Emodin is a hydroxyanthraquinone compound that is widely distributed and has multiple pharmacological activities, including anti-diarrheal, anti-inflammatory, and liver-protective effects. Research indicates that emodin may be one of the main components responsible for inducing hepatotoxicity. However, studies on the mechanisms of liver injury are relatively limited, particularly those related to bile acids(BAs) metabolism. This study aims to systematically investigate the effects of different dosages of emodin on BAs metabolism, providing a basis for the safe clinical use of traditional Chinese medicine(TCM)containing emodin. First, this study evaluated the safety of repeated administration of different dosages of emodin over a 5-week period, with a particular focus on its impact on the liver. Next, the composition and content of BAs in serum and liver were analyzed. Subsequently, qRT-PCR was used to detect the mRNA expression of nuclear receptors and transporters related to BAs metabolism. The results showed that 1 g·kg~(-1) emodin induced hepatic damage, with bile duct hyperplasia as the primary pathological manifestation. It significantly increased the levels of various BAs in the serum and primary BAs(including taurine-conjugated and free BAs) in the liver. Additionally, it downregulated the mRNA expression of farnesoid X receptor(FXR), retinoid X receptor(RXR), and sodium taurocholate cotransporting polypeptide(NTCP), and upregulated the mRNA expression of cholesterol 7α-hydroxylase(CYP7A1) in the liver. Although 0.01 g·kg~(-1) and 0.03 g·kg~(-1) emodin did not induce obvious liver injury, they significantly increased the level of taurine-conjugated BAs in the liver, suggesting a potential interference with BAs homeostasis. In conclusion, 1 g·kg~(-1) emodin may promote the production of primary BAs in the liver by affecting the FXR-RXR-CYP7A1 pathway, inhibit NTCP expression, and reduce BA reabsorption in the liver, resulting in BA accumulation in the peripheral blood. This disruption of BA homeostasis leads to liver injury. Even doses of emodin close to the clinical dose can also have a certain effect on the homeostasis of BAs. Therefore, when using traditional Chinese medicine or formulas containing emodin in clinical practice, it is necessary to regularly monitor liver function indicators and closely monitor the risk of drug-induced liver injury.
Emodin/administration & dosage* ; Bile Acids and Salts/metabolism* ; Animals ; Male ; Liver/injuries* ; Chemical and Drug Induced Liver Injury/genetics* ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Rats, Sprague-Dawley ; Mice ; Rats

Objective To explore the effect of the knockdown of transmembrane 9 superfamily protein member 2 (TM9SF2) on the replication of vesicular stomatitis virus (VSV), and investigate its role in the mechanism of antiviral innate immunity. Methods Small interfering RNA (siRNA) was used to knock down the TM9SF2 gene in human non-small cell lung cancer A549 cells. The CCK-8 method was used to assess cell proliferation. A VSV-green fluorescent protein (VSV-GFP) infected cell model was established. The plaque assay was used to measure the viral titer in the supernatant. RT-qPCR and Western blotting were employed to quantify the mRNA and protein levels of VSV genome replication in A549 cells following VSV infection, as well as the expression of interferon β (IFN-β) mRNA and interferon regulatory factor 3 (IRF3) protein phosphorylation following polyinosinic-polycytidylic acid (poly(I:C)) stimulation. Results Compared to the negative control, the knockdown of TM9SF2 exhibited a significant effect, with no observed impact on A549 cell proliferation. The VSV-GFP infected A549 cell model was successfully established. After viral stimulation, fluorescence intensity was reduced following TM9SF2 knockdown, and the mRNA and protein levels of VSV were significantly downregulated. The viral titer of VSV was decreased. After poly(I:C) stimulation, TM9SF2 knockdown significantly upregulated the mRNA level of IFN-β and the phosphorylation level of IRF3 protein. Conclusion The knockdown of TM9SF2 inhibits the replication of vesicular stomatitis virus, and positively regulates the type I interferon signaling pathway, thus enhancing the host's antiviral innate immune response.
Humans ; Virus Replication/genetics* ; Signal Transduction ; Membrane Proteins/metabolism* ; A549 Cells ; Vesiculovirus/physiology* ; Interferon-beta/metabolism* ; Interferon Regulatory Factor-3/genetics* ; Interferon Type I/metabolism* ; Vesicular Stomatitis/immunology* ; Gene Knockdown Techniques ; Vesicular stomatitis Indiana virus/physiology* ; RNA, Small Interfering/genetics*

The disturbance of the human microbiota influences the occurrence and progression of many diseases. Live therapeutic bacteria, with their genetic manipulability, anaerobic tendencies, and immunomodulatory properties, are emerging as promising therapeutic agents. However, their clinical applications face challenges in maintaining activity and achieving precise spatiotemporal release, particularly in the harsh gastrointestinal environment. This review highlights the innovative bacterial functionalized encapsulation strategies developed through advances in physicochemical and biological techniques. We comprehensively review how bacterial encapsulation strategies can be used to provide physical barriers and enhanced adhesion properties to live microorganisms, while introducing superior material properties to live bacteria. In addition, this review outlines how bacterial surface coating can facilitate targeted delivery and precise spatiotemporal release of live bacteria. Furthermore, it elucidates their potential applications for treating different diseases, along with critical perspectives on challenges in clinical translation. This review comprehensively analyzes the connection between functionalized bacterial encapsulation and innovative biomedical applications, providing a theoretical reference for the development of next-generation bacterial therapies.

