BACKGROUND:Acetaminophen (APAP) can induce liver injury and even acute liver failure (ALF) or death when administered in overdose. Current treatments may be associated with significant adverse effects, so it is urgent to explore other safe and effective alternative therapeutic drugs. Artemisia keiskeana Miq. (AKM), a traditional Chinese medicine, is frequently employed in clinical settings for the management of liver-related disorders. To date, no studies have been reported regarding the pharmacological effects of AKM on APAP-induced liver injury and its underlying mechanisms of action. This study is designed to investigate this unexplored area for the first time, thereby addressing the current scientific gap in this domain. PURPOSE:This study aims to systematically investigate the potential of AKM to alleviate APAP-induced liver injury and elucidate its underlying mechanisms. METHODS:Mice were pre-treated with AKM via intragastric administration and subsequently injected with APAP to establish a liver injury model. The liver-to-body weight ratio was measured, and biochemical markers associated with liver injury as well as pathological alterations in liver tissues were analyzed. Quantitative proteomics, Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and network pharmacology were employed to identify differentially expressed proteins, chemical constituents, and potential targets, followed by intersection analysis to determine core targets. Oxidative stress-related parameters in liver tissues were quantified using enzyme-linked immunosorbent assay (ELISA) kits. To further explore the hepatoprotective effects of AKM and its association with ferroptosis, the ferroptosis inhibitor Ferrostatin-1 (Fer-1) was utilized in conjunction with the MTT assay and C11 BODIPY 581/591 fluorescence staining to perform functional validation. Furthermore, the direct binding ability between AKM and core target proteins was verified through surface plasmon resonance (SPR) experiments. Finally, Western blot analysis was conducted to assess the effects of AKM on the ESR1/Nrf2/GPX4 signaling pathway and the expression levels of NF-κB and NLRP3 proteins. RESULT:AKM significantly alleviated liver tissue stasis and edema, reduced the liver-to-body weight ratio, markedly decreased serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (p < 0.05), and mitigated pathological alterations including inflammatory infiltration, fibrosis, and apoptosis, in mice with APAP-induced liver injury. By integrating quantitative proteomics, UPLC-MS/MS, and network pharmacology, we identified an important overlapping target, estrogen receptor alpha (ESR1). Additionally, the differentially expressed proteins were predominantly associated with oxidative stress pathways. Further investigations revealed that AKM significantly enhanced the levels of antioxidant enzymes GSH-PX and SOD in liver tissue (p < 0.001), while reducing the levels of MDA, ROS, IL-1β, IL-6 and TNF-α (p < 0.001). Co-treatment with the ferroptosis inhibitor Fer-1 and AKM was found to significantly improve the viability and lipid peroxidation status of LX-2 cells (p < 0.001). SPR experiments further confirmed a direct interaction between AKM and the ESR1 protein (KD = 3.57E-03M). Western-blot showed that AKM promoted the expression of ESR1, Nrf2, and GPX4 proteins while inhibiting the expression of Keap-1, HO-1, NLRP3, NF-κB, and 5-LOX proteins (p < 0.001). CONCLUSION:This study provides the first evidence that AKM, as a potential natural therapeutic agent, effectively alleviates APAP-induced liver injury. Its mechanism of action is likely associated with the activation of the Nrf2/GPX4 pathway and the suppression of the NF-κB signaling pathway mediated by ESR1.

Luteolin, a flavonoid present in botanical drugs, plants, and dietary sources, has demonstrated anticancer properties against various tumors, yet its role in diffuse large B-cell lymphoma (DLBCL) remains unclear. This study aimed to uncover the molecular mechanism of luteolin in DLBCL treatment using a combination of in vitro and in vivo experiments and computational analysis. Human DLBCL cell lines U2932 and OCI-LY10 were utilized to assess luteolin’s impact on cell growth, apoptosis, cell cycle progression, and the modulation of JAK2/STAT3 pathway proteins. In vivo, a U2932 tumor-bearing nude mice model was employed to evaluate luteolin’s antitumor efficacy and its effects on JAK2/STAT3 pathway protein expression. Additionally, molecular dynamics simulations were conducted to explore the interaction between luteolin and JAK2. The findings revealed that luteolin significantly suppressed cell proliferation, induced apoptosis, and arrested the cell cycle at the G2/M phase in both cell lines. In the mouse model, luteolin effectively inhibited tumor growth and downregulated the expression of phosphorylated JAK2 and STAT3 without altering the total protein levels of JAK2 and STAT3. Computational analysis indicated stable binding of luteolin to JAK2. Collectively, these results suggest that luteolin’s anti-DLBCL activity may be mediated through the regulation of the JAK2/STAT3 signaling pathway, positioning it as a potential therapeutic agent for DLBCL.

