Polymer-mediated nanoformulations: a promising strategy for cancer immunotherapy.

Engineering polymer-based nano-systems have attracted many researchers owing to their unique qualities like shape, size, porosity, mechanical strength, biocompatibility, and biodegradability. Both natural and synthetic polymers can be tuned to get desired surface chemistry and functionalization to improve the efficacy of cancer therapy by promoting targeted delivery to the tumor site. Recent advancements in cancer immunoediting have been able to manage both primary tumor and metastatic lesions via activation of the immune system. The combinations of nano-biotechnology and immunotherapeutic agents have provided positive outcomes by enhancing the host immune response in cancer therapy. The nanoparticles have been functionalized using antibodies, targeted antigens, small molecule ligands, and other novel agents that can interact with biological systems at nanoscale levels. Several polymers, such as polyethylene glycol (PEG), poly(lactic-co-glycolic acid) (PLGA), poly(ε-caprolactone) (PCL), and chitosan, have been approved by the Food and Drug Administration for clinical use in biomedicine. The polymeric nanoformulations such as polymers-antibody/antigen conjugates and polymeric drug conjugates are currently being explored as nanomedicines that can target cancer cells directly or target immune cells to promote anti-cancer immunotherapy. In this review, we focus on scientific developments and advancements on engineered polymeric nano-systems in conjugation with immunotherapeutic agents targeting the tumor microenvironment to improve their efficacy and the safety for better clinical outcomes.

Fumarate and nitrite reduction by Prevotella nigrescens and Prevotella buccae isolated from Chronic Periodontitis patients.

OBJECTIVE: This study is an investigation of anaerobic nitrite and fumarate reduction/respiration abilities of two characterised Prevotella species namely Prevotella nigrescens (SS6B) and Prevotella buccae (GS6B) isolated from the periodontal pockets of chronic periodontitis (ChP) patients. METHODS: Isolation and identification of the periodontal bacteria from 20 patients showing clinical symptoms of ChP. Characterisation of anaerobic nitrite and fumarate reduction was done in P. nigrescens (SS6B) and P. buccae (GS6B) using reduction assays, inhibition assays with use of specific inhibitors, growth assays and enzyme activity assays. Degenerate PCR was used to detect and amplify nitrite reductase (nrfA) and fumarate reductase (frdA) gene sequences in these Prevotella isolates. In addition, molecular and in silico analysis of the amplified anaerobic reductase gene sequences was performed using NCBI conserved domain analysis, Interpro database and MegaX. RESULTS: We provided experimental evidence for presence of active nitrite and fumarate reductase activities through enzyme activity, reduction, inhibitor and growth assays. Moreover, we were able to detect presence of 505 bps nrfA gene fragment and 400 bps frdA gene fragment in these Prevotella spp. These fragments show similarity to multiheme ammonia forming cytochrome c nitrite reductases and fumarate reductases flavoprotein subunit, respectively. CONCLUSION: Anaerobic nitrite and fumarate respiration abilities in P. nigrescens and P. buccae isolates appear to be important for detoxification process and growth, respectively.

Prevotella: An insight into its characteristics and associated virulence factors.

Prevotella species, a gram-negative obligate anaerobe, is commonly associated with human infections such as dental caries and periodontitis, as well as other conditions such as chronic osteomyelitis, bite-related infections, rheumatoid arthritis and intestinal diseases like ulcerative colitis. This generally harmless commensal possesses virulence factors such as adhesins, hemolysins, secretion systems exopolysaccharide, LPS, proteases, quorum sensing molecules and antibiotic resistance to evolve into a well-adapted pathogen capable of causing successful infection and proliferation in the host tissue. This review describes several of these virulence factors and their advantage to Prevotella spp. in causing inflammatory diseases like periodontitis. In addition, using genome analysis of Prevotella reference strains, we examined other putative virulence determinants which can provide insights as biomarkers and be the targets for effective interventions in Prevotella related diseases like periodontitis.

Studies on bromadiolone resistance in Rattus rattus populations from Punjab, India.

There are several reports on development of resistance to bromadiolone in different species of rodents around the globe, however, there is no such report involving systematic study from India. Hence, present study was carried out to investigate current status of bromadiolone resistance in house rat (Rattus rattus; n=154) collected from different poultry farms (n=8) based on feeding test, blood clotting response (BCR) test and molecular characterization of VKORC1 gene. Based on feeding test and BCR test, 28% rats were suspected to be resistant. Molecular analysis of VKORC1 gene of four suspected to be resistant rats having Prothrombin Time (PT) <70s, International Normalized Ratio (INR) <4.0 and died between 26 and 73days after treatment revealed no single nucleotide polymorphism (SNP) in nucleotide sequences. None of the sample under study showed complete nucleotide homology with previously reported nucleotide sequences of R. rattus. The sequences of VKORC1 gene under study can thus be considered as the novel sequences. Present investigation on molecular characterization of VKORC1 gene did not reveal any genetic resistance in Rattus rattus population against bromadiolone though rats could be considered resistant based on BCR and feeding tests.