OBJECTIVE: Resveratrol (Res) is a promising anticancer drug against hepatocellular carcinoma (HCC), but whether its anti-HCC effects implicate mitophagy remains unclear. Therefore, we aimed to explore the specific role of Res in mitophagy and the related mechanisms during the treatment of HCC. METHODS: HepG2 cells and tumor-grafted nude mice were used to investigate the effects of low-, middle- and high-dose of Res on HCC progression and mitophagy in vitro and in vivo, respectively. A series of approaches including cell counting kit-8, flow cytometry, wound healing and transwell assays were used to evaluate tumor cell functions. Transmission electron microscopy, immunofluorescence and Western blotting were used to assess mitophagy. Mitochondrial oxygen consumption rate, reactive oxygen species and membrane potential were used to reflect mitochondrial function. After disrupting the expression of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), miR-143-3p, and ribonucleoside reductase M2 (RRM2), the effects of the MALAT1/miR-143-3p/RRM2 axis on cell function and mitophagy under Res treatment were explored in vitro. Additionally, dual-luciferase reporter and chromatin immunoprecipitation were used to confirm interactions between target genes. RESULTS: Res significantly inhibited the proliferation and promoted apoptosis of HCC cells in vitro, while significantly suppressing tumor growth in a dose-dependent manner and inducing mitophagy and mitochondrial dysfunction in vivo. Interestingly, MALAT1 was highly expressed in HCC cells and its knockdown upregulated miR-143-3p expression in HCC cells, which subsequently inhibited RRM2 expression. Furthermore, in nude mice grafted with HCC tumors and treated with Res, the expression of MALAT1, miR-143-3p and RRM2 were altered significantly. In vitro data further supported the targeted binding relationships between MALAT1 and miR-143-3p and between miR-143-3p and RRM2. Therefore, a series of cell-based experiments were carried out to study the mechanism of the MALAT1/miR-143-3p/RRM2 axis involved in mitophagy and HCC; these experiments revealed that MALAT1 knockdown, miR-143-3p mimic and RRM silencing potentiated the antitumor effects of Res and its activation of mitophagy. CONCLUSION Res facilitated mitophagy in HCC and exerted anti-cancer effects by targeting the MALAT1/miR-143-3p/RRM2 axis. Please cite this article as: Feng CY, Cai CS, Shi XQ, Zhang ZJ, Su D, Qiu YQ. Resveratrol promotes mitophagy via the MALAT1/miR-143-3p/RRM2 axis and suppresses cancer progression in hepatocellular carcinoma. J Integr Med. 2025; 23(1): 79-91.
Humans ; MicroRNAs/genetics* ; Liver Neoplasms/metabolism* ; Carcinoma, Hepatocellular/metabolism* ; Mitophagy/drug effects* ; Resveratrol/pharmacology* ; Animals ; Mice, Nude ; RNA, Long Noncoding/genetics* ; Hep G2 Cells ; Mice ; Disease Progression ; Mice, Inbred BALB C

Sarin(GB)is a typical representative of nerve agents with high toxicity,and very low amount can cause death.GB can cause water and atmospheric environment poisoning,so the detection of GB in water and air is of great significance.In this work,a colorimetric sensor array(CSA)based on GB inhibition of cholinesterase activity was constructed to detect GB with high selectivity.A 4×4 colorimetric array was constructed using acetylcholinesterase(AChE),butyryl cholinesterase(BuChE)and the corresponding substrate acetylthiocholine iodide(S-ACh),butyryl thiocholine iodide(S-BCh),acetylcholine chloride(ACh),butyryl choline chloride(BCh)and 2,6-dichloroindophenol ethyl ester(DCIE).The linear curve of the sensor was Y=131.3×lgC+271.6(R2=0.997),where Y was the array response Euclidean distance,C was the concentration of GB(mg/L),the linear range was 0.03?0.32 mg/L,and the detection limit was 27.6 μg/L.The method could effectively distinguish chemical warfare agents(CWA)such as VX,Soman(GD),mustard gas(HD),Louie reagent(L),and had high anti-interference ability,sensitivity and good repeatability.It was successfully applied to the detection of GB in simulated water and simulated air samples,and the sample recovery rate was 97.2% ?100.9%.This method would be potentially applied to the field rapid detection of nerve agents.