Objective:This study aimed to explore the differences of the psychological states and total testosterone (TT) in patients with erectile dysfunction (ED) across various age groups. Methods:A total of 1411 ED patients were enrolled from the Department of Andrology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine from September 2018 to September 2021. The SCL-90 was used to evaluate the psychological condition of patients while the 5-item international index of erectile function (IIEF-5) questionnaire was applied to estimate the severity of ED. The serum TT level of patients was also measured. ED patients were divided into three groups (group A: 20-30 years old; group B: 31-40 years old; group C: 41-50 years old). In addition, patients in each group were divided into three groups including mild group (12<IIEF-5<21), moderate group (8<IIEF-5<11), and severe group (IIEF-5<7). The level of TT and SCL-90 scores were compared between groups. Finally, relationships between SCL-90, STAI scores and TT were explored. Results:(1) Differences of TT between groups with different ages: The TT level of group A was higher than that of group B and C (P<0.05). (2) Differences of TT between patients with different ED severity in each age group: The TT level of severe ED patients was lower than that of mild ED patients in group B (P<0.05) while the TT level of severe ED patients was lower than that of mild and moderate ED patients in group C (P<0.05). (3) Differences of SCL-90 and STAI scores between patients with different severity in each age group: The factor scores of anxiety, psychoticism, obsession, interpersonal relationship, depression and total scores of SCL-90 of group A and B were higher than those of group C (P<0.05). (4) Differences of SCL-90 and STAI scores between patients with different severity in each age group: 1) The factor scores of hostility, anxiety, phobia, paranoid, psychoticism, obsession, depression and total scores of SCL-90 of mild ED patients were lower than those of moderate and severe ED patients in group B (P<0.05); 2) The factor scores of anxiety and other of SCL-90, as well as the state anxiety scores of STAI of mild ED patients were lower than those of severe ED patients in group C (P<0.05). (5) The level of TT was positively related to IIEF-5 scores of ED patients (r = 0.06; P = 0.02). Both SCL-90 (r = -0.08; P < 0.01) and STAI (r = -0.06; P = 0.04) scores were negatively associated with IIEF-5 scores of ED patients. STAI scores were positively related to SCL-90 scores of ED patients (r = 0.64; P < 0.01). Conclusion:Age-stratified results demonstrate a pronounced differential impact of TT and psychological factors on ED. Compared with younger patients, serum TT has more significant effects on elderly patients with ED. For young ED patients, the influences of psychological factors are significantly higher than that of elderly patients, and young patients show more severe anxiety and depression.

ABSTRACT:The relationship between hyperuricemia (HUA) and erectile dysfunction (ED) remains inadequately understood. Given that HUA is often associated with various metabolic disorders, this study aims to explore the multivariate linear impacts of metabolic parameters on erectile function in ED patients with HUA. A cross-sectional analysis was conducted involving 514 ED patients with HUA in the Department of Andrology, Jiangsu Province Hospital of Chinese Medicine (Nanjing, China), aged 18 to 60 years. General demographic information, medical history, and laboratory results were collected to assess metabolic disturbances. Sexual function was evaluated using the 5-item version of the International Index of Erectile Function (IIEF-5) questionnaire. Based on univariate analysis, variables associated with IIEF-5 scores were identified, and the correlations between them were evaluated. The effects of these variables on IIEF-5 scores were further explored by multiple linear regression models. Fasting plasma glucose ( β = -0.628, P < 0.001), uric acid ( β = -0.552, P < 0.001), triglycerides ( β = -0.088, P = 0.047), low-density lipoprotein cholesterol ( β = -0.164, P = 0.027), glycated hemoglobin (HbA1c; β = -0.562, P = 0.012), and smoking history ( β = -0.074, P = 0.037) exhibited significant negative impacts on erectile function. The coefficient of determination ( R ²) for the model was 0.239, and the adjusted R ² was 0.230, indicating overall statistical significance ( F -statistic = 26.52, P < 0.001). Metabolic parameters play a crucial role in the development of ED. Maintaining normal metabolic indices may aid in the prevention and improvement of erectile function in ED patients with HUA.

