Microplastics pollution in the marine environment: A review of sources, impacts and mitigation.

Over the past few years, microplastics (MPs) pollution in the marine environment has emerged as a significant environmental concern. Poor management practices lead to millions of tons of plastic waste entering oceans annually, primarily from land-based sources like mismanaged waste, urban runoff, and industrial activities. MPs pollution in marine environments poses a significant threat to ecosystems and human health, as it adsorbs pollutants, heavy metals, and leaches additives such as plasticizers and flame retardants, thus contributing to chemical pollution.

Envisioning Glucose Transporters (GLUTs and SGLTs) as Novel Intervention against Cancer: Drug Discovery Perspective and Targeting Approach.

Metabolic reprogramming and altered cellular energetics have been recently established as an important cancer hallmark. The modulation of glucose metabolism is one of the important characteristic features of metabolic reprogramming in cancer. It contributes to oncogenic progression by supporting the increased biosynthetic and bio-energetic demands of tumor cells.

Phytochemicals and Nanotechnology: A Powerful Combination against Breast Cancer.

Considerable advancements have been made in breast cancer therapeutics in the past few decades. However, the advent of chemo-resistance and adverse drug reactions coupled with tumor metastasis and recurrence posed a serious threat to combat this lethal disease. Novel anti-cancer agents, as well as new therapeutic strategies, are needed to complement conventional breast cancer therapies.

A cub and sushi domain-containing protein with esterase-like activity confers insecticide resistance in the Indian malaria vector Anopheles stephensi.

Chemical insecticides (organophosphates and pyrethroids) in the form of IRS (Indoor Residual Sprays) and LLINs (Long Lasting Insecticidal Nets) are the cornerstone for vector control, globally. However, their incessant use has resulted in widespread development of resistance in mosquito vectors, warranting continuous monitoring and investigation of the underlying mechanisms of resistance. Here, we identified a previously uncharacterized- Cub and Sushi Domain containing Insecticide Resistance (CSDIR) protein and generated evidence for its role in mediating insecticide resistance in the Anopheles stephensi.

Expression of major facilitator superfamily protein in transporters - Δ identifies a drug transporter.

To assess the functional relevance of a putative Major Facilitator Superfamily protein (PF3D7_0210300; 'MFSDT') as a drug transporter, using for orthologous protein expression. Complementary Determining Sequence encoding MFSDT was integrated into the genome of genetically engineered strain MSY8 via homologous recombination, followed by assessing its functional relevance as a drug transporter. The modified strain exhibited plasma membrane localization of MFSDT and characteristics of an Major Facilitator Superfamily transporter, conferring resistance to antifungals, ketoconazole and itraconazole.

Targeting host inducible-heat shock protein 70 with PES-Cl is a promising antiviral strategy against SARS-CoV-2 infection and pathogenesis.

One of the fundamental mechanisms developed by the host to contain the highly infectious and rapidly proliferating SARS-coronavirus is elevation of body temperature, a natural fallout of which is heat shock proteins over-expression. Here, for the first time, we demonstrate that the SARS-CoV-2 exploits the host Heat shock protein 70 (Hsp70) chaperone for its entry and propagation, and blocking it can combat the infection. SARS-CoV-2 infection as well as febrile temperature enhanced Hsp70 expression in host Vero E6 cells.

Mass Spectrometric and Artificial Intelligence-Based Identification of the Secretome of Plasmodium falciparum Merozoites to Provide Novel Candidates for Vaccine Development Pipeline.

Purpose: Merozoites are the only extracellular form of blood stage parasites, making it a worthwhile target. Multiple invasins that are stored in the merozoite apical organelles, are secreted just prior to invasion, and mediates its interaction with RBC. A comprehensive identification of all these secreted invasins is lacking and this study addresses that gap.

G6PD deficiency mediated impairment of iNOS and lysosomal acidification affecting phagocytotic clearance in microglia in response to SARS-CoV-2.

The glucose-6-phosphate dehydrogenase (G6PD) deficiency is X-linked and is the most common enzymatic deficiency disorder globally. It is a crucial enzyme for the pentose phosphate pathway and produces NADPH, which plays a vital role in regulating the oxidative stress of many cell types. The deficiency of G6PD primarily causes hemolytic anemia under oxidative stress triggered by food, drugs, or infection.

Prefoldins are novel regulators of the unfolded protein response in artemisinin resistant Plasmodium falciparum malaria.

Emerging Artemisinin (ART) resistance in Plasmodium falciparum (Pf) poses challenges for the discovery of novel drugs to tackle ART-resistant parasites. Concentrated efforts toward the ART resistance mechanism indicated a strong molecular link of ART resistance with upregulated expression of unfolded protein response pathways involving Prefoldins (PFDs). However, a complete characterization of PFDs as molecular players taking part in ART resistance mechanism, and discovery of small molecule inhibitors to block this process have not been identified to date.

Targeting Prohibitin 2-Hu-Hsp70A1A complex as a unique approach towards malaria vaccine development.

Malaria parasite invasion to host erythrocytes is mediated by multiple interactions between merozoite ligands and erythrocyte receptors that contribute toward the development of disease pathology. Here, we report a novel antigen prohibitin "PHB2" and identify its cognate partner "Hsp70A1A" in host erythrocyte that plays a crucial role in mediating host-parasite interaction during merozoite invasion. Using small interfering RNA (siRNA)- and glucosamine-6-phosphate riboswitch (glmS) ribozyme-mediated approach, we show that loss of Hsp70A1A in red blood cells (RBCs) or PHB2 in infected red blood cells (iRBCs), respectively, inhibit PHB2-Hsp70A1A interaction leading to invasion inhibition.

