Search

Heavy metals are well-recognised as environmental hazards due to their toxicity, environmental persistence, and bioaccumulation in living organisms. Human health is a crucial concern related to terrestrial and aquatic ecosystems poisoned by harmful heavy metals. Most heavy metals pollute the air, water, and soil, which can be fatal to humans. Humans and other species can be exposed to heavy metals through the food chain if the metals oxidise or combine with other environmental elements (such as water, soil, or air). Their entry into the food chain assures interactions with biological macromolecules in living systems, including humans, resulting in undesirable outcomes. Human poisonings have typically been caused by mercury, lead, chromium, cadmium, and arsenic. The build-up of these metals in living organisms causes various harmful consequences on different organs and tissues. The gravitas of heavy metal toxicity regarding molecular impact and carcinogenesis needs in-depth understanding despite the plethora of available data. Hence, additionally, we attempt to elaborate on the multi-level impact of five heavy metals and emphasise their role in cancer development. The rationale of this essay is thus to understand the role of five heavy metals, viz., lead (Pb), cadmium (Cd), chromium (Cr), arsenic (As), and mercury (Hg), in carcinogenesis. Heavy metals interfere with various biological functions, including proliferation, differentiation, repair of damage, and apoptosis. By comparing their modes of action, we see that these metals share common mechanisms for inducing toxicity, such as reactive oxygen species (ROS) production, antioxidant defence weakening, enzyme inactivation, and oxidative stress. [ABSTRACT FROM AUTHOR]

Background: In cancer research, one of the most significant findings was to characterize the DNA repair deficiency as carcinogenic. Amongst the various repair mechanisms, mismatch repair (MMR) and direct reversal of DNA damage systems are designated as multilevel safeguards in the human genome. Defects in these elevate the rate of mutations and results in dire consequences like cancer. Of the several molecular signatures in human genome, tandem repeats (TRs) appear at various frequencies in the exonic, intronic, and regulatory regions of the DNA. Hypervariability among these repeats in the coding and non-coding regions of the genes is well characterized for solid tumours, but its significance in haematologic malignancies remains to be explored. The purpose of our study was to elucidate the role of nucleotide repeat instability in the coding and non-coding regions of 10 different repair genes in myeloid and lymphoid cell lines compared to the control samples. Methods and Results: We selected MMR deficient extensively studied microsatellite instable colorectal cancer (HCT116), and MMR proficient breast cancer (MCF-7) cells along with underemphasized haematologic cancer cell lines to decipher the hypermutability of tandem repeats. A statistically significant TR variation was observed for MSH2 and MSH6 genes in 4 and 3 of the 6 cell lines respectively. KG1 (AML) and Daudi (Burkitt's lymphoma) were found to have compromised DNA repair competency with highly unstable nucleotide repeats. Conclusion: Taken together, the results suggest that mutable TRs in intronic and non-intronic regions of repair genes in blood cancer might have a tumorigenic role. Since this is a pilot study on cell lines, high throughput research in large cohorts can be undertaken to reveal novel diagnostic markers for unexplained blood cancer patients with normal karyotypes or otherwise with karyotypic defects. [ABSTRACT FROM AUTHOR]

Melanoma is one of the most aggressive forms of skin cancer with a steady increase in global incidence and mortality rate over the past five decades. Paradoxically, both reduced and excessive sun exposure has been linked to increased risk of melanoma incidence and death. Although the histological classification of melanoma is useful in diagnosis, its molecular subtypes are often determined by somatic mutations, which could be UV-dependent or -independent. Multiple genes involved in cancer development are often mutated dysregulating molecular pathways with concomitant phenotypic heterogeneity. Hence, treating melanoma has been a challenge, with patients experiencing poor clinical outcomes to current therapeutic options. This presents an unmet need to understand the interaction of molecular networks underpinning melanogenesis. This review describes the crosstalk of signaling cascades in melanoma development and the putative druggable targets, with the view of elucidating newer and better therapeutic strategies for the disease. [ABSTRACT FROM AUTHOR]

Plant derived products have steadily gained momentum in treatment of cancer over the past decades. Curcuma and its derivatives, in particular, have diverse medicinal properties including anticancer potential with proven safety as supported by numerous in vivo and in vitro studies. A defective Mis-Match Repair (MMR) is implicated in solid tumors but its role in haematologic malignancies is not keenly studied and the current literature suggests that it is limited. Nonetheless, there are multiple pathways interjecting the mismatch repair proteins in haematologic cancers that may have a direct or indirect implication in progression of the disease. Here, through computational analysis, we target proteins that are involved in rewiring of multiple signaling cascades via altered expression in cancer using various curcuma derivatives (Curcuma longa L. and Curcuma caesia Roxb.) which in turn, profoundly controls MMR protein function. These biomolecules were screened to identify their efficacy on selected targets (in blood-related cancers); aberrations of which adversely impacted mismatch repair machinery. The study revealed that of the 536 compounds screened, six of them may have the potential to regulate the expression of identified targets and thus revive the MMR function preventing genomic instability. These results reveal that there may be potential plant derived biomolecules that may have anticancer properties against the tumors driven by deregulated MMR-pathways. [ABSTRACT FROM AUTHOR]

