Through network pharmacology and molecular docking technology, combined with in vitro experiment verification, we explored the mechanism of action of Porana racemosa Roxb. (PRA) in the treatment of rheumatoid arthritis (RA), and provided a modern pharmacological basis for the treatment of RA by PRA. The potential target of chemical components in the analyzed moth rattan was predicted by Swiss Target Prediction database; OMIM, GeneCards, TTD and Disgenet databases were used to search the disease targets of RA; the protein interaction (PPI) network and medicine-composition-target network were constructed using STRING database and Cytoscape software; GO (gene ontology) functional enrichment and KEGG (kyoto encyclopedia of genes and genomes) pathway analysis were carried out using DAVID database, and molecular docking software was used to dock the potentially active ingredients of PRA and core targets; finally, MH7A cells were selected for cell viability, scratch healing and mRNA expression level analysis of key genes to explore the effects of PRA and their potentially active ingredients on the proliferation, migration and apoptosis of MH7A cells. In this study, a total of 628 potentially active ingredient targets, 1 890 RA targets and 235 intersection targets were identified. It was screened that the potentially active ingredients of RA treatment by PRA were ethylcaffeate, N-p-coumaroyltyramine, 9,12,15-octadecatrienoic acid, methyl ester and so on, and the core targets involved tumor necrosis factor (TNF), matrix metalloproteinase 9 (MMP9), prostaglandin-endoperoxide synthase 2 (PTGS2) and so on. 1 200 GO entries and 166 KEGG pathway entries were obtained from the enrichment analysis; molecular docking results showed that N-p-coumaroyltyramine and ethylcaffeate had good binding activity with TNF, MMP9, cysteine-aspartate protease 3 (CASP3), PTGS2, B-cell lymphoma 2 (BCL2) proteins. In vitro experiments showed that PRA, ethylcaffeate and N-p-coumaroyltyramine could inhibit the proliferation, migration and invasion of MH7A cells, up-regulate the expression of apoptosis-related gene CASP3 mRNA, and down-regulate the expression of MMP9, PTGS2 and BCL2 mRNA, and it can also down-regulate the expression of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT) mRNA and PI3K and p-AKT proteins. This study preliminarily revealed that the treatment of RA by PRA may be related to proliferation, migration, invasion, apoptosis and regulation of PI3K/AKT signaling pathway.

Humans ; Adolescent ; Fractures, Avulsion ; Fractures, Bone ; Fracture Fixation, Internal ; Ischium/surgery*

Intermittent theta burst stimulation (iTBS), a time-saving and cost-effective repetitive transcranial magnetic stimulation regime, has been shown to improve cognition in patients with Alzheimer's disease (AD). However, the specific mechanism underlying iTBS-induced cognitive enhancement remains unknown. Previous studies suggested that mitochondrial functions are modulated by magnetic stimulation. Here, we showed that iTBS upregulates the expression of iron-sulfur cluster assembly 1 (ISCA1, an essential regulatory factor for mitochondrial respiration) in the brain of APP/PS1 mice. In vivo and in vitro studies revealed that iTBS modulates mitochondrial iron-sulfur cluster assembly to facilitate mitochondrial respiration and function, which is required for ISCA1. Moreover, iTBS rescues cognitive decline and attenuates AD-type pathologies in APP/PS1 mice. The present study uncovers a novel mechanism by which iTBS modulates mitochondrial respiration and function via ISCA1-mediated iron-sulfur cluster assembly to alleviate cognitive impairments and pathologies in AD. We provide the mechanistic target of iTBS that warrants its therapeutic potential for AD patients.
Humans ; Mice ; Animals ; Transcranial Magnetic Stimulation ; Alzheimer Disease/therapy* ; Cognitive Dysfunction/therapy* ; Cognition ; Sulfur ; Iron ; Iron-Sulfur Proteins ; Mitochondrial Proteins

Glutamate-ammonia ligase (GLUL, also known as glutamine synthetase) is a crucial enzyme that catalyzes ammonium and glutamate into glutamine in the ATP-dependent condensation. Although GLUL plays a critical role in multiple cancers, the expression and function of GLUL in gastric cancer remain unclear. In the present study, we have found that the expression level of GLUL was significantly lower in gastric cancer tissues compared with adjacent normal tissues, and correlated with N stage and TNM stage, and low GLUL expression predicted poor survival for gastric cancer patients. Knockdown of GLUL promoted the growth, migration, invasion and metastasis of gastric cancer cells in vitro and in vivo, and vice versa, which was independent of its enzyme activity. Mechanistically, GLUL competed with β-Catenin to bind to N-Cadherin, increased the stability of N-Cadherin and decreased the stability of β-Catenin by alerting their ubiquitination. Furthermore, there were lower N-Cadherin and higher β-Catenin expression levels in gastric cancer tissues compared with adjacent normal tissues. GLUL protein expression was correlated with that of N-Cadherin, and could be the independent prognostic factor in gastric cancer. Our findings reveal that GLUL stabilizes N-Cadherin by antagonizing β-Catenin to inhibit the progress of gastric cancer.

