Nanomaterial in controlling biofilms and virulence of microbial pathogens.

The escalating threat of antimicrobial resistance (AMR) poses a grave concern to global public health, exacerbated by the alarming shortage of effective antibiotics in the pipeline. Biofilms, intricate populations of bacteria encased in self-produced matrices, pose a significant challenge to treatment, as they enhance resistance to antibiotics and contribute to the persistence of organisms. Amid these challenges, nanotechnology emerges as a promising domain in the fight against biofilms. Nanomaterials, with their unique properties at the nanoscale, offer innovative antibacterial modalities not present in traditional defensive mechanisms. This comprehensive review focuses on the potential of nanotechnology in combating biofilms, focusing on green-synthesized nanoparticles and their associated anti-biofilm potential. The review encompasses various aspects of nanoparticle-mediated biofilm inhibition, including mechanisms of action. The diverse mechanisms of action of green-synthesized nanoparticles offer valuable insights into their potential applications in addressing AMR and improving treatment outcomes, highlighting novel strategies in the ongoing battle against infectious diseases.

Chromiomics: Chromium detoxification and approaches for engineering tolerance in plants.

Chromium (Cr) is a heavy metal that poses a grave threat to the ecosystem including plants. Chromium is very harmful to plants due to its effects on many physiological and metabolic pathways culminating in a negative impact on plant's growth, development, and ability to take up nutrients. Plants have developed physiological, biochemical, and molecular ways of defense against Cr, such as by augmenting antioxidant potential to reduce reactive oxygen species (ROS). A number of genes have been discovered to play a significant role in the defense mechanisms of plants against Cr, for example, genes associated with the activation of phytochelatins, metallothioneins, and those of enzymes like glutathione-S-transferases. Along with this, a few miRNAs have been found to be associated in alleviating Cr stress and, to augment plant tolerance by controlling transcription factors, HSPs, and the expression of a few proteins and hormones. Defense pathway genes and miRNAs have been used for the generation of transgenic phytoremediator plants. Not only do the transgenic plants have a higher tolerance to Cr, but they also act as hyperaccumulators for Cr and have the potential to remediate other heavy metals. This article describes about environmental Cr contamination, Cr effects on plants, different genes and miRNAs involved in Cr stress mitigation and use of candidate genes, microRNAs for creating transgenic plant systems for phytoremediation, and the applications of CRISPR technology. It is expected that the integration of omics approach and advanced genomics will offer scope for more effective phytoremediation of Chromium in the coming years.

Probing the Potential: Exploring Probiotics as a Novel Frontier in Cancer Prevention and Therapeutics.

Cancer has emerged as one of the most prevalent diseases worldwide, with a consistent rise in the number of cases observed over the past few decades. The rising mortality rates associated with cancer have transformed it into a significant global challenge. Despite the presence of various anti-cancer drugs, the complete eradication of cancer remains an elusive goal. The numerous undesirable effects associated with cancer therapy further emphasize the importance of developing an alternative technique of cancer treatment. Recent research has established the beneficial effects of a probiotic diet or supplementation against cancer without displaying any detrimental consequences. An alteration in the gut microbiome balance in humans can result in the development of various diseases, including cancer. Probiotics play a pivotal role in restoring the balance of gut flora, potentially contributing to cancer prevention. Furthermore, they have the capacity to curb the invasion and dissemination of infections that carry the risk of triggering cancer. Probiotics can combat cancer in various ways, such as by eliciting and boosting the immune response, secreting metabolites, preventing cancer cells from metastasizing, inhibiting carcinogenic chemicals, and mitigating their toxicity, etc. The present review intends to outline the significance of probiotics and their underlying mechanisms in combating various cancer types. Additionally, this review highlights the benefits of probiotic use in pre- and post-operative cancer patients.

Treatment of type 2 diabetes mellitus with stem cells and antidiabetic drugs: a dualistic and future-focused approach.

