syedzayyan/paper_mill_benchmark huggingface dataset:
Sophocarpine ameliorates cardiac hypertrophy through activation of autophagic responses

Mounting evidences indicate that autophagy is an essential homeostatic mechanism to maintain the global cardiac structure function.Sophocarpine (sop), a major bioactive compound derived from the natural plant sophora flavescens.However, the role of sop in cardiac hypertrophy remain to be fully elucidated.In the present study, we tested the hypothesis that sop protects against ang ii–induced cardiac hypertrophy by mediating the regulation of autophagy.The results demonstrated that sop attenuated the ang ii–induced cardiac hypertrophy, as assessed by measurements of echocardiography parameters, the ratios of heart weight/body weight and left ventricle weight/body weight, histopathological staining, cross-sectional cardiomyocyte area, and the expression levels of cardiac hypertrophic markers.The anti-hypertrophic effect of sop was mediated by activating autophagy-related pathway, as revealed by reversal of the increased autophagy marker protein expression.These findings reveal a novel mechanism of sop attenuating cardiac hypertrophy via activating autophagy-related signaling pathways.

Journal: Bioscience, Biotechnology, and Biochemistry (2020)
Publication types: Research Article;
TRIM25 blockade by RNA interference inhibited migration and invasion of gastric cancer cells through TGF-β signaling

Tripartite motif containing 25 (trim25), a member of trim proteins, has been found abnormally expressed in cancers of female reproductive system.Here, trim25 was conspicuously expressed in human gastric cancer (gc) tissues in which its higher expression generally correlated with the poor prognosis of patients.Small interfering rna (si rna)-mediated knockdown of trim25 expression in mgc-803 and ags cells had no effects on cell proliferation, whereas reduced cell migration and invasion.Gene set enrichment analysis on the cancer genome atlas stomach adenocarcinoma (stad) dataset revealed that several signaling pathways, including the migration, e-cadherin and transforming growth factor-β (tgf-β) pathways, were enriched in trim25 higher expression patients.Moreover, ectopic expression of trim25 in a gc cell line with lower expression of trim25 significantly promoted the migration and invasion.Further experiments with tgf-β inhibitor suggested that trim25 may exert its function through tgf-β pathway.In summary, our results indicate that trim25 acts as an oncogene in gc and thus presents a novel target for the detection and treatment of gc.

Journal: Scientific Reports (2016)
Publication types: Research Article;
Shikonin causes cell-cycle arrest and induces apoptosis by regulating the EGFR-NF-κB signalling pathway in human epidermoid carcinoma A431 cells

Shikonin, a naphthoquinone pigment isolated from the chinese herbal zicao, has been shown to exhibit antioxidant and anticancer effects.In the present study, we investigated the antiproliferative and pro-apoptotic effects of shikonin on a431 cells and explored the underlying molecular mechanisms.In the present study, our results showed that shikonin significantly inhibited the growth of a431 cells in a concentration- and time-dependent manner, and caused cell cycle arrest by upregulation of p21 and p27, and downregulation of cyclins and cyclin-dependent kinases.In addition, shikonin evidently induced apoptosis due to decreasing bcl-2 expression, increasing bax expression, activating caspase and inactivating nf-κb, while pretreatment with a pan-caspase inhibitor z-asp-ch2-dcb abrogated shikonin-induced apoptosis.Moreover, egf could significantly increase the nf-κb dna-binding activity and reversed the shikonin-induced inactivation of nf-κb.As anticipated ag1478 (egfr inhibitor) and bay11-7082 (nf-κb inhibitor) blocked egf-reversed the inactivation of nf-κb induced by shikonin.Our data also showed that egf could evidently reverse the shikonin-induced decreases in cell viability and increases in apoptosis.Then, the nf-κb inhibitors such as bay11-7082, sn50, helenalin and the egfr inhibitor ag1478 and its downstream inhibitor such as pi3k inhibitor ly294002 and stat3 inhibitor stattic dramatically blocked egf-reversed decreases in cell viability and increases in apoptosis induced by shikonin.Collectively, our findings indicated that shikonin inhibited cell growth and caused cell cycle arrest of the a431 cells through the regulation of apoptosis.Moreover, these effects were mediated at least partially by suppressing the activation of the egfr–nf-κb signaling pathways.

