Background:Ziwan and Taoren(ZT)is a classic medicine pair in the formula of Mai Dong Di Shao Decoction,has been used to treat primary Sjogren’s syndrome(pSS)for more than 20 years.But its action mechanism is still un...Background:Ziwan and Taoren(ZT)is a classic medicine pair in the formula of Mai Dong Di Shao Decoction,has been used to treat primary Sjogren’s syndrome(pSS)for more than 20 years.But its action mechanism is still unknown.This study is aimed to reveal the potential mechanism of ZT treated pSS and discover its active compounds of ZT and therapeutic target for pSS.Methods:Firstly,the potential pathways of ZT for pSS treatment were predicted through network pharmacology and GO and KEGG enrichment analysis.Secondly,the inter-structural relationships between active compounds of ZT and target proteins were visualized using molecular docking techniques.Finally,efficacy and mechanism were conducted through in vivo experiments,such as water intake,spleen index,hematoxylin-eosin staining pathological changes,ELISA,Western Blot analysis,and immunofluorescence staining.Results:Nine active compounds were extracted from network pharmacology,including quercitrin,luteolin,kaempferol,β-sitosterol,isorhamnetin,galangin,hederagenin,diosmetin and gibberellin 7.Seven disease targets were identified:RELA,TP53,AKT1,interleukin(IL)6,MAPK1,ESR1,IL10;with RELA being the most core target.KEGG and GO enrichment analysis indicated that ZT may act through the TLR/NF-κB/RELA inflammatory mechanism process.preliminary results of molecular docking showed that ZT’s active compounds bind well to the RELA(p65)receptor.In vivo results demonstrated that a high dose of ZT significantly improved water intake and reduced lymphocytes infiltration in submandibular gland pathology in NOD mice.The expression content of AQP5 and vasoactive intestinal peptide in the submaxillary gland was significantly increased,while levels of inflammatory factors such as tumor necrosis factor-α,IL-6,and IL-1βalong with protein expressions including toll-like receptor4,p-p65 and p-IKKα/βin NF-κB pathway were reduced.Conclusions:The ZT treatment exhibits a promising efficacy in mitigating dryness symptoms of pSS,potentially attributed to its capacity for suppressing the TLR/NF-κB inflammatory signaling pathway.展开更多
BACKGROUND Serotonin receptor 2B(5-HT2B receptor)plays a critical role in many chronic pain conditions.The possible involvement of the 5-HT2B receptor in the altered gut sensation of irritable bowel syndrome with diar...BACKGROUND Serotonin receptor 2B(5-HT2B receptor)plays a critical role in many chronic pain conditions.The possible involvement of the 5-HT2B receptor in the altered gut sensation of irritable bowel syndrome with diarrhea(IBS-D)was investigated in the present study.AIM To investigate the possible involvement of 5-HT2B receptor in the altered gut sensation in rat model and patients with IBS-D.METHODS Rectosigmoid biopsies were collected from 18 patients with IBS-D and 10 patients with irritable bowel syndrome with constipation who fulfilled the Rome IV criteria and 15 healthy controls.The expression level of the 5-HT2B receptor in colon tissue was measured using an enzyme-linked immunosorbent assay and correlated with abdominal pain scores.The IBS-D rat model was induced by intracolonic instillation of acetic acid and wrap restraint.Alterations in visceral sensitivity and 5-HT2B receptor and transient receptor potential vanilloid type 1(TRPV1)expression were examined following 5-HT2B receptor antagonist adminis-tration.Changes in visceral sensitivity after administration of the TRPV1 antago-INTRODUCTION Irritable bowel syndrome(IBS)is a chronic functional bowel disorder characterized by recurrent abdominal pain with altered bowel habits that affects approximately 15%of the population worldwide[1].IBS significantly impacts the quality of life of patients.Although the pathogenesis of IBS is not completely understood,the role of abnormal visceral sensitivity in IBS has recently emerged[2,3].5-Hydroxytryptamine(5-HT)is known to play a key role in the physiological states of the gastrointestinal tract.Plasma 5-HT levels in IBS with diarrhea(IBS-D)patients were greater than those in healthy controls[4],suggesting a possible role of 5-HT in the pathogenesis of IBS-D.The serotonin receptor 2(5-HT2 receptor)family comprises three subtypes:5-HT2A,5-HT2B,and 5-HT2c.All 5-HT2 receptors exhibit 46%-50%overall sequence identity,and all of these receptors preferentially bind to Gq/11 to increase inositol phosphates and intracellular calcium mobilization[5].5-HT2B receptors are widely expressed throughout the gut,and experimental evidence suggests that the primary function of 5-HT2B receptors is to mediate contractile responses to 5-HT through its action on smooth muscle[6].The 5-HT2B receptor is localized to both neurons of the myenteric nerve plexus and smooth muscle in the human colon.The 5-HT2B receptor mediates 5-HT-evoked contraction of longitudinal smooth muscle[6].These findings suggest that the 5-HT2B receptor could play an important role in modulating colonic motility,which could affect sensory signaling in the gut.Other laboratories have shown that the 5-HT2B receptor participates in the development of mechanical and formalin-induced hyperalgesia[7,8].A 5-HT2B receptor antagonist reduced 2,4,6-trinitrobenzene sulfonic acid(TNBS)and stress-induced visceral hyperalgesia in rats[9,10].However,the role of the 5-HT2B receptor in IBS-D patients and in acetic acid-and wrap restraint-induced IBS-D rat models was not investigated.展开更多
Background:Shengxuebao mixture(SXBM)is a novel herbal drug approved by China State Food and Drug Administration for the treatment of Leukopenia and iron deficiency anemia caused by radiotherapy and chemotherapy.Method...Background:Shengxuebao mixture(SXBM)is a novel herbal drug approved by China State Food and Drug Administration for the treatment of Leukopenia and iron deficiency anemia caused by radiotherapy and chemotherapy.Methods:To explore the mechanism of SXBM in treating blood deficiency syndrome(BDS).Firstly,network pharmacology and in vivo experiments were used to screen candidate targets and important signaling pathways of SXBM,GO functional enrichment and KEGG pathway analysis were performed.Secondly,a BDS rat model was established to verify the results of the analysis of network pharmacological enrichment.Histopathology and routine peripheral blood examination were observed.The expressions of tumor necrosis factor-α,interleukin(IL)-6,HIF-1αand NF-κB were detected by Western blot,and the expressions of IL-6,IL-1βwere detected by ELISA.Results:62 bioactive components,66 potential targets and 131 signaling pathways of BDS were successfully identified by network pharmacology.Molecular docking simulation techniques showed that key targets tumor necrosis factor-α,IL-6,IL-1βcan dock well with crucial components,and the BDS-related signaling pathways HIF-1 and JAK-STAT play a vital role.The combined model experiment of acetylphenylhydrazine and cyclophosphamide showed that the model group had obvious blood deficiency,and the histopathology and blood routine were effectively restored after administration.Our findings indicate that SXBM’s therapeutic effect on BDS primarily involves the mediation of the HIF-1α/NF-κB signaling pathway and the regulation of hematopoietic factor expression.Conclusion:This study not only affirmed the protective properties of SXBM against BDS but also provided insights into a potential mechanism for blood replenishment in the treatment of BDS using SXBM.展开更多
