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Abstract Background Conventional treatments for the articular diseases are often effective for symptom relief, but can also cause significant side effects and do not slow the progression of the disease. Several natural substances have been shown to be effective at relieving the symptoms of osteoarthritis (OA), and preliminary evidence suggests that some of these compounds may exert a favorable influence on the course of the disease. The objective of this study was to investigate the anti-inflammatory/chondroprotective potential of a Herbal and amino acid mixture containing extract of the Uncaria tomentosa, Boswellia spp., Lepidium meyenii and L-Leucine on the IL-1β-induced production of nitric oxide (NO), glycosaminoglycan (GAG), matrix metalloproteinases (MMPs), aggrecan (ACAN) and type II collagen (COL2A1) in human OA chondrocytes and OA cartilage explants. Methods Primary OA chondrocytes or OA cartilage explants were pretreated with Herbal-Leucine mixture (HLM, 1-10 μg/ml) and then stimulated with IL-1β (5 ng/ml). Effect of HLM on IL-1β-induced gene expression of iNOS, MMP-9, MMP-13, ACAN and COL2A1 was verified by real time-PCR. Estimation of NO and GAG release in culture supernatant was done using commercially available kits. Results HLM tested in these in vitro studies was found to be an effective anti-inflammatory agent, as evidenced by strong inhibition of iNOS, MMP-9 and MMP-13 expression and NO production in IL-1β-stimulated OA chondrocytes (p < 0.05). Supporting these gene expression results, IL-1β-induced cartilage matrix breakdown, as evidenced by GAG release from cartilage explants, was also significantly blocked (p < 0.05). Moreover, in the presence of herbal-Leucine mixture (HLM) up-regulation of ACAN and COL2A1 expression in IL-1β-stimulated OA chondrocytes was also noted (p < 0.05). The inhibitory effects of HLM were mediated by inhibiting the activation of nuclear factor (NF)-kB in human OA chondrocytes in presence of IL-1β. Conclusion Our data suggests that HLM could be chondroprotective and anti-inflammatory agent in arthritis, switching chondrocyte gene expression from catabolic direction towards anabolic and regenerative, and consequently this approach may be potentially useful as a new adjunct therapeutic/preventive agent for OA or injury recovery.

Abstract Background Mast cells and basophils are multifunctional effector cells and contain plentiful secretary granules in their cytoplasm. These cell types are involved in several inflammatory and immune events and are known to produce an array of mediators including a broad spectrum of cytokines. Pomegranate fruit is rich in anthocyanins and hydrolysable tannins; a group of polyphenolic compounds shown to be potent antioxidant with anti-inflammatory activity. However, no studies have been undertaken to investigate whether a polyphenol-rich pomegranate fruit extract (POMx) inhibits the inflammatory activity of activated human mast cells and basophils. The aim of this study was to examine whether POMx modulates inflammatory reactions using human basophilic cell line KU812. Methods KU812 cells were stimulated with phorbol-12-myristate 13-acetate plus calcium inophore A23187 (PMACI). The inhibitory effect of POMx on pro-inflammatory cytokine gene expression and production by stimulated KU812 cells was measured by quantitative RT-PCR, and cytokine-specific ELISA assays, respectively. Western blotting was used to analyze the effect of POMx on the activation of mitogen-activated protein kinases (MAPKs), and the nuclear factor (NF)-κB in PMACI stimulated KU812 cells. Effect on the activity of NF-κB was determined using Luciferase reporter assay. Significance of differences from control values were analyzed by means of standard statistical methods. Results POMx significantly decreased PMACI stimulated inflammatory gene expression and production of interleukin (IL)-6 and IL-8 in KU812 cells. The inhibitory effect of POMx on the pro-inflammatory cytokines was MAPK subgroups c-jun N-terminal kinase (JNK)- and extracellular-regulated kinase (ERK) dependent. In addition, POMx suppressed the NF-κB activation induced by PMACI by inhibiting IκB-degradation in human basophil cells. POMx also suppressed the powerful induction of NF-κB promoter-mediated luciferase activity in transiently transfected KU812 cells. Conclusion These novel pharmacological actions of POMx provide new suggestion that POMx or POMx-derived compounds may be of therapeutic use for the treatment of inflammatory diseases by suppressing mast cells/basophils activation.

