syedzayyan/paper_mill_benchmark huggingface dataset:
Ketamine and Propofol Protect Neuron Cells from Oxygen-Glucose Deprivation-Induced Injury through SAPK/JNK Signalling Pathway

Ketamine and propofol are commonly used anaesthetic reagents.Recent research revealed that ketamine and propofol have an important role in cell survival.However, it remains unknown whether they affect the outcome of hypoxic‐ischemic brain injury.To address this issue, we in this study investigated the effects of ketamine and propofol on the survival and proliferation of neuronal pc12 cells after exposure to oxygen‐glucose deprivation‐ (ogd‐) induced injury.Pc12 cells were maintained under a 3‐dimensional (3d) culture system to mimic a real physiological microenvironment.The cell injury was induced by 5% co 2 and 95% n 2 for a different time point.Mtt assay was used for the cell proliferation assay.The cell apoptosis was evaluated by annexin v and propidium iodide (pi) labeling, immunofluorescence staining, transmission electron microscopy (tem), flow cytometry, and western blot, respectively.Our results showed that pc12 cell apoptosis was significantly increased for up to 70% after the cells were treated with ogd for 24 hours and reduced to baseline at the 72‐hour time point.However, pretreatment with ketamine and propofol significantly protected the cells from ogd‐induced cell apoptosis, as evidenced by more expression of antiapoptotic bcl‐2 and lower expression of proapoptotic cleaved caspase‐3, phosphor‐sapk/jnk, and phosphor‐c‐jun than those of untreated control cells.Thus, we conclude that ketamine and propofol protected pc12 cells from ogd‐induced cell apoptosis, at least partially through the sapk/jnk signalling pathway.

Journal: BioMed Research International (2020)
Publication types: Research Article;
Spondias purpurea L. Bark Extract Protects against Oxidative Stress and Reduces Hypercholesterolemia in Mice Fed High-Fat Diet

Oxidative stress plays a key role in the initiation and progression of metabolic diseases, including obesity.Preventing the accumulation of reactive oxygen species and oxidative damage to macromolecules is a beneficial strategy for reducing comorbidities associated with obesity.Fruits from the spondias genus are known for their antioxidant activity, but they are not available year-round due to their seasonality.In this context, we investigated the antioxidant activity and identified the chemical constituents of the aqueous extract of the stem bark of spondias purpurea l.(ebsp).Additionally, we evaluated the effect of ebsp consumption on metabolic parameters in mice with obesity induced by a high-fat diet.Chemical analyses revealed 19 annotated compounds from ebsp, including flavan-3-ols, proanthocyanidins, methoxylated coumarin, and gallic and ellagic acids, besides other phenolic compounds.In vitro, ebsp showed antioxidant activity through the scavenging of the free radicals and the protection of macromolecules against oxidative damage.Cellular assays revealed that ebsp reduced the levels of malondialdehyde produced by erythrocytes exposed to the oxidizing agent aaph.Flow cytometry studies showed that ebsp reduced reactive oxygen species levels in human peripheral blood mononuclear cells treated with hydrogen peroxide.Obese mice treated with ebsp (400 mg.kg-1) for 60 days showed reduced levels of malondialdehyde in the heart, liver, kidneys, and nervous system.The total cholesterol levels in mice treated with ebsp reached levels similar to those after treatment with the drug simvastatin.Together, the results show that the combination of the different phenolic compounds in s.Purpurea l.Bark promotes antioxidant effects in vitro and in vivo, resulting in cytoprotection in the context of oxidative stress associated with obesity and a reduction in hypercholesterolemia.From a clinical perspective, the reduction in oxidative stress in obese individuals contributes to the reduction in the emergence of comorbidities associated with this metabolic syndrome.

