Empathy alleviates the learning burnout of medical college students through enhancing resilience.

OBJECTIVE: The problem of learning burnout of medical students is becoming prominent, and empathy can play a good predictive role in learning burnout. The present study aimed to investigate the relationship between empathy and learning burnout, as well as the mediation effect of resilience in this relation. METHODS: Five hundred and eighty-eighth college students from a key medical university in Yunnan Province was investigated using the Basic Empathy Scale, Learning Burnout Scale, and Connor-Davidson Resilience Scale. All the measures showed good reliability and validity in the present study. Data were analyzed using SPSS 23.0 and Amos 22.0. RESULTS: Using structural equation modeling, we tested a conceptual model indicated that: (1) medical students' empathy negatively and significantly predicted learning burnout; (2) medical students' empathy positively predicts mental resilience; (3) resilience of medical students negatively predicts learning burnout; (4) resilience partially mediated the relationship between empathy and learning burnout of medical students, while also controlling for family socioeconomic status. CONCLUSION: These findings highlight the mediating role of resilience in the effect of empathy on learning burnout of medical college students. It may contribute to a better understanding of the effect of empathy. Moreover, it can also provide constructive suggestions for protecting and improve empathy and resilience of medical college students.

SEMA3B-AS1-inhibited osteogenic differentiation of human mesenchymal stem cells revealed by quantitative proteomics analysis.

Human mesenchymal stem cells (hMSCs) are fibroblastoid multipotent adult stem cells with capacities of differentiation into osteoblasts and chondrocytes and show great potential in new bone formation and bone repair-related clinical settings, such as osteoporosis. Long noncoding RNAs (lncRNAs) have been demonstrated to play important roles in various biological processes. Here, we report an antisense lncRNA SEMA3B-AS1 regulating hMSCs osteogenesis. SEMA3B-AS1 is proximal to a member of the semaphorin family Sema3b. Overexpression of SEMA3B-AS1 using the lentivirus system markedly inhibits the proliferation of hMSCs and meanwhile reduces osteogenic differentiation. Using a comprehensive proteomic technique named isobaric tag for relative and absolute quantitation, we found that SEMA3B-AS1 significantly alters the process of osteogenesis through downregulating the expression of proteins involved in actin cytoskeleton, focal adhesion, and extracellular matrix-receptor interaction, while increasing the expression of proteins in the spliceosome. Collectively, we find that SEMA3B-AS1 is a target for controlling osteogenesis of hMSCs.

HERV-W env regulates calcium influx via activating TRPC3 channel together with depressing DISC1 in human neuroblastoma cells.

The activation and involvement of human endogenous retroviruses W family envelope gene (HERV-W env, also called ERVWE1) have been reported in several neuropsychiatric disorders, including schizophrenia, as well as in multiple sclerosis (MS). Dysregulation of intracellular calcium content is also involved in the pathogenesis of these diseases. Our previous studies showed that HERV-W env overexpression results in activation of small conductance Ca2+-activated K+ channel protein 3 (SK3), a potential risk factor for schizophrenia. In the present study, we aimed to elucidate the relationship between HERV-W env and calcium signaling in schizophrenia. Our results showed that HERV-W env could induce Ca2+ influx in two human neuroblastoma cell lines and upregulate the expression and activation of TRPC3 in cells. The abnormal increase in intracellular Ca2+ concentration was inhibited by addition of the TRPC3 channel blocker pyr3, demonstrating that the Ca2+ influx induced by HERV-W env was TRPC3-dependent. Further experiments showed that HERV-W env overexpression downregulated DISC1, while knockdown of DISC1 promoted activation of TRPC3 without affecting TRPC3 expression. In conclusion, HERV-W env induced Ca2+ influx in human neuroblastoma cells by activating the TRPC3 channel through directly regulating its expression or downregulating DISC1, which could also increase TRPC3 activation without affecting TRPC3 expression. These findings provide new insights into how HERV-W env affects neuronal activity and contributes to the pathogenesis of schizophrenia.

Activation of elements in HERV-W family by caffeine and aspirin.

