NEUROPROTECTIVE ROLE OF ASCORBIC ACID: ANTIOXIDANT AND NON-ANTIOXIDANT FUNCTIONS

Ascorbic acid (AA) or Vitamin C is an important antioxidant which participates in numerous cellular functions. Although in human plasma its concentration is in micromolars but it reaches millimolar concentrations in most of the human tissues. The high ascorbate cellular concentrations are generated and maintained by a specific sodium-dependent Vitamin C transporter type 2 (SVCT2, member of Slc23 family). Metabolic processes recycle Vitamin C from its oxidized forms (ascorbate) inside the cells. AA concentration is highest in the neurons of the central nervous system (CNS) of mammals, and deletion of its transporter affects mice brain and overall survival. In the CNS, intracellular ascorbate serves several functions including antioxidant protection, peptide amidation, myelin formation, synaptic potentiation, and protection against glutamate toxicity. SVCT2 maintains neuronal ascorbate content in CNS which has relevance for neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's disease. As ascorbate supplements decrease infarct size in ischemia-reperfusion injury and protect neurons from oxidative damage, it is a vital dietary antioxidant. The aim of this review is to assess the role of the SVCT2 in regulating neuronal ascorbate homeostasis in CNS and the extent to which ascorbate affects brain function as an antioxidant

NATURAL ANTIOXIDANTS AS DEFENSE SYSTEM AGAINST CANCER

In living cells, the production of free radicals that comprise both reactive oxygen species (ROS) and reactive nitrogen species is highly regulated that help the cells to sustain redox homeostasis. Overproduction of ROS from mitochondrial electron transport chain leakage or excessive stimulation of xanthine oxidase and other oxidative enzymes leads to the uncontrolled production of free radicals leading to oxidative stress that can mediate damage to cell structures. This damage can be repaired by the antioxidant defense system. Antioxidants are capable of stabilizing, or deactivating, free radicals before they attack cellular components such as DNA, proteins, and lipids. The use of antioxidants in cancer prevention is a rapidly evolving research area where antioxidants scavenge free radicals and thus, indirectly help in the prevention of cancer. A wide range of antioxidants such as glutathione, N-acetylcysteine, coenzyme Q10, lycopene, flavonoids, and isoflavones when used in combination with chemotherapy and radiotherapy, result in the reduction of drug toxicity and enhanced efficacy of anticancer agents. This review aims at the use of these exogenous antioxidants as disease-oriented therapy and elucidating the relation of antioxidant enzymes with different types of cancers to overcome the harmful effects of cancer treatment

New insights into molecular links between microbiota and gastrointestinal cancers:A literature review

Despite decades of exhaustive research on cancer, questions about cancer initiation, development, recurrence, and metastasis have still not been completely answered. One of the reasons is the plethora of factors acting simultaneously in a tumour microenvironment, of which not all have garnered attention. One such factor that has long remained understudied and has only recently received due attention is the host microbiota. Our sheer-sized microbiota exists in a state of symbiosis with the body and exerts significant impact on our body’s physiology, ranging from immune-system development and regulation to neurological and cognitive development. The presence of our microbiota is integral to our development, but a change in its composition (microbiota dysbiosis) can often lead to adverse effects, increasing the propensity of serious diseases like cancers. In the present review, we discuss environmental and genetic factors that cause changes in microbiota composition, disposing of the host towards cancer, and the molecular mechanisms (such as β-catenin signalling) and biochemical pathways (like the generation of oncogenic metabolites like N-nitrosamines and hydrogen sulphide) that the microbiota uses to initiate or accelerate cancers, with emphasis on gastrointestinal cancers. Moreover, we discuss how microbiota can adversely influence the success of colorectal-cancer chemotherapy, and its role in tumour metastasis. We also attempted to resolve conflicting results obtained for the butyrate effect on tumour suppression in the colon, often referred to as the ‘butyrate paradox’. In addition, we suggest the development of microbiota-based biomarkers for early cancer diagnosis, and a few target molecules of which the inhibition can increase the overall chances of cancer cure

Recent Advancements in the Technologies Detecting Food Spoiling Agents

To match the current life-style, there is a huge demand and market for the processed food whose manufacturing requires multiple steps. The mounting demand increases the pressure on the producers and the regulatory bodies to provide sensitive, facile, and cost-effective methods to safeguard consumers’ health. In the multistep process of food processing, there are several chances that the food-spoiling microbes or contaminants could enter the supply chain. In this contest, there is a dire necessity to comprehend, implement, and monitor the levels of contaminants by utilizing various available methods, such as single-cell droplet microfluidic system, DNA biosensor, nanobiosensor, smartphone-based biosensor, aptasensor, and DNA microarray-based methods. The current review focuses on the advancements in these methods for the detection of food-borne contaminants and pathogens

Comparison of BACTEC MGIT with conventional methods for detection of Mycobacteria in clinically suspected patients of extra pulmonary tuberculosis in a tertiary care hospital

Background: Tuberculosis is an important public health problem in India and globally.  Extra pulmonary tuberculosis (EPTB) constitutes for approximately 15 to 20 per cent of all cases of tuberculosis in immunocompetent patients and accounts for more than 50 per cent of the cases in HIV- positive individuals. Main problem with the extra-pulmonary tuberculosis is the paucibacillary nature of the specimen, which makes the diagnosis difficult and delay the treatment. With this in background, this study aimed at the isolation of Mycobacteria from clinical specimens of patients suspected of extra pulmonary tuberculosis using BACTEC MGIT, Lowenstein Jensen (LJ) media and direct acid-fast bacilli smear examination.Methods: A total of 66 samples were processed for direct AFB smear examination, and culture on MGIT and LJ media. Acid fast staining of the specimens was done using the Ziehl-Neelsen method.Results: Among 66 specimens, MGIT gave a higher yield of mycobacteria (46.9%), lower contamination rate (3%) and shorter time to positive culture as compared to LJ media.Conclusions: MGIT gives higher yield and faster results