Psychogenic erectile dysfunction (pED) is a prevalent form of erectile dysfunction in younger men and is strongly linked to mood disturbances such as anxiety and depression. While previous functional connectivity studies have reported abnormal interactions in cortical and subcortical networks, the causal architecture of the reward circuit in pED remains poorly understood. In this study, we applied spectral dynamic causal modeling (spDCM) to resting-state fMRI data from 27 patients with pED and 31 matched healthy controls to investigate alterations in effective connectivity within the reward circuit. At the group level, parametric empirical Bayes and Bayesian model reduction identified 14 connections that survived a stringent posterior probability threshold (PP > 0.99). Correlation analyses revealed three robust associations after false discovery rate correction: stronger vmPFC-PCC connectivity was negatively correlated with erectile function, while reduced LAI-RAI connectivity and increased LAI self-connectivity were associated with depressive symptoms. These findings suggest that abnormal interactions among default mode, salience, and reward networks may underlie both sexual dysfunction and comorbid mood disturbances in pED. Our results highlight candidate neural pathways that may inform mechanistic understanding and guide future therapeutic strategies, while emphasizing the need for replication in larger samples.

INTRODUCTION:Sexual desire has been found to be associated with brain areas involved in sexual excitation and inhibition. However, little is known regarding whether hypoactive sexual desire disorder patients have structural abnormalities related to hypofunctional excitation or hyperfunctional inhibition in the brain. METHODS:Magnetic resonance imaging data were collected from 26 hypoactive sexual desire disorder patients and 28 healthy controls. The structural brain networks were constructed based on diffusion tensor imaging data. Finally, the nodal parameters were calculated by the graph theoretical analysis and were compared between hypoactive sexual desire disorder and healthy controls. RESULTS:There were no significant differences in the age, education level, and scores of emotional scales between groups. Meanwhile, all hypoactive sexual desire disorder patients showed normal hormone levels. Compared with healthy controls, hypoactive sexual desire disorder patients showed higher scores on the Arizona Sexual Experience Scale and its sexual desire subscale. In fractional anisotropy-weighted brain networks, a decreased clustering coefficient was found in the left middle frontal gyrus (orbital part), and decreased local efficiency was found in the left amygdala of hypoactive sexual desire disorder patients when compared with healthy controls. CONCLUSION:The present study demonstrated impaired left middle orbital frontal gyrus and amygdala in the structural brain network of hypoactive sexual desire disorder patients, which might be the central pathological mechanisms underlying hypoactive sexual desire disorder and could be used as a neuroimaging diagnostic biomarker for hypoactive sexual desire disorder.

Psychogenic erectile dysfunction (pED) is often accompanied by abnormal brain activities. This study aimed to develop an automaticclassifier to distinguish pED from healthy controls (HCs) by identified brain-basedcharacteristics. Resting-state functional magnetic resonance imaging data were acquired from 45 pED patients and 43 HCs. Regional homogeneity (ReHo) and functional connectivity (FC) values were calculated and compared between groups. Moreover, based on altered ReHo and FC values, support vector machine (SVM) classifier, incorporating recursive feature elimination (RFE), an SVM-RFE diagnostic model was established using leave-one-out cross-validation. Patients demonstrated reduced ReHo values in the left middle temporal gyrus (had decreased FC values with the left medial superior frontal gyrus and cuneus), orbital part of inferior frontal gyrus (had decreased FC values within the same region), triangular part of inferior frontal gyrus, anterior cingulate gyrus (had decreased FC values with the left inferior temporal gyrus, anterior cingulate gyrus, cuneus and right supplementary motor area) and middle frontal gyrus. The right calcarine fissure displayed increased ReHo values. The diagnostic model demonstrated excellent performance, achieving an accuracy rate of 90.80%. This study identified altered regional activity and FC in specific brain regions of pED patients, which might be related to the development of pED. The application of machine learning confirmed the distinctive characteristics of these functional changes in the brain. The high accuracy of our diagnostic model suggested a promising direction for developing objective diagnostic tools for psychological disorders.

