Recent Strategies for the Remediation of Textile Dyes from Wastewater: A Systematic Review.

The presence of dye in wastewater causes substantial threats to the environment, and has negative impacts not only on human health but also on the health of other organisms that are part of the ecosystem. Because of the increase in textile manufacturing, the inhabitants of the area, along with other species, are subjected to the potentially hazardous consequences of wastewater discharge from textile and industrial manufacturing. Different types of dyes emanating from textile wastewater have adverse effects on the aquatic environment. Various methods including physical, chemical, and biological strategies are applied in order to reduce the amount of dye pollution in the environment. The development of economical, ecologically acceptable, and efficient strategies for treating dye-containing wastewater is necessary. It has been shown that microbial communities have significant potential for the remediation of hazardous dyes in an environmentally friendly manner. In order to improve the efficacy of dye remediation, numerous cutting-edge strategies, including those based on nanotechnology, microbial biosorbents, bioreactor technology, microbial fuel cells, and genetic engineering, have been utilized. This article addresses the latest developments in physical, chemical, eco-friendly biological and advanced strategies for the efficient mitigation of dye pollution in the environment, along with the related challenges.

Valorization of dragon fruit waste to value-added bioproducts and formulations: A review.

Owing to the increasing worldwide population explosion, managing waste generated from the food sector has become a cross-cutting issue globally, leading to environmental, economic, and social issues. Circular economy-inspired waste valorization approaches have been increasing steadily, generating new business opportunities developing valuable bioproducts using food waste, especially fruit wastes, that may have several applications in energy-food-pharma sectors. Dragon fruit waste is one such waste resource, which is rich in several value-added chemicals and oils, and can be a renewable resource to produce several value-added compounds of potential applications in different industries. Pretreatment and extraction processes in biorefineries are important strategies for recovering value-added biomolecules. There are different methods of valorization, including green extractions and biological conversion approaches. However, microbe-based conversion is one of the advanced technologies for valorizing dragon fruit waste into bioethanol, bioactive products, pharmaceuticals, and other valued products by reusing or recycling them. This state-of-the-art review briefly overviews the dragon fruit waste management strategies and advanced eco-friendly and cost-effective valorization technologies. Furthermore, various applications of different valuable bioactive components obtained from dragon fruit waste have been critically discussed concerning various industrial sectors. Several industrial sectors, such as food, pharmaceuticals, and biofuels, have been critically reviewed in detail.

Bioactive Compounds, Antioxidant, and Antibacterial Activity Against MDR and Food-Borne Pathogenic Bacteria of Psidium guajava. L Fruit During Ripening.

Psidium guajava fruits are highly appreciated for their nutrients and bioactive compounds content, which contribute to their antioxidant and antimicrobial capacities. The purpose of this study was to determine bioactive compound (phenolic, flavonoids, and carotenoid contents), antioxidant activity (DPPH, ABTS, ORAC, and FRAP), and antibacterial potential against MDR and food-borne pathogenic strains of Escherichia coli, and Staphylococcus aureus during different stages of fruit ripening.The results elucidated that ripe fruits (methanolic extract) contain the highest total phenolic, flavonoids, and carotenoid contents (417.36 ± 2.63 µg GAE/gm of FW, 711.78 ± 0.70 µg QE/gm of FW and 0.683 ± 0.06 µg/gm of FW) followed by hexane, ethyl acetate, and aqueous. Methanolic extract of the ripe fruits showed the highest antioxidant activity when measured by DPPH (61.55 ± 0.91%), FRAP (31.83 ± 0.98 mM Fe(II)/gm of FW), ORAC (17.19 ± 0.47 mM TE/ gm of FW), and ABTS (41.31 ± 0.99 µmol Trolox/gm of FW) assays. In the antibacterial assay, the ripe stage had the highest antibacterial activity against MDR and food-borne pathogenic strains of Escherichia coli, and Staphylococcus aureus. The methanolic ripe extract was found to possess maximum antibacterial activity ZOI, MIC, and IC50 18.00 ± 1.00 mm, 95.95 ± 0.05%, and 0.58 µg/ml; 15.66 ± 0.57 mm, 94.66 ± 0.19%, and 0.50 µg/ml, respectively, against pathogenic and MDR strains of E. coli and 22.33 ± 0.57 mm, 98.97 ± 0.02%, and 0.26 µg/ml; 20.33 ± 1.15 mm, 96.82 ± 0.14%, and 0.39 µg/ml, respectively, against pathogenic and MDR strains of S. aureus. Considering the bioactive compounds and beneficial effects, these fruit extracts could be promising antibiotic alternatives, avoiding antibiotic overuse and its negative effects on human health and the environment, and can be recommended as a novel functional food.

