Gut Microbiota Modulation by Selenium and Zinc Enrichment Postbiotic on Dysbiosis Associated with Hypertension.

BACKGROUND: Targeting gut dysbiosis to treat chronic diseases or to alleviate the symptoms is a new direction for medical adjuvant therapies. Recently, postbiotics have received considerable attention as they are non-viable probiotic preparations that confer various health benefits to the host without the safety problems associated with using live microbial cells. OBJECTIVE: The aim of the study is to obtain selenium (Se) and zinc (Zn) enriched Saccharomyces boulardii postbiotic biomass and to analyze its modulation effect because these minerals play an important role in reducing gut dysbiosis linked to cardiovascular (CV) diseases. METHOD: The effect of the S. boulardii and Se/Zn enriched yeast postbiotics on CV microbial fingerprint was studied in vitro using the gastrointestinal system (GIS 1) and analyzed by microbiological, chemical, and qPCR methods. RESULT: There was a 2.2 log CFU/mL increase in the total bacterial load after SeZn postbiotic treatment and in the qPCR counts of Firmicutes phyla for both treatments. Beneficial taxa, Bifidobacterium spp. and Lactobacillus spp., as well as Bacteroides spp. were up to 1.5 log higher after mineral- enriched postbiotic application, while the acetic acid level increased. CONCLUSION: These preliminary studies highlight the therapeutic potential of using Se/Zn enriched yeast postbiotics as adjuvants for clinical treatments of CV diseases.

Role of nutraceutical against exposure to pesticide residues: power of bioactive compounds.

Pesticides play a crucial role in modern agriculture, aiding in the protection of crops from pests and diseases. However, their indiscriminate use has raised concerns about their potential adverse effects on human health and the environment. Pesticide residues in food and water supplies are a serious health hazards to the general public since long-term exposure can cause cancer, endocrine disruption, and neurotoxicity, among other health problems. In response to these concerns, researchers and health professionals have been exploring alternative approaches to mitigate the toxic effects of pesticide residues. Bioactive substances called nutraceuticals that come from whole foods including fruits, vegetables, herbs, and spices have drawn interest because of their ability to mitigate the negative effects of pesticide residues. These substances, which include minerals, vitamins, antioxidants, and polyphenols, have a variety of biological actions that may assist in the body's detoxification and healing of harm from pesticide exposure. In this context, this review aims to explore the potential of nutraceutical interventions as a promising strategy to mitigate the toxic effects of pesticide residues.

Toxic heavy metal ions contamination in water and their sustainable reduction by eco-friendly methods: isotherms, thermodynamics and kinetics study.

Heavy metal ions can be introduced into the water through several point and non-point sources including leather industry, coal mining, agriculture activity and domestic waste. Regrettably, these toxic heavy metals may pose a threat to both humans and animals, particularly when they infiltrate water and soil. Heavy metal poisoning can lead to many health complications, such as liver and renal dysfunction, dermatological difficulties, and potentially even malignancies. To mitigate the risk of heavy metal ion exposure to humans and animals, it is imperative to extract them from places that have been polluted. Several conventional methods such as ion exchange, reverse osmosis, ultrafiltration, membrane filtration and chemical precipitation have been used for the removal of heavy metal ions. However, these methods have high operation costs and generate secondary pollutants during water treatment. Biosorption is an alternative approach to eliminating heavy metals from water that involves employing eco-friendly and cost-effective biomass. This review is focused on the heavy metal ions contamination in the water, biosorption methods for heavy metal removal and mathematical modeling to explain the behaviour of heavy metal adsorption. This review can be helpful to the researchers to design wastewater treatment plants for sustainable wastewater treatment.

Gut Microbiota Modulators Based on Polyphenols Extracted from Winery By-Products and Their Applications in the Nutraceutical Industry.