Elicitation, the process of stimulating plants to enhance the production of valuable secondary metabolites, has emerged as a significant avenue in the field of plant biotechnology. This review paper provides a comprehensive examination of elicitation, encompassing its mechanisms, the imperative for its utilization, and the diverse array of elicitors employed, including abiotic, biotic, and nanoparticle-based agents. By exploring the intricate signaling pathways and molecular responses triggered by external stimuli in this review, we gain insights into how plants tailor their metabolite production in reaction to their environment. Intricately intertwined with the mechanisms, the types of elicitors utilized are extensively discussed. Abiotic elicitors, encompassing physical factors and chemicals, biotic elicitors involving microbe-derived molecules, plant hormones and symbiotic microorganisms, and the emerging application of nanoparticles as elicitation agents are explored. The review further examines the application of these elicitors in both in-vitro and in-vivo cultures, showcasing their practical utility in controlled laboratory settings and real-world environments. By assessing the efficacy of diverse elicitors, this paper provides valuable insights into tailoring elicitation strategies to enhance secondary metabolite yields for various applications. Addressing the limitations and leveraging emerging technologies will undoubtedly steer elicitation research towards innovative breakthroughs, further enhancing our capacity to harness plants for sustainable and efficient secondary metabolite production. [ABSTRACT FROM AUTHOR]

The seafood industry generates waste, including shells, bones, intestines, and wastewater. The discards are nutrient-rich, containing varying concentrations of carotenoids, proteins, chitin, and other minerals. Thus, it is imperative to subject seafood waste, including shrimp waste (SW), to secondary processing and valorization for demineralization and deproteination to retrieve industrially essential compounds. Although several chemical processes are available for SW processing, most of them are inherently ecotoxic. Bioconversion of SW is cost-effective, ecofriendly, and safe. Microbial fermentation and the action of exogenous enzymes are among the significant SW bioconversion processes that transform seafood waste into valuable products. SW is a potential raw material for agrochemicals, microbial culture media, adsorbents, therapeutics, nutraceuticals, and bio-nanomaterials. This review comprehensively elucidates the valorization approaches of SW, addressing the drawbacks of chemically mediated methods for SW treatments. It is a broad overview of the applications associated with nutrient-rich SW, besides highlighting the role of major shrimp-producing countries in exploring SW to achieve safe, ecofriendly, and efficient bio-products. [ABSTRACT FROM AUTHOR]

Antibiotic pollution poses a potential risk of genotoxicity, as antibiotics released into the environment can induce DNA damage and mutagenesis in various organisms. This pollution, stemming from pharmaceutical manufacturing, agriculture, and improper disposal, can disrupt aquatic ecosystems and potentially impact human health through the consumption of contaminated water and food. The removal of genotoxic antibiotics using algae-mediated approaches has gained considerable attention due to its potential for mitigating the environmental and health risks associated with these compounds. The paper provides an in-depth examination of the molecular aspects concerning algae and bioreactor-driven methodologies utilized for the elimination of deleterious antibiotics. The molecular analysis encompasses diverse facets, encompassing the discernment and profiling of algae species proficient in antibiotic degradation, the explication of enzymatic degradation pathways, and the refinement of bioreactor configurations to augment removal efficacy. Emphasizing the significance of investigating algal approaches for mitigating antibiotic pollution, this paper underscores their potential as a sustainable solution, safeguarding both the environment and human health. [ABSTRACT FROM AUTHOR]

Microplastics (MPs) are ubiquitous pollutants persisting almost everywhere in the environment. With the increase in anthropogenic activities, MP accumulation is increasing enormously in aquatic, marine, and terrestrial ecosystems. Owing to the slow degradation of plastics, MPs show an increased biomagnification probability of persistent, bioaccumulative, and toxic substances thereby creating a threat to environmental biota. Thus, remediation of MP-pollutants requires efficient strategies to circumvent the mobilization of contaminants leaching into the water, soil, and ultimately to human beings. Over the years, several microorganisms have been characterized by the potential to degrade different plastic polymers through enzymatic actions. Metagenomics (MGs) is an effective way to discover novel microbial communities and access their functional genetics for the exploration and characterization of plastic-degrading microbial consortia and enzymes. MGs in combination with metatranscriptomics and metabolomics approaches are a powerful tool to identify and select remediation-efficient microbes in situ. Advancement in bioinformatics and sequencing tools allows rapid screening, mining, and prediction of genes that are capable of polymer degradation. This review comprehensively summarizes the growing threat of microplastics around the world and highlights the role of MGs and computational biology in building effective response strategies for MP remediation. [ABSTRACT FROM AUTHOR]

