Change of the microvascularization in systemic sclerosis,a matter of air

Systemic sclerosis (SSc) is a rare complex disease, characterized by microvascular damage, auto-immunity, and fibrosis. Nailfold capillary microscopy (NCM), a safe and noninvasive imaging technique, can be used to visualize specific microvascular alterations in SSc. In this review, we discuss an interesting case of a patient with changes in microvascular pattern on NCM after pulmonary transplantation. We provide an overview of microvascular alterations in systemic sclerosis and the evidence in the literature about the effect of vasoactive and immunomodulation therapy on these vascular changes. We also outline the influence of pulmonal pathology, such as interstitial lung disease and pulmonary arterial hypertension, on the capillaroscopic pattern, and finally, we discuss how NCM could possibly serve as a biomarker of treatment.     

Thymosin alpha 1: A comprehensive review of the literature

Thymosin alpha 1 is a peptide naturally occurring in the thymus that has long been recognized for modifying, enhancing, and restoring immune function. Thymosin alpha 1 has been utilized in the treatment of immunocompromised states and malignancies, as an enhancer of vaccine response, and as a means of curbing morbidity and mortality in sepsis and numerous infections. Studies have postulated that thymosin alpha 1 could help improve the outcome in severely ill corona virus disease 2019 patients by repairing damage caused by overactivation of lymphocytic immunity and how thymosin alpha 1 could prevent the excessive activation of T cells. In this review, we discuss key literature on the background knowledge and current clinical uses of thymosin alpha 1. Considering the known biochemical properties including antibacterial and antiviral properties, time-honored applications, and the new promising findings regarding the use of thymosin, we believe that thymosin alpha 1 deserves further investigation into its antiviral properties and possible repurposing as a treatment against severe acute respiratory syndrome coronavirus-2.     

蒙医温针抗炎镇痛及免疫作用研究

目的 探讨蒙医温针对佐剂型关节炎（AA）大鼠的疗效机制.方法 30只雄性Wistar大鼠随机分为3组,每组10只.正常组：不造模,不治疗;模型组：大鼠右后足掌皮下注射弗氏完全佐剂0.1ml,造成佐剂性关节炎模型.正常组与模型组每日以与蒙医温针组相同的方式捆绑固定15min,连续7d;蒙医温针组：于造模当天,取大鼠蒙医脏腑总穴（位于第三腰椎上凹正中）,用特制银针斜刺后,接MYL-Ⅰ型蒙医疗术温针仪,电流强度100mA,温度40℃,持续15min.每3天治疗1次,连续7次.检测其痛阈、肿胀度及T细胞亚群的变化.结果 蒙医温针治疗明显提高AA大鼠痛阈,显著抑制致炎大鼠原发足肿胀,显著提高CD8＋细胞百分率,降低CD4＋/CD8＋比值.结论 蒙医温针疗法有明显的抗炎镇痛作用,其机制可能与有效调整AA大鼠T细胞亚群有关.     

Dry powder inhalations containing thymopentin and its immunomodulating effects in Wistar rats

Thymopentin (TP5), a synthetic pentapeptide, has been used in clinic as a modulator for immunodeficiences through intramuscular administration. The purpose of this study was to design and evaluate dry powder inhalations (DPIs) for pulmonary delivery of TP5. Dry powder inhalations containing leucine (a dispersibility enhancer), mannitol, and lactose (bulking agents) were prepared by spray-drying from aqueous formulations. The formulation components on the aerosolisation characteristics of spray-dried powders were investigated through the use of various amount of leucine, lactose and mannitol. Following spray-drying, resultant powders were characterized using scanning electron microscopy, laser diffraction and tapped density measurements, and the aerosolisation performance was determined using Twin Stage Impinger. The immunosuppression Wistar rats model was constructed to evaluate the immunomodulating effects of TP5 DPIs in vivo. The results of T-lymphocyte subsets (CD3+, CD4+, CD8+, CD4+/CD8+ ratio) analyses suggest that TP5 DPIs have modulating effects. On an overall evaluation, TP5 pulmonary delivery DPIs may be feasible for the future clinical application.     

In vitro and in vivo immunomodulating and immunorestorative effects of Astragalus membranaceus

Astragalus membranaceus is a common traditional Chinese medicinal plant widely used as a tonic to enhance the body's natural defense mechanisms. In this study, bioactive fractions were isolated from the roots of Astragalus membranaceus. One of these fractions, designated as AI, was found to be the most potent with respect to its mitogenicity on murine splenocytes. Effects of AI on both specific and nonspecific immunity in mouse models were examined. Results showed that AI could exhibit mitogenic and co-mitogenic activities on mouse splenocytes, both in vitro and in vivo. Experiments in human cell culture demonstrated that AI was also active on human lymphocytes. It was found that AI was mitogenic to T cell depleted population but virtually inactive on B cell depleted population. Intraperitoneal injection of AI into mice markedly augmented the antibody response to sheep red blood cells. Besides, both the influx of macrophages into the peritoneal cavity and the phagocytic activity of macrophages were found to be enhanced by AI in vivo. On the other hand, AI could significantly increase the interleukin-2 receptor expression on mouse splenocytes in vitro. In terms of immunorestorative activity, it was found that AI could restore the lymphocyte blastogenic response of the older mice to values that are normally found in the younger mice. Moreover, administration of AI in vivo could partially restore the depressed immune functions in tumour-bearing mice and cyclophosphamide-treated mice. Collectively, the results clearly showed that AI could exhibit immunomodulating and immunorestorative effects, both in vitro and in vivo.     