Journal: Oxidative Medicine and Cellular Longevity (2022)
Publication types: Research Article;
Isovitexin Suppresses Stemness of Lung Cancer Stem-Like Cells through Blockage of MnSOD/CaMKII/AMPK Signaling and Glycolysis Inhibition

Manganese superoxide dismutase (mn sod) has been reported to promote stemness of lung cancer stem‐like cells (lcslcs) which had higher glycolytic rates compared with non‐cslcs.Isovitexin exhibited an inhibitory effect on the stemness of hepatocellular carcinoma cells.However, whether isovitexin could inhibit the promotion of stemness of lcslcs mediated by mn sod through glycolysis remains unclear.Objective .Our study was aimed at investigating whether isovitexin inhibits lung cancer stem‐like cells (lcslcs) through mn sod signaling blockage and glycolysis suppression.Methods .Sphere formation and soft agar assays were conducted to determine self‐renewal ability.The migration and invasion of lcslcs were determined by wound healing and transwell assay.The glycolytic activity was assessed by determination of l‐lactate metabolism rate.The influences of isovitexin on mn sod, ca mkii, and ampk activations as well as the metabolic shift to glycolysis were determined by manipulating mn sod expression.Results .It was found that mn sod and glycolysis enhanced simultaneously in lcslcs compared with parental h460 cells.Overexpression of mn sod activated ca mkii/ampk signaling and glycolysis in lcslcs with increased self‐renewal, migration, invasion, and expression of stemness‐associated markers in vitro and elevated carcinogenicity in vivo .Knockdown of mn sod induced an inverse effect in lcslcs.Isovitexin blocked mn sod/ca mkii/ampk signaling axis and suppressed glycolysis in lcslcs, resulting in inhibition of stemness features in lcslcs.The knockdown of mn sod significantly augmented isovitexin‐associated inhibition of ca mkii/ampk signaling, glycolysis, and stemness in lcslcs.However, the overexpression of mn sod could attenuate the inhibition of isovitexin on lcslcs.Importantly, isovitexin notably suppressed tumor growth in nude mice bearing lcslcs by downregulation of mn sod expression.Conclusion .Mn sod promotion of stemness of lcslcs derived from h460 cell line is involved in the activation of the ca mkii/ampk pathway and induction of glycolysis.Isovitexin‐associated inhibition of stemness in lcslcs is partly dependent on blockage of the mn sod/ca mkii/ampk signaling axis and glycolysis suppression.

Journal: BioMed Research International (2021)
Publication types: Research Article;
Inter-Relationship Between a Transcriptional Regulator of Flagella Genes cj0440c and Thiamine Metabolic Pathway in Campylobacter jejuni

Campylobacter jejuni is a major cause of gastroenteritis in humans.It has been reported that the pathogenesis of c.Jejuni is closely related to the formation, adhesion, and invasion of flagella toxin in host epithelial cells.A putative transcriptional regulator, known as cj0440c , is thought to be involved in the regulation of flagellar synthesis.However, confirmation of this hypothesis requires deep insight into the regulation mechanism of cj0440c and its possible relationship with different antibiotics.Therefore, the study explained here was designed to determine the relationship and function (phenotypically and genotypically) of cj0440c in the flagellar synthesis of c.Jejuni nctc11168.The study determined the mode of expression of cj0440c and flagella‐related genes under exposure to various drugs.To verify the involvement of cj0440c protein in the metabolic pathway of thiamine, an enzymatic hydrolysis experiment was performed and analyzed through the application of mass spectrometry.The overexpression vector of c.Jejuni nctc11168 was also constructed to find out whether or not target genes were regulated by cj0440c .The findings of the study showed that cj0440c and other flagella‐related genes were expressed differentially under the influence of various antibiotics including erythromycin, tylosin, azithromycin, gentamicin, etimicin, enrofloxacin, gatifloxacin, tetracycline, and tigecycline.The analysis showed that the cj0440c protein did not catalyze the degradation of thiamine.In conclusion, the study aids in the understanding of the inter‐relationship between the regulatory mechanism of flagella genes and the thiamine metabolic pathway.

Journal: BioMed Research International (2022)
Publication types: Research Article;
Insight into the Protective Effect of Salidroside against H2O2-Induced Injury in H9C2 Cells

Salidroside is the important active ingredient of rhodiola species, which shows a wide range of pharmacological activities such as antioxidative stress, anti‐inflammation, and antiliver fibrosis.In this paper, we aimed to study the protective effect and mechanism of salidroside against h 2 o 2 ‐induced oxidative damage in h9c2 cells by determining cell proliferation rate, intracellular reactive oxygen species (ros) level, antioxidant enzyme activities, and the expression of apoptosis‐related proteins.The results showed that salidroside significantly alleviated cell growth inhibition induced by h 2 o 2 treatment in h9c2 cells, decreased the levels of intracellular ros and malondialdehyde (mda), and increased the activity of superoxide dismutase (sod) and catalase (cat); meanwhile, salidroside upregulated the expression of bcl‐2 while downregulated the expression of bax, p53, and caspase‐3 in h 2 o 2 ‐treated h9c2 cells.Furthermore, the antiapoptotic effect of salidroside was almost eliminated by the knockdown of bcl‐2.In the further exploration, the bcl‐2 expression was decreased by the p53 overexpression and increased by p53 knockdown in h 2 o 2 ‐treated h9c2 cells.Consequently, salidroside could protect h9c2 cells against h 2 o 2 ‐induced oxidative damage, and the underlying mechanism may be related to scavenging intracellular ros, increasing the activities of intracellular antioxidant enzymes and inhibiting the expression of apoptosis‐related proteins.

