A combined application of molecular docking technology and indirect ELISA for the serodiagnosis of bovine tuberculosis

Background@#There is an urgent need to find reliable and rapid bovine tuberculosis (bTB) diagnostics in response to the rising prevalence of bTB worldwide. Toll-like receptor 2 (TLR2) recognizes components of bTB and initiates antigen-presenting cells to mediate humoral immunity. Evaluating the affinity of antigens with TLR2 can form the basis of a new method for the diagnosis of bTB based on humoral immunity. @*Objectives@#To develop a reliable and rapid strategy to improve diagnostic tools for bTB. @*Methods@#In this study, we expressed and purified the sixteen bTB-specific recombinant proteins in Escherichia coli. The two antigenic proteins, MPT70 and MPT83, which were most valuable for serological diagnosis of bTB were screened. Molecular docking technology was used to analyze the affinity of MPT70, MPT83, dominant epitope peptide of MPT70 (M1), and dominant epitope peptide MPT83 (M2) with TLR2, combined with the detection results of enzyme-linked immunosorbent assay to evaluate the molecular docking effect. @*Results@#The results showed that interaction surface Cα-atom root mean square deviation of proteins (M1, M2, MPT70, MPT83)-TLR2 protein are less than 2.5 A, showing a high affinity.It is verified by clinical serum samples that MPT70, MPT83, MPT70-MPT83 showed good diagnostic potential for the detection of anti-bTB IgG and M1, M2 can replace the whole protein as the detection antigen. @*Conclusions@#Molecular docking to evaluate the affinity of bTB protein and TLR2 combined with ELISA provides new insights for the diagnosis of bTB.

Effect of ubiquitin-editing protein A20 on monocytes activity in patients with ventilator-associated pneumonia / 中华急诊医学杂志

Objective:To investigate and analyze the effect of ubiquitin-editing protein A20 on monocytes activity in patients with ventilator-associated pneumonia (VAP).Methods:Twenty-four VAP patients (VAP group) and twelve healthy controls (control group) were included from the First Affiliated Hospital of Zhengzhou University between February 2019 and September 2019. Peripheral blood mononuclear cells (PBMCs) and bronchial alveolar lavage fluid (BALF) (both infection site and non-infection site) were collected from VAP patients, while PBMCs were collected from healthy controls. A20 level in CD14 + monocytes were measured. CD14 + monocytes and CD4 + T cells were purified from VAP patients. CD14 + monocytes were transfected by A20 siRNA. Transfected CD14 + monocytes were directly/indirectly co-cultured with autologous CD4 + T cells. The secretion of interferon-γ (IFN-γ) and interleukin-17 (IL-17) by CD4 + T cells was investigated. Transfected CD14 + monocytes were directly/indirectly co-cultured with NCI-H889 cells. Cytotoxicity, and cytokines/granzyme B level, and tumor necrosis factor-related apoptosis inducing ligand (TRAIL)/Fas ligand (FasL) level was assessed. Student t test or SNK-q test was used for comparison. Results:VAP group had elevated percentage of circulating CD14 +A20 + cells than control group [(66.14±19.62)% vs. (52.52±13.71)%, P<0.05], and also had increased A20 mean fluorescence intensity (MFI) than control group [(268.0±72.56) vs. (197.4±60.01), P<0.05]. The percentage of CD14 +A20 + cells in BALF from infection site was higher than from non-infection site in VAP group [(66.14±19.62)% vs. (52.52±13.71)%, P<0.05], while A20 MFI in infection site was also up-regulated compared with non-infection site [(268.0±72.56) vs. (197.4±60.01), P<0.05]. In direct contact co-culture, A20 siRNA transfected CD14 + monocytes, which were purified from peripheral blood and BALF of VAP patients, induced elevated percentage of IFN-γ and IL-17 secreting CD4 + T cells than un-transfection or control siRNA transfection ( P<0.05). However, there were no significant differences of CD4 +IFN-γ + or CD4 +IL-17 + percentages among un-transfection, control siRNA transfection, and A20 siRNA transfection ( P>0.05). A20 siRNA transfected CD14 + monocytes, which were purified from peripheral blood and BALF of VAP patients, induced increased target cell death in both direct and indirect contact co-culture than un-transfection or control siRNA transfection ( P<0.05). Tumor necrosis factor-α, IL-6, granzyme B level and TRAIL MFI was also up-regulated ( P<0.05). There was no remarkable difference of target cell death between direct and indirect contact co-culture ( P>0.05). Conclusions:A20 was increasingly expressed in monocytes of VAP patients, and might dampen the activity of monocytes.

