Reprogramming Carbohydrate Metabolism in Cancer and Its Role in Regulating the Tumor Microenvironment.

Altered metabolism has become an emerging feature of cancer cells impacting their proliferation and metastatic potential in myriad ways. Proliferating heterogeneous tumor cells are surrounded by other resident or infiltrating cells, along with extracellular matrix proteins, and other secretory factors constituting the tumor microenvironment. The diverse cell types of the tumor microenvironment exhibit different molecular signatures that are regulated at their genetic and epigenetic levels. The cancer cells elicit intricate crosstalks with these supporting cells, exchanging essential metabolites which support their anabolic processes and can promote their survival, proliferation, EMT, angiogenesis, metastasis and even therapeutic resistance. In this context, carbohydrate metabolism ensures constant energy supply being a central axis from which other metabolic and biosynthetic pathways including amino acid and lipid metabolism and pentose phosphate pathway are diverged. In contrast to normal cells, increased glycolytic flux is a distinguishing feature of the highly proliferative cancer cells, which supports them to adapt to a hypoxic environment and also protects them from oxidative stress. Such rewired metabolic properties are often a result of epigenetic alterations in the cancer cells, which are mediated by several factors including, DNA, histone and non-histone protein modifications and non-coding RNAs. Conversely, epigenetic landscapes of the cancer cells are also dictated by their diverse metabolomes. Altogether, this metabolic and epigenetic interplay has immense potential for the development of efficient anti-cancer therapeutic strategies. In this book chapter we emphasize upon the significance of reprogrammed carbohydrate metabolism in regulating the tumor microenvironment and cancer progression, with an aim to explore the different metabolic and epigenetic targets for better cancer treatment.

A Review on Carbon Quantum Dot Based Semiconductor Photocatalysts for the Abatement of Refractory Pollutants.

Photocatalysis is a green approach frequently utilised to eliminate a variety of environmentally hazardous refractory pollutants. Accordingly, the modification of semiconductor photocatalysts with Carbon Quantum Dots (CQDs) is of great importance for the treatment of such pollutants due to their attractive physical and chemical properties. CQDs are a perfect candidate to handle photocatalysts of high-performance since they operate as co-catalysts and as visible light harvesters. The higher separation rate of electron-hole pairs in the photocatalytic system is attributable to better photodegradation efficiency. This review classifies CQD based photocatalysts as pure, doped and composite materials and discusses the specific advantages of CQDs in visible light-driven photocatalysis. In this work, the versatile roles of CQDs in CQD-based photocatalytic systems are thoroughly discussed and summarised.

Histone and Chromatin Dynamics Facilitating DNA repair.

Our nuclear genomes are complexed with histone proteins to form nucleosomes, the repeating units of chromatin which function to package and limit unscheduled access to the genome. In response to helix-distorting DNA lesions and DNA double-strand breaks, chromatin is disassembled around the DNA lesion to facilitate DNA repair and it is reassembled after repair is complete to reestablish the epigenetic landscape and regulating access to the genome. DNA damage also triggers decondensation of the local chromatin structure, incorporation of histone variants and dramatic transient increases in chromatin mobility to facilitate the homology search during homologous recombination. Here we review the current state of knowledge of these changes in histone and chromatin dynamics in response to DNA damage, the molecular mechanisms mediating these dynamics, as well as their functional contributions to the maintenance of genome integrity to prevent human diseases including cancer.

An unusual case of bilateral pulmonary embolism in a patient on dual venous thromboprophylaxis, secondary to heparin induced thrombocytopenia.

Heparin Induced thrombocytopenia (HIT) is a rare, immune-mediated complication of heparin, associated with both thrombocytopenia and paradoxical thrombotic events. Initial diagnosis is made clinically when platelet count falls by 30% to <100 × 109cells/l or a > 50% decrease from baseline count in association with heparin therapy. Thromboembolic complications are seen in 50% of the cases. We present a case of acute pulmonary embolism (aPE) in a 65 year old male secondary to HIT while on unfractionated heparin for venous thromboprophylaxis. He was admitted to the hospital for severe acute exacerbation of asthma and was on heparin and venodyne boots for venous thrombo-prophylaxis. His chief presenting complaints improved until day 13, when he had severe pleuritic chest pain with worsening of shortness of breath and was desaturating while breathing ambient air. Computed tomography (CT) of the chest with intravenous contrast revealed aPE involving bilateral upper lobe segmental pulmonary arteries. Given the pattern and timing of thrombocytopenia prior to onset of his symptoms and acute thromboembolism, diagnosis of HIT was made which was later supported by positive platelet factor- ELISA and serotonin release assay (SRA) laboratory testing. Heparin and heparin-related products were promptly discontinued and argatroban was started. Later platelet count increased over 150 × 103/µL and argatroban was switched to warfarin prior to discharge. As heparin is extensively used, all physicians are required to be attentive of this life threatening complication. Discontinuing heparin while substituting with an alternative anticoagulant such as argatroban may become a life-saving strategy in such a case.

VivosX, a disulfide crosslinking method to capture site-specific, protein-protein interactions in yeast and human cells.

VivosX is an in vivo disulfide crosslinking approach that utilizes a pair of strategically positioned cysteines on two proteins to probe physical interactions within cells. Histone H2A.Z, which often replaces one or both copies of H2A in nucleosomes downstream of promoters, was used to validate VivosX. Disulfide crosslinks between cysteine-modified H2A.Z and/or H2A histones within nucleosomes were induced using a membrane-permeable oxidant. VivosX detected different combinations of H2A.Z and H2A within nucleosomes in yeast cells. This assay correctly reported the change in global H2A.Z occupancy previously observed when the deposition and eviction pathways of H2A.Z were perturbed. Homotypic H2A.Z/H2A.Z (ZZ) nucleosomes accumulated when assembly of the transcription preinitiation complex was blocked, revealing that the transcription machinery preferentially disassembles ZZ nucleosomes. VivosX works in human cells and distinguishes ZZ nucleosomes with one or two ubiquitin moieties, demonstrating that it can be used to detect protein-protein interactions inside cells from different species.