Type 2 Diabetes Mellitus (T2DM) accounts for more than 90% of total diabetes mellitus cases all over the world. Obesity and lack of balance between energy intake and energy expenditure are closely linked to T2DM. Initial pharmaceutical treatment and lifestyle interventions can at times lead to remission but usually help alleviate it to a certain extent and the condition remains, thus, recurrent with the patient being permanently pharmaco-dependent. Mesenchymal stromal cells (MSCs) are multipotent, self-renewing cells with the ability to secrete a variety of biological factors that can help restore and repair injured tissues. MSC-derived exosomes possess these properties of the original stem cells and are potentially able to confer superior effects due to advanced cell-to-cell signaling and the presence of stem cell-specific miRNAs. On the other hand, the repository of antidiabetic agents is constantly updated with novel T2DM disease-modifying drugs, with higher efficacy and increasingly convenient delivery protocols. Delving deeply, this review details the latest progress and ongoing studies related to the amalgamation of stem cells and antidiabetic drugs, establishing how this harmonized approach can exert superior effects in the management and potential reversal of T2DM.

Unlocking the Therapeutic Potential of Stevia rebaudiana Bertoni: A Natural Antiglycating Agent and Non-Toxic Support for HDF Cell Health.

Sugar carbonyl groups interact with protein amino groups, forming toxic components referred to as advanced glycation end products (AGEs). The glycation system (BSA, a model protein, and fructose) was incubated for five weeks at 37 °C in the presence and absence of Stevia leaf extract. The results indicated that the leaf extract (0.5 mg/mL) decreased the incidence of browning (70.84 ± 0.08%), fructosamine (67.27 ± 0.08%), and carbonyl content (64.04 ± 0.09%). Moreover, we observed an 81 ± 8.49% reduction in total AGEs. The inhibition of individual AGE (argpyrimidine, vesper lysine, and pentosidine) was ~80%. The decrease in the protein aggregation was observed with Congo red (46.88 ± 0.078%) and the Thioflavin T (31.25 ± 1.18%) methods in the presence of Stevia leaf extract. The repercussion of Stevia leaf extract on DNA glycation was examined using agarose gel electrophoresis, wherein the DNA damage was reversed in the presence of 1 mg/mL of leaf extract. When the HDF cell line was treated with 0.5 mg/mL of extract, the viability of cells decreased by only ~20% along with the same cytokine IL-10 production, and glucose uptake decreased by 28 ± 1.90% compared to the control. In conclusion, Stevia extract emerges as a promising natural agent for mitigating glycation-associated challenges, holding potential for novel therapeutic interventions and enhanced management of its related conditions.

A turn-on fluorescence sensor for detection of heparinase with heparin templated aggregation of tetracationic porphyrin derivative.

Heparinase is the only mammalian endoglycosidase that breaks down the commonly used blood-anticoagulant heparin into therapeutically relevant low-molecular-weight-heparin. Importantly, heparinase has been considered a malignant disease diagnostic marker. Thus, it is essential to develop detection scheme for heparinase. However, optical methods for heparinase determination are limited. In the present work, we report a turn-on fluorescence sensor for detection of heparinase that utilizes heparin-templated aggregation of a tetra-cationic porphyrin derivative, TMPyP4+, as a sensing framework. Heparinase cleaves the glycosidic linkage between hexosamine and uronic acid in the structure of heparin to destroy its polyelectrolytic nature that originally causes the aggregation of TMPyP4+. Thus, heparinase leads to dissociation of TMPyP4+ aggregates and generates an optical signal. This system leads to a sensitive and selective response towards heparinase with a Limit of Detection (LOD) of 0.3 pmol/L. Further, the same system is demonstrated to sense a trace amount of Oversulfated Chondrootin Sulphate (OSCS) in heparin, which is a heparin adulterant, by utilizing the fact that OSCS serves as an inhibitor for heparinase activity, which leads to reverse modulation in the photo-physical features of the monomer/aggregate equilibrium of the TMPyP4+-heparin-heparinase system. The sensing mechanism has been thoroughly demonstrated by ground-state absorption, steady-state emission, and time-resolved emission measurements. The selectivity of the sensor was tested using lysozyme, α-amylase, pepsin, trypsin, lipase, and glucose oxidase in the heparinase selectivity study and the method is also validated using another method reported in the literature. The study provides a new approach for the development of optical methods for the detection of heparinase and oversulfated chondroitin sulfate, which is currently limited.

