syedzayyan/paper_mill_benchmark huggingface dataset:
Roles of the Exogenous H2S-Mediated SR-A Signaling Pathway in Renal Ischemia/ Reperfusion Injury in Regulating Endoplasmic Reticulum Stress-Induced Autophagy in a Rat Model

This study aims to explore the effects of the exogenous hydrogen sulfide (h2s)-mediated scavenger receptor a (sr-a) signaling pathway on renal ischemia/reperfusion injury (iri) by regulating endoplasmic reticulum (er) stress-induced autophagy in rats.Methods: a total of 48 normal sprague-dawley (sd) rats and sr-a knockout rats were selected and divided into six groups (n = 8): wild-type (wt) + sham, wt + ischemia-reperfusion (i/r), wt + i/r + na hs, sr-a-/- + sham, sr-a-/- + i/r and sr-a-/- + i/r + na hs.The concentrations of urinary protein, blood urea nitrogen (bun), serum creatinine (scr), malondialdehyde (mda) and h2s in renal tissue were detected.Q rt-pcr and western blotting were used to detect the m rna and protein levels of il-6, tgf-β, sr-a, lc3i, lc3ii, p62, perk, atf6 and ire1 pathway-related genes.A tunel assay was used to detect cell apoptosis.Electron microscopy was applied to observe the structure of renal autophagosomes.Results: compared with the wt + sham group, in the rates of the wt + i/r group, the urine volume, urinary protein, bun, scr and mda concentrations, the m rna and protein expression of il-6, tgf-β, lc3ii/i, and er stress pathway-related genes, the cell apoptosis index, and the number of autophagosomes were significantly increased 24 h after i/r, while p62 and sr-a protein expression and sod and h2s concentrations were significantly decreased (all p &lt; 0.05).The levels of renal injury, autophagy and er stress pathway-related genes were decreased in the wt + i/r + na hs group but were increased in the sr-a-/- + i/r group relative to the wt + i/r group.No significant differences were observed in the urine volume; the concentrations of urinary protein, bun, scr and mda; the sod activity; the m rna and protein expression of il-6, tgf-β, sr-a, grp78, sr-a, gpr94, atf4, ire1, xbp1, atf6, and e if2α; the cell apoptosis index; or the number of autophagosomes in rats of the sr-a-/- + i/r and sr-a-/- + i/r + na hs groups (all p &gt; 0.05).Conclusion: these results demonstrate that the exogenous h2s-mediated sr-a signaling pathway reduces renal iri injury by up-regulating er stress-induced autophagy in rats.

Journal: Cellular Physiology and Biochemistry (2017)
Publication types: Research Article;
Thermal Preconditioning May Prevent Tendon Adhesion by Up-Regulating HSP72 in Rats

The study aims to determine the effects of thermal preconditioning on tendon adhesion by regulating the expression of heat shock protein 72 (hsp72) in rat models.Methods: sixty male wistar rats were collected and randomly assigned into the thermal preconditioning and control groups.During the 4th and 8th weeks following surgery, 15 rats were sacrificed in each period respectively, and their tendon adhesion was observed and evaluated.Biomechanical testing was performed to measure the tensile strength and gliding distance of tendons.Hematoxylin-eosin (he) was used to observe the morphological structure of the tendons.Immunohistochemical staining, quantitative real-time polymerase chain reaction (q rt-pcr) and western blotting were used to detect the hsp72, fibroblast growth factor-2 (fgf-2), fibroblast growth factor receptor-1 (fgfr-1), β-catenin, epithelial cell adhesion molecule (epcam), tenomodulin and scleraxis protein expressions.Pearson correlation analysis was applied to analyze the correlation between hsp72 expression and tendon adhesion.Results: at the 4th week after surgery, we found no differences in the tendon adhesion scores or m rna and protein expressions of hsp72 between the thermal preconditioning and control groups.However, after the 8th week after surgery, the thermal preconditioning group had a lower tendon adhesion score and higher m rna and protein expressions of hsp72 than the control group.During the same period, we found longer gliding distance and higher expression levels of fgf-2, fgfr-1, β-catenin, tenomodulin and scleraxis, but lower epcam expression in the thermal preconditioning group.Pearson correlation analysis indicated that hsp72 m rna and protein expression levels were negatively correlated with tendon adhesion.Conclusions: these findings provide evidence that thermal preconditioning may alleviate tendon adhesions via upregulation of hsp72 expression.

