Search

The anti-apoptotic and pro-survival effects of exercise training were evaluated on the early aged hypertensive rat cerebral cortex. The brain tissues were analysed from ten sedentary male Wistar Kyoto normotensive rats (WKY), ten sedentary spontaneously 12 month early aged hypertensive rats (SHR), and ten hypertensive rats undergoing treadmill exercise training (60 min/day, 5 days/week) for 12 weeks (SHR-EX). TUNEL-positive apoptotic cells, the expression levels of endonuclease G (EndoG) and apoptosis-inducing factor (AIF) (caspase-independent apoptotic pathway), Fas ligand, Fas death receptor, tumor necrosis factor (TNF)-α, TNF receptor 1, Fas-associated death domain, active caspase-8 and active caspase-3 (Fas-mediated apoptotic pathways) as well as t-Bid, Bax, Bak, Bad, cytochrome c, active caspase 9 and active caspase-3 (mitochondria-mediated apoptotic pathways) were reduced in SHR-EX compared with SHR. Pro-survival Bcl2, Bcl-xL, p-Bad, 14-3-3, insulin-like growth factor (IGF)-1, pPI3K/PI3K, and pAKT/AKT were significantly increased in SHR-EX compared to those in SHR. Exercise training suppressed neural EndoG/AIF-related caspase-independent, Fas/FasL-mediated caspase-dependent, mitochondria-mediated caspase-dependent apoptotic pathways as well as enhanced Bcl-2 family-related and IGF-1-related pro-survival pathways in the early aged hypertensive cerebral cortex. These findings indicated new therapeutic effects of exercise training on preventing early aged hypertension-induced neural apoptosis in cerebral cortex.

Objectives : To explore the associations of FKBP4 and FKBP5 gene polymorphisms with disease susceptibility, glucocorticoid (GC) efficacy, anxiety, depression, and health-related quality of life (HRQOL) in systemic lupus erythematosus (SLE) patients. Methods : All subjects were collected from the First and the Second Affiliated Hospital of Anhui Medical University in Hefei, China, during 2011 to 2015. In the case–control study, 541 SLE patients and 543 controls were recruited. In the follow-up study, 466 patients completed the 12-week follow-up and then were divided into GC-sensitive and GC-insensitive groups. Genotyping was determined using Multiplex SNaPshot technique. Data were analyzed using chi-square test and univariate and multivariate logistic regression analyses. Results : rs4713904, rs9368878, and rs7757037 of FKBP5 were associated with depression in SLE patients (rs4713904, PBH = 0.037; rs9368878, PBH = 0.001; rs7757037, PBH = 0.003). Moreover, rs4713904 was associated with GC efficacy in males with SLE (PBH = 0.011). The rs755658 of FKBP5 was associated with improvement in social function (PBH = 0.022) and mental component summary (PBH = 0.028). The rs4713907 of FKBP5 was related to improvement in total score of SF-36, bodily pain, and mental component summary score (all PBH = 0.018). Furthermore, the rs12582595 of FKBP4 was correlated with general health improvement (PBH = 0.033). No associations were seen between FKBP4/FKBP5 gene polymorphisms and SLE susceptibility and anxiety. Conclusions : FKBP5 gene polymorphisms may be associated with depression and GC efficacy of SLE patients. Meanwhile, the genetic polymorphisms of FKBP4 and FKBP5 genes may be associated with HRQOL improvement in SLE patients.Key Points• FKBP5 gene polymorphisms were associated with depression of SLE patients.• FKBP5 gene polymorphisms were associated with GC efficacy of SLE patients.• FKBP5 gene polymorphisms were associated with HRQOL improvement in SLE patients.• FKBP4 gene polymorphisms were associated with HRQOL improvement in SLE patients.