Caffeine and aspirin have been suggested to be involved in neurologic diseases, such as schizophrenia, and previous data have revealed that abnormal expression of HERV-W elements may be an important factor in the etiopathogenesis of those diseases. In this article, we reported that caffeine and aspirin contributed to the expression of HERV-W env and gag in Human SH-SY5Y neuroblastoma cells. Semi-quantitative RT-PCR and quantitative Real-time PCR were used to detect the mRNA of HERV-W env and gag in cells exposed to caffeine or aspirin. Western blotting was used to detect the protein of HERV-W env. Luciferase activity assay was employed to detect the activity of HERV-W env promoter. It was found that both caffeine and aspirin could increase the expression of HERV-W env and gag in human SH-SY5Y neuroblastoma cells. Caffeine could activate the HERV-W env promoter, while aspirin could not. With previous studies we can conjecture that HERVs might play a bridging role between environmental factors, such as drugs and neurologic diseases.

Eczema is a shared risk factor for anxiety and depression: A meta-analysis and systematic review.

Globally, anxiety and depression are the most common psychiatric disorders that add large burdens to individuals and society; however, the mechanisms underlying these disorders are unclear. Several studies have found that eczema is a shared risk factor for both these conditions. We identified and evaluated eligible observational studies from EMBASE and PubMed. In total, 20 relevant cohort and case-control studies comprising 141,910 patients with eczema and 4,736,222 control participants fulfilled our established criteria. Information extracted included study design, location, sample size, sex distribution of cases and controls or reference cohorts, measurements of outcomes, odds ratio (OR) with 95% confidence interval (CI), and adjusted factors for exposure associated with outcome risk. The meta-analysis was performed by calculating the pooled OR with 95% CI, and heterogeneity was assessed using Cochrane Q and I2 statistics. The pooled effect showed a positive association (n = 4,896,099, OR = 1.63, 95% CI [1.42-1.88], p<0.001) between eczema and depression or anxiety, with positive associations also observed in the depression (n = 4,878,746, OR = 1.64, 95% CI [1.39-1.94], p<0.001) and anxiety (n = 4,607,597, OR = 1.68, 95% CI [1.27-2.21], p<0.001) groups. Subgroup and sensitivity analyses confirmed that these findings were stable and reliable. This study suggests that eczema is associated with an increased risk of developing depression and anxiety, which may assist clinicians in the prevention or treatment of these disorders.

In-depth investigations of the molecular basis underlying sex differences among middle-aged and elderly schizophrenia populations.

Sex can influence almost all aspects of schizophrenia. However, the molecular mechanisms underlying sex differences in schizophrenia remain poorly understood. In this project, the dataset GSE107638 containing neuronal RNA-seq data and age/sex information of individuals with or without schizophrenia were retrieved. Schizophrenia samples were divided into young male (M-1), young female (F-1), middle-aged and elderly male (M-2) and middle-aged and elderly female (F-2) groups. Next, green/yellow/turquoise modules related to the M-2 trait and turquoise module correlated with the F-2 trait were identified by weighted correlation network analysis (WGCNA) analysis (soft thresholding power: 13; min module size: 200). Crucial genes in the M-2 green, M-2 turquoise and F-2 turquoise modules were identified by WGCNA, gene significance/module membership, and protein-protein interaction (PPI) analysis. Moreover, 2067 and 934 differentially expressed genes (|log2 fold-change| ≥0.58 and P-value < 0.05) in M-2 and F-2 schizophrenia subgroups versus same-age and same-sex counterparts were identified, respectively. Additionally, 82 core genes in the M-2 turquoise module and 4 hub genes in the F-2 turquoise module were differentially expressed in M-2 and F-2 schizophrenia subgroups versus their counterparts, respectively. Among the 82 hub genes, 15 genes were found to be correlated with neuronal development by the Kyoto Encyclopedia of Genes and Genomes enrichment analysis. Also, 2 potential PPI networks related to neuronal development were identified. Taken together, multiple potential hub genes and 2 potential neurobiological networks related to schizophrenia sex differences and disease progression were identified among middle-aged and elderly schizophrenia populations.

The Mobile Phone Addiction and Depression Among High School Students: The Roles of Cyberbullying Victimization, Perpetration, and Gender.