Chronic hepatitis B(CHB)is a global health issue that increases the risk of liver cirrhosis and hepatocellular carcinoma in infected patients.Metabolic syndrome(Met S)is a disease endemic mostly to the developed count...Chronic hepatitis B(CHB)is a global health issue that increases the risk of liver cirrhosis and hepatocellular carcinoma in infected patients.Metabolic syndrome(Met S)is a disease endemic mostly to the developed countries.It is associated with high cardiovascular mortality and morbidity,diabetes mellitus as well as cancer.In this manuscript,we systematically review the published data on the relationship between Met S and CHB infection.Multiple studies have described highly variable correlations between CHB on one hand and Met S,non-alcoholic fatty liver disease and dyslipidemia on the other.No association between CHB and diabetes mellitus or atherosclerosis has been described as of now.The presence of Met S in patients infected with hepatitis B virus increases the risk of fibrosis,cirrhosis and hepatocellular carcinoma.Appropriate lifestyle,but also pharmacological interventions are needed to prevent the development of these complications.展开更多
AIM:To investigate the roles of toll-like receptor 4(TLR4) and nuclear factor(NF)-κB on cystathionine βsynthetase(CBS) expression and visceral hypersensitivity in rats.METHODS:This study used 1-7-wk-old male Sprague...AIM:To investigate the roles of toll-like receptor 4(TLR4) and nuclear factor(NF)-κB on cystathionine βsynthetase(CBS) expression and visceral hypersensitivity in rats.METHODS:This study used 1-7-wk-old male SpragueDawley rats.Western blot analysis was employed to measure the expression of TLR4,NF-kB and the endogenous hydrogen sulfide-producing enzyme CBS in colon dorsal root ganglia(DRG) from control and "irritable bowel syndrome" rats induced by neonatal colonic inflammation(NCI).Colon-specific DRG neurons were labeled with Dil and acutely dissociated to measure excitability with patch-clamp techniques.Immunofluorescence was employed to determine the co-expression of TLR4,NF-kB and CBS in Dil-labeled DRG neurons.RESULTS:NCI significantly upregulated the expression of TLR4 in colon-related DRGs(0.34 ± 0.12 vs 0.72 ±0.02 for the control and NCI groups,respectively,P <0.05).Intrathecal administration of the TLR4-selective inhibitor CLI-095 significantly enhanced the colorectal distention threshold of NCI rats.CLI-095 treatment also markedly reversed the hyperexcitability of colonspecific DRG neurons and reduced the expression of CBS(1.7 ± 0.1 vs 1.1 ± 0.04,p < 0.05) and of the NF-kB subunit p65(0.8 ± 0.1 vs 0.5 ± 0.1,P< 0.05).Furthermore,the NF-KB-selective inhibitor pyrrolidine dithiocarbamate(PDTC) significantly reduced the upregulation of CBS(1.0 ± 0.1 vs 0.6 ± 0.1,P< 0.05)and attenuated visceral hypersensitivity in the NCI rats.In vitro,incubation of cultured DRG neurons with the TLR4 agonist lipopolysaccharide significantly enhanced the expression of p65(control vs 8 h:0.9 ± 0.1 vs1.3 ± 0.1;control vs 12 h:0.9 ± 0.1 vs 1.3 ± 0.1,P< 0.05;control vs 24 h:0.9 ± 0.1 vs 1.6 ± 0.1,P <0.01) and CBS(control vs 12 h:1.0 ± 0.1 vs 2.2 ±0.4;control vs 24 h:1.0 ± 0.1 vs 2.6 ± 0.1,P< 0.05),whereas the inhibition of p65 via pre-incubation with PDTC significantly reversed the upregulation of CBS expression(1.2 ± 0.1 vs 0.6 ± 0.0,P< 0.01).CONCLUSION:Our results suggest that the activation of TLR4 by NCI upregulates CBS expression,which is mediated by the NF-kB signaling pathway,thus contributing to visceral hypersensitivity.展开更多
The present study aimed to investigate the clinical value of serum anti-mullerian hormone(AMH) and inhibin B(INHB) in predicting the ovarian response of patients with polycystic ovary syndrome(PCOS). A total of ...The present study aimed to investigate the clinical value of serum anti-mullerian hormone(AMH) and inhibin B(INHB) in predicting the ovarian response of patients with polycystic ovary syndrome(PCOS). A total of 120 PCOS patients were enrolled and divided into three groups in terms of the ovarian response: a low-response group(n=36), a normal-response group(n=44), and a high-response group(n=40). The serum AMH and INHB levels were measured by enzyme-linked immunosorbent assay(ELISA). The follicle stimulating hormone(FSH), luteinizing hormone(LH), and estradiol(E2) levels were determined by chemiluminescence microparticle immunoassay. The correlation of the serum AMH and INHB levels with other indicators was analyzed. A receiver operating characteristic(ROC) curve was established to analyze the prediction of ovarian response by AMH and INHB. The results showed that there were significant differences in age, body mass index(BMI), FSH, total gonadotropin-releasing hormone(Gn RH), LH, E2, and antral follicle counts(AFCs) between the groups(P〈0.05). The serum AMH and INHB levels were increased significantly with the ovarian response of PCOS patients increasing(P〈0.05). The serum AMH and INHB levels were negatively correlated with the age, BMI, FSH level, Gn, and E2 levels(P〈0.05). They were positively correlated with the LH levels and AFCs(P〈0.05). ROC curve analysis of serum AMH and INHB in prediction of a low ovarian response showed that the area under the ROC curve(AUC) value of the serum AMH level was 0.817, with a cut-off value of 1.29 ng/m L. The sensitivity and specificity were 71.2% and 79.6%, respectively. The AUC value of serum INHB was 0.674, with a cut-off value of 38.65 ng/m L, and the sensitivity and specificity were 50.7% and 74.5%, respectively. ROC curve analysis showed when the serum AMH and INHB levels were used to predict a high ovarian response, the AUC value of the serum AMH level was 0.742, with a cut-off value of 2.84 ng/m L, and the sensitivity and specificity were 72.7% and 65.9%, respectively; the AUC value of the serum INHB level was 0.551 with a cut-off of 45.76 ng/m L, and the sensitivity and specificity were 76.3% and 40.2%, respectively. It was suggested the serum AMH and INHB levels have high clinical value in predicting the ovarian response of PCOS patients.展开更多
