to remember that the NCCIH was established specifically to serve the needs of supplement peddlers and Alt-Med scammers, and tasked with finding evidence to support Alt-Med claims, whatever level of mendacity that might require.

      “Ayurvedic treatment combines products (mainly derived from plants, but may also include animal, metal, and mineral), diet, exercise, and lifestyle.”

      It would be more accurate and perhaps less tendentious if they wrote “Ayurvedic treatment combines whatever crap a given ayurvedic scammer happens to be selling”. There is no single coherent scholium of thought… just a loose bundle of different traditions of medieval superstition. The toxic-metal alchemy aspect is pretty pervasive, though (not just “may include”).

      This compels the ideologues, apologists and more dedicated fraudsters to explain that the Ayurvedic processing of arsenic (and lead, mercury, cadmium, whatever) performs an Alchemical transformation so that they are no longer toxic: https://www.npr.org/sections/health-shots/2015/07/31/428016419/toxic-lead-contaminates-some-traditional-ayurvedic-medicines

      These bhasmas are put through a complicated process sometimes involving goat’s urine or other acidic liquids that are said to detoxify heavy metals. In an email, Ayurveda scientist Kalpana Joshi at the University of Pune in India says Western scientists might have a lack of understanding about this process. “I do understand the skepticism of Western doctors. I believe adverse effects [experienced by patients] are due to not following right Ayurvedic methods and faulty shortcuts for large scale productions,” she writes.

      In recent years, scientists like Joshi have been trying to use Western scientific method approaches to validate Ayurvedic claims. “Rasa sindur is a mercury preparation, and papers have proved it to be safe, nontoxic and improving life-span in fly models,” Joshi writes.

      There are no adverse effects, and when there are, it wasn’t really Ayurveda.

      Like

  10. Pingback: CSIR-IITR case is being investigated speedily: CSIR Director-General Shekhar Mande – Science Chronicle

  11. Zebedee

    “Shukla, who probably will proclaim resveratrol’s antioxidative powers even after his 5th bottle of red wine, also used to be the General Secretary of Environmental Mutagen Society of India and the Indian Society of Toxicology.”

    Shukla is only following tradition. Not such an old one, but a tradition nevertheless.

    http://retractionwatch.com/2012/01/11/uconn-resveratrol-researcher-dipak-das-fingered-in-sweeping-misconduct-case/

    “One area of interest for Das, a government-funded professor of surgery and director of the Cardiovascular Research Center, has been resveratrol, a substance in red wine that has allegedly been linked to improved cardiac health.”

    https://retractionwatch.com/2014/03/27/late-resveratrol-researcher-dipak-das-up-to-20-retractions/

    http://retractiondatabase.org/RetractionSearch.aspx#?auth%3dDas%252c%2bDipak%2bK
    .

    Like

  12. Leuk Res. 2010 Apr;34(4):463-70. doi: 10.1016/j.leukres.2009.07.042. Epub 2009 Aug 25.
    4 comments on PubPeer (by: Unregistered Submission, Peer 1, Peer 3)

    Elevated mRNA level of hST6Gal I and hST3Gal V positively correlates with the high risk of pediatric acute leukemia.
    Mondal S1, Chandra S, Mandal C.
    Author information
    1
    Infectious Diseases and Immunology Division, Indian Institute of Chemical Biology, An Unit of Council of Scientific and Industrial Research, Govt of India, 4 Raja SC Mullick Road, Kolkata 700032, India.

    Already has this at Pubpeer: https://pubpeer.com/publications/46E0DEB435501F731F2DCA48A462C9#2

    Figure 4(A) is also problematic.

    Like

    • Smut Clyde

      Problematic? You think so?

      Like

      • Yeah! Problematic.
        Rightmost two lanes are from different leukemias (B-ALL and T-ALL) so should be different samples.
        Odd that many features in those lanes are very similar.
        I did notice the rectangular defect and the vertical defect in the lanes to the left of those, but image duplication is the most difficult to explain away.

