Modulatory effect of Tim-3/Galectin-9 axis on T-cell-mediated immunity in pulmonary tuberculosis

Patients affected by pulmonary tuberculosis (PTB) manifest deficiencies in innate cellular immunity. The Tim3/Galectin-9 axis is an important regulator of Th1 cell immunity, leading to Th1 cell apoptosis. Herein, thisstudy aims to clarify the underlying roles of the Tim-3/Galectin-9 axis in T-cell immunity in PTB. Peripheralblood mononuclear cells (PBMCs) were extracted from subjects with and without PTB to examine theexpression of CD4, CD8, CD25, and Tim-3 under the stimulation of Mycobacterium tuberculosis (MTB) andpurified protein derivative (PPD). In addition, the expression of Tim-3 and Galectin-9 in PBMCs was determined. The Tim-3/Galectin-9 axis in the PBMCs was activated or blocked to detect the secreted levels of IFNc, TNF-a, IL-2, and IL-22. MTB stimulation increased the expression of CD4, CD8, CD25, Tim-3, andGalectin-9 in PBMCs. The blockade of Tim-3/Galectin-9 axis resulted in reduced secretion of IFN-c, TNF-a,IL-2, and IL-22 from T-cells. Moreover, Tim-3?CD4?T, Tim-3?CD8?, and Tim-3?CD25?T cells exhibited agreater ability to inhibit the replication of MTB in macrophages. Taken conjointly, the blockade of Tim-3/Galectin-9 axis inhibits the secretion of inflammatory cytokines in T-cells to regulate the T-cell immunity inPTB.

Pharmacological and Toxicological Effect of Tripterygii Radix et Rhizoma Polyglycosides / 中国实验方剂学杂志

In recent years, Tripterygii Radix et Rhizoma polyglycosides have been used more and more widely in clinic, mostly in the treatment of rheumatoid arthritis. Besides, it is also used as a basic immunosuppressive drug to treat various kidney diseases, such as nephrotic syndrome. However, there are many adverse reactions in clinic, as well as controversies over its medication regimen, especially its dosage and time. To make rational use of Tripterygii Radix et Rhizoma polyglycosides in clinic and further study, the pharmacological and toxicological research progress of Tripterygii Radix et Rhizoma polyglycosides was reviewed. The author collected pharmacological and toxicological research literatures of Tripterygii Radix et Rhizoma polyglycosides at home and abroad in recent years, finding that Tripterygii Radix et Rhizoma polyglycosides have the pharmacological effects of anti-inflammation, anti-tumor, kidney protection and immunosuppression, and mainly plays a pharmacological role by regulating the expression of cytokines in NF-<italic>κ</italic>B signaling pathway, mTOR signaling pathway and apoptosis-related signaling pathway. And the toxicological effects of Tripterygii Radix et Rhizoma polyglycosides mostly focused on hepatotoxicity, nephrotoxicity and reproductive system toxicity, which are mostly related to oxidative stress response and expression of inflammatory factors. The main components of Tripterygii Radix et Rhizoma polyglycosides are triptolide and celastrol. The pharmacological and toxicological studies of Tripterygii Radix et Rhizoma polyglycosides are in-depth, the results showed that the efficacy and toxicity were dose-dependent and time-dependent, with no toxicity study of Tripterygii Radix et Rhizoma polyglycosides varying with dosage and time in the context of efficacy, indicating dose-effect, time-effect, dose-toxicity, time-toxicity relationships. Relevant mechanisms still need further study.

Urine alpha1-microglobulin is a better marker for early tubular dysfunction than beta2-microglobulin among tenofovir-exposed human immunodeficiency virus-infected men who have sex with men

Objectives: Men who have sex with men are at risk of tenofovir nephrotoxicity due to its wide use in both treatment and prophylaxis for human immunodeficiency virus infection, but little is known about the urinary biomarkers of early renal dysfunction in this population. This study aims to identify useful biomarkers of early renal dysfunction among human immunodeficiency virus-infected men who have sex with men exposed to tenofovir.Methods: In a cross-sectional study urinary alpha1-microglobulin, beta2-microglobulin, N-acetyl-B-n-glucosaminidase and albumin were measured and expressed as the ratio-to-creatinine in 239 human immunodeficiency virus-infected men who have sex with men who were treatment naïve or receiving antiretroviral therapy with tenofovir-containing or non-tenofovir-containing regimens. Additionally, 56 patients in the non-antiretroviral therapy group started a tenofovir-containing regimen and were assessed after 3 and 6 months on antiretroviral therapy.Results: Both the frequency of alpha1-microglobulin proteinuria (alpha1-microglobulin-creatinine ratio >25.8 mg/g) and the median urinary alpha1-microglobulin-creatinine ratio were higher in the tenofovir disoproxil fumarate group than the other two groups (all p< 0.05). A higher frequency of beta2-microglobulin proteinuria (beta2-microglobulin-creatinine ratio >0.68 mg/g) was also observed in the tenofovir group (28.9%) compared to the non-tenofovir group (13.6%, p= 0.024). There were no significant differences between groups for N-acetyl-β-n-glucosaminidase and albumin. In the longitudinal study, the median urinary alphat-microglobulin-creatinine ratio after 3 and 6 months on tenofovir-containing therapy (16.8 and 17.3 mg/g) was higher than baseline (12.3 mg/g, p= 0.023 and 0.011, respectively), while no statistically important changes were observed in urinary beta2-microglobulin-creatinine ratio or in the other biomarkers after 3 and 6 months on antiretroviral therapy (all p> 0.05).Conclusion: Urinary alphat-microglobulin seems to be a more sensitive and stable indicator of tubular dysfunction than urinary beta2-microglobulin for assessing tenofovir-related nephrotoxicity and can be significantly altered after tenofovir exposure.

Numerical analysis of morphological variation of germplasm resources of dioscorea / 中国中药杂志

<p><b>OBJECTIVE</b>Botanical characters of germplasm resources of Dioscorea were observed and compared, which could to offer reference for its genetic improvement, germplasm resource identification and classification.</p><p><b>METHOD</b>Based on field cultivation, twenty-four morphological traits of ninety-four Dioscorea germplasm resources were observed or determined. And the morphological differences among germplasm resources were compared by principal component analysis and cluster analysis.</p><p><b>RESULT</b>There were ample morphological diversity in the twenty-four traits, in especially in leaf size and tuber characters of the ninety-four Dioscorea germplasm resources. The first seven principal components which accounted for 80. 957% of total variance were extracted from the principal component analysis. The ninety-four germplasm resources could be divided into four clusters, which belonging to Dioscorea opposite, D. persimili, D. fordii and D. alata respectively.</p><p><b>CONCLUSION</b>There were large morphological variation among germplasm resources on Dioscorea. Identification of germplasm resources of Dioscorea should focus on leaf size and tuber characters.</p>