Increasing the planting density of maize is an effective measure to improve its yield.However,plants under high planting density tend to trigger shade avoidance syndrome(SAS),reducing lodging resistance and ultimately...Increasing the planting density of maize is an effective measure to improve its yield.However,plants under high planting density tend to trigger shade avoidance syndrome(SAS),reducing lodging resistance and ultimately yield drop.Phytochrome B(phyB)plays a dominant role in mediating shade avoidance response.This study constructed two hyperactive mutated alleles of maize PHYB1:ZmPHYB1^(Y98F)(mimicking Y104F of AtPHYB)and ZmPHYB1^(Y359F)(mimicking Y361F of AtPHYB).Ectopic expression of ZmPHYB1^(Y98F) and ZmPHYB1^(Y359F) under the control of the ZmPHYB1 promoter in the Arabidopsis phyB-9 background rendered enhanced activity on complementing the phyB-9 related phenotypes compared with ZmPHYB1^(WT).Moreover,similar to the behavior of ZmPHYB1^(WT),ZmPHYB1Y98F and ZmPHYB1^(Y359F) proteins are localized to the nucleus after red light exposure,and could interact with PIF proteins of maize.In addition,expression of ZmPHYB1^(Y98F) and ZmPHYB1^(Y359F) variants under the control of the native ZmPHYB1 promoter attenuated SAS of maize seedlings subjected to simulated shade treatment.It effectively reduced mature maize’s plant height and ear height in field conditions.The results combined demonstrate the utility of ZmPHYB1^(Y98F) and ZmPHYB1^(Y359F) for attenuating SAS and breeding high density-tolerant varieties of maize.展开更多
BACKGROUND Budd-Chiari syndrome(BCS)is an uncommon disorder characterized by obstruction of hepatic venous outflow.To date,the exact mechanism underlying hepatic injury derived from the hepatic venous outflow obstruct...BACKGROUND Budd-Chiari syndrome(BCS)is an uncommon disorder characterized by obstruction of hepatic venous outflow.To date,the exact mechanism underlying hepatic injury derived from the hepatic venous outflow obstruction in BCS remains largely unknown.AIM To assess the role of NF-κB-mediated inflammation in BCS-induced liver injury in humans and rats.METHODS A total of 180 rats were randomly assigned into nine groups,including four BCS model groups(1,3,6 and 12 wk),four sham-operated groups(1,3,6 and 12 wk),and a control group.Lipopolysaccharide(LPS)levels in each group were detected by the Tachypleus Amebocyte Lysate assay.The mRNA and protein levels of TLR4,NF-κB,tumor necrosis factor(TNF)-α,interleukin(IL)-2 and interferon(IFN)-γwere quantified.In addition,60 patients with BCS and 30 healthy controls were enrolled,and their blood samples were analyzed.RESULTS Hepatic and plasma LPS levels were significantly increased in rats.The mRNA and protein expression levels of TLR4,NF-κB and inflammatory cytokines(TNF-α,IL-2 and IFN-γ)in liver tissues were significantly higher in the BCS model groups compared with the other two groups.In addition,the model groups(1,3,6 and 12 wk after BCS induction)showed significant differences in the levels of LPS,TLR4,NF-κB,TNF-α,IL-2 and IFN-γ.Notably,there was a significant correlation between the LPS concentrations and mRNA and protein levels of TLR4,NF-κB and inflammatory cytokines.Importantly,it was revealed that the levels of LPS,TLR4,NF-κB and inflammatory cytokines were significantly greater in chronic BCS patients than healthy controls and acute BCS patients.CONCLUSION LPS level is markedly elevated in BCS,in turn activating the TLR4/NF-κB signaling pathway,leading to induction of inflammatory cytokines(TNF-α,IL-2 and IFN-γ)in response to BCS-induced liver injury.展开更多
Previous studies have demonstrated a strong association between carbamazepine(CBZ)-induced Stevens-Johnson syndrome(SJS) and HLA-B 1502 in Han Chinese. Here, we extended the study of HLA-B 1502 susceptibility to t...Previous studies have demonstrated a strong association between carbamazepine(CBZ)-induced Stevens-Johnson syndrome(SJS) and HLA-B 1502 in Han Chinese. Here, we extended the study of HLA-B 1502 susceptibility to two different antiepileptic drugs, oxcarbazepine(OXC) and phenobabital(PB). In addition, we genotyped HLA-B 1511 in a case of CBZ-induced SJS with genotype negative for HLA-B 1502. The presence of HLA-B 1502 was determined using polymerase chain reaction with sequence-specific primers(PCR-SSP). Moreover, we genotyped HLA-B 1502 in 17 cases of antiepileptic drugs(AEDs)-induced cutaneous adverse drug reactions(cADRs), in comparison with AEDs-tolerant(n=32) and normal controls(n=38) in the central region of China. The data showed that HLA-B 1502 was positive in 5 of 6 cases of AEDs-induced SJS(4 CBZ, 1 OXC and 1 PB), which was significantly more frequent than AEDs-tolerant(2/32, 18 CBZ, 6 PB and 8 OXC) and normal controls(3/38). Compared with AEDs-tolerant and normal controls, the OR for patients carrying the HLA-B 1502 with AEDs-induced SJS was 6.25(95% CI: 1.06–36.74) and 4.86(95% CI: 1.01–23.47). The sensitivity and specificity of HLA-B 1502 for prediction of AEDs-induced SJS were 71.4%. The sensitivity and specificity of HLA-B 1502 for prediction of CBZ-induced SJS were 60% and 94%. HLA-B 1502 was not found in 11 children with maculopapular exanthema(MPE)(n=9) and hypersensitivity syndrome(HSS)(n=2). However, we also found one case of CBZ-induced SJS who was negative for HLA-B 1502 but carried HLA-B 1511. It was suggested that the association between the CBZ-induced SJS and HLA-B 1502 allele in Han Chinese children can extend to other aromatic AEDs including OXC and PB related SJS. HLA-B 1511 may be a risk factor for some patients with CBZ-induced SJS negative for HLA-B 1502.展开更多
AIM:To investigate if non-alcoholic fatty liver disease (NAFLD) is an early mediator for prediction of metabolic syndrome,and if liver B-ultrasound can be used for its diagnosis.METHODS:We classified 861 obese childre...AIM:To investigate if non-alcoholic fatty liver disease (NAFLD) is an early mediator for prediction of metabolic syndrome,and if liver B-ultrasound can be used for its diagnosis.METHODS:We classified 861 obese children (6-16 years old) into three subgroups:group 0 (normal liver in ultrasound and normal transaminases);group 1 (fatty liver in ultrasound and normal transaminases);and group 2 (fatty liver in ultrasound and elevated transaminases).We measured the body mass index,waist and hip circumference,blood pressure,fasting blood glucose,insulin,homeostasis model assessment of insulin resistance (HOMA-IR),whole-body insulin sensitivity index (WBISI),lipid profile and transaminases in all the participants.The risk of developing metabolic syndrome (MS) was assessed according to the degree of liver fatty infiltration based on the B-ultrasound examination.RESULTS:Among the 861 obese children,587 (68.18%) were classified as having NAFLD,and 221 (25.67%) as having MS.The prevalence of MS in NAFLD children (groups 1 and 2) was 37.64% (221/587),which was much higher than that in non-NAFLD group (group 0,12.04%) (P < 0.01).There were significantly higher incidences concerning every component of MS in group 2 compared with group 0 (P < 0.05).The incidence of NAFLD in MS patients was 84.61% (187/221),which was significantly higher than that of hypertension (57.46%,127/221) and glucose metabolic anomalies (22.62%,50/221),and almost equal to the prevalence of dyslipidemia (89.14%,197/221).Based on the B-ultrasound scales,the presence of moderate and severe liver fatty infiltration carried a high risk of hypertension [odds ratio (OR):2.18,95% confidence interval (95% CI):1.27-3.75],dyslipidemia (OR:7.99,95% CI:4.34-14.73),impaired fasting glucose (OR:3.65,95% CI:1.04-12.85),and whole MS (OR:3.77;95% CI:1.90-7.47,P < 0.01).The state of insulin resistance (calculated by HOMA-IR and WBISI) deteriorated as the degree of fatty infiltration increased.CONCLUSION:NAFLD is not only a liver disease,but also an early mediator that reflects metabolic disorder,and liver B-ultrasound can be a useful tool for MS screening.展开更多