Modulation of rifampicin toxicity by 6 MFA, an interferon inducer obtained from fungus Aspergillus ochraceus

The effect of 6 MFA (Sixth mycelial fraction of acetone), an interferon inducer obtained from fungus Aspergillus ochraceus, on rifampicin toxicity was studied in rats. Chronic oral administration of rifampicin (1 g/kg per day) for 30 days produced thrombocytopenia, hemolytic anaemia, transient leukopenia and increased nucleated cells in bone marrow and decreased weights of thymus and spleen significantly in male rats. Furthermore, chronic administration of rifampicin induced significant increase in cytochrome P-450 contents, lipid peroxidation (LPO) and superoxide dismutase (SOD) activity in liver and bone marrow. Simultaneous administration of 6 MFA (100 mg/kg; i.p.) on alternate days for a period of 30 days prevented most of the adverse effects of rifampicin, mentioned earlier and also restored the hepatic architecture histologically. The LPO, cytochrome P 450 content, lymphocyte and bone marrow cell counts returned to normal level whereas SOD activity was further increased. The 6 MFA treatment enhanced the SRBC antibody litre in rifampicin-treated rats. Thus, beneficial effects of 6 MFA in the amelioration of mediated rifampicin toxicity observed in the present study may be through induction of interferons and their associated effects.     

多糖对免疫细胞调节作用的新视角 ——对树突状细胞的影响

多糖作为一种免疫调节和促进剂对巨噬细胞、T/B淋巴细胞、自然杀伤细胞(NK)和淋巴因子激活的杀伤细胞(LAK)的功能都有调节作用,树突状细胞(DC)是功能最强大的抗原提呈细胞,多糖对树突状细胞功能的影响近年来也有所报道,主要包括多糖对树突状细胞表面分子的表达、细胞因子分泌、吞噬功能、多糖受体及信号转导途径等方面的调节作用。     

Effects of immunomodulating therapy in systemic sclerosis

Summary We reviewed studies concerning immunomodulating therapy in systemic sclerosis. These comprise mostly uncontrolled trials and case reports. Some of these studies hint at a possible beneficial effect of antimetabolites (azathioprine, 5-fluoro-uracil and methotrexate), cyclosporine and interferon-. However, to give a clearcut answer on the efficacy of these drugs in systemic sclerosis, controlled studies are urgently needed.     

免疫调节药联合应用治疗慢性乙型肝炎的临床疗效

目的: 观察干扰素和胸腺五肽联合应用治疗慢性乙型肝炎的临床疗效和不良反应.方法: 64例慢性乙型肝炎患者,随机分为治疗组和对照组.治疗组使用干扰素α-2b6个月和胸腺五肽3个月;对照组单纯使用干扰素α-2 b 6个月.结果: 治疗6个月后,两组ALT复常显著.HBV-DNA、HBeAg阴转率治疗组分别为65.63%,62.5%;对照组分别为46.88%,37.5%,两组相比,HBeAg阴转率有显著性差异(P<0.05).停药1年后,HBV-DNA阴转率治疗组为71.88%;对照组为43.75%.HBeAg阴转率治疗组为62.5%,对照组为34.38%,两组相比,差异显著(P<0.05).结论: 胸腺五肽能调节和提高受损的细胞免疫功能,与干扰素联合应用,抗病毒作用显著提高,并能明显抑制HBV复制.     

Prevention of recurrent but not spontaneous autoimmune diabetes by transplanted NOD islets adenovirally transduced with immunomodulating molecules

Pancreatic islet transplantation has the potential to maintain normoglycemia in patients with established type 1 diabetes, thereby obviating the need for frequent insulin injections. Our previous study showed that recombinant IL-12p40-producing islets prevented the recurrence of NOD diabetes. First, to see which immunomodulating molecule-secreting islet grafts can most powerfully prevent diabetes development in NOD mice without immunosuppressant, NOD islets were transfected with one of the following adenoviral vectors: Ad.IL-12p40, Ad.TGF-β, Ad.CTLA4-Ig, or Ad.TNF-α after which they were transplanted under the renal capsule of acutely diabetic NOD mice. The immunomodulating molecules produced by these adenovirus-transfected islets in vitro were 74 ± 19 ng, 50 ± 4 ng, 821 ± 31 ng, and 77 ± 18 ng/100 islets, respectively. Transplantation of IL-12p40, TNF-α, and CTLA4-Ig but not TGF-β-secreting islets displayed enhanced survival and delayed diabetes recurrence in recent-onset diabetic recipients. IL-12p40-producing islet grafts most powerfully prevented recurrent diabetes in NOD mice. In addition, local production of TNF-α and CTLA4-Ig significantly prolonged islet graft survival. In second series of experiment, these manipulated islets were transplanted under the renal capsule of 10-week-old NOD recipients and were also transplanted subcutaneously into 2-week-old NOD recipients. Transplantation of these islets into 2- or 10-week-old pre-diabetic mice failed to protect them from developing diabetes; in fact, transplantation of Ad.TNF-α-transfected islets into 2-week-old mice actually accelerated diabetes onset. Taken together, this approach was ineffectual as a prophylactic protocol. In conclusion, this study showed comparisons of the immunomodulating effects of 4 different adenoviral vectors in the same transplantation model and local production of IL-12p40, TNF-α and CTLA4-Ig significantly prevented recurrent diabetes in NOD mice.