PReD-Bench/PRed-Bench huggingface dataset:
<p>lncRNA MALAT1 modulates oxaliplatin resistance of gastric cancer via sponging miR-22-3p</p>
Authors: Ming Li
Zhenming Zhang
Zhitao Zhang
Journal: OncoTargets and Therapy (2020)
Discipline: CLINICAL MEDICINE
Keywords: GC; MALAT1/miR-22-3p/ZFP91; cell progression; oxaliplatin.
Affiliations: Department II of General Surgery, Zhangye People's Hospital Affiliated to Hexi University, Zhangye, Gansu, China., Department of Oncology, Zhangye People's Hospital Affiliated to Hexi University, Zhangye, Gansu, China.

Abstract:  Objective: Various regulatory mechanisms have been demonstrated to be associated with cancer progression. ncRNA and mRNA play important roles in gastric cancer (GC) cell growth and drug resistance, respectively. However, the regulatory network of ncRNA and mRNA in GC oxaliplatin (OXA) resistance has not been fully clarified. Methods: The expression of miR-22-3p, MALAT1, and zinc finger protein 91 (ZFP91) was detected in tissues and cells using quantitative real-time PCR. The protein level of ZFP91 was measured by Western blot analysis. Luciferase reporter, pull-down, and RNA immunoprecipitation assays were used to determine the relationship between MALAT1, miR-22-3p, and ZFP91. MTT assay was applied to measure cell survival and proliferation. Cell apoptosis was detected using flow cytometry. Tumor xenograft assay was used to detect the function of miR-22-3p in vivo. Results: In this study, we found that MALAT1 and ZFP91 expression was upregulated while the expression of miR-22-3p was downregulated in GC/OXA tissues and cells. Additionally, miR-22-3p was a target miRNA of MALAT1 and ZFP91 was a target mRNA of miR-22-3p. Functional studies showed that the knockdown of MALAT1 or overexpression of miR-22-3p inhibited GC/OXA cell survival, proliferation, and drug resistance as well as induced apoptosis, which could be reversed by the inhibition of miR-22-3p or overexpression of ZFP91. Conclusion: We observed a new regulatory network for MALAT1 in drug resistance of GC. MALAT1 modulates ZFP91 to promote GC cells OXA resistance via sponging miR-22-3p. 

Retracted: No

PubPeer comments:
 This study in gastric cancer cells uses the cell lines uses the SGC-7901 BGC-823 cervical cancer cell lines for no apparent reason, despite labelling them as gastric cancer. Also there is a suspiciously high level of concordance between these lines in the experiments used. ,
Characterization of 4 TaGAST genes during spike development and seed germination and their response to exogenous phytohormones in common wheat
Authors: Jin Seok Yoon
Yun Jeong Kim
Min Jeong Hong
Dae Yeon Kim
Jae Yoon Kim
Yong Weon Seo
Journal: Molecular biology reports (2016)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Common wheat; Gibberellic acid-stimulated transcript gene; Spike development; TaCypA1; TaGASTs.
Affiliations: Division of Biotechnology, Korea University, Anam-Dong, Seongbuk-Gu, Seoul, 136-713, Republic of Korea., Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, 29 Geumgu, Jeongeup, 580-185, Republic of Korea., Division of Biotechnology, Korea University, Anam-Dong, Seongbuk-Gu, Seoul, 136-713, Republic of Korea. .

Abstract:  Gibberellic acid (GA) is involved in the regulation of plant growth and development. We defined GA-stimulated transcript (GAST) gene family and characterized its four members (TaGAST1, 2, 3, and 4) in wheat spikes. Triticum aestivum whole spikes were collected at ten developmental stages and dehulled spikelets were obtained at various days after flowering. Expression of TaGAST1, 2, 3, and 4 was analyzed using RT-PCR at inflorescence development stages, in different tissues, and after phytohormones application. To identify proteins interacting with TaGAST1, yeast two-hybridization was performed and BiFC analysis was used for verification. TaGAST1 was expressed at the inflorescence stage and only expressed in seedlings under abscisic acid (ABA) treatment after phytohormone treatment. TaGAST2 and TaGAST3 showed moderate expression in the spike, vigorous transcript accumulation in the seedling, and up-regulation by exogenous GA in early germination stages. TaGAST4 was predominantly expressed in the seedling. Wheat cyclophilin A-1 (TaCypA1), identified as a TaGAST1-interacting protein, showed opposite expression pattern in the developing spike to TaGAST1. TaCypA1 transcript was slightly up-regulated by GA, slightly down-regulated by paclobutrazol, and was maintained after ABA treatment. The interaction of TaGAST1 with TaCypA1 is targeted to the plasma membrane. TaGAST1 was specifically expressed in the wheat spike and was stimulated by exogenous GA treatment. TaGAST2 and TaGAST3 expression in germinating seeds and seedlings was higher than that in the spike stage. TaGAST4 was not expressed in all developmental stages. TaGAST1 and TaCypA1 might be expressed antagonistically during wheat spike development. 

Retracted: No

PubPeer comments:
 In supplementary Figure S3, the two regions highlighted in red are identical. One of them is rotated by 180 degrees. ![file] ,
Proteasome inhibitor sensitizes oral squamous cell carcinoma cells to TRAIL-mediated apoptosis
Authors: Sayaka Kurihara
Sayaka Yoshiba
Yuji Kurihara
Makiko Uchida
Hitoshi Watanabe
Masayasu Iwase
Satoru Shintani
Journal: Oncology Reports (2011)
Discipline: CLINICAL MEDICINE
Keywords: Oral squamous cell carcinoma; TRAIL-mediated apoptosis; proteasome inhibitor; MG132; HSC-2
Affiliations: Department of Oral and Maxillofacial Surgery, Showa University School of Dentistry, 2-1-1 Kitasenzoku, Ota-ku, Tokyo 145-8515, Japan. 