BACKGROUND Antisynthetase syndrome(ASS)is characterized by the presence of antisynthetase antibodies coupled with clinical findings such as fever,polymyositis-dermatomyositis and interstitial lung disease.It is,howeve...BACKGROUND Antisynthetase syndrome(ASS)is characterized by the presence of antisynthetase antibodies coupled with clinical findings such as fever,polymyositis-dermatomyositis and interstitial lung disease.It is,however,rare to observe ASS association with B cell lymphoma presenting severe pneumonia as the first clinical manifestation.CASE SUMMARY We evaluated a 59-year-old male patient who presented with cough with sputum,shortness of breath and fever for 13 d.A chest computed tomography radiograph revealed bilateral diffuse ground-glass infiltrates in both upper fields,left lingual lobe and right middle lobe.Initially,the patient was diagnosed with severe community-acquired pneumonia and respiratory failure.He was empirically treated with broad-spectrum antibiotics,without improvement.Further analysis showed an ASS panel with anti-PL7 antibodies.Besides,electromyography evaluation demonstrated a manifestation of myogenic damage,while deltoid muscle biopsy showed irregular muscle fiber bundles especially abnormal lymphocyte infiltration.In addition,bone marrow biopsy revealed high invasive B cell lymphoma.Thus,the patient was diagnosed with a relatively rare anti–PL7 antibody positive ASS associated with B cell lymphoma.CONCLUSION This case highlights that rapidly progressive lung lesions and acute hypoxemic respiratory failure associated with heliotrope rash and extremely high lactate dehydrogenase level should be considered as the characteristics of non-infectious diseases,especially ASS and B cell lymphoma.展开更多
Globally,a shift in the epidemiology of chronic liver disease has been observed.This has been mainly driven by a marked decline in the prevalence of chronic hepatitis B virus infection(CHB),with the greatest burden re...Globally,a shift in the epidemiology of chronic liver disease has been observed.This has been mainly driven by a marked decline in the prevalence of chronic hepatitis B virus infection(CHB),with the greatest burden restricted to the Western Pacific and sub-Saharan African regions.Amidst this is a growing burden of metabolic syndrome(MetS)worldwide.A disproportionate co-burden of human immunodeficiency virus(HIV)infection is also reported in sub-Saharan Africa,which poses a further risk of liver-related morbidity and mortality in the region.We reviewed the existing evidence base to improve current understanding of the effect of underlying MetS on the development and progression of chronic liver disease during CHB and HIV co-infection.While the mechanistic association between CHB and MetS remains poorly resolved,the evidence suggests that MetS may have an additive effect on the liver damage caused by CHB.Among HIV infected individuals,MetS-associated liver disease is emerging as an important cause of non-AIDS related morbidity and mortality despite antiretroviral therapy(ART).It is plausible that underlying MetS may lead to adverse outcomes among those with concomitant CHB and HIV co-infection.However,this remains to be explored through rigorous longitudinal studies,especially in sub-Saharan Africa.Ultimately,there is a need for a comprehensive package of care that integrates ART programs with routine screening for MetS and promotion of lifestyle modification to ensure an improved quality of life among CHB and HIV coinfected individuals.展开更多
Objective:To evaluate the potential effect of human Wharton’s jelly mesenchymal stem cells(hWJMSCs)on acute respiratory distress syndrome in lipopolysaccharide(LPS)-induced rats.Methods:The hWJMSCs(5×10^(4)/mL,5...Objective:To evaluate the potential effect of human Wharton’s jelly mesenchymal stem cells(hWJMSCs)on acute respiratory distress syndrome in lipopolysaccharide(LPS)-induced rats.Methods:The hWJMSCs(5×10^(4)/mL,5×10^(5)/mL,5×10^(6)/mL)were administered to rats on day 1 and day 8 after being induced by LPS(5 mg/kg body weight).TNF-αlevels in the lung and IL-18 and IL-1βlevels in the serum were measured using ELISA.In addition,caspase-1 expression in lung tissues was quantified using qRT-PCR,and NF-κB and IL-6 expressions were assessed using immunohistochemistry.Results:The hWJMSCs decreased TNF-αlevels in the lung and plasma IL-18 and IL-1βlevels.Moreover,the hWJMSCs downregulated the expressions of caspase-1,IL-6,and NF-κB in lung tissues.Conclusions:The hWJMSCs can decrease inflammatory markers of acute respiratory distress syndrome in a rat model and may be further investigated for the treatment of acute respiratory distress syndrome.展开更多
BACKGROUND The VPS33B(OMIM:608552)gene is located on chromosome 15q26.1.We found a female infant with autosomal recessive arthrogryposis,renal dysfunction and cholestasis syndrome 1(ARCS1)caused by mutation in VPS33B....BACKGROUND The VPS33B(OMIM:608552)gene is located on chromosome 15q26.1.We found a female infant with autosomal recessive arthrogryposis,renal dysfunction and cholestasis syndrome 1(ARCS1)caused by mutation in VPS33B.The child was diagnosed with ARCS1(OMIM:208085)after the whole exome sequencing revealed two heterozygous mutations(c.96+1G>C,c.242delT)in the VPS33B gene.CASE SUMMARY We report a Chinese female infant with neonatal cholestasis disorder,who was eventually diagnosed with ARCS1 by genetic analysis.Genetic testing revealed two new mutations(c.96+1G>C and c.242delT)in VPS33B,which is the causal gene.The patient was compound heterozygous,and her parents were both heterozygous.CONCLUSION This study extends the mutational spectrum of the VPS33B gene to provide a molecular basis for the etiological diagnosis of ARCS1 and for genetic counseling of the family.展开更多
基金grants from the National Natural Science Foundation of China(82274454).
