syedzayyan/paper_mill_benchmark huggingface dataset:
Molecular Pathways Involved in Promoting Activity of Timosaponin BII on Hair Growth in C57BL/6 Mice

Hair loss is a common disease in dermatology, while the approved drugs may have unpredictable side effects.In this study, the effect of timosaponin bii extracted from anemarrhena asphodeloides on hair growth of c57bl/6 mice was investigated by measuring the hair follicle morphology, hair growth length and area in c57bl/6 male mice, and the immunohistochemical analysis of β ‐catenin, wnt3a, and wnt10b in the dorsal skins of mice after topical application with minoxidil and timosaponin bii for 15 days.The decrease in skin brightness, the increase in the regrowing area of hair and hair follicles numbers, and the improvement of hair follicle morphology in the group applied with 0.5% timosaponin bii indicated an induction of the anagen phase in telogenic mice skin, which were comparative to the 2% minoxidil treatment.The immunohistochemical analysis detected an increase in the expression of β ‐catenin and wnt10b, supporting the theory of the activation of the β ‐catenin/wnt pathway was one of the pathways that are related to anagen phase induction.Anemarrhena asphodeloides is a herb commonly used for metabolic disorders in china.The present study is the first to show that the timosaponin bii, which is present at a high concentration in a.Asphodeloides , promotes hair growth in c57bl/6 male mice.The results indicate that timosaponin bii may be a potential promoting agent for hair growth.

Journal: BioMed Research International (2020)
Publication types: Research Article;
Molecular Mechanism of Secondary Endocrine Resistance in Luminal Breast Cancer

The molecular mechanism of secondary resistance in luminal breast cancer was studied to provide new ideas for the treatment of breast cancer.Methods .The sensitivity of the downregulation of myeloid leukemia factor 1‐interacting proteins (mlf1ip) to tamoxifen (tam) was tested by the cell counting kit‐8 (cck‐8).The apoptosis of mlf1ip‐mediated resistance was analyzed by flow cytometry (fcm) with/without tam.Western blot was used in detecting various kinds of apoptosis and the expression of the protein related to the phosphatidylinositol 3‐kinase (pi3k)/akt signaling pathway to study the molecular mechanism of secondary endocrine resistance in luminal breast cancer.Results .The downregulation of mlf1ip could significantly increase the drug sensitivity of michigan cancer foundation‐7 (mcf‐7) cells and also inhibit the proliferation of mcf‐7 cells under the stimulation of drugs.Western blot results showed that the expression of bcl‐2‐associated x (bax), caspase3, caspase7, and caspase9 proteins increased when mlf1ip was downregulated.The results of the pi3k/akt signaling pathway revealed that the phosphatase and tensin homolog deleted on chromosome ten (pten) protein expression of mcf7‐sh rna was higher than that of mcf7‐nc cells, while the expression of p‐akt was lower than that of mcf7‐nc cells.Conclusions .(1) mlf1ip‐related apoptosis resistance plays an essential role in mlf1ip‐mediated secondary resistance of breast cancer cells.(2) mlf1ip promotes akt phosphorylation by inhibiting the pten expression, thus activating the pi3k/akt signaling pathway and causing the secondary resistance of luminal breast cancer.(3) mlf1ip can be used as a factor to predict the endocrine resistance of luminal breast cancer.

Journal: BioMed Research International (2021)
Publication types: Research Article;
Molecular Mechanism of Palmitic Acid on Myocardial Contractility in Hypertensive Rats and Its Relationship with Neural Nitric Oxide Synthase Protein in Cardiomyocytes