Biodegradable PEG-PCL Nanoparticles for Co-delivery of MUC1 Inhibitor and Doxorubicin for the Confinement of Triple-Negative Breast Cancer

Combating triple-negative breast cancer (TNBC) is still a problem, despite the development of numerous drug delivery approaches. Mucin1 (MUC1), a glycoprotein linked to chemo-resistance and progressive malignancy, is unregulated in TNBC. GO-201, a MUC1 peptide inhibitor that impairs MUC1 activity, promotes necrotic cell death by binding to the MUC1-C unit. The current study deals with the synthesis and development of a novel nano-formulation (DM-PEG-PCL NPs) comprising of polyethylene glycol-polycaprolactone (PEG-PCL) polymer loaded with MUC1 inhibitor and an effective anticancer drug, doxorubicin (DOX). The DOX and MUC1 loaded nanoparticles were fully characterized, and their different physicochemical properties, viz. size, shape, surface charge, entrapment efficiencies, release behavior, etc., were determined. With IC(50) values of 5.8 and 2.4 nm on breast cancer cell lines, accordingly, and a combination index (CI) of < 1.0, DM-PEG-PCL NPs displayed enhanced toxicity towards breast cancer cells (MCF-7 and MDA-MB-231) than DOX-PEG-PCL and MUC1i-PEG-PCL nanoparticles. Fluorescence microscopy analysis revealed DOX localization in the nucleus and MUC1 inhibitor in the mitochondria. Further, DM-PEG-PCL NPs treated breast cancer cells showed increased mitochondrial damage with enhancement in caspase-3 expression and reduction in Bcl-2 expression.In vivo evaluation using Ehrlich Ascites Carcinoma bearing mice explicitly stated that DM-PEG-PCL NPs therapy minimized tumor growth relative to control treatment. Further, acute toxicity studies did not reveal any adverse effects on organs and their functions, as no mortalities were observed. The current research reports for the first time the synergistic approach of combination entrapment of a clinical chemotherapeutic (DOX) and an anticancer peptide (MUC1 inhibitor) encased in a diblock PEG-PCL copolymer. Incorporating both DOX and MUC1 inhibitors in PEG-PCL NPs in the designed nanoformulation has provided chances and insights for treating triple-negative breast tumors. Our controlled delivery technology is biodegradable, non-toxic, and anti-multidrug-resistant. In addition, this tailored smart nanoformulation has been particularly effective in the therapy of triple-negative breast cancer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10924-022-02654-4

Air Pollutants Removal Using Biofiltration Technique: A Challenge at the Frontiers of Sustainable Environment

[Image: see text] Air pollution is a central problem faced by industries during the production process. The control of this pollution is essential for the environment and living organisms as it creates harmful effects. Biofiltration is a current pollution management strategy that concerns removing odor, volatile organic compounds (VOCs), and other pollutants from the air. Recently, this approach has earned vogue globally due to its low-cost and straightforward technique, effortless function, high reduction efficacy, less energy necessity, and residual consequences not needing additional remedy. There is a critical requirement to consider sustainable machinery to decrease the pollutants arising within air and water sources. For managing these different kinds of pollutant reductions, biofiltration techniques have been utilized. The contaminants are adsorbed upon the medium exterior and are metabolized to benign outcomes through immobilized microbes. Biofiltration-based designs have appeared advantageous in terminating dangerous pollutants from wastewater or contaminated air in recent years. Biofiltration uses the possibilities of microbial approaches (bacteria and fungi) to lessen the broad range of compounds and VOCs. In this review, we have discussed a general introduction based on biofiltration and the classification of air pollutants based on different sources. The history of biofiltration and other mechanisms used in biofiltration techniques have been discussed. Further, the crucial factors of biofilters that affect the performance of biofiltration techniques have been discussed in detail. Finally, we concluded the topic with current challenges and future prospects

In Silico Targeting of influenza virus haemagglutinin receptor protein using Diosmetin, Tangeritin, and Anthocyanidins as potential drugs

Influenza viruses cause acute respiratory illnesses in birds, humans, and other mammals, and are a major public health concern around the world. Pandemic flu could be caused by an unforeseen human adaptation of an influenza subtype or strain rather than currently circulating influenza viruses. The need for plant metabolites-based new anti-influenza drugs appears to be urgent. Blocking Haemeagglutinin (HA) protein is one of the most appealing drug targets to halt the growth of the virus. The influenza virus can acquire resistance to currently existing therapies, therefore necessitating the development of new medications. The plant's bioactive metabolites, flavanoids are having potential medicinal efficacy. The current study aimed to identify certain flavonoids (Diosmetin, Tangeritin, and Anthocyanidins) that might interact with the HA protein of the influenza virus and help in inhibiting its growth. We used PyRx v0.8 for virtual screening and docking studies. The highest binding affinity docked structures were analyzed using PyMOL and Discovery Studio Visualizer. The present study revealed that these naturally occurring compounds interacted with HA protein, resulting in the minimization of energy in the range of -5.2 to -7.0 kcal/mol. Diosmetin showed the best binding affinity of -7.0Kcal/mol. The molecular binding studies revealed that Diosmetin, Tangeritin, and Anthocyanidins are potential compounds to test against HA protein and can be used to develop effective anti-influenza agents