MiR-22-3p regulates the proliferation and invasion of Wilms' tumor cells by targeting AKT3.

OBJECTIVE: In this study, the regulatory mechanism of miR-22-3p/AKT3 in the development of Wilms' tumor (WT) was investigated. PATIENTS AND METHODS: Twenty-seven pairs of surgical tumor specimens and adjacent normal tissues were obtained from Jining No. 1 People's Hospital. The expression level of miR-22-3p in WT tissues and cell lines was measured by quantitative RT-PCR. MTT and transwell assays were performed to analyze cell proliferation and invasion in WT. The relationship between miR-22-3p and AKT3 was verified by a Dual-Luciferase assay. The protein expression of AKT3 was evaluated by Western blotting analysis. RESULTS: MiR-22-3p was downregulated and AKT3 was upregulated in WT. Functionally, overexpression of miR-22-3p inhibited cell proliferation and invasion in WT. Moreover, miR-22-3p directly targets AKT3. The knockdown of AKT3 suppressed cell proliferation and invasion in WT. In addition, upregulation of AKT3 restored the tumor suppressive effect of miR-22-3p in WT. CONCLUSIONS: MiR-22-3p inhibits the proliferation and invasion of WT cells by downregulating AKT3, indicating that miR-22-3p may be developed as a new biomarker for the diagnosis of WT.

MiRNA-411 attenuates inflammatory damage and apoptosis following spinal cord injury.

OBJECTIVE: To investigate the role and regulate the target of miRNA-411 on spinal cord injury. MATERIALS AND METHODS: The microglia cultured in vitro was activated by lipopolysaccharide (LPS) to express the inflammatory phenotype. The inflammatory response through miRNA-411 transfection in microglia was measured to certain whether increased miRNA-411 suppressed interleukin-18 (IL-18) level to attenuate the inflammation amplification via downregulating JNK pathway. Furthermore, we established spinal cord injury (SCI) model in SD rats and further explored the glial inflammatory degree and neurological recovery following miRNA-411 treatment. Lastly, we estimated the hindlimbs function of SCI rats with miRNA-411 administration or not within four weeks at post-SCI. RESULTS: In vitro, miRNA-411 inhibited IL-18 expression and downregulated JNK pathway, along with that inflammatory microglia were declined. In SCI rats, we detected the decreased amounts of inflammatory microglia and reduction of the inflammatory factors after miRNA-411 treatment. IL-18 and JNK pathway was also restrained resulted from increased miRNA-411. In addition, apoptosis degree in injury site reduced and survived axons were relatively multiple in the miRNA-411 group compared with the SCI group. The Basso-Beattie-Bresnahan (BBB) locomotor scores of miRNA-411 treated rats were superior to those in rats with no treatment. CONCLUSIONS: MiRNA-411 increase ameliorates the inflammatory microglia-induced neurological lesion and promotes neural recovery by JNK pathway inhibition via negative targeting IL-18 in SCI.

Up-regulation of long non-coding RNA SNHG6 predicts poor prognosis in renal cell carcinoma.

OBJECTIVE: We aim to investigate the expression of long non-coding RNA SNHG6 and analyze its clinicopathological significance in renal cell carcinoma (RCC). PATIENTS AND METHODS: A total of 81 cases of RCC tissues were collected and enrolled. Total RNA was extracted using the TRIzol method followed by qRT-PCR detection of the mRNA level of SNHG6. The x2-test was used to analyze the correlation between SNHG6 expression and clinicopathological variables, including age, gender, TNM stage, Fuhrman grade, tumor size, and overall prognosis. Kaplan-Meier survival curve was plotted to analyze the association between SNHG6 expression and overall survival. Univariate and multivariate analysis were carried out with the Cox proportional hazard analysis. RESULTS: SNHG6 was shown to be markedly upregulated in RCC tissues as compared with normal controls. Elevated SNHG6 was found to significantly correlate with clinical stage, lymph node metastasis, Fuhrman grade, and tumor size (p<0.05). Kaplan-Meier survival analysis exhibited that elevated SNHG6 was remarkably associated with poor overall survival (p<0.001). Moreover, multivariate analysis revealed that SNHG6 expression was an independent prognostic factor in RCC. CONCLUSIONS: We showed that up-regulated SNHG6 was significantly associated with tumor progression and was an independent prognostic factor in RCC, suggesting that SNHG6 can work as a promising prognostic predictor in RCC.

MiR-183 maintains canonical Wnt signaling activity and regulates growth and apoptosis in bladder cancer via targeting AXIN2.

OBJECTIVE: Previous investigations have shown that miR-183 is upregulated in bladder cancer (BC); however, its biological significance is not fully investigated. The goal of the current study is to analyze the function of miR-183 in BC development and progression. PATIENTS AND METHODS: 23 pairs of BC tumor and adjacent tissues were analyzed for miR-183 and c-Myc expression using Real-time polymerase chain reaction (PCR). MiR-183 expression was modulated by transfection of miR-183 or miR-183 inhibitor (miR-183-in). Protein expression of AXIN2, c-Myc and Cyclin D1 was determined by western blot. Cell growth activity and apoptotic potential were evaluated by cell viability assay and flow cytometry assay, respectively. Luciferase activity assay was conducted to determine whether AXIN2 is a direct target of miR-183. RESULTS: The expression of miR-183 is upregulated in BC tissues and cell lines, and is positively correlated with the expression of the Wnt target gene, c-Myc. MiR-183 positively regulated Wnt signaling activity by directly suppressing its negative feedback regulator, AXIN2. Overexpression of miR-183 promoted cell growth and inhibited apoptosis. Inhibition of miR-183 attenuated cell growth and enhanced apoptosis. The effect of miR-183 on cell growth and apoptosis can be abolished by knockdown of AXIN2. CONCLUSIONS: MiR-183 functions as an oncomiR in BC and upregulates Wnt signaling activity by directly suppressing AXIN2 expression.