        Like

  13. Pingback: De coccio - Ocasapiens - Blog - Repubblica.it

  14. 5 retractions: https://www.ncbi.nlm.nih.gov/pubmed/?term=shukla%20y%20retracted

    RETRACTED: Tea polyphenols enhance cisplatin chemosensitivity in cervical cancer cells via induction of apoptosis.
    Singh M, Bhui K, Singh R, Shukla Y.
    Life Sci. 2013 Jul 19;93(1):7-16. doi: 10.1016/j.lfs.2013.02.001. Epub 2013 Feb 9. Erratum in: Life Sci. 2019 Aug 19;:116690.
    PMID: 23399702
    Resveratrol and black tea polyphenol combination synergistically suppress mouse skin tumors growth by inhibition of activated MAPKs and p53.
    George J, Singh M, Srivastava AK, Bhui K, Roy P, Chaturvedi PK, Shukla Y.
    PLoS One. 2011;6(8):e23395. doi: 10.1371/journal.pone.0023395. Epub 2011 Aug 26. Retraction in: PLoS One. 2019 Apr 19;14(4):e0215980.
    PMID: 21887248
    Role of senescence and mitotic catastrophe in cancer therapy.
    Singh R, George J, Shukla Y.
    Cell Div. 2010 Jan 21;5:4. doi: 10.1186/1747-1028-5-4. Retraction in: Cell Div. 2012;7:15.
    PMID: 20205872
    RETRACTED: Resveratrol induces apoptosis involving mitochondrial pathways in mouse skin tumorigenesis.
    Kalra N, Roy P, Prasad S, Shukla Y.
    Life Sci. 2008 Feb 13;82(7-8):348-58. doi: 10.1016/j.lfs.2007.11.006. Epub 2007 Nov 28. Erratum in: Life Sci. 2019 Aug 19;:116691. Retraction in: Life Sci. 2016 Jul 15;157:107.
    PMID: 18201729
    Theaflavins induced apoptosis of LNCaP cells is mediated through induction of p53, down-regulation of NF-kappa B and mitogen-activated protein kinases pathways.
    Kalra N, Seth K, Prasad S, Singh M, Pant AB, Shukla Y.
    Life Sci. 2007 May 16;80(23):2137-2146. doi: 10.1016/j.lfs.2007.04.009. Epub 2007 Apr 21. Retraction in: Life Sci. 2019 Feb 15;219:364.
    PMID: 17499812

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  15. Large swathes of the western middle-class lap this stuff up. I think that the word “ayurvedic” really helps the scammers. Difficult to pronounce and difficult to spell. Once you say this word you are under its spell, which is what ayurvedic medicine is about.

    Like

  16. Smut Clyde

    Recent correction for “Inhibitory effects of tea polyphenols by targeting cyclooxygenase-2 through regulation of nuclear factor kappa B, Akt and p53 in rat mammary tumors” (Preeti Roy , Jasmine George , Smita Srivastava , Shilpa Tyagi , Yogeshwer Shukla; Investigational New Drugs, 2011).
    https://pubpeer.com/publications/309118EE39149EF7FDAB4E323994A1

    “The authors regret to inform that there were unknowing errors in figures. The corrected images are given below. These figures are not affecting the results and conclusion of the manuscript. Hence, the text in original paper remains unchanged.”

    “Unknowing errors”.

    Like

  17. https://thewire.in/the-sciences/csir-says-its-probing-scientific-misconduct-allegations-drafting-new-guidelines

    “one common name on 49 of the articles was Yogeshwer Shukla, IITR’s chief scientist of food, drug and chemical toxicology. Shukla is a senior scientist, and has claimed to have cured cancer in mice using nano-encapsulated elements from plants with Ayurvedic relevance. Several of these claims, however, are now under question due to image manipulation.”

    Like

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