莫西沙星联合用药方案对耐多药肺结核患者血清游离氨基酸和免疫功能的影响

目的:探讨莫西沙星联合用药方案对耐多药肺结核(MDR-TB)患者血清游离氨基酸和免疫功能的影响。方法:选取2015年9月到2018年1月期间我院收治的90例MDR-TB患者,根据乱数表法将患者分为研究组(n=45)、对照组(n=45),其中对照组给予左氧氟沙星联合常规化疗治疗,研究组则给予莫西沙星联合常规化疗治疗,比较两组临床疗效、痰菌转阴率、病灶吸收率、空洞闭合率、血清游离氨基酸和免疫功能,记录两组治疗期间不良反应情况。结果:研究组治疗18个月后的临床总有效率为71.11%(32/45),高于对照组的46.67%(21/45)(P0.05)。研究组治疗18个月后痰菌转阴率、病灶吸收率、空洞闭合率均较对照组高(P0.05)。两组患者治疗18个月后CD4+、免疫球蛋白A(Ig A)、免疫球蛋白G(Ig G)均升高,CD8+降低(P0.05),研究组治疗18个月后CD4+、Ig A、Ig G高于对照组,而CD8+低于对照组(P0.05)。两组治疗18个月后缬氨酸、谷氨酸均升高,且研究组高于对照组(P0.05)。两组患者总不良反应发生率比较无明显差异(P0.05)。结论:莫西沙星联合常规化疗治疗MDR-TB的疗效确切,可有效改善患者血清游离氨基酸水平,提高机体免疫功能,同时不增加不良反应发生率。     

全反式维甲酸对骺软骨细胞生物学行为及其功能影响的研究

该研究主要探讨了体外高浓度全反式维甲酸(all-trans retinoic acid,ATRA)对SD大鼠骺软骨细胞生物学性状和功能的影响以及体内ATRA对SD大鼠胫骨生长板的影响。以SD大鼠骺软骨细胞为研究对象、ATRA为干预因素,采用CCK-8、细胞流式术、HE染色、Annexin V-FITC细胞凋亡流式检测术、Hoechst染色、细胞划痕、Transwell实验分别评估ATRA处理后细胞的增殖、周期、形态、凋亡及迁移情况,Western blot检测蛋白聚糖、Ⅱ型胶原、X型胶原等相关功能蛋白的变化;以3周雄性SD大鼠为实验对象,分为对照组、60 mg/kg·d ATRA组、80 mg/kg·d ATRA组,进行10天连续ATRA灌胃处理,测量每只SD大鼠灌胃第1天、第10天的头尾长,处理10天后对胫骨生长板进行HE染色。结果表明,ATRA作用SD大鼠骺软骨细胞后,增殖能力减弱且细胞周期被阻滞在S期(P<0.01),细胞形态由三角形、多边形变为长条状,凋亡的发生增多(P<0.01),迁移能力受到抑制(P<0.05)以及Western blot结果显示蛋白聚糖、Ⅱ型胶原、X型胶原等功能相关蛋白较对照组表达均明显降低(P<0.01);对SD大鼠进行ATRA灌胃处理后,与对照组比较,60 mg/kg·d ATRA组和80 mg/kg·d ATRA组的头尾长均变短(P<0.01);胫骨生长板HE染色显示,ATRA灌胃组的生长板变窄甚至闭合。该研究证实了体外高浓度ATRA能够对SD大鼠骺软骨细胞的增殖、迁移起抑制作用,同时能够诱导凋亡,降低相关功能蛋白的表达,在SD大鼠体内证实,过量ATRA可影响生长板软骨内成骨过程,最终使生长板部分或全部提前闭合,进而影响SD大鼠身长的增长。     

The fungal community and its interaction with the concentration of short-chain fatty acids in the faeces of Chenghua,Yorkshire and Tibetan pigs

Despite their important roles in host nutrition and metabolism, and potential to cause disease, our knowledge of the fungal community in the mammalian gut is quite limited. To date, diversity and composition of fungi in swine gut still remains unknown. Therefore, the first internal transcribed spacer of fungi in faecal samples from three breeds of pigs (10 pigs for each breed) was sequenced based on an Illumina HiSeq 2500 platform, and the relationship between the fungal community and the concentrations of main short-chain fatty acids (SCFAs) was also analysed. Results indicated that Chenghua (local, higher body fat rate), Yorkshire (foreign, higher lean meat and growth rate) and Tibetan (plateau, stronger disease resistance) pigs harboured distinct fungal community. The Basidiomycota and Ascomycota presented as the two predominant phyla, with Loreleia, Russula and Candida as the top three genera in all samples. Network analysis revealed a total of 35 correlations among different fungal genera, with 27 (77.14%) positive and 8 (22.86%) negative pairwise interactions. Canonical correspondence analysis suggested that fungi in the faeces of pigs were more correlated to the concentration of acetate and butyrate rather than propionate. Spearman’s correlation further showed that Tomentella was positively correlated to both acetate and butyrate, and Loreleia was positively correlated to propionate (P < 0.05), while Nephroma and Taiwanofungus were negatively correlated to acetate and propionate (P < 0.05). These findings expanded our knowledge on the intestinal fungi in pigs with different genotypes and phenotypes, indicating that fungi may play an indispensable role during the metabolism of host and the maintenance of intestinal health. The cross-feeding between fungi and other microorganisms may be crucial during the digestion of dietary carbohydrates and the associated physiological processes, which is worthy to be further studied.     