文摘Background:Ziwan and Taoren(ZT)is a classic medicine pair in the formula of Mai Dong Di Shao Decoction,has been used to treat primary Sjogren’s syndrome(pSS)for more than 20 years.But its action mechanism is still unknown.This study is aimed to reveal the potential mechanism of ZT treated pSS and discover its active compounds of ZT and therapeutic target for pSS.Methods:Firstly,the potential pathways of ZT for pSS treatment were predicted through network pharmacology and GO and KEGG enrichment analysis.Secondly,the inter-structural relationships between active compounds of ZT and target proteins were visualized using molecular docking techniques.Finally,efficacy and mechanism were conducted through in vivo experiments,such as water intake,spleen index,hematoxylin-eosin staining pathological changes,ELISA,Western Blot analysis,and immunofluorescence staining.Results:Nine active compounds were extracted from network pharmacology,including quercitrin,luteolin,kaempferol,β-sitosterol,isorhamnetin,galangin,hederagenin,diosmetin and gibberellin 7.Seven disease targets were identified:RELA,TP53,AKT1,interleukin(IL)6,MAPK1,ESR1,IL10;with RELA being the most core target.KEGG and GO enrichment analysis indicated that ZT may act through the TLR/NF-κB/RELA inflammatory mechanism process.preliminary results of molecular docking showed that ZT’s active compounds bind well to the RELA(p65)receptor.In vivo results demonstrated that a high dose of ZT significantly improved water intake and reduced lymphocytes infiltration in submandibular gland pathology in NOD mice.The expression content of AQP5 and vasoactive intestinal peptide in the submaxillary gland was significantly increased,while levels of inflammatory factors such as tumor necrosis factor-α,IL-6,and IL-1βalong with protein expressions including toll-like receptor4,p-p65 and p-IKKα/βin NF-κB pathway were reduced.Conclusions:The ZT treatment exhibits a promising efficacy in mitigating dryness symptoms of pSS,potentially attributed to its capacity for suppressing the TLR/NF-κB inflammatory signaling pathway.
基金The Health Commission of Jinshan District,Shanghai,China,No.JSKJ-KTMS-2019-01The Youth Research Foundation of Jinshan Hospital of Fudan University,No.JYQN-JC-202101 and No.JYQN-JC-202216The Reserve Discipline Construction of Jinshan Hospital of Fudan University,No.HBXK-2021-2.
文摘BACKGROUND Serotonin receptor 2B(5-HT2B receptor)plays a critical role in many chronic pain conditions.The possible involvement of the 5-HT2B receptor in the altered gut sensation of irritable bowel syndrome with diarrhea(IBS-D)was investigated in the present study.AIM To investigate the possible involvement of 5-HT2B receptor in the altered gut sensation in rat model and patients with IBS-D.METHODS Rectosigmoid biopsies were collected from 18 patients with IBS-D and 10 patients with irritable bowel syndrome with constipation who fulfilled the Rome IV criteria and 15 healthy controls.The expression level of the 5-HT2B receptor in colon tissue was measured using an enzyme-linked immunosorbent assay and correlated with abdominal pain scores.The IBS-D rat model was induced by intracolonic instillation of acetic acid and wrap restraint.Alterations in visceral sensitivity and 5-HT2B receptor and transient receptor potential vanilloid type 1(TRPV1)expression were examined following 5-HT2B receptor antagonist adminis-tration.Changes in visceral sensitivity after administration of the TRPV1 antago-INTRODUCTION Irritable bowel syndrome(IBS)is a chronic functional bowel disorder characterized by recurrent abdominal pain with altered bowel habits that affects approximately 15%of the population worldwide[1].IBS significantly impacts the quality of life of patients.Although the pathogenesis of IBS is not completely understood,the role of abnormal visceral sensitivity in IBS has recently emerged[2,3].5-Hydroxytryptamine(5-HT)is known to play a key role in the physiological states of the gastrointestinal tract.Plasma 5-HT levels in IBS with diarrhea(IBS-D)patients were greater than those in healthy controls[4],suggesting a possible role of 5-HT in the pathogenesis of IBS-D.The serotonin receptor 2(5-HT2 receptor)family comprises three subtypes:5-HT2A,5-HT2B,and 5-HT2c.All 5-HT2 receptors exhibit 46%-50%overall sequence identity,and all of these receptors preferentially bind to Gq/11 to increase inositol phosphates and intracellular calcium mobilization[5].5-HT2B receptors are widely expressed throughout the gut,and experimental evidence suggests that the primary function of 5-HT2B receptors is to mediate contractile responses to 5-HT through its action on smooth muscle[6].The 5-HT2B receptor is localized to both neurons of the myenteric nerve plexus and smooth muscle in the human colon.The 5-HT2B receptor mediates 5-HT-evoked contraction of longitudinal smooth muscle[6].These findings suggest that the 5-HT2B receptor could play an important role in modulating colonic motility,which could affect sensory signaling in the gut.Other laboratories have shown that the 5-HT2B receptor participates in the development of mechanical and formalin-induced hyperalgesia[7,8].A 5-HT2B receptor antagonist reduced 2,4,6-trinitrobenzene sulfonic acid(TNBS)and stress-induced visceral hyperalgesia in rats[9,10].However,the role of the 5-HT2B receptor in IBS-D patients and in acetic acid-and wrap restraint-induced IBS-D rat models was not investigated.
基金National Natural Science Foundation of China(81503280,81573549)Key Industry Innovation Chain(Cluster)Foundation of Shaanxi Province(2022ZDLSF05-04).