Abstract:  Oral squamous cell carcinoma (OSCC) cells are relatively resistant to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis during culture. We investigated the role of a proteaosome inhibitor in the survival and apoptosis of these cells. We found that the proteasome inhibitor MG132 markedly accelerated TRAIL-mediated apoptosis in OSCC cell lines HSC-2 and HSC-3. Addition of TRAIL to MG132-treated cells resulted in Bid cleavage. Furthermore, the inhibitors of caspase-3, caspase-8 and caspase-9 reduced the accelerative effect of MG132 on TRAIL-mediated apoptosis. These results suggest that the pro-apoptotic effect of a proteasome inhibitor on TRAIL-mediated apoptosis may contribute to both extrinsic and intrinsic pathways. MG132 enhanced the expression of the TRAIL receptors DR4 and DR5, and neutralization of DR5 receptors showed a marked reduction of TRAIL-mediated apoptosis, whereas that of DR4 was a partial reduction. MG132 also markedly reduced cellular FLICE-inhibitory protein (c-FLIP), cellular inhibitor of apoptosis protein-1 (cIAP-1), X-linked IAP (XIAP) and survivin. Therefore, MG132 provides partial regulation of TRAIL-mediated apoptosis in OSCC cells via modulation of DR5, c-FLIP, cIAP-1, XIAP and survivin. The proteasome inhibitor MG132 may therefore represent a novel strategy for overcoming resistance to TRAIL-mediated apoptosis in OSCC cells. 

Retracted: No

PubPeer comments:
 Figure 4: same actin control (red boxes) used for experiments with different cell types (HSC-2 and HSC-3). Blue box: likely itu2019s a typo and it should read ++. ![file] , 
 Dear Dr. Aneurus Inconstans Thank you for your new comments. Dr. Yoshiba was unaware of your comment. I let her know about your comment. Only she works in academia. I urged her to respond to your comments promptly. ,
Valproate improves middle cerebral artery occlusion-induced ischemic cerebral disorders in mice and oxygen-glucose deprivation-induced injuries in microglia by modulating RMRP/PI3K/Akt axis
Authors: Xuetang Li
Yuling Sui
Journal: Brain Research (2020)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Ischemia; PI3K; RMRP; Valproate.
Affiliations: Department of Pharmacy, Linyi Central Hospital, Linyi, China. Electronic address: ., Department of Pharmacy, Linyi Central Hospital, Linyi, China.

Abstract:  Valproate (VPA) is capable of attenuating ischemic stroke (IS)-related disorders in brain tissues. Long non-coding RNAs (lncRNAs) are involved in the progression of IS. In the current study, the role of lncRNA RMRP in the protective effects of VPA against IS was explored. Mice were subjected to middle cerebral artery occlusion (MCAO) model to induce IS injures and then were administrated with VPA. The effects of VPA on infarction area and apoptosis in brain tissues, and the RMRP-regulated PI3K/Akt signaling activity were detected. Thereafter, oxygen-glucose deprivation (OGD) BV-2 cells were used as the in vitro model to further explore the mechanism underlying VPA function. The administration of VPA reduced infarction area and suppressed apoptosis in brain tissues of MCAO mice. VPA also inhibited RMRP expression and activated PI3K/Akt signaling. In OGD BV-2 cells, the treatment of VPA increased viability and attenuated apoptosis, which was associated with the inhibition of RMRP and the activation of PI3K/Akt pathway. Moreover, the induced expression of RMRP blocked the anti-OGD function of VPA, indicating the key role of RMRP inhibition in the effects of VPA on nerve system. Collectively, VPA attenuated MCAO/OGD-induced disorders in mice and microglia. The effects were dependent on the inhibition of RMRP, which subsequently induced the activation of PI3K/Akt signaling. 

Retracted: No

PubPeer comments:
 Too heavy to be C57BL 6 mice. ![file] , 
 To add to the confusion, rats make an appearance in Figures 1 2. ![file] ![file] ,
Urinary Extracellular Vesicles Carrying Klotho Improve the Recovery of Renal Function in an Acute Tubular Injury Model
Authors: Laura J Niedernhofer
Cristina Grange
Jordi Molina
Cecilia Pastorino
Elli Papadimitriou
Paul D Robbins
Ryan O&#x27;Kelly
Veronica Dimuccio
Benedetta Bussolati
Giovanni Camussi
Journal: Molecular Therapy (2020)
Discipline: CLINICAL MEDICINE
Keywords: AKI; Klotho; damage; engineering; injury markers
Affiliations: Department of Medical Sciences, University of Turin, Turin, Italy., Department of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy., Institute on the Biology of Aging and Metabolism, Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota Medical School, Minneapolis, MN, USA., Department of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy. Electronic address: .

Abstract:  Acute kidney injury, defined by a rapid deterioration of renal function, is a common complication in hospitalized patients. Among the recent therapeutic options, the use of extracellular vesicles (EVs) is considered a promising strategy. Here we propose a possible therapeutic use of renal-derived EVs isolated from normal urine (urine-derived EVs [uEVs]) in a murine model of acute injury generated by glycerol injection. uEVs accelerated renal recovery, stimulating tubular cell proliferation, reducing the expression of inflammatory and injury markers, and restoring endogenous Klotho loss. When intravenously injected, labeled uEVs localized within injured kidneys and transferred their microRNA cargo. Moreover, uEVs contained the reno-protective Klotho molecule. Murine uEVs derived from Klotho null mice lost the reno-protective effect observed using murine EVs from wild-type mice. This was regained when Klotho-negative murine uEVs were reconstituted with recombinant Klotho. Similarly, ineffective fibroblast EVs acquired reno-protection when engineered with human recombinant Klotho. Our results reveal a novel potential use of uEVs as a new therapeutic strategy for acute kidney injury, highlighting the presence and role of the reno-protective factor Klotho. 