Epilepsy is a common neurological disease,has the characteristics of recurrent attacks and long-term treatment,thus bringing great pressure to patients and their families.Therefore,it is particularly important to do a good job of disability assessment.In recent years,with the development of the discipline,academic organizations such as the International League Against Epilepsy(ILAE)and China Association Against Epilepsy(CAAE)have successively updated the definition and diagnostic criteria of epilepsy and seizures.However,some items of epilepsy in the current Criteria for Disability Rating of Military Personnel(Trial)issued by People's Liberation Army(PLA)in 2011 can no longer meet the latest guidelines at home and abroad.Therefore,we suggest that the items related to epilepsy in the Criteria for Disability Rating of Military Personnel(Trial)should be revised to ensure that the disability evaluation being completed fairly and successfully.

Objective:To construct the regulatory network of competitive endogenous RNA(ceRNA)and explore the mo-lecular mechanism of ischemic stroke(IS)by using bioinformatic analysis to screen the differentially-expressed genes. Method:The expression profiles of miRNA,mRNA and lncRNA in IS were downloaded from the NCBI GEO database.Differentially-expressed miRNAs,lncRNAs,and mRNAs were identified by the limma package in R software.The prediction of the relationship of lncRNA-miRNA and miRNA-mRNA were performed by starBase,miRDB and miRwalk databases.The results of prediction and differential analysis were taken to inter-sect and screened out differentially-expressed target mRNA(DETmRNAs),Kyoto Encyclopedia of Genes and Genomes(KEGG)and gene ontology(GO)enrichment analysis was performed by using the DAVID database.The protein-protein interaction(PPI)network was constructed by using the STRING database and the core tar-get genes in the network were identified by Cytoscape software. Result:A total of 20 differentially-expressed miRNAs,1512 lncRNAs,and 278 mRNAs were identified,and a ceRNA network was successfully constructed with the interactions of 5 lncRNAs-6 miRNAs-102 mRNAs in IS.The 285 DETmRNAs functions are mostly involved in the biological process such as chromatin organization,negative regulation of phosphoprotein phosphatase activity,or cell cycle.KEGG mainly enriched the signaling pathway including leukocyte trans-endothelial migration and platelet activation.The top 10 core genes were CREB1,MAPK1,GSK3B,SP1,PIK3R1,NR3C1,NCOR1,NFATC1,SETD2,and NSD1. Conclusion:The construction of the ceRNA network can help to further understand the molecular mechanism of IS and screen potential biomarkers,providing clues to further define rehabilitation targets and develop reha-bilitation strategies.

AIM To establish an HPLC method for the simultaneous content determination of gallic acid,protocatechuic acid,morroniside,loganin,sweroside,paeoniflorin,hypericin,astragalin,salvianolic acid B,salvianolic acid A,epimedin C and icariin in Bushen Huoxue Sanjie Capsules.METHODS The analysis was performed on a 30℃thermostatic Agilent 5 TC-C18 column(250 mm×4.6 mm,5 μm),with the mobile phase comprising of acetonitrile-0.1%phosphoric acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelength was set at 240 nm.RESULTS Twelve constituents showed good linear relationships within their own ranges(r≥0.999 8),whose average recoveries were 97.11%-101.14%with the RSDs of 0.60%-2.65%.CONCLUSION This simple,accurate and reproducible method can be used for the quality control of Bushen Huoxue Sanjie Capsules.