OBJECTIVES: To explore the association between GPSM2 expression level and gastric cancer progression and analyze the functional pathways and action mechanism of GPSM2. METHODS: We analyzed GPSM2 expression levels in gastric cancer tumors based on data from the GEPIA database and the clinical data of 109 patients. Public databases enrichment analysis were used to assess the impact of GPSM2 expression level on survival outcomes and the functional pathways and action mechanism of GPSM2. We further observed the effects of GPSM2 knockdown and overexpression on proliferation, migration and apoptosis of MGC803 cells using CCK-8 assay, colony formation assay, flow cytometry and immunoblotting and on the growth of MGC803 cell xenografts in nude mice. RESULTS: Bioinformatic analysis and immunohistochemical staining of the clinical specimens both revealed high GPSM2 expressions in gastric cancer (P<0.01). A high GPSM2 expression was significantly correlated with T3-4 stages, N2-3 stages, a carcinoembryonic antigen (CEA) level ≥5 μg/L, and a carbohydrate antigen (CA) 19-9 level ≥37 kU/L (P<0.05). Cox regression analysis identified high GPSM2 expression as an independent risk factor affecting 5-year survival of the patients (P<0.05). Gene ontology (GO) analysis suggested that GPSM2 was involved in cell cycle regulation. In MGC803 cells, GPSM2 overexpression significantly promoted cell proliferation and G1/S transition and xenograft growth in nude mice. KEGG pathway enrichment analysis indicated that GPSM2 executed its biological functions by regulating the p53 signaling pathway, which was confirmed by the results of immunoblotting experiments showing suppression of p53 signaling pathway activity in GPSM2-over expressing MGC803 cells. CONCLUSIONS GPSM2 is highly expressed in gastric cancer to affect patient prognosis by promoting tumor cell proliferation and G1/S transition possibly via inhibiting the p53 pathway.
Stomach Neoplasms/metabolism* ; Humans ; Cell Proliferation ; Prognosis ; Animals ; Mice, Nude ; Cell Line, Tumor ; Mice ; Apoptosis ; Tumor Suppressor Protein p53/metabolism* ; Cell Movement

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 the nutritional status and influencing factors among Tibetan and Mongolian children and adolescents aged 7-18 years in high-altitude regions, so as to provide evidence for early prevention and control of malnutrition in this population. Methods: From May to June 2022, a cluster sampling method was employed to recruit 1 019 Tibetan and Mongolian children and adolescents aged 7-18 years from two primary and secondary schools in Golmud City. Physical examinations, dietary frequency questionnaires, and physical activity assessments were conducted. Nutritional status was classified as obesity, combined overweight/obesity, underweight, or central obesity according to national standards including Screening for Overweight and Obesity among School-age Children and Adolescents, Screening Standard for Malnutrition of School-age Children and Adolescents, Blue Book on Obesity Prevention and Control in China. Chi-square tests, t-test and Logistic regression analyses were performed to identify factors associated with different nutritional statuses. Results: The detection rates of obesity, combined overweight/obesity, underweight, and central obesity were 8.0%, 18.1%, 5.2%, and 19.7%, respectively. The height of children and adolescents across all age groups was generally lower than the national standard values. Tibetan participants exhibited significantly lower height-for-age Z-scores (HAZ)(9-10, 13-17 years, Z =2.01, 2.78, 4.16, 3.38, 4.12, 3.63, 3.00) and BMI-for-age Z-scores (BAZ) compared to Mongolian participants ( Z =-2.95, -2.47, -2.31, -2.89, -2.14, -2.17)( P < 0.05 ). Multivariate Logistic regression revealed that Mongolian children and adolescents had higher risks of obesity ( OR =2.20) and combined overweight/obesity ( OR = 2.18 ) ( P <0.05). Additionally, insufficient moderate-to-vigorous physical activity (MVPA) was associated with an increased risk of central obesity ( OR =1.48, P <0.05), compared with children and adolescents who meet the standard of MVPA. Conclusions The rates of overweight and obesity among Tibetan and Mongolian children and adolescents in Golmud City are higher, influenced by multiple factors. Nutrition interventions and physical activity strategies tailored to ethnic characteristics should be implemented, with emphasis on promoting MVPA to improve nutritional outcomes in this population.