Microbial biosorbent for remediation of dyes and heavy metals pollution: A green strategy for sustainable environment.

Toxic wastes like heavy metals and dyes are released into the environment as a direct result of industrialization and technological progress. The biosorption of contaminants utilizes a variety of biomaterials. Biosorbents can adsorb toxic pollutants on their surface through various mechanisms like complexation, precipitation, etc. The quantity of sorption sites that are accessible on the surface of the biosorbent affects its effectiveness. Biosorption's low cost, high efficiency, lack of nutrient requirements, and ability to regenerate the biosorbent are its main advantages over other treatment methods. Optimization of environmental conditions like temperature, pH, nutrient availability, and other factors is a prerequisite to achieving optimal biosorbent performance. Recent strategies include nanomaterials, genetic engineering, and biofilm-based remediation for various types of pollutants. The removal of hazardous dyes and heavy metals from wastewater using biosorbents is a strategy that is both efficient and sustainable. This review provides a perspective on the existing literature and brings it up-to-date by including the latest research and findings in the field.

Etiology of Meningoencephalitis in children aged less than 5 years.

BACKGROUND: The incidence of meningoencephalitis (ME) in India is poorly understood, and the exact etiological diagnosis is often not possible. This study was planned to elucidate the bacterial and viral etiological diagnosis of ME in children less than 5 years of age. MATERIAL AND METHODS: The present study was conducted in Virus Research and Diagnostic Laboratory (VRDL), Department of Microbiology, King George's Medical University, Lucknow, from July 2020 to June 2022. Serum, cerebrospinal fluid (CSF), and nose/throat swabs were collected from all the enrolled cases of meningoencephalitis in children below 5 years of age and tested for various etiological agents by ELISA and/or real-time PCR. RESULTS: Of 130 enrolled cases, 50 (38.5%) cases tested positive for one or more etiological agents. Etiological agents of ME detected were Japanese encephalitis virus (JEV) (8.46%), adenovirus (6.92%), influenza virus (5.38%), dengue virus (3.85%), Parvo B-19 virus (3.08%), Orientia tsutsugamushi (3.08%), Herpes Simplex Virus-1 (HSV-1) (1.54%), measles virus (1.54%), and Varicella-Zoster Virus (VZV) (1.54%). Rubella virus, Chikungunya virus (CHKV), Mumps virus, Enteroviruses, Parecho virus, John Cunningham virus (JC), BK virus, Nipah virus, Kyasanur Forest Disease virus (KFD), Chandipura virus, Herpes Simplex Virus (HSV-2), SARS CoV-2, N. Meningitides, and H. Influenzae were tested but not detected in any of the cases. CONCLUSION: We identified the etiological agents in 50/130 (38.5%) suspected ME cases in children less than 5 years of age, using molecular and ELISA-based diagnostic methods. The four most common pathogens detected were JEV, adenovirus, influenza virus, and dengue virus.

Valorization of jackfruit waste into value added products and their potential applications.