Journal: Oxidative Medicine and Cellular Longevity (2021)
Publication types: Research Article;
Inhibition of Oxidative Stress: An Important Molecular Mechanism of Chinese Herbal Medicine (Astragalus membranaceus, Carthamus tinctorius L., Radix Salvia Miltiorrhizae, etc.) in the Treatment of Ischemic Stroke by Regulating the Antioxidant System

Ischemic stroke is a severe cerebrovascular disease with high mortality and morbidity.Traditional chinese medicine (tcm) has been utilized for thousands of years in china and is becoming increasingly popular all over the world, especially for the treatments of ischemic stroke.More and more evidences have implicated that oxidative stress has been closely related with ischemic stroke.This review will concentrate on the evidence of the action mechanism of chinese herbal medicine and its active ingredient in preventing ischemic stroke by modulating redox signaling and oxidative stress pathways and providing references for clinical treatment and scientific research applications.

Journal: Oxidative Medicine and Cellular Longevity (2022)
Publication types: Review Article;
Inhibition Effect of Zoledronate on the Osteoclast Differentiation of RAW264.7 Induced by Titanium Particles

This study is aimed at studying the effect of zoledronate (zol) on the differentiation of osteoclast precursor raw264.7 cells induced by titanium (ti) particles and explores the possibility of preventing and treating periprosthetic osteoporosis using zol.Methods .Raw264.7 cells were cultured in vitro.Ti particles were prepared.The cell proliferation curve of raw264.7 cells was plotted using the mtt assay to find the best concentration of zol for intervention.The cells were divided into three groups: control, ti particles, and ti particles+zol.The cell morphology was observed using tartaric acid–resistant acid phosphatase (trap) staining, and the activity of trap in cell supernatant was determined using the biochemical method.The number of bone resorption lacunae was detected using toluidine blue staining.The m rna expression of rank , nfatcl , caii , and mmp-9 was detected using real‐time polymerase chain reaction.The protein expression of rank, nfatcl, and mmp‐9 was detected using western blot analysis.Results .Ti particles stimulated the differentiation of raw264.7 cells into osteoclasts.They also increased the activity of trap, number of bone resorption lacunae, and m rna and protein expression of rank, nfatcl, and mmp‐9.However, zol could suppress the effect of ti particles on the osteoclast differentiation of raw264.7 cells.Conclusions .Zol could effectively inhibit the differentiation of raw264.7 cells into osteoclasts induced by ti particles, decrease the activity of trap, reduce the number of bone resorption lacunae, and decrease the m rna and protein expression of rank, nfatcl, and mmp‐9.Hence, it may be a promising candidate for preventing and treating periprosthetic osteoporosis after the artificial joint operation.

Journal: BioMed Research International (2021)
Publication types: Research Article;
Influence of miRNA-30a-5p on Pulmonary Fibrosis in Mice with Streptococcus pneumoniae Infection through Regulation of Autophagy by Beclin-1