Retracted: No

PubPeer comments:
 Figure 2B appears to have a repeated image after flipping horizontally and vertically. *** ![file] , 
 We are deeply sorry for this gross mistake. During manuscript revision, we changed the order of the panels and the original figure of MSC-EVs was overlapped. We will contact the Editor for a possible replacement. We also here add the link to the complete original data set, containing all photos of the analyzed murine experiments https: www.dropbox.com sh ihshd7nu22h5rtu AADnKQCd4SXw3GSBOoYlA_vka?dl=0 Thank you for pointing out this problem, Sincerely Benedetta Bussolati , 
 #2 Thank you for responding and for sharing the original data in this fashion. In my (admittedly limited) experience, no other authors have responded as swiftly with this level of transparency. Much appreciated. , 
 Thank you for your kind reply, data sharing is simply part of the scientific method. Best Regards Benedetta ,
RP11‐81H3.2 promotes gastric cancer progression through miR‐339‐HNRNPA1 interaction network
Authors: Hai-Tao Shi
Lei Dong
Miao An
Shen-Hao Wang
Fen-Rong Chen
Yan Wang
Jun Zhang
Dong Liu
Yan Cheng
Su-Mei Sha
Journal: Cancer Medicine (2020)
Discipline: CLINICAL MEDICINE
Keywords: HNRNPA1; RP11-81H3.2; gastric cancer; miR-339; tumor metastasis.
Affiliations: Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Abstract:  Recent studies have demonstrated that various long non-coding RNAs (lncRNAs) participate in the gastric cancer (GC) development and metastasis. Some lncRNAs exert their regulatory function by interacting with microRNAs. Here we identified a novel lncRNA RP11-81H3.2 that was highly expressed in the GC tissue and cell lines. RP11-81H3.2 knockdown significantly inhibited the proliferation, migration, and invasion of GC cells. Mechanistically, we demonstrated that RP11-81H3.2 directly interacted with miR-339 while miR-339 regulated the HNRNPA1 expression by targeting HRRNPA1 3'-UTR. RP11-81H3.2-miR-339-HNRNPA1 interaction network regulated the GC cell proliferation, migration, and invasion. Moreover, our results confirmed that RP11-81H3.2 knockdown suppressed the tumor growth of GC in a xenograft model in vivo. In summary, the results suggest that RP11-81H3.2 functions as an oncogene in GC and could be utilized as a promising diagnosis and therapeutic marker for GC treatment. 

Retracted: No

PubPeer comments:
 Figure 4D * Red boxes: The top left and bottom left panel appear to show an area of overlap. ![file] , 
 Figure 4D got silently replaced with a corrected version without any notification to the reader. Old version left, new version right. ![file] , 
 Still, there are additional problems not yet addressed in this new version. * Green boxes: An additional potential area of overlap in Figure 4D (also present in new version) ![file] * Orange and pink boxes: potential overlaps in Figure 6C ![file] ,
Mybl2 expression is under genetic control and contributes to determine a hepatocellular carcinoma susceptible phenotype
Authors: Francesco Feo
Sara Ladu
Diego F Calvisi
Piero Bonelli
Maddalena Frau
Maria M Simile
Lucia Daino
Maria L Tomasi
Maria A Seddaiu
Rosa M Pascale
Journal: Journal of Hepatology (2011)
Discipline: CLINICAL MEDICINE
Keywords: MYBL2; hepatocellular carcinoma; cell proliferation; cell cycle regulation; gene expression
Affiliations: Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy.

Abstract:  Background &amp; aims: MYBL2 is implicated in human malignancies and over expressed in hepatocellular carcinoma (HCC). We investigated Mybl2 role in the acquisition of susceptibility to HCC and tumor progression. Methods: MYBL2 mRNA and protein levels were evaluated by quantitative RT-PCR and immunoblotting, respectively. MYBL2 expression in HCC cell lines was controlled through MYBL2 cDNA or anti-MYBL2 siRNA transfection. Gene expression profile of cells transfected with MYBL2 was analyzed by microarray. Results: Low induction of Mybl2 and its target Clusterin mRNAs, in low-grade dysplastic nodules (DN), progressively increased in fast growing high-grade DN and HCC of F344 rats, susceptible to hepatocarcinogenesis, whereas no/lower increases occurred in slow growing lesions of resistant BN rats. Highest Mybl2 protein activation, prevalently nuclear, occurred in F344 than BN lesions. Highest Mybl2, Clusterin, Cdc2, and Cyclin B1 expression occurred in fast progressing DN and HCC of E2f1 transgenics, compared to c-Myc transgenics, and anti-Mybl2 siRNA had highest anti-proliferative and apoptogenic effects in cell lines from HCC of E2f1 transgenics. MYBL2 transfected HepG2 and Huh7 cells exhibited increased cell proliferation and G1-S and G2-M cell cycle phases. The opposite occurred when MYBL2 was silenced by specific siRNA. MYBL2 transfection in Huh7 cells led to upregulation of genes involved in signal transduction, cell proliferation, cell motility, and downregulation of oncosuppressor and apoptogenic genes. Conclusions: mybl2 expression and activation are under genetic control. Mybl2 upregulation induces fast growth and progression of premalignant and malignant liver, through cell cycle deregulation and activation of genes and pathways related to tumor progression. 

Retracted: No

PubPeer comments:
 Figure 2 has what appear to be overlapping images when they should be different: ![file] ,
Unprofessional content on Facebook accounts of US urology residency graduates
Authors: E Ann Gormley
Kevin Koo
Zita Ficko
Journal: BJU international (2017)
Discipline: CLINICAL MEDICINE
Keywords: graduate medical education; professionalism; residency; social media; unprofessional behaviour.
Affiliations: Section of Urology, Department of Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA.