Objective:To investigate the relationship between screen time and content, and the mental health status of adolescents. The findings will inform the formulation of targeted intervention policies to enhance adolescent mental health.Methods:Between September and November 2023, 5 197 students from 64 junior high, senior high, and vocational schools across 13 districts in Wuhan were recruited, using the stratified whole-cluster random sampling to investigate their screen behavior and mental health status. Mental health status was measured using the Mental Health Inventory for Chinese Middle School Students (MMHI-60). A generalized additive model was used to explore the nonlinear association between screen time and mental health status. Additionally, a mixed-effects model was utilized to explore the dose-response associations between average daily total screen time, screen time for different content types, and adolescents' mental health status and the impact of the proportion of different screen contents on mental health outcomes.Results:The age of the participants was (14.40±1.48) years, with 56.07% being boys. The MMHI-60 score averaged 1.73±0.70. The M( Q1,Q3) for daily total screen time was 50.00 (0.00,128.57) minutes. The M( Q1,Q3) for screen time dedicated to gaming, studying, socializing, and watching videos were 0.00 (0.00, 20.00), 8.57 (1.64, 44.50), 4.28 (0.00, 30.00), and 0.00 (0.00, 25.71) minutes, respectively. A non-linear association was observed between average daily screen time and adolescent mental health problem score, 0-1 hour of daily screen time was beneficial for adolescent mental, compared to no screen time. However, screen time exceeding 1 hour was detrimental, with the negative impact increasing alongside screen time duration. When total daily screen time was held constant, the proportion of time spent on gaming ( β=0.14, 95% CI: 0.05-0.23, P=0.003) and video ( β=0.21, 95% CI: 0.09-0.28, P<0.001) was positively correlated with mental health problems, whereas the proportion of time spent on studying was negatively correlated with mental health problems ( β=-0.17, 95% CI: -0.24 - -0.11, P<0.001). Conclusions:Moderate screen time is advantageous for adolescent mental health. However, it is crucial to minimize the proportion of screen time dedicated to video and gaming activities to mitigate potential adverse effects.

Objective To explore the role of miR-429 in synovial mesenchymal stem cell-derived exosomes(SMSC-Exos)in repairing cartilage damage in temporomandibular joint osteoarthritis(TMJ OA)by extracting SMSC-Exos from human synovial tissue and screening differentially expressed microRNA(miRNA)through transcriptome sequencing.Methods Human synovial tissues were obtained from 6 patients who underwent surgery at the First Medical Center of the Chinese PLA General Hospital from June to December 2023,including 3 patients with osteoarthritis(OA group)and 3 control patients(control group),all of whom were male.SMSC-Exos were extracted from the synovial tissues for miRNA sequencing and differential expression analysis.Further,Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed on the target genes of differentially expressed miRNA to identify key functional miRNA and construct miRNA-target gene regulatory networks and protein-protein interaction(PPI)networks of target genes.An in vitro model of rabbit condylar cartilage cell inflammatory microenvironment induced by interleukin-1β(IL-1β)was established,with the control group cultured in DMEM/F12 basic medium and the inflammation-induced group cultured in DMEM/F12 basic medium containing 10 ng/ml IL-1β.RT-qPCR was used to detect the effects of overexpressed target miRNA on the mRNA expression levels of cartilage phenotype factors such as type Ⅱ collagen α1 chain(Col2a1),aggrecan(Acan),as well as inflammatory factors including a disintegrin and metalloproteinase with thrombospondin motifs 5(Adamts5)and cyclooxygenase-2(Cox-2).Results(1)SMSC-Exos were successfully isolated,cultured,and identified.(2)miRNA sequencing of SMSC-Exos from OA and control groups revealed 16 differentially expressed miRNAs(|log2FC|>2,P<0.05).Compared with control group,7 miRNAs were up-regulated and 9 were down-regulated in OA group.GO and KEGG analysis indicated that the target genes of miR-429 were mainly involved in development process,anatomical structure development,system development,cell development and differentiation,and were enriched in inflammation-related pathways such as mitogen-activated protein kinase(MAPK)and phosphatidylinositol 3-kinase-protein kinase B(PI3K-Akt).(3)Functional validation of miR-429 in the rabbit condylar cartilage cell inflammatory model showed that overexpression of miR-429 increased the mRNA expression levels of Col2a1 and Acan(P<0.05)and decreased the mRNA expression levels of Adamts5 and Cox-2(P<0.05)in the inflammation-induced group.Conclusions miRNA sequencing of SMSC-Exos isolated and identified from human synovial tissues reveals a specific miRNA expression profile in OA patients,with miR-429 significantly down-regulated.Functional validation demonstrates that overexpression of miR-429 has reparative and anti-inflammatory effects on condylar cartilage cells in an inflammatory microenvironment.