Vine-growing for the production of wine is one of the oldest and most important agricultural activities worldwide, but the winemaking process leads to vast amounts of waste. Viticulture and vinification by-products have many bioactive molecules, including polyphenols, prebiotic fibers, organic acids, and minerals. While research on the specific human health effects of grapevine residues (pomace, seeds, barks, stalks, canes, and leaves) is still ongoing, the available data suggest the potential to positively modulate the normal and dysbiotic gut microbiota (GM) using polyphenol-rich extracts obtained from winery by-products. This review provides an updated summary of the in vitro and in vivo evidence in animal models and humans concerning the ability of polyphenol-rich winery residue to be used as a GM modulator that supports their nutraceutical applications as a functional ingredient. Additionally, this review aims to enhance interest in viticulture waste (grapevine stems and leaves), as the levels of polyphenols are similar to those found in red grapes or seeds. However, more research is still needed to obtain innovative products. The valorization of winery residues is not only environmentally friendly; it can also be economically beneficial, creating added-value nutraceuticals that modulate microbiota and a new revenue stream for wine producers.

Arsenic exposure to mouse visceral leishmaniasis model through their drinking water linked to the disease exacerbation via modulation in host protective immunity: a preclinical study.

A large body of evidence has shown a direct link between arsenic exposure and drug resistance to Leishmania parasites against antimonial preparations in visceral leishmaniasis (VL) hyper-endemic regions, especially in India and its sub-continent. However, the implicated roles of arsenic on the VL host, pathophysiological changes, and immune function have not yet been clarified, particularly at the reported concentration of arsenic in the VL hyper-endemic area of Bihar, India. Herein, we exposed the mouse VL model to arsenic (0.5 mg/L to 2 mg/L) through their drinking water and analyzed its effect on T cells proliferation, Th1/Th2-mediators, MAPK signaling cascade, and parasite load in preclinical models. Coherently, the parasite count in Giemsa stained spleen imprint has been investigated and found significant positive associations with levels of arsenic exposure. The liver and kidney function tests (AST, ALT, ALP, BUN, Creatinine, Urea, etc.) are apparent to hepatonephric toxicity in arsenic exposed VL mice compared to unexposed. This observation appears to be consistent with the up-regulated expression of immune regulatory Th2 mediators (IL-4, IL-10, TGF-ß) and down-regulated expression of Th1 mediators (IL-12, IFN-γ, TNF-α) with a suppressed leishmanicidal function of macrophage (ROS, NO, iNOS). We also established that arsenic exposure modulated the host ERK-1/2 and p38 MAPK signaling cascade, limited T lymphocyte proliferation, and a lower IgG2a/IgG1 ratio to favor the Leishmania parasite survival inside the host. This study suggests that the contorted Th1-subtype and exacerbated Th2-subtype immune responses are involved in the increased susceptibility and pathogenesis of Leishmania parasite among subjects/individuals regularly exposed to arsenic.

The General Composition of Polyhydroxyalkanoates and Factors that Influence their Production and Biosynthesis.