It is aimed at investigating the mechanism of palmitic acid (pa) on myocardial contractility in hypertensive rats and its relationship with myocardial neural nitric oxide synthase (n nos) protein.Methods .The rats were randomly divided into sham operation group and hypertensive group, with thirty rats in each group, to prepare angiotensin ii‐induced hypertensive model rats.The blood pressure of rats was measured by the multianimal multichannel tail cuff noninvasive blood pressure system of kent coda, usa.The ionoptix single‐cell contraction detection system was used to detect myocardial cells.Atp level of left ventricular cardiomyocytes was determined by luminescence method, and protein was measured by western blot.Results .Compared with the sham group, systolic blood pressure and diastolic blood pressure were increased in the hypertensive group over 4 weeks; pa increased the contractility of left ventricular cardiomyocytes in normal rats, but not in hypertensive rats, and pa increased the intracellular atp level of rats in the sham group but not in the hypertension group.In the hypertension group, the expression of n nos in the cardiomyocytes was significantly increased, and specific n nos inhibitor s‐methyl‐l‐thiocitrulline (smtc) was found to restore the positive inotropic effect of pa in the myocardium of the hypertension group.Pa was supplemented after using cpt‐1 inhibitor etomoxir (eto); it was found that eto inhibited the positive inotropic effect of pa on left ventricular cardiomyocytes in the sham group, and pa was supplemented after using smtc and eto, it was found that smtc + eto could inhibit the positive inotropic effect of pa on left ventricular cardiomyocytes in myocardium of hypertensive rats.Conclusion .Pa could increase the contractility of healthy cardiomyocytes, but had no obvious positive effect on the cardiomyocytes of hypertensive rats, pa enhanced the contractility of cardiomyocytes by increasing atp level in them, and the inhibitory effect of pa on myocardial contractility in hypertensive rats may be related to the increased n nos and cpt‐1 in cardiomyocytes.

Journal: BioMed Research International (2021)
Publication types: Research Article;
Molecular Mechanism of Expression Changes of Immunological Indexes of PD-1/sPD-L1 after Radiotherapy in Nonsmall Cell Lung Cancer

It is aimed at investigating the changes of serum soluble programmed death‐ligand 1 (s pd‐l1) expression level in nonsmall cell lung cancer (nsclc) before and after radiotherapy, the correlation of pd‐l1, pd‐1, and proteins of akt (protein kinase b), m tor, and hif‐1 α , and the molecular mechanism of the pd‐1/pd‐l1 pathway in the development of nscls.A total of 126 nsclc patients receiving radiotherapy in liaoning cancer hospital from september 2018 to september 2019 were selected as the observation group, and another 58 healthy volunteers were selected as the control group.Nsclc patients were divided into group a (stage i‐ii, stereotactic radiotherapy) and group b (stage iii, intensity‐modulated radiation therapy) according to the cancer stage.The efficacy of radiotherapy was evaluated, and s pd‐l1 expression was detected by elisa.The immunohistochemical staining was adopted to detect protein expressions of akt, m tor, and hif‐1 α in nsclc tissues.The correlation between their expression and expression of pd‐l1 and pd‐1 was analyzed.The results showed that the overall response rate (orr) of group a was 89.29%, the clinical benefit response (cbr) was 96.43%, the median survival time (mst) was 25 months, and the survival rate within three years was 72.56%.In group b, the orr was 70.41%, the cbr was 97.96%, the mst was 18 months, and the survival rate within three years was 34.67%.Comparison of overall serum s pd‐l1 expression in the control group, group a, and group b and between groups before radiotherapy was statistically significant ( p &lt; 0.01).After radiotherapy, serum s pd‐l1 expression in group a and group b decreased compared with that before radiotherapy ( p &lt; 0.01).Among nsclc patients, the positive expression rate of akt, m tor, and hif‐1 α was 71.32%, 41.26%, and 80.65%, respectively.Pd‐l1 expression and akt, m tor, and hif‐1 α expression showed a significant correlation.Pd1 expression and akt, m tor, and hif‐1 α expression also showed a significant correlation.It indicated that the expression level of s pd‐l1 in nsclc patients was higher than that in normal subjects, but the expression level of s pd‐l1 was decreased after radiotherapy.Pd‐1/pd‐l1 may play important roles in nsclc procession through the akt/m tor and hif‐1 α pathway.