Journal: Cellular Physiology and Biochemistry (2017)
Publication types: Research Article;
Inhibition of MicroRNA-21-5p Promotes the Radiation Sensitivity of Non-Small Cell Lung Cancer Through HMSH2

This study aimed to explore the effects of micro rna-21-5p (mi r-21-5p) on the radiation sensitivity of non-small cell lung cancer (nsclc) and the involvement of human mut s homolog 2 (h msh2) one hundred fourteen nsclc patients at stage ii or iii who received surgery and postoperative radiotherapy were enrolled in this study.Methods: the patients were assigned into radiation-sensitive and -insensitive groups.Nsclc a549 cells were transfected to generate control, negative control (nc), mi r-21-5p inhibitor, mi r-21-5p mimic, small interfering h msh2 (sih msh2), mi r-21-5p inhibitor + sih msh2 and h msh2 overexpression groups.Immunohistochemistry was performed to detect the h msh2 expression in transfected and irradiated cells.Quantitative real-time polymerase chain reaction (q rt-pcr) and western blotting were performed to evaluate a549 mi r-21-5p and h msh2 expression in transfected and irradiated cells.A colony formation assay was adopted for cell survival analysis.The relationship between mi r-21-5p and h msh2 was verified by a luciferase reporter assay.Cell viability was measured by the mtt (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, and apoptosis was assessed by flow cytometry.Nsclc nude mouse models were established, and tumor volumes and tumor weights were recorded.Results: the radiation-sensitive group of patients exhibited lower mi r-21-5p but higher h msh2 expression than the insensitive group.For irradiated a549 cells, lower cell survival, higher apoptosis, increased mi r-21-5p expression and decreased h msh2 expression were observed at 6 and 8 gy than at 0, 2 and 4 gy; compared to 6 gy, cell survival and h msh2 expression were decreased and apoptosis and mi r-21-5p expression were increased at 8 gy.Additionally, mi r-21-5p was found to target h msh2.Compared with the control group, the cell survival rate was lower and the apoptosis rate higher in the mi r-21-5p inhibitor group, whereas the opposite was observed for the mi r-21-5p mimic and sih msh2 groups.For the mouse model, decreased tumor volume and tumor weight and higher h msh2 expression were found in the mi r-21-5p inhibitor, radiation, h msh2 overexpression, mi r-21-5p inhibitor + radiation and h msh2 overexpression + radiation groups compared with the control group.In addition, tumor volume and tumor weight were decreased and h msh2 expression increased in the mi r-21-5p inhibitor + radiation and h msh2 overexpression + radiation groups compared with the radiation alone group.Conclusion: these findings indicate that inhibition of mi r-21 can promote the radiation sensitivity of nsclc by targeting h msh2.

Journal: Cellular Physiology and Biochemistry (2017)
Publication types: Research Article;
Role of the TGFβ/PDCD4/AP-1 Signaling Pathway in Nasopharyngeal Carcinoma and Its Relationship to Prognosis

The objective of the present study was to evaluate the role of the tgfβ/pdcd4/ap-1 pathway in nasopharyngeal carcinoma (npc) and its relationship to npc prognosis.Methods: npc tissues collected from 66 npc patients were compared to 17 nasopharyngeal mucosa biopsy specimens collected as normal tissues.Immunohistochemical staining was performed to assess expression of transforming growth factor-β receptor i (tgfβri), programmed cell death 4 (pdcd4) and activator protein-1 (ap-1).The kaplan-meier method was applied to evaluate npc patient overall survival (os) and progression-free-survival (pfs).Cox regression analysis was used to estimate independent prognostic factors for npc.The human npc cell line cne2 was selected and treated with sb431542, an inhibitor of tgfβri; expression of tgfβri and pdcd4 in cne2 cells was determined by western blotting.Npc tissues showed higher expression of tgfβri and ap-1 but lower expression of pdcd4 than normal tissues (all p &lt; 0.05).Results: the results of kaplan-meier analysis showed that tgfβri-positive patients and ap-1-positive patients had shorter os and pfs than tgfβri-negative patients and ap-1-negative patients; additionally, pdcd4-positive patients had higher os and pfs than pdcd4-negative patients.Cox regression analysis revealed that advanced tumor stage, overexpression of tgfβri and ap-1, and low expression of pdcd4 were unfavorable factors influencing os and pfs in npc patients.Compared with the control group, expression of tgfβri decreased and that of pdcd4 increased significantly in cne2 cells treated with the inhibitor (all p &lt; 0.05).These findings indicate that the tgfβ/pdcd4/ap-1 pathway may be associated with npc development and progression.Conclusion: high expression of tgfβri and ap-1 and low expression of pdcd4 may be unfavorable prognostic factors for npc.