Abstract:  Objective: To characterize unprofessional content on public Facebook accounts of contemporary US urology residency graduates. Methods: Facebook was queried with the names of all urologists who graduated from US urology residency programmes in 2015 to identify publicly accessible profiles. Profiles were assessed for unprofessional or potentially objectionable content using a prospectively designed rubric, based on professionalism guidelines by the American Urological Association, the American Medical Association, and the Accreditation Council for Graduate Medical Education. Content authorship (self vs other) was determined, and profiles were reviewed for self-identification as a urologist. Results: Of 281 graduates, 223 (79%) were men and 267 (95%) held MD degrees. A total of 201 graduates (72%) had publicly identifiable Facebook profiles. Of these, 80 profiles (40%) included unprofessional or potentially objectionable content, including 27 profiles (13%) reflecting explicitly unprofessional behaviour, such as depictions of intoxication, uncensored profanity, unlawful behaviour, and confidential patient information. When unprofessional content was found, the content was self-authored in 82% of categories. Among 85 graduates (42%) who self-identified as a urologist on social media, nearly half contained concerning content. No differences in content were found between men and women, MD and DO degree-holders, or those who did or did not identify as a urologist (all P &gt; 0.05). Conclusion: The majority of recent residency graduates had publicly accessible Facebook profiles, and a substantial proportion contained self-authored unprofessional content. Of those identifying as urologists on Facebook, approximately half violated published professionalism guidelines. Greater awareness of trainees' online identities is needed. 

Retracted: No

PubPeer comments:
 Some odd choices of Reference have been made. It is not obvious how [1-6] relate to energy .  With the rapid development of the world economy and the sustained rising population of humans, the demand for energy is increasingly prominent and environmental pollution is becoming a serious problem [1-6]. ![file] ,
A novel transdermal nanoethosomal gel of betahistine dihydrochloride for weight gain control: in-vitro and in-vivo characterization
Authors: Adel Ahmed Ali
Ahmed Sg Srag El-Din
Abdelkhalk Ali Halawa
Shahira F El-Menshawe
Journal: Drug Design Development and Therapy (2017)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Box–Behnken design; neural histamine; obesity; pharmacodynamics; regression modeling.
Affiliations: Department of Pharmaceutics and Industrial Pharmacy, Beni-Suef University, Beni-Suef., Department of Pharmaceutics and Clinical Pharmacy, Nahda University, Beni-Suef, Egypt.

Abstract:  Background: Betahistine dihydrochloride (BDH) is a histamine analog used to control weight gain, with short elimination half-life and gastric irritation as side effects. Objective: The aim of the current investigation is to formulate and optimize a topical BDH ethosomal gel for weight gain control. Materials and methods: Box-Behnken design was applied to study the effect of independent variables: phosphatidylcholine (PC), propylene glycol (PG), and ethanol on vesicle size; entrapment efficiency; % drug release; and flux. The morphology and zeta potential of the optimized formulation were evaluated. The % drug release, flux, and pharmacodynamics of the optimized formulation gel were studied. Results: The size and entrapment efficiency percent had a direct positive relationship with the concentration of PC and negative relationship with ethanol and PG. The % drug release and flux decreased with increasing PC and PG, while ethanol enhanced both responses. Regression modeling indicated a good correlation between dependent and independent variables, where F16 was chosen as the optimized formulation. F16 showed well-defined spherical vesicles and zeta potential of -24 mV, and % release from the gel exceeded 99.5% over 16 h with the flux of 0.28 mg/cm2/h. Food intake and weight gain of rats were significantly decreased after transdermal application of the BDH ethosomal gel when compared with control, placebo, and BDH gel. The histopathological findings proved the absence of inflammation and decrease in adipose tissue. Conclusion: Results obtained showed a significant, sustained transdermal absorption of BDH ethosomal gel and, consequently, a decrease in food intake and weight gain. 

Retracted: No

PubPeer comments:
 Two images in Figure 7 appear to be images of the same sample, although described differently. Also the magnification may be different although the scale bars appear to be the same. *** ![file] ,
MiR-137 functions as a tumor suppressor in pancreatic cancer by targeting MRGBP
Authors: Ning Cui
Yanxia Li
Shuang Zhang
Feng Ding
Qiu Zhao
Jian Shang
Shaoyang Gao
Journal: Journal of Cellular Biochemistry (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: MRGBP; apoptosis; miR-137; pancreatic cancer (PanCa); proliferation.
Affiliations: Department of Gastroenterology/Hepatology, ZhongNan Hospital of Wuhan University, Wuhan, China., The Hubei Clinical Center & Key Laboratory of Intestinal & Colorectal Diseases, Wuhan, China., Laboratory of Clinical Immunology, Wuhan No.1 Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China., Department of Pathology, Hubei Cancer Hospital, Wuhan, China., Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China.

Abstract:  miRNAs are small noncoding RNAs that act as critical epigenetic regulators in tumor carcinogenesis. In this study, our data showed that miR-137 was significantly downregulated in 58 pairs of human pancreatic cancer (PanCa) tissues and PanCa cell lines. Furthermore, the deregulated miR-137 was correlated with increased tumor size, higher TNM stage, and worse prognosis in pancreatic cancer. Functional studies demonstrated that overexpression of miR-137 dramatically suppressed cell proliferation and induced cell apoptosis in vitro. Meanwhile, upregulated miR-137 remarkably inhibited migration and invasion of pancreatic cancer cells. Further studies indicated that MRGBP was identified as the direct downstream target gene of miR-137. In addition, MRGBP expression is significantly downregulated in miR-137-transfected cells. Our previous study revealed that silencing of MRGBP suppressed the growth of PanCa cells in vitro and in vivo and also promoted apoptosis, and inhibited migration and invasion of PanCa cells, which are consistent with the effects of miR-137 overexpression. Taken together, our findings suggest that miR-137 may function as a novel tumor promoter through directly targeting MRGBP in PanCa. 

