OBJECTIVE: Gastric cancer (GC) is one of the most common malignancies seen in clinic and requires novel treatment options. Morin is a natural flavonoid extracted from the flower stalk of a highly valuable medicinal plant Prunella vulgaris L., which exhibits an anti-cancer effect in multiple types of tumors. However, the therapeutic effect and underlying mechanism of morin in treating GC remains elusive. The study aims to explore the therapeutic effect and underlying molecular mechanisms of morin in GC. METHODS: For in vitro experiments, the proliferation inhibition of morin was measured by cell counting kit-8 assay and colony formation assay in human GC cell line MKN45, human gastric adenocarcinoma cell line AGS, and human gastric epithelial cell line GES-1; for apoptosis analysis, microscopic photography, Western blotting, ubiquitination analysis, quantitative polymerase chain reaction analysis, flow cytometry, and RNA interference technology were employed. For in vivo studies, immunohistochemistry, biomedical analysis, and Western blotting were used to assess the efficacy and safety of morin in a xenograft mouse model of GC. RESULTS: Morin significantly inhibited the proliferation of GC cells MKN45 and AGS in a dose- and time-dependent manner, but did not inhibit human gastric epithelial cells GES-1. Only the caspase inhibitor Z-VAD-FMK was able to significantly reverse the inhibition of proliferation by morin in both GC cells, suggesting that apoptosis was the main type of cell death during the treatment. Morin induced intrinsic apoptosis in a dose-dependent manner in GC cells, which mainly relied on B cell leukemia/lymphoma 2 (BCL-2) associated agonist of cell death (BAD) but not phorbol-12-myristate-13-acetate-induced protein 1. The upregulation of BAD by morin was due to blocking the ubiquitination degradation of BAD, rather than the transcription regulation and the phosphorylation of BAD. Furthermore, the combination of morin and BCL-2 inhibitor navitoclax (also known as ABT-737) produced a synergistic inhibitory effect in GC cells through amplifying apoptotic signals. In addition, morin treatment significantly suppressed the growth of GC in vivo by upregulating BAD and the subsequent activation of its downstream apoptosis pathway. CONCLUSION Morin suppressed GC by inducing apoptosis, which was mainly due to blocking the ubiquitination-based degradation of the pro-apoptotic protein BAD. The combination of morin and the BCL-2 inhibitor ABT-737 synergistically amplified apoptotic signals in GC cells, which may overcome the drug resistance of the BCL-2 inhibitor. These findings indicated that morin was a potent and promising agent for GC treatment. Please cite this article as: Wang Y, Sun XY, Ma FQ, Ren MM, Zhao RH, Qin MM, Zhu XH, Xu Y, Cao ND, Chen YY, Dong TG, Pan YF, Zhao AG. Morin inhibits ubiquitination degradation of BCL-2 associated agonist of cell death and synergizes with BCL-2 inhibitor in gastric cancer cells. J Integr Med. 2025; 23(3): 320-332.
Humans ; Flavonoids/therapeutic use* ; Stomach Neoplasms/pathology* ; Animals ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Cell Line, Tumor ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Ubiquitination/drug effects* ; Mice ; Drug Synergism ; Mice, Inbred BALB C ; Mice, Nude ; Xenograft Model Antitumor Assays ; Flavones

Drugs under special management include narcotic drugs,psychotropic drugs,toxic drugs for medical use,radiopharmaceuticals,and pharmaceutical precursor chemicals.Supervising and guiding the clinical use of drugs under special management is one of the important responsibilities of the Pharmaceutical Management and Drug Therapy Committee(Group)of medical institutions.The standard for drugs under special management is led by the Pharmaceutical Professional Committee of the China Hospital Association,which standardizes 16 key elements of organizational management,process management,and quality control management drugs under special management in medical institutions.It can guide the standardized implementation of Pharmaceuticals under special control work in various levels and types of medical institutions.This article elaborates on the methods and contents of formulating standards for Pharmaceuticals under special management,to provide reference and inspiration for medical institutions to carry out special drug drug management and daily related work.

