Nitrate associated health risks from groundwater of Kadava River Basin Nashik,Maharashtra, India

Abstract

The present study was carried out to evaluate the nitrate contamination in groundwater and ascertain the associated health risks to rural populations in the agricultural area of the Kadava River basin. A total of (80) eighty representative samples from rural habitat located in agricultural fields were collected during pre- and postmonsoon seasons of 2011, which are mainly used for drinking and irrigation. The chemical results confirm that, 52.5 and 65% groundwater samples from pre- and postmonsoon season are unfit for drinking because of high nitrate contents exceeding the limit of nitrate (>45?mg L^?1) recommended by the BIS. The oral and dermal exposure pathways were calculated for different age group based on US EPA and ICMR standards. HQ₁ is much higher than the critical limit of 1 which increases the risk from 92.5 to 95% groundwater samples, while value of HQ₂ is far below to the critical value of 1; hence, all age groups free from risk. THQ values depicts that, children were at greater risk followed by infants and adults. Therefore, it is immensely important to regulate the use of nitrogen complex fertilizer and groundwater management practices should be implemented to prevent the associated risks to human health.     

Monocytic MDSC mobilization promotes tumor recurrence after liver transplantation via CXCL10/TLR4/MMP14 signaling

Tumor recurrence is the major obstacle for pushing the envelope of liver transplantation for hepatocellular carcinoma (HCC) patients. The inflammatory cascades activated by acute liver graft injury promote tumor recurrence. We aimed to explore the role and mechanism of myeloid-derived suppressor cell (MDSC) mobilization induced by liver graft injury on tumor recurrence. By analyzing 331 HCC patients who received liver transplantation, the patients with graft weight ratio (GWR, the weight of liver graft divided by the estimated standard liver weight of recipient) <60% had higher tumor recurrence than GWR ≥60% ones. MDSCs and CXCL10/TLR4 levels were significantly increased in patients with GWR <60% or tumor recurrence. These findings were further validated in our rat orthotopic liver transplantation model. In CXCL10^−/− and TLR4^−/− mice of hepatic ischemia/reperfusion injury plus major hepatectomy (IRH) model, monocytic MDSCs, instead of granulocytic MDSCs, were significantly decreased. Importantly, CXCL10 deficiency reduced the accumulation of TLR4⁺ monocytic MDSCs, and CXCL10 increased MDSC mobilization in the presence of TLR4. Moreover, MMP14 was identified as the key molecule bridging CXCL10/TLR4 signaling and MDSC mobilization. Knockout or inhibition of CXCL10/TLR4 signaling significantly reduced the tumor growth with decreased monocytic MDSCs and MMP14 in the mouse tumor recurrent model. Our data indicated that monocytic MDSCs were mobilized and recruited to liver graft during acute phase injury, and to promote HCC recurrence after transplantation. Targeting MDSC mobilization via CXCL10/TLR4/MMP14 signaling may represent the therapeutic potential in decreasing post-transplant liver tumor recurrence.Subject terms: Liver cancer, Experimental models of disease