OBJECTIVE: To evaluate the efficacy and safety of a hospital-made resuscitation pack, a Chinese medicinal herbal compound formula designed to enhance recovery in post-bronchoscopy patients. METHODS: In this randomized, single-blind, placebo-controlled clinical trial, eligible patients were randomly assigned 1:1 to either the treatment or control groups. The patients in the treatment group applied the resuscitation pack, which contained aromatic compounded Chinese herbs. The patients in the control group applied a hospital-made, single herb placebo pack. Packs were placed on the Tiantu (CV 22) acupuncture point for 4 h as soon as the bronchoscopy finished. Efficacy indicators, such as recovery time, patients' symptoms including nausea and dizziness, and adverse events (AEs) were observed and compared. The outcome indices were evaluated at baseline, 1 and 24 h after the bronchoscopy. Subgroup analysis was further performed by patients' age and depth of sedation. RESULTS: When applying generalized estimating equations (GEE) to evaluate the intensity of post-bronchoscopy nausea and vomiting, the intensity was lower in the treatment group (163 cases) compared with the control group (162 cases; 95% CI: 0.004, 0.099, P=0.03]. Also, significantly lower intensity of nausea was observed in the 60-70 years of age subgroup (95% CI: 0.029, 0.169, P=0.006) and deep sedation subgroup (95% CI: 0.002, 0.124; P=0.04). There was no significant difference in dizziness between two groups by GEE (95% CI: -0.134, 0.297; P=0.459). In addition, no serious AEs were observed in either group. CONCLUSIONS Our study found that the resuscitation pack markedly improved patients' symptoms by reducing nausea and vomiting after bronchoscopy without AEs, compared with placebo in the perioperative period. (Trial registration No. ChiCTR2000038299).
Humans ; Male ; Middle Aged ; Female ; Bronchoscopy/adverse effects* ; Single-Blind Method ; Aged ; Drugs, Chinese Herbal/adverse effects* ; Treatment Outcome ; Resuscitation ; Adult ; Medicine, Chinese Traditional

Objective:To explore the association between cardiometabolic multimorbidity(CMM), the number of cardiometabolic diseases(CMD)and mild cognitive impairment(MCI)among the older adults in urban communities.Methods:Based on the baseline data of the Hubei Memory and Aging Cohort Study(HMACS)from 2018 to 2023, CMM was defined as the coexistence of two or more CMDs(Type 2 diabetes, stroke and ischemic heart disease). Multivariate logistic regression was employed to examine the association between CMM, the number of CMDs and the prevalence of MCI, as well as subgroup heterogeneity.Results:This study included 6 113 urban participants aged ≥65 years(55.6% were female; mean age 71.9±5.7 years). The prevalence of MCI was 19.3%, with an increasing trend observed as the number of CMD increased(17.7%, 20.5%, 24.6%, 28.3%). After adjusting for all variables, a significant association was observed between CMM group and the prevalence of MCI( OR: 1.24, 95% CI: 1.01-1.52)compared with the non-CMM group.As the number of CMD increased, the prevalence of MCI increased( Ptrend=0.011), but the association was only significant in the group with two CMDs.Subgroup analyses revealed that in males( OR: 1.48, 95% CI: 1.10-2.00), those with more than 9 years of education( OR: 1.52, 95% CI: 1.15-2.02), and those with hypertension( OR: 1.33, 95% CI: 1.05-1.67), CMM was significantly associated with MCI, and the association with MCI increased significantly with the increase in the number of CMDs(all Pfor trend <0.05). Conclusions:Among urban community-dwelling older adults aged ≥65 years in China, CMM and the cumulative number of CMDs are significantly associated with an increase of MCI, particularly in males, those with higher education levels, and those with hypertension.In the future, the need for enhanced MCI screening for CMM patients should be strengthened, and targeted prevention and control of cognitive impairment should be implemented for high-risk populations.