Abetalipoproteinemia ; Cilia ; Humans ; Kartagener Syndrome

A new isoflavone derivative was isolated from Rosa damascena by using various chromatographic techniques including silica gel, Sephadex LH-20, and preparative RP-HPLC separation. Its structure was identified as 4'-hydroxy-7-(3-hydroxypropanoyl)-6-methoxy-isoflavone using combined examinations of their UV, IR, MS, and NMR spectroscopic data. Biological activity test showed that this compound showed prominent antibacterial activity with MIC₉₀ value of (46±4) mg·L⁻¹ for methicillin resistant Staphylococcus aureus(MRSA) strain. This value is close to that of levofloxacin [with MIC₉₀ value (53±5) mg·L⁻¹].
Anti-Bacterial Agents ; isolation & purification ; pharmacology ; Isoflavones ; isolation & purification ; pharmacology ; Methicillin-Resistant Staphylococcus aureus ; drug effects ; Microbial Sensitivity Tests ; Phytochemicals ; isolation & purification ; pharmacology ; Rosa ; chemistry

Objective:To describe the prevalence of anxiety disorders and distribution in Chifeng City,and explore the related risk factors and health service seeking.Methods:Individuals aged 18 years and over were sampled by stratified,probability-proportional-to-size sampling,randomized cluster sampling in Chifeng City through November,2010 to April,2011.All respondents were interviewed by trained interviewers face-to-face.The Composite International Diagnostic Interview-3.0 Computer Assisted Personal Interview (CIDI-3.0-CAPI) was used to diagnose anxiety disorders according to the criteria and definition of the Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition (DSM-Ⅳ).Single and multivariate analysis were applied to explore risk factors of anxiety disorder.Results:Totally 4528 subjects were interviewed with CIDI-3.0-CAPI.The 12-month prevalence rate of anxiety disorders was significantly higher in rural area than in urban area (4.62％ vs.2.61％,P ＜0.01).The rate was significantly higher in female than in male (4.92％ vs.2.82％,P ＜0.01).The rate was significantly higher in the unmarried,the divorced and the widowed than in the married (5.91％ vs.3.70％,P ＜0.01).Logistic regression analysis indicated that dwelling in urban areas and education level of 7-9 years were the protective factors of anxiety disorders,while being female,unmarried,divorced or widowed were the risk factors of anxiety disorders.It was found that only 3.1％ of the patients with anxiety disorders reported to seek help from psychiatrists.Conclusion:The anxiety disorder is a common mental disorder in Chifeng City,while few people with anxiety disorders seek mental health professionals.Therefore,it should be paid attentions to anxiety disorder,especially in rural area,women,and low educated people for enhancing mental health service and knowledge popularization.

Objective To study the protection of total Hedysaripolysaccharide in lipopolysaccharide (LPS) induced acute lung injury (ALI) of mice.Methods The mice were randomly divided into 6 groups:normal group,model group (8 mg · kg-1 lipopolysaccharide),control group (dexamethasone 3 mg· kg-1),and experimental groups in low,middle and high dose (50,100,200 mg · kg-1 total Hedysaripolysaccharide).Tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10)levels in serum were measured with enzyme-linked immunosorbent assay.Total antioxidant capacity (T-AOC),the activities of super oxide dismutase (SOD) and malondialdehyde (MDA) contents in serum were detected by spectrophotometer.And DNA damage of peripheral blood lymphocytes was observed by single cell gel electrophoresis.Results The serum TNF-α and IL-10 levels in model group were (156.23 ± 7.39),(44.24 ± 2.89) ng · L-1,which in middle and high dose of experimental groups were (139.45 ± 6.57),(35.30 ± 1.88);(120.13 ± 6.81),(33.11 ±2.71) ng · L-1,the difference was significant(all P ＜0.01).T-AOC,SOD activities in middle and high dose of experimental groups were (5.91 ± 0.10),(70.00 ± 3.04);(6.10 ± 0.09),(76.21 ± 4.03) U · mg-1,which were obviously higher than those of model group which were (5.56 ± 0.13),(67.68 ± 4.86) U · mg-1 (all P ＜0.01).MDA contents of middle and high dose experimental groups were (5.01 ± 0.11),(4.17 ± 0.12) nmol · mg-1,which were obviously lower than that of model group with(5.55 ±0.11) nmol · mg-1 (all P ＜0.01).DNA tail length (TL) were (5.81 ±0.10),(5.24 ±0.10) μm,tail moment (TM)were (2.86 ±0.12),(2.71 ±0.16) μm,and Olive tail moment(OTM) were (2.67 ±0.10),(2.17 ±0.18) μm in middle and high dose of experimental groups,which were significantly lower than those of model group:TL was (6.45 ± 0.08) μm,TM was (3.22 ± 0.14) μm,and OTM was (3.35 ± 0.12) μm,the differences were all significant (all P ＜ 0.01).Conclusion Total Hedysaripolysaccharide had a protective effect against the lipopolysaccharide-induced acute lung injury.The possible mechanisms may be due to the regulation the proportional imbalance of TNF-α and IL-10,as well as the balance oxidative and anti-oxidative.