Prospective Use of Probiotics to Maintain Astronaut Health during Spaceflight.

Maintaining an astronaut's health during space travel is crucial. Multiple studies have observed various changes in the gut microbiome and physiological health. Astronauts on board the International Space Station (ISS) had changes in the microbial communities in their gut, nose, and skin. Additionally, immune system cell alterations have been observed in astronauts with changes in neutrophils, monocytes, and T-cells. Probiotics help tackle these health issues caused during spaceflight by inhibiting pathogen adherence, enhancing epithelial barrier function by reducing permeability, and producing an anti-inflammatory effect. When exposed to microgravity, probiotics demonstrated a shorter lag phase, faster growth, improved acid tolerance, and bile resistance. A freeze-dried Lactobacillus casei strain Shirota capsule was tested for its stability on ISS for a month and has been shown to enhance innate immunity and balance intestinal microbiota. The usage of freeze-dried spores of B. subtilis proves to be advantageous to long-term spaceflight because it qualifies for all the aspects tested for commercial probiotics under simulated conditions. These results demonstrate a need to further study the effect of probiotics in simulated microgravity and spaceflight conditions and to apply them to overcome the effects caused by gut microbiome dysbiosis and issues that might occur during spaceflight.

A computational overview of integrase strand transfer inhibitors (INSTIs) against emerging and evolving drug-resistant HIV-1 integrase mutants.

AIDS (Acquired immunodeficiency syndrome) is one of the chronic and potentially life-threatening epidemics across the world. Hitherto, the non-existence of definitive drugs that could completely cure the Human immunodeficiency virus (HIV) implies an urgent necessity for the discovery of novel anti-HIV agents. Since integration is the most crucial stage in retroviral replication, hindering it can inhibit overall viral transmission. The 5 FDA-approved integrase inhibitors were computationally investigated, especially owing to the rising multiple mutations against their susceptibility. This comparative study will open new possibilities to guide the rational design of novel lead compounds for antiretroviral therapies (ARTs), more specifically the structure-based design of novel Integrase strand transfer inhibitors (INSTIs) that may possess a better resistance profile than present drugs. Further, we have discussed potent anti-HIV natural compounds and their interactions as an alternative approach, recommending the urgent need to tap into the rich vein of indigenous knowledge for reverse pharmacology. Moreover, herein, we discuss existing evidence that might change in the near future.

Exploring Mushroom Polysaccharides for the Development of Novel Prebiotics: A Review.

Prebiotics have gained much attention in recent years as functional food ingredients. This has encouraged researchers to look for sustainable alternative sources of prebiotics. Prebiotics help in the modulation of the human intestinal microbiota and thereby improve host health. Chicory, asparagus, and Jerusalem artichoke are some conventional prebiotics that have been extensively studied. Mushrooms are rich sources of medicinal foods as well as bioactive polysaccharides and essential amino acids. They contain large amounts of chitin, mannans, galactans, xylans, glucans, krestin, lentinan, and hemicellulose, thus making it a potential candidate for prebiotics. They are also rich sources of fibers, proteins, and antioxidants. Several mushroom species like Ganoderma lucidum, Pleurotus ostreatus, Hericium erinaceus, Agaricus bisporus, and Lentinula edodes are rich in medicinal properties that have an array of applications. These medicinal mushrooms can be repurposed to regulate gut microbiota. In this review, we discuss the prebiotic effects of different mushroom species on probiotic organisms. We also reviewed the potential of mushroom waste as novel, cheap, and alternative sources of prebiotics.

Toxicity Mitigation of Textile Dye Reactive Blue 4 by Hairy Roots of Helianthus annuus and Testing Its Effect in In Vivo Model Systems.