Polyhydroxyalkanoates (PHAs) have been a current research topic for many years. PHAs are biopolymers produced by bacteria under unfavorable growth conditions. They are biomaterials that exhibit a variety of properties, including biocompatibility, biodegradability, and high mechanical strength, making them suitable for future applications. This review aimed to provide general information on PHAs, such as their structure, classification, and parameters that affect the production process. In addition, the most commonly used bacterial strains that produce PHAs are highlighted, and details are provided on the type of carbon source used and how to optimize the parameters for bioprocesses. PHAs present a challenge to researchers because a variety of parameters affect biosynthesis, including the variety of carbon sources, bacterial strains, and culture media. Nevertheless, PHAs represent an opportunity to replace plastics, because they can be produced quickly and at a relatively low cost. With growing environmental concerns and declining oil reserves, polyhydroxyalkanoates are a potential replacement for nonbiodegradable polymers. Therefore, the study of PHA production remains a hot topic, as many substrates can be used as carbon sources. Both researchers and industry are interested in facilitating the production, commercialization, and application of PHAs as potential replacements for nonbiodegradable polymers. The fact that they are biocompatible, environmentally biodegradable, and adaptable makes PHAs one of the most important materials available in the market. They are preferred in various industries, such as agriculture (for bioremediation of oil-polluted sites, minimizing the toxicity of pollutants, and environmental impact) or medicine (as medical devices). The various bioprocess technologies mentioned earlier will be further investigated, such as the carbon source (to obtain a biopolymer with the lowest possible cost, such as glucose, various fatty acids, and especially renewable sources), pretreatment of the substrate (to increase the availability of the carbon source), and supplementation of the growth environment with different substances and minerals). Consequently, the study of PHA production remains a current topic because many substrates can be used as carbon sources. Obtaining PHA from renewable substrates (waste oil, coffee grounds, plant husks, etc.) contributes significantly to reducing PHA costs. Therefore, in this review, pure bacterial cultures (Bacillus megaterium, Ralstonia eutropha, Cupriavidus necator, and Pseudomonas putida) have been investigated for their potential to utilize by-products as cheap feedstocks. The advantage of these bioprocesses is that a significant amount of PHA can be obtained using renewable carbon sources. The main disadvantage is that the chemical structure of the obtained biopolymer cannot be determined in advance, as is the case with bioprocesses using a conventional carbon source. Polyhydroxyalkanoates are materials that can be used in many fields, such as the medical field (skin grafts, implantable medical devices, scaffolds, drug-controlled release devices), agriculture (for polluted water cleaning), cosmetics and food (biodegradable packaging, gentle biosurfactants with suitable skin for cosmetics), and industry (production of biodegradable biopolymers that replace conventional plastic). Nonetheless, PHA biopolymers continue to be researched and improved and play an important role in various industrial sectors. The properties of this material allow its use as a biodegradable material in the cosmetics industry (for packaging), in the production of biodegradable plastics, or in biomedical engineering, as various prostheses or implantable scaffolds.

Computational Approaches to Designing Antiviral Drugs against COVID-19: A Comprehensive Review.

The global impact of the COVID-19 pandemic caused by SARS-CoV-2 necessitates innovative strategies for the rapid development of effective treatments. Computational methodologies, such as molecular modelling, molecular dynamics simulations, and artificial intelligence, have emerged as indispensable tools in the drug discovery process. This review aimed to provide a comprehensive overview of these computational approaches and their application in the design of antiviral agents for COVID-19. Starting with an examination of ligand-based and structure-based drug discovery, the review has delved into the intricate ways through which molecular modelling can accelerate the identification of potential therapies. Additionally, the investigation extends to phytochemicals sourced from nature, which have shown promise as potential antiviral agents. Noteworthy compounds, including gallic acid, naringin, hesperidin, Tinospora cordifolia, curcumin, nimbin, azadironic acid, nimbionone, nimbionol, and nimocinol, have exhibited high affinity for COVID-19 Mpro and favourable binding energy profiles compared to current drugs. Although these compounds hold potential, their further validation through in vitro and in vivo experimentation is imperative. Throughout this exploration, the review has emphasized the pivotal role of computational biologists, bioinformaticians, and biotechnologists in driving rapid advancements in clinical research and therapeutic development. By combining state-of-the-art computational techniques with insights from structural and molecular biology, the search for potent antiviral agents has been accelerated. The collaboration between these disciplines holds immense promise in addressing the transmissibility and virulence of SARS-CoV-2.

The Modulation Effect of a Fermented Bee Pollen Postbiotic on Cardiovascular Microbiota and Therapeutic Perspectives.