Compounds isolated from Epimedium include the total flavonoids of Epimedium , icariin, and its metabolites (icaritin, icariside I, and icariside II), which have similar molecular structures. Modern pharmacological research and clinical practice have proved that Epimedium and its active components have a wide range of pharmacological effects, especially in improving sexual function, hormone regulation, anti-osteoporosis, immune function regulation, anti-oxidation, and anti-tumor activity. To date, we still need a comprehensive source of knowledge about the pharmacological effects of Epimedium and its bioactive compounds on the male reproductive system. However, their actions in other tissues have been reviewed in recent years. This review critically focuses on the Epimedium , its bioactive compounds, and the biochemical and molecular mechanisms that modulate vital pathways associated with the male reproductive system. Such intrinsic knowledge will significantly further studies on the Epimedium and its bioactive compounds that protect the male reproductive system and provide some guidances for clinical treatment of related male reproductive disorders.
Male ; Epimedium/chemistry* ; Humans ; Genitalia, Male/drug effects* ; Flavonoids/therapeutic use* ; Animals

Objective To investigate the effect of peptidyl arginine deiminase 4(PAD4)on the differentiation of mesenchymal stem cells isolated from oral bones(OMSC)and craniomaxillofacial development.Methods Immunofluorescence was used to detect the ex-pression of PAD4 in the mandibular of mice E13.5 embryo.A peptidyl arginine deiminase 4 knockout(PAD4-KO)mouse model was constructed.Craniomaxillofacial development was investigated by micro-CT.CCK-8 assay and Transwell assay were used to detect the OMSC proliferation ability and migration ability of PAD4-KO and wild type(WT)mouse.ALP staining was used to detect the changes in OMSC osteogenic differentiation ability.The expression of osteogenesis-related genes was detected by immunofluorescence and PCR assay.Results PAD4 was highly expressed in the mandibular tissue of mouse embryos at E13.5.On the cellular level,PAD4 was ex-pressed in the nucleus and mitochondria of OMSC.Compared to the WT mice,micro-CT showed that PAD4-KO mice had retrusive jaw and decreased mineralization.The proliferation and migration ability of OMSC in PAD4-KO mice were decreased.OMSCs lacking PAD4 had significantly decreased ALP staining level,and the expression levels of osteogenesis-related genes were decreased.In addition,it was found that PAD4 might affect OMSC mineralization by regulating Runx2 transcription.Conclusion PAD4 is expressed in the jaw during embryonic development.It might affect the embryonic development by regulating the proliferation and differentiation of OMSC,leading to craniomaxillofacial abnormalities

Objective:To explore the association between cardiometabolic multimorbidity(CMM), the number of cardiometabolic diseases(CMD)and mild cognitive impairment(MCI)among the older adults in urban communities.Methods:Based on the baseline data of the Hubei Memory and Aging Cohort Study(HMACS)from 2018 to 2023, CMM was defined as the coexistence of two or more CMDs(Type 2 diabetes, stroke and ischemic heart disease). Multivariate logistic regression was employed to examine the association between CMM, the number of CMDs and the prevalence of MCI, as well as subgroup heterogeneity.Results:This study included 6 113 urban participants aged ≥65 years(55.6% were female; mean age 71.9±5.7 years). The prevalence of MCI was 19.3%, with an increasing trend observed as the number of CMD increased(17.7%, 20.5%, 24.6%, 28.3%). After adjusting for all variables, a significant association was observed between CMM group and the prevalence of MCI( OR: 1.24, 95% CI: 1.01-1.52)compared with the non-CMM group.As the number of CMD increased, the prevalence of MCI increased( Ptrend=0.011), but the association was only significant in the group with two CMDs.Subgroup analyses revealed that in males( OR: 1.48, 95% CI: 1.10-2.00), those with more than 9 years of education( OR: 1.52, 95% CI: 1.15-2.02), and those with hypertension( OR: 1.33, 95% CI: 1.05-1.67), CMM was significantly associated with MCI, and the association with MCI increased significantly with the increase in the number of CMDs(all Pfor trend <0.05). Conclusions:Among urban community-dwelling older adults aged ≥65 years in China, CMM and the cumulative number of CMDs are significantly associated with an increase of MCI, particularly in males, those with higher education levels, and those with hypertension.In the future, the need for enhanced MCI screening for CMM patients should be strengthened, and targeted prevention and control of cognitive impairment should be implemented for high-risk populations.

