Distribution, toxicity load and risk assessment of heavy metals in the groundwater of Dhemaji, Assam, India.

Metal contamination in drinking water has drawn attention since it gravely jeopardizes human health. This study was conducted in pre- and post-monsoon season in 2021 at Dhemaji, Assam, India. It characterized metal pollutants in groundwater, their distribution, possible sources, and evaluated the potential toxicity and associated health risk assessment. The seasonal mean concentration of Fe in both seasons is observed highest followed by Mn, Zn, Cu, As, and Ni. Furthermore, the metal concentrations during pre-monsoon are comparatively higher. The geogenic processes and agricultural practices are the major sources of groundwater metal contamination as evident from the statistical analysis. The different pollution indices viz. Heavy-metal Pollution Index (HPI), Heavy-metal Evaluation Index (HEI) and Degree of Contamination (Cd) suggested that groundwater is not suitable for drinking uses. The Heavy Metal Toxicity Load (HMTL) suggesting As, Co, Mn and Hg should be removed from the groundwater to ensure safety. Water pollution indices (WPI) suggest that Fe, Mn, As and Ni are the main pollution-causing metals in the study area which may be restored under the BIS and WHO limit by diluting the water. The human health risk has been calculated by carcinogenic and non-carcinogenic risk assessment. The non-carcinogenic risk for adults and children is within the threshold limit. The carcinogenic risk shows that continuous exposure of As and Ni may give rise to cancer among adults and children in the region. Therefore, comprehensive groundwater quality monitoring with well-planned treatment should be needed to provide safe and clean drinking water in the studied area.

Very Small Embryonic-Like Stem Cells Transform Into Cancer Stem Cells and Are Novel Candidates for Detecting/Monitoring Cancer by a Simple Blood Test.

Cancer continues to remain a "Black Box," as there is no consensus on how it initiates, progresses, metastasizes, or recurs. Many imponderables exist about whether somatic mutations initiate cancer, do cancer stem cells (CSCs) exist, and if yes, are they a result of de-differentiation or originate from tissue-resident stem cells; why do cancer cells express embryonic markers, and what leads to metastasis and recurrence. Currently, the detection of multiple solid cancers through liquid biopsy is based on circulating tumor cells (CTCs) or clusters, or circulating tumor DNA (ctDNA). However, quantity of starting material is usually adequate only when the tumor has grown beyond a certain size. We posit that pluripotent, endogenous, tissue-resident, very small embryonic-like stem cells (VSELs) that exist in small numbers in all adult tissues, exit from their quiescent state due to epigenetic changes in response to various insults and transform into CSCs to initiate cancer. VSELs and CSCs share properties like quiescence, pluripotency, self-renewal, immortality, plasticity, enrichment in side-population, mobilization, and resistance to oncotherapy. HrC test, developed by Epigeneres, offers the potential for early detection of cancer using a common set of VSEL/CSC specific bio-markers in peripheral blood. In addition, NGS studies on VSELs/CSCs/tissue-specific progenitors using the All Organ Biopsy (AOB) test provide exomic and transcriptomic information regarding impacted organ(s), cancer type/subtype, germline/somatic mutations, altered gene expressions, and dysregulated pathways. To conclude, HrC and AOB tests can confirm the absence of cancer and categorize the rest of subjects into low/moderate/high risk of cancer, and also monitor response to therapy, remission, and recurrence.

Antimicrobial Agents Based on Metal Complexes: Present Situation and Future Prospects.

The rise in antimicrobial resistance is a cause of serious concern since the ages. Therefore, a dire need to explore new antimicrobial entities that can combat against the increasing threat of antibiotic resistance is realized. Studies have shown that the activity of the strongest antibiotics has reduced drastically against many microbes such as microfungi and bacteria (Gram-positive and Gram-negative). A ray of hope, however, was witnessed in early 1940s with the development of new drug discovery and use of metal complexes as antibiotics. Many new metal-based drugs were developed from the metal complexes which are potentially active against a number of ailments such as cancer, malaria, and neurodegenerative diseases. Therefore, this review is an attempt to describe the present scenario and future development of metal complexes as antibiotics against wide array of microbes.

