syedzayyan/paper_mill_benchmark huggingface dataset:
Soyasapogenol B Attenuates Laryngeal Carcinoma Progression through Inducing Apoptotic and Autophagic Cell Death

Soyasapogenol b (soy b), a constituent of soybean, has been shown to exhibit antitumor activities against different types of cancers.However, to our knowledge, no studies so far have investigated the effect of soy b in human laryngeal carcinoma.This study, therefore, aimed to determine the effect of soy b in human laryngeal carcinoma cell lines he p‐2 and tu212 and to elucidate the possible underlying mechanisms by which soy b can induce its antitumor effects.The results showed that soy b effectively attenuated the cell growth by causing g0/g1 phase cell cycle arrest in laryngeal carcinoma cell lines.Moreover, the percentage of apoptotic and autophagic cells dramatically increased upon exposure to soy b.Western blotting results confirmed that soy b can alter the expression levels of established markers of apoptosis and autophagy.Interestingly, both apoptosis inhibitor (zvad‐fmk) and autophagy inhibitor (3‐ma) could partially reverse the effect of soy b, while blocking autophagy did not cause obvious alteration in the percentage of apoptotic cells.Similarly, in vivo studies validated that soy b could effectively reduce the size of the tumor and induce apoptosis and autophagy in tumor tissues.Collectively, these results suggested that soy b can exert anticancer activities against laryngeal carcinoma through inducing apoptotic and autophagic cell death.Our study highlighted the potential role of soy b as a chemotherapeutic agent for laryngeal carcinoma.Anat rec, 2019.© 2019 american association for anatomy anat rec, 303:1851–1858, 2020.© 2019 american association for anatomy

Journal: The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology (2019)
Publication types: Research Article;
Furowanin A Exhibits Antiproliferative and Pro-Apoptotic Activities by Targeting Sphingosine Kinase 1 in Osteosarcoma

Osteosarcoma (os) is one of the most common malignant bone tumors among children and young adults.Furowanin a (fur a), one of the active ingredients of millettia pachycarpa benth, has been found to exert pro‐apoptotic activity in human leukemia cells.This study is designed to evaluate the efficacy of fur a against os.The effect of fur a on cell viability was assessed by cell counting kit‐8 (cck‐8) assay.Western blotting and quantitative real‐time pcr (q rt‐pcr) were performed to determine the protein and m rna level of sphingosine kinase 1 (sph k1), respectively.To validate the role of sph k1 in the pro‐apoptotic activity of fur a, overexpressing sph k1 vector and si rna targeting sph k1 were utilized to transfect os cells.Moreover, an os xenograft murine model was used to analyze the therapeutic efficacy of fur a in vivo .Fur a treatment led to a dose‐dependent decrease in the number of viable cells.It also exhibited antiproliferative activity and significantly promoted apoptotic cell death in os cell lines.Our results showed that the anticancer activity of fur a was associated with downregulation of sph k1 and inactivation of its downstream signaling.The mediatory role of sph k1 was validated when the pro‐apoptotic activity of fur a was significantly blocked by sph k1 overexpression, while sph k1 knockdown sensitized the os cells to fur a.We concluded that fur a can exhibit anti‐growth and pro‐apoptotic activities in vitro and in vivo in os by downregulating sph k1.Our study highlights the possibility of utilizing fur a as a chemotherapeutic agent in the treatment of os.Anat rec, 302:1941–1949, 2019.© 2019 american association for anatomy

Journal: The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology (2019)
Publication types: Research Article;
Long noncoding RNA TUG1 facilitates cell ovarian cancer progression through targeting MiR-29b-3p/MDM2 axis

Ovarian cancer (oc) is one of the most aggressive female cancers in the world.Oc trends to be diagnosed at an advanced stage with abdominal metastasis.Our study explored the biological function and underlying mechanism of lnc rna on oc cell proliferation and migration.The expression of turine up‐regulated gene 1 ( tug1 ) in human oc tissues and cell lines was measured by q rt‐pcr.Oc cell proliferation, viability, migration, and invasion were measured by mtt assays, colony formation assays, and transwell assays in vitro.Furthermore, the nude mice xenograft model was established to determine the effects of tug1 in vivo.The relationship between tug1 and mi r‐29b‐3p, as well as mi r‐29b‐3p and mdm2 were identified using the luciferase reporter assays.We showed that the expression of tug1 and mdm2 were significantly increased, but the expression of mi r‐29b‐3p was remarkably decreased in oc tissues and cell lines.Knockdown of tug1 strongly inhibited the ability of cell proliferation, colony formation, migration, and invasion in vitro.The relationship between tug1 and mi r‐29b‐3p, or mi r‐29b‐3p and mdm2 were predicted by star base and mi randa online software.Besides, mi r‐29b‐3p reversed the positive effect of tug1 on the oc cell proliferation, migration, and invasion through inhibiting mdm2 expression and increasing p53 phosphorylation level.Moreover, knockdown of tug1 suppressed tumor growth in vivo.Taken all together, this study shows that tug1 plays a crucial oncogenic role and facilitates cell proliferation, migration, and invasion in oc through regulating mi r‐29b‐3p/mdm2 axis.

