Matrix metalloproteinases and gastrointestinal cancers: Impacts of dietary antioxidants

The process of carcinogenesis is tightly regulated by antioxidant enzymes and matrix degrading enzymes, namely, matrix metalloproteinases(MMPs). Degradation of extracellular matrix(ECM) proteins like collagen, proteoglycan, laminin, elastin and fibronectin is considered to be the prerequisite for tumor invasion and metastasis. MMPs can degrade essentially all of the ECM components and, most MMPs also substantially contribute to angiogenesis, differentiation, proliferation and apoptosis. Hence, MMPs are important regulators of tumor growth both at the primary site and in distant metastases; thus the enzymes are considered as important targets for cancer therapy. The implications of MMPs in cancers are no longer mysterious; however, the mechanism of action is yet to be explained. Herein, our major interest is to clarify how MMPs are tied up with gastrointestinal cancers. Gastrointestinal cancer is a variety of cancer types, including the cancers of gastrointestinal tract and organs, i.e., esophagus, stomach, biliary system, pancreas, small intestine, large intestine, rectum and anus. The activity of MMPs is regulated by its endogenous inhibitor tissue inhibitor of metallopro-teinase(TIMP) which bind MMPs with a 1:1 stoichiometry. In addition, RECK(reversion including cysteinerich protein with kazal motifs) is a membrane bound glycoprotein that inhibits MMP-2,-9 and-14. Moreover, α2-macroglobulin mediates the uptake of several MMPs thereby inhibit their activity. Cancerous conditions increase intrinsic reactive oxygen species(ROS) through mitochondrial dysfunction leading to altered protease/anti-protease balance. ROS, an index of oxidative stress is also involved in tumorigenesis by activation of different MAP kinase pathways including MMP induction. Oxidative stress is involved in cancer by changing the activity and expression of regulatory proteins especially MMPs. Epidemiological studies have shown that high intake of fruits that rich in antioxidants is associated with a lower cancer incidence. Evidence indicates that some antioxidants inhibit the growth of malignant cells by inducing apoptosis and inhibiting the activity of MMPs. This review is discussed in six subchapters, as follows.

Engineered magnetic core shell nanoprobes:Synthesis and applications to cancer imaging and therapeutics

Magnetic core shell nanoparticles are composed of a highly magnetic core material surrounded by a thin shell of desired drug, polymer or metal oxide. These magnetic core shell nanoparticles have a wide range of applications in biomedical research, more specifically in tissue imaging, drug delivery and therapeutics. The present review discusses the up-to-date knowledge on the various procedures for synthesis of magnetic core shell nanoparticles along with their applications in cancer imaging, drug delivery and hyperthermia or cancer therapeutics. Literature in this area shows that magnetic core shell nanoparticle-based imaging, drug targeting and therapy through hyperthermia can potentially be a powerful tool for the advanced diagnosis and treatment of various cancers.

Pathophysiological responses from human gut microbiome

The human gastrointestinal tract harbors a vast collection of symbiotic microorganisms-collectively termed as "gut microbiome". This microbiota has important effect in immune system and other host activities. Recent studies have suggested that alterations of the normal gut microbiota are associated with various human diseases and psychological disorders. The underlying cause, once proven, may provide novel insights into the importance of gut flora in human health. In this review, we give an attempt to describe how the alteration in the microbial community causes the development of certain widespread pathophysiological disorders; focusing on inflammatory bowel disease, colorectal cancer, obesity and autism. Proper knowledge about the hostmicrobiota interaction and linkage could be essential for the development of future personalized strategies of therapeutics.

Acquisition and dissemination mechanisms of CTXΦ in Vibrio cholerae : New paradigm for dif residents