Potential mechanisms of action of celastrol against rheumatoid arthritis: Transcriptomic and proteomic analysis.

The clinical efficacy for treating of celastrol rheumatoid arthritis (RA) has been well-documented, but its mechanism of action remains unclear. Here we explored through what proteins and processes celastrol may act in activated fibroblast-like synoviocytes (FLS) from RA patients. Differential expression of genes and proteins after celastrol treatment of FLS was examined using RNA sequencing, label-free relatively quantitative proteomics and molecular docking. In this paper, expression of 26,565 genes and 3,372 proteins was analyzed. Celastrol was associated with significant changes in genes that respond to oxidative stress and oxygen levels, as well as genes that stabilize or synthesize components of the extracellular matrix. These results identify several potential mechanisms through which celastrol may inhibit inflammation in RA.

Molecular mechanism of celastrol in the treatment of systemic lupus erythematosus based on network pharmacology and molecular docking technology.

BACKGROUND: Network pharmacology uses bioinformatics to broaden our understanding of drug actions and thereby advance drug discovery. Here we apply network pharmacology to generate testable hypotheses about the multi-target mechanism of celastrol against systemic lupus erythematosus (SLE). METHODS: We reconstructed drug-target pathways and networks to predict the likely protein targets of celastrol and the main interactions between those targets and the drug. Then we validated our predictions of candidate targets by performing docking studies with celastrol. RESULTS: The results suggest that celastrol acts against SLE by regulating the function of several signaling proteins, such as interleukin 10, tumor necrosis factor, and matrix metalloprotein 9, which regulate signaling pathways involving mitogen-activated protein kinase and tumor necrosis factor as well as apoptosis pathways. Celastrol is predicted to affect networks involved mainly in cytokine activity, cytokine receptor binding, receptor ligand activity, receptor regulator activity, and cofactor binding. Molecular docking analysis showed that hydrogen bonding and π-π stacking were the main forms of interaction. CONCLUSIONS: This network pharmacology strategy may be useful for discovery of multi-target drugs against complex diseases, specifically, it provides protein targets associated with SLE that may be further tested for therapeutic potential by celastrol.

Progress in Research on Correlation Between Toll-like Receptors and Barrett's Esophagus / 胃肠病学

Barrett's esophagus (BE), the only recognizable precancerous lesion of esophageal adenocarcinoma (EAC), is a common disease characterized by abnormal transformation of squamous epithelium into intestinal columnar epithelium. Toll-like receptors (TLRs) are important pattern recognition receptors that play a central role in innate and adaptive immunity. TLRs are involved in the identification of almost all pathogens. In addition, TLRs signaling pathway is important for the occurrence and development of BE. This article reviewed the progress in research on the correlation between TLRs and BE.

Clinical effect of trimetazidine combined with ticagrelor in the treatment of unstable angina pectoris complicated with chronic heart failure / 中国基层医药

Objective@#To observe the clinical efficacy and safety of trimetazidine combined with ticagrelor in the treatment of unstable angina pectoris (UAP) complicated with chronic heart failure (CHF).@*Methods@#From January 2016 to September 2018, 60 UAP patients complicated with CHF in Taizhou Cancer Hospital were selected and randomly divided into two groups according to the random number table method, with 30 cases in each group.The control group was given ticagrelor, while the observation group was given ticagrelor + trimetazidine.The clinical efficacy, angina attack, cardiac function indicators, adverse reactions were compared between the two groups.@*Results@#The total effective rate of the observation group was 96.67%, which was higher than 80.00% of the control group (χ2=4.043, P<0.05). With in 3 months after treatment, the number of angina attacks (6.59±1.32)times and the duration of single angina pectoris [(2.24±0.92)min] in the observation group were all lower than those in the control group(t=4.277, 4.076, all P<0.05). After treatment, the left ventricular ejection fraction [(49.36±6.25)%] and stroke output [(76.29±5.31)mL] of the observation group were higher than those of the control group (t=4.066, 4.093, all P<0.05), and the level of brain natriuretic peptide [(378.32±27.82)μg/L] of the observation group was lower than that of the control group (t=4.152, P<0.05). The incidence rate of adverse reactions of the observation group was 6.67%, which of the control group was 3.33%, there was no statistically significant difference between the two groups (χ2=0.351, P>0.05).@*Conclusion@#The combination of ticagrelor and trimetazidine can effectively reduce the attack of angina pectoris, improve cardiac function and has less adverse reactions.It is effective and safe for UAP patients complicated with CHF.