Journal: The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology (2020)
Publication types: Research Article;
CircFBXW7 alleviates glioma progression through regulating miR-23a-3p/PTEN axis

Increasing evidence has confirmed that circular rnas (circ rnas) are involved in regulating the development and progression of various tumors.The aim of this study was to examine the effect of circ fbxw7 on the progression of glioma and to determine its underlying mechanism.Q rt‐pcr was performed to measure the expression of circ fbxw7, mi r‐23a‐3p, and pten in tissues and cell lines of glioma.The proliferation ability of glioma cells was examined using the cck‐8 assay.Glioma cell migration and invasion capacity were detected using transwell assays.The dual‐luciferase reporter gene assay was employed to examine the correlation between mi r‐23a‐3p and circ fbxw7 or pten.The expression levels of the related genes were determined using western blotting analysis.A glioma xenograft tumor model was employed to evaluate the functional roles of circ fbxw7 in vivo.Circ fbxw7 was found to be aberrantly downregulated in glioma tumor tissues and cell lines.Overexpression of circ fbxw7 was found to significantly inhibit the proliferation, migration and invasion ability of the glioma cells.Moreover, bioinformatic analysis and dual‐luciferase reporter assays confirmed that circ fbxw7 can directly target mi r‐23a‐3p, which then blocks the binding of mi r‐23a‐3p to the 3′ un‐translated region (utr) of pten.Mechanically, circ fbxw7 suppresses cell proliferation and metastasis in glioma by sponging mi r‐23a‐3p, resulting in elevated pten expression.In addition, in vivo experiments also confirmed that circ fbxw7 overexpression effectively halts tumor growth and metastasis.Consistent with the in vitro observations, circ fbxw7 overexpression significantly decreased mi r‐23a‐3p, ki‐67, and n‐cadherin, as well as increased pten and e‐cadherin levels.Our results revealed that circ fbxw7 exhibits antiproliferative and antimetastasis activities via sponging mi r‐23a‐3p to elevate pten expression in glioma, which may offer a novel target for clinical therapy and diagnosis of glioma.

Journal: The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology (2020)
Publication types: Research Article;
Resibufogenin inhibited colorectal cancer cell growth and tumorigenesis through triggering ferroptosis and ROS production mediated by GPX4 inactivation

Resibufogenin (rb) has been used for cancer treatment, but the underlying mechanisms are still unclear.This study aimed to investigate the effects of rb treatment on colorectal cancer (crc) cells, and to determine the underlying mechanisms.The cell counting kit‐8 assay was used to determine cell viability.Cell morphology was observed under light microscopy, and terminal deoxynucleotidyl transferase‐mediated d utp nick‐end labeling assay was employed to detect cell apoptosis.Intracellular ferrous iron (fe 2+ ), malondialdehyde (mda), glutathione (gsh), and reactive oxygen species levels were detected by using commercial iron assay kit, mda assay kit, gsh assay kit, and 2,7‐dichlorodihydrofluorescein diacetate probes, respectively.The protein expressions were determined by western blot and immunohistochemistry.Rb inhibited cell viability in the crc cell lines (ht29 and sw480) in a dose‐ and time‐dependent manner, and caused cytotoxicity to the normal colonic epithelial cell line (ncm460) at high dose.Similarly, rb induced morphological changes in crc cells from normal to round shape, and promoted cell death.Of note, rb triggered oxidative stress and ferroptotic cell death in crc cells, and only ferroptosis inhibitors (deferoxamine and ferrostatin‐1), instead of inhibitors for other types of cell death (apoptosis, autophagy, and necroptosis), reversed the inhibitory effects of rb on crc cell proliferation.Furthermore, glutathione peroxidase 4 (gpx4) was inactivated by rb treatment, and overexpression of gpx4 alleviated rb‐induced oxidative cell death in crc cells.Consistently, the in vivo experiments validated that rb also triggered oxidative stress, and inhibited crc cells growth and tumorigenicity in mice models.Rb can inhibit crc cells growth and tumorigenesis by triggering ferroptotic cell death in a gpx4 inactivation‐dependent manner.