Paracrine effect of bone marrow mesenchymal stem cells on proliferation, apoptosis, and alpha-actin-2 expression in hepatic stellate cells.

We investigated the paracrine effects of bone marrow mesenchymal stem cells (BMSCs) on the proliferation, apoptosis, and alpha-actin-2 (ACTA2) expression of hepatic stellate cells (HSCs), and explored the possible mechanisms of hepatocyte growth factor (HGF). We established a co-culture system by culturing BMSCs on the upper layer and HSCs on the lower layer of a 6-well Transwell plate. Normal HSCs were cultured alone as a control. Cell apoptosis was determined by flow cytometry. We detected the expression of ACTA2 mRNA and ACTA2 protein in HSC using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blotting, respectively. ACTA2 in HSCs was detected by fluorescent staining, and HGF in the co-culture supernatant was detected by enzyme-linked immunosorbent assay (ELISA). The apoptotic rate of HSCs in the experiment group was 2.6 times that in the control group (P < 0.05). The expression levels of ACTA2 mRNA and ACTA2 protein were significantly inhibited in HSCs compared with the control group (P < 0.05). HGF concentration in the co-culture supernatant was 0.43 ± 0.47 mM in the experimental group, which was significantly higher than in the control group (0.16 ± 0.43 mM) (P < 0.05). The paracrine effect of BMSCs, which was caused by the suppression of ACTA2 and HGF expression, induced HSC apoptosis.

Hydrogen sulfide in posthemorrhagic shock mesenteric lymph drainage alleviates kidney injury in rats

Posthemorrhagic shock mesenteric lymph (PHSML) is a key factor in multiple organ injury following hemorrhagic shock. We investigated the role of hydrogen sulfide (H2S) in PHSML drainage in alleviating acute kidney injury (AKI) by administering D,L-propargylglycine (PPG) and sodium hydrosulfide hydrate (NaHS) to 12 specific pathogen-free male Wistar rats with PHSML drainage. A hemorrhagic shock model was established in 4 experimental groups: shock, shock+drainage, shock+drainage+PPG (45 mg/kg, 0.5 h prehemorrhage), and shock+drainage+NaHS (28 µmol/kg, 0.5 h prehemorrhage). Fluid resuscitation was performed after 1 h of hypotension, and PHMSL was drained in the last three groups for 3 h after resuscitation. Renal function and histomorphology were assessed along with levels of H2S, cystathionine-γ-lyase (CSE), Toll-like receptor 4 (TLR4), interleukin (IL)-10, IL-12, and tumor necrosis factor (TNF)-α in renal tissue. Hemorrhagic shock induced AKI with increased urea and creatinine levels in plasma and higher H2S, CSE, TLR4, IL-10, IL-12, and TNF-α levels in renal tissue. PHSML drainage significantly reduced urea, creatinine, H2S, CSE, and TNF-α but not TLR4, IL-10, or IL-12. PPG decreased creatinine, H2S, IL-10, and TNF-α levels, but this effect was reversed by NaHS administration. In conclusion, PHSML drainage alleviated AKI following hemorrhagic shock by preventing increases in H2S and H2S-mediated inflammation.

Integrating tuberculosis screening into annual health examinations for the rural elderly improves case detection.

OBJECTIVE: To assess the feasibility and effects of identifying tuberculosis (TB) cases by integrating TB screening into routine health examinations for the elderly in rural China. METHODS: Three counties in Shandong Province were randomly selected for TB screening among three groups of elderly individuals (aged ⩾60 years) at high risk for TB: 1) those with symptoms of TB, 2) patients with type 2 diabetes mellitus (DM), and 3) close contacts of TB cases. Individuals with X-rays suggestive of TB were referred to the county TB dispensary for further investigation. RESULTS: Among the 93 094 elderly residents who underwent health examinations, 9044 (9.7%) were identified as high risk for TB. TB detection rates were 0.87 per 1000 among those who showed TB symptoms only and 3.36/1000 among those with DM only; however, the rate was significantly higher (115/1000) among those who had both DM and TB symptoms. No TB cases were identified from the close contacts group. CONCLUSION: Integrating TB screening into annual health examinations for the elderly in rural areas was effective in identifying new cases, especially among elderly DM patients with TB symptoms.

Interleukin-1ß +3954 polymorphisms and risk of external apical root resorption in orthodontic treatment: a meta-analysis.

The purpose of this meta-analysis was to determine whether genetic variants of the interleukin-1ß[+3954 C>T (rs1143634)] (IL-1ß +3954 C>T) gene polymorphisms were associated with orthodontic external apical root resorption (EARR). A meta-analysis was carried out using data entered into the PubMed and Embase electronic databases before October 5, 2012. A total of 7 studies were identified for meta-analysis. The strength of the relationship between IL-1ß +3954 C>T polymorphism and the risk of EARR was assessed using odds ratio (OR). The studies provided overall OR estimates for EARR. Overall, the variant genotypes (CC and CT) of the IL-1ß +3954 C>T polymorphism were unassociated with EARR risk compared with the TT homozygote [CC vs TT, OR = 1.28, 95% confidence interval (95%CI) = 0.27-6.08; CT vs TT, OR = 0.74, 95%CI = 0.11-5.02]. Similarly, no associations were found in the dominant and recessive models (dominant model, OR = 1.08, 95%CI = 0.24-4.86; recessive model, OR = 1.85, 95%CI = 0.87-3.93). No publication bias was found, and no association was apparent between the IL-1ß +3954 C>T polymorphism and risk of EARR in orthodontic treatment patients. Further multicenter and better-controlled studies are required to confirm these findings.