The incidence of cervical cancer is high among women globally. The potential therapeutic efficacy of luteolin in the treatment of cervical cancer has been identified. Therefore, we aim to elucidate the mechanism of action of luteolin in the treatment of cervical cancer through a comprehensive approach that integrates metabolomics with bioinformatics. The first step involved the identification of differential metabolites through UHPLC-Q-Orbitrap-MS, which were then utilized for enrichment analysis of metabolic pathways and to determine the targets associated with these differential metabolites. Subsequently, the differential analysis and WGCNA were employed to identify DEGs and functional module genes respectively. The common targets were obtained by intersecting the results from the aforementioned three analyses, followed by conducting GO and KEGG pathway enrichment analysis on these targets. Subsequently, PPI networks were constructed using these common targets, and key targets were identified utilizing the MCC, EPC, Degree, Closeness Centrality, Betweenness Centrality, and Bottleneck algorithms in the CytoHubba plug-in. The subsequent steps involved the analysis of key genes for constructing a nomogram, conducting a ROC curve, examining content expression and survival analysis, and ultimately employing molecular docking to investigate the interaction between luteolin and crucial targets. The metabolomics analysis revealed the identification of a total of 45 distinct metabolites in this study, primarily associated with amino acid and nucleotide metabolism. The intersection of 773 differential metabolite targets, 3493 cervical cancer differential genes, and 3245 WGCNA-associated module genes yielded a set of 32 target genes associated with luteolin therapy for cervical cancer. The GO and KEGG pathway enrichment analysis also revealed that these targets were primarily associated with amino acid metabolism and nucleotide metabolism. The CytoHubba plug-in was utilized to identify three key genes (DMNT1, EZH2, and GMPS) through the application of multiple algorithms. Additionally, the datasets GSE63514, GSE67522, and GEPIA2 revealed a significant upregulation of all three genes in tumor tissue. ROC analysis demonstrated the good predictive ability of these three hub genes. Finally, the molecular docking results demonstrated the high binding affinity of luteolin towards DMNT1, EZH2, and GMPS. In conclusion, this study has unveiled the potential of luteolin in modulating amino acid and nucleotide metabolism for the treatment of cervical cancer, thereby providing a theoretical foundation for further investigation into the intricate association between luteolin and cervical cancer.

OBJECTIVE:To investigate the clinical efficacy of moxibustion (Mox) combined with low-dose tadalafil (TAD) in the treatment of diabetes mellitus-induced erectile dysfunction (DMED) with the syndrome of Qi deficiency and blood stasis. METHODS:According to the inclusion and exclusion criteria, we selected 90 patients with DMED for this trial and equally randomized them into a Mox, a TAD, and a Mox combined with TAD (Mox+TAD) group to be treated by mild Mox applied to the acupoints Zusanli, Sanyinjiao and Yinlingquan qd alt, oral medication with low-dose TAD at 5 mg per dose qd, and combination of the above two therapies, respectively, all for 4 weeks. We obtained from the patients their IIEF-5 scores, traditional Chinese medicine (TCM) symptoms scores, Erectile Hardness Scale (EHS) scores, corpus cavernosal hemodynamic indexes, and the peak systolic velocity (PSV), end diastolic velocity (EDV) and resistance index (RI) of the corpus cavernosal arteries before and after treatment, and compared them among the three groups. RESULTS:The total effectiveness rate was significantly higher in the Mox+TAD (90.0%) than in the Mox (46.7%) and TAD groups (60.0%) (P< 0.05). Compared with the baseline, the IIEF-5 and EHS scores were increased, while the TCM symptoms scores decreased in all the three groups after treatment, more significantly in the Mox+TAD group than in the other two (P< 0.05). And the PSV and RI were remarkably increased, while the EDV decreased (P< 0.05) in all the three groups (P< 0.05) after treatment, with PSV even higher in the Mox+TAD than in the Mox and TAD groups (P< 0.05). CONCLUSION:Moxibustion combined with tadalafil has a definite efficacy and safety for the treatment of DMED, which can effectively improve the erectile function of the patients by increasing penile blood supply, benefiting qi and activating blood circulation.

The marital status of elderly people in rural areas directly affects their health and cognitive status, and potentially affects their understanding and identification with rural pension insurance, affecting the scale and structure of rural pension insurance. This article takes Jilin Province as the research sample, adopts the fourth national survey data on the living conditions of elderly people in cities, and establishes an empirical model to analyze the relationship between the marital status of rural elderly people and their participation in pension insurance. The research findings indicate that individuals who have never been married have a positive impact on pension insurance; The marital status of widowhood has a positive impact on the elderly's pension insurance situation; Divorce has a positive impact on the elderly's pension insurance. The marital status of being married but not cohabiting has no significant impact on the elderly's pension insurance.