Journal: BioMed Research International (2021)
Publication types: Research Article;
Molecular Mechanism of 73HOXC-AS1-Activated Wntβ-Catenin Signaling and eIF4AIII in Promoting Progression of Gastric Cancer

This study is aimed at exploring the regulatory mechanism of 73hoxc‐as1 overexpression plasmid‐activated wnt β ‐catenin classic signaling pathway and eukaryotic initiation factor 4a (e if4aiii) expression increased by lentivirus‐e if4aiii‐rnai (44682‐1) (lv‐e if4aiii‐rnai (44682‐1)).Methods .Focusing on the occurrence and progression of gastric cancer, the human gastric cancer cell line bgc823 (university experimental center) was taken as the research object and was transfected after subculture.According to the different ways of transfection, the cells were divided into the p1 group (lv‐e if4aiii‐rnai (44682‐1) overexpressed plasmid), the p2 group (pc dna‐hoxc‐as1 overexpressed plasmid), the p3 group (lv‐e if4aiii‐rnai (44682‐1) + pc dna‐hoxc‐as1), and the p4 group (no transfection, control group).Cell proliferation was detected by cck‐8 (cell counting kit‐8) assay, western blotting was adopted to detect wnt3a and p‐gsk3 β proteins, transwell assay was adopted to detect the ability of cell migration and invasion, and cell cycle and apoptosis were detected by flow cytometry.Results .The results show that the protein expression levels of wnt3a and p‐gsk3 β (glycogen synthase kinase‐3 β ) in the p1 and p4 groups were lower than those in the p2 and p3 groups ( p &lt; 0.05).The cell activity and clone number of bgc823 in the p3 group were higher than those in the p1, p2, and p4 groups ( p &lt; 0.05).The apoptosis rate of bgc823 cells in the p3 group was significantly higher than those in the p1, p2, and p4 groups ( p &lt; 0.05).The proportion of bgc823 cells in the p3 group at the s phase was significantly higher than those in the p1, p2, and p4 groups, while the proportion in the g2 phase was significantly lower than those in the p1, p2, and p4 groups ( p &lt; 0.05).The number of migrating and invading bgc823 cells in the p3 group was significantly higher than those in the p1, p2, and p4 groups, while the number of migrating bgc823 cells in the p4 group was significantly lower than those in the p1 and p2 groups ( p &lt; 0.05).Conclusion .The 73hoxc‐as1 overexpression plasmid‐activated wnt β ‐catenin classic signaling pathway and e if4aiii expression increased by lv‐e if4aiii‐rnai (44682‐1) could act together on bgc823 cells to improve cell proliferation activity, migration, and invasion; inhibit cell apoptosis; and prevent cells from entering the s phase.

Journal: BioMed Research International (2021)
Publication types: Research Article;
Model of Human Tongue Squamous Cell Lines Stably Transfected with Human Papillomavirus (HPV)16 E6 and E7 Genes and Biological Characteristic Analysis

Human tongue squamous cell carcinoma (tscc) is the most common oral cancer with the highest human papillomavirus (hpv) infection rate in oral cancer.The purpose of this study was to research the correlation between hpv and tscc.Method .Plasmid p egfp/hpv16 e6e7 and plasmid p egfp/no hpv16 e6e7 were constructed.Tscc cell lines scc9 and scc15 were infected by liposome transfection and would be highly selected by antibiotic.Fluorescence imaging, pcr, and western blot were used to detect the expression of hpv16 e6e7 in cells.The biological characteristics were detected by cck‐8, wound healing assay, q rt‐pcr, and western blot.Result .Tscc cell lines transfected with hpv16 e6e7 gene were successfully established and identified.And the proliferation and migration ability of the tscc cell lines infected with hpv16 e6e7 gene were significantly stronger than that of the blank group.Conclusion .Tscc cell lines infected with hpv16 e6e7 with significantly higher ability of proliferation and migration were more malignant than those not infected with hpv16 e6e7.

