Liver ischemia-reperfusion injury (LIRI) is a pathological process involving multiple injury factors and cell types, with different stages. Currently, protective drugs targeting a single condition are limited in efficacy, and interventions on immune cells will also be accompanied by a series of side effects. In the current bottleneck research stage, the multi-target and obvious clinical efficacy of Chinese medicine (CM) is expected to become a breakthrough point in the research and development of new drugs. In this review, we summarize the roles of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in various stages of hepatic ischemia-reperfusion and on various types of cells. Combined with the current research progress in reducing ROS/RNS with CM, new therapies and mechanisms for the treatment of hepatic ischemia-reperfusion are discussed.
Reperfusion Injury/drug therapy* ; Reactive Oxygen Species/metabolism* ; Reactive Nitrogen Species/metabolism* ; Humans ; Liver/drug effects* ; Animals ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/pharmacology*

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

BACKGROUND: Acupuncture therapy provides a complementary and alternative approach to treating major depressive disorder (MDD), but its efficacy and safety have still not been comprehensively assessed. Recently published systematic reviews remain confusing and inconclusive. OBJECTIVE: This systematic review evaluated the efficacy and safety of acupuncture therapy alone or combined with antidepressants for adult patients with mild and moderate MDD. SEARCH STRATEGY: Chinese Biomedical Literature Database, China National Knowledge Infrastructure Database, Wanfang Database, Chinese Science and Technology Journal Database, PubMed, Embase, and Cochrane Library were searched from their inceptions to March 2025. INCLUSION CRITERIA: Randomized controlled trials that compared acupuncture therapy with antidepressants, or acupuncture therapy plus antidepressants with acupuncture therapy or antidepressants for adult patients with mild and moderate MDD were included. DATA EXTRACTION AND ANALYSIS: Five reviewers independently extracted data from original literature using a standardized form, and the data were verified by two reviewers to ensure accuracy. Statistical meta-analyses, publication bias analyses, and subgroup analyses were performed by using Review Manager 5.3 software. The Grading of Recommendations Assessment, Development, and Evaluation approach was used to assess the certainty of the evidence. RESULTS: A total of 60 eligible studies including 4675 participants were included. Low-certainty evidence showed that compared with antidepressants, acupuncture therapy (standardized mean difference [SMD] = -0.57; 95% confidence interval [CI] = [-0.87, -0.27]; I² = 86%; P = 0.006) or acupuncture therapy plus antidepressants (SMD = -1.00; 95% CI = [-1.18, -0.81]; I² = 77%; P < 0.00001) may reduce the severity of depression at the end of treatment. Low-certainty evidence indicated that compared with acupuncture therapy alone, acupuncture therapy plus antidepressants slightly reduced the severity of depression at the end of treatment (SMD = -0.38; 95% CI = [-0.61, -0.14]; I² = 18%; P = 0.002). Similar results were also found for acupuncture's relief of insomnia. The reported adverse effects of acupuncture therapy were mild and transient. For most of the subgroup analyses, acupuncture type, scale type, and the course of treatment did not show a significant relative effect. CONCLUSION Acupuncture therapy may provide antidepressant effects and relieve insomnia with mild adverse effects for adult patients with mild and moderate MDD. But the certainty of evidence was very low. More high-quality, well designed, large-scale studies with long-term follow-up are needed in the future. Please cite this article as: Kuang HJ, Yang HS, Feng YX, Tang H, Fan Q, Xu YQ, Cui S, Musil R, Luxenburger H, Zhang YX, Zhao H, Zhang YQ. Efficacy and safety of acupuncture therapies for adult patients with mild and moderate major depressive disorder: A systematic review and meta-analysis. J Integr Med. 2025; 23(5):471-491.
Humans ; Acupuncture Therapy/methods* ; Depressive Disorder, Major/therapy* ; Adult ; Antidepressive Agents/therapeutic use* ; Treatment Outcome ; Randomized Controlled Trials as Topic

