Potent immunosuppressive mechanisms within the tumor microenvironment contribute to the resistance of aggressive human cancers to immune checkpoint blockade (ICB) therapy. One of the main mechanisms for myeloid-derived suppressor cells (MDSCs) to induce T cell tolerance is through secretion of reactive nitrogen species (RNS), which nitrates tyrosine residues in proteins involved in T cell function. However, so far very few nitrated proteins have been identified. Here, using a transgenic mouse model of prostate cancer and a syngeneic cell line model of lung cancer, we applied a nitroproteomic approach based on chemical derivation of 3-nitrotyrosine and identified that lymphocyte-specific protein tyrosine kinase (LCK), an initiating tyrosine kinase in the T cell receptor signaling cascade, is nitrated at Tyr394 by MDSCs. LCK nitration inhibits T cell activation, leading to reduced interleukin 2 (IL2) production and proliferation. In human T cells with defective endogenous LCK, wild type, but not nitrated LCK, rescues IL2 production. In the mouse model of castration-resistant prostate cancer (CRPC) by prostate-specific deletion of ,, and , CRPC is resistant to an ICB therapy composed of antiprogrammed cell death 1 (PD1) and anticytotoxic-T lymphocyte-associated protein 4 (CTLA4) antibodies. However, we showed that ICB elicits strong anti-CRPC efficacy when combined with an RNS neutralizing agent. Together, these data identify a previously unknown mechanism of T cell inactivation by MDSC-induced protein nitration and illuminate a clinical path hypothesis for combining ICB with RNS-reducing agents in the treatment of CRPC.

The long-term success of the reimplanted teeth is related to the maintenance of periodontal ligament (PDL) cell viability. Dental tissues are unique in comparison to most other tissues in the body due to their marked capacity for regeneration. Understanding the circumstances leading to repair and regeneration in oral tissues has been a formidable challenge. Numerous storage media have been introduced by many authors that help to maintain the PDL cell viability. To present an overview of the various available storage media. A literature search for the past 20 years was performed across the Internet database (Pubmed) and relevant citations using the keywords PDL cell viability, tooth avulsion, storage media, and the combination of all to retrieve around (n=225) citations. Articles that included follow-up of intervention for avulsed and re-implanted teeth were considered (n=44) and some literature review from well-known text books were considered. Literature supports that moist storage appears to be a more productive approach to optimize PDL cell survival. However, no medium is ideal and in vivo studies are inadequate.

A study was undertaken to evaluate the in vitro and in vivo antidiarrhoeal potential of chloroform extract of the root of Aegle marmelos (Correa) Linn. The in vitro activity was determined by agar dilution and disc diffusion techniques. The extract was studied in vivo in rats. Of the 35 tested pathogenic diarrhoea causing strains, the extract was found to be mostly active against the strains of Vibrio cholerae, followed by Escherichia coli and Shigella spp. The in vitro activity was found to be comparable to that of ciprofloxacin. Further, Aegle marmelos root extract (AMRE) treated animals showed significant inhibitory activity against castor oil-induced diarrhoea. The results so obtained thus established the efficacy of AMRE as an effective antidiarrhoeal agent.

No abstract

Heat Tolerance in Crops contrasting genotypes and would pave the way for characterizing the underlying molecular mechanisms, which could be valuable for engineering plants with enhanced thermotolerance. Wherever possible, we discussed breeding and biotechnological approaches for using these traits to develop heat-tolerant genotypes of various food crops.

The causes for initial acquisition of oral S. mutans in infants were postnatal factors like feeding and oral hygiene practices.

Background & objectives:Cervical cancer is a major health problem and a leading cause of death among women in India. Of all the associated risk factors, high-risk human papillomavirus (HPV) infections being the principal aetiologic agent, two HPV vaccines are in use for the control of cervical cancer. The present study was undertaken to explore the knowledge, attitude and practice (KAP) on HPV vaccination among the healthcare providers in India.Methods:A cross-sectional study was conducted among 590 healthcare professionals from 232 hospitals and 80 PHCs of nine districts of Delhi-NCR (National Capital Region). A total of 590 (526 female, 64 male) healthcare providers were surveyed.Results:Only 47 per cent of respondents recommended young women to get vaccinated against HPV. Majority of respondents (81%) were found to be aware about the existence of vaccines for cervical cancer prevention. District-wise, highest (88.3%) awareness about the existence of vaccines against HPV was reported from Gautam Budh Nagar and lowest (64%) in Faridabad. Although 86 per cent of gynaecologists were aware about the names of HPV vaccines available in the market, only 27 per cent of paramedical staff had this knowledge. There was a significant difference between the respondents from government and private sectors regarding their awareness about HPV vaccines. Lack of awareness about the principal cause, risk factors and symptoms for cervical cancer and HPV vaccination was significantly (P< 0.05) reported in the respondents from paramedical staff category.Interpretation & conclusions:The findings reinforce continued medical education of healthcare providers, particularly those from the government sector on HPV vaccination for cervical cancer prevention. Public education is also pertinent for a successful HPV vaccination programme in the country.

No abstract