Among brain tumors, Medulloblastoma (MB) is one of the most common, malignant, pediatric tumors of the cerebellum. It accounts for ~20% of all childhood central nervous system (CNS) tumors. Despite, tremendous advances in drug development processes, as well as novel drugs for MB the morbidity and mortality rates, remain high. Craniospinal radiation, high-dose chemotherapy, and surgical resection are the primary therapeutic strategies. Tremendous progress in the field of "genomics" with vast amounts of data has led to the identification of four distinct molecular subgroups in medulloblastoma: WNT group, SHH group, group-III, and group-IV. The identification of these subgroups has led to individualized treatment strategies for each subgroup. Here, we discuss the various molecular subgroups of medulloblastoma as well as the differences between them. We also highlight the latest treatment strategies available for medulloblastoma. [ABSTRACT FROM AUTHOR]

Purpose: Gut microbiota is predicted to play a key role in manifestation of gastrointestinal tract cancers. The human gastrointestinal tract is a complex and abundant network of microbial community. Gut microbiota depicts the microbe population living in our intestine. Humans harbour more than 10 microbes in the gut, and the diversity and densities of the microbiota increase from stomach to colon. Methods: The beneficial relationship between endogenous microbiota and the eukaryotic hosts helps in maintaining various metabolic activities of the body as well as temperature and pH balance. Studies using culturing methods have suggested that the oesophagus is either sterile or contains only a few transient microbes that originates from the oropharynx by swallowing or from the stomach by gastroesophageal reflux. However, metagenomics suggest that large numbers of uncultured organisms are harboured in the human gut. Results: Observations suggest that research directed towards manipulation of the gut microbiota can be employed in prevention as well as treatment of these conditions. Well-designed, randomized, placebo-controlled human studies using probiotics and/or prebiotics are necessary to formulate the directions for prevention and therapy. Conclusions: Change in gut microbes in gastrointestinal (GI) tract may have major implication in gastric cancer, the fifth most occurring malignancy in the world. Affected population manifests multiple conditions and diseases, which majorly includes inflammatory bowel disease and colorectal malignancy. [ABSTRACT FROM AUTHOR]

The exfoliation of oxygenated functional groups from 60 W hydrogen plasma treated graphene oxide films was investigated using X-ray diffractometric (XRD), Raman spectroscopic and atomic force microscopic techniques. The interlayer spacing of the graphene oxide sheets was found from the XRD pattern to decrease from 0.88 to 0.35 nm after plasma treatment. The reduced intensity ratio of the D and G peaks of the Raman spectra indicates a decrease in the crystallite size of the sp domains due to plasma treatment. Atomic force microscope showed the continuous morphology of the plasma treated film. The electrical properties of plasma treated samples spin-coated on silicon were studied using Van Der Pauw and non contacting microwave techniques. The sheet resistivity determined from Van der Pauw measurements was $$1.62\,{\text{M}}\Omega /{\text{sq}}$$ , yielding the value of $$3.1\,{\text{S}}\,{\text{m}}^{ - 1}$$ for the bulk conductivity. The charge mobility of $$3.8\,{\text{m}}^{2} \,{\text{V}}^{ - 1} \,{\text{s}}^{ - 1}$$ has been determined from Hall measurement technique. [ABSTRACT FROM AUTHOR]

The epimutational event, i.e., ectopic methylation in tumor suppressor genes, can lead to gene silencing, thus promoting prognosis of cancer. The progression of DNA methylation is a cycle of demethylation, de novo methylation, and maintenance methylation. The enzyme responsible for maintenance of methylation status is DNA methyltransferase 1 (DNMT1), the continuous activity of which is required to maintain the pattern of epimutation; thus, its inhibition is a promising strategy for the treatment of cancer. To the best of our knowledge, this study is the first to focus on the recently developed crystal structure of the catalytic site of DNMT1. Here in this study, we have used the crystal structure for the development of non-nucleoside DNMT1 inhibitors using virtual screening (VS), absorption, distribution, metabolism, elimination/toxicology analysis, and molecular docking studies. In this study, VS was carried out on 48,531 natural products to create a subset of lead-like natural products. Three of them were found to form hydrogen bonds with the catalytic site of the DNMT1 (Cys 1226). Thus, this study adumbrates potential lead compounds for treatment of epimutation. [ABSTRACT FROM AUTHOR]