Silenced miR-21 inhibits renal interstitial fibrosis via targeting ERK1/2 signaling pathway in mice.

OBJECTIVE: To study the influence of micro ribonucleic acid (miR)-21 on the renal interstitial fibrosis (RIF) model mice, and to preliminarily elucidate the mechanism of action of miR-21 in the development of RIF by studying the influences of miR-21 on the expressions of the proteins related to the extracellular signal-regulated kinase (ERK) 1/2 signaling pathway and its downstream proteins. MATERIALS AND METHODS: The mouse model of the left unilateral ureteral obstruction (UUO) was established. The experimental mice were divided into the Sham group and UUO group and were normally fed for 3 weeks. Then, they were executed, and their blood was extracted to determine the renal function-related indicators. The left kidney was excised, and the corresponding specimens were reserved for observing the appearance of the kidney and the morphology of the renal tubules and interstitium. The relative expression levels of epithelial (E-)cadherin, α-smooth muscle actin (α-SMA), and ERK1/2 phosphorylated ERK1/2 (p-ERK1/2), the transforming growth factor-ß1 (TGF-ß1) and the connective tissue growth factor (CTGF) proteins in renal tissues were determined. After the human renal proximal tubular epithelial cell line, the human kidney-2 (HK-2) was treated with high glucose (HG) combined with silenced miR-21 or the ERK1/2 inhibitor PD98059, the relative expression levels of ɑ-SMA and TGF-ß1 protein were measured. RESULTS: UUO group had significantly higher content of blood urea nitrogen (BUN), serum creatinine (SCr), and uric acid (UA) than the Sham group, and exhibited the infiltration of renal interstitial monocytes and lymphocytes, renal tubular podocyte damage, phenotypic transformation and atrophy, the activation and proliferation of interstitial fibroblasts, and excessive deposition of extracellular matrix (ECM). Moreover, the expression level of E-cadherin in the renal tissues was decreased, but the relative expression levels of ɑ-SMA, and TGF-ß1, CTGF, and p-ERK1/2 proteins were evidently elevated. Lower relative expression levels of ɑ-SMA and TGF-ß1 protein were detected in the human renal proximal tubular epithelial cell line HK-2 after the combined treatment with HG and silenced miR-21 or the ERK1/2 inhibitor PD98059. CONCLUSIONS: MiR-21 may be related to the occurrence and development of RIF. Silenced miR-21 probably suppresses RIF via the ERK1/2 signaling pathway.

[The efficacy of cognitive behavioral therapy in insomnic patients with or without comorbidities: a pilot study].

Objectives: To evaluate the effectiveness of cognitive behavior therapy for insomnia (CBT-i) in chronic insomnia patients in terms of the improvements of psychological and sleep diary parameters. Methods: Patients who met the diagnostic criteria of chronic insomnia, were divided into primary group or comorbid group. Both groups received standard CBT-i interventions. Psychological scales and sleep diaries were used to evaluate participants' severity of insomnia and psychological conditions related to insomnia at four time points: before intervention (baseline), immediate after intervention, 4 weeks and 16 weeks after intervention. Results: Both groups achieved significant improvements after intervention on psychological measurements and sleep diary parameters. Such improvements were maintained at 4-week and 16-week follow-ups. The sleep diary data indicated that by the end of the intervention, there were significant differences on sleep onset latency (51.72 min to 10.53 min in primary group, P<0.01; 59.26 min to 15.67min in comorbid group, P<0.01) and sleep efficiency (71% to 95% in primary group, P<0.01; 68% to 90% in comorbid group, P<0.01). There were differences on sleep onset latency (10.00 min vs. 13.93 min, P<0.05), total sleep time (355.71 min vs. 327.85 min, P<0.05) and sleep efficiency (95% vs. 91%, P<0.01) in primary group and comorbid group respectively. No differences were found on wake after sleep onset in the two groups. Conclusions: Chronic insomnia patients with or without comorbidities both have improvements after CBT-i. Sleep diary parameters rather than psychological measurements are different in two groups. Thus, CBT-i is an effective non-pharmaceutical therapy inpatients with chronic insomnia.

[Studies on ultrastructure and histochemistry of Trichomonas vaginalis adhering to vaginal mucosa of rats].

OBJECTIVE: To study interaction between Trichomonas vaginalis and epithelium of genital tract of host as well as the pathogenesis of T. vaginalis. METHODS: Immunohistochemical technique was used to observe the adhering process of T. vaginalis to vaginal mucosa in rats by transmission and scanning microscopy. RESULTS: T. vaginalis were shown to be PAS positive and clusters of T. vaginalis were found to adhere to columnar epithelium rich in mucopolysaccharide on the surface of vaginal mucosa as viewed in sections of the middle and upper parts of the orgen. T. vaginalis was positive for cathepsin. And the membrane of epithelial cells was often damaged by the released hydrolase. The parasite was also positive for actin; the microfilament bundles were arranged in reticular form in ameboid T. vaginalis. The latter would penetrate between epithelial cells, and its filiform pseudopodia would invade the interspace of microvilli of the epithelium, to encircle and gradually phagocytize microvilli. Digitiform pseudopodia would insert between epithelial cells and encircle part of them. A few T. vaginalis were found to adhere to the keratinized epithelium between mucosal folds as shown in the sections of the lower part of vagina. CONCLUSION: T. vaginalis is inclined to parasitise vaginal fornix because the superficial epithelial cells there are rich in mucinogen granules and abundant microvilli exist. After adhering, T. vaginalis releases hydrolase to digest and phagocytize epithelium which may directly damage the epithelium of the genital canal. Moreover, T. vaginalis would take in mucopolysaccharide to affect the normal clearance process of vagina, resulting in inflammation of parasitized tissue. The cytoskeleton, cell coat, polymorphism of pseudopodia and lysosome of T. vaginalis play an important role in the courses of movement, adhesion, encirclement, phagocytosis and digestion.

[Effect of enkephalin on glial neurotrophic function related to the reduction of nitric oxide production].

The effect of methionine-enkephalin (ME) on glial neurotrophic function was studied in rat cortical glial-neuronal coculture. The results showed that ME-treated glia enhanced neuronal survival by 28% (P < 0.05), and increased total neurite length per neuron by 11% (P < 0.05), while the expression of GAP-43 mRNA by 26% (P < 0.05). The effect of ME on NO production of glia was also studied in rat cortical glial culture. The result showed that different concentrations of ME (10(-12), 10(-10), 10(-8), 10(-6) mol/L) inhibited glial NO production. All the above show that the increase of glial neurotrophic ability by ME may be due to the inhibition of glial NO production.