文摘Background:Shengxuebao mixture(SXBM)is a novel herbal drug approved by China State Food and Drug Administration for the treatment of Leukopenia and iron deficiency anemia caused by radiotherapy and chemotherapy.Methods:To explore the mechanism of SXBM in treating blood deficiency syndrome(BDS).Firstly,network pharmacology and in vivo experiments were used to screen candidate targets and important signaling pathways of SXBM,GO functional enrichment and KEGG pathway analysis were performed.Secondly,a BDS rat model was established to verify the results of the analysis of network pharmacological enrichment.Histopathology and routine peripheral blood examination were observed.The expressions of tumor necrosis factor-α,interleukin(IL)-6,HIF-1αand NF-κB were detected by Western blot,and the expressions of IL-6,IL-1βwere detected by ELISA.Results:62 bioactive components,66 potential targets and 131 signaling pathways of BDS were successfully identified by network pharmacology.Molecular docking simulation techniques showed that key targets tumor necrosis factor-α,IL-6,IL-1βcan dock well with crucial components,and the BDS-related signaling pathways HIF-1 and JAK-STAT play a vital role.The combined model experiment of acetylphenylhydrazine and cyclophosphamide showed that the model group had obvious blood deficiency,and the histopathology and blood routine were effectively restored after administration.Our findings indicate that SXBM’s therapeutic effect on BDS primarily involves the mediation of the HIF-1α/NF-κB signaling pathway and the regulation of hematopoietic factor expression.Conclusion:This study not only affirmed the protective properties of SXBM against BDS but also provided insights into a potential mechanism for blood replenishment in the treatment of BDS using SXBM.
文摘Chronic hepatitis B(CHB)is a global health issue that increases the risk of liver cirrhosis and hepatocellular carcinoma in infected patients.Metabolic syndrome(Met S)is a disease endemic mostly to the developed countries.It is associated with high cardiovascular mortality and morbidity,diabetes mellitus as well as cancer.In this manuscript,we systematically review the published data on the relationship between Met S and CHB infection.Multiple studies have described highly variable correlations between CHB on one hand and Met S,non-alcoholic fatty liver disease and dyslipidemia on the other.No association between CHB and diabetes mellitus or atherosclerosis has been described as of now.The presence of Met S in patients infected with hepatitis B virus increases the risk of fibrosis,cirrhosis and hepatocellular carcinoma.Appropriate lifestyle,but also pharmacological interventions are needed to prevent the development of these complications.
基金Supported by National Natural Science Foundation of China,No.81230024,No.81471137(to GYX)and No.31400947(to HHZ)Priority Academic Program Development of Jiangsu Higher Education Institutions
文摘AIM:To investigate the roles of toll-like receptor 4(TLR4) and nuclear factor(NF)-κB on cystathionine βsynthetase(CBS) expression and visceral hypersensitivity in rats.METHODS:This study used 1-7-wk-old male SpragueDawley rats.Western blot analysis was employed to measure the expression of TLR4,NF-kB and the endogenous hydrogen sulfide-producing enzyme CBS in colon dorsal root ganglia(DRG) from control and "irritable bowel syndrome" rats induced by neonatal colonic inflammation(NCI).Colon-specific DRG neurons were labeled with Dil and acutely dissociated to measure excitability with patch-clamp techniques.Immunofluorescence was employed to determine the co-expression of TLR4,NF-kB and CBS in Dil-labeled DRG neurons.RESULTS:NCI significantly upregulated the expression of TLR4 in colon-related DRGs(0.34 ± 0.12 vs 0.72 ±0.02 for the control and NCI groups,respectively,P <0.05).Intrathecal administration of the TLR4-selective inhibitor CLI-095 significantly enhanced the colorectal distention threshold of NCI rats.CLI-095 treatment also markedly reversed the hyperexcitability of colonspecific DRG neurons and reduced the expression of CBS(1.7 ± 0.1 vs 1.1 ± 0.04,p < 0.05) and of the NF-kB subunit p65(0.8 ± 0.1 vs 0.5 ± 0.1,P< 0.05).Furthermore,the NF-KB-selective inhibitor pyrrolidine dithiocarbamate(PDTC) significantly reduced the upregulation of CBS(1.0 ± 0.1 vs 0.6 ± 0.1,P< 0.05)and attenuated visceral hypersensitivity in the NCI rats.In vitro,incubation of cultured DRG neurons with the TLR4 agonist lipopolysaccharide significantly enhanced the expression of p65(control vs 8 h:0.9 ± 0.1 vs1.3 ± 0.1;control vs 12 h:0.9 ± 0.1 vs 1.3 ± 0.1,P< 0.05;control vs 24 h:0.9 ± 0.1 vs 1.6 ± 0.1,P <0.01) and CBS(control vs 12 h:1.0 ± 0.1 vs 2.2 ±0.4;control vs 24 h:1.0 ± 0.1 vs 2.6 ± 0.1,P< 0.05),whereas the inhibition of p65 via pre-incubation with PDTC significantly reversed the upregulation of CBS expression(1.2 ± 0.1 vs 0.6 ± 0.0,P< 0.01).CONCLUSION:Our results suggest that the activation of TLR4 by NCI upregulates CBS expression,which is mediated by the NF-kB signaling pathway,thus contributing to visceral hypersensitivity.
文摘The present study aimed to investigate the clinical value of serum anti-mullerian hormone(AMH) and inhibin B(INHB) in predicting the ovarian response of patients with polycystic ovary syndrome(PCOS). A total of 120 PCOS patients were enrolled and divided into three groups in terms of the ovarian response: a low-response group(n=36), a normal-response group(n=44), and a high-response group(n=40). The serum AMH and INHB levels were measured by enzyme-linked immunosorbent assay(ELISA). The follicle stimulating hormone(FSH), luteinizing hormone(LH), and estradiol(E2) levels were determined by chemiluminescence microparticle immunoassay. The correlation of the serum AMH and INHB levels with other indicators was analyzed. A receiver operating characteristic(ROC) curve was established to analyze the prediction of ovarian response by AMH and INHB. The results showed that there were significant differences in age, body mass index(BMI), FSH, total gonadotropin-releasing hormone(Gn RH), LH, E2, and antral follicle counts(AFCs) between the groups(P〈0.05). The serum AMH and INHB levels were increased significantly with the ovarian response of PCOS patients increasing(P〈0.05). The serum AMH and INHB levels were negatively correlated with the age, BMI, FSH level, Gn, and E2 levels(P〈0.05). They were positively correlated with the LH levels and AFCs(P〈0.05). ROC curve analysis of serum AMH and INHB in prediction of a low ovarian response showed that the area under the ROC curve(AUC) value of the serum AMH level was 0.817, with a cut-off value of 1.29 ng/m L. The sensitivity and specificity were 71.2% and 79.6%, respectively. The AUC value of serum INHB was 0.674, with a cut-off value of 38.65 ng/m L, and the sensitivity and specificity were 50.7% and 74.5%, respectively. ROC curve analysis showed when the serum AMH and INHB levels were used to predict a high ovarian response, the AUC value of the serum AMH level was 0.742, with a cut-off value of 2.84 ng/m L, and the sensitivity and specificity were 72.7% and 65.9%, respectively; the AUC value of the serum INHB level was 0.551 with a cut-off of 45.76 ng/m L, and the sensitivity and specificity were 76.3% and 40.2%, respectively. It was suggested the serum AMH and INHB levels have high clinical value in predicting the ovarian response of PCOS patients.