Journal: The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology (2020)
Publication types: Research Article;
Alpinumisoflavone triggers GSDME-dependent pyroptosis in esophageal squamous cell carcinomas

Esophageal squamous cell carcinoma (escc) presents a common human malignancy in the digestive system.We aimed to explore the critical effects of alpinumisoflavone (aif) on escc in vitro and in vivo.The cell counting kit‐8 assay was used to determine cell viability.Colony formation assay was employed to examine the effect of aif on the long‐term growth of escc cells.Cell apoptosis was determined by flow cytometry and terminal deoxynucleotidyl transferase‐mediated d utp nick‐end labeling assay.Cell morphologies were observed by light microscopy.The enzyme‐linked immunosorbent assay was performed to examine the lactate dehydrogenase release from aif‐treated cells.Immunofluorescent labeling was utilized to examine aif‐induced gsdme expression.Western blot was employed to determine the expression levels of the associated proteins.Immunohistochemistry was performed to determine the localization and expression of the associated proteins in mice tumor tissues.Aif inhibited escc cell viability and suppressed cell growth in a dose‐ and time‐dependent fashion.Results showed that aif promoted apoptosis in escc cells.Meanwhile, our results also showed that aif triggered pyroptotic cell death in escc, which was mediated by gasdermin e (gsdme) cleavage.In addition, our experiments provided experimental evidence that aif‐induced gsdme cleavage was dependent on caspase‐3 activation.Moreover, the inhibition of gsdse by knockdown was able to switch the form of cell death from pyroptosis to apoptosis.Furthermore, the results from the xenograft animal model also supported our findings in vitro that aif was able to promote gsdme‐mediated pyroptotic cell death in escc.Aif inhibited escc growth in vitro and in vivo by triggering gsdme‐mediated pyroptotic cell death, which is dependent on caspase‐3 activation.

Journal: The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology (2020)
Publication types: Research Article;
Alpinumisoflavone suppresses human glioblastoma cell growth and induces cell cycle arrest through activating peroxisome proliferator-activated receptor-γ

As a common subtype of malignant gliomas, glioblastoma multiforme (gbm) is associated with poor prognosis.This study is aimed to examine the anticancer activities of alpinumisoflavone (aif) and its underlying mechanisms.Our results demonstrated that aif inhibited the proliferation of gbm cells (u373 and t98g) in a time and dose‐dependent manner.In addition, flow cytometry analysis not only confirmed aif arrested cell cycle at the g0/g1 phase but also the induced apoptosis of u373 and t98g cells.Western blotting also confirmed that aif altered the expression levels of cell cycle‐related proteins.Further mechanism studies revealed that aif inhibited cell proliferation, induced g0/g1 phase arrest and induced apoptosis of u373 and t98g cells through activating pparγ, as evidenced by the fact that gw9662 (pparγ inhibitor) could effectively reverse the effects of aif on u373 and t98g cells.Furthermore, the in vivo study also revealed that aif suppressed tumor growth and caused cell cycle arrest.Collectively, these results highlighted the potential use of aif in the treatment of gbm.

Journal: The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology (2020)
Publication types: Research Article;
microRNA-137 promotes endothelial progenitor cell proliferation and angiogenesis in cerebral ischemic stroke mice by targeting NR4A2 through the Notch pathway

