syedzayyan/paper_mill_benchmark huggingface dataset:
Green tea polyphenols attenuate LPS-induced inflammation through upregulating microRNA-9 in murine chondrogenic ATDC5 cells

Background osteoarthritis (oa), a universal chronic musculoskeletal disorder, is closely related to inflammation.More effective drugs for improving oa outcome are definitely needed.Herein, we attempted to verify the protective role of green tea polyphenols (gtp) after treatment with murine in atdc5 cells to reveal the regulatory mechanism.Methods atdc5 cells were stimulated with lipopolysaccharide (lps) to mimic an inflammatory response during oa.Cell activity, apoptosis, levels of relative proteins, and prophlogistic factors were tested via a cell counting kit‐8 experiment, a flow cytometry experiment, western blot, and rt‐q pcr (elisa and western blot), separately.Mi r‐9 level was detected by rt‐q pcr and altered via mi r‐9 mimic and inhibitor transfection.We finally studied mapk and nf‐κb pathways in gtp‐related modulations using western blot.Results lps caused inflammatory cell damage in atdc5 cells, showing decreased cell activity, enhanced apoptosis, and increased levels of pro‐inflammatory cytokines.Gtp pretreatments could significantly attenuate lps‐induced alterations.In addition, lps‐induced mi r‐9 upregulation was further positively regulated in atdc5 cells.The effects of gtp pretreatments in lps‐caused atdc5 cells were enhanced via mi r‐9 upregulation, whereas they were reduced via mi r‐9 suppression.Finally, we found that gtp pretreatments could suppress the mapk and nf‐κb pathways through mi r‐9 regulation.Conclusion gtp pretreatments attenuated lps‐induced inflammatory response accompanied by the suppression of the mapk and nf‐κb pathways via positively regulating mi r‐9 in atdc5 cells.

Journal: Journal of Cellular Physiology (2019)
Publication types: Research Article;
microRNA-203 promotes proliferation, differentiation, and migration of osteoblasts by upregulation of Msh homeobox 2

Despite the improvements in fracture healing, about 10% of patients undergo abnormal healing.As a tumor suppressor, upregulation of micro rna (mi r)‐203 has been observed in osteogenic differentiation.Herein, we aimed to explore the functional role of mi r‐203 in osteoblasts as well as the underlying mechanisms.The expression of mi r‐203 in mc3t3‐e1 cells that underwent osteogenic differentiation was determined by quantitative reverse transcription pcr (q rt‐pcr).The effects of aberrantly expressed mi r‐203 on cell viability, migration, and expressions of proteins associated with proliferation, migration, and osteogenic differentiation were measured by using a cell counting kit‐8 assay, transwell cell migration assay, and western blot/q rt‐pcr, respectively.The possible downstream factor of mi r‐203 was subsequently studied.Finally, involvements of the mitogen‐activated protein kinase (mapk)/activator of transcription (stat) pathways were assessed by western blot.We found that the mi r‐203 level was increased in osteogenic differentiation of mc3t3‐e1 cells with increasing duration time (28th day, p &lt; 0.001).After cell transfection, we interestingly found that mi r‐203 overexpression could increase cell viability ( p &lt; 0.05), promote proliferation, migration ( p &lt; 0.05), and osteogenic differentiation, and upregulate msh homeobox 2 (msx2) expression.Furthermore, msx2 knockdown was proved to abrogate the effects of mi r‐203 overexpression on mc3t3‐e1 cells.Finally, phosphorylated levels of key kinases in the mapk/stat pathways were increased by mi r‐203 overexpression via upregulating msx2 expression.In conclusion, mi r‐203 overexpression promoted proliferation, migration, and osteogenic differentiation of mc3t3‐e1 cells through upregulating msx2 along with activation of the mapk/stat pathways.

Journal: Journal of Cellular Physiology (2019)
Publication types: Research Article;
Ras-PI3K-AKT signaling promotes the occurrence and development of uveal melanoma by downregulating H3K56ac expression