Objective To determine the clinical effect of warmed iodophor for preoperative disinfection in elderly patients undergoing laparoscopic hysterectomy.Methods A total of 84 elderly patients who underwent laparoscopic hysterectomy were selected and randomly divided into the room temperature group(disinfected with iodophor at a temperature of 24℃)and the warmed group(disinfected with iodophor at a temperature of 39℃),with 42 cases in each group.The disinfection qualification status,incision infection status,nasopharyngeal temperature,awakening time,adverse reactions,intraoperative blood loss,incision drainage volume,and hidden blood loss of patients in the two groups were compared.Results There was no statistically significant difference in the disinfection qualification rate or incision infection rate between the two groups(P>0.05).At 10 minutes,30 minutes,60 minutes after disinfection and the end of the operation,the nasopharyngeal temperatures of patients in the warmed group were significantly higher than those in the room temperature group(P<0.05).The awakening time of patients in the warmed group was significantly shorter than that in the room temperature group(P<0.05),and the incidences of intraoperative hypothermia and shivering reaction after awakening were significantly lower than those in the room temperature group(P<0.05).There was no statistically significant difference in the intraoperative blood loss or incision drainage volume of patients between the two groups(P>0.05),while the hidden blood loss of patients in the room temperature group was significantly higher than that in the warmed group(P<0.05).Conclusion The iodophor at a temperature of 39℃for preoperative disinfection in elderly patients undergoing laparoscopic hysterectomy can not only ensure the disinfection effect and surgical safety,but also effectively maintain intraoperative body temperature stability,promote postoperative awakening,and reduce hidden blood loss.

Objective To investigate the effect of peptidyl arginine deiminase 4(PAD4)on the differentiation of mesenchymal stem cells isolated from oral bones(OMSC)and craniomaxillofacial development.Methods Immunofluorescence was used to detect the ex-pression of PAD4 in the mandibular of mice E13.5 embryo.A peptidyl arginine deiminase 4 knockout(PAD4-KO)mouse model was constructed.Craniomaxillofacial development was investigated by micro-CT.CCK-8 assay and Transwell assay were used to detect the OMSC proliferation ability and migration ability of PAD4-KO and wild type(WT)mouse.ALP staining was used to detect the changes in OMSC osteogenic differentiation ability.The expression of osteogenesis-related genes was detected by immunofluorescence and PCR assay.Results PAD4 was highly expressed in the mandibular tissue of mouse embryos at E13.5.On the cellular level,PAD4 was ex-pressed in the nucleus and mitochondria of OMSC.Compared to the WT mice,micro-CT showed that PAD4-KO mice had retrusive jaw and decreased mineralization.The proliferation and migration ability of OMSC in PAD4-KO mice were decreased.OMSCs lacking PAD4 had significantly decreased ALP staining level,and the expression levels of osteogenesis-related genes were decreased.In addition,it was found that PAD4 might affect OMSC mineralization by regulating Runx2 transcription.Conclusion PAD4 is expressed in the jaw during embryonic development.It might affect the embryonic development by regulating the proliferation and differentiation of OMSC,leading to craniomaxillofacial abnormalities

Objective To determine the clinical effect of warmed iodophor for preoperative disinfection in elderly patients undergoing laparoscopic hysterectomy.Methods A total of 84 elderly patients who underwent laparoscopic hysterectomy were selected and randomly divided into the room temperature group(disinfected with iodophor at a temperature of 24℃)and the warmed group(disinfected with iodophor at a temperature of 39℃),with 42 cases in each group.The disinfection qualification status,incision infection status,nasopharyngeal temperature,awakening time,adverse reactions,intraoperative blood loss,incision drainage volume,and hidden blood loss of patients in the two groups were compared.Results There was no statistically significant difference in the disinfection qualification rate or incision infection rate between the two groups(P>0.05).At 10 minutes,30 minutes,60 minutes after disinfection and the end of the operation,the nasopharyngeal temperatures of patients in the warmed group were significantly higher than those in the room temperature group(P<0.05).The awakening time of patients in the warmed group was significantly shorter than that in the room temperature group(P<0.05),and the incidences of intraoperative hypothermia and shivering reaction after awakening were significantly lower than those in the room temperature group(P<0.05).There was no statistically significant difference in the intraoperative blood loss or incision drainage volume of patients between the two groups(P>0.05),while the hidden blood loss of patients in the room temperature group was significantly higher than that in the warmed group(P<0.05).Conclusion The iodophor at a temperature of 39℃for preoperative disinfection in elderly patients undergoing laparoscopic hysterectomy can not only ensure the disinfection effect and surgical safety,but also effectively maintain intraoperative body temperature stability,promote postoperative awakening,and reduce hidden blood loss.