Noncoding RNAs as therapeutic targets in autophagy-related diabetic cardiomyopathy.

Diabetic cardiomyopathy, a multifaceted complication of diabetes mellitus, remains a major challenge in clinical management due to its intricate pathophysiology. Emerging evidence underscores the pivotal role of autophagy dysregulation in the progression of diabetic cardiomyopathy, providing a novel avenue for therapeutic intervention. Noncoding RNAs (ncRNAs), a diverse class of regulatory molecules, have recently emerged as promising candidates for targeted therapeutic strategies. The exploration of various classes of ncRNAs, including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) reveal their intricate regulatory networks in modulating autophagy and influencing the pathophysiological processes associated with diabetic cardiomyopathy. The nuanced understanding of the molecular mechanisms underlying ncRNA-mediated autophagic regulation offers a rationale for the development of precise and effective therapeutic interventions. Harnessing the regulatory potential of ncRNAs presents a promising frontier for the development of targeted and personalized therapeutic strategies, aiming to ameliorate the burden of diabetic cardiomyopathy in affected individuals. As research in this field advances, the identification and validation of specific ncRNA targets hold immense potential for the translation of these findings into clinically viable interventions, ultimately improving outcomes for patients with diabetic cardiomyopathy. This review encapsulates the current understanding of the intricate interplay between autophagy and diabetic cardiomyopathy, with a focus on the potential of ncRNAs as therapeutic targets.

Sustainable production of algae-bacteria granular consortia based biological hydrogen: New insights.

Microbes recycling nutrient and detoxifying ecosystems are capable to fulfil the future energy need by producing biohydrogen by due to the coupling of autotrophic and heterotrophic microbes. In granules microbes mutualy exchanging nutrients and electrons for hydrogen production. The consortial biohydrogen production depend upon constituent microbes, their interdependence, competition for resources, and other operating parameters while remediating a waste material in nature or bioreactor. The present review deals with development of granular algae-bacteria consortia, hydrogen yield in coculture, important enzymes and possible engineering for improved hydrogen production.

Biologically Active α-Amino Amide Analogs and γδ T Cells-A Unique Anticancer Approach for Leukemia.

Advanced stage cancers are aggressive and difficult to treat with mono-therapeutics, substantially decreasing patient survival rates. Hence, there is an urgent need to develop unique therapeutic approaches to treat cancer with superior potency and efficacy. This study investigates a new approach to develop a potent combinational therapy to treat advanced stage leukemia. Biologically active α-amino amide analogs (RS)-N-(2-(cyclohexylamino)-2-oxo-1-phenylethyl)-N-phenylpropiolamide (α-AAA-A) and (RS)-N-(2-(cyclohexylamino)-2-oxo-1-phenylethyl)-N-phenylbut2-enamide (α-AAA-B) were synthesized using linear Ugi multicomponent reaction. Cytotoxicities and IC50 values of α-AAA-A and α-AAA-B against leukemia cancer cell lines (HL-60 and K562) were analyzed though MTT assay. Cytotoxic assay analyzed percent killing of leukemia cell lines due to the effect of γδ T cells alone or in combination with α-AAA-A or α-AAA-B. Synthesized biologically active molecule α-AAA-A exhibited increased cytotoxicity of HL-60 (54%) and K562 (44%) compared with α-AAA-B (44% and 36% respectively). Similarly, α-AAA-A showed low IC50 values for HL-60 (1.61 ± 0.11 µM) and K562 (3.01 ± 0.14 µM) compared to α-AAA-B (3.12 ± 0.15 µM and 6.21 ± 0.17 µM respectively). Additive effect of amide analogs and γδ T cells showed significantly high leukemia cancer cell killing as compared to γδ T cells alone. A unique combinational therapy with γδ T cells and biologically active anti-cancer molecules (α-AAA-A/B), concomitantly may be a promising cancer therapy.

Optimization of methods for peripheral blood mononuclear cells isolation and expansion of human gamma delta T cells.

Human Vg9/Vδ2 T cells (γδ T cells) are immune surveillance cells both in innate and adaptive immunity and are a possible target for anticancer therapies, which can induce immune responses in a variety of cancers. Small non-peptide antigens such as zoledronate can do activation and expansion of T cells in vitro. It is evident that for adoptive cancer therapies, large numbers of functional cells are needed into cancer patients. Hence, optimization of methods needs to be carried out for the efficient expansion of these T cells. Standardization of peripheral blood mononuclear cells (PBMCs) isolation was devised. Cytokines (interleukin 2 (IL-2) and interleukin 15 (IL-15)) and zoledronate were also standardized for different concentrations. It was found that an increased number of PBMCs were recovered when washing was done at 1100 revolution per minute (rpm). Significantly high expansion fold was (2524 ± 787 expansion fold) achieved when stimulation of PBMCs was done with 1 µM of zoledronate and both cytokines IL-2 and IL-15 supported the expansion and survival of cells at the concentrations of 100 IU/ml and 10 ng/ml respectively. 14-day cultures showed highly pure (91.6 ± 5.1%) and live (96.5 ± 2.5%) expanded γδ T cells. This study aimed to standardize an easy to manipulate technique for the expansion of γδ T cells, giving a higher yield.

Combinational therapeutics to combat cancer.

Mono-therapeutics is rarely effective as a treatment option, which limits the survival of patients in advanced grade aggressive cancers. Combinational therapeutics (multiple drugs for multiple targets) to combat cancer is gaining momentum in recent years. Hence, it is of interest to document known data for combinational therapeutics in cancer treatment. An amalgamation of therapeutic agents enhances the efficacy and potency of the therapy. Combinational therapy can potentially target multiple pathways that are necessary for the cancer cells to proliferate, and/or target molecules, which may help cancer to become more aggressive and metastasize. In this review, we discuss combinational therapeutics, which include human γδ T cells in combinations with biologically active anti-cancer molecules, which synergistically may produce promising combinational therapeutics.