Excessive dietary fat intake is closely associated with an increased risk of obesity, type 2 diabetes, cardiovascular disease, gastrointestinal diseases, and certain types of cancer. The administration of multi-strain probiotics has shown a significantly beneficial effect on the mitigation of obesity induced by high-fat diets (HFDs). In this study, Amuc_1100, an outer membrane protein of Akkermansia muciniphila, was fused with green fluorescent protein and LPXTG motif anchor protein and displayed on the surface of Lactobacillus rhamnosus (pLR-GAA) and Lactobacillus plantarum (pLP-GAA), respectively. The localization of the fusion protein on the bacterial cell surface was confirmed via fluorescence microscopy and Western blotting. Both recombinant strains demonstrated the capacity to ameliorate hyperglycemia and decrease body weight gain in a dose-dependent manner. Moreover, daily oral supplementation of pLR-GAA or pLP-GAA suppressed the HFD-induced intestinal permeability by regulating the mRNA expressions of tight junction proteins and inflammatory cytokines, thereby reducing gut microbiota-derived lipopolysaccharide concentration in serum and mitigating damage to the gut, liver, and adipose tissue. Compared with Lactobacillus rhamnosus treatment, high-dose pLR-GAA restored the expression level of anti-inflammatory factor interleukin-10 in the intestine. In conclusion, our approach enables the maintenance of intestinal health through the use of recombinant probiotics with surface-displayed functional protein, providing a potential therapeutic strategy for HFD-induced obesity and associated metabolic comorbidities.

Androgen deficiency is a common medical conditions that affects males of all ages. Transplantation of testosterone-producing cells is a promising treatment for male hypogonadism. However, getting a cell source with the characteristics of Leydig cells (LCs) is still a challenge. Here, a high-efficiency reprogramming of skin-derived fibroblasts into functional Leydig-like cells (LLCs) based on epigenetic mechanism was described. By performing an integrated analysis of genome-wide DNA methylation and transcriptome profiling in LCs and fibroblasts, the potentially epigenetic-regulating steroidogenic genes and signaling pathways were identified. Then by using CRISPR/dCas9 activation system and signaling pathway regulators, the male- or female-derived fibroblasts were reprogrammed into LLCs with main LC-specific traits. Transcriptomic analysis further indicated that the correlation coefficients of global genes and transcription factors between LLCs and LCs were higher than 0.81 and 0.96, respectively. After transplantation in the testes of hypogonadal rodent models, LLCs increased serum testosterone concentration significantly. In type 2 diabetic rats model, LLCs which were transplanted in armpit, have the capability to restore the serum testosterone level and improve the hyperglycemia status. In conclusion, our approach enables skin-derived fibroblasts reprogramming into LLCs with high fidelity, providing a potential cell source for the therapeutics of male hypogonadism and metabolic-related comorbidities.

血管球瘤(glomus tumor ,GT )临床常见于四肢末端,少见于内脏器官,其中肾血管球瘤更为罕见,暨南大学附属第一医院泌尿外科于2018年7月收治1例,报告如下.

1 病例介绍 患者,女,51岁,因“反复胸闷,胸痛5年,加重头痛1个月”入住本院心内科.CT检查发现左肾积水后,患者转至泌尿外科.无腹胀、腹痛,无尿频、尿急、尿痛、排尿困难及尿流中断等,无烟酒嗜好,无手术史,无家族病史.查体:生命体征平稳,神清,心、肺未见异常,腹平软,全腹未扪及肿块,无压痛、反跳痛,双肾区无叩痛.入院后行尿常规检查,尿白细胞计数为87/μl,尿潜血阳性.血清肌酐79 μmol/L,血常规、肝功能及凝血参数均在正常范围.

Objective To analyze the expression difference and significance of glucocorticoid receptor gene(NR3C1)in renal clear cell carcinoma.Methods The Oncomine database was used to retrieve and screen out the information of NR3C1,so as to obtain the expressions of NR3C1 in ccRCC and normal kidney tissues.The GEPIA database was used to analyze the relationship between the expression of NR3C1 and the survival rate of ccRCC patients in TCGA data.Protein interaction on one hand and upstream and downstream regulation of NR3C1 gene on the other hand were analyzed by the String database.Results The NR3C1 expression in ccRCC tissue was statistically different from that in normal renal tissue(P ＜ 0.05).The overall survival rate of the patients with a high NR3C1 expression was significantly higher than that of ones with a low NR3C1 expression(P ＜ 0.05).NR3C1 interacted with NCOA1,NCOA2,NOCR01,HSP90AA1,FKBP5,and other proteins,and participates in inflammatory response,as well as in cell proliferation and differentiation and other biological processes.Condusion NR3C1 is highly expressed in ccRCC and is related to the prognosis of ccRCC,so it can be used as a potential target for diagnosis and treatment.