Leishmania major degrades murine CXCL1 - An immune evasion strategy.

Leishmaniasis is a global health problem with an estimated report of 2 million new cases every year and more than 1 billion people at risk of contracting this disease in endemic areas. The innate immune system plays a central role in controlling L. major infection by initiating a signaling cascade that results in production of pro-inflammatory cytokines and recruitment of both innate and adaptive immune cells. Upon infection with L. major, CXCL1 is produced locally and plays an important role in the recruitment of neutrophils to the site of infection. Herein, we report that L. major specifically targets murine CXCL1 for degradation. The degradation of CXCL1 is not dependent on host factors as L. major can directly degrade recombinant CXCL1 in a cell-free system. Using mass spectrometry, we discovered that the L. major protease cleaves at the C-terminal end of murine CXCL1. Finally, our data suggest that L. major metalloproteases are involved in the direct cleavage and degradation of CXCL1, and a synthetic peptide spanning the CXCL1 cleavage site can be used to inhibit L. major metalloprotease activity. In conclusion, our study has identified an immune evasion strategy employed by L. major to evade innate immune responses in mice, likely reservoirs in the endemic areas, and further highlights that targeting these L. major metalloproteases may be important in controlling infection within the reservoir population and transmittance of the disease

Colorectal Cancer in Different Age Groups in a Tertiary Hospital in Nepal

Introduction: Some studies have suggested that colorectal cancer at a younger age had distinct biological characteristics: different clinical presentations, more advanced stage at time of diagnosis and poorly differentiated carcinoma. The aim of the study is to analyze clinical and histopathological differences between younger (≤40 years of age) and older (>40 years of age) colorectal cancer patients. Methods: A cross-sectional analysis was conducted amongst the colorectal cancer patients who visited Bir Hospital between July 2015 and April 2017. All colonoscopically diagnosed and histopathologically proven cases of colon cancer were included. Chi-square test and independent t – test was performed to analyze the difference between clinical presentations and histopathological findings among two groups of patients and p value of <0.05 was considered as significant. Results: Thirty younger patients and thirty older patients were enrolled without any differences in gender proportion. There were no statistical differences between clinical presentation and histological grade and type in younger and older patients. The younger patients had more complaints of altered bowel habit (p <0.001) while older patients mostly presented with per rectal bleeding (p< 0.008). Conclusions: In this study, colorectal cancer at younger ages showed similar characteristics to those of older patients except altered bowel habit was more common in younger patients while per rectal bleeding was more common in older patients. Although colorectal cancer incidence increases with age, younger patients with altered bowel habits, weight loss, anemia and anorexia should also be given due medical attention and undergo evaluation promptly.   Keywords: carcinoma; colon; per rectal bleeding; younger group. [PubMed