Jackfruit is a potential natural resource for many valuable biomaterials. The wastes from jackfruit are rich in carbohydrate, proteins, fats and phytochemicals. These wastes can be used as feedstock for the development of various bioproducts. The pretreatment strategies like biological, physical and chemical methods are being used for effective valorization of fruit wastes into value added products, like bioethanol, biogas, bioplastics, feeds, functional food additives, and other useful compounds. Bioenergy production from such renewable resources is an eco-friendly and cost-effective alternative option of fuels, unlike fossil fuels. The efficient bioconversion of fruit waste into useful biomaterials is facilitated by microbial fermentation process. Also, jackfruit peel is applied in the pollution abatement by remediation of dyes color from contaminated aquatic environment. Such technology can be used to develop a green economic model for waste utilization. This review addressed the utilization feasibility of jackfruit waste to produce value added products in order to reduce wastes and protect environment in a sustainable way.

Consequences of Arsenic Contamination on Plants and Mycoremediation-Mediated Arsenic Stress Tolerance for Sustainable Agriculture.

Arsenic contamination in water and soil is becoming a severe problem. It is toxic to the environment and human health. It is usually found in small quantities in rock, soil, air, and water which increase due to natural and anthropogenic activities. Arsenic exposure leads to several diseases such as vascular disease, including stroke, ischemic heart disease, and peripheral vascular disease, and also increases the risk of liver, lungs, kidneys, and bladder tumors. Arsenic leads to oxidative stress that causes an imbalance in the redox system. Mycoremediation approaches can potentially reduce the As level near the contaminated sites and are procuring popularity as being eco-friendly and cost-effective. Many fungi have specific metal-binding metallothionein proteins, which are used for immobilizing the As concentration from the soil, thereby removing the accumulated As in crops. Some fungi also have other mechanisms to reduce the As contamination, such as biosynthesis of glutathione, cell surface precipitation, bioaugmentation, biostimulation, biosorption, bioaccumulation, biovolatilization, methylation, and chelation of As. Arsenic-resistant fungi and recombinant yeast have a significant potential for better elimination of As from contaminated areas. This review discusses the relationship between As exposure, oxidative stress, and signaling pathways. We also explain how to overcome the detrimental effects of As contamination through mycoremediation, unraveling the mechanism of As-induced toxicity.

ACC Deaminase Produced by PGPR Mitigates the Adverse Effect of Osmotic and Salinity Stresses in Pisum sativum through Modulating the Antioxidants Activities.

Salinity-induced ethylene production and reactive oxygen species (ROS) inhibit agricultural productivity. The plant synthesizes ethylene directly from aminocyclopropane-1-carboxylic acid (ACC). By using ACC as a nitrogen source, bacteria with ACC deaminase (ACCD) inhibit the overproduction of ethylene, thereby maintaining the ROS. The present study investigated the ACCD activity of previously identified rhizobacterial strains in Dworkin and Foster (DF) minimal salt media supplemented with 5 mM ACC (as N-source). Bacterial isolates GKP KS2_7 (Pseudomonas aeruginosa) and MBD 133 (Bacillus subtilis) could degrade ACC into α-ketobutyrate, exhibiting ACCD activity producing more than ~257 nmol of α-ketobutyrate mg protein−1 h−1, and were evaluated for other plant growth-promoting (PGP) traits including indole acetic acid production (>63 µg/mL), phosphate solubilization (>86 µg mL−1), siderophore (>20%) ammonia and exopolysaccharide production. Furthermore, Fourier Transform Infrared analysis also demonstrated α-ketobutyrate liberation from ACC deamination in DF minimal salt media, thereby confirming the ACCD activity. These isolates also showed enhanced tolerance to salinity stress of 3% w/v NaCl in vitro, in addition to facilitating multifarious PGP activities. Seed bacterization by these ACCD-producing bacterial isolates (GKP KS2_7 and MBD 133) revealed a significant decline in stress-stimulated ethylene levels and its associated growth inhibition during seedling germination. They also mitigated the negative effects of salt stress and increased the root-shoot length, fresh and dry weight of root and shoot, root-shoot biomass, total sugar, protein, reducing sugar, chlorophyll content, and antioxidants enzymes in Pisum sativum. As a result, these strains (GKP KS2_7 and MBD 133) might be applied as biofertilizers to counteract the negative effects of soil salinity.