Cerebral ischemic stroke (cis) is one of the common causes of death and disability worldwide.This study aims to investigate effect of mi r‐137 on endothelial progenitor cells and angiogenesis in cis by targeting nr4a2 via the notch pathway.Brain tissues were extracted from cis and normal mice.Immunohistochemistry was used to determine positive rate of nr4a2 expression.Serum vegf, ang, hgf, and iκbα levels were determined by elisa.Rt‐q pcr and western blotting were used to determine expression of related factors.Endothelial progenitor cells in cis mice were treated and grouped into blank, nc, mi r‐137 mimic, mi r‐137 inhibitor, si rna‐nr4a2, and mi r‐137 inhibitor + si rna‐nr4a2 groups, and cells in normal mice into normal group.Proliferation and apoptosis were determined by mtt and flow cytometry, respectively.Nr4a2 protein expression was strongly positive in cis mice, which showed higher serum levels of vegf, ang, and hgf but lower iκbα than normal mice.Compared with normal group, the rest groups (endothelial progenitor cells from cis mice) showed decreased expressions of mi r‐137, hes1, hes5, and iκbα but elevated nr4a2, notch, jagged1, hey‐2, vegf, ang, and hgf, inhibited proliferation and enhanced apoptosis.Compared with blank and nc groups, the mi r‐137 mimic and si rna‐nr4a2 groups exhibited increased expression of mi r‐137, hes1, hes5, and iκbα, but decreased nr4a2, notch, jagged1, and hey‐2, with enhanced proliferation and attenuated apoptosis.The mi r‐137 inhibitor group reversed the conditions.Mi r‐137 enhances the endothelial progenitor cell proliferation and angiogenesis in cis mice by targeting nr4a2 through the notch signaling pathway.

Journal: Journal of Cellular Physiology (2017)
Publication types: Research Article;
Effects of microRNA-129 and its target gene c-Fos on proliferation and apoptosis of hippocampal neurons in rats with epilepsy via the MAPK signaling pathway

This study aims to investigate the effect of micro rna‐129 (mi r‐129) on proliferation and apoptosis of hippocampal neurons in epilepsy rats by targeting c‐fos via the mapk signaling pathway.Thirty rats were equally classified into a model group (successfully established as chronic epilepsy models) and a normal group.Expression of mi r‐129, c‐fos, bax, and mapk was detected by rt‐q pcr and western blotting.Hippocampal neurons were assigned into normal, blank, negative control (nc), mi r‐129 mimic, mi r‐129 inhibitor, si rna‐c‐fos, mi r‐129 inhibitor+si rna‐c‐fos groups.The targeting relationship between mi r‐129 and c‐fos was predicted and verified by bioinformatics websites and dual‐luciferase reporter gene assay.Cell proliferation after transfection was measured by mtt assay, and cell cycle and apoptosis by flow cytometry.C‐fos is a potential target gene of mi r‐129.Compared with the normal group, the other six groups showed a decreased mi r‐129 expression; increased expression of expression of c‐fos, bax, and mapk; decreased proliferation; accelerated apoptosis; more cells arrested in the g1 phase; and fewer cells arrested in the s phase.Compared with the blank and nc groups, the mi r‐129 mimic group and the si rna‐c‐fos group showed decreased expression of c‐fos, bax, and mapk, increased cells proliferation, and decreased cell apoptosis, fewer cells arrested in the g1 phase and more cells arrested in the s phase.However, the mi r‐129 inhibitor groups showed reverse consequences.This study suggests that mi r‐129 could inhibit the occurrence and development of epilepsy by repressing c‐fos expression through inhibiting the mapk signaling pathway.

Journal: Journal of Cellular Physiology (2017)
Publication types: Research Article;
Effects of microRNA-206 and its target gene IGF-1 on sevoflurane-induced activation of hippocampal astrocytes in aged rats through the PI3K/AKT/CREB signaling pathway

The study aims to explore the effects of micro rna‐206 (mi r‐206) targeting igf‐1 on the activation of hippocampal astrocytes in aged rats induced by sevoflurane through the pi3k/akt/creb signaling pathway.Wistar rats and astrocytes were divided into the normal/blank, sham/negative control (nc), sevoflurane (sevo), mi r‐206 mimics+sevo, mi r‐206 inhibitors+sevo, mi r‐206 nc+sevo, igf‐1 sh rna+sevo, and mi r‐206 inhibitors+igf‐1 sh rna+sevo groups.The morris water maze test was exhibited to assess the cognitive functions.Glial fibrillary acidic protein (gfap) expression was detected by immunofluorescence assay.Western blotting and rt‐q pcr were used to detect the expression of mi r‐206, igf‐1, pi3k, akt, creb, p pi3k, p akt, p creb, cytochrome‐c (cyt‐c), and caspase‐3.Cell viability and apoptosis were detected by mtt assay and annexin v/pi double staining respectively.Mitochondrial transmembrane potential (mtp) were determined by flow cytometry.The igf‐1 sh rna+sevo group showed reduced mi r‐206 expression.Compared with the normal/blank group, the sevo, and mi r‐206 nc+sevo groups showed decreased mi r‐206 and gfap expressions, cell viability and mtp but increased expressions of igf‐1, pi3k, akt, creb, p pi3k, p akt, p creb, cyt‐c and caspase‐3, as well as cell apoptosis.Similar trends were observed in the mi r‐206 inhibitors+sevo group when compared with the sevo group.The study provides evidence that mi r‐206 alleviates the inhibition of activation of hippocampal astrocytes in aged rats induced by sevoflurane by targeting igt‐1 through suppressing the pi3k/akt/creb signaling pathway.