Background uveal melanoma (um) is an intraocular malignant tumor characterized by rapid progression and recurrence.The current conventional treatments are unsatisfactory.Histone acetylation at h3 lysine 56 (h3k56ac) has been reported to be a tumor suppressor in breast cancer.However, whether h3k56ac prevents the occurrence and development of um remains uninvestigated.The study aimed to explore the regulatory effect of h3k56ac on ras‐pi3k‐akt induced um cells proliferation and migration.Methods the vectors of p egfp‐ras wt , p egfp‐k‐ras g12v/y40c , and p egfp‐n1 were transfected into mp46 cells, and protein levels of phosphorylated akt ser473 and h3k56ac were examined using western blot analysis.The effect of h3k56ac on cell proliferation and migration were studied using 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5 diphenyl tetrazolium bromide, colony formation, and transwell assays.Reverse transcription‐quantitative polymerase chain reaction (rt‐q pcr) and chromatin immunoprecipitation assays were performed to determine the phosphoinositide 3‐kinase/protein kinase b (pi3k/akt) downstream genes.Further, the regulatory effects of silent mating type information regulation 2 homolog‐1 (sirt1), general control nonderepressible 5 (gcn5), and mouse double minute 2 homolog (mdm2) on ras‐pi3k‐akt affected h3k56ac expression were also investigated.Results h3k56ac expression was specifically downregulated by ras‐pi3k‐akt activation pathway.H3k56ac inhibited the tumorigenic effect of ras‐pi3k‐akt on mp46 cells viability, colony formation, and migration, as well as participated in regulating the transcription of pi3k/akt downstream genes.Sirt1 silence recovered h3k56ac expression, and reversed the tumorigenic effect of ras‐pi3k‐akt activation on mp46 cells.Downregulation of h3k56ac induced by ras‐pi3k‐akt activation was found to be associated with mdm2‐mediated the degradation of gcn5.Conclusions the results demonstrated that ras‐pi3k‐akt signaling promoted um cells proliferation and migration via downregulation of h3k56ac expression, which might be related to mdm2‐mediated the degradation of gcn5.

Journal: Journal of Cellular Physiology (2019)
Publication types: Research Article;
Carcinogenic role of K-Ras-ERK1/2 signaling in bladder cancer via inhibition of H1.2 phosphorylation at T146

It has been reported that ras‐erk signaling regulated tumor suppressive genes via epigenetic mechanisms.Herein, we set out to investigate the correlation between k‐ras‐erk1/2 signaling and h1.2 phosphorylation, to provide a better understanding of k‐ras‐erk signaling in cancer.A plasmid for expression of mutated k‐ras was transfected into human bladder carcinoma ht1197 cells.Western blot was carried out for testing the expression changes of erk1/2 and h1.2.The 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (mtt) assay, soft‐agar colony formation assay, and transwell assay were used to test the effects of h1.2 phosphorylation at t146 (h1.2 t146ph ) on ht1197 cells growth and migration.Quantitative reverse transcription polymerase chain reaction (q rt‐pcr) and chromatin immunoprecipitation (ch ip) were performed to test whether h1.2 t146ph regulated k‐ras‐erk1/2 downstream genes.Furthermore, how k‐ras‐erk1/2 regulated h1.2 t146ph expression was studied.We found that the erk1/2 was activated when k‐ras was mutated, and h1.2 t146ph expression was significantly downregulated by k‐ras mutation.H1.2 t146e for mimicking h1.2 t146ph significantly attenuated k‐ras mutation induced increases in ht1197 cells viability, colony formation, and relative migration.Besides, h1.2 t146ph regulated the transcription of k‐ras‐erk1/2 downstream genes, including nt5e , gdf15 , card16 , cyr61 , igfbp3 , and wnt16b .Furthermore, k‐ras‐erk1/2 signaling inhibited h1.2 phosphorylation at t146 through degradation of dna‐pk, and the degraded dna‐pk by k‐ras‐erk1/2 possibly via modulation of mdm2.In conclusion, the activation of k‐ras‐erk1/2 signaling will repress the phosphorylation of h1.2 at t146, and thereby, promoted the growth and migration of bladder cancer cells.K‐ras‐erk1/2 signaling repressed h1.2 phosphorylation possibly by mdm2‐mediated degradation of dna‐pk.

Journal: Journal of Cellular Physiology (2019)
Publication types: Research Article;
Curcumin ameliorates atherosclerosis through upregulation of miR-126