Biopolymeric nanoparticles based effective delivery of bioactive compounds toward the sustainable development of anticancerous therapeutics.

Nowadays, effective cancer therapy is a global concern, and recent advances in nanomedicine are crucial. Cancer is one of the major fatal diseases and a leading cause of death globally. Nanotechnology provides rapidly evolving delivery systems in science for treating diseases in a site-specific manner using natural bioactive compounds, which are gaining widespread attention. Nanotechnology combined with bioactives is a very appealing and relatively new area in cancer treatment. Natural bioactive compounds have the potential to be employed as a chemotherapeutic agent in the treatment of cancer, in addition to their nutritional benefits. Alginate, pullulan, cellulose, polylactic acid, chitosan, and other biopolymers have been effectively used in the delivery of therapeutics to a specific site. Because of their biodegradability, biopolymeric nanoparticles (BNPs) have received a lot of attention in the development of new anticancer drug delivery systems. Biopolymer-based nanoparticle systems can be made in a variety of ways. These systems have developed as a cost-effective and environmentally friendly solution to boost treatment efficacy. Effective drug delivery systems with improved availability, increased selectivity, and lower toxicity are needed. Recent research findings and current knowledge on the use of BNPs in the administration of bioactive chemicals in cancer therapy are summarized in this review.

Crosstalk Between ROS and Autophagy in Tumorigenesis: Understanding the Multifaceted Paradox.

Cancer formation is a highly regulated and complex process, largely dependent on its microenvironment. This complexity highlights the need for developing novel target-based therapies depending on cancer phenotype and genotype. Autophagy, a catabolic process, removes damaged and defective cellular materials through lysosomes. It is activated in response to stress conditions such as nutrient deprivation, hypoxia, and oxidative stress. Oxidative stress is induced by excess reactive oxygen species (ROS) that are multifaceted molecules that drive several pathophysiological conditions, including cancer. Moreover, autophagy also plays a dual role, initially inhibiting tumor formation but promoting tumor progression during advanced stages. Mounting evidence has suggested an intricate crosstalk between autophagy and ROS where they can either suppress cancer formation or promote disease etiology. This review highlights the regulatory roles of autophagy and ROS from tumor induction to metastasis. We also discuss the therapeutic strategies that have been devised so far to combat cancer. Based on the review, we finally present some gap areas that could be targeted and may provide a basis for cancer suppression.

Mechanistic Insights of Plant Growth Promoting Bacteria Mediated Drought and Salt Stress Tolerance in Plants for Sustainable Agriculture.

Climate change has devastating effects on plant growth and yield. During ontogenesis, plants are subjected to a variety of abiotic stresses, including drought and salinity, affecting the crop loss (20-50%) and making them vulnerable in terms of survival. These stresses lead to the excessive production of reactive oxygen species (ROS) that damage nucleic acid, proteins, and lipids. Plant growth-promoting bacteria (PGPB) have remarkable capabilities in combating drought and salinity stress and improving plant growth, which enhances the crop productivity and contributes to food security. PGPB inoculation under abiotic stresses promotes plant growth through several modes of actions, such as the production of phytohormones, 1-aminocyclopropane-1-carboxylic acid deaminase, exopolysaccharide, siderophore, hydrogen cyanide, extracellular polymeric substances, volatile organic compounds, modulate antioxidants defense machinery, and abscisic acid, thereby preventing oxidative stress. These bacteria also provide osmotic balance; maintain ion homeostasis; and induce drought and salt-responsive genes, metabolic reprogramming, provide transcriptional changes in ion transporter genes, etc. Therefore, in this review, we summarize the effects of PGPB on drought and salinity stress to mitigate its detrimental effects. Furthermore, we also discuss the mechanistic insights of PGPB towards drought and salinity stress tolerance for sustainable agriculture.