Journal: Journal of Cellular Physiology (2017)
Publication types: Research Article;
Silencing SUMO2 promotes protection against degradation and apoptosis of nucleus pulposus cells through p53 signaling pathway in intervertebral disc degeneration

Intervertebral disc degeneration (idd), as a common cause of back pain, is related to the promotion of cellular senescence and reduction in proliferation.Based on recent studies, small ubiquitin-related modifier (sumo) proteins have been implicated in various biological functions.Therefore, in the present study, we investigated the effects of sumo2 on proliferation and senescence of nucleus pulposus cells (npcs) via mediation of p53 signaling pathway in rat models of idd.Methods: after the establishment of rat models of idd for the measurement of positive expression of sumo2/3 protein, the m rna and protein levels of sumo2, molecular phenotype [matrix metalloproteinase-2 (mmp-2) and hypoxia-inducible factor-1α (hif-1α)] and p53 signaling pathway-related genes [p21, murine double minute-2 (mdm2), growth arrest and dna-damage-inducible protein 45 α (gadd45α), cyclin-dependent kinase 2/4 (cdk2/4), and cyclin b1] were determined, followed by the detection of cell proliferation, cell cycle, apoptosis, and cell senescence.Results: the rat models of idd were successfully constructed.The results obtained showed that there was a higher positive expression of sumo2/3 protein in idd rats.Moreover, the silencing of the sumo2 gene decreases the levels of sumo2, p53, p21, mdm2, gadd45α, mmp-2, and hif-1α expressions and p53 phosphorylation level while it increases the levels of cdk2/4 and cyclin b1 expressions.In addition, sumo2 gene silencing enhances proliferation and suppresses apoptosis and cell senescence of npcs.Conclusion: in conclusion, sumo2 gene silencing promotes proliferation, and inhibits the apoptosis and senescence of npcs in rats with idd through the down-regulation of the p53 signaling pathway.Thus, sumo2 is a potential target in the treatment of idd.

Journal: Bioscience Reports (2018)
Publication types: Research Article;
LncRNA LINC01305 silencing inhibits cell epithelial-mesenchymal transition in cervical cancer by inhibiting TNXB-mediated PI3K/Akt signalling pathway

Cervical cancer (cc) remains one of the leading malignancies afflicting females worldwide, with its aetiology associated with long‐term papillomavirus infection.Recent studies have shifted their focus and research attention to the relationship between long non‐coding rnas (lnc rnas) and cc therapeutic.Thus, the aim of the current study was to investigate the underlying mechanism of lnc rna linc01305 on the cell invasion, migration and epithelial‐mesenchymal transition (emt) of cc cells via modulation of the pi3k/akt signalling pathway by targeting tenascin‐x b (tnxb).The expressions of linc01305, tnxb, mmp2, mmp9, e‐cadherin, vimentin, pi3k, akt, p‐pi3k, p‐akt and tnxb were detected in this study.After which, the cell invasion and migration abilities of the cc cells were determined respectively.Bioinformatics and the application of a dual luciferase reporter gene assay provided verification indicating that tnxb is the target gene of lnc rna linc01305.Reverse transcription quantitative polymerase chain reaction (rt‐q pcr) and western blot analysis methods revealed that the expressions of mmp2, mmp9, vimentin, pi3k, akt, p‐pi3k and p‐akt were decreased following the down‐regulation of lnc rna linc01305 or overexpression of tnxb.Lnc rna linc01305 silencing or tnxb overexpression was noted to decrease the migration and invasion of si ha cells.Taken together, the key findings of the current study present evidence suggesting that lnc rna linc01305 silencing suppresses emt, invasion and migration via repressing the pi3k/akt signalling pathway by means of targeting tnxb in cc cells, which ultimately provides novel insight and identification of potential therapeutic targets for cc.

Journal: Journal of Cellular and Molecular Medicine (JCMM) (2019)
Publication types: Research Article;