ABSTRACT
Objective:To investigate the protective effect and mechanism of microRNA-210 agonist (agomiR-210) on kidney in diabetic kidney disease (DKD) rats.Methods:Thirty-six 5-week-old male SD rats were divided into normal control (NC) group, agomiR-NC control group, agomiR-210 control group, DKD model group, DKD+agomiR-NC group and DKD+agomiR-210 group, with 6 rats in each group. Diabetic rats were established by a high-fat diet combined with intraperitoneal injection of streptozotocin (STZ), then were fed for 12 consecutive weeks to construct DKD model rats. During 2nd-4th week of continuous feeding, the rats in DKD+agomiR-210 group were injected with 20 nmol/kg agomiR-210 via tail vein twice a week. Blood glucose levels, 24 h urine albumin (Alb) and 24 h urine microalbumin (MAU) contents were measured regularly. At the end of the 12th week, the rats were sacrificed, and renal tissues were collected. The renal histopathological changes were assessed by HE, PAS and Masson staining methods. The mRNA and protein expression levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 in renal tissues were detected by RT-qPCR and Western blot. The distributions and expressions of α-smooth muscle actin (α-SMA), typeⅠ collagen (Col-Ⅰ), type Ⅳ collagen (Col-Ⅳ) and fibronectin (FN) in renal tissues were detected by immunohistochemical method. The protein expression levels of phospho(p)-Smad3 and p-NF-κB p65 in renal tissues were detected by Western blot and immunohistochemical methods.Results:Compared with DKD model group, the renal pathological damages in DKD+agomiR-210 group were improved, the blood glucose level, glycogen deposition and collagen accumulation were significantly decreased (all P<0.05), the urinary excretions of Alb and MAU were significantly reduced (all P<0.01), and the expressions of TNF-α, IL-1β, IL-6, α-SMA, Col-Ⅰ, Col-Ⅳ, FN, p-Smad3 and p-NF-κB p65 in renal tissues were significantly decreased (all P<0.01). Conclusion:AgomiR-210 can alleviate renal pathological changes and urinary Alb and MAU excretion in rats with DKD, which may be related to its inhibition of Smad3 and NF-κB activity.
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Objective@#To study the clinicopathologic characteristics, immunophenotype, pathologic diagnosis and differential diagnosis of myxoid adrenocortical adenomas.@*Methods@#The clinical data, histological features and immunohistochemical results of 4 cases of myxoid adrenocortical adenomas were analyzed, which were collected from January 2014 to December 2016 at Guangdong General Hospital, with review of literature.@*Results@#Four cases of myxoid adrenocortical adenomas were presented. The patients ages ranged from 26 to 45 years (mean =35 years). Microscopically, it showed a typical morphology, characterized by small-sized tumor cell cords or pseudo-glands embedded in an abundant extracellular myxoid matrix. Immunohistochemical staining showed tumor cells were strongly positive for Melan A, vimentin and focally for α-inhibin, one case showed strong and diffuse positivity for CAM5.2, and two cases showed diffuse positivity for synaptophysin, while negative for CgA, S-100 protein, epithelial antigen, CK7, CK20 and CKpan.@*Conclusions@#Myxoid adrenocortical adenomas are extremely rare, which may cause confusion with metastatic well-differentiated neuroendocrine tumours, sex cord-stromal tumoursor metanephric adenoma. Recognition of this entity would be beneficial for pathologists to avoid misdiagnosis, and unnecessary treatment.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate mutations frequencies of KRAS,NRAS and BRAF genes in colorectal carcinoma.</p><p><b>METHODS</b>Tissue specimens from 200 colorectal cancer patients at diagnosis were collected and subject to KRAS,NRAS and BRAF mutation analyses by PCR-based direct DNA sequencing targeting exons 2, 3 and 4 of KRAS gene, exons 2, 3 and 4 of NRAS gene and exon 15 of BRAF gene.</p><p><b>RESULTS</b>Activating mutations were detected in KRAS (44%, 88/200), NRAS (2%, 4/200) and BRAF (5%, 10/200) in this study cohort.Among KRAS mutations, 64.8% (57/88) occurred in codon 12 and 12.5% (11/88) occurred in codon 13. KRAS gene mutation in exon 3 mainly involved codons 59 and 61. KRAS gene mutation in exon 4 mainly involved codons 117 and 146.</p><p><b>CONCLUSIONS</b>Mutations at exon 2 of KRAS gene have the highest frequency in colorectal carcinoma. Expanding the detection sites of KRAS gene combined with NRAS and BRAF genes may help to identify patients who will most likely benefit from targeted therapies.</p>