The study is aimed at observing the influence of microribonucleic acid‐ (mi rna‐) 30a‐50p on the pulmonary fibrosis in mice with streptococcus pneumoniae infection through the regulation of autophagy by beclin‐1.Specific pathogen‐free mice were instilled with streptococcus pneumoniae through the trachea to establish the pulmonary fibrosis model.Then, they were divided into the mi rna‐30a‐50p mimics group (mimics group, n = 10) and mi rna‐30a‐5p inhibitors group (inhibitors group, n = 10), with the control group ( n = 10) also set.Pulmonary tissue wet weight/dry weight (w/d) was detected.The content of tumor necrosis factor‐ α (tnf‐ α ), interleukin‐ (il‐) 6, and myeloperoxidase (mpo) was determined using enzyme‐linked immunosorbent assay (elisa).Besides, the changes in the pulmonary function index dynamic lung compliance (cdyn), plateau pressure (pplat), and peak airway pressure (ppeak) were monitored, and the gene and protein expression levels were measured via quantitative pcr (q pcr) and western blotting.The expression level of mi rna‐30a‐5p was substantially raised in the mimics group ( p &lt; 0.05), but extremely low in the inhibitors group ( p &lt; 0.05).The mimics group had obviously raised levels of serum aminotransferase (ast), glutamic‐pyruvic transaminase (gpt), alkaline phosphatase (alp), and pulmonary tissue w/d ( p &lt; 0.05).Additionally, the expression levels of tnf‐ α , il‐6, and mpo were notably elevated in the mimics group, while their expression levels showed the opposite conditions in the inhibitors group ( p &lt; 0.05).According to the he staining results, the inhibitors group had arranged orderly cells, while the mimics group exhibited lung injury, pulmonary edema, severe inflammatory response, and alveolar congestion.In the inhibitors group, cdyn was remarkably elevated, but pplat and ppeak declined considerably ( p &lt; 0.05).Besides, the inhibitors group exhibited elevated messenger rna (m rna) levels of beclin‐1 and lc3, lowered m rna levels of α ‐sma and p62, a raised protein level of beclin‐1, and a markedly decreased protein level of p62 ( p &lt; 0.05).Silencing mi rna‐30a‐5p expression can promote the expression of beclin‐1 to accelerate the occurrence of autophagy, thereby treating pulmonary fibrosis in mice with streptococcus pneumoniae infection.

Journal: BioMed Research International (2021)
Publication types: Research Article;
Influence Factors and Predictive Models for the Outcome of Patients with Ischemic Stroke after Intravenous Thrombolysis: A Multicenter Retrospective Cohort Study

Intravenous thrombolysis (ivt) is currently the main effective treatment for patients with ischemic stroke.This study aimed to analyze the factors affecting the early neurological recovery and prognosis of thrombolytic therapy after surgery and to construct predictive models.Materials and methods.A total of 849 patients with ischemic stroke who received ivt treatment at six centers from june 2017 to march 2021 were included.Patients were divided into the training cohort and the validation cohort.Based on the independent factors that influence the early recovery of neurological function and the prognosis, the respective predictive nomograms were established.The predictive accuracy and discrimination ability of the nomograms were evaluated by roc and calibration curve, while the decision curve and clinical impact curve were adopted to evaluate the clinical applicability of the nomograms.Results.The nomogram constructed based on the factors affecting the prognosis in 3 months had ideal accuracy as the auc (95% ci) was 0.901 (0.874~0.927) in the training cohort and 0.877 (0.826~0.929) in the validation cohort.The accuracy of the nomogram is required to be improved, since the auc (95% ci) of the training cohort and the validation cohort was 0.641 (0.597~0.685) and 0.627 (0.559~0.696), respectively.Conclusions.Based on this ideal and practical prediction model, we can early identify and actively intervene in patients with ischemic stroke after ivt to improve their prognosis.Nevertheless, the accuracy of predicting nomograms for the recovery of early neurological function after ivt still needs improvement.

Journal: Oxidative Medicine and Cellular Longevity (2022)
Publication types: Research Article;
In Silico Structural and Functional Analyses of NLRP3 Inflammasomes to Provide Insights for Treating Neurodegenerative Diseases

Inflammasomes are cytoplasmic intracellular multiprotein complexes that control the innate immune system’s activation of inflammation in response to derived chemicals.Recent advancements increased our molecular knowledge of activation of nlrp3 inflammasomes.Although several studies have been done to investigate the role of inflammasomes in innate immunity and other diseases, structural, functional, and evolutionary investigations are needed to further understand the clinical consequences of nlrp3 gene.The purpose of this study is to investigate the structural and functional impact of the nlrp3 protein by using a computational analysis to uncover putative protein sites involved in the stabilization of the protein‐ligand complexes with inhibitors.This will allow for a deeper understanding of the molecular mechanism underlying these interactions.It was found that human nlrp3 gene coexpresses with pycard, nlrc4, casp1, mavs, and ctsb based on observed coexpression of homologs in other species.The nacht, lrr, and pyd domain‐containing protein 3 is a key player in innate immunity and inflammation as the sensor subunit of the nlrp3 inflammasome.The inflammasome polymeric complex, consisting of nlrp3, pycard, and casp1, is formed in response to pathogens and other damage‐associated signals (and possibly casp4 and casp5).Comprehensive structural and functional analyses of nlrp3 inflammasome components offer a fresh approach to the development of new treatments for a wide variety of human disorders.