The potential usage of curcumin in diverse human diseases has been widely studied, including arteriosclerosis (as).This study focused on investigating the relationship between curcumin and as‐associated micro rna, which may provide a better understanding of curcumin in a different mechanism.Human microvascular endothelial hmec‐1 cells were treated by curcumin alone or oxidized low‐density lipoprotein (ox‐ldl) plus curcumin, after which the following parameters were analyzed: cell viability, migration, and the expression of as‐associated factors.The regulatory effects of curcumin on mi r‐126 and signaling pathways involved in as were then studied.Further, an animal model of as was stimulated by feeding rabbits with 1% cholesterol diet.The effects of curcumin on the animal model were explored.We found that curcumin treatment significantly reduced hmec‐1 cells viability, migration, and the protein levels of mmp‐2, mmp‐9, and vascular endothelial growth factor (vegf) in the presence or absence of ox‐ldl.Meanwhile, the expression of vegfr1 and vegfr2 was repressed by curcumin.Mi r‐126 was upregulated by curcumin.The abovementioned effects of curcumin on hmec‐1 cells were all attenuated when mi r‐126 was silenced.And also, vegf was a target gene of mi r‐126, and curcumin could inhibit the activation of pi3k/akt jak2/stat5 signaling pathways via mi r‐126.The effects of curcumin and its regulation on mi r‐126 and vegf were confirmed in the animal model of as.To sum up, curcumin exerted potent anti‐as property possibly via upregulating mi r‐126 and thereby inhibiting pi3k/akt and jak2/stat5 signaling pathways.

Journal: Journal of Cellular Physiology (2019)
Publication types: Research Article;
Nimotuzuma restrains proliferation and induces apoptosis in human osteosarcoma cells by regulation of EGFR/PI3K/AKT signal pathway

Osteosarcoma (os) is a conversant malignant bone tumor, commonly occurs in children and adolescents.Nimotuzuma is an epidermal growth factor receptor (egrf) monoclonal antibody agent, which has been exploited in varied solid tumors.Nevertheless, the functions of nimotuzuma in os remain blurry.We attempted to disclose the impacts of nimotuzuma on os cells proliferation and apoptosis.Os mg‐63 and u2os cells were stimulated with the disparate doses of nimotuzuma.Then, cell viability, cell cycle, and apoptosis were appraised through executing cck‐8 and flow cytometry assays.Moreover, the change of mitochondrial membrane potential (δψm) was estimated via jc‐1 fluorescent probe to further probe the impacts of nimotuzuma on cell apoptosis.The proteins of cell apoptosis, cell cycle, and egfr/pi3k/akt were appraised via western blot.Eventually, nimotuzuma together egrf or pi3k inhibitor (ly294002) were utilized to dispose mg‐63 to further uncover the latent mechanism.We found that nimotuzuma remarkably repressed cell viability at a time‐ and dose‐dependent manners in mg‐63 and u2os cells.The percentage of the s phase cells was evidently reduced by nimotuzuma through regulating p21, cyclin e1, and cyclin d1.In addition, nimotuzuma obviously evoked cell apoptosis, meanwhile elevated bid, bax, and cleaved‐caspase‐3.Further exploration showed that nimotuzuma decreased δψm in a dose‐dependent manner in mg‐63 and u2os cells.Besides, we discovered the repressive functions of nimotuzuma in os cells proliferation and apoptosis via hindering the egfr/pi3k/akt pathway.These investigations testified that nimotuzuma repressed cell growth by restraining the egfr/pi3k/akt pathway in os cells, hinting the antitumor activity of nimotuzuma in os.

Journal: Journal of Cellular Physiology (2019)
Publication types: Research Article;
Long noncoding RNA PEG10 facilitates bladder cancer cells proliferation, migration, and invasion via repressing microRNA-29b

Long noncoding rna paternally expressed gene 10 (lnc rna peg10) has been certified to regulate cell proliferation, metastasis, and apoptosis in diversified cancer cells.Nevertheless, the functions of peg10 in bladder cancer cells remain uninvestigated.We tried to probe the impacts of peg10 on proliferation, migration, and invasion of bladder cancer cells.Peg10 expression in sv‐huc‐1, t24, rt4, and 253j‐bv cells was estimated by quantitative reverse transcription‐polymerase chain reaction (rt‐q pcr).After pc‐peg10 or sh‐peg10 transfection, the impacts of peg10 on t24 and 253j‐bv cell viability, migration, invasion, and the relevant proteins were disclosed via employing cck‐8, transwell, and western blot.The relevancy between mi r‐29b and peg10 was probed, and the influences of overexpressed mi r‐29b in above‐mentioned cell biological processes were reassessed.Wnt/β‐catenin and jnk pathways were ultimately analyzed to unmake the underling mechanism.We found that overexpressed peg10 facilitated cell viability and upregulated cyclin d1, cdk4, and cdk6 in t24 and 253j‐bv cells.Cell migration and invasion were also elevated by overexpressed peg10 through the enhancement of mmp‐2, mmp‐9, and vimentin.In addition, repressed mi r‐29b was observed in peg10‐overexpressed t24 and 253j‐bv cells.Moreover, overexpressed mi r‐29b overtly overturned the carcinogenic impacts of peg10 on t24 cells.The activations of wnt/β‐catenin and jnk pathways were enhanced by overexpressed peg10 via mediating mi r‐29b.Sp600125 (jnk inhibitor) disposition reversed the acceerative impacts of peg10 on cell proliferation, migration, and invasion in t24 cells.In conclusion, the investigations testified that peg10 gave play to the carcinogenic impacts on bladder cancer cells via mediating mi r‐29b‐wnt/β‐catenin‐jnk axis.