Retracted: No

PubPeer comments:
 Fig 4,  (A) Migration capability was evaluated by transwell assay in ASPC-1 (left) and Mia PaCa-2 (right) cells after the cells were transfected with miR-137 mimics or control. (B) Invasion capability was assessed by transwell assay with matrigel in ASPC-1 (left) and Mia PaCa-2 cells (right) after the cells were transfected with miR-137 mimics or control . ![file] Could the authors comment on the appearance of an image twice, as the results of Migration *and* Invasion assays? Is it the Mimic or Control condition? And how some cells came to be present in one version but not the other? ,
Effects of lamotrigine on behavior, oxidative parameters and signaling cascades in rats exposed to the chronic mild stress model
Authors: Helena M Abelaira
Francielle Mina
João Quevedo
Gislaine Z Réus
Cíntia V Santana
Daniela V F Rosa
Karine F Ribeiro
Marco Aurélio Romano-Silva
Felipe Dal-Pizzol
Amanda V Steckert
Journal: Neuroscience Research (2013)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: rats; stress protocol; sucrose consumption; lamotrigine; signaling cascade

Abstract:  The rats were subjected to 40 days of stress protocol, during which the sucrose consumption was assessed in rats chronically treated with lamotrigine (20mg/kg) or with saline. The signaling cascade and oxidative stress parameters were assessed in the brain rat. Both control and stressed rats treated with lamotrigine showed an increase on malondialdehyde equivalents (MDA) in the prefrontal cortex, and that there was also an increase in the amygdala of the control rats treated with lamotrigine. The carbonyl protein was increased in the prefrontal cortex of the stressed group treated with saline, however, the lamotrigine treatment reversed this effect. The treatment with lamotrigine increased the superoxide dismutase (SOD) and catalase activity (CAT) activities in the amygdala of stressed rats. The protein kinase B (PKB/Akt) was reduced in the amygdala in the stressed group treated with saline or lamotrigine. We suggest that the antidepressant-like effect of lamotrigine on anhedonic behavior may be related at least in part to its effects on the oxidative stress parameters and AKT. 

Retracted: No

PubPeer comments:
 Fig 2e.  Tumor weight changes in the mice bearing PaCa-2 and SW1990 cells with si-AFAP1-AS1 or si-Scramble. si-AFAP1-AS1 vs. si-Scramble . Shadows in the si-Scramble row are not compatible with lighting from a single direction. Is this a digital composite? ![file] ,
Differential regulation of mitogen- and stress-activated protein kinase-1 and -2 (MSK1 and MSK2) by CK2 following UV radiation
Authors: Kellie A Jacks
C Anne Koch
Journal: Journal of Biological Chemistry (2010)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: MSK1; MSK2; CK2; UV radiation; NF-kappaB activation
Affiliations: Ontario Cancer Institute, Princess Margaret Hospital (University Health Network), Toronto, Ontario M5G2M9, Canada.

Abstract:  Mitogen- and stress-activated protein kinases, MSK1 and the closely related isoform MSK2, are nuclear kinases that are activated following mitogen stimulation or cellular stress, including UV radiation, by the ERK1/2 and p38 MAPK signaling cascades, respectively. However, factors that differentially regulate MSK1 and MSK2 have not been well characterized. Here we report that the CK2 protein kinase, which contributes to NF-kappaB activation following UV radiation in a p38-dependent manner, physically interacts with MSK2 but not MSK1 and that CK2 inhibition specifically impairs UV-induced MSK2 kinase activation. A putative site of CK2 phosphorylation was mapped to MSK2 residue Ser(324) and when substituted to alanine (S324A) also compromised MSK2 activity. RNA interference-mediated depletion of MSK2 in human MDA-MB-231 cells, but not MSK1 depletion, resulted in impaired UV-induced phosphorylation of NF-kappaB p65 at Ser(276) in vivo, which was restored by the ectopic expression of MSK2 but not by MSK2-S324A. Furthermore, UV radiation led to the activation of NF-kappaB-responsive gene expression in MDA-MB-231 cells and induced p65 transactivation capacity that was dependent on MSK2, MSK2 residue Ser(324), and p65-Ser(276). These results suggest that MSK1 and MSK2 are differentially regulated by CK2 during the UV response and that MSK2 is the major protein kinase responsible for the UV-induced phosphorylation of p65 at Ser(276) that positively regulates NF-kappaB activity in MDA-MB-231 cells. 

Retracted: No

PubPeer comments:
 undeclared splicing site was seen in MSK1 immunoblot data in Fig 5C. ![file] ,
Fennel main constituent, trans‑anethole treatment against LPS‑induced acute lung injury by regulation of Th17/Treg function
Authors: Ichinkhorloo Devshilt
Xi Chen
Sichao Zhang
Xin He
Cong Huang
Lijun An
Qi Yun
Sosorburam Dorjbat
Journal: Molecular Medicine Reports (2018)
Discipline: CLINICAL MEDICINE
Keywords: Fennel; trans-anethole; anti-inflammatory; acute lung injury; interleukin
Affiliations: School of Chinese Materia Medica, Tianjin University Traditional Chinese Medicine, Tianjin 300193, P.R. China., Xinjiang Tefeng Pharmaceutical Co., Ltd., Urumqi, Xinjiang 830054, P.R. China.