Journal: BioMed Research International (2021)
Publication types: Research Article;
ML-Based Texture and Wavelet Features Extraction Technique to Predict Gastric Mesothelioma Cancer

Microsatellites are small, repetitive sequences found all across the human genome.Microsatellite instability is the phenomenon of variations in the length of microsatellites induced by the insertion or deletion of repeat units in tumor tissue (msi).Msi‐type stomach malignancy has distinct genetic phenotypes and clinic pathological characteristics, and the stability of microsatellites influences whether or not patients with gastric mesothelioma react to immunotherapy.As a result, determining msi status prior to surgery is critical for developing treatment options for individuals with gastric cancer.Traditional msi detection approaches need immunological histochemistry and genetic analysis, which adds to the expense and makes it difficult to apply to every patient in clinical practice.In this study, to predict the msi status of gastric cancer patients, researchers used image feature extraction technology and a machine learning algorithm to evaluate high‐resolution histopathology pictures of patients.279 cases of raw data were obtained from the tcga database, 442 samples were obtained after preprocessing and upsampling, and 445 quantitative image features, including first‐order statistics of impressions, texture features, and wavelet features, were extracted from the histopathological images of each sample.To filter the characteristics and provide a prediction label (risk score) for msi status of gastric cancer, lasso regression was utilized.The predictive label’s classification performance was evaluated using a logistic classification model, which was then coupled with the clinical data of each patient to create a customized nomogram for msi status prediction using multivariate analysis.

Journal: BioMed Research International (2022)
Publication types: Research Article;
miRNA-221 Regulates Spinal Cord Injury-Induced Inflammatory Response through Targeting TNF-α Expression

S .To investigate the roles of mi r‐221 in spinal cord injury (sci) as well as the underlying mechanism.Methods .A mouse model of sci was generated and used to examine dynamic changes in grip strength of the mouse upper and lower limbs.The expression of mi r‐221 and tumor necrosis factor‐ α (tnf‐ α ) was detected by rt‐q pcr and western blot.Levels of inflammation and oxidative stress in microglia cells of the injured mice overexpressing mi r‐221 were then measured by elisa.Bioinformatics analysis and dual‐luciferase reporter assay were conducted to identify the mi r‐221 target.Results .We successfully constructed sci mouse model.The results of q rt‐pcr showed that mi r‐221 was gradually upregulated in the spinal cord tissue of mice in the sci group with the prolonged injury time.At the same time, the m rna and protein of tnf‐ α gradually decreased.We further confirmed through cell experiments that the inflammatory factors tnf‐ α and il‐6, as well as i nos and e ros, were upregulated in spinal cord microglia cells of sci mice, and upregulation of mi r‐122 can inhibit their expression.Finally, the luciferase reporter experiment confirmed that mi r‐122 targeted tnf‐ α .Conclusions .We present evidence that mi r‐221 promotes functional recovery of the injured spinal cord through targeting tnf‐ α , while alleviating inflammatory response and oxidative stress.

Journal: BioMed Research International (2021)
Publication types: Research Article;
miRNA-187-5p Regulates Osteoblastic Differentiation of Bone Marrow Mesenchymal Stem Cells in Mice by Targeting ICAM1

Osteoporosis (op) is a common bone metabolic disease, the process of which is fundamentally irreversible.Therefore, the investigation into osteoblastic differentiation of bone marrow mesenchymal stem cells (bmscs) will provide more clues for op treatment.In the present study, we found that micro rna‐187‐5p (mi r‐187‐5p) played a key role on osteoblastic differentiation, which was significantly upregulated during osteogenic differentiation of bmscs in mice.Moreover, overexpression of mi r‐187‐5p suppressed osteoblastic differentiation of bmscs through increasing alkaline phosphatase (alp), matrix mineralization, and levels of osterix (osx), and osteopontin (opn) as well as runt‐related transcription factor 2 (runx2) in vitro .The results in vivo indicated that the upregulation of mi r‐187‐5p enhanced the efficacy of new bone formation in the heterotopic bone formation assay.Luciferase reporter assay and western blot analysis revealed that mi r‐187‐5p was involved in osteogenesis by targeting intracellular adhesion molecule 1 (icam‐1).Furthermore, icam‐1 silence inhibited osteoblastic differentiation of bmscs.Taken together, our results suggested for the first time that mi r‐187‐5p may promote osteogenesis by targeting icam‐1, and provided a possible therapeutic target for bone metabolic diseases.