Mannose glycosylation is an integral step for NIS localization and function in human breast cancer cells.

Chasing an intriguing biological question on the disparity of sodium iodide symporter (NIS, officially known as SLC5A5) expression and function in the clinical scenario of breast cancer, this study addresses key molecular defects involved. NIS in cancer patients has primarily been recorded to be a cytoplasmic protein, thus limiting the scope for targeted radio-iodine therapy. We developed NIS transgene-overexpressing MCF-7 breast cancer cells, and found a few clonal derivatives that show predominant expression of NIS in the plasma membrane. The majority of clones, however, showed cytosolic NIS expression over long passages. Cells expressing membranous NIS show unperturbed dynamic trafficking of NIS through secretory pathway organelles when compared to cells expressing cytoplasmic NIS or to parental cells. Further, treatment of cells expressing membranous NIS with specific glycosylation inhibitors highlighted the importance of inherent glycosylation processing and an 84 gene signature glycosylation RT-Profiler array revealed that clones expressing NIS in their membrane cluster separately compared to the other cells. We further confirm a role of three differentially expressed genes, i.e. MAN1B1, MAN1A1 and MAN2A1, in regulating NIS localization by RNA interference. Thus, this study shows the important role of mannosidase in N-glycosylation processing in order to correctly traffic NIS to the plasma membrane in breast cancer cells.This article has an associated First Person interview with the first author of the paper.

Image Guidance in Stem Cell Therapeutics: Unfolding the Blindfold.

Stem cell therapeutics is the future of regenerative medicine in the modern world. Many studies have been instigated with the hope of translating the outcome for the treatment of several disease conditions ranging from heart and neuronal disease to malignancies as grave as cancers. Stem cell therapeutics undoubtedly holds great promise on the front of regenerative medicine, however, the correct distribution and homing of these stem cells to the host site remained blinded until the recent advances in the discipline of molecular imaging. Herein, we discuss the various imaging guidance applied for determination of the proper delivery of various types of stem cell used as therapeutics for various maladies. Additionally, we scrutinize the use of several indirect labeling mechanisms for efficient tagging of the reporter entity for image guidance. Further, the promise of improving patient healthcare has led to the initiation of several clinical trials worldwide. However, in number of the cases, the benefits arrive with a price heavy enough to pose a serious health risk, one such being formation of teratomas. Thus numerous challenges and methodological obstacles must be overcome before their eloquent clinical impact can be realized. Therefore, we also discuss several clinical trials that have taken into consideration the various imaging guided protocols to monitor correct delivery and understand the distribution of therapeutic stem cells in real time.

Genetic defects in Indian Wilson disease patients and genotype-phenotype correlation.

Wilson disease (WD) is caused by defects in ATP7B gene due to impairment of normal function of the copper transporting P-type ATPase. This study describes a comprehensive genetic analysis of 199 Indian WD patients including mutations detected in our previous studies, undertakes functional assessment of the nucleotide variants in ATP7B promoter and correlates genotype with disease phenotype. The patient cohort harbors a total of 10 common and 48 rare mutations in the coding region of ATP7B including 21 novel changes. The common mutations represent 74% of characterized coding mutant alleles with p.C271X (63/260) and p.G1101R (7/31) being the most prevalent in eastern and western Indian patients, respectively. The mutation spectrum between east and west is mostly different with only three mutations (p.G1061E, p.N1270S and p.A1049A-fs) being shared between both the groups. Eight novel and 10 reported variants have been detected in the promoter and non-coding regions (5' and 3'UTRs) of ATP7B. Promoter reporter assay demonstrated that 3 novel variants and 5 reported polymorphisms alter the gene expression to a considerable extent; hence might play important role in ATP7B gene regulation. We devised the neurological involvement score to capture the spectrum of neurological involvement in WD patients. By utilizing the age at onset, neurological involvement score and ATP7B mutation background, we generated a genotype-phenotype matrix that could be effectively used to depict the phenotypic spectra of WD affected individuals and serve as a platform to identify prospective "outliers" to be investigated for their remarkable phenotypic divergence.