Objective: To examine the relation between mobile phone addiction and high school students' depression, and its inner mechanism-the sequential mediating roles of the cyberbullying victimization and the cyberbullying perpetration in this relationship. Methods: 1297 high school students were recruited to complete the Smartphone Addiction Scale, European Cyberbullying Intervention Project Questionnaire and the Center for Epidemiological Studies Depression Scale. Results: (1) Mobile phone addiction was positively correlated with and high school students' depression; (2) cyberbullying victimization and the cyberbullying perpetration significantly mediated the relation between mobile phone addiction and high school students' depression, which contained tow mediating paths-the independent mediating effects of cyberbullying victimization and the sequential mediating effect of cyberbullying victimization and the cyberbullying perpetration; (3) there are gender differences in the sequential mediation model, and boys who are victims of cyberbullying are more likely to develop into cyberbullying perpetrators than girls. Conclusion: The results of this study indicate that depression among high school students with mobile phone addiction can be eliminated through the development of cyberbullying victimization and the cyberbullying perpetration.

The influence of parental autonomy support on cyberbullying victimization of high school students: A latent moderation analysis.

OBJECTIVE: To explore the relationship between parental autonomy support and cyberbullying victimization and the role of mobile phone addiction and teacher-student relationships. METHOD: Using the Perceived parental autonomy support scale, the Smartphone Addiction Scale, the Teacher-Student Relationship Questionnaire, and the Cyberbullying Victimization Scale, 1297 high school students were surveyed and a model based on latent moderated structural equation method was adopted. RESULTS: (1) Parental autonomy support can predict the level of cyberbullying victimization of high school students; (2) Mobile phone addiction plays a part of the mediating role between parental autonomy support and high school students' cyberbullying victimization; (3) With the increase of the level of teacher-student relationship, the predictive effect of parental autonomy support on mobile phone addiction gradually increases, and the predictive effect of parental autonomy support and mobile phone addiction on internet victimization becomes insignificant. CONCLUSION: A good teacher-student relationship helps to enhance the positive effect of parental autonomy support on high school students' mobile phone addiction and alleviate the negative effects of parental autonomy support as well as mobile phone addiction on increasing the risk of cyberbullying victimization among high school students.

Streptococcus mutans PrsA mediates AtlA secretion contributing to extracellular DNA release and biofilm formation in the pathogenesis of infective endocarditis.

The role of secretion chaperone-regulated virulence proteins in the pathogenesis of infective endocarditis (IE) induced by viridans streptococci such as Streptococcus mutans is unclear. In this study, we investigated the contribution of the foldase protein PrsA, a putative parvulin-type peptidyl-prolyl isomerase, to the pathogenesis of S. mutans-induced IE. We found that a prsA-deficient strain had reduced virulence in terms of formation of vegetation on damaged heart valves, as well as reduced autolysis activity, eDNA release and biofilm formation capacity. The secretion and surface exposure of AtlA in vitro was reduced in the prsA-deficient mutant strain, and complementation of recombinant AtlA in the culture medium restored a wild type biofilm phenotype of the prsA-deficient mutant strain. This result suggests that secretion and surface localization of AtlA is regulated by PrsA during biofilm formation. Together, these results demonstrate that S. mutans PrsA could regulate AtlA-mediated eDNA release to contribute to biofilm formation in the pathogenesis of IE.

Relationship Between Family Socioeconomic Status and Learning Burnout of College Students: The Mediating Role of Subjective Well-Being and the Moderating Role of Resilience.

Objective: Learning burnout affects the positive development of college students. The present study aimed to investigate the relationship between family socioeconomic status (FSES) and learning burnout, as well as the mediation effect of subjective well-being and the moderation effect of resilience in this relation. Methods: A total of 550 Chinese college students from Yunnan completed a questionnaire measuring the research variables in this study. Results: (1) After controlling for participants' gender and age, FSES negatively, and significantly predicted learning burnout; (2) subjective well-being partially mediated the relationship between FSES and learning burnout; and (3) the direct effect of FSES on learning burnout and the mediation effect of subjective well-being was moderated by resilience. The level of learning burnout of individuals with low resilience increased significantly with the decrease of FSES, and the level of learning burnout of individuals with high resilience decreased significantly with the increase in subjective well-being. Conclusion: The present findings support the moderated mediation model underlying the relationship between FSES and learning burnout. This also has significant implications for formulating prevention and intervention measures on learning burnout among college students. Limitations: First of all, this study used the cross-sectional study design, which cannot make a causal inference. In addition, the sample in this study is university students from Kunming, which may affect the popularity of the results.