BackgroundObstruction is a common complication of advanced colorectal cancer. This study was aimed at investigating the safety, efficacy, and feasibility of transcatheter arterial perfusion chemotherapy combined with lipiodol chemoembolization for treating advanced colorectal cancer complicated by obstruction.Patients and methodsThis retrospective analysis was conducted using clinical data of patients with advanced colorectal cancer who received arterial infusion chemotherapy combined with lipiodol chemoembolization treatment at our center. Treatment efficacy was evaluated in terms of obstruction-free survival and overall survival, and treatment complications were monitored.ResultsFifty-four patients with colorectal cancer complicated by obstruction were included. All patients successfully underwent transcatheter arterial infusion combined with lipiodol chemoembolization treatment. The average lipiodol dose administered was 2.62 ± 1.45 ml (0.5–5.5 ml). No serious complications such as perforation or tumor dissemination occurred. The clinical success rate was 83.3% (45/54). One month after treatment, the objective response rate (ORR) and disease control rate (DCR) were 66.67% and 88.9%, respectively. The median obstruction-free survival was 5.0 months. No serious adverse events occurred. As of the last follow-up, 6 patients survived, 44 died, and 4 were lost to follow-up.ConclusionOur findings revealed that transcatheter arterial infusion chemotherapy combined with lipiodol chemoembolization is safe and effective for treating advanced colorectal cancer complicated by obstruction. It may serve as a new treatment strategy for patients with advanced colorectal cancer complicated by obstruction.

Background Rheumatoid arthritis is a chronic autoimmune disease. However, the specific role of senescence in rheumatoid arthritis (RA) is unknown. This study aimed to identify potential aging-related genes that have diagnostic and therapeutic value for RA. Methods The GSE89408 dataset was downloaded from the Gene Expression Omnibus (GEO). Aging-related genes were downloaded from the HAGR database. Differentially expressed genes (DEGs) were subsequently identified with the “edgeR” tool. Next, hub genes were identified with a PPI network and CytoHubba analysis. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic value of these hub genes. Immune infiltration analysis was performed with the CIBERSORT algorithm. Additionally, molecular docking was performed with CB-Dock2. Finally, correlation experiments were performed to validate the bioinformatics and molecular docking results. Results A total of 22 ADEGs were identified. Combined PPI network and CytoHubba analyses identified a total of 7 hub genes, including IL-6, IL7R, IL2RG, CDK1, PTGS2, and LEP, which are associated mainly with inflammation and immune responses. ROC analysis revealed that the hub genes were highly predictive of RA. Analysis of immune infiltration revealed that the 6 hub genes were positively associated with M1 macrophages. Validation experiments revealed that the inhibition of IL-6 significantly decreased the degree of synovial fibroblast (FLS) senescence. Furthermore, molecular docking and validation experiments revealed that IL-6 is a potential target for drug therapy. Conclusion This study demonstrated that RA-FLS senescence may promote the development of RA via inflammatory and immune mechanisms. Seven hub genes were identified, of which IL-6 is a reliable biomarker for the diagnosis and treatment of RA.

Abstract Erectile Dysfunction (ED) is considered a physical and mental illness. A variety of potential associations between gut microbiota and health or disease have been found. By comparing the gut microbiota of healthy controls and ED patients, our study investigated the relationship between ED and gut microbiota. The results revealed that the ED group exhibited a significantly higher relative abundance of Bacteroides, Fusobacterium, Lachnoclostridium, Escherichia‐Shigella and Megamonas, while showing a significantly lower relative abundance of Bifidobacterium compared to the control group. The dysbiosis of gut microbiota played a role in the onset and progression of ED by influencing the gut barrier, cardiovascular system and mental health, which provided a novel perspective on understanding the pathophysiology of ED. What is more, we had identified several key gut microbiota. By combining 16S rRNA sequencing with machine learning techniques, we were able to uncover the significant value and impact of gut microbiota in the early detection of ED.