The treatment of application of pedicled myocutaneous island flap of anterolateral thigh muscle for the suprapubic defect in adolescent with bladder exstrophy / 中华整形外科杂志

Objective@#To explore the treatment effect of pedicled myocutaneous island flap of anterolateral thigh muscle on the suprapubic defect caused by bladder exstrophy in children.@*Methods@#The clinical data of 3 adolescents with bladder exstrophy were analyzed. All 3 cases underwent one-stage Kelly procedure and received the treatment using pedicled myocutaneous island flap of anterolateral thigh muscle to repair the suprapubic defect. The bladder expansion was performed with ileal sarcoplasmic layer graft, and the Cohen ureteral reimplantation was performed as well, for 1 case 1, 1 year after the first operation. The others 2 patients didn′t receive the second operation.@*Results@#All operations were successful. The femoral donor regions were directly closed. Postoperative follow-up period was 1-7 years. The myocutaneous island flaps were survived and grew well. All incisions of the femoral donor region were primary healing without scar hypertrophy. Urinary continence was achieved in 2 cases, and partially achieved in 1 case. Recurrent urinary tract infection, recurrent fever or abdominal pain were not observed in all patients.@*Conclusions@#The pedicled anterolateral thigh myocutaneous island flap is an alternative way to repair suprapubic defect caused by bladder exstrophy.

Exosomes as therapeutic drug carriers and delivery vehicles across biological membranes: current perspectives and future challenges

Exosomes are small intracellular membrane-based vesicles with different compositions that are involved in several biological and pathological processes. The exploitation of exosomes as drug delivery vehicles offers important advantages compared to other nanoparticulate drug delivery systems such as liposomes and polymeric nanoparticles; exosomes are non-immunogenic in nature due to similar composition as body׳s own cells. In this article, the origin and structure of exosomes as well as their biological functions are outlined. We will then focus on specific applications of exosomes as drug delivery systems in pharmaceutical drug development. An overview of the advantages and challenges faced when using exosomes as a pharmaceutical drug delivery vehicles will also be discussed.

Application of Quality Control Circle in Health Education in Stroke Rehabilitation Nursing / 中国康复理论与实践

@#Objective To explore the effect of quality control circle (QCC) on health education in stroke rehabilitation nursing. Methods Such activities were conducted in the VIP ward of neurological rehabilitation in our hospital as: theme selecting, activity planning, status mastering, cause analyzing, countermeasures formulating and implementing, etc., in accordance with QCC theory from January to April, 2014. Results The satisfaction of stroke patients to health education rose from 80.1% to 91.1% (P<0.001), and the dissatisfaction to guidance of activities of daily living and prevention of complications decreased significantly (P<0.05) after the implementation of QCC program. All the circle members benefited from the improvement of QCC technique, team work, professional knowledge, communication and coordination, activity confidence, duty and honor. Conclusion Carrying out the QCC activities can play a positive role on health education in stroke rehabilitation nursing.

Application of Quality Control Circle in Health Education in Stroke Rehabilitation Nursing / 中国康复理论与实践

Objective To explore the effect of quality control circle (QCC) on health education in stroke rehabilitation nursing. Methods Such activities were conducted in the VIP ward of neurological rehabilitation in our hospital as:theme selecting, activity planning, status mastering, cause analyzing, countermeasures formulating and implementing, etc., in accordance with QCC theory from January to April, 2014. Results The satisfaction of stroke patients to health education rose from 80.1%to 91.1%(P<0.001), and the dissatisfaction to guid-ance of activities of daily living and prevention of complications decreased significantly (P<0.05) after the implementation of QCC pro-gram. All the circle members benefited from the improvement of QCC technique, team work, professional knowledge, communication and coordination, activity confidence, duty and honor. Conclusion Carrying out the QCC activities can play a positive role on health education in stroke rehabilitation nursing.