ATP13A2 variability in Taiwanese Parkinson's disease.

Mutations in ATP13A2 have been reported to associate with Parkinson's disease (PD). This study investigates the contribution of genetic variants in ATP13A2 to Taiwanese PD. ATP13A2 cDNA fragments from 65 early onset PD (onset <50 years) were sequenced. The identified variants were validated in a cohort of PD (n = 493) and ethnically matched controls (n = 585). A novel heterozygous G1014S, located at the conserved seventh transmembrane domain of ATP13A2 protein, was identified in an early onset PD patient, which was absent in 585 normal controls. Additionally, a reported heterozygous A746T was found in two PD patients and four controls. The clinical features and 99mTc-TRODAT-1 single photon emission computed tomography (SPECT) image of the patients carrying G1014S and A746T were similar to that of idiopathic PD. One normal control with A746T showed an asymmetric reduction of 99mT TRODAT-1 uptake in the right striatum. Under oxidative stress or apoptotic stimulus, lymphoblastoid cells carrying either A764T or G1014S showed increased caspase 3 activity compared with the controls. The rates of decay for G1014S and A746T proteins were more or less reduced in cycloheximide chase experiment. In silico modeling of G1014S exhibited a more stable feature than wild-type, and G1014S is mislocalized mainly in the intralysosomal space, which is coherent with the prediction of prohibiting N-myristoylation and membrane association. We therefore hypothesize that rare variants of ATP13A2 may contribute to PD susceptibility in Taiwan. The role played by ATP13A2 variants in PD remains to be clarified.

Relationship Between Medical Students' Empathy and Occupation Expectation: Mediating Roles of Resilience and Subjective Well-Being.

Background: The occupation expectation of medical students can predict the possibility of their future employment in the medical industry, and empathy is the special ability of medical students in their study and career, which affects the development of their occupation expectation. Objective: To explore the relationship between resilience and subjective well-being between medical students' empathy and occupation expectation and their internal mechanisms. Design: Data were collected from October 2020 to March 2021 using a paper questionnaire survey. Subjective: 586 medical students at a key medical university in Yunnan Province were invited to complete the survey. Main Measures: The Basic Empathy Scale, Connor-Davidson Resilience Scale, Subjective Well-Being Questionnaire, and Occupation Expectation Scale. Key Results: The empathy is intended to affect the occupation expectation of medical students through four paths. The direct path effect value is 0.073 (95% CI: 0.007∼0.217), the indirect path 1 effect value is 0.078 (95% CI: 0.022∼0.134), indirect path 2 effect value is 0.010 (95% CI: 0.005∼0.022), indirect path 3 effect value is 0.022 (95% CI: 0.0604∼0.039), all the confidence intervals do not contain 0, and the mediated effect ratio is 60.109%. Conclusion: Empathy has an impact on occupation expectation of medical students through the sequential mediating effects of resilience and subjective well-being. Medical colleges should fully consider the role of protective factors when cultivating and enhancing the occupation expectation of clinical medical students. Strengthening the intervention of emotional factors (empathy), self-regulating ability (psychological toughness) and cognitive factors (subjective well-being) is an important way to effectively establish professional values, improve occupation expectation of medical students and reduce the turnover rate of medical students.

[Dynamic observation on splenocyte subsets in mice immunized with recombinant Bb-Eg95-EgA31 vaccine of Echinococcus granulosus].