ACC deaminase producing plant growth promoting rhizobacteria enhance salinity stress tolerance in Pisum sativum.

Salinity stress is one of the most serious environmental stresses which limit plant growth, development and productivity. In this study, we screened 25 bacterial isolates based on the biochemical activity of ACC deaminase. Two potent PGPR namely Bacillus marisflavi (CHR JH 203) and Bacillus cereus (BST YS1_42) having the highest ACC deaminase (ACCD) activity were selected for further analyses such as polymerase chain reaction (PCR), salt tolerance assay, expression analysis, antioxidant assay, etc. The structural gene for ACCD activity was further confirmed by PCR showing the amplicon size ~ 800 bp. The acdS positive isolates exhibited optimum growth at 3% w/v (NaCl), indicating its ability to survive and thrive in induced saline soil. Inoculation of acdS + strain on pea plants was found to be efficient and ameliorated the induced NaCl-stress by enhancing the various parameters like plant-biomass, carbohydrates, reducing sugars, protein, chlorophylls, phenol, flavonoids content and increasing antioxidants enzymes levels in plants. Moreover, the expression of ROS scavenging genes (PsSOD, PsCAT, PsPOX, PsNOS, PsAPX, PsChla/bBP), defense genes and cell rescue genes (PsPRP, PsMAPK, PsFDH) were analyzed. Inoculated plants exhibited a higher gene expression level and salt tolerance under 1%NaCl concentration. Thus, our results indicate that CHR JH 203 and BST YS1_42 strain showed the highest plant growth-promoting attributes could be used as bio-inoculants for crops under saline stress in the field towards sustainable crop development. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-021-03047-5.

Nanotechnology in reproductive medicine: Opportunities for clinical translation.

In recent years, nanotechnology has revolutionized global healthcare and has been predicted to exert a remarkable effect on clinical medicine. In this context, the clinical use of nanomaterials for cancer diagnosis, fertility preservation, and the management of infertility and other pathologies linked to pubertal development, menopause, sexually transmitted infections, and HIV (human immunodeficiency virus) has substantial promise to fill the existing lacunae in reproductive healthcare. Of late, a number of clinical trials involving the use of nanoparticles for the early detection of reproductive tract infections and cancers, targeted drug delivery, and cellular therapeutics have been conducted. However, most of these trials of nanoengineering are still at a nascent stage, and better synergy between pharmaceutics, chemistry, and cutting-edge molecular sciences is needed for effective translation of these interventions from bench to bedside. To bridge the gap between translational outcome and product development, strategic partnerships with the insight and ability to anticipate challenges, as well as an in-depth understanding of the molecular pathways involved, are highly essential. Such amalgamations would overcome the regulatory gauntlet and technical hurdles, thereby facilitating the effective clinical translation of these nano-based tools and technologies. The present review comprehensively focuses on emerging applications of nanotechnology, which holds enormous promise for improved therapeutics and early diagnosis of various human reproductive tract diseases and conditions.

Production, characterization and antibacterial activity of silver nanoparticles produced by Fusarium oxysporum and monitoring of protein-ligand interaction through in-silico approaches.

The present study envisages biological production of silver nanoparticles using Fusarium oxysporum and in-silico identification of the antibacterial activity of the nanoparticles using protein-ligand interaction studies. The morphology of the nanoparticles was variable, with majority of them spherical in the size range 1-50 nm. For in-silico studies, two microorganisms, Escherichia coli and Pseudomonas aeruginosa were selected and metal docking was carried out using the licensed software SYBYL X 1.1.1. The ligand docked deeply into the binding pockets of the outer membrane proteins (OMPs) of both E. coli and P. aeruginosa. The results showed that silver may prove to be a strong antibacterial agent against both the pathogens, with the antibacterial action of silver being greater in the case of P. aeruginosa. The results obtained through in-silico studies were further validated by in-vitro approaches on both solid and liquid media to confirm the results obtained by in-silico analysis. The corroboration of in-silico and in-vitro results amply demonstrates the immense antibacterial potential of silver nanoparticles against the selected pathogens.