Abstract:  Fennel, commonly used in traditional Chinese medicine, is known as Foeniculum vulgare Mill. And its clinical application has been shown to target many biological systems including gastroenterology, endocrinology, gynecology and respiratory. The main constituent of the fennel essential oil is trans‑anethole, which has been described to have anti‑inflammatory and antibacterial activities. The aim of the present study was to define the anti‑inflammatory influence in acute lung injury (ALI)‑bearing mice. For 3 days, ALI‑bearing mice were induced by lipopolysaccharide (LPS) suspension in normal saline (24 mg/kg). On the fourth day, the trans‑anethole was administrated (36.4, 72.8 or 145.6 mg/kg) as well as dexamethasone (5 mg/kg) once per day for 7 consecutive days in mice. Following the completion of drug administration mice were sacrificed. Hematoxylin and eosin staining was performed in the lung paraffin section, for comparisons between monocyte and eosinophil cells in bronchoalveolar lavage fluid. The relative gene expression of interleukin (IL)‑10 and IL‑17 was determined by reverse transcription‑quantitative polymerase chain reaction. These two cytokines and the proportion of T helper 17 (Th17) cells and T regulatory (Treg) cells were determined by flow cytometry. The main constituent of fennel, trans‑anethole, eliminated LPS‑induced histopathological changes, decreased the number of inflammatory cells and resulted in a notable reduction in IL‑17 mRNA expression. In addition, trans‑anethole increased IL‑10 mRNA expression in isolated lung tissues and resulted in a marked elevation in Treg cells and reduction in Th17 cells in spleen tissues. The results of the present study indicated that the main constituent of fennel, trans‑anethole may be an anti‑inflammation component, which influenced the regulation of Th17/Treg responses. Therefore, this medicinal herb may support a healing effect on diseases of inflammatory. 

Retracted: No

PubPeer comments:
 Figure 7B. Two cytometry images appear partially identical, shown within color box and circle. Maybe the authors could provide some explanations for what happened here. ![file] ,
Type 2 antidiabetic activity of bergenin from the roots of Caesalpinia digyna Rottler
Authors: S Hemalatha
Sairam Krishnamurthy
Damiki Laloo
Dinesh K Patel
Satyendra K Prasad
Rajesh Kumar
Journal: Fitoterapia (2012)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Bergenin; Caesalpinia digyna; antidiabetic activity; streptozotocin; nicotinamide
Affiliations: Department of Pharmaceutics, Institute of Technology, Banaras Hindu University, Varanasi, India.

Abstract:  Bergenin, a major constituent of Caesalpinia digyna Rottler (Leguminosae) was isolated from its roots and was characterized by comparing its melting point and spectroscopic data (IR, (1)H, (13)C, Mass Spectra) with standard bergenin. Isolated bergenin was then evaluated for antidiabetic (Type 2) activity in streptozotocin (STZ)-nicotinamide induced diabetic rats. Bergenin was administered at doses of 2.5, 5, and 10 mg/kg; p.o. to normal rats which were subjected to oral glucose tolerance test (OGTT). Bergenin at same dose level was given to diabetic rats and fasting blood glucose level was estimated on 0th, 7th and 14th day of treatment while plasma lipids, antioxidant enzymes and liver glycogen level in diabetic rats were estimated on 14th day of treatment followed by histopathological studies of pancreas. Bergenin at 10mg/kg; p.o. was found to reduce blood glucose level significantly in OGTT (P&lt;0.01) while it showed a significant reduction in fasting blood glucose level in diabetic rats at same dose level only on 14th day of treatment. Bergenin in all dose levels reversed plasma lipid (reduced elevated TC, LDL-C and increased HDL-C level) profile to normal values except TG. However, bergenin showed no significant effect on liver glycogen at all dose level. The decrease in lipid peroxides and increase in superoxide dismutase (SOD) and catalase (CAT) in liver illustrated the antioxidant potential of bergenin. Histopathological studies demonstrated the regenerative effect of bergenin on pancreatic β cells. Hence, bergenin isolated from C. digyna possesses significant antidiabetic, hypolipidemic and antioxidant activity in Type 2 diabetic rats. 

Retracted: No

PubPeer comments:
 Figure 4 shows 4 pancreatic tissues, each from a differently treated rat, so no overlapping areas are expected. However, as shown with blue and green boxes, panels B (diabetic control) and D diabetic treated with bergenin) both appear to be zoomed-in versions of areas visible in panel A (control). The  crawling cat feature visible in the top left of panel A (blue box) is a bit different from the version in panel B, though, in that the staining is in slightly different locations. ![file] ,
Enteric glial cells and their role in gastrointestinal motor abnormalities: introducing the neuro-gliopathies
Authors: Paola Baronio
Elisabetta Antonelli
Carlo Clerici
Elisa Rossi
Simona Fisogni
Vincenzo Villanacci
Gabrio Bassotti
Christoph A Maurer
Gieri Cathomas
Journal: World journal of gastroenterology (2007)
Discipline: CLINICAL MEDICINE
Keywords: Enteric glial cells; gut motor function; inflammatory events; myenteric plexuses; neurotransmitters

Abstract:  The role of enteric glial cells has somewhat changed from that of mere mechanical support elements, gluing together the various components of the enteric nervous system, to that of active participants in the complex interrelationships of the gut motor and inflammatory events. Due to their multiple functions, spanning from supporting elements in the myenteric plexuses to neurotransmitters, to neuronal homeostasis, to antigen presenting cells, this cell population has probably more intriguing abilities than previously thought. Recently, some evidence has been accumulating that shows how these cells may be involved in the pathophysiological aspects of some diseases. This review will deal with the properties of the enteric glial cells more strictly related to gastrointestinal motor function and the human pathological conditions in which these cells may play a role, suggesting the possibility of enteric neuro-gliopathies. 

Retracted: No

PubPeer comments:
 ![file] ![file] ![file] ![file] ![file] , 
 ![file] ![file] ,
T helper 1 response is correlated with widespread pain, fatigue, sleeping disorders and the quality of life in patients with fibromyalgia and is modulated by hyperbaric oxygen therapy
Authors: Piercarlo Sarzi-Puttini
Giuliana Guggino
Domenico Garbo
Claudia Schinocca
Roberto Casale
Stefania Raimondo
Marianna Lo Pizzo
Guido Sireci
Francesco Dieli
Roberto Giacomelli
Riccardo Alessandro
Piero Ruscitti
Diana Di Liberto
Giovanni Triolo
Filippo Brighina
Journal: Clinical and experimental rheumatology (0)
Discipline: CLINICAL MEDICINE
Keywords: Hyperbaric oxygen therapy; fibromyalgia; immune system dysregulation; quality of life; CD4 T lymphocytes
Affiliations: Dipartimento Biomedico di Medicina Interna e Specialistica, Sezione di Reumatologia, Università di Palermo, Italy. ., Dipartimento Biomedico di Medicina Interna e Specialistica, Sezione di Reumatologia, Università di Palermo, Italy., Dipartimento di Biopatologia e Biotecnologie Mediche, Università di Palermo, Italy., Unità di Medicina Iperbarica, Policlinico P. Giaccone, Palermo, Italy., Department of Experimental Biomedicine and Clinical Neurosciences, University of Palermo, Italy., Department of Biotechnological and Applied Clinical Science, Rheumatology Unit, School of Medicine, University of L'Aquila, Italy., OPUSmedica, PC & R, Persons, Care & Research Network, Piacenza, Italy., Rheumatology Unit, Luigi Sacco University Hospital, Milan, Italy.