OBJECTIVE: To dynamically observe changes of subsets of splenocytes in mice immunized with recombinant Bifidobacteria bifidum (Bb)-Eg95-EgA31 vaccine of Echinococcus granulosus (Eg). METHODS: BALB/c mice were vaccinated by 5 x 10(8) colony forming unit (CFU) orally and 5 x 10(5) CFU intranasally respectively. Mice were killed on week 0, 2, 4, 6, 8, 10, 12, 14, 16, 18 and 20 after immunization respectively, and spleens were separated for cell preparation. CD4+ and CD8+ T cells were determined by flow cytometry (FCM), with MRS as control. RESULTS: In the oral immunization group, CD4+ cells showed a significant increase during the 4th-10th week after vaccination, and reached the highest level on the 6th week, whereas no obvious changes in CD8+ cells numbers were observed. In the intranasal immunization group, CD4+ cells showed an obvious increase during the 4th-8th week after vaccination, and reached the highest level on the 6th week, CD8+ subsets had no obvious changes. CONCLUSION: CD4+ T cell cells may play a key role in immune response in mice immunized with the recombinant Bb-Eg95-EgA31 vaccine of Echinococcus granulosus.

[Construction and expression of recombinant plasmid pET28alpha-Sj26GST of Schistosoma japonicum in Escherichia coli BL21].

OBJECTIVE: To construct and express recombinant plasmid pET28a-Sj26GST of Schistosoma japonicum (Sj) in Escherichia coli BL21 (DE3). METHODS: The total RNA was extracted from Sj adult worms by ultrasound-breaking. The Sj26GST antigen gene was amplified by RT-PCR from the total RNA, and then cloned into prokaryotic expression plasmid pET28alpha and transformed into E. coli BL2 (DE3). The BL21(pET28a-Sj26GST) was induced with isopropyl-beta-D-thiogalactopyranosid (IPTG), and the expressed products were analyzed and identified with SDS-PAGE and Western blot. RESULTS: The 676 bp Sj26GST gene was successfully amplified by RT-PCR and cloned into pET28alpha. The recombinant plasmid pET28a-Sj26GST was successfully constructed, with a relative molecular weight of expressed recombinant protein at approximately 36 x 10(3) as determined by SDS-PAGE. The amount of the expressed protein comprised 26% of the total bacterial proteins. The fusion protein could be recognized by the sera of rabbits infected with Sj. CONCLUSION: The recombinant plasmid pET28alpha-Sj26GST is successfully constructed and highly expressed in E. coli in a fused form with His-tag. The expressed fusion protein shows specific antigenicity.

[Research status on DNA vaccine against Cysticercus cellulosae infection].

DNA vaccine against Cysticercus cellulosae infection is a newly emerging vaccine in recent years. It can induce not only humoral immune response, but also a high level cellular immune response. The DNA vaccine displays prominent advantages in the prevention on cysticercosis. This article reviews the current situation on several DNA vaccines.

[Changes of spleen cytokines in mice immunized with recombinant Bb-Eg95-EgA31 vaccine against Echinococcus granulosus].

OBJECTIVE: To investigate the level of cytokines in spleen from mice immunized with recombinant Bifidobacteria bifidum(Bb)-Eg95-EgA31 vaccine of Echinococcus granulosus (Eg) and challenged with Eg protoscoleces. METHODS: 56 female BALB/c mice were randomly divided into 7 groups: Recombinant Bb-Eg9S-95-EgA31 vaccine subcutaneous injection (group A), intramuscular injection (B), intranasal immunization (C), oral administration (D), blank vector control (E), Bb control (F) and MRS control (G). Mice in all groups were challenged with 50 Eg protoscoleces on the 8th week after vaccination and sacrificed on the 25th week after infection. Spleens were collected to prepare splenocytes, which were cultured under activation of crude Eg antigen (EgAg), with concanavalin A (ConA) or lipopolysaccharide (LPS) stimulation and non-stimulation as control. The splenocyte supernatants were collected to determine the levels of interferon-gamma (IFN-gamma), interleukin-12 (IL-12), tumour necrosis factor-alpha (TNF-alpha) and IL-10 by ELISA. RESULTS: The level of IFN-gamma in groups A [(137.5 +/- 23.2) pg/ml], B [(162.5 +/- 23.2) pg/ml], C [(250.0 +/- 53.5) pg/ml] and D [(215.0 +/- 37.4) pg/ml] was higher than that of group G [(50.0 +/- 10.7) pg/ml] (P < 0.01). The level of IL-12 in groups A [(27.5 +/- 4.6) pg/ml], B [(32.5 +/- 4.6) pg/ml], C [(45.0 +/- 5.4) pg/ml] and D [(35.0 +/- 5.4) pg/ml] was higher than that of group G [(15.0 +/- 5.4) pg/ml] (P < 0.01). The level of TNF-alpha in groups A [(275.0 +/- 46.3) pg/ml], B [(325.0 +/- 46.3) pg/ml], C [(450.0 +/- 53.5) pg/ml] and D [(350.0 +/- 53.5) pg/ml] was higher than that of group G [(150.0 +/- 53.5) pg/ml] (P < 0.01). The level of IL-10 in groups A [(37.5 +/- 4.6) pg/ml], B [(35.0 +/- 5.4) pg/ml], C [(25.0 +/- 5.4) pg/ml] and D [(32.5 +/- 4.6) pg/ml] was lower than that of group G [(45.0 +/- 5.4) pg/ml] (P < 0.05 or P < 0.01). CONCLUSION: The recombinant Bb-Eg95-EgA31 vaccine can induce a protective Th1 type immune response in mice