Hesperidin Induces ROS-Mediated Apoptosis along with Cell Cycle Arrest at G2/M Phase in Human Gall Bladder Carcinoma.

A natural predominant flavonoid hesperidin rich in citrus fruits exhibits multifunctional medicinal properties. The anticancerous potential of hesperidin has been widely explored; however, the gall bladder carcinoma (GBC) still remains untouched due to the unavailability of efficient experimental model. The aim of our study was to identify the apoptotic and antiproliferative potential of hesperidin in GBC. The promising efficacy of hesperidin was assessed through the generation of reactive oxygen species (ROS), cellular apoptosis, and loss of mitochondrial membrane potential (MMP) in the primary cells generated from surgically removed cancerous gall bladder tissues. Moreover, cell cycle analysis and caspases-3 activity were performed to confirm the apoptosis inducing potential of hesperidin. Results revealed that hesperidin exposure for 24 h at a dose of 200 µM reduced the cell proliferation of GBC cells significantly. In addition, hesperidin treatment further resulted in an increased ROS generation and nuclear condensation at the same dose. Caspase-3 activation and cell cycle arrest at G2/M phase were also accelerated in a dose-dependent manner. Together, these results suggest that hesperidin can be considered as a potential anticancerous compound for the treatment of GBC. Furthermore, evaluation of the pharmacological aspects of hesperidin is desirable for drug development.

ADNCD: a compendious database on anti-diabetic natural compounds focusing on mechanism of action.

Diabetes is a deteriorating metabolic ailment which negatively affects different organs; however, its prime target is insulin secreting pancreatic ß-cells. Although, different medications have been affirmed for diabetes management and numerous drugs are undergoing clinical trials, no significant breakthrough has yet been achieved. Available drugs either show some side effects or provide only short-term alleviation. The rationales behind the failure of current anti-diabetic treatment strategy are association of complex patho-physiologies and participation of various organs. Consequently, there is a critical need to search for multi-effect drugs that might impede various patho-physiological mechanisms related to diabetes. Fortunately, one natural compound could act on several diabetes linked targets. Thus, natural compounds might be regarded as a viable alternative choice to improve the progression as well as side effects of diabetes. Despite the fact that immense literatures are available on natural compounds indicating promising outcomes against diabetes, more systematic studies are still needed to establish them as effective anti-diabetic agents. Till date, we are unable to access all the information regarding modes of action, toxicity risks and physicochemical properties of anti-diabetic natural compounds on one platform. Hence, anti-diabetic natural compounds database (ADNCD) has been created to categorize each anti-diabetic natural compound on the basis of their mode of action and to provide compendious information of their physicochemical properties and toxicity risks. In short, ADNCD has imperative information for the researchers working in the field of diabetes drug development.

Phytochemical Study of Aegle marmelos: Chromatographic Elucidation of Polyphenolics and Assessment of Antioxidant and Cytotoxic Potential.