Abstract:  Objectives: Hyperbaric oxygen therapy (HBOT) has been used as treatment for different clinical conditions, including fibromyalgia (FM). HBOT modulates brain activity, ameliorates chronic pain and modifies the ratio of immune cells. Clinical studies have provided evidence that FM is associated with immune system dysregulation. In the present study we aimed to evaluate the effect of HBOT on immune system and on the quality of life-style of FM patients. Methods: Patients with primary FM and controls were treated with HBOT. Physical, emotional and social assessment, quality of sleep, tender points, intensity score, WPI and symptom severity were evaluated before and after HBOT. Furthermore, a characterisation of CD4 T lymphocytes and their cytokine production was performed by flow cytometry. The expression of TNF-α, IFN-γ, IL-17, IL-9 and IL-22 was also assessed by RT-PCR. Finally, the serum levels of serotonin were evaluated by ELISA. Results: Our results confirm the participation of immune system in the pathogenesis of FM and highlight the impact of HBOT treatment, with particular regard to the changes on proinflammatory cytokines production by CD4 T cells subsets. Conclusions: FM patients show a Th1 signature and the activation of this subset is modulated by HBOT. 

Retracted: No

PubPeer comments:
 The Zoombie green images of Fig 3C and 4A have a striking similarity ![file] ,
MicroRNA-384 inhibits the progression of esophageal squamous cell carcinoma through blockade of the LIMK1/cofilin signaling pathway by binding to LIMK1
Authors: Xiao-Long Wang
Wei Zhao
Ji Zhang
Le-Ning Zhang
Hai-Xiang Yu
Journal: Biomedicine & Pharmacotherapy (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Cell apoptosis; Cell proliferation; Esophageal squamous cell carcinoma; LIMK1; LIMK1/cofilin signaling pathway
Affiliations: Department of Thoracic Surgery, China-Japan Union Hospital of Jilin University, Changchun, 130033, PR China., Department of Thoracic Surgery, China-Japan Union Hospital of Jilin University, Changchun, 130033, PR China. Electronic address: .

Abstract:  Introduction: Esophageal squamous cell carcinoma (ESCC) represents an aggressive malignancy often accompanied with a poor prognosis. Owing to the poor mortality and morbidity rates associated with this malignancy, a deeper understanding of the finer molecular changes that occur in ESCC is required in order to identify novel potential targets for early detection and therapy. At present the mechanism by which ESCC functions on a molecular level is not fully understood. Hence, the aim of the present study was to ascertain as to whether microRNA-384 (miR-384) influences the progression of ESCC. Material and methods: Bioinformatics analysis was initially conducted to identify ESCC-related differentially expressed genes and predict regulatory miRs. After the target relationship between miR-384 and LIMK1 had been verified, the expression of miR-384 and LIMK1 in the EC9706 cell line was altered in an attempt to investigate the regulatory roles of miR-384 in the expression of the LIMK1/cofilin signaling pathway-related genes, cell proliferation, invasion, cell cycle distribution and apoptosis, in addition to lymph node metastasis (LNM) and tumor growth in nude mice. Results: Microarray-based gene expression profiling indicated that miR-384 affected the progression of ESCC through the LIMK1-mediated LIMK1/cofilin signaling pathway. Furthermore, miR-384 and Bax were observed to be poorly expressed, while LIMK1, cofilin and Bcl-2 were highly expressed in ESCC. The obtained evidences indicating that miR-384 targeted and negatively regulated LIMK1. Upregulation of miR-384 or LIMK1 inhibition was determined to block the LIMK1/cofilin signaling pathway, repress cell proliferation, invasion, cell cycle, LNM and tumor growth, while promote cell apoptosis in ESCC. Conclusion: Collectively, based on the key findings of the study, miR-384 could sequester LIMK1, which acts to suppress activation of the LIMK1/cofilin signaling pathway, thus ultimately inhibiting the development and progression of ESCC. 

Retracted: No

PubPeer comments:
 Fig 4A: ![file] Two FACS plots are unexpectedly similar to plots in Figs 4A,B of  Overexpression of miR-203 increases the sensitivity of NSCLC A549 H460 cell lines to cisplatin by targeting Dickkopf-1 [(Cheng et al. 2017)] ![file] ![file] , 
 [Perhaps a systemic problem] . Journals and readers may wish to proceed with caution. ,
Euxanthone exhibits anti-proliferative and anti-invasive activities in hepatocellular carcinoma by inducing pyroptosis: preliminary results
Authors: F-L Wu
Y-F Chen
H-Y Qi
Journal: European review for medical and pharmacological sciences (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Hepatocellular carcinoma; Euxanthone; Anti-cancer activities; Marker proteins; Cell proliferation
Affiliations: Department of Gastroenterology, Xinxiang Central Hospital, Xinxiang, Henan, China. .