Background: AKT1 is a serine/threonine kinase necessary for the mediation of apoptosis, angiogenesis, metabolism, and cell proliferation in both normal and cancerous cells. The mutations in the AKT1 gene have been associated with different types of cancer. Further, the AKT1 gene mutations are also reported to be associated with other diseases such as Proteus syndrome and Cowden syndromes. Hence, this study aims to identify the deleterious AKT1 missense SNPs and predict their effect on the function and structure of the AKT1 protein using various computational tools. Methods: Extensive in silico approaches were applied to identify deleterious SNPs of the human AKT1 gene and assessment of their impact on the function and structure of the AKT1 protein. The association of these highly deleterious missense SNPs with different forms of cancers was also analyzed. The in silico approach can help in reducing the cost and time required to identify SNPs associated with diseases. Results: In this study, 12 highly deleterious SNPs were identified which could affect the structure and function of the AKT1 protein. Out of the 12, four SNPs—namely, G157R, G159V, G336D, and H265Y—were predicted to be located at highly conserved residues. G157R could affect the ligand binding to the AKT1 protein. Another highly deleterious SNP, R273Q, was predicted to be associated with liver cancer. Conclusions: This study can be useful for pharmacogenomics, molecular diagnosis of diseases, and developing inhibitors of the AKT1 oncogene. [ABSTRACT FROM AUTHOR]

Candida auris is a major public health concern due to its high transmission and mortality rates, as well as the emergence of pan-resistant strains. This study aimed to identify an antifungal compound from Sarcochlamys pulcherrima, an ethnomedicinal plant, that can inhibit the growth of C. auris.Methanol and ethyl acetate extracts of the plant were obtained, and high-performance thin-layer chromatography (HPTLC) analysis was conducted to identify the major compounds in the extracts. The major compound detected by HPTLC was subjected to in vitro antifungal activity testing, and its antifungal mechanism was determined. The plant extracts inhibited the growth of both C. auris and Candida albicans. HPTLC analysis revealed the presence of gallic acid in the leaf extract. Furthermore, the in vitro antifungal assay showed that gallic acid inhibited the growth of different C. auris strains. In silico studies indicated that gallic acid can bind to the active sites of carbonic anhydrase (CA) proteins in both C. auris and C. albicans, affecting their catalytic activities. Compounds that target virulent proteins such as CA can aid in the reduction of drug-resistant fungi and the development of novel antifungal compounds with unique modes of action. However, additional in vivo and clinical studies are required to conclusively determine gallic acid's antifungal properties. Gallic acid derivatives may be developed in the future to possess more potent antifungal properties and target various pathogenic fungi. [ABSTRACT FROM AUTHOR]

Apoptosis is the elimination of functionally non-essential, neoplastic, and infected cells via the mitochondrial pathway or death receptor pathway. The process of apoptosis is highly regulated through membrane channels and apoptogenic proteins. Apoptosis maintains cellular balance within the human body through cell cycle progression. Loss of apoptosis control prolongs cancer cell survival and allows the accumulation of mutations that can promote angiogenesis, promote cell proliferation, disrupt differentiation, and increase invasiveness during tumor progression. The apoptotic pathway has been extensively studied as a potential drug target in cancer treatment. However, the off-target activities of drugs and negative implications have been a matter of concern over the years. Phytochemicals (PCs) have been studied for their efficacy in various cancer cell lines individually and synergistically. The development of nanoparticles (NPs) through green synthesis has added a new dimension to the advancement of plant-based nanomaterials for effective cancer treatment. This review provides a detailed insight into the fundamental molecular pathways of programmed cell death and highlights the role of PCs along with the existing drugs and plant-based NPs in treating cancer by targeting its programmed cell death (PCD) network. [ABSTRACT FROM AUTHOR]