Objective: The effects of arsenic trioxide (As2O3) on hepatocellular carcinoma have been documented widely. Autophagy plays dual roles in the survival and death of cancer cells. Therefore, we investigated the exact role of autophagy in As2O3-induced apoptosis in liver cancer cells. Methods: The viability of hepatoma cells was determined using the MTT assay with or without fetal bovine serum. The rate of apoptosis in liver cancer cells treated with As2O3 was evaluated using flow cytometry, Hoechst 33258 staining, and TUNEL assays. The rate of autophagy among liver cancer cells treated with As2O3 was detected using immunofluorescence, Western blot assay and transmission electron microscopy. Results: Upon treatment with As2O3, the viability of HepG2 and SMMC-7721 cells was decreased in a time- and dose-dependent manner. The apoptosis rates of both liver cancer cell lines increased with the concentration of As2O3, as shown by flow cytometry. Apoptosis in liver cancer cells treated with As2O3 was also shown by the activation of the caspase cascade and the regulation of Bcl-2/Bax expression. Furthermore, As2O3 treatment induced autophagy in liver cancer cells; this finding was supported by Western blot, immunofluorescence of LC3-II and beclin 1, and transmission electron microscopy. In liver cancer cells, As2O3 inhibited the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signal pathway that plays a vital role in both apoptosis and autophagy. The PI3K activator SC-79 partially reversed As2O3-induced autophagy and apoptosis. Furthermore, inhibiting autophagy with 3-methyladenine partially reversed the negative effects of As2O3 on cell viability. Serum starvation increased autophagy and amplified the effect of As2O3 on cell death. Conclusion: As2O3 induces apoptosis and autophagy in liver cancer cells. Autophagy induced by As2O3 may have a proapoptotic effect that helps to reduce the viability of liver cancer cells. This study provides novel insights into the effects of As2O3 against liver cancer. Please cite this article as: Deng ZT, Liang SF, Huang GK, Wang YQ, Tu XY, Zhang YN, Li S, Liu T, Cheng BB. Autophagy plays a pro-apoptotic role in arsenic trioxide-induced cell death of liver cancer. J Integr Med. 2024; 22(3): 295-302. (c) 2024 Shanghai Yueyang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine. All rights reserved.

Background: Cellular senescence is associated with a dysregulated inflammatory response, which is an important driver of the development of liver fibrosis (LF). This study aimed to investigate the effect of cellular senescence on LF and identify potential key biomarkers through bioinformatics analysis combined with validation experiments in vivo and in vitro. Methods: The Gene Expression Omnibus (GEO) database and GeneCards database were used to download the LF dataset and the aging-related gene set, respectively. Functional enrichment analysis of differential genes was then performed using GO and KEGG. Hub genes were further screened using Cytoscape's cytoHubba. Diagnostic values for hub genes were evaluated with a receiver operating characteristic (ROC) curve. Next, CIBERSORTx was used to estimate immune cell types and ratios. Finally, in vivo and in vitro experiments validated the results of the bioinformatics analysis. Moreover, molecular docking was used to simulate drug-gene interactions. Results: A total of 44 aging-related differentially expressed genes (AgDEGs) were identified, and enrichment analysis showed that these genes were mainly enriched in inflammatory and immune responses. PPI network analysis identified 6 hub AgDEGs (STAT3, TNF, MMP9, CD44, TGFB1, and TIMP1), and ROC analysis showed that they all have good diagnostic value. Immune infiltration suggested that hub AgDEGs were significantly associated with M1 macrophages or other immune cells. Notably, STAT3 was positively correlated with alpha-SMA, COL1A1, IL-6 and IL-1 beta, and was mainly expressed in hepatocytes (HCs). Validation experiments showed that STAT3 expression was upregulated and cellular senescence was increased in LF mice. A co-culture system of HCs and hepatic stellate cells (HSCs) further revealed that inhibiting STAT3 reduced HCs senescence and suppressed HSCs activation. In addition, molecular docking revealed that STAT3 was a potential drug therapy target. Conclusions: STAT3 may be involved in HCs senescence and promote HSCs activation, which in turn leads to the development of LF. Our findings suggest that STAT3 could be a potential biomarker for LF.