To evaluate the clinical efficacy and safety of Shugan Jieyu Capsules,Jieyu Pills and Xiaoyao Pills in the treatment of liver-stagnation and spleen-deficiency depression by the network Meta-analysis( NMA),so as to provide evidence-based clinical practice. Chinese databases,including CNKI,VIP,Wan Fang Data,CBM as well as English databases including the Cochrane Library,PubMed,EMbase and Web of Science were retrieved from inception to October 30,2018,to collect randomized controlled trials( RCTs) about clinical study of the three kinds of Chinese patent medicines. The quality and bias risk of the included studies were assessed by 5. 1 standard in Cochrane Handbook,ADDIS software was applied in the statistical analysis,and the result were compared by NMA. A total of 37 studies involving 3 105 patients were included. The results of NMA showed that the adjuvant therapy with the three kinds of traditional Chinese patent medicines could improve the clinical efficacy. Jieyu Pills had the most significant effect( OR = 4. 59,95%CI[1. 94,12. 71],Plt;0. 05). In HAMD,Shugan Jieyu Capsules( MD = 3. 22,95%CI[2. 07,4. 39],Plt; 0. 05) and Xiaoyao Pills( MD= 2. 23,95%CI[0. 41,4. 03],Plt;0. 05) can effectively reduce the depression scale indicators. In the incidence of adverse reactions,the three kinds of Chinese patent medicines can reduce the incidence of adverse reactions. The three kinds of Chinese patent medicines can be combined with auxiliary Western medicine to treat liver-stagnation and spleen-deficiency depression,with complementary advantages in action mechanisms. In the clinical efficacy and safety,the Chinese patent medicines had good clinical manifestations. Although this study showed that Jieyu Pills may be the referred medicine for depression,this conclusion is still immature and needs to be further verified by high-quality RCTs studies,and the application shall be selective based on specific characteristics in clinic.

Although the current glucocorticoids (GCs) treatment for systemic lupus erythematosus (SLE) is effective to a certain extent, the difference in therapeutic effect between patients is still a widespread problem. Some patients can have repeated attacks that greatly diminish their quality of life. This study was conducted to investigate the relationship between HSP90AA2 polymorphisms and disease susceptibility, GCs efficacy and health-related quality of life (HRQoL) in Chinese SLE patients. A case-control study was performed in 470 SLE patients and 470 normal controls. Then, 444 patients in the case group were followed up for 12 weeks to observe efficacy of GCs and improvement of HRQoL. Two single nucleotide polymorphisms (SNPs) of HSP90AA2 were selected for genotyping: rs1826330 and rs6484340. HRQoL was assessed using the SF-36 questionnaire. The minor T allele of rs1826330 and the TT haplotype formed by rs1826330 and rs6484340 showed associations with decreased SLE risk (T allele: PBH = 0.022; TT haplotype: PBH = 0.033). A significant association between rs6484340 and improvement of HRQoL was revealed in the follow-up study. Five subscales of SF-36 were appeared to be influenced by rs6484340: total score of SF-36 (additive model: PBH = 0.026), physical function (additive model: PBH = 0.026), role-physical (recessive model: PBH = 0.041), mental health (dominant model: PBH = 0.047), and physical component summary (additive model: PBH = 0.026). No statistical significance was found between HSP90AA2 gene polymorphisms and GCs efficacy. These results revealed a genetic association between HSP90AA2 and SLE. Remarkably, HSP90AA2 has an impact on the improvement of HRQoL in Chinese population with SLE.

Interleukin (IL)-15 is an important inflammatory cytokine and plays a key role in autoimmune disease. At present, IL-15 gene expression and regulation related to many innate immunity trigger signals have been clarified in some specific cell types, but the relationship of IL-6 and IL-15 in the human keratinocyte cell line (HaCaT) is unknown. In this study, we investigated the effect of IL-6 on the expression of IL-15 and selected signaling pathways in HaCaT cells. Results demonstrated that IL-6 up-regulated the expression of IL-15 both at the mRNA and protein levels. Meanwhile, IL-6 was able to activate MAPKs-ERK1/2 and PI3K-AKT signaling pathways. Furthermore, the high expression of IL-15 induced by IL-6 was down-regulated while MAPKs-ERK1/2 and PI3K-AKT signaling pathways were, respectively, blocked by PD98059 and LY294002. These findings indicate that the expression of IL-15 up-regulated by IL-6 is associated with MAPKs-ERK1/2 and PI3K-AKT signaling pathways in HaCaT cells.