Journal: Bioscience Reports (2015)
Publication types: Research Article;
MicroRNA-9 inhibits high glucose-induced proliferation, differentiation and collagen accumulation of cardiac fibroblasts by down-regulation of TGFBR2

To investigate the effects of mi r-9 on high glucose (hg)-induced cardiac fibrosis in human cardiac fibroblasts (hcfs), and to establish the mechanism underlying these effects.Hcfs were transfected with mi r-9 inhibitor or mimic, and then treated with normal or hg.Cell viability and proliferation were detected by using the cell counting kit-8 (cck-8) assay and brdu-elisa assay.Cell differentiation and collagen accumulation of hcfs were detected by q rt-pcr and western blot assays respectively.The m rna and protein expressions of transforming growth factor-β receptor type ii (tgfbr2) were determined by q rt-pcr and western blotting.Up-regulation of mi r-9 dramatically improved hg-induced increases in cell proliferation, differentiation and collagen accumulation of hcfs.Moreover, bioinformatics analysis predicted that the tgfbr2 was a potential target gene of mi r-9.Luciferase reporter assay demonstrated that mi r-9 could directly target tgfbr2.Inhibition of tgfbr2 had the similar effect as mi r-9 overexpression.Down-regulation of tgfbr2 in hcfs transfected with mi r-9 inhibitor partially reversed the protective effect of mi r-9 overexpression on hg-induced cardiac fibrosis in hcfs.Up-regulation of mi r-9 ameliorates hg-induced proliferation, differentiation and collagen accumulation of hcfs by down-regulation of tgfbr2.These results provide further evidence for protective effect of mi r-9 overexpression on hg-induced cardiac fibrosis.

Journal: Bioscience Reports (2016)
Publication types: Research Article;
Knockdown of Tcf3 enhances the wound healing effect of bone marrow mesenchymal stem cells in rats

The aim of the present study was to explore the wound healing effect of tcf3 in rat bone marrow mesenchymal stem cells (bmscs) and their effects on wound healing.Epidermal growth factor (egf) and fibroblast growth factors (fgfs) were used to induce bmscs differentiation into epithelial-like cells.Western blotting analysis and rt-q pcr were performed to assess the expression levels of tcf3 and the markers of epithelial-like cells, such as cytokeratin-18 (ck-18), ck-19 and p63.Cell counting kit-8 (cck-8) and clone formation assay were carried out to detect cell viability.Immunohistochemistry and he staining were used to assess the level of tcf3 protein and skin repair degree, respectively.Rat wound healing model was built to evaluate the effects of bmscs with altered expression of tcf3 on wound healing.Results showed that egf and fgfs stimulation increased the expression of ck-18, ck-19 and p63, improved bmscs viability, but decreased the expression of tcf3.Knockdown of tcf3 in bmscs increased ck-18, ck-19 and p63 expression and improved cell proliferation, as well as accelerated wound healing process.Moreover, inhibition of wnt/β-catenin signaling weakened the effect of tcf3 down-regulation on bmscs proliferation enhancement.And inhibition of notch1 signaling impeded the epithelial-like cell differentiation of bmscs induced by tcf3 down-regulation.Our study reveals that knockdown of tcf3 enhances the wound healing process of bmscs in rat, which provides new approach for accelerating skin regeneration.

Journal: Bioscience Reports (2019)
Publication types: Research Article;
Exosome-mediated transfer of lncRNA PART1 induces gefitinib resistance in esophageal squamous cell carcinoma via functioning as a competing endogenous RNA

Background currently, resistance to tyrosine kinase inhibitors, such as gefitinib, has become a major obstacle in improving the clinical outcome of patients with metastatic and advanced-stage esophageal squamous cell carcinoma (escc).While cell behavior can be modulated by long non-coding rnas (lnc rnas), the roles of lnc rnas within extracellular vesicles (exosomes) are largely unknown.Therefore, we investigated the involvement and regulatory functions of potential lnc rnas enclosed in exosomes during formation of chemoresistance in human escc.Methods gefitinib-resistant cell lines were established by continuously grafting te1 and kyse-450 cells into gefitinib-containing culture medium.Lnc rna microarray assay followed by rt-q pcr were used to verify the differential expression of lnc rna prostate androgen-regulated transcript 1 (part1) between gefitinib resistant and parental cell lines.Rna fluorescence in situ hybridization (fish) was used to investigate whether extracellular part1 could be incorporated into exosomes and transmitted to recipient cells.Subsequently, a series of in vitro assays and a xenograft tumor model were used to observe the functions of lnc rna part1 in escc cells.A signal transduction reporter array, bioinformatics analysis, western blotting, and immunofluorescence were carried out to verify the regulation of part1 and its downstream bcl-2 signaling pathway.Results lnc rna part1 was upregulated in gefitinib-resistant cells when compared to parental escc cells.It was found that stat1 can bind to the promoter region of lnc rna part1, resulting in its activation.Knockdown of lnc rna part1 potently promoted the gefitinib-induced cell death, while elevated part1 promoted gefitinib resistance by competitively binding to mi r-129 to facilitate bcl-2 expression in escc cells.In addition, extracellular part1 could be incorporated into exosomes and transmitted to sensitive cells, thus disseminating gefitinib resistance.Clinically, high levels of serum lnc rna part1 in exosome were associated with poor response to gefitinib treatment in escc patients.Conclusions lnc rna part1 promotes gefitinib resistance by regulating mi r-129/bcl-2 pathway, and may serve as a therapeutic target for escc patients.