Candida dubliniensis is an opportunistic pathogen associated with oral and invasive fungal infections in immune-compromised individuals. Furthermore, the emergence of C. dubliniensis antifungal drug resistance could exacerbate its treatment. Hence, in this study a multi-epitope vaccine candidate has been designed using an immunoinformatics approach by targeting C. dubliniensis secreted aspartyl proteinases (SAP) proteins. In silico tools have been utilized to predict epitopes and determine their allergic potential, antigenic potential, toxicity, and potential to elicit interleukin-2 (IL2), interleukin-4 (IL4), and IFN-γ. Using the computational tools, eight epitopes have been predicted that were then linked with adjuvants for final vaccine candidate development. Computational immune simulation has depicted that the immunogen designed emerges as a strong immunogenic candidate for a vaccine. Further, molecular docking and molecular dynamics simulation analyses revealed stable interactions between the vaccine candidate and the human toll-like receptor 5 (TLR5). Finally, immune simulations corroborated the promising candidature of the designed vaccine, thus calling for further in vivo investigation. [ABSTRACT FROM AUTHOR]

Livestock is an essential life commodity in modern agriculture involving breeding and maintenance. The farming practices have evolved mainly over the last century for commercial outputs, animal welfare, environment friendliness, and public health. Modifying genetic makeup of livestock has been proposed as an effective tool to create farmed animals with characteristics meeting modern farming system goals. The first technique used to produce transgenic farmed animals resulted in random transgene insertion and a low gene transfection rate. Therefore, genome manipulation technologies have been developed to enable efficient gene targeting with a higher accuracy and gene stability. Genome editing (GE) with engineered nucleases-Zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs) regulates the targeted genetic alterations to facilitate multiple genomic modifications through protein-DNA binding. The application of genome editors indicates usefulness in reproduction, animal models, transgenic animals, and cell lines. Recently, CRISPR/Cas system, an RNA-dependent genome editing tool (GET), is considered one of the most advanced and precise GE techniques for on-target modifications in the mammalian genome by mediating knock-in (KI) and knock-out (KO) of several genes. Lately, CRISPR/Cas9 tool has become the method of choice for genome alterations in livestock species due to its efficiency and specificity. The aim of this review is to discuss the evolution of engineered nucleases and GETs as a powerful tool for genome manipulation with special emphasis on its applications in improving economic traits and conferring resistance to infectious diseases of animals used for food production, by highlighting the recent trends for maintaining sustainable livestock production. [ABSTRACT FROM AUTHOR]

Microorganisms dwell in diverse plant niches as non-axenic biotic components that are beneficial as well pathogenic for the host. They improve nutrients-uptake, stress tolerance, phytohormone synthesis, and strengthening the defense system through phyllosphere, rhizosphere, and endosphere. The negative consequences of the microbial communities are largely in the form of diseases characterized by certain symptoms such as gall, cankers, rots etc. Uncultivable and unspecified nature of different phytomicrobiomes communities is a challenge in the management of plant disease, a leading cause for the loss of the plant products. Metagenomics has opened a new gateway for the exploration of microorganisms that are hitherto unknown, enables investigation of the functional aspect of microbial gene products through metatranscriptomics and metabolomics. Metagenomics offers advantages of characterizing previously unknown microorganisms from extreme environments like hot springs, glaciers, deep seas, animal gut etc. besides bioprospecting gene products such as Taq polymerase, bor encoded indolotryptoline, hydrolases, and polyketides. This review provides a detailed account of the phytomicrobiome networks and highlights the importance and limitations of metagenomics and other meta-omics approaches for the understanding of plant microbial diversity with special focus on the disease control and its management. [ABSTRACT FROM AUTHOR]