Abstract:  Objective: Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related deaths. Euxanthone, a xanthone compound extracted from Polygala caudata, possesses a variety of pharmacological activities. This work aimed to explore whether euxanthone exhibits anti-cancer activities in HCC. Patients and methods: Tissue specimen was collected and the mRNA and protein expression of marker proteins were detected by qRT-PCR and Western blot, respectively. The viable cell number was assessed by CCK-8 assay. TUNEL assay was utilized to determine cell death. Cell migration was measured by Wound healing. Cell invasion was measured by transwell assay. Xenograft model was established to evaluate the efficacy of euxanthone in vivo. Results: We demonstrated that HCC tissue and HCC cell line presented with lower expression of caspase-1, IL-1β, and IL-18. Euxanthone markedly suppressed the proliferation of HCC cells and induced cell death. In addition, euxanthone inhibited cell migration and invasion. Meanwhile, our results showed that euxanthone promoted cell death in a caspase-2 dependent manner. In vivo data also showed that euxanthone suppressed tumor growth and promoted pyroptotic cell death. Conclusions: We showed that that euxanthone may be a candidate of anticancer agent and provide clinical benefits for patients with HCC. 

Retracted: No

PubPeer comments:
 Fig 5C:  Euxanthone suppresses tumor growth of xenograft model. ... C. IHC assay was performed to examine the expression levels of caspase-1, IL-1u03b2 and IL-18 These tissue slides come from a repertoire which appears in a variety of combinations, with arbitrary labels, across a sprawling oeuvre of papers from nominally different teams of authors. Here for comparison I have chosen Fig 8D of [Li et al (2019)] , but there were many other options. ![file] ,
Magnolol induces apoptosis in osteosarcoma cells via G0/G1 phase arrest and p53‐mediated mitochondrial pathway
Authors: Haiyan Wen
Siqi Zhou
Haohuan Li
Journal: Journal of Cellular Biochemistry (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: apoptosis; magnolol; mitochondria; osteosarcoma; p53.
Affiliations: Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, China., Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan, China.

Abstract:  Osteosarcoma is a highly invasive primary malignancy of bone. Magnolol is biologically active, which shows antitumor effects in a variety of cancer cell lines. However, it has not been elucidated magnolol's effects on human osteosarcoma cells (HOC). This study aimed to determine antitumor activity of magnolol and illustrate the molecular mechanism in HOC. Magnolol showed significant inhibition effect of growth on MG-63 and 143B cells and induced apoptosis and cell cycle arrest at G0/G1. In osteosarcoma cells, magnolol upregulated expressions of proapoptosis proteins and suppressed expressions of antiapoptosis proteins. Additionally, under the pretreatment of pifithrin-a (PFT-a, a p53 inhibitor), the magnolol-induced apoptosis was significantly reversed. The results above indicated that magnolol induces apoptosis in osteosarcoma cells may via G0/G1 phase arrest and p53-mediated mitochondrial pathway. 

Retracted: No

PubPeer comments:
 Most of the bands in Figures 3C and 5D have the feature of  blobs drawn on a featureless flat gray background , as described by Smut Clyde in one of his reports. This feature of blots has also been described by Dr. Bik in her blog. Both point this feature to a group of mass produced papers. It would be helpful if the authors can post their original blot images. ![file] , 
 #1 Dear Dr.Oeneis buddha Thanks for you comments for concerning our article, we must state that it is not a group of mass-produced papers. If you need, we will provide original blot images for you for the next few days. Thank you very much again. ,
Diallyl Trisulfide Inhibits Growth of NCI-H460 in Vitro and in Vivo, and Ameliorates Cisplatin-Induced Oxidative Injury in the Treatment of Lung Carcinoma in Xenograft Mice
Authors: Hongya Xu
Xiaoyan Jiang
Jimin Cao
Zhongxi Zhao
Shanzhong Li
Xiaosong Zhu
Siying Li
Na Liu
Jianhua Cai
Journal: International Journal of Biological Sciences (2017)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Diallyl trisulfide; attenuate side effect.; cisplatin; enhanced effect; lung carcinoma.
Affiliations: School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, Jinan, Shandong 250012, P.R. China., School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, Jinan, Shandong 250012, P.R. China.; Shandong Provincial Key Laboratory of Mucosal and Transdermal Drug Delivery Technologies, Shandong Academy of Pharmaceutical Sciences, 989 Xinluo Street, Jinan, Shandong 250101, P.R. China.; Jiangsu Shengshi Kangde Biotech Corporation, Lianyungang, Jiangsu 222006, P.R. China., Jiangsu Shengshi Kangde Biotech Corporation, Lianyungang, Jiangsu 222006, P.R. China.

Abstract:  Diallyl trisulfide (DATS), an organosulfuric component of garlic oil, exhibits potential anticancer and chemopreventive effects. Cisplatin (DDP), a common chemotherapeutic agent, has provided great therapeutic contributions to treating solid tumors, but with serious side effects. Here, we verified the anti-tumor properties of DATS on lung cancer in vitro and in vivo, and evaluated synergistic effects of DATS combined with DDP on the NCI-H460 xenograft model. Significantly decreased cell viabilities, cell cycle G1 arrest, and apoptosis induction were observed in DATS treated NCI-H460 cells (p&lt;0.05). And injection of DATS (30 or 40 mg/kg) to female Balb/c mice significantly inhibited the growth of human NCI-H460 cell tumor xenograft (p&lt;0.001). Moreover, DATS in combination with DDP exhibited enhanced anti-tumor activity via induction of apoptosis. Apoptosis pathways were confirmed by modulation of p53, Bcl-2 family members; induction of active caspase-3/8/9 and activation of JNK- and p38-MAPK pathways. Interestedly, DATS+DDP administration exerted fewer side effects, such as suppressing the weight loss and ameliorating DDP-induced oxidative injury, especially in renal parenchyma. In addition, increased E-cadherin and decreased MMP-9 expression levels were observed in DATS-treated tumor tissues. These studies provide supports that DATS might be a potential candidate for combination with DDP in cancer treatment. 

Retracted: No

PubPeer comments:
 In Figure 3A, the Western immunoblots of Bax and cytochrome C are identical (the Bax blot is a bit more compressed vertically). ![file] ,