Journal: Journal of Experimental & Clinical Cancer Research: (CR) (2018)
Publication types: Research Article;
Tripartite motif-containing 14 (TRIM14) promotes epithelial-mesenchymal transition via ZEB2 in glioblastoma cells

Background several members of the tripartite motif-containing (trim) protein family have been reported to serve as vital regulators of tumorigenesis.Recent studies have demonstrated an oncogenic role of trim 14 in multiple human cancers; however, the importance of this protein in glioblastoma remains to be elucidated.Methods the expression levels of trim14 were analyzed in a series of database and were examined in a variety of glioblastoma cell lines.Two independent trim14 sh rna were transfected into ln229 and u251 cells, and the effect of trim14 depletion was confirmed.Transwell assay and wound healing assay assay were carried out to assess the effect of trim14 depletion on glioblastoma cell invasion and migration.Western blotting was performed to screen the downstream gene of trim14.The stability analysis and ubiquitylation assays and orthotopic xenograft studies were also performed to investigate the role of trim14 and the relationship with downstream gene.Human glioblastoma tissues were obtained and immunohistochemical staining were carried out to confirm the clinical significance of trim14.Results in this study, we showed that trim14 was upregulated in human glioblastoma specimens and cell lines, and correlated with glioblastoma progression and shorter patient survival times.Functional experiments showed that decreased trim14 expression reduced glioblastoma cell invasion and migration.Furthermore, we identified that zinc finger e-box binding homeobox 2 (zeb2), a transcription factor involved in epithelial–mesenchymal transition, is a downstream target of trim14.Further investigation revealed that trim14 inactivation significantly facilitated zeb2 ubiquitination and proteasomal degradation, which led to aggressive invasion and migration.Our findings provide insight into the specific biological role of trim14 in tumor invasion.Conclusions our findings provide insight into the specific biological role of trim14 in tumor invasion, and suggest that targeting the trim14/zeb2 axis might be a novel therapeutic approach for blocking glioblastoma.

Journal: Journal of Experimental & Clinical Cancer Research: (CR) (2019)
Publication types: Research Article;
MicroRNA-181 inhibits proliferation and promotes apoptosis of chondrocytes in osteoarthritis by targeting PTEN

To investigate the effects of micro rna-181 (mi r-181) on the proliferation and apoptosis of chondrocytes in osteoarthritis (oa) by targeting pten.Methods: the chondrocytes in logarithmic growth phase were selected and divided into 6 test groups: the normal, blank, negative control, mi r-181 mimic, mi r-181 inhibitor, and mi r-181 inhibitor + pten-si rna groups.Reverse transcription q pcr was used to detect the expressions of mi r-181 and pten m rna.Mtt assay and flow cytometry were performed to detect cell proliferation and apoptosis.The protein expressions of parp and caspase-3 and the activity of mmp-2 and mmp-9 were detected by western blotting and gelatin zymography assay.Results: the mi r-181 mimic group showed increased mi r-181 expression and decreased pten expression compared with the other 5 groups.Also, by comparison with the other 5 groups, the cell proliferation rate declined and the rate of cell apoptosis was elevated in the mi r-181 mimic group.The mi r-181 mimic group showed remarkably increased protein expression of caspase-3 and parp compared with the other 5 groups.The activity of mmp-2 and mmp-9 was higher in the mi r-181 mimic group than the other 5 groups.Conclusion: mi r-181 could up-regulate the expressions of caspase-3, parp, mmp-2, and mmp-9, and thereby inhibit cell proliferation and promote apoptosis of chondrocytes in oa by targeting pten.