Journal: Journal of Cellular Physiology (2019)
Publication types: Research Article;
Silencing circular RNA circANKRD36 remits lipopolysaccharide-induced inflammatory damage by regulating microRNA-15/MyD88

Bedsore is a familiar disease, which fearfully harms the health of the patients.We investigated the efficacy and mechanism of circular rna circ ankrd36 on ha ca t cell in inflammatory damage.Cck‐8 and flow cytometry were respectively used to investigate the efficacies of lipopolysaccharide (lps), circ ankrd36, and micro rna (mi r)‐15 on cell viability and apoptosis.Moreover, circ ankrd36 and mi r‐15 expression were changed by cell transfection and investigated by reverse transcription‐quantitative polymerase chain reaction.Furthermore, the levels of bax, pro caspase‐3, cleaved caspase‐3, interleukin (il)‐1β, il‐6, and proteins of the pathway were investigated by western blot.Otherwise, the levels of il‐1β and il‐6 were investigated by enzyme‐linked immunosorbent assay.Reactive oxygen species (ros) was investigated by ros assay.The relation between myeloid differentiation factor 88 (my d88) and mi r‐15 was investigated by luciferase assay.Lps caused inflammatory damage and upregulated circ ankrd36.Circ ankrd36 was silenced in cells and si‐circ ankrd36 remitted inflammatory damage.Furthermore, si‐circ ankrd36 negatively regulated mi r‐15 and mi r‐15 inhibitor could reverse the efficacies of si‐circ ankrd36.Besides, si‐circ ankrd36 restrained the nf‐κb pathway by upregulating mi r‐15.Finally, my d88 was authenticated as a target of mi r‐15.Circ ankrd36 remitted cell inflammatory damage upregulating mi r‐15/my d88 via the nf‐κb pathway in ha ca t cells.

Journal: Journal of Cellular Biochemistry (2019)
Publication types: Research Article;
Silence of cZNF292 suppresses the growth, migration, and invasion of human esophageal cancer Eca-109 cells via upregulating miR-206

Circular rna (circ rna) c znf292 has been previously revealed as a circular oncogenic rna.This study attempted to illustrate the functions of c znf292 in human esophageal carcinoma eca‐109 cells.Eca‐109 cells were transfected with the short hairpin rna specific against c znf292 (sh‐c znf292) and/or mi r‐206 inhibitor.C znf292 and mi r‐206 expression was examined by quantitative reverse transcriptase polymerase chain reaction (q rt‐pcr).Cell counting kit‐8 and flow cytometry were performed for detecting cell growth including cell viability as well as apoptosis.Various kinds of factors, which are involved in cell development including proliferation, apoptosis, migration, and invasion were determined by western blot analysis.Besides, the activation of amp‐activated protein kinase (ampk) and pi3k/akt signaling was measured by western blot analysis.It was found that c znf292 silencing decreased eca‐109 cell viability and induced apoptosis.In the meantime, c znf292 silencing inhibited cell migration and invasion.C znf292 silencing upregulated mi r‐206 expression.And mi r‐206 downregulation impaired the suppressive effects of c znf292 silence toward eca‐109 cell growth, migration, and invasion.C znf292 silencing activated ampk signaling and inactivated pi3k/akt signaling also via regulating mi r‐206.In conclusion, silencing of c znf292 abated growth, migration, and invasion of eca‐109 cells by upregulating mi r‐206, which subsequently modulated ampk and pi3k/akt signaling pathways.

Journal: Journal of Cellular Biochemistry (2019)
Publication types: Research Article;
Dexmedetomidine alleviates neuropathic pain by regulating JAK/STAT pathway in rats