Hypertension is a frequent comorbidity in patients with heart failure; therefore, blood pressure management for these patients is widely recommended in medical guidelines. Bee pollen and postbiotics that contain inactivated probiotic cells and their metabolites have emerged as promising bioactive compounds sources, and their potential role in mitigating cardiovascular (CV) risks is currently being unveiled. Therefore, this preliminary study aimed to investigate the impact of a lactic-fermented bee pollen postbiotic (FBPP) on the CV microbiota via in vitro tests. A new isolated Lactobacillus spp. strain from the digestive tract of bees was used to ferment pollen, obtaining liquid and dried atomized caps postbiotics. The modulating effects on a CV microbiota that corresponds to the pathophysiology of hypertension were investigated using microbiological methods and qPCR and correlated with the metabolic profile. Both liquid and dried FBPPs increased the number of the beneficial Lactobacillus spp. and Bifidobacterium spp. bacteria by up to 2 log/mL, while the opportunistic pathogen E. coli, which contributes to CV pathogenesis, decreased by 3 log/mL. The short-chain fatty acid (SCFA) profile revealed a significant increase in lactic (6.386 ± 0.106 g/L) and acetic (4.284 ± 0.017 g/L) acids, both with known antihypertensive effects, and the presence of isovaleric acid, which promotes a healthy gut microbiota. Understanding the impact of the FBPP on gut microbiota could lead to innovative strategies for promoting heart health and preventing cardiovascular diseases.

Therapeutic Potential of Green-Engineered ZnO Nanoparticles on Rotenone-Exposed D. melanogaster (Oregon R+): Unveiling Ameliorated Biochemical, Cellular, and Behavioral Parameters.

Nanotechnology holds significant ameliorative potential against neurodegenerative diseases, as it can protect the therapeutic substance and allow for its sustained release. In this study, the reducing and capping agents of Urtica dioica (UD), Matricaria chamomilla (MC), and Murraya koenigii (MK) extracts were used to synthesize bio-mediated zinc oxide nanoparticles (ZnO-NPs) against bacteria (Staphylococcus aureus and Escherichia coli) and against rotenone-induced toxicities in D. melanogaster for the first time. Their optical and structural properties were analyzed via FT-IR, DLS, XRD, EDS, SEM, UV-Vis, and zeta potential. The antioxidant and antimicrobial properties of the fabricated ZnO-NPs were evaluated employing cell-free models (DPPH and ABTS) and the well diffusion method, respectively. Rotenone (500 µM) was administered to Drosophila third instar larvae and freshly emerged flies for 24-120 h, either alone or in combination with plant extracts (UD, MC, an MK) and their biogenic ZnO-NPs. A comparative study on the protective effects of synthesized NPs was undertaken against rotenone-induced neurotoxic, cytotoxic, and behavioral alterations using an acetylcholinesterase inhibition assay, dye exclusion test, and locomotor parameters. The findings revealed that among the plant-derived ZnO-NPs, MK-ZnO NPs exhibit strong antimicrobial and antioxidant activities, followed by UD-ZnO NPs and MC-ZnO NPs. In this regard, ethno-nano medicinal therapeutic uses mimic similar effects in D. melanogaster by suppressing oxidative stress by restoring biochemical parameters (AchE and proteotoxicity activity) and lower cellular toxicity. These findings suggest that green-engineered ZnO-NPs have the potential to significantly enhance outcomes, with the promise of effective therapies for neurodegeneration, and could be used as a great alternative for clinical development.

Toxicological Profile of Polyethylene Terephthalate (PET) Microplastic in Ingested Drosophila melanogaster (Oregon R+) and Its Adverse Effect on Behavior and Development.

Microplastics are readily available in the natural environment. Due to the pervasiveness of microplastic pollution, its effects on living organisms necessitate further investigation. The size, time of exposure, and amount of microplastic particles appear to be the most essential factor in determining their toxicological effects, either organismal or sub-organismal. For our research work, we preferred to work on a terrestrial model organism Drosophila melanogaster (Oregon R+). Therefore, in the present study, we characterized 2-100 µm size PET microplastic and confirmed its accumulation in Drosophila, which allowed us to proceed further in our research work. At larger dosages, research on locomotory activities such as climbing, jumping, and crawling indicated a decline in physiological and neuromuscular functions. Our studies also determined retarded development in flies and decreased survival rate in female flies after exposure to the highest concentration of microplastics. These experimental findings provide insight into the possible potential neurotoxic effects of microplastics and their detrimental effects on the development and growth of flies.