BACKGROUND:With the rapid development of minimally invasive spinal surgery and enhanced recovery after surgery,endoscopic intervertebral fusion techniques have gradually emerged and been widely used in clinical practice in recent years. OBJECTIVE:To analyze the early clinical efficacy of uniaxial spinal endoscopic intervertebral fusion combined with posterior percutaneous pedicle screw fixation in the treatment of lumbar degenerative diseases. METHODS:135 patients with lumbar degenerative diseases treated by uniaxial spinal endoscopic intervertebral fusion combined with posterior percutaneous pedicle screw fixation in the Suining Central Hospital from October 2020 to December 2021 were enrolled in this study.There were 59 males and 76 females,aged 47-79 years.The lower limb and lumbar pain was evaluated by visual analog scale and lumbar function was assessed by Oswestry disability index before the operation,1 week,1,and 6 months after the operation,and at the end of follow-up.The overall pain recovery of patients was evaluated by the scoring criteria for low back pain surgery of Spine Group of Chinese Orthopedic Association and the lumbar physiological curvature and intervertebral fusion were evaluated on lumbar lateral X-ray preoperatively and at the end of follow-up. RESULTS AND CONCLUSION:(1)The 135 patients were followed up for(17.8±3.0)months after surgery.There was 1 case of endplate injury,1 case of cerebrospinal fluid leakage,1 case of nerve root injury,1 case of intervertebral cage subsidence and displacement,1 case of chronic infection,and 1 case of pedicle screw rupture.The complication rate was 5.2%.(2)The lumbar visual analog scale score and Oswestry disability index significantly decreased in the waist and lower limbs at various time points postoperatively compared with those preoperatively in 135 patients(P<0.05).The scoring criteria for low back pain surgery of the Spine Group of the Chinese Orthopedic Association were significantly better at the last follow-up than that preoperatively in 135 patients(P<0.05).(3)At the last follow-up,there was no significant difference in physiological curvature of lumbar vertebra as compared with that preoperatively in 135 patients(P>0.05),with a fusion rate of 95.8%.(4)It is concluded that uniaxial spinal endoscopic intervertebral fusion combined with posterior percutaneous pedicle screw fixation in the treatment of lumbar degenerative diseases has shown satisfactory early clinical results and is a highly safe minimally invasive spinal surgery mode.

ObjectiveGastric cancer (GC) seriously affects human health and life, and research has shown that it is closely related to the serine/glycine metabolism. The proliferation ability of tumor cells is greatly influenced by the metabolism of serine and glycine. The aim of this study was to investigate the molecular mechanism of serine/glycine metabolism can affect the proliferation of gastric cancer cells. MethodsIn this work, a stable metabolic dynamic model of gastric cancer cells was established via a large-scale metabolic network dynamic modeling method in terms of a potential landscape description of stochastic and non-gradient systems. Based on the regulation of the model, a quantitative analysis was conducted to investigate the dynamic mechanism of serine/glycine metabolism affecting the proliferation of gastric cancer cells. We introduced random noise to the kinetic equations of the general metabolic network, and applied stochastic kinetic decomposition to obtain the Lyapunov function of the metabolic network parameter space. A stable metabolic network was achieved by further reducing the change in the Lyapunov function tied to the stochastic fluctuations. ResultsDespite the unavailability of a large number of dynamic parameters, we were able to successfully construct a dynamic model for the metabolic network in gastric cancer cells. When extracellular serine is available, the model preferentially consumes serine. In addition, when the conversion rate of glycine to serine increases, the model significantly upregulates the steady-state fluxes of S-adenosylmethionine (SAM) and S-adenosyl homocysteine (SAH). ConclusionIn this paper, we provide evidence supporting the preferential uptake of serine by gastric cancer cells and the important role of serine/glycine conversion rate in SAM generation, which may affect the proliferation ability of gastric cancer cells by regulating the cellular methylation process. This provides a new idea and direction for targeted cancer therapy based on serine/glycine metabolism.

Seven triterpenoids were isolated and purified from the 95% aqueous EtOH extract whole plants of P. villosa by various chromatographic techniques, such as silica gel, ODS, Sephadex LH-20 gel column chromatography and preparative high performance liquid chromatography. Based on physicochemical properties and spectral analyses, the structures of the seven compounds were identified as 29-acetoxyoleanolic acid-3-O-α-L-arabinopyranoside (1), oleanolic acid (2), 3β-hydroxy-24-norursa-4(23),12,20(30)-trien-28-oic acid (3), 3β-hydroxy-24-nor-urs-4(23),12-dien-28-oic acid (4), ursolic acid (5), hederagenin (6), oleanolic acid 3-O-arabinoside (7). Compound 1 is a new compound. Compounds 3, 4, 6, and 7 are isolated from P. villosa for the first time. All compounds were assayed for their anti-inflammatory activity by the prodution of NO in lipopolysaccharide-stimulated RAW 264.7 cells. The results showed that compounds 1, 2, 3, 4, 6, and 7 significantly inhibited the NO release.