Journal: Biochemistry and Cell Biology: Biochimie et Biologie Cellulaire (2017)
Publication types: Research Article;
Clinical grade adjuvants to mature CD141+ DCs for immunotherapy

Stimulation of dendritic cells (dc) is considered critical in cancer immunotherapy.Batf-3-dependent subsets, that express in humans cd141 (bdca-3), promote cd8 t-cell cross-priming against tumor antigens.Here, we evaluate two clinical-grade stimuli for peripheral blood cd141+ myeloid dendritic cells (m dcs), a rare dc subset that is currently being explored for use in immunotherapy.In contrast to routine evaluation methods, which focus on predefined maturation markers on the surface or factors released from the activated cells, we applied an unbiased transcriptome-based method using both rna-sequencing (rna-seq) and microarrays.Specifically, we analyzed the m rna of cd141+ m dcs from five human donors upon activation with two clinical-grade adjuvants, hiltonol (poly-iclc, a tlr3 ligand) and protamine rna (p rna, a tlr7/8 ligand), and compared these samples to unstimulated counterparts.Both methods, rna-seq, and microarray showed that hiltonol and p rna lead to almost identical changes in the transcriptome of cd141+ m dcs.A gene ontology (go) term analysis suggested that these changes were mainly related to activation and maturation pathways, including induction of type i ifn and il-12 transcription, while pathways related to adverse effects or cell damage were not strongly affected.The combination of both reagents in the dc cultures gave a very similar result as compared to either stimulus alone, suggesting no synergistic effect.Furthermore, our analysis demonstrates that microarray and rna-seq analysis gave similar conclusions about the activation status of these cells.Importantly, microarray analyses instead of the advantages of rna sequencing may still be suitable for studying the activation of rare cell types that are minimally represented or in very low frequency in the organism.Together, our results indicate that both stimuli are potent clinical grade adjuvants with comparable effects to mature cd141+ m dcs in short-term cultures to be used in immunotherapy.

Journal: Frontiers in Bioscience-Elite (2022)
Publication types: Research Article;
MicroR-9-5p suppresses EV71 replication through targeting NFκB of the RIG-I-mediated innate immune response

Accumulating evidence demonstrates that there is a causative link between hsa‐micro rna ‐9‐5p (mi r‐9) and pathophysiological processes.Enterovirus 71 ( ev 71) has been found to contribute to numerous severe clinical symptoms which result in death.The exact mechanism by which ev 71 influences mi r‐9 expression is unknown, and the relationship between mi r‐9 and ev 71 is still unclear.Here, mi r‐9 expression was found to be impaired upon ev 71 infection in several cell lines and in an ev 71 infection mouse model.Additionally, we confirmed that ev 71 infection induces robust expression of pro‐inflammatory cytokines ( tnf ‐α, il ‐6, and il ‐1) and interferons ( ifn ‐α and ifn ‐β).Overexpression of mi r‐9 attenuated ev 71 proliferation and reduced protein and gene expressions of virion protein 1 ( vp 1) of ev 71.Furthermore, we observed that the inflammation caused by ev 71 infection was restored to a moderate level via mi r‐9 overexpression.Nuclear factor kappa b ( nf κb) in the retinoic acid‐induced gene 1 ( rig ‐i) signaling pathway, but not interferon regulating factor 3 ( irf 3), was significantly decreased and inactivated by ectopic mi r‐9 expression.Moreover, in mouse infection experiments, administration of mi r‐9 agomirs caused a significant decrease in vp 1 levels and pro‐inflammatory cytokine production after viral inoculation.Taken together, the present data demonstrate that mi r‐9 exerts an anti‐ ev 71 effect in cells and a mouse model via mediating nf κb activity of the rig ‐i signal pathway, thereby suggesting a new candidate for antiviral drug development.

Journal: FEBS Open Bio (2018)
Publication types: Research Article;
Trastuzumab induces PUMA-dependent apoptosis and inhibits tumor growth in gastric cancer

Gastric cancer ( gc ) is one of the most prevalent cancers worldwide.Trastuzumab has been approved for the treatment of metastatic gc , gastroesophageal junction cancer, and breast cancer.However, the mechanisms involved in trastuzumab‐induced gc cell apoptosis remain largely unknown.In this study, we investigated the underlying mechanisms of trastuzumab‐mediated suppression of gc cell growth both in vitro and in vivo .We found that trastuzumab treatment induces p53 upregulated modulator of apoptosis ( puma ) expression in gc cells, through the nf ‐κb pathway following akt inhibition and glycogen synthase kinase 3β ( gsk 3β) activation.We also observed that puma was necessary for trastuzumab‐induced apoptosis in gc cells.Moreover, puma deficiency suppressed apoptosis and the antitumor effect of trastuzumab in xenograft models.Finally, computerized tomography ( ct ) and immunohistochemistry results showed that patients with increased activation of puma were more sensitive to trastuzumab treatment than those with low puma expression.These results indicate that trastuzumab induces puma ‐dependent apoptosis and inhibits tumor growth in gc , suggesting that puma plays a critical role in mediating the antitumor effects of trastuzumab in gc .Puma induction may be used as a marker of trastuzumab sensitivity.