Journal: Cellular Physiology and Biochemistry (2017)
Publication types: Research Article;
Artesunate Decreases β-Catenin Expression, Cell Proliferation and Apoptosis Resistance in the MG-63 Human Osteosarcoma Cell Line

This study aims to determine the effects of artesunate on proliferation, apoptosis and β-catenin expression in the human osteosarcoma cell line mg-63.Methods: mg-63 cells in the logarithmic growth phase were collected and cultured with different concentrations of artesunate (12.5 μg/m l, 25 μg/m l and 50 μg/m l) for 24 h, 48 h and 72 h.The total number of mg-63 cells and the morphological changes were observed under an inverted microscope.The mtt assay was adopted to test the inhibition rate (ir) of cell growth.The apoptosis rate was detected using annexin v/propidium iodide (pi) staining.Cell cycle distribution was identified by flow cytometry (fcm), and the expression levels of β-catenin, cyclins and cyclin dependent kinases (cdks) were measured using western blotting.Results: the results of the mtt assay indicated that artesunate could remarkably inhibit mg-63 cell proliferation compared with the rates in the untreated control group (0 μg/m l artesunate), and the inhibitory effect was dose-dependent.The apoptosis rate of mg-63 cells was elevated as the concentration of artesunate increased, and all the rates were significantly higher than that in the control group.Additionally, as the artesunate concentration increased, the proportion of mg-63 cells in g0/g1 phase gradually declined whereas that of cells in the g2/m and s phases increased.Western blotting confirmed that a higher concentration of artesunate reduced the expression levels of β-catenin, cyclin a, cyclin d1 and cdk1 and increased the expression levels of cyclin b1; however, artesunate had no impact on cdk2 expression in mg-63 cells.Conclusion: these results demonstrated that artesunate can inhibit β-catenin expression and cell proliferation as well as promote cell apoptosis in mg-63 cells, which indicates that artesunate may serve as a promising drug in the clinical treatment of osteosarcoma.

Journal: Cellular Physiology and Biochemistry (2017)
Publication types: Research Article;
Inhibition of the SOCS1-JAK2-STAT3 Signaling Pathway Confers Neuroprotection in Rats with Ischemic Stroke

The present study aims to investigate the protective effects of the socs1-jak2-stat3 signaling pathway on neurons in a rat model of ischemic stroke.Methods: our study was conducted using an ischemic stroke rat model.After the microglia were extracted, 40 neonatal sprague-dawley (sd) rats were assigned into the blank, ag490, model and negative control (nc) groups.The neurological function of all the rats was evaluated.Histopathological changes were observed.Q rt-pcr and western blotting were applied to measure the expression of genes and proteins in the socs1-jak2-stat3 signaling pathway and related to apoptosis.The tunel assay was conducted to calculate the cellular morphology and apoptosis of neuronal cells.Cell viability was detected using the mtt assay.In addition, immunoassays were used to measure the content of superoxide dismutase (sod), glutathione (gsh) and malondialdehyde (mda) as well as the levels of oxidative stress.Results: compared with the blank group, the model and nc groups showed higher neurological function scores—the cytoplasm of the neurons were cavitated, the organelles were reduced with unclear margins, some of the neurons were necrotic, and apoptosis was increased.In addition, the nc and model groups exhibited decreased cell viability, lower m rna and protein expression of socs1 socs3 and bcl-2 and reduced sod and gsh levels but higher m rna and protein expression levels of ak2, stat3,bax and caspase-3 as well as increased protein expression of p-jak2, p-stat3 and activated caspase-3 (c-caspase-3).Moreover, the mda levels were up-regulated in the nc and model groups.In contrast, opposing trends were found in the ag490 group compared with the nc and model groups.Conclusion: these data demonstrate that inhibiting the socs1-jak2-stat3 signaling pathway can reduce the loss of nerve function and apoptosis of neuronal cells, which provides a new target for the clinical treatment of ischemic stroke.

Journal: Cellular Physiology and Biochemistry (2017)
Publication types: Research Article;
Effects of MicroRNA-499 On the Inflammatory Damage of Endothelial Cells During Coronary Artery Disease Via the Targeting of PDCD4 Through the NF-Κβ/TNF-α Signaling Pathway

