Study from the United States: increased prevalence of kidney stones in patients with high weight-adjusted waist index.

Objective: Using data from NHANES 2007-2018, to examine the association between WWI (weight-adjusted waist index) index and prevalence of kidney stones. Methods: Using multiple logistic regression analysis of the National Health and Nutrition Examination Survey (NHANES) 2007-2018, we evaluated the association between WWI index and the prevalence of kidney stones, followed by subgroup analysis of sensitive populations. Smooth curve fitting was used to determine whether there was a non-linear relationship between the WWI index and kidney stone prevalence, and threshold effect analysis was used to test this relationship. Results: Among 29,280 participants, 2,760 self-reported renal calculi. After adjustment for all confounders, there was a positive association between WWI and kidney stone prevalence (OR = 1.20, 95% CI: 1.12, 1.28), and this positive association was stronger with increasing WWI (and P = 0.01 for trend). Our results indicate a non-linear positive correlation between WWI index and kidney stones, with the saturation threshold effect analysis and the most important threshold value at 11.02. According to subgroup analysis, WWI showed the strongest association with kidney stone prevalence in participants aged 20-39 years, males, other US ethnic groups, and participants without hypertension and diabetes. Conclusion: Increased WWI is positively associated with increased incidence of kidney stones, and increased WWI is a high risk for kidney stones that should be treated with caution. This association should be more pronounced in people between the ages of 20 and 39 years, in men, in other US ethnic populations, and in participants who do not have hypertension or diabetes.

Aberrant activation of Wnt/catenin signaling and overexpression of ABCG2 contributes to apoptosis down regulation and tumor progression of high grade ovarian cancer.

Side Population (SP) cells are the small pool of CSC like progenitor cells, which are drug resistant and recapitulate tumor generation. The occurrence of SP cells is the major inference for attaining a better treatment and improved patient survival. In this work, we have isolated 6% SP cells from a high grade ovarian carcinoma. Our functional characterization of SP cells revealed that elevated ABCG2 and anti-apoptotic factors contribute to chemoresistance and increased life span of SP cells. Further, the overexpression of surface antigens, such as CD133 and CD117 in SP cells, are the key driving forces for high clonogenic and invasion properties of SP cells. More importantly, we found by RT-PCR aberrant activation and upregulation of Wnt/ ß-catenin and its downstream targeting genes, such as DKK1 and AXIN2 in SP cells. These findings suggest that development of new anticancer drugs which target Wnt/ß-catenin signaling might effectively exterminate the SP cells and aid in disease free survival.

miR128-1 inhibits the growth of glioblastoma multiforme and glioma stem-like cells via targeting BMI1 and E2F3.

MicroRNA128-1 (miR128-1), as a brain-specific miRNA, is downregulated in glioblastoma multiforme (GBM) and closely associated with the progression of GBM. However, the underlying molecular mechanism of the downregulation and its role in the regulation of tumorigenesis and anticancer drug resistance in GBM remains largely unknown. In the current study,we found that miR128-1 was downregulated in GBM and glioma stem-like cells (GSCs). Intriguingly, treatment with the DNA methylation inhibitors 5-Aza-CdR (Aza) and 4-phenylbutyric acid (PBA) resulted in miR128-1 upregulation in both GBM cells and GSCs. Either forced expression of miR128-1 or Aza/PBA treatment inhibited tumor cell proliferation, migration and invasion in vitro. Moreover, overexpression of miR128-1 inhibited the growth of transplant tumor in vivo. BMI1 and E2F3 were found to be direct targets of miR128-1 and downregulated by miR128-1 in vitro and in vivo. Our results revealed a mechanism of methylation that controls miR128-1 expression in GBM cells and GSCs and indicate miR128-1 could function as a tumor suppressor in GBM by negatively regulating tumor cell proliferation, invasion and self-renewal through direct targeting BMI1 and E2F3. Our findings suggest that DNA methylation inhibitors are potential agents for GBM treatment by upregulating miR-128-1.

Downregulation of miR-362-5p inhibits proliferation, migration and invasion of human breast cancer MCF7 cells.

An increasing number of studies have indicated that the deregulation of microRNAs (miRNAs) contributes to tumorigenesis and metastasis. In the present study, significant upregulation of miR-362-5p was identified in the breast cancer MDA-MB-231 and MCF7 cell lines compared with the control CCD-1095Sk cell line. The inhibition of miR-362-5p was demonstrated to significantly inhibit the cell proliferation, migration and invasion of human breast cancer MCF7 cells. In addition, the knockdown of miR-362-5p induced G1 arrest and promoted apoptosis in the breast cancer cells. Mechanistic investigations confirmed that the tumor suppressor gene CYLD is a direct target of miR-362-5p. The ectopic expression of miR-362-5p represses CYLD expression, whereas miR-362-5p inhibitor treatment induces CYLD protein expression and decreases NF-κB expression in the downstream signaling pathway. Thus, these findings may provide novel insights into the molecular mechanisms through which miR-362-5p regulates breast cancer cell proliferation, migration and invasion. This study also suggests that miR-362-5p may act as a novel potential therapeutic target for the treatment of breast cancer.