Journal: FEBS Open Bio (2018)
Publication types: Research Article;
MicroRNA-1271 functions as a potential tumor suppressor in hepatitis B virus-associated hepatocellular carcinoma through the AMPK signaling pathway by binding toCCNA1

Hepatocellular carcinoma (hcc) is mainly associated with hepatitis b virus (hbv) infection and characterized by metastasizing and infiltrating adjacent and distant tissues.Notably, micro rna‐1271 (mi r‐1271) is a tumor suppressor in various cancers.Therefore, we evaluate the ability of mi r‐1271 to influence cell proliferation, migration, invasion, and apoptosis in hbv‐associated hcc through the adenosine monophosphate–activated protein kinase (ampk) signaling pathway via targeting ccna1 .Hbv‐associated hcc and adjacent normal tissues were collected to identify the expression of mi r‐1271 and ccna1.To verify the relationship between mi r‐1271 and ccna1 , we used bioinformatics prediction and the dual‐luciferase reporter gene assay.The effects of mi r‐1271 on hbv‐associated hcc cell behaviors were investigated by treatment of the mi r‐1271 mimic, the mi r‐1271 inhibitor, or small interfering rna against ccna1.The hbv‐dna quantitative assay, 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromid assay, scratch test, transwell assay, and flow cytometry were used to detect hbv‐dna replication, cell proliferation, invasion, migration, and apoptosis.Mi r‐1271 showed a low expression, whereas ccna1 showed a high expression in hbv‐associated hcc tissues.We identified that mi r‐1271 targeted and negatively regulated ccna1 .Upregulated mi r‐1271 and downregulated ccna1 inhibited the hbv‐associated hcc cell hbv‐dna replication, proliferation, migration, and invasion, while accelerating apoptosis by activating the ampk signaling pathway.Mi r‐1271 promotes the activation of the ampk signaling pathway by binding to ccna1 , whereby mi r‐1271 suppresses hbv‐associated hcc progression.This study points to a potential therapeutic approach of downregulation of mi r‐1271 in hbv‐associated hcc treatment.

Journal: Journal of Cellular Physiology (2018)
Publication types: Research Article;
LncRNA HAND2-AS1 exerts anti-oncogenic effects on ovarian cancer via restoration of BCL2L11 as a sponge of microRNA-340-5p

In the early stage of ovarian cancer (oc), molecular biomarkers are critical for its diagnosis and treatment.Nevertheless, there is little research on the mechanism underlying tumorigenesis in oc.Herein, we aimed to explore whether long noncoding rna (lnc rna) hand2‐as1 participated in the regulation of the cell proliferation, migration, and apoptosis of oc by regulating b‐cell lymphoma 2 like 11 (bcl2l11) and micro rna‐340‐5p (mi r‐340‐5p).Differentially expressed lnc rnas in oc were screened by microarray‐based analysis.Hand2‐as1, bcl2l11, and mi r‐340‐5p expression was assessed in normal ovarian and oc tissues and human oc cell lines.Then, the relationships among hand2‐as1, bcl2l11, and mi r‐340‐5p were explored.Ectopic expression and depletion experiments were applied to analyze the effects of hand2‐as1, mi r‐340‐5p and bcl2l11 on migration, invasion, and proliferation of oc cells, as well as apoptosis.Lastly, the tumor xenograft in nude mice was conducted to test the tumorigenesis in vivo.In silico analysis displayed poor expression of hand2‐as1 in oc.Hand2‐as1 specifically sponged with mi r‐340‐5p which was found to directly target bcl2l11.Importantly, hand2‐as1 or bcl2l11 overexpression or mi r‐340‐5p downregulation resulted in reduction of cell invasion and migration, together with decrease of cell proliferation and increase of cell apoptosis in oc.Besides, high‐expressed hand2‐as1 inhibited the tumorigenesis in nude mice.To sum up, these data suggests hand2‐as1 as an anti‐oncogene in oc through upregulation of bcl2l11 by competitively binding to mi r‐340‐5p, which demonstrates that there are potential diagnosis and therapy values of hand2‐as1 in oc.

Journal: Journal of Cellular Physiology (2019)
Publication types: Research Article;