基金financially supported by the Major Program of Guangdong Basic and Applied Research,China(2019B030302006)the National Natural Science Foundation of China(31801377)the funding from the State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources,China(SKLCUSA-b201801)。
文摘Increasing the planting density of maize is an effective measure to improve its yield.However,plants under high planting density tend to trigger shade avoidance syndrome(SAS),reducing lodging resistance and ultimately yield drop.Phytochrome B(phyB)plays a dominant role in mediating shade avoidance response.This study constructed two hyperactive mutated alleles of maize PHYB1:ZmPHYB1^(Y98F)(mimicking Y104F of AtPHYB)and ZmPHYB1^(Y359F)(mimicking Y361F of AtPHYB).Ectopic expression of ZmPHYB1^(Y98F) and ZmPHYB1^(Y359F) under the control of the ZmPHYB1 promoter in the Arabidopsis phyB-9 background rendered enhanced activity on complementing the phyB-9 related phenotypes compared with ZmPHYB1^(WT).Moreover,similar to the behavior of ZmPHYB1^(WT),ZmPHYB1Y98F and ZmPHYB1^(Y359F) proteins are localized to the nucleus after red light exposure,and could interact with PIF proteins of maize.In addition,expression of ZmPHYB1^(Y98F) and ZmPHYB1^(Y359F) variants under the control of the native ZmPHYB1 promoter attenuated SAS of maize seedlings subjected to simulated shade treatment.It effectively reduced mature maize’s plant height and ear height in field conditions.The results combined demonstrate the utility of ZmPHYB1^(Y98F) and ZmPHYB1^(Y359F) for attenuating SAS and breeding high density-tolerant varieties of maize.
基金Natural Science Foundation Project of Anhui Province,No.1708085QH218。
文摘BACKGROUND Budd-Chiari syndrome(BCS)is an uncommon disorder characterized by obstruction of hepatic venous outflow.To date,the exact mechanism underlying hepatic injury derived from the hepatic venous outflow obstruction in BCS remains largely unknown.AIM To assess the role of NF-κB-mediated inflammation in BCS-induced liver injury in humans and rats.METHODS A total of 180 rats were randomly assigned into nine groups,including four BCS model groups(1,3,6 and 12 wk),four sham-operated groups(1,3,6 and 12 wk),and a control group.Lipopolysaccharide(LPS)levels in each group were detected by the Tachypleus Amebocyte Lysate assay.The mRNA and protein levels of TLR4,NF-κB,tumor necrosis factor(TNF)-α,interleukin(IL)-2 and interferon(IFN)-γwere quantified.In addition,60 patients with BCS and 30 healthy controls were enrolled,and their blood samples were analyzed.RESULTS Hepatic and plasma LPS levels were significantly increased in rats.The mRNA and protein expression levels of TLR4,NF-κB and inflammatory cytokines(TNF-α,IL-2 and IFN-γ)in liver tissues were significantly higher in the BCS model groups compared with the other two groups.In addition,the model groups(1,3,6 and 12 wk after BCS induction)showed significant differences in the levels of LPS,TLR4,NF-κB,TNF-α,IL-2 and IFN-γ.Notably,there was a significant correlation between the LPS concentrations and mRNA and protein levels of TLR4,NF-κB and inflammatory cytokines.Importantly,it was revealed that the levels of LPS,TLR4,NF-κB and inflammatory cytokines were significantly greater in chronic BCS patients than healthy controls and acute BCS patients.CONCLUSION LPS level is markedly elevated in BCS,in turn activating the TLR4/NF-κB signaling pathway,leading to induction of inflammatory cytokines(TNF-α,IL-2 and IFN-γ)in response to BCS-induced liver injury.
基金supported by a grant from Clinical Scientific Research of Wuhan Sanitary Bureau(No.WX11C26)research fund from Janssen Research Council of China(No.JRCC2011-01)
文摘Previous studies have demonstrated a strong association between carbamazepine(CBZ)-induced Stevens-Johnson syndrome(SJS) and HLA-B 1502 in Han Chinese. Here, we extended the study of HLA-B 1502 susceptibility to two different antiepileptic drugs, oxcarbazepine(OXC) and phenobabital(PB). In addition, we genotyped HLA-B 1511 in a case of CBZ-induced SJS with genotype negative for HLA-B 1502. The presence of HLA-B 1502 was determined using polymerase chain reaction with sequence-specific primers(PCR-SSP). Moreover, we genotyped HLA-B 1502 in 17 cases of antiepileptic drugs(AEDs)-induced cutaneous adverse drug reactions(cADRs), in comparison with AEDs-tolerant(n=32) and normal controls(n=38) in the central region of China. The data showed that HLA-B 1502 was positive in 5 of 6 cases of AEDs-induced SJS(4 CBZ, 1 OXC and 1 PB), which was significantly more frequent than AEDs-tolerant(2/32, 18 CBZ, 6 PB and 8 OXC) and normal controls(3/38). Compared with AEDs-tolerant and normal controls, the OR for patients carrying the HLA-B 1502 with AEDs-induced SJS was 6.25(95% CI: 1.06–36.74) and 4.86(95% CI: 1.01–23.47). The sensitivity and specificity of HLA-B 1502 for prediction of AEDs-induced SJS were 71.4%. The sensitivity and specificity of HLA-B 1502 for prediction of CBZ-induced SJS were 60% and 94%. HLA-B 1502 was not found in 11 children with maculopapular exanthema(MPE)(n=9) and hypersensitivity syndrome(HSS)(n=2). However, we also found one case of CBZ-induced SJS who was negative for HLA-B 1502 but carried HLA-B 1511. It was suggested that the association between the CBZ-induced SJS and HLA-B 1502 allele in Han Chinese children can extend to other aromatic AEDs including OXC and PB related SJS. HLA-B 1511 may be a risk factor for some patients with CBZ-induced SJS negative for HLA-B 1502.