Interplay Between Diabetes Mellitus and the Occurrence of Osteoarthritis and Associated Conditions in Women of Menopausal Age.

Osteoarthritis (OA) and diabetes mellitus (DM) have long-term deleterious chronic effects and are among the most prevalent chronic disorders. DM and its associated factors, such as hyperglycemia, have a significant contribution to the pathophysiology of OA, particularly in post-menopausal women. Women who have uncontrolled diabetes (DM) are more prone to develop osteoarthritis (OA), which may be exacerbated by poor glycemic control.

Unique Synthetic Strategy for Probing in Situ Lysosomal NO for Screening Neuroinflammatory Phenotypes against SARS-CoV-2 RNA in Phagocytotic Microglia.

In the pathogenesis of microglia, brain immune cells promote nitrergic stress by overproducing nitric oxide (NO), leading to neuroinflammation. Furthermore, NO has been linked to COVID-19 progression, which has caused significant morbidity and mortality. SARS-CoV-2 infection activates inflammation by releasing excess NO and causing cell death in human microglial clone 3 (HMC3).

Inhibitors to degraders: Changing paradigm in drug discovery.

The chemical understanding of biological processes provides not only a deeper insight but also a solution to abnormal biological functioning. Protein degradation, a natural biological process for debris removal in the cell, has been studied for years. The recent finding that natural degradation pathways can be utilized for therapeutic purposes is a paradigm shift in the drug discovery approach.

Spatiotemporal variations, sources, pollution status and health risk assessment of dissolved trace elements in a major Arabian Sea draining river: insights from multivariate statistical and machine learning approaches.

River Mahi drains through semi-arid regions (Western India) and is a major Arabian Sea draining river. As the principal surface water source, its water quality is important to the regional population. Therefore, the river water was sampled extensively (n = 64, 16 locations, 4 seasons and 2 years) and analyzed for 11 trace elements (TEs; Sr, V, Cu, Ni, Zn, Cd, Ba, Cr, Mn, Fe, and Co).

Understanding the complex formation of falstatin; an endogenous macromolecular inhibitor of falcipains.

Proteolytic activity constitutes a fundamental process essential for the survival of the malaria parasite and is thus highly regulated. Falstatin, a protease inhibitor of Plasmodium falciparum, tightly regulates the activity of cysteine hemoglobinases, falcipain-2 and 3 (FP2, FP3), by inhibiting FP2 through a single surface exposed loop. However, the multimeric nature of falstatin and its interaction with FP2 remained unexplored.

Development of pathophysiologically relevant models of sickle cell disease and β-thalassemia for therapeutic studies.

Ex vivo cellular system that accurately replicates sickle cell disease and β-thalassemia characteristics is a highly sought-after goal in the field of erythroid biology. In this study, we present the generation of erythroid progenitor lines with sickle cell disease and β-thalassemia mutation using CRISPR/Cas9. The disease cellular models exhibit similar differentiation profiles, globin expression and proteome dynamics as patient-derived hematopoietic stem/progenitor cells.

Mesenchymal stem cells-derived extracellular vesicles for therapeutics of renal tuberculosis.

Extrapulmonary tuberculosis with a renal involvement can be a manifestation of a disseminated infection that requires therapeutic intervention, particularly with a decrease in efficacy of conventional regimens. In the present study, we investigated the therapeutic potency of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) in the complex anti-tuberculosis treatment (ATT). A rabbit model of renal tuberculosis (rTB) was constructed by injecting of the standard strain Mycobacterium tuberculosis H37Rv into the cortical layer of the kidney parenchyma.

Biological evaluation of novel side chain containing CQTrICh-analogs as antimalarials and their development as CDPK1 kinase inhibitors.

The rapid emergence of resistance to existing frontline antimalarial drugs emphasizes a need for the development of target-oriented molecules with novel modes of action. Given the importance of a plant-like Calcium-Dependent Protein Kinase 1 (CDPK1) as a stand-alone multistage signalling regulator of . , we designed and synthesized 7-chloroquinoline-indole-chalcones tethered with a triazole (CQTrICh-analogs - and directed towards CDPK1.

Mesenteric Cyst: A Rare Entity.

Mesenteric cysts are rare entities that are challenging to diagnose and treat because of their variable presentation and histological characteristics. They have been majorly classified into six groups, out of which, the chylo-lymphatic type is the most common. Their etiology remains poorly understood but is usually linked to lymphatic pathologies.

Blood-stage antimalarial activity, favourable metabolic stability and in vivo toxicity of novel piperazine linked 7-chloroquinoline-triazole conjugates.

The persistence of drug resistance poses a significant obstacle to the advancement of efficacious malaria treatments. The remarkable efficacy displayed by 1,2,3-triazole-based compounds against Plasmodium falciparum highlights the potential of triazole conjugates, with diverse pharmacologically active structures, as potential antimalarial agents. We aimed to synthesize 7-dichloroquinoline-triazole conjugates and their structure-activity relationship (SAR) derivatives to investigate their anti-plasmodial activity.

X-ray reflectivity study of the heat shock protein Hsp70 interaction with an artificial cell membrane model.

Membrane-bound heat shock protein 70 (Hsp70) apart from its intracellular localization was shown to be specifically expressed on the plasma membrane surface of tumor but not normal cells. Although the association of Hsp70 with lipid membranes is well documented the exact mechanisms for chaperone membrane anchoring have not been fully elucidated. Herein, we addressed the question of how Hsp70 interacts with negatively charged phospholipids in artificial lipid compositions employing the X-ray reflectivity (XRR) studies.