Monkeypox is a self-limiting zoonotic viral disease and causes smallpox-like symptoms. The disease has a case fatality ratio of 3–6% and, recently, a multi-country outbreak of the disease has occurred. The currently available vaccines that have provided immunization against monkeypox are classified as live attenuated vaccinia virus-based vaccines, which pose challenges of safety and efficacy in chronic infections. In this study, we have used an immunoinformatics-aided design of a multi-epitope vaccine (MEV) candidate by targeting monkeypox virus (MPXV) glycoproteins and membrane proteins. From these proteins, seven epitopes (two T-helper cell epitopes, four T-cytotoxic cell epitopes and one linear B cell epitopes) were finally selected and predicted as antigenic, non-allergic, interferon-γ activating and non-toxic. These epitopes were linked to adjuvants to design a non-allergic and antigenic candidate MPXV-MEV. Further, molecular docking and molecular dynamics simulations predicted stable interactions between predicted MEV and human receptor TLR5. Finally, the immune-simulation analysis showed that the candidate MPXV-MEV could elicit a human immune response. The results obtained from these in silico experiments are promising but require further validation through additional in vivo experiments. [ABSTRACT FROM AUTHOR]

The association of microorganisms with livestock as endosymbionts, opportunists, and pathogens has been a matter of debate for a long time. Several livestock-associated bacterial and other microbial species have been identified and characterized through traditional culture-dependent genomic approaches. However, it is imperative to understand the comprehensive microbial network of domestic animals for their wellness, disease management, and disease transmission control. Since it is strenuous to provide a niche replica to any microorganisms while culturing them, thus a substantial number of microbial communities remain obscure. Metagenomics has laid out a powerful lens for gaining insight into the hidden microbial diversity by allowing the direct sequencing of the DNA isolated from any livestock sample like the gastrointestinal tract, udder, or genital system. Through metatranscriptomics and metabolomics, understanding gene expression profiles of the microorganisms and their molecular phenotype has become unchallenging. With large data sets emerging out of the genomic, metagenomic, and other meta-omics methods, several computational tools have also been developed for curation, assembly, gene prediction, and taxonomic profiling of the microorganisms. This review provides a detailed account of the beneficial and pathogenic organisms that dwell within or on farm animals. Besides, it highlights the role of meta-omics and computational tools in a comprehensive analysis of livestock-associated microorganisms. [ABSTRACT FROM AUTHOR]

Dark septate endophytes (DSE) exert a plethora of effects in regulating plant growth, signalling and stress tolerance. The advent of metagenomics has led to the identification of various species of DSE to be associated with plant organs. They are known to modulate growth, nutrient uptake, phytohormone biosynthesis and production of active bioconstituents in several plants. The interactions between the DSE and host plants are mostly mutualistic but they can also be neutral or exhibit negative interactions. The DSE has beneficial role in removal/sequestration of toxic heavy metals from various environmental sites. Here, we discuss the beneficial role of DSE in enhancing plant tolerance to heavy metal stress, drought conditions, high salinity and protection from various plant pathogens. Furthermore, the underlying mechanism of stress resilience facilitated by DSE-plant interaction has also been discussed. The article also provides insights to some important future perspectives associated with DSE-mediated phytoremediation and reclamation of polluted land worldwide thus facilitating sustainable agriculture. [ABSTRACT FROM AUTHOR]

Microorganisms are ubiquitous on Earth and can inhabit almost every environment. In a complex heterogeneous environment or in face of ecological disturbance, the microbes adjust to fluctuating environmental conditions through a cascade of cellular and molecular systems. Their habitats differ from cold microcosms of Antarctica to the geothermal volcanic areas, terrestrial to marine, highly alkaline zones to the extremely acidic areas and freshwater to brackish water sources. The diverse ecological microbial niches are attributed to the versatile, adaptable nature under fluctuating temperature, nutrient availability and pH of the microorganisms. These organisms have developed a series of mechanisms to face the environmental changes and thereby keep their role in mediate important ecosystem functions. The underlying mechanisms of adaptable microbial nature are thoroughly investigated at the cellular, genetic and molecular levels. The adaptation is mediated by a spectrum of processes like natural selection, genetic recombination, horizontal gene transfer, DNA damage repair and pleiotropy-like events. This review paper provides the fundamentals insight into the microbial adaptability besides highlighting the molecular network of microbial adaptation under different environmental conditions. [ABSTRACT FROM AUTHOR]