This study aimed to analyze the impact of micro rna-499 (mi r-499) on the inflammatory damage of endothelial cells during coronary artery disease (cad) via the targeting of pdcd4 through the nf-k b/ tnf-α signaling pathway.Methods: a total of 216 cad patients (cad group) and 90 healthy people (normal group) were enrolled in our study.Endothelial cells were collected and assigned into normal, ox-ldl, negative control (nc), mi r-499 inhibitor, mi r-499 mimic, pdcd4 si rna, and mi r-499 inhibitor + pdcd4 si rna groups.The q rt-pcr and western blotting were performed to detect the m rna and protein expression levels of pdcd4 and mi r-499.The mtt assay was performed to determine cell viability, elisa was performed to determine the expression levels of inflammatory factors, and flow cytometry assay to evaluate cell apoptosis.Results: increased mi r-499 expression and decreased pdcd4 expression in the plasma were observed in the cad group compared with the normal group, demonstrating a negative correlation between mi r-499 and pdcd4.Compared to the normal and mi r-499 inhibitor groups, the survival rate of cells and pdcd4 expression were decreased; and the expressions of mi r-499, il-6, il-8, il-1β, tnf-α, nf-k b, vcam-1, icam-1 and mcp-1 and the apoptosis rate were all elevated in the ox-ldl, nc, mi r-499 mimic, pdcd4 si rna and mi r-499 inhibitor + pdcd4 si rna groups.Compared to the ox-ldl, nc and mi r-499 inhibitor + pdcd4 si rna groups, pdcd4 expression and the survival rate of cells were increased; and the il-6, il-8, il-1β, tnf-α, nf-κb, vcam-1, icam-1 and mcp-1 expression levels and the apoptosis rate were all reduced in the mi r-499 inhibitor group.In the pdcd4 si rna group, pdcd4 expression and the survival rate of cells were lower, and the expression levels of il-6, il-8, il-1β, tnf-α, nf-κb, vcam-1, icam-1 and mcp-1 and the apoptosis rate were all higher compared with the mi r-499 mimic group.In the mi r-499 inhibitor + pdcd4 si rna group, pdcd4 expression and the survival rate of cells were higher, and the expression levels of il-6, il-8, il-1β, tnf-α, nf-κb, vcam-1, icam-1, and mcp-1 and the apoptosis rate were all lower than those in the pdcd4 si rna group.Conclusion: down-regulated mi r-499 expression increased pdcd4 expression and protected endothelial cells from inflammatory damage during cad by inhibiting the nf-κb/tnf-α signaling pathway.

Journal: Cellular Physiology and Biochemistry (2017)
Publication types: Research Article;
Salidroside Protection Against Oxidative Stress Injury Through the Wnt/β-Catenin Signaling Pathway in Rats with Parkinson’s Disease

Parkinson’s disease (pd) is the second most common neurodegenerative disease after alzheimer’s disease, and recent studies suggested that oxidative stress (os) contributes to the cascade that leads to dopamine cell degeneration in pd.In this study, we hypothesized that salidroside (sds) offers protection against os injury in 6-hydroxydopamine (6-ohda) unilaterally lesioned rats as well as the underlying mechanism.Methods: sds and li cl (activators of the wnt/β-catenin signaling pathway) administration alone and in combination with 6-ohda injection in rats was performed 3 days before modeling for 17 consecutive days to verify the regulatory mechanism by which sds affects the wnt/β-catenin signaling pathway as well as to evaluate the protective effect of sds on pd in relation to os in vivo.In addition, pheochromocytoma 12 (pc12) cells were incubated with 10 μmol/l sds or li cl alone or with both in combination for 1 h followed by a 24-h incubation with 100 μmol/l 6-ohda to obtain in vitro data.Results: in vivo the administration of li cl was found to ameliorate behavioral deficits and dopaminergic neuron loss; increase superoxide dismutase (soa) activity, glutathione peroxidase (gsh-px) levels, and glycogen synthase kinase 3β phosphorylation (gsk-3β-ser9); reduce malondialdehyde (mda) accumulation in the striatum and the gsk-3β m rna level; as well as elevate β-catenin and cyclin d1 m rna and protein levels in 6-ohda-injected rats.This sds treatment regimen was found to strengthen the beneficial effect of li cl on 6-ohda-injected rats.In vitro li cl treatment decreased the toxicity of 6-ohda on pc12 cells and prevented apoptosis.Additionally, li cl treatment increased soa activity, gsh-px levels, and gsk-3β-ser9 phosphorylation; decreased mda accumulation in the striatum and gsk-3β m rna levels; as well as increased β-catenin and cyclin d1 m rna and protein levels in 6-ohda-treated pc12 cells.Additionally, sds treatment increased the protective effect of li cl on 6-ohda-treated pc12 cells.Conclusion: evidence from experimental models suggested that sds may confer neuroprotection against the neurotoxicity of 6-ohda in response to os injury and showed that these beneficial effects may be related to regulation of the wnt/β-catenin signaling pathway.Therefore, sds might be a potential therapeutic agent for treating pd.