基金Supported by Zhejiang Provincial Natural Science Foundation,No.Y2080047funds for Zhejiang Major Medical and Health Science and Technology Program+2 种基金 funds from Ministry of Health,No.WKJ2008-2-026Major Special Zhejiang Provincial Science and Technology Fund,No.2008c03002-1the National Key Technology R&D Program of China,No.2009BAI80B01
文摘AIM:To investigate if non-alcoholic fatty liver disease (NAFLD) is an early mediator for prediction of metabolic syndrome,and if liver B-ultrasound can be used for its diagnosis.METHODS:We classified 861 obese children (6-16 years old) into three subgroups:group 0 (normal liver in ultrasound and normal transaminases);group 1 (fatty liver in ultrasound and normal transaminases);and group 2 (fatty liver in ultrasound and elevated transaminases).We measured the body mass index,waist and hip circumference,blood pressure,fasting blood glucose,insulin,homeostasis model assessment of insulin resistance (HOMA-IR),whole-body insulin sensitivity index (WBISI),lipid profile and transaminases in all the participants.The risk of developing metabolic syndrome (MS) was assessed according to the degree of liver fatty infiltration based on the B-ultrasound examination.RESULTS:Among the 861 obese children,587 (68.18%) were classified as having NAFLD,and 221 (25.67%) as having MS.The prevalence of MS in NAFLD children (groups 1 and 2) was 37.64% (221/587),which was much higher than that in non-NAFLD group (group 0,12.04%) (P < 0.01).There were significantly higher incidences concerning every component of MS in group 2 compared with group 0 (P < 0.05).The incidence of NAFLD in MS patients was 84.61% (187/221),which was significantly higher than that of hypertension (57.46%,127/221) and glucose metabolic anomalies (22.62%,50/221),and almost equal to the prevalence of dyslipidemia (89.14%,197/221).Based on the B-ultrasound scales,the presence of moderate and severe liver fatty infiltration carried a high risk of hypertension [odds ratio (OR):2.18,95% confidence interval (95% CI):1.27-3.75],dyslipidemia (OR:7.99,95% CI:4.34-14.73),impaired fasting glucose (OR:3.65,95% CI:1.04-12.85),and whole MS (OR:3.77;95% CI:1.90-7.47,P < 0.01).The state of insulin resistance (calculated by HOMA-IR and WBISI) deteriorated as the degree of fatty infiltration increased.CONCLUSION:NAFLD is not only a liver disease,but also an early mediator that reflects metabolic disorder,and liver B-ultrasound can be a useful tool for MS screening.
基金Supported by National Natural Science Foundation of China,No.81900020Natural Science Foundation of Zhejiang Province,China,No.LQ19H160020.
文摘BACKGROUND Antisynthetase syndrome(ASS)is characterized by the presence of antisynthetase antibodies coupled with clinical findings such as fever,polymyositis-dermatomyositis and interstitial lung disease.It is,however,rare to observe ASS association with B cell lymphoma presenting severe pneumonia as the first clinical manifestation.CASE SUMMARY We evaluated a 59-year-old male patient who presented with cough with sputum,shortness of breath and fever for 13 d.A chest computed tomography radiograph revealed bilateral diffuse ground-glass infiltrates in both upper fields,left lingual lobe and right middle lobe.Initially,the patient was diagnosed with severe community-acquired pneumonia and respiratory failure.He was empirically treated with broad-spectrum antibiotics,without improvement.Further analysis showed an ASS panel with anti-PL7 antibodies.Besides,electromyography evaluation demonstrated a manifestation of myogenic damage,while deltoid muscle biopsy showed irregular muscle fiber bundles especially abnormal lymphocyte infiltration.In addition,bone marrow biopsy revealed high invasive B cell lymphoma.Thus,the patient was diagnosed with a relatively rare anti–PL7 antibody positive ASS associated with B cell lymphoma.CONCLUSION This case highlights that rapidly progressive lung lesions and acute hypoxemic respiratory failure associated with heliotrope rash and extremely high lactate dehydrogenase level should be considered as the characteristics of non-infectious diseases,especially ASS and B cell lymphoma.
文摘Globally,a shift in the epidemiology of chronic liver disease has been observed.This has been mainly driven by a marked decline in the prevalence of chronic hepatitis B virus infection(CHB),with the greatest burden restricted to the Western Pacific and sub-Saharan African regions.Amidst this is a growing burden of metabolic syndrome(MetS)worldwide.A disproportionate co-burden of human immunodeficiency virus(HIV)infection is also reported in sub-Saharan Africa,which poses a further risk of liver-related morbidity and mortality in the region.We reviewed the existing evidence base to improve current understanding of the effect of underlying MetS on the development and progression of chronic liver disease during CHB and HIV co-infection.While the mechanistic association between CHB and MetS remains poorly resolved,the evidence suggests that MetS may have an additive effect on the liver damage caused by CHB.Among HIV infected individuals,MetS-associated liver disease is emerging as an important cause of non-AIDS related morbidity and mortality despite antiretroviral therapy(ART).It is plausible that underlying MetS may lead to adverse outcomes among those with concomitant CHB and HIV co-infection.However,this remains to be explored through rigorous longitudinal studies,especially in sub-Saharan Africa.Ultimately,there is a need for a comprehensive package of care that integrates ART programs with routine screening for MetS and promotion of lifestyle modification to ensure an improved quality of life among CHB and HIV coinfected individuals.
基金the Ministry of Research,Technology and Higher Education of the Republic of Indonesia(Penelitian Terapan Unggulan Perguruan Tinggi,2022).
文摘Objective:To evaluate the potential effect of human Wharton’s jelly mesenchymal stem cells(hWJMSCs)on acute respiratory distress syndrome in lipopolysaccharide(LPS)-induced rats.Methods:The hWJMSCs(5×10^(4)/mL,5×10^(5)/mL,5×10^(6)/mL)were administered to rats on day 1 and day 8 after being induced by LPS(5 mg/kg body weight).TNF-αlevels in the lung and IL-18 and IL-1βlevels in the serum were measured using ELISA.In addition,caspase-1 expression in lung tissues was quantified using qRT-PCR,and NF-κB and IL-6 expressions were assessed using immunohistochemistry.Results:The hWJMSCs decreased TNF-αlevels in the lung and plasma IL-18 and IL-1βlevels.Moreover,the hWJMSCs downregulated the expressions of caspase-1,IL-6,and NF-κB in lung tissues.Conclusions:The hWJMSCs can decrease inflammatory markers of acute respiratory distress syndrome in a rat model and may be further investigated for the treatment of acute respiratory distress syndrome.
基金Supported by the Hainan Province Clinical Medical Center,No.(2021)75 and(2021)276。
文摘BACKGROUND The VPS33B(OMIM:608552)gene is located on chromosome 15q26.1.We found a female infant with autosomal recessive arthrogryposis,renal dysfunction and cholestasis syndrome 1(ARCS1)caused by mutation in VPS33B.The child was diagnosed with ARCS1(OMIM:208085)after the whole exome sequencing revealed two heterozygous mutations(c.96+1G>C,c.242delT)in the VPS33B gene.CASE SUMMARY We report a Chinese female infant with neonatal cholestasis disorder,who was eventually diagnosed with ARCS1 by genetic analysis.Genetic testing revealed two new mutations(c.96+1G>C and c.242delT)in VPS33B,which is the causal gene.The patient was compound heterozygous,and her parents were both heterozygous.CONCLUSION This study extends the mutational spectrum of the VPS33B gene to provide a molecular basis for the etiological diagnosis of ARCS1 and for genetic counseling of the family.