BACKGROUND: The antioxidant potential of medicinal plants has been illustrated through many reports clearly depicting that plants are a rich source of antioxidants, making them a great resource of novel drugs and health-care products. OBJECTIVES: The current study is, therefore, focused toward the assessment of antioxidant properties along with the presence of phytochemicals in leaves of 18 varieties/accessions of Aegle marmelos. MATERIALS AND METHODS: The antioxidant activities were initially measured using superoxide radical scavenging method, 2, 2-diphenyl-1-picrylhydrazyl (DPPH), and ferric-reducing ability of plasma assays. Further, thin-layer chromatography (TLC), high-performance TLC, and column chromatography were performed to isolate the potentially active fraction and anti-inflammatory activity of crude, and the isolated fraction was tested on J774 macrophage cell line. RESULTS: The maximum inhibition of superoxide anions was shown by Pant Aparna. Additionally, Pant Aparna extract was most efficient, exhibiting 92.0% inhibition in scavenging the DPPH radicals. The content of total carotenoids was found to be higher in Pant Aparna among all the varieties/accessions. Furthermore, the crude extract and the fraction A. marmelos methanolic fraction 21 (AMMF21) were found to be nontoxic and significant reactive oxygen species, and NO inhibition was observed in a concentration-dependent manner. Moreover, the methanolic extract of variety Pant Aparna showed promising in vitro antioxidant activity, indicating its potency for therapeutic applications. CONCLUSION: In brief, this is the first ever report on Pant Aparna as the best variety in terms of phytocompounds and identification of potential antioxidant activity. In addition, the AMMF21 fraction of methanolic extract possessing best antioxidant activity on macrophage cells indicates its use as a novel phytotherapeutic agent. SUMMARY: Our study identifies the best variety/accession of Aegle marmelos possessing the potential antioxidant and reactive oxygen species scavenging activity possessed by the methanolic crude extract of variety Pant Aparna along with the fraction A. marmelos methanolic fraction 21 isolated through column chromatography on J774 murine macrophage cell lineThe high-performance thin-layer chromatography fingerprinting profile obtained acts as a diagnostic tool to identify and determine the quality and purity of this extract and fraction in future studiesOn the basis of the results obtained, the above variety should be taken further to exploit its immense potential for other biological activities of medicinal importancePant Aparna is an outstanding variety of A. marmelos and should be extensively studied for isolation of a novel and potential therapeutic agent. Abbreviations used: AMMF21: Aegle marmelos methanolic fraction 21, DPPH: (2, 2-diphenyl-1-picrylhydrazyl), FRAP: Ferric-reducing ability of plasma, HP-TLC: High-performance-thin-layer chromatography, TLC: Thin-layer chromatography, TCA: Trichloroacetic acid, TPTZ: 2,4,6-Tripyridyl-s-triazine, DNPH: 2,4-dinitrophenyl hydrazine, NBT: Nitroblue tetrazolium, NADH: Nicotinamide adenine dinucleotide, PMS: Phenazine metho-sulfate, DMEM: Dulbecco's modified Eagle medium; MTT: (3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide, DCFDA: 2',7'-dichlorofluorescein diacetate, LPS: Lipopolysaccharide, NED: N-(1-Naphthyl) ethylenediamine.

Pre-clinical Validation of Mito-targeted Nano-engineered Flavonoids Isolated From Selaginella bryopteris (Sanjeevani) As A Novel Cancer Prevention Strategy.

BACKGROUND: Novel bioactive plant secondary metabolites, including flavonoids, offer a spectrum of chemo-protective responses against a range of human tumor models. However, the clinical translation of these promising anti-cancer agents has been hindered largely by their poor solubility, rapid metabolism, or a combination of both, ultimately resulting in poor bioavailability upon oral administration. OBJECTIVE: To circumvent the challenges associated with herbal drug development and for effective integration into clinical setting, nano-engineering is one of the emerging pragmatic strategies which has promise to deliver therapeutic concentrations of bio-actives upon oral administration. METHOD: We assessed the nano-encapsulated flavonoid-rich fraction isolated from a traditional Indian herb Selaginella bryopteris (Sanjeevani) (NP.SB). Both in vitro and in vivo studies were performed to evidence the epigenetic protection mechanisms of NP.SB through a mitochondrial-targeted pre-clinical validation strategy. RESULTS: The mito-protective activity of NP.SB revealed a dose-dependent effect when tested in GC-1 spg (mouse spermatogonial epithelial) and B/CMBA.Ov (mouse ovarian epithelial) following exposure to Nsuccinimidyl N-methylcarbamate, a potential human carcinogen. Smaller size, rapid internalization, faster mobility and site specific delivery conferred significant cancer protection in cultured cells. Notably, this encapsulated flavonoid supplementation; prevented emergence of neoplastic daughter clones from senescent mother phenotypes in pro-oxidant treated GC-1 spg and B/CMBA.Ov cells by selective abrogation of mitochondrial oxidative stress-induced aberrant epigenetic modifications. In vivo studies using a diethylnitrosamine and 2- acetylaminofluorene mouse model demonstrated that NP.SB has a significant inhibitory effect on tumor growth which clearly substantiated our in vitro findings. CONCLUSION: Anti-carcinogenic property in conjunction with low toxicity of NP.SB, underscores the translational significance of dietary flavonoids as cancer-protective agents for preferential application in clinical settings.