Silene viscidula Franch is mainly produced in southwest China. The region has a vast area and rich climate, which has an impact on the quality of the plants due to the differences in distribution between the origins. There is a lack of systematic research on its chemical compounds in the existing literature, and fewer studies have been reported for the active compounds of this plant. Therefore, high-resolution liquid mass spectrometry was used in this study. Sixty batches of Silene viscidula Franch samples from twenty origins in three provinces were analyzed for compounds. A database of chemical compounds of Silene viscidula Franch was established through node-to-node information in the GNPS molecular network, as well as literature records. The ion fragmentation information obtained was compared with the literature data and analyzed and identified by importing the mass spectrometry software PeakView 1.2. Then, the MarkerView t-test was applied to analyze and identify the compounds of Silene viscidula Franch from different origins. Afterwards, the antioxidant activity of Silene viscidula Franch from different origins was preliminarily evaluated using DPPH and ABTS free radical scavenging assays. The results showed a total of 78 compounds, including 34 steroids, 14 triterpenoid saponins, 30 flavonoid glycosides, and other classes of compounds, such as alkaloids. The cleavage patterns of steroids, triterpenoid saponins, and flavonoids in positive-ion mode were also summarized. Based on the p-value of the t-test (p < 0.05), 29 differential compounds were screened out. The relative contents of saponins and steroidal compounds in these samples were found to be associated with antioxidant activity. This study provided a preliminary reference for the establishment of a comprehensive evaluation system for the quality of Silene viscidula Franch.

Abstract Background Few studies have investigated psychogenic sexual dysfunction including psychogenic erectile dysfunction (pED); the effect of tadalafil on sexual behavior of male rats induced by chronic unpredictable mild stress (CUMS) remains unclear. Aim The aim was to explore the influence of CUMS on sexual behavior of male rats and the effects of tadalafil on that. Methods Adult male rats were divided into 3 groups, including the normal group without CUMS, the model group with 6 weeks’ CUMS, and the tadalafil group with treatment of tadalafil during CUMS. CUMS consists of water deprivation, food deprivation, stroboscopic lightning, white noise, cage tilting, weeding packing, and housing 2 unfamiliar rats. The apomorphine test and vaginal smear test were conducted with the aim to screen out male rats with good erectile function and make preparation for the sexual behavior test, respectively. Outcomes At the end of the study period, the level of anhedonia and sexual function were evaluated by the sucrose preference test, sexual behavior test, and measurement of serum testosterone, dopamine, and 5-HT. Results Sucrose preference showed significant decrease in rats after CUMS. The intromission ratio and total intromission frequency decreased significantly, while the mount latency and ejaculation latency prolonged significantly in CUMS-induced rats when compared with normal rats. Meanwhile, the treatment of tadalafil reversed the level of anhedonia and sexual function in CUMS-induced rats. However, there were no statistical differences in the levels of serum testosterone, dopamine, and 5-HT among groups. Clinical Implications The study constructed an animal model that can provide clinical insights into the mechanism of psychogenic sexual dysfunction and supports the application of tadalafil in pED therapy. Strengths and Limitations We found that CUMS-induced rats exhibited anhedonia and poor sexual function that could be prevented by tadalafil administration. Future research needs to construct the standard of pED model and explore the mechanism of tadalafil on central nervous system. Conclusion Tadalafil could prevent the changes of depression and poor sexual function in rats induced by CUMS, and the method of CUMS and the sexual behavior test should be used in the future for pED modeling.

BACKGROUND:Cervical cancer is a prevalent malignancy among women globally.OBJECTIVE:We aimed to uncover the mechanism of action of kaempferol in the treatment of cervical cancer using an integrated approach that combines metabolomics with network pharmacology.METHODS:Initially, we investigated the specific metabolites and potential pathways influenced by kaempferol in the pathological progression of cervical cancer, employing UHPLC-Q-Orbitrap MS metabolomics. In addition, network pharmacology analysis was performed to ascertain the pivotal targets of kaempferol in the context of CC therapy.RESULTS:Metabolomics analysis indicated that the therapeutic effect of kaempferol on cervical cancer is primarily associated with 11 differential metabolites and 7 metabolite pathways. These pathways include arginine and proline metabolism, the tricarboxylic acid cycle, phenylalanine, tyrosine, and tryptophan biosynthesis, fatty acid biosynthesis, glycerophospholipid metabolism, pantothenate and CoA biosynthesis, and tyrosine metabolism. Additionally, kaempferol was found to regulate 3 differential metabolites, namely palmitic acid, citric acid, and L-tyrosine, by directly targeting 7 specific proteins, including AKR1B1, CS, EGFR, PLA2G1B, PPARG, SLCO2B1, and SRC. Furthermore, molecular docking demonstrated strong binding affinities between kaempferol and 7 crucial targets.CONCLUSION:This study elucidates the intricate mechanisms by which kaempferol acts against cervical cancer. Furthermore, this research offers a novel approach to investigating the potential pharmacological mechanisms of action exhibited by natural compounds.