An anthraquinone textile dye, Reactive Blue 4 (RB4), poses environmental health hazards. In this study, remediation of RB4 (30-110 ppm) was carried out by hairy roots (HRs). UV-visible spectroscopy and FTIR analysis showed that the dye undergoes decolourization followed by degradation. In addition, toxicity and safety analyses of the bioremediated dye were performed on Allium cepa and zebrafish embryos, which revealed lesser toxicity of the bioremediated dye as compared to untreated dye. For Allium cepa, the highest concentration, i.e., 110 ppm of the treated dye, showed less chromosomal aberrations with a mitotic index of 8.5 ± 0.5, closer to control. Two-fold decrease in mortality of zebrafish embryos was observed at the highest treated dye concentration indicating toxicity mitigation. A higher level of lipid peroxidation (LPO) was recorded in the zebrafish embryo when exposed to untreated dye, suggesting a possible role of oxidative stress-inducing mortality of embryos. Further, the level of LPO was significantly normalized along with the other antioxidant enzymes in embryos after dye bioremediation. At lower concentrations, mitigated samples displayed similar antioxidant activity comparable to control underlining the fact that the dye at lesser concentration can be more easily degraded than the dye at higher concentration.

Bacteriocins from lactic acid bacteria and their potential clinical applications.

Bacteriocins are ribosomally synthesized antimicrobial peptides that have long been used in the food industry. Being a highly diverse and heterogeneous group of molecules the classification is ever-evolving. Their production is widespread among bacteria; nevertheless, their biosynthesis and mode of action remain fairly similar. With the advances in drug resistance mechanisms, it is important to look for alternatives to conventional approaches. Therefore, the advantages of bacteriocin over antibiotics need to be considered to provide a scientific basis for their use. Particularly in the last decade, intensive studies look at their potential as next-generation therapeutics against drug-resistant bacteria. Bacteriocins from lactic acid bacteria are being tested as controlling agents for bacterial and viral infections; they can inhibit biofilm synthesis and have potential as contraceptives. Bioengineered peptides have shown enhanced activity and thereby indicate the lack of knowledge we possess regarding these bacteriocins. In this review, we have listed various Gram-positive LAB bacteriocins with their synthesis and mechanism of action. Recent developments in screening and purification technologies have been analyzed with an emphasis on their potential clinical applications. Although extensive research has been done to identify multifunctional bacteriocins, it is important to focus on the mechanism of action of these peptides to get them from bench to bedside.

Identification and characterization of chlorine-resistant bacteria from water distribution sites of Mumbai.

Chlorination is the oldest and widely practiced method for disinfection of potable water across the globe but some microorganisms survive the chlorine treatment and become resistant. In this study, chlorine-resistant bacteria were isolated from 36 reservoirs of the Municipal Corporation of Greater Mumbai. Water was collected in winter, summer and rainy season. The 8 isolates (out of 89) found to be resistant to 20 ppm of chlorine were identified and belong to the Acinetobacter and Serratia sp. The antibiotic resistance profile showed that the isolates were resistant to a broad spectrum of antibiotics which is of concern. Biofilm production was also observed in most of the isolates. Presence of chlorine-resistant bacteria in drinking water is an alarming situation which needs further analysis especially to understand the further characteristics of these isolates for their antibiotic resistance.

Biotransformation of xenobiotics by hairy roots.

The exponential industrial growth we see today rides on the back of large scale production of chemicals, explosives and pharmaceutical products. However, the effluents getting released from their manufacturing units are greatly compromising the sustainability of our environment. With greater awareness of the imperative for environmental clean-up, a promising approach that is attracting increasing research interests is biodegradation of xenobiotics. In this approach, biotransformation has proven to be one of the most effective tools. While many different model frameworks have been used to study different aspects of biotransformation, hairy roots (HRs) have been found to be exceptionally valuable. HR cultures are preferred over other in-vitro model systems due to their biochemical stability and hormone-autotrophy. In addition, the multi-enzyme biosynthetic potential of HRs which is similar to the parent plant and their relatively low-cost cultural requirements further characterize their suitability for biotransformation. The recent progress observed in scale-up of HR cultures and understanding of functional genomics has opened up new dimensions providing valuable insights for industrial application. This review article summarizes the potential of HR cultures in the biotransformation of xenobiotics, their limitations in the application on a large scale and current strategies to alleviate them. Advancement in bioreactors engineering enabling large scale cultivation and modern gene technologies improving biotransformation efficiency promises to extend laboratory results to industrial applications.