Background Supraglottic jet ventilation (SJV) via the "jet endotracheal tube" (JET) designed by Wei (WEI JET; Wei Medical LLC, Cherry Hill, NJ) provides adequate oxygenation and ventilation during direct laryngoscopy and tracheal intubation in animals. It has facilitated intubation in apneic pigs with a simulated difficult airway. Objective To report on the first clinical study to examine the efficacy of using SJV via the WEI JET, in combination with end-tidal CO 2 pressure (PetCO 2 ) monitoring during SJV, in maintaining oxygenation during direct laryngoscopy, and in facilitating placement of the WEI JET, and comparing it to the standard intubation technique using a conventional endotracheal tube. The relative safety of using SJV via the WEI JET in airway management was also addressed to provide the foundation for a larger-scale clinical study using the WEI JET, to be carried out in the future. Methods Patients in the control group were intubated with a conventional endotracheal tube, and patients in the experimental group were intubated with a WEI JET. The effectiveness of SJV through a WEI JET in maintaining proper oxygenation, and the use of PetCO 2 monitoring to facilitate intubation, were studied and compared to the control group. Complications such as sore throat, laryngospasm, and barotrauma were recorded during the study and 24 h after extubation. Results In the WEI JET group, pulse oxygen saturation (SpO 2 ) was 100% in all patients during intubation. No serious complications were detected, and the incidence of minor complications was comparable to the control group. Under PetCO 2 guidance, 100% of patients in the WEI JET group were intubated on the first attempt, compared to 30% of Grade III view patients in the control group, who required two attempts. Conclusion Using the WEI JET with SJV provides adequate oxygenation during tracheal intubation in apneic patients for a prolonged period of time, with no difference in complications compared to the standard intubation technique. PetCO 2 monitoring facilitated intubation in patients with a Grade III glottis view.

Interferons (IFNs) can activate the PI3K-AKT and Raf-MEK-ERK signal pathways and induce antiviral proteins (MxA, 2′,5′-OAS and PKR) expression in specific cell lines. However, the relationship between those antiviral proteins expression and signal pathways remains unknown at present. Thus our experiments were designed to determine the exact relationship in HepG2.2.15 cell line. The results demonstrated that IFN-α and IL-29 were both able to activate PI3K-AKT and Raf-MEK-ERK signal pathways, and IFN-α up-regulated the expression of MxA, 2′,5′-OAS and PKR whereas IL-29 increased mRNA expression of MxA and 2′,5′-OAS and had no influence on PKR. Furthermore, MxA, 2′,5′-OAS and PKR expression were down-regulated while PI3K-AKT signal pathway was blocked by LY294002. And MxA was up-regulated after Raf-MEK-ERK signal pathway being blocked by PD98059. These findings indicate that the expression of MxA, 2′,5′-OAS and PKR are up-regulate by PI3K-AKT signal pathway, and Raf-MEK-ERK signal pathway has a negative regulatory effect on the expression of MxA and no significant effect on 2′,5′-OAS and PKR.

Interleukin 29 (IL-29) is a class II cytokine and displays numerous immune functions other than its anti-viral and antiproliferation activities. This study is focused on the effect of IL-29 on human keratinocytes (KCs). Primary KCs were stimulated by various concentrations of IL-29 for different time periods, and antiviral proteins and TLR3 gene expression were then analyzed by real-time PCR. The signal pathways activated by IL-29 in KCs were detected by western blot. The antiviral activity of IL-29 was determined by methylthiazolyldiphenyl-tetrazolium bromide, and small interfering RNA knockdown was used to analyze the role of toll receptor 3 (TLR3) in the antiviral activity of IL-29. IL-29 was able to induce expression of antiviral proteins and TLR3 gene expression in KCs. IL-29 pretreatment strongly enhanced herpes simplex virus type 1 (HSV-1)-induced expression of the interferon β (IFN-β) gene and protected the KCs from HSV-1 challenge. The IL-29 antiviral activity was partially dependent on TLR3 expression induced by this cytokine, and mechanistic studies demonstrated that the regulation of TLR3 expression by IL-29 might be partially dependent on Janus kinase /signal transducer and activator of transcription (JAK–STATs) activation. IL-29-induced TLR3 expression is involved in antiviral activity of IL-29 in KCs, which suggests a feasible method to cure certain viral infections of the skin.