OBJECTIVETo investigate the protective effects of selenium on rat hippocampal neurons against ischemia-reperfusion (IR) injury.

METHODSThirty-two rats were randomly divided into sham-operated group, IR group and selenium-treated group, and in the latter two groups, cerebral IR injury was induced by middle cerebral artery occlusion; Na2SeO3 treatment was administer in selenium-treated group. At 14 days after reperfusion, the brain tissues were harvested from the rats and hippocampal neuron injuries were observed by TUNEL and Methylene Blue staining. The levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and nerve growth factor (NGF) in the hippocampal tissues were measured by ELISA.

RESULTSCompared with IR group, the rats in selenium-treated group showed no significant increase in the expression of m-NGF (P>0.05), but pro-NGF expression was significantly increased (P<0.05) in the hippocampal tissue. Na2SeO3 treatment significantly inhibited the expressions of TNF-α and IL-1β and decreased the apoptosis of hippocampal neurons following cerebral IR injury (P<0.05).

CONCLUSIONSelenium produces antiapoptotic effect to protect the hippocampal neurons following cerebral IR injury possibly not by increasing the level of m-NGF but by decreasing the expressions of the inflammatory factors.

Animals ; Apoptosis ; Brain Ischemia ; metabolism ; pathology ; Hippocampus ; cytology ; metabolism ; pathology ; Interleukin-1beta ; metabolism ; Male ; Nerve Growth Factor ; metabolism ; Neurons ; drug effects ; metabolism ; pathology ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; metabolism ; pathology ; Sodium Selenite ; pharmacology ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVETo explore the relationship between risk factors for coronary heart disease (CHD) and coronary artery lesions.

METHODPotential risk factors were studied in 341 patients underwent coronary angiography.

RESULTS(1) Coronary angiography showed coronary artery lesions in 214 patients (lesion group), and no lesion in 127 patients (non-lesion group). There was significant difference in age, past history of diabetes, family history of CHD, smoking history, high-density lipoprotein cholesterol (HDL-C), lower-density lipoprotein cholesterol (LDL-C), ratio of total cholesterol to HDL-C (TC/HDL-C), lipoprotein(a) [Lp(a)], fibrinogen (Fbg) and high-sensitivity C-reactive protein (hs-CRP) between two groups (P < 0.05). (2) There was significant correlation between severity of coronary artery lesions and hs-CRP, Lp(a), TC/HDL-C, Fbg, hyperlipidemia, TC, LDL-C and TG (with coefficients of correlation of 0.338, 0.250, 0.241, 0.207, 0.167, 0.147, 0.140 and 0.139; respectively, P < 0.05). (3) Analysis of receiver operating characteristics (ROC) curve for patients with coronary angiography and risk factors for CHD showed that the areas under ROC curve were 0.810, 0.669, 0.626, 0.625, 0.619 and 0.618 for hs-CRP, TC/HDL-C, Lp(a), Fbg, LDL-C and past history of hyperlipidemia, respectively.

CONCLUSIONSPast history of hyperlipidemia was a predictor for occurrence of CHD. Ratio of TC/HDL-C and blood level of Lp(a) could be used as predictors in screening for high blood lipid, which were much stronger than others. It is suggested that hs-CRP had an excellent predictive value in current coronary inflammatory lesions.

Adult ; Aged ; Aged, 80 and over ; C-Reactive Protein ; metabolism ; Coronary Disease ; etiology ; Female ; Humans ; Hyperlipidemias ; complications ; Male ; Middle Aged ; ROC Curve ; Risk Factors

OBJECTIVETo search for a simple and non-invasive method to assist the treatment of the complications of breast augmentation with polyacrylamide hydrogel injection.

METHODSHigh-frequency ultrasound was used to examine the breast and observe the distributions of the injected polyacrylamide hydrogel. The operation procedure was predetermined according to the ultrasound information. The ultrasound results were compared with what was seen during the operation.

RESULTS40 patients (80 breasts) were examined. The ultrasound results were coincident with the outcomes of surgery. The results of postoperative follow-up were coincident with the predicted.

CONCLUSIONUltrasound is an accurate method for examining the augmented breast with polyacrylamide hydrogel injection. It is helpful in predetermining the operation procedure, predicting postoperative results.

Acrylic Resins ; adverse effects ; Adult ; Breast ; pathology ; surgery ; Female ; Humans ; Injections ; Surgery, Plastic ; adverse effects ; Treatment Outcome ; Ultrasonography, Mammary