Exploring Probiotic Activity of Lactobacillus sp. Isolated from Indigenous Breeds of Cattle Milk and Fecal Samples in Bhatan Village, MH., IN.

Probiotics are defined as live organisms that are able to confer health benefits to the host by improving their intestinal microbial balance. In the last decade, there has been an increasing interest to reveal health benefits associated with them. The objective of this study was to isolate indigenous probiotic organisms and assess their probiotic activity and therapeutic characteristics. The isolates were identified as Lactobacillus fermentum (isolates 2, 4, 6, 7, 8, and 9), Lactobacillus salivarius (isolate 13), and Lactobacillus plantarum (isolates 32 and 36). Five isolates showed growth at pH 2.5, while all isolates could grow at pH 8.5. All isolates showed good growth upto 5% NaCl concentration while two isolates showed growth in 7% NaCl concentration. All the isolates were susceptible to most of the broad-spectrum antibiotics. Cell-free suspensions from the isolates showed antimicrobial activity against the tested strains of Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi, and Staphylococcus aureus. Two of the isolates 32 and 36 showed good revival after long-term storage, without any change in the morphology. Hence among all the other isolates these two isolates could have a good marketable potential. These strains can further be formulated into a probiotic drink that can be used as a health supplement.

Dietary Phytonutrients in the Prevention of Diabetes-related Complications.

BACKGROUND: The increasing prevalence of reported cases of diabetes has evidently become a major global public health concern. Although diabetes management is possible by the administration of synthetic anti-diabetic agents, there are profound side-effects associated with their long-term usage. Hence there is a demand for safer alternatives which could be possibly formulated using specific yet common phytonutrients. OBJECTIVES: The main objective of this review is to describe the cellular mechanisms of phytonutrients as an alternative to commercially available synthetic anti-diabetic agents in the management of diabetes and related complications. Furthermore, the clinical evidence that supports this view is also highlighted. METHODOLOGY: An in-depth review of published literature was carried out to identify the most promising phytonutrients in the management of diabetes and related complications. RESULTS: A number of phytonutrients are reported to be potential anti-diabetic agents. Few examples include biguanides, resveratrol, lycopene, thymoquinone and quercetin. However, suitable formulations using these phytonutrients and their clinical trials are still underway. Most of the reported findings focus on one aspect of several biochemical processes e.g. enhancement of glucose utilization, antioxidation, induction of insulin production, antiglycation, etc. An in-depth study of phytonutrients with respect to functional, immunological as well as biochemical factors suggesting their efficacy, as well as safety in the management of diabetes, is rarely reported. CONCLUSION: Our study thus highlights the abundance of clinical evidence of the efficiency of phytonutrients, and at the same time, the scarcity of clinically approved and marketed phytonutrients, as drugs, for the management of diabetes and related complications.

Biotransformation of chromium by root nodule bacteria Sinorhizobium sp. SAR1.