Journal: BioMed Research International (2020)
Publication types: Research Article;
MiR-502 Suppresses TNF-α-Induced Nucleus Pulposus Cell Apoptosis by Targeting TARF2

Intervertebral disc degeneration (ivdd) is a common cause of low back pain.This study is aimed at investigating the role of micro rnas (mi rnas) in regulating human nucleus pulposus (np) cell injury induced by tumor necrosis factor‐ (tnf‐) α in ivdd.In this study, we induced np cells with 20 ng/m l tnf‐ α in vitro, which promoted the obvious apoptosis of np cells and the activation of nuclear transcription factor (nf)‐ κ b.In contrast, using the specific nf‐ κ b inhibitor bay 11‐7082 to treat cells greatly impaired the activation of nf‐ κ b and increased the sensitivity of np cells to tnf‐ α ‐induced apoptosis.Moreover, both tnf‐ α and bay 11‐7082 treatments were associated with marked mi rna dysregulation, with mi r‐502 being upregulated by tnf‐ α treatment and downregulated by bay 11‐7082 treatment, respectively.And the overexpression of mi r‐502 enhanced nf‐ κ b activation and suppressed apoptosis of human np cells induced by tnf‐ α , whereas the opposite was observed following mi r‐502 inhibition.Last, through bioinformatic analyses and luciferase reporter gene experiments, we identified traf2, an important activator of nf‐ κ b, as a mi r‐502 target gene.Similarly, si rna‐mediated knockdown of the traf2 expression also suppressed tnf‐ α ‐induced apoptosis and enhanced nf‐ κ b activation.Our findings provide evidence indicating that mi r‐502 is a key regulator of apoptosis of human np cells induced by tnf‐ α by targeting traf2 and activating nf‐ κ b.

Journal: BioMed Research International (2021)
Publication types: Research Article;
miR-451 on Myocardial Ischemia-Reperfusion in Rats by Regulating AMPK Signaling Pathway

Myocardial infarction is the main cause of death in patients with coronary heart disease.At present, the main method to treat cardiovascular disease is perfusion therapy.Myocardial ischemia‐reperfusion will inevitably lead to reperfusion injury, which is also a major problem in the treatment of cardiovascular diseases.It has been reported that mir‐451 in micro rna family participates in the protection of myocardial ischemia‐reperfusion by regulating ampk.The aim of this study was to investigate the effect of mir‐451 on myocardial ischemia‐reperfusion in rats by regulating ampk signaling pathway.Sixty adult male rats were selected to establish myocardial ischemia‐reperfusion animal model by ligating and loosening coronary artery.The expression level of mir‐451 was regulated by injection of mir‐451 virus vector and antibody, and the effect of increased or decreased mir‐451 expression level on the activity of ampk signaling pathway was detected.The myocardial infarct area and apoptosis rate of myocardial tissue were detected after 75 min ischemia‐reperfusion.The results showed that when the expression level of mir‐451 decreased by 15.7%, the activity index of ampk signaling pathway was increased by 18.3%, the infarct area was reduced by 22.4%, and the apoptosis rate of myocardial cells was decreased by 25.2%.At the same time, the pathological structure of myocardial tissue was improved.Therefore, mir‐451 is an inhibitor gene of ampk signaling pathway.Reducing the expression of mir‐451 can enhance the activity of ampk signal pathway, and the increase of ampk signal pathway activity is beneficial to reduce myocardial ischemia‐reperfusion injury.