[Inhibition on apoptosis of splenocytes in infected mice by immunization with recombinant Bb-Eg95-EgA31 protein of Echinococcus granulosus].

OBJECTIVE: To investigate the weight reduction of hydatid cysts and apoptosis of splenocytes in infected mice by recombinant Bifidobacteria bifidum (Bb)-Eg95-EgA31 protein of Echinococcus granulosus (Eg) and challenged with Eg protoscoleces. METHODS: 56 female BALB/c mice were randomly divided into 7 groups. Groups A and B were injected subcutaneously and intramuscularly respectively with 5 x 10(6) colony-forming unit (CFU) recombinant Bb-Eg95-EgA31 protein, group C was immunized intranasally by 5 x 10(5) CFU protein, group D was vaccinated transgastrically by 5 x 10(8) CFU protein, groups E and F were injected subcutaneously with 5 x 10(6) CFU blank vector [Bb (pGEX-1 lambda T)] and Bb respectively, and group G was injected subcutaneously with 100 microl MRS. Mice in all groups were challenged with 50 Eg protoscoleces on the 8th week after vaccination and sacrificed on the 25th week after infection. The weight of hydatid cysts was measured and weight-reduction rate was calculated. Spleens were collected to prepare splenocytes which were cultured under stimulation with concanavalin A (ConA). The apoptotic rate was determined by flow cytometry (FCM). RESULTS: The average weight of hydatid cysts in groups A [(41.0 +/- 23.0) mg], B [(44.0 +/- 22.0) mg], C [(22.0 +/- 21.0) mg], and D [(28.0 +/- 16.0) mg] was lower than that of group G [(75.0 +/- 33.0) mg] (P<0.05, P<0.01), and there was no significant difference among groups A, B, C and D (P>0.05); no significant difference was found between group G and groups E [(63.0 +/- 30.0) mg], F [(69.0 +/- 22.0) mg] (P>0.05). The apoptotic rate of splenocytes cultured with no ConA in groups A (0.14 +/- 0.01), B (0.14 +/- 0.01), C (0.13 +/- 0.01), and D (0.141 +/- 0.01) was lower than that of group G (0.21 +/- 0.01) (P<0.05); that of group C was lower than groups A, B, and D (P<0.05); there was no significant difference between groups D and A, between groups A and B, and between groups E (0.20 +/- 0.01), F (0.20 +/- 0.01) and group G. The apoptotic rate of splenocytes cultured with ConA in group A (0.19 +/- 0.01), B (0.20 +/- 0.00), C (0.17 +/- 0.01), and D (0.19 +/- 0.01) were lower than that of group G (0.26 +/- 0.01) (P<0.01), that of group C was lower than groups A and B (P<0.01), group C was lower than group D (P<0.05), group D was lower than group B (P<0.05); there was no significant difference between groups A and B, and between groups A and D, and between groups E (0.25 +/- 0.01), F (0.25 +/- 0.01), and group G (P>0.05). The apoptotic rate of splenocytes cultured with ConA was higher than those cultured without ConA (P<0.01). CONCLUSIONS: Apoptosis of splenocytes may be induced by infection of Echinococcus granulosus protoscoleces in mice, while the recombinant Bb-Eg95-EgA31 protein may inhibit the apoptosis of splenocytes in mice challenged with Eg, and induce certain protective immunity in the host.