The present study aims to address the problem of chromium (Cr) toxicity by providing important insights into the mechanisms involved in its bioremediation. Among the 22 Rhizobium and Sinorhizobium isolates obtained from Sesbania sesban root nodules, Sinorhizobium sp. SAR1 (JX174035.1) tolerated the maximum Cr concentration (1mM) and hence was used for further studies. The excess secretion of extra polymeric substances, as seen from scanning electron micrographs, could be a probable mechanism of adaptation to the Cr stress. The Energy dispersive X-ray spectroscopy data did not show any peaks of Cr. The biosorption studies done on the isolate gave maximum adsorption capacity as 285.71mg/g. The isotherm studies showed a better fit to Langmuir isotherm. The Weber and Morris plot established that the phenomenon of adsorption was governed by film diffusion mechanism. The FTIR analysis suggested the role of cell wall components and extracellular polymeric substances in Cr adsorption to the biomass of Sinorhizobium. On the basis of these results a compiled mechanism of Cr (VI) adsorption and its biotransformation into Cr (III) by Sinorhizobium sp. SAR1 is explained. This work outlines a comprehensive detail for the exact phenomenon of Cr biotransformation by Sinorhizobium sp. SAR1. These results may further help in developing and enhancing effective bioremediation approaches.

Biosorption and biotransformation of hexavalent chromium [Cr(VI)]: A comprehensive review.

Chromium (VI) is one of the most common environmental contaminant due to its tremendous industrial applications. It is non-biodegradable as it is a heavy metal, and hence, of major concern. Therefore, it is pertinent that the remediation method should be such that brings chromium within permissible limits before the effluent is discharged. Several different strategies are adopted by microorganisms for Cr (VI) removal mostly involving biosorption and biotransformation or both. These mechanisms are based on the surface nature of the biosorbent and the availability of reductants. This review article focuses on chromium pollution problem, its chemistry, sources, effects, remediation strategies by biological agents and detailed chromium detoxification mechanism in microbial cell. A summary of applied in situ and ex situ chromium bioremediation technologies is also listed. This can be helpful for developing technologies to be more efficient for Cr (VI) removal thereby bridging the gap between laboratory findings and industrial application for chromium remediation.

Remediation of textile azo dye acid red 114 by hairy roots of Ipomoea carnea Jacq. and assessment of degraded dye toxicity with human keratinocyte cell line.

Bioremediation has proven to be the most desirable and cost effective method to counter textile dye pollution. Hairy roots (HRs) of Ipomoea carnea J. were tested for decolourization of 25 textile azo dyes, out of which >90% decolourization was observed in 15 dyes. A diazo dye, Acid Red 114 was decolourized to >98% and hence, was chosen as the model dye. A significant increase in the activities of oxidoreductive enzymes was observed during decolourization of AR114. The phytodegradation of AR114 was confirmed by HPLC, UV-vis and FTIR spectroscopy. The possible metabolites were identified by GCMS as 4- aminobenzene sulfonic acid 2-methylaniline and 4- aminophenyl 4-ethyl benzene sulfonate and a probable pathway for the biodegradation of AR114 has been proposed. The nontoxic nature of the metabolites and toxicity of AR114 was confirmed by cytotoxicity tests on human keratinocyte cell line (HaCaT). When HaCaT cells were treated separately with 150 µg mL(-1) of AR114 and metabolites, MTT assay showed 50% and ≈100% viability respectively. Furthermore, flow cytometry data showed that, as compared to control, the cells in G2-M and death phase increased by 2.4 and 3.6 folds respectively on treatment with AR114 but remained unaltered in cells treated with metabolites.

Differential Expression of Antioxidant Enzymes During Degradation of Azo Dye Reactive black 8 in Hairy roots of Physalis minima L.

The enzymes involved in the protection of plant metabolism in presence of azo dye was characterized by studying activities of the role of antioxidant enzymes in the hairy roots (HRs) of Physalis minima L. during degradation of an azo dye, Reactive Black 8 (RB8). When the HRs were exposed to RB8 (30 mg L(-1)), a  nine fold increase in SOD activity was observed after 24 h, while 22 and 50 fold increase in activity was observed for POX and APX respectively after 72 h, whereas there was no significant change in activity of CAT. The activation of different antioxidant enzymes at different time intervals under dye stress suggests the synchronized functioning of antioxidant machinery to protect the HRs from oxidative damage. FTIR analysis confirmed the degradation of dye and the non-toxic nature of metabolites formed after dye degradation was confirmed by phytotoxicity study.