Journal: BioMed Research International (2021)
Publication types: Research Article;
mir-126-5p Promotes Cisplatin Sensitivity of Non-Small-Cell Lung Cancer by Inhibiting ADAM9

The aim of the study was to investigate molecular mechanisms underlying the role of mi r‐126‐5p in cisplatin (ddp) sensitivity of non‐small‐cell lung cancer (nsclc).Methods .The expression of mi r‐126‐5p and adam9 in nsclc cancer tissues and adjacent tissues, cisplatin‐sensitive and drug‐resistant nsclc patient tissues, human normal lung epithelial cells (besa‐2b), human lung adenocarcinoma cell lines a549 and h1560, and cisplatin‐resistant mutant cell lines a549/ddp and h1560/ddp was detected by q rt‐pcr.After overexpression of mi r‐126‐5p or adam9 in a549/ddp and h1560/ddp, mtt and clone formation were used to detect the cell proliferation ability of each treatment group.Flow cytometry was used to detect changes in cell apoptosis.The protein expression of adam9 and key molecules of pten/pi3k/akt pathways in cells was measured by western blot.Results .Compared with nsclc adjacent tissues and nsclc cisplatin‐sensitive tissues, mi r‐126‐5p expression was downregulated in nsclc tissues and cisplatin‐resistant nsclc tissues and adam9 was upregulated.Q rt‐pcr further detected that mi r‐126‐5p was downregulated in a549, h1560, and their cisplatin‐resistant strains a549/ddp and h1560/ddp, while adam9 was upregulated.Moreover, overexpression of mi r‐126‐5p inhibited a549/ddp and h1560/ddp cell proliferation and promoted cell apoptosis.The results of dual luciferase showed that mi r‐126‐5p targeted and negatively regulated adam9.We also found that overexpression of adam9 could reverse the effects of mi r‐126‐5p on nsclc cell proliferation, apoptosis, and cisplatin sensitivity, and this effect may be achieved by inhibiting the activity of the pten/pi3k/akt signaling pathway.Conclusion .Our data indicated that mi r‐126‐5p may negatively regulate adam9 to promote the sensitivity of clinical ddp treatment of nsclc and be a potential therapeutic target for nsclc treatment.

Journal: BioMed Research International (2021)
Publication types: Research Article;
MicroRNA-4325 Suppresses Cell Progression in Hepatocellular Carcinoma via GATA-Binding Protein 6

Micro rnas (mi rs) are regulators of the formation and development of hepatocellular carcinoma (hcc).The biological role of mi r‐4325 in hcc has yet to be determined.This study is aimed at dissecting the role of mi r‐4325 in hcc and the underlying mechanism.Reverse transcription‐quantitative pcr (rt‐q pcr) was used to detect mi r‐4325 expression in hcc tissue specimens and cells.Cell proliferation, migration, and invasion were assessed by using the mtt assay and transwell assay, respectively.The mi r‐4325 target was predicted based on bioinformatics analysis and validated using the dual‐luciferase reporter assay.Rescue experiments in the cells were utilized to functionally characterize the downstream molecular targets of mi r‐4325.We observed that mi r‐4325 expression levels were significantly reduced in both hcc tissue specimens and cell lines.Meanwhile, a lower mi r‐4325 level was associated with a poorer prognosis.Gain and loss of function assays revealed that mi r‐4325 markedly downregulated hcc cell growth, migration, and invasion.Moreover, we identified gata‐binding protein 6 (gata6) as a mi r‐4325 target and found that gata6 was abnormally expressed in hcc.Rescue assays demonstrated that the regulatory function of mi r‐4325 in hcc was mediated by gata6.Taken together, mi r‐4325 suppresses hcc cell growth, migration, and invasion by targeting gata6, suggesting that mi r‐4325 may potentially serve as a novel therapeutic target for hcc.

Journal: BioMed Research International (2021)
Publication types: Research Article;