OBJECTIVE: To investigate the associations between eight serum per- and polyfluoroalkyl substances (PFASs) and regional fat depots, we analyzed the data from the National Health and Nutrition Examination Survey (NHANES) 2011-2018 cycles. METHODS: Multiple linear regression models were developed to explore the associations between serum PFAS concentrations and six fat compositions along with a fat distribution score created by summing the concentrations of the six fat compositions. The associations between structurally grouped PFASs and fat distribution were assessed, and a prediction model was developed to estimate the ability of PFAS exposure to predict obesity risk. RESULTS: Among females aged 39-59 years, trunk fat mass was positively associated with perfluorooctane sulfonate (PFOS). Higher concentrations of PFOS, perfluorohexane sulfonate (PFHxS), perfluorodecanoate (PFDeA), perfluorononanoate (PFNA), and n-perfluorooctanoate (n-PFOA) were linked to greater visceral adipose tissue in this group. In men, exposure to total perfluoroalkane sulfonates (PFSAs) and long-chain PFSAs was associated with reductions in abdominal fat, while higher abdominal fat in women aged 39-59 years was associated with short-chain PFSAs. The prediction model demonstrated high accuracy, with an area under the curve (AUC) of 0.9925 for predicting obesity risk. CONCLUSION PFAS exposure is associated with regional fat distribution, with varying effects based on age, sex, and PFAS structure. The findings highlight the potential role of PFAS exposure in influencing fat depots and obesity risk, with significant implications for public health. The prediction model provides a highly accurate tool for assessing obesity risk related to PFAS exposure.
Humans ; Fluorocarbons/blood* ; Female ; Adult ; Middle Aged ; Male ; Environmental Pollutants/blood* ; Abdominal Fat ; Nutrition Surveys ; Alkanesulfonic Acids/blood* ; Obesity ; Environmental Exposure

OBJECTIVE: We aimed to investigate the patterns of fasting blood glucose (FBG) trajectories and analyze the relationship between various occupational hazard factors and FBG trajectories in male steelworkers. METHODS: The study cohort included 3,728 workers who met the selection criteria for the Tanggang Occupational Cohort (TGOC) between 2017 and 2022. A group-based trajectory model was used to identify the FBG trajectories. Environmental risk scores (ERS) were constructed using regression coefficients from the occupational hazard model as weights. Univariate and multivariate logistic regression analyses were performed to explore the effects of occupational hazard factors using the ERS on FBG trajectories. RESULTS: FBG trajectories were categorized into three groups. An association was observed between high temperature, noise exposure, and FBG trajectory ( P < 0.05). Using the first quartile group of ERS1 as a reference, the fourth quartile group of ERS1 had an increased risk of medium and high FBG by 1.90 and 2.21 times, respectively (odds ratio [ OR] = 1.90, 95% confidence interval [ CI]: 1.17-3.10; OR = 2.21, 95% CI: 1.09-4.45). CONCLUSION An association was observed between occupational hazards based on ERS and FBG trajectories. The risk of FBG trajectory levels increase with an increase in ERS.
Humans ; Male ; Adult ; Blood Glucose/analysis* ; China ; Prospective Studies ; Occupational Exposure/adverse effects* ; Risk Factors ; Middle Aged ; Steel ; Fasting/blood* ; Metal Workers ; East Asian People

OBJECTIVE: To investigate chronic hepatitis C virus (HCV) infection's effect on gestational liver function, pregnancy and delivery complications, and neonatal development. METHODS: A total of 157 HCV antibody-positive (anti-HCV[+]) and HCV RNA(+) patients (Group C) and 121 anti-HCV(+) and HCV RNA(-) patients (Group B) were included as study participants, while 142 anti-HCV(-) and HCV RNA(-) patients (Group A) were the control group. Data on biochemical indices during pregnancy, pregnancy complications, delivery-related information, and neonatal complications were also collected. RESULTS: Elevated alanine aminotransferase (ALT) rates in Group C during early, middle, and late pregnancy were 59.87%, 43.95%, and 42.04%, respectively-significantly higher than Groups B (26.45%, 15.70%, 10.74%) and A (23.94%, 19.01%, 6.34%) ( P < 0.05). Median ALT levels in Group C were significantly higher than in Groups A and B at all pregnancy stages ( P < 0.05). No significant differences were found in neonatal malformation rates across groups ( P > 0.05). However, neonatal jaundice incidence was significantly greater in Group C (75.16%) compared to Groups A (42.25%) and B (57.02%) ( χ ² = 33.552, P < 0.001). HCV RNA positivity during pregnancy was an independent risk factor for neonatal jaundice ( OR = 2.111, 95% CI 1.242-3.588, P = 0.006). CONCLUSIONS Chronic HCV infection can affect the liver function of pregnant women, but does not increase the pregnancy or delivery complication risks. HCV RNA(+) is an independent risk factor for neonatal jaundice.
Humans ; Female ; Pregnancy ; Adult ; Pregnancy Complications, Infectious/epidemiology* ; Retrospective Studies ; Pregnancy Outcome ; Infant, Newborn ; Viremia/virology* ; Hepatitis C ; Hepacivirus/physiology* ; Hepatitis C, Chronic/virology* ; Young Adult ; Alanine Transaminase/blood*