Age attenuates the T‐type CaV3.2‐RyR axis in vascular smooth muscle

Caveolae position Ca_V3.2 (T‐type Ca²⁺ channel encoded by the α‐3.2 subunit) sufficiently close to RyR (ryanodine receptors) for extracellular Ca²⁺ influx to trigger Ca²⁺ sparks and large‐conductance Ca²⁺‐activated K⁺ channel feedback in vascular smooth muscle. We hypothesize that this mechanism of Ca²⁺ spark generation is affected by age. Using smooth muscle cells (VSMCs) from mouse mesenteric arteries, we found that both Ca_v3.2 channel inhibition by Ni²⁺ (50 µM) and caveolae disruption by methyl‐ß‐cyclodextrin or genetic abolition of Eps15 homology domain‐containing protein (EHD2) inhibited Ca²⁺ sparks in cells from young (4 months) but not old (12 months) mice. In accordance, expression of Ca_v3.2 channel was higher in mesenteric arteries from young than old mice. Similar effects were observed for caveolae density. Using SMAKO Ca_v1.2^?/? mice, caffeine (RyR activator) and thapsigargin (Ca²⁺ transport ATPase inhibitor), we found that sufficient SR Ca²⁺ load is a prerequisite for the Ca_V3.2‐RyR axis to generate Ca²⁺ sparks. We identified a fraction of Ca²⁺ sparks in aged VSMCs, which is sensitive to the TRP channel blocker Gd³⁺ (100 µM), but insensitive to Ca_V1.2 and Ca_V3.2 channel blockade. Our data demonstrate that the VSMC Ca_V3.2‐RyR axis is down‐regulated by aging. This defective Ca_V3.2‐RyR coupling is counterbalanced by a Gd³⁺ sensitive Ca²⁺ pathway providing compensatory Ca²⁺ influx for triggering Ca²⁺ sparks in aged VSMCs.     

DJ‐1 inhibits autophagy activity of prostate cancer cells by repressing JNK–Bcl2–Beclin1 signaling

The regulation of DJ‐1 on AR signaling plays an important role in the pathogenesis of prostate cancer (PCa). DJ‐1 could alter autophagy and regulate Beclin1‐involved autophagy response through JNK‐dependent pathway. JNK is known to mediate autophagy through Bcl2–Beclin1 complex. Therefore, this study aimed to investigate the significance of autophagy in DJ‐1‐modulated PCa cells. The current studies showed that DJ‐1 overexpression in LNCaP decreased LC3 transformation and autophagosome formation. However, DJ‐1 knockdown exerted the opposite effect. Moreover, DJ‐1 silencing inhibited survival and promoted death in LNCaP, which was recovered by autophagy inhibition with 3‐MA. In addition, DJ‐1 overexpression inhibited the phosphorylation of JNK and Bcl2, and the dissociation of Beclin1 and Bcl2; while the effect of silencing DJ‐1 was completely opposite. More important, JNK activated by anisimycin inhibited the proliferation and promoted death of DJ‐1‐overexpressed LNCaP while increasing LC3 transformation and LC3‐puncta formation, but these results were reversed by the decrease of Beclin1 (by spautin‐1). In contrast, when DJ‐1 was silenced, the death of LNCaP, LC3 transformation, and LC3‐puncta formation were inhibited by JNK inhibitor SP600125, which promoted cell proliferation. However, Bcl2 inhibition (by ABT737) reversed all the effects of SP600125. Our results suggested that DJ‐1 in PCa cells could promote the growth of PCa through autophagy inhibition, and JNK–Bcl2–Beclin1 signaling played an important role in it. The study provided new insights into the role of DJ‐1 in the development of PCa.     

Spatial distribution and environmental risk assessment of heavy metals identified in soil of a decommissioned uranium mining area

Abstract

The spatial distribution of six heavy metals (Cd, As, Zn, Pb, Cr, and Cu) in the soil of a decommissioned uranium mining area was investigated and their potential environmental risk was assessed. Soil samples were collected along the main riversides enclosing the mining area. The heavy metal distribution was determined by geospatial interpolation. Pearson correlation coefficient and principal component analysis were used to locate the sources of pollution which are the mine ore as natural source, and dressing plants and tailing area from human activity. The results indicate that the average concentrations of As and Cd strongly exceed the recommended EQSS (Environmental Quality Standard for Soils of China) limits at all sampling sites, whereas Zn concentrations were found to be slightly over the limit only at sampling sites close to the mining area. The concentrations of Cr, Cu and Pb were all within the recommended limits. Environmental risk was assessed using the toxicity characteristic leaching procedure defining the degree to which extend the metal is released into the solution. High leaching rates were found only for Zn and Cd, suggesting that together with its high concentrations Cd is the most toxic metal around the mining area, followed by As.