Objective To observe the effects of general anesthesia with remazolam on electrophysiological monitoring indicators and cerebral oxygen saturation(ScO2)in patients undergoing carotid endarterectomy(CEA).Methods Patients who underwent elective CEA from July 2022 to June 2024 in neurosurgery department of our hospital were randomly divided into the ramazolam group(R group)and the propofol group(P group).Patients in both groups were given propofol 1.5 to 2.0 mg/kg,cisatracurium 0.1 to 0.2 mg/kg,and sufentanil 0.3 to 0.4 μg/kg for anesthesia induction.Anesthesia maintenance:patients in the R group received intravenous infusion of remifentanil 0.5 to 1.0 mg·kg-1·h-1,while patients in the P group received intravenous infusion of propofol 5.0 to 7.0 mg·kg-1·h-1.Both groups received intravenous infusion of remifentanil 0.1 to 0.2 μg·kg-1·min-1 for anesthesia maintenance.The operation time,carotid artery occlusion time,intraoperative infusion volume,remifentanil and norepinephrine dosage,and awakening time of patients in the two groups were recorded.The hemodynamic and cerebral oxygen indicators,amplitude and latency of evoked potentials before anesthesia(T0),after anesthesia(T1),5 minutes before blockade(T2),5 minutes after blockade(T3),5 minutes after unblocking(T4)and at the end of surgery(T5)of patients in the two groups were observed and compared,and the total incidence of postoperative complications was followed up and calculated.Results Compared with the P group,the dosage of intraoperative norepinephrine of patients in the R group was reduced(P<0.05),and the awakening time was shortened(P<0.05).At T2,the average arterial pressure(MAP)of patients in the R group was higher than that in the P group(P<0.05).At T3,the ScO2 of patients in the R group was significantly higher than that in the P group,and the percentages of prolonged latency and decreased amplitude of motor evoked potentials(MEP)were significantly lower than those in the P group(P<0.05),the percentage of decreased amplitude of lower limb somatosensory evoked potentials(SSEP)was lower than that in the P group(P<0.05);At T5,the MEP amplitude of patients in the R group was significantly increased compared to that at T2,while the MEP amplitude of patients in the P group was significantly decreased compared to that at T2,and the differences were statistically significant(P<0.05).There was no statistically significant difference in the total incidence of postoperative complications between the two groups(P>0.05).Conclusion As a general anesthesia maintenance drug,remazolam can achieve satisfactory anesthesia effects for CEA,with more stable intraoperative hemodynamics,and less impact on ScO2 and evoked potential monitoring during carotid artery occlusion compared to propofol,resulting in higher safety.

Aim To study the possibility of luteolin(LUT)as a new drug of traditional Chinese medicine and its improving effect on glucose and lipid metabo-lism and liver oxidative stress injury in db/db mice,and to explore the possible mechanism.Methods AI was used to predict the drug toxicity,evaluate the phys-ical and chemical properties and segment the molecular structure of LUT.Molecular docking was used to verify the binding ability of LUT with Nrf2 and HMOX1;db/m mice were divided into the group C,and db/db mice were randomly divided into the T,L,M,H and P groups.The body weight and FBG changes were ob-served within 12 weeks of intervention.The expres-sions of FBG,HbA1c,Fins,TC,TG,HDL-C,LDL-C were detected.The pathomorphological changes and steatosis of mouse liver were observed by HE and oil red O staining.The expression of MDA,SOD and GSH-Px in liver was detected by Kit.The protein and mRNA expressions of Nrf2 and HMOX1 were detected by immunohistochemistry,WB and qPCR.Results AI algorithm predicted the safety and easy synthesis of LUT.LUT intervention had no significant effect on the body weight of db/db mice.After 12 weeks,compared with the group C,the livers of mice in group T showed disordered structure of hepatic lobules,irregular ar-rangement of hepatocytes,and a large number of fat vacuoles and lipid droplets in the cytoplasm.Compared with the group T,LUT intervention could improve the pathological changes of liver,reduce the expression of FBG,HbA1c,fins,TC,TG,LDL-C,MDA,improve the level of HOMA-IR,and upregulate the activities of SOD and GSH-Px.Molecular docking results showed LUT had strong binding with Nrf2 and HMOX1,and could increase the expression of Nrf2 and HMOX1.Conclu-sion LUT can correct the disorder of glucose and lip-id metabolism in db/db mice,and improve the level of oxidative stress in liver of mice through Nrf2/HMOX1 pathway,which has the development prospect as a new Chinese medicine for the treatment of T2DM.