Inhibition of Intracellular Type 10 Adenylyl Cyclase Protects Cortical Neurons Against Reperfusion-Induced Mitochondrial Injury and Apoptosis.

Mitochondrial injury significantly contributes to the neuronal death under cerebral ischemia and reperfusion. Within several signaling pathways, cyclic adenosine monophosphate (cAMP) signaling plays a substantial role in mitochondrial injury and cell death. Traditionally, the source of cellular cAMP has been attributed to the membrane-bound adenylyl cyclase, whereas the role of the intracellular localized type 10 soluble adenylyl cyclase (sAC) in neuronal pathology has not been considered. Since neurons express an active form of sAC, we aimed to investigate the role of sAC in reperfusion-induced neuronal apoptosis. For this purpose, the in vitro model of oxygen/glucose deprivation (simulated ischemia, 1 h), followed by recovery (simulated reperfusion, 12 h) in rat embryonic neurons, was applied. Although ischemia alone had no significant effect on apoptosis, reperfusion led to an activation of the mitochondrial pathway of apoptosis, hallmarked by mitochondrial depolarization, cytochrome c release, and mitochondrial ROS formation. These effects were accompanied by significantly augmented sAC expression and increased cellular cAMP content during reperfusion. Pharmacological suppression of sAC during reperfusion reduced cellular cAMP and ameliorated reperfusion-induced mitochondrial apoptosis and ROS formation. Similarly, sAC knockdown prevented neuronal death. Further analysis revealed a role of protein kinase A (PKA), a major downstream target of sAC, in reperfusion-induced neuronal apoptosis and ROS formation. In conclusion, the results show a causal role of intracellular, sAC-dependent cAMP signaling in reperfusion-induced mitochondrial injury and apoptosis in neurons. The protective effect of sAC inhibition during the reperfusion phase provides a basis for the development of new strategies to prevent the reperfusion-induced neuronal injury.

Toxicity and immunomodulatory efficacy of biosynthesized silver myconanosomes on pathogenic microbes and macrophage cells.

Silver myconanosomes prepared from Alternaria brassicae may exhibit potential antimicrobial and immunomodulatory activity due to their inimitable character. The prepared myconanosomes were characterized by using differential light scattering, zeta potential, UV-visible spectroscopy and transmission electron microscopic analyses. Mycologically produced AgNPs were found as spherical and irregular shaped measuring size range between 55.4 and 70.23 nm. The antimicrobicidal activity of these AgNPs against pathogenic microbes was evaluated by agar well diffusion method. Results showed that AgNPs inhibit the growth of various bacteria and fungi, which may be due to the disruption of cell membranes, leakage of cytoplasm and DNA degradation. Cytotoxicity analysis of AgNPs on cell lines revealed its dose dependent effect. Moreover, significant increase of intracellular reactive oxygen species was characterized in AgNPs treated cells after 4 h of incubation. Thus, AgNPs may have a significant advantage over conventional antibiotics as microorganisms are acquiring resistance against the broad range of available antibiotics.