OBJECTIVE: CRISPR-Cas protects bacteria from exogenous DNA invasion and is associated with bacterial biofilm formation and pathogenicity. METHODS: We analyzed the type I-F CRISPR-Cas system of Legionella pneumophila WX48, including Cas1, Cas2-Cas3, Csy1, Csy2, Csy3, and Cas6f, along with downstream CRISPR arrays. We explored the effects of the CRISPR-Cas system on the in vitro growth, biofilm-forming ability, and pathogenicity of L. pneumophila through constructing gene deletion mutants. RESULTS: The type I-F CRISPR-Cas system did not affect the in vitro growth of wild-type or mutant strains. The biofilm formation and intracellular proliferation of the mutant strains were weaker than those of the wild type owing to the regulation of type IV pili and Dot/Icm type IV secretion systems. In particular, Cas6f deletion strongly inhibited these processes. CONCLUSION The type I-F CRISPR-Cas system may reduce biofilm formation and intracellular proliferation in L. pneumophila.
Legionella pneumophila/pathogenicity* ; CRISPR-Cas Systems ; Biofilms/growth & development* ; Phenotype ; Bacterial Proteins/metabolism* ; Gene Deletion

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection,with a high mortality rate.Sirtuin 3,a deacetylase within mitochondria,plays an important regulatory role in cellular metabolism,oxidative stress,and inflammatory responses.In recent years,significant progress has been made in the study of the function and regulatory role of sirtuin 3 in sepsis-related diseases.Research has shown that sirtuin 3 can alleviate organ damage caused by sepsis by regulating mitochondrial function,reducing oxidative stress,and inhibiting inflammatory responses.The specific mechanisms include the regulation of mitochondrial bioenergetics,activation of antioxidant enzyme systems,and inhibition of inflammatory mediator expression.In addition,sirtuin 3 plays a protective role in the pathological process of sepsis by interacting with multiple signaling pathways.This article summarizes the functions and regulatory mechanisms of sirtuin 3 in various sepsis-related diseases,aiming to provide new targets and strategies for the prevention and treatment of sepsis in the future.
Sepsis/metabolism* ; Sirtuin 3/physiology* ; Humans ; Animals ; Oxidative Stress ; Mitochondria/metabolism* ; Signal Transduction

Objective To explore the mechanism by which curcumin improves behavioral deficits in mice with Parkinson's disease(PD)through fecal microbiota transplantation.Methods A subacute model of PD in mice was induced by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP).Fecal microbiota from both the model group and the curcumin(Cur)-treated group(80 m g/kg)were collected and analyzed.The experiment involving fecal microbiota transplantation was structured into four distinct groups,fecal microbiota solvent transplantation group(FMTcon),model fecal microbiota transplantation group(FMTmodel),MPTP-induced model group(model),and model group subjected to fecal microbiota transplantation following curcumin treatment(model+FMTCur).The motor skills of the mice were assessed by using rod rotation,pole climbing experiment,and open field tests.Immunofluorescence techniques were employed to observe the expression tyrosine hydroxylase(TH)-positive neurons in the substantia nigra of the brain.Additionally,the gene expression of tumor necrosis factor-α(TNF-α)in the midbrain of mice was analyzed,alongside the protein expression of nuclear factor-κB(NF-κB)and nucleotide binding oligomerization domain-like receptor protein 3(NLRP3).Results The subacute PD animal model in mice was successfully established,and fecal microbiota were separated and gathered.The model group exhibited significant motor impairment,as evidenced by a shortened rod rotation time(P＜0.05),prolonged pole climbing time(P＜0.05),significantly reduced total movement distance within the open field(P＜0.001),and decreased time spent in the central zone(P＜0.01).The relative expression level of TH+neurons in the substantia nigra was significantly reduced(P＜0.01).Moreover,mRNA expression of TNF-α in the midbrain increased significantly(P＜0.01),along with significant elevations in protein expression of NF-κB(P＜0.001),phosphorylated NF-κB(p-NF-κB)(P＜0.01),NLRP3(P＜0.001),and Caspase-1(P＜0.01).The transplanted model microbial group(FMTmodel)also exhibited motor impairment,manifested by a trend of shortened rod rotation time,prolonged pole climbing time,a significant decrease in total movement distance within the open field(P＜0.01),and a trend of shortened time spent in the central zone.The relative expression level of TH+neurons in the substantia nigra decreased significantly(P＜0.05).Additionally,mRNA expression of TNF-α in the midbrain increased significantly(P＜0.01),along with notable elevations in the protein expression of NF-κB(P＜0.05),and Caspase-1(P＜0.01).Treatment with curcumin in the fecal microbiota transplantation group of mice(model+FMTCur)showed improvements in motor abilities,evidenced by shortened pole climbing time(P＜0.05),significantly prolonged rod rotation time(P＜0.01),and extended time spent in the central zone(P＜0.05).The relative expression level of TH+dopaminergic neurons in the substantia nigra increased significantly(P＜0.05).Moreover,mRNA expression of TNF-α in the midbrain decreased significantly(P＜0.01),along with notable reductions in the protein expression of NF-κB(P＜0.001),p-NF-κB(P＜0.01),NLRP3(P＜0.05),and Caspase-1(P＜0.01).Conclusion Fecal microbiota transplantation in PD model mice can induce behavioral deficits,damage TH+neurons in the substantia nigra,and trigger neuroinflammation in the brain.Subsequent curcumin treatment can ameliorate these deficits,reverse damage to TH+neurons,reduce neuroinflammatory factors,and decrease the expression of NF-κB and NLRP3 pathways.This preliminary evidence suggests that curcumin may improve Parkinsonian behavioral deficits in mice by modulating the gut microbiota.