Journal: Cellular Physiology and Biochemistry (2018)
Publication types: Research Article;
MicroRNA-141 Inhibits the Proliferation of Penile Cavernous Smooth Muscle Cells Associated with Down-Regulation of the Rhoa/Rho Kinase Signaling Pathway

The role of the rho a/rho kinase signaling pathway in diabetes mellitus-induced erectile dysfunction has been partially understood.Methods: in the present study, we explored the changes of the rho a/rho associated kinase (rock) signaling pathway in diabetic erectile dysfunction in vivo and the effects of micro rna-141 on the rho a/rock signaling pathway in vitro.Results: the m rna and protein expressions of rho a and rock2 were significantly increased while the expression of micro rna-141 was decreased in the penile cavernous smooth muscle cells of rats with diabetic erectile dysfunction.Moreover, increased expression of micro rna-141, decreased expressions of rho a and rock2 (m rna and protein), accelerated cell proliferation rate and reduced cell apoptosis were found in the micro rna-141 mimics group and the si rna-rho group.The micro rna-141 expression in the micro rna-141 inhibitors + si rna-rho group was significantly decreased.Micro rna-141 specifically bound to rho-3’-utr and down-regulated the expression of rho gene at the post transcriptional level.Conclusion: decreased expression of mi r-141 is associated with up-regulation of rho a and rock2 in the rho a/rock signaling pathway in rats with diabetic erectile dysfunction.Mi r-141 inhibits the growth of penile cavernous smooth muscle cells associated with down-regulation of the rho a/rock signaling pathway in vitro.

Journal: Cellular Physiology and Biochemistry (2018)
Publication types: Research Article;
Erinacine Facilitates the Opening of the Mitochondrial Permeability Transition Pore Through the Inhibition of the PI3K/Akt/GSK-3β Signaling Pathway in Human Hepatocellular Carcinoma

Erinacine, which is extracted from the medicinal mushroom hericium erinaceus, is known to play anticancer roles in human cancers.The following study aims to investigate the role of erinacine in the opening of the mitochondrial permeability transition pore (mptp) in hepatocellular carcinoma (hcc) through the pi3k/akt/gsk-3β signaling pathway and highlights the applicability of erinacine in hcc treatments.Methods: hcc and paracancerous tissues were obtained from 85 hcc patients who’ve undergone surgical resection.Immunohistochemistry was adopted to detect positive expression of pi3k, akt, and gsk-3β.Treatment of hep g-2 with ly294002 (an inhibitor of the pi3k/akt/gsk-3β signaling pathway) and different concentration of erinacine was performed to determine the involvement of ly294002 in erinacine action.The expressions of pi3k, akt, gsk-3β, cyclin d1, vimentin, β-catenin, bcl-2, e-cadherin, bax, and caspase-9 were determined by rt-q pcr and western blot analysis.Cell viability, colony formation rate, migration, invasion, cycle, and apoptosis were detected by mtt, colony formation, wound healing assay, transwell assay, and flow cytometry, respectively.The size and weight of xenograft tumors were observed in nude mice.Mitochondrial membrane potential in hep g-2 was determined using laser scanning confocal microscopy following jc-1 staining.Mitochondrial ca2+ indicator rhod-2, am was used to detect the changes of mitochondrial ca2+, while western blot analysis was employed to detect the presence levels of cytochrome c (cyt-c).Results: the results revealed that pi3k, akt, and gsk-3β were up-regulated in hcc tissues.Erinacine or ly294002 led to a decrease in mitochondrial membrane potential, increase in intracellular mitochondrial ca2+, and the release of cyt-c in mitochondria.In addition, erinacine was found to decrease the mitochondrial membrane potential, expression of pi3k, akt, gsk-3β, cyclin d1, vimentin, β-catenin, and bcl-2, cell proliferation, colony formation ability, migration, invasion, and xenograft tumor size, while e-cadherin, bax, and caspase-9 expression, and cell apoptosis were elevated in a dose-dependent manner.Erinacine also stimulated the effects of ly294002 on the hcc.Following the addition of 500 μm erinacine and mptp opening inhibitor cs a, we found that the mitochondrial membrane potential level increased, while mitochondrial ca2+ and cyt-c decreased from the mitochondria.Conclusion: the results from the study demonstrated that erinacine induced mptp opening, facilitates the release of cyt-c, and inhibited cell proliferation, migration, and invasion, while it promotes apoptosis by inactivating the pi3k/akt/gsk-3β signaling pathway, preventing the progression of hcc.

Journal: Cellular Physiology and Biochemistry (2018)
Publication types: Research Article;