Serum mir-195-5p exhibits clinical significance in the diagnosis of essential hypertension with type 2 diabetes

OBJECTIVES: Diagnosis and management of essential hypertension (EH) or type 2 diabetes mellitus (T2DM) by combining comprehensive treatment and classificatory diagnosis have been continuously improved. However, understanding the pathogenesis of EH patients with concomitant T2DM and subsequent treatment remain the major challenges owing to the lack of non-invasive biomarkers and information regarding the underlying mechanisms. METHODS: Herein, we collected 200 serum samples from EH and/or T2DM patients and healthy donors (N). Gene-expression profiling was conducted to identify candidate microRNAs with clinical significance. Then, a larger cohort of the aforementioned patients and 50 N were used to identify the correlation between the tumor suppressor miR-195-5p and EH and/or T2DM. The dual-luciferase reporter assay was used to explore the target genes of miR-195-5p. The suppressive effects of miR-195-5p on the 3′-UTR of the dopamine receptor D1 (DRD1) transcript in EH patients with concomitant T2DM were verified as well. RESULTS: Compared with that in other groups, serum miR-195-5p was highly downregulated in EH patients with concomitant T2DM. miR-195-5p overexpression efficiently suppressed DRD1 expression by binding to the two 3′-UTRs. Additionally, two single nucleotide polymorphisms, including 231T-A and 233C-G, in the miR-195-5p binding sites of the DRD1 3′-UTR were further identified. Collectively, we identified the potential clinical significance of DRD1 regulation by miR-195-5p in EH patients with concomitant T2DM. CONCLUSIONS: Our data suggested that miR-195-5p circulating in the peripheral blood served as a novel biomarker and therapeutic target for EH and T2DM, which could eventually help address major challenges during the diagnosis and treatment of EH and T2DM.

A novel effect of geraniin on OPG/RANKL signaling in osteoblasts

In this study, the effects of geraniin on osteoprotegerin/receptor activator of nuclear factor-κB ligand(OPG/RANKL) in regulating the proliferation of osteoblasts and suppression of osteoclast-like cells (OLC) in OLC-osteoblast co-cultured system in vitro were investigated. Osteoblasts were cultured and identified with alkaline phosphatase (ALP), gomori stain, and mineralized nodule stain. OLCs were isolated from long bones of Sprague-Dawley (SD) rats and identified with tartrate-resistant acid phosphatase(TRAP) stain. Methyl thiazolyl tetrazolium assay was used to examine the proliferation of osteoblasts, and immunocytochemistry and in situ hybridization to analyze the expression OPG/RANKL in osteoblasts co-cultured with osteoclasts under the action of geraniin, respectively. Geraniin could regulate the proliferation of osteoblasts MC3T3-E1, decrease the number of OLC in OLC-osteoblast co-cultured system, and inhibit the bone resorption areas and resorption pits of OLC in vitro experiments. Geraniin could promote the mRNA and protein expression levels of OPG and suppress those of RANKL in osteoblasts. These results indicate that geraniin has a promoting effect on the proliferation of osteoblasts and an inhibitory effect on the osteoclastic bone-resorption through regulating OPG/RANKL signaling pathway in OLC-OB co-cultured system.

Identifying risk factors of immune reconstitution inflammatory syndrome in AIDS patients receiving highly active anti-retroviral therapy

Immune reconstitution inflammation syndrome typically occurs within days after patients undergo highly active anti-retroviral therapy and is a big hurdle for effective treatment of AIDS patients. In this study, we monitored immune reconstitution inflammation syndrome occurrence in 238 AIDS patients treated with highly active anti-retroviral therapy. Among them, immune reconstitution inflammation syndrome occurred in 47 cases (19.7%). Immune reconstitution inflammation syndrome patients had significantly higher rate of opportunistic infection (p < 0.001) and persistently lower CD4+ cell count (p < 0.001) compared to the non-immune reconstitution inflammation syndrome patients. In contrast, no significant differences in HIV RNA loads were observed between the immune reconstitution inflammation syndrome group and non-immune reconstitution inflammation syndrome group. These data suggest that a history of opportunistic infection and CD4+ cell counts at baseline may function as risk factors for immune reconstitution inflammation syndrome occurrence in AIDS patients as well as potential prognostic markers. These findings will improve the management of AIDS with highly active anti-retroviral therapy.

Study of the gene deletions and the immunofluorescence of muscle in patients with DMD/BMD / 中国应用生理学杂志

<p><b>AIM</b>To detect the deletion distribution of dystrophin gene and dystrophin changes in muscle cells of the patients with Duchenne/Becker muscular dystrophy (DMD/BMD), furthermore to investigate the relationship between them and clinical symptoms.</p><p><b>METHODS</b>42 patients with DMD/BMD were screened by 9 primers multiplex PCR. The patients from 5 DMD and 2 BMD were detected by immunofluorescence technique for analyzing dystrophin located in muscle cell membrane, compared with 2 normal males.</p><p><b>RESULTS</b>The deletion of one or more exons was found in 21 patients. 16 cases (76.2%) were detected in the central region and 5 patients (23.8%) in the 5' extreme region, especially in exon 48 (6 patients). Negative result of staining was seen in 5 DMD patients. Of these, one case of DMD had no detectable levels of dystrophin, but no deletion of DMD gene. Dystrophin immunostaining from two BMD patients consisted of a discontinuous staining pattern around most fibers.</p><p><b>CONCLUSION</b>It might be possible that some correlation existed between the type of gene deletion and the degree of severity of the disease. The amount and size of exon deletion may not affect the symptoms. DMD/BMD are highly heterogeneous in clinical manifestation and in inheritance pattern. The pathologic foundation of DMD and BMD is the absence or abnormal expression of dystrophin. The consequence of that depends not only on the degree, but also on the function.</p>