Neuropathic pain (npp) is an unfavorable pathological pain with the characteristics of hyperalgesia, allodynia, and spontaneous pain.This study aimed to study the influence of dexmedetomidine (dex) on npp.Chronic constriction injury (cci) was operated to form the npp rat model.The ox42 and anti‐glial fibrillary acidic protein (gfap), the nerve growth factors (ngfs), and the janus kinase/signal transducers and activators of transcription (jak/stat) proteins were separately detected by quantitative reverse transcription‐polymerase chain reaction or western blot.Inflammatory factors were detected by enzyme‐linked immunosorbent assay.The results demonstrated that dex obviously alleviated cci‐stimulated mechanical allodynia and thermal hyperalgesia.Meanwhile, the expressions of interleukin‐1β, tumor necrosis factor‐α, chemokine c‐x3‐c‐motif ligand 1, and c‐c motif chemokine ligand 2 were greatly increased in cci rats, but these effects were reversed by dex.In addition, dex promoted the expressions of ngf, brain‐derived neurotrophic factor, neurotrophins‐3 (nt‐3), and nt‐4 in cci rats.Moreover, the rna or protein expression levels of ox42 and gfap were significantly increased in cci rats, while dex inhibited the expressions of ox42 and gfap.Furthermore, dex blocked jak/stat signaling pathway by decreasing p‐jak and p‐stat in cci rats.Dex had the potential to alleviate npp by regulating jak/stat pathway in cci rat.

Journal: Journal of Cellular Biochemistry (2019)
Publication types: Research Article;
The circular RNA-NRIP1 plays oncogenic roles by targeting microRNA-505 in the renal carcinoma cell lines

We explored the roles and regulatory mechanisms of the circular rna (circ rna) nuclear receptor‐interacting protein 1 (nrip1; circ nrip1) in achn and caki‐1 cells.Achn and caki‐1 cells were transfected with small‐interfering‐circ nrip1 (si‐circ nrip1) and micro rna‐505 (mi r‐505) inhibitor or the corresponding controls.Cell viability was detected with the cell counting kit‐8.The protein expression levels of bcl‐2, bax, cleaved‐caspase‐3, matrix metalloproteinase (mmp)‐2, mmp‐9, adenosine 5′‐monophosphate (amp)‐activated protein kinase (ampk), protein kinase b (akt), phosphatidylinositol 3‐kinase (pi3k), and mammalian target of rapamycin (m tor) were individually determined via western blot.Quantitative reverse transcription polymerase chain reaction was used to examine the expressions of circ nrip1 and mi r‐505 both in tumor cells and tissues.The apoptotic rate, the colony numbers, and the migration rate were separately determined by the annexin v‐fluorescein isothiocyanate/propidium iodide and flow cytometer, colony formation assay, and migration assay.We found that circ nrip1 was overexpressed in tumor tissue but mi r‐505 was overproduced.Silencing circ znf292 induced inhibition of cell viability, colony formation, and migration, as well as the activity of ampk and pi3k/akt/m tor cascades but enhancement of apoptosis.Si‐circ nrip1 stimulated the upregulation of mi r‐505, whose silence abolished the effects of si‐circ nrip1 on these elements mentioned above.In conclusion, the circ nrip1 played oncogenic roles in the achn and the caki‐1 cell lines by targeting mi r‐505 via stimulating ampk and pi3k/akt/m tor cascades.

Journal: Journal of Cellular Biochemistry (2019)
Publication types: Research Article;
Long noncoding RNA PCAT-1 knockdown prevents the development of ovarian cancer cells via microRNA-124-3p

Long noncoding rna prostate cancer‐associated transcript 1 (pcat‐1) is overexpressed in human malignancies and its silence abates the exaggeration of cancers.Whereas, the activity of pcat‐1 silence in ovarian cancer (oc) remains elusive.Here, our study was designed to corroborate the function of pcat‐1 silence in cellular activities and the molecular mechanisms.Pcat‐1 in human ovarian tumor tissue specimens and cell lines (a2780 and skov3) were quantified by real‐time quantitative reverse polymerase chain reaction (q rt‐pcr).Reinforced silence of pcat‐1 and micro rna (mi r)‐124‐3p was established by transfection and identified by q rt‐pcr.The viability, apoptosis as well as migration and invasion were examined.Western blot was exploited for analysis of proteins involved in proliferation, apoptosis, migration and invasion, and signaling transduction.Oc tissues showed the accumulation of pcat‐1.Silencing pcat‐1 caused the impediment of proliferation, migration, and invasion with the increase in apoptosis.Pcat‐1 knockdown repressed the expression of cyclin d1, cdk6, p53, bax, cleaved caspase‐3, metallopeptidases, and vimentin with the restoration of mi r‐124‐3p.However, the roles of pcat‐1 silence were weakened in the absence of mi r‐124‐3p.Pcat‐1 silence caused decrease in wnt3a, β‐catenin, and phosphorylation of protein kinase b and mechanistic target of rapamycin was abolished by mi r‐124‐3p inhibitor.The tumor‐suppressive role of pcat‐1 silence was mediated by mi r‐124‐3p.

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