This study aims to investigate the action mechanism of Shenzhuo Decoction(SZT, i.e., Ganjiang Lingzhu Decoction) in treating knee osteoarthritis(KOA). Network pharmacology was used to analyze the key targets of SZT in the treatment of KOA. At the cellular experimental level, primary chondrocytes extracted from rats were used for in vitro validation. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL) staining was employed to detect chondrocyte apoptosis in the knee joint. Western blot was performed to analyze the expression of the anti-apoptotic factor(Bcl2), the apoptosis marker gene Bax, and key proteins in the phosphoinositide 3-kinase(PI3K)-protein kinase B(Akt) signaling pathway. In animal experiments, 60 7-week-old male SD rats were used to establish a KOA model and randomly divided into a control group, a KOA model group, high-, medium-, and low-dose SZT groups, and a celecoxib group, with 10 rats in each group. Micro-CT was used to observe changes in bone mineral density and osteophytes at the articular cartilage surface. Hematoxylin-eosin(HE) staining and safranin O-fast green(SFO) staining were used to observe pathological changes in cartilage tissue. Immunohistochemistry was used to detect the expression of inflammatory factor matrix metalloproteinase 13(MMP13) and cartilage marker collagen Ⅱ. Quantitative reverse transcription-polymerase chain reaction(qRT-PCR) was used to detect the expression of chondrocyte marker SRY-box transcription factor 9(SOX9) and inflammatory markers matrix metalloproteinase 9(MMP9), interleukin-6(IL-6), interleukin-1β(IL-1β), and tumor necrosis factor-α(TNF-α). Cell experiments revealed that SZT effectively improved KOA, and the results of micro-CT and HE and SFO staining showed that compared with the control group, the model group had obvious formation of osteophytes on the joint surface, which became rough, with significant decreases in the trabecular bone volume fraction(BV/TV), trabecular number(Tb.N), and trabecular thickness(Tb.Th) and a significant increase in trabecular spacing(Tb.Sp). The SZT groups had few osteophytes and a smoother joint surface than the model group. Additionally, BV/TV, Tb.N, and Tb.Th were significantly increased, while Tb.Sp was gradually decreased. A SZT-component-KOA target network was constructed to locate the core targets in KOA treatment, which was further validated through in vivo and in vitro animal experiments. The immunohistochemistry results of the pathological section of rat joint tissue showed that compared with the control group, the model group had a significant increase in MMP13 and a decrease in collagen Ⅱ, while SZT could inhibit inflammation and strengthen the protection of collagen Ⅱ in articular cartilage. The qRT-PCR results showed that SZT could significantly inhibit the mRNA expression of IL-6, IL-1β, TNF-α, and MMP9 and upregulate the mRNA level of SOX9. The TUNEL detection results showed that in the lipopolysaccharide(LPS)-induced KOA model group, chondrocyte apoptosis was significantly increased, and the fluorescence intensity was significantly enhanced. SZT, however, significantly reduced the trend of chondrocyte apoptosis and decreased the fluorescence intensity. The Western blot results showed that SZT could effectively inhibit the phosphorylation level of proteins in the PI3K-Akt pathway, reduce the expression of Bax, increase the expression of Bcl2, and inhibit the degradation of SOX9. In conclusion, SZT may alleviate the degenerative damage of KOA by inhibiting the phosphorylated expression of key proteins in the PI3K-Akt signaling pathway, reducing the release of inflammatory factors, and inhibiting chondrocyte apoptosis.
Animals ; Chondrocytes/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Osteoarthritis, Knee/physiopathology* ; Rats, Sprague-Dawley ; Rats ; Apoptosis/drug effects* ; Signal Transduction/drug effects* ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/immunology* ; Humans