Vibrio cholerae(V. cholerae) genome is equipped with a number of integrative mobile genetic element(IMGE) like prophages, plasmids, transposons or genomic islands, which provides fitness factors that help the pathogen to survive in changing environmental conditions. Metagenomic analyses of clinical and environmental V. cholerae isolates revealed that dimer resolution sites(dif) harbor several structurally and functionally distinct IMGEs. All IMGEs present in the dif region exploit chromosomally encoded tyrosine recombinases, Xer C and Xer D, for integration. Integration takes place due to site-specific recombination between two specific DNA sequences; chromosomal sequence is called att B and IMGEs sequence is called att P. Different IMGEs present in the att P region have different attP structure but all of them are recognized by Xer C and Xer D enzymes and mediate either reversible or irreversible integration. Cholera toxin phage(CTXΦ), a lysogenic filamentous phage carrying the cholera toxin genes ctx AB, deserves special attention because it provides V. cholerae the crucial toxin and is always present in the dif region of all epidemic cholera isolates. Therefore, understanding the mechanisms of integration and dissemination of CTXΦ, genetic and ecological factors which support CTXΦ integration as well as production of virion from chromosomally integrated phage genome and interactions of CTXΦ with other genetic elements present in the genomes of V. cholerae is important for learning more about the biology of cholera pathogen.

Author affiliation addition:“Hepatitis B virus detected in paper currencies in a densely populated city of India:A plausible source of horizontal transmission?”

Addition of authors’affiliation to"Hepatitis B virus detected in paper currencies in a densely populated city of India:A plausible source of horizontal transmission?"World J Hepatol 2020 Oct 27;12(10):775-791.In this article,one of the affiliations of two authors was not mentioned.Ruchi Supekar,a joint first author and Subhajit Biswas,the corresponding author are affiliated to Academy of Scientific and Innovative Research(AcSIR)Ghaziabad-201002,India.

Biomimetically Synthesized Aqueous Ferrofluids Having Antibacterial and Anticancer Properties

Synthesis of functional iron oxide nanoparticles, well dispersed in aqueous fluids still remains a challenge as its stability requires a delicate balance between electrostatic and magnetic interactions. Templated synthesis using biomolecules is useful because the biomolecules have their unique arrangement in aqueous systems that enhance stability, commonly called “biomimetic synthesis”. We have developed a one-pot in-situ, low energy process for the synthesis of highly monodispersed, Collagen Functionalized Ferrofluids (CFF) as a templating agent in an aqueous medium. The nanoparticles so obtained were characterized by X-ray diffraction (XRD), dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR). The antibacterial activity in terms of minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and growth inhibition has been assessed against gram positive, Staphylococcus aureus, ATCC 13709 (native strain) and in Escherichia coli, DH5α gram negative bacteria. The cytotoxicity of the CFFs on cancer cell lines human embryonic kidney (HEK), breast adenocarcinoma (MCF-7) and Ehrlich ascitic carcinoma (EAC) have also been investigated. CFFs indicated variable MIC and MBC values against S. aureus and E. coli being minimum for 1.5% CFF (MIC:23.43 μg/ml and 93.75 μg/ml and MBC: 46.87 μg/ml and 187.5 μg/ml). The observed cytotoxicity in mammalian cells indicated the susceptibility of MCF-7 breast cancer cells when compared to HEK cells.

The curative effect of fucoidan on visceral leishmaniasis is mediated by activation of MAP kinases through specific protein kinase C isoforms

Fucoidan can cure both antimony-sensitive and antimony-resistant visceral leishmaniasis through immune activation. However, the signaling events underlying this cellular response remain uncharacterized. The present study reveals that fucoidan induces activation of p38 and ERKI/2 and NF-κB DNA binding in both normal and Leishmania donovani.infected macrophages, as revealed by western blotting and electrophoretic mobility shift assay （EMSA）, respectively. Pharmacological inhibition of p38, ERKI/2 or the NF-κB pathway markedly attenuated fucoidan-induced pro-inflammatory cytokine synthesis and inducible nitric oxide synthase （iNOS） gene transcription, resulting in a reduction of parasite clearance. To decipher the underlying mechanism of fucoidan-mediated parasite suppression, the expression and functionality of various protein kinase C （PKC） isoforms were evaluated by immunoblotting and enzyme activity assay. Fucoidan elicited an increase in expression and activity of PKC-α, -β1 and -βⅡ isoforms in infected macrophages. Functional knockdown of PKC-α and -β resulted in downregulation of p38 and ERKI/2, along with a marked reduction of IL-12 and TNF-α production in fucoidan-treated infected macrophages. Collectively, these results suggest that the curative effect of fucoidan is mediated by PKC-dependent activation of the mitogen-activated protein kinase （MAPK）/NF-κB pathway, which ultimately results in the production of nitric oxide （NO） and disease-resolving pro-inflammatory cytokines.