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

Hypovolemic shock and septic shock present similar symptoms, such as increased heart rate and decreased blood pressure. However, the two conditions have different causes, mechanisms, and treatment approaches. Early differentiation between the two conditions can have a positive impact on patient prognosis. In this case, the patient underwent a right ovarian cystectomy due to a teratoma torsion during a previous pregnancy, followed by treatment for a postoperative infection. While recovering, the patient underwent an emergency cesarean section due to sudden severe abdominal pain. After the surgery, unstable vital signs were suggestive of hypovolemia due to massive bleeding from the cesarean section. Therefore, fluid infusion and blood transfusion were initiated. The vital signs did not improve. So, the patient was reassessed. Body temperature and the previously elevated C-reactive protein levels were remeasured. The results of the reassessment indicated a septic condition due to previous infection. The patient was prescribed additional vasopressors and antibiotics for the following week. Subsequently, the patient’s vital signs stabilized, and the treatment was discontinued.

Hypovolemic shock and septic shock present similar symptoms, such as increased heart rate and decreased blood pressure. However, the two conditions have different causes, mechanisms, and treatment approaches. Early differentiation between the two conditions can have a positive impact on patient prognosis. In this case, the patient underwent a right ovarian cystectomy due to a teratoma torsion during a previous pregnancy, followed by treatment for a postoperative infection. While recovering, the patient underwent an emergency cesarean section due to sudden severe abdominal pain. After the surgery, unstable vital signs were suggestive of hypovolemia due to massive bleeding from the cesarean section. Therefore, fluid infusion and blood transfusion were initiated. The vital signs did not improve. So, the patient was reassessed. Body temperature and the previously elevated C-reactive protein levels were remeasured. The results of the reassessment indicated a septic condition due to previous infection. The patient was prescribed additional vasopressors and antibiotics for the following week. Subsequently, the patient’s vital signs stabilized, and the treatment was discontinued.

This study was aimed at creating an engineered strain of Bacillus subtilis for efficient expression of biologically active type 2 toxin B(TcdB2)derived from a highly virulent strain of Clostridium difficile.The TcdB2 gene was cloned from ST1/RT027 strain genome DNA,incorporated into the PHT01 vector,and then transformed into B.subtilis strain WB800N for prokaryotic expression.Cell toxicity assays revealed that the recombinant TcdB2 exhibited cytotoxic effects in various cells.The engineered B.subtilis strain effectively expressed biologically active TcdB2,thus providing a basis for further exploration of the pathogenic mechanisms of highly virulent strains of C.difficile and establishing a foundation for potential vaccine can-didate targets.

Aim To investigate the effects of Ginkgo biloba extract(GBE)on vascular endothelial dysfunc-tion induced by chronic intermittent hypoxia(CIH)in rats and its related mechanisms.Methods The CIH rat model was established,and 50 and 100 mg·kg-1 GBE was administered by intragastric administration.The systolic blood pressure(SBP)of the tail artery was detected in each group.HE staining was used to detect the morphology of aorta tissue.DAF-FM DA staining and nitric reductase assay were used to detect NO levels.ELISA was used to detect serum ET-1,TNF-α and IL-6 levels.DHE staining was used to de-tect reactive oxygen species(ROS)levels of aortic tis-sue.Kits were used to detect the serum levels of MDA,SOD and GSH-Px.Western blot was used to detect the levels of VCAM-1,ICAM-1,nucleus Nrf2,HO-1 and NQO1 of aortic tissue.Results GBE sig-nificantly decreased the levels of SBP,ET-1,ROS,MDA,VCAM-1,ICAM-1,TNF-α and IL-6,and sig-nificantly increased the levels of NO,SOD,GSH-Px,nuclear Nrf2,HO-1 and NQO1 in CIH rats.GBE sig-nificantly improved the histomorphology of aorta in CIH rats.Conclusions GBE can improve vascular endo-thelial dysfunction and reduce blood pressure in CIH model rats.The mechanism may be related to the acti-vation of Nrf2/ARE pathway and the inhibition of oxi-dative stress and inflammation by GBE.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.

Hypovolemic shock and septic shock present similar symptoms, such as increased heart rate and decreased blood pressure. However, the two conditions have different causes, mechanisms, and treatment approaches. Early differentiation between the two conditions can have a positive impact on patient prognosis. In this case, the patient underwent a right ovarian cystectomy due to a teratoma torsion during a previous pregnancy, followed by treatment for a postoperative infection. While recovering, the patient underwent an emergency cesarean section due to sudden severe abdominal pain. After the surgery, unstable vital signs were suggestive of hypovolemia due to massive bleeding from the cesarean section. Therefore, fluid infusion and blood transfusion were initiated. The vital signs did not improve. So, the patient was reassessed. Body temperature and the previously elevated C-reactive protein levels were remeasured. The results of the reassessment indicated a septic condition due to previous infection. The patient was prescribed additional vasopressors and antibiotics for the following week. Subsequently, the patient’s vital signs stabilized, and the treatment was discontinued.

Hypovolemic shock and septic shock present similar symptoms, such as increased heart rate and decreased blood pressure. However, the two conditions have different causes, mechanisms, and treatment approaches. Early differentiation between the two conditions can have a positive impact on patient prognosis. In this case, the patient underwent a right ovarian cystectomy due to a teratoma torsion during a previous pregnancy, followed by treatment for a postoperative infection. While recovering, the patient underwent an emergency cesarean section due to sudden severe abdominal pain. After the surgery, unstable vital signs were suggestive of hypovolemia due to massive bleeding from the cesarean section. Therefore, fluid infusion and blood transfusion were initiated. The vital signs did not improve. So, the patient was reassessed. Body temperature and the previously elevated C-reactive protein levels were remeasured. The results of the reassessment indicated a septic condition due to previous infection. The patient was prescribed additional vasopressors and antibiotics for the following week. Subsequently, the patient’s vital signs stabilized, and the treatment was discontinued.

Hypovolemic shock and septic shock present similar symptoms, such as increased heart rate and decreased blood pressure. However, the two conditions have different causes, mechanisms, and treatment approaches. Early differentiation between the two conditions can have a positive impact on patient prognosis. In this case, the patient underwent a right ovarian cystectomy due to a teratoma torsion during a previous pregnancy, followed by treatment for a postoperative infection. While recovering, the patient underwent an emergency cesarean section due to sudden severe abdominal pain. After the surgery, unstable vital signs were suggestive of hypovolemia due to massive bleeding from the cesarean section. Therefore, fluid infusion and blood transfusion were initiated. The vital signs did not improve. So, the patient was reassessed. Body temperature and the previously elevated C-reactive protein levels were remeasured. The results of the reassessment indicated a septic condition due to previous infection. The patient was prescribed additional vasopressors and antibiotics for the following week. Subsequently, the patient’s vital signs stabilized, and the treatment was discontinued.