[Research progress in antigens for the diagnosis of alveolar echinococcosis].

Specific antigens of Echinococcus multilocularis is essential for the diagnosis of alveolar echinococcosis and vaccine development. Because of the limited source of nature antigen, its application is restricted. The development of recombinant antigens can provide large amount of antigen under effective quality control. This review summarizes the recent progress in antigen research, especially the recombinant antigen used for diagnosis of the disease.

Ginsenoside Rg1 ameliorates liver fibrosis via suppressing epithelial to mesenchymal transition and reactive oxygen species production in vitro and in vivo.

Liver fibrosis remains a major cause of morbidity and mortality with a complicated etiology and notorious complications, but there is a lack of efficacious therapeutics. Epithelial to mesenchymal transition (EMT) has a central role in the course of liver fibrosis, and thus, prevention of the development of EMT may control and even reverse liver fibrosis. This study aimed to examine the beneficial effect of ginsenoside Rg1, a phrenological active component isolated from Ginseng, and interrogate the mechanism in vitro and in vivo, with a focus on transforming growth factor-ß (TGF-ß)/Smad and Nrf2-mediated signaling pathways. We employed a TGF-ß-induced EMT model in HSC-T6 cells and CCl4 -induced liver fibrosis in animal. We found that ginsenoside Rg1 significantly reduced cell proliferation and reversed transforming growth factor-ß (TGF-ß)-induced EMT in HSC-T6 cells; and ginsenoside Rg1 induced cell apoptosis, Ginsenoside Rg1 decreased the cellular level of collagen I and III in HSC-T6 cells, indicating the amelioration of fibrosis. We showed that ginsenoside Rg1 reduced cellular reactive oxygen species (ROS). We also observed similar beneficial effects of ginsenoside Rg1 in vivo. The data showed that ginsenoside Rg1 decreased the level of alanine aminotransferase and aspartate aminotransferase, and collage type IV (IV-C), hyaluronic acid, and laminin in carbon tetrachloride (CCl4)-induced liver fibrotic model. Mechanistically, we showed that ginsenoside Rg1 tuned down the TGF-ß/Smad and stimulated Nrf-2 nuclear translocation, which could explain the beneficial effects. In aggregate, our results demonstrate that ginsenoside Rg1 exhibits a protective effect on liver fibrosis via suppressing EMT and cellular ROS level. © 2018 BioFactors, 2018.

Ginsenoside Rg1 inhibits inflammatory responses via modulation of the nuclear factor­κB pathway and inhibition of inflammasome activation in alcoholic hepatitis.

Ginsenoside Rg1 (G­Rg1) is an active ingredient of Panax ginseng, which has previously been reported to attenuate alcohol­induced hepatic damage; however, the underlying mechanisms remain largely unknown. The present study aimed to investigate the protective effects of G­Rg1 on alcohol­induced cell injury in vitro and on a rat model of alcoholic hepatitis in vivo. For the in vitro model, L­O2 cells were incubated with ethanol in the presence or absence of G­Rg1. For the in vivo model, rats were administered ethanol by intragastric injection and were treated with G­Rg1, or dexamethasone as a control. The results indicated that serum biochemical parameters, including alanine aminotransferase, aspartate aminotransferase and total bilirubin, as well as the expression of nuclear factor (NF)­κB pathway­associated inflammatory cytokines, including interleukin (IL)­6, tumor necrosis factor­α and IL­1ß, were elevated in response to alcohol; however, they were significantly decreased by G­Rg1 treatment. Furthermore, NF­κB pathway activation was reduced by treatment with G­Rg1. G­Rg1 also decreased oxidative stress by inhibiting cytochrome P450 2E1 expression and reactive oxygen species production, and promoting glutathione peroxidase expression. Furthermore, G­Rg1 inhibited the expression levels of caspase­3 and ­8, which may be associated with decreased hepatocyte apoptosis. These data suggested that G­Rg1 may protect hepatocytes against alcohol­induced injury, through preventing excessive inflammation and hepatocellular apoptosis.