Journal: BioMed Research International (2023)
Publication types: Research Article;
In Silico Identification and Mechanism Exploration of Active Ingredients against Stroke from An-Gong-Niu-Huang-Wan (AGNHW) Formula

An-gong-niu-huang-wan (agnhw) is a well-known formula for treating cerebrovascular diseases, with roles including clearing away heat, detoxification, and wake-up consciousness.In recent years, agnhw has been commonly used for the treatment of ischemic stroke, but the mechanism by which agnhw relieves stroke has not been clearly elucidated.In the current study, we developed a multiple systems pharmacology-based framework to identify the potential antistroke ingredients in agnhw and explore the underlying mechanisms of action (moa) of agnhw against stroke from a holistic perspective.Specifically, we performed a network-based method to identify the potential antistroke ingredients in agnhw by integrating the drug-target network and stroke-associated genes.Furthermore, the oxygen-glucose deprivation/reoxygenation (ogd/r) model was used to validate the anti-inflammatory effects of the key ingredients by determining the levels of inflammatory cytokines, including interleukin (il)-6, il-1β, and tumor necrosis factor (tnf)-α.The antiapoptotic effects of the key ingredients were also confirmed in vitro.Integrated pathway analysis of agnhw revealed that it might regulate three biological signaling pathways, including il-17, tnf, and pi3k-akt, to play a protective role in stroke.Moreover, 30 key antistroke ingredients in agnhw were identified via network-based in silico prediction and were confirmed to have known neuroprotective effects.After drug-like property evaluation and pharmacological validation in vitro, scutellarein (scu) and caprylic acid (ca) were selected for further antistroke investigation.Finally, systems pharmacology-based analysis of ca and scu indicated that they might exert antistroke effects via the apoptotic signaling pathway and inflammatory response, which was further validated in an in vitro stroke model.Overall, the current study proposes an integrative systems pharmacology approach to identify antistroke ingredients and demonstrate the underlying pharmacological moa of agnhw in stroke, which provides an alternative strategy to investigate novel traditional chinese medicine formulas for complex diseases.

Journal: Oxidative Medicine and Cellular Longevity (2022)
Publication types: Research Article;
Importance of Gedunin in Antagonizing Rheumatoid Arthritis via Activating the Nrf2/ARE Signaling

This study assessed the anti-arthritic effect and protection of gedunin (gdn) on joint tissues and revealed the possible mechanism in suppressing rheumatoid arthritis (ra).Methods.Lps-induced macrophages and tnf-α-stimulated synovial fibroblasts (mh7a) or il-1β-stimulated primary rheumatoid arthritis synovial fibroblasts (rasfs) were used to evaluate the antiinflammatory effect of gdn.In addition, cia-induced arthritis was employed here to evaluate the anti-arthritic effect.Mtt and brdu assays were utilized to evaluate the cell viability and proliferation, q-pcr was conducted to detect the m rna expression of cytokines, facs was adopted to monitor ros production, while western blotting (wb) and si rna interference were applied in confirming the anti-arthritic effects of gdn via the nrf2 signaling.Results.In vitro, cell viability was inhibited in macrophages and mh7a cells, but not in rasfs; but the proliferation of rasfs was significantly suppressed in time- and dose-dependent manners.Gdn suppressed cytokine levels in lps-stimulated macrophages and tnf-α-stimulated mh7a cells or rasfs.Gdn suppressed ros expression.Furthermore, gdn treatment notably dose-dependently decreased the m rna and protein expression of i nos in lps-induced macrophages.Sip62 interference results showed that gdn cause the less expression of ho-1 and keap1 and also fail to inhibit cytokines after sip62 interference.In vivo, gdn effectively inhibited paw swelling, arthritis score, and arthritis incidence and cytokines.Conclusions.Our study suggested that gdn exhibited strong antagonistic effect on arthritis both in vitro and in vivo via activation of nrf2 signaling.Our work will provide a promising therapeutic strategy for ra.

Journal: Oxidative Medicine and Cellular Longevity (2022)
Publication types: Research Article;