In Silico Insight to Identify Potential Inhibitors of BUB1B from Mushroom Bioactive Compounds to Prevent Breast Cancer Metastasis.

BACKGROUND: Breast cancer is one of the most common types of cancer among women worldwide, and its metastasis is a significant cause of mortality. Therefore, identifying potential inhibitors of proteins involved in breast cancer metastasis is crucial for developing effective therapies. BUB1 mitotic checkpoint serine/threonine kinase B (BUB1B) is a key regulator of mitotic checkpoint control, which ensures the proper segregation of chromosomes during cell division. Dysregulation of BUB1B has been linked to a variety of human diseases, including breast cancer. Overexpression of BUB1B has been observed in various cancer types, and its inhibition has been shown to induce cancer cell death. Additionally, BUB1B inhibition has been suggested as a potential strategy for overcoming resistance to chemotherapy and radiation therapy. Given the importance of BUB1B in regulating cell division and its potential as a therapeutic target, the development of BUB1B inhibitors has been the focus of intense research efforts. Despite these efforts, few small molecule inhibitors of BUB1B have been identified, highlighting the need for further research in this area. In this study, the authors aimed to identify potential inhibitors of BUB1B from mushroom bioactive compounds using computational methods, which could ultimately lead to the development of new treatments for breast cancer metastasis. METHODS: This study has incorporated 70 bioactive compounds (handpicked through literature mining) of distinct mushrooms that were considered and explored to identify a suitable drug candidate. Their absorption, distribution, metabolism and excretion (ADME) properties were obtained to predict the drug-likeness of these 70 mushroom compounds based on Lipinski's rule of 5 (RO5). Screening these bioactive compounds and subsequent molecular docking against BUB1B provided compounds with the best conformation-based binding affinity. The best two complexes, i.e., BUB1B-lepitaprocerin D and BUB1B-peptidoglycan, were subjected to molecular dynamic simulations. Both complexes were assessed for their affinity, stability, and flexibility in protein-ligand complex systems. RESULTS: The molecular dynamic (MD) simulation studies revealed that lepitaprocerin D has an energetically favorable binding affinity with BUB1B. Results showed that the formation of a hydrogen bond between residues ASN123 and SER157, and lepitaprocerin D had strengthened the affinity of lepitaprocerin D with BUB1B. CONCLUSIONS: This study identified lepitaprocerin D as a potential and novel inhibitor for BUB1B that could be a plausible drug candidate for identifying and controlling the spread of breast cancer metastasis.

Boletus edulis Extract-A New Modulator of Dysbiotic Microbiota.

The regular administration of antibiotics is a public concern due to the prejudices of large population groups and the high frequency with which antimicrobial products are prescribed. The current study aimed to evaluate the in vitro effect of a new extract from Boletus edulis (BEE) on the human microbiota. One of the disadvantages of this extensive use is the disruption of the human microbiota, leading to potential negative health consequences. The in vitro evaluation of BEE consisted in determining its cytotoxicity, influence on the concentration of four types of cytokines (IL-6, IL-10, IL-1ß, TNFα), and capacity to modulate the human microbiota after administering antibiotics. The latter was assessed by microbiome analysis and the evaluation of short-chain fatty acid synthesis (SCFAs). Simultaneously, the content of total polyphenols, the antioxidant capacity, and the compositional analysis of the extract (individual polyphenols composition) were determined. The results showed that BEE modulates the microbial pattern and reduces inflammatory progression. The data demonstrated antioxidant properties correlated with the increase in synthesizing some biomarkers, such as SCFAs, which mitigated antibiotic-induced dysbiosis without using probiotic products.

Metabolic and Phenotypic Changes Induced during N-Acetylglucosamine Signalling in the Fungal Pathogen Candida albicans.

The human commensal yeast Candida albicans is pathogenic and results in a variety of mucosal and deep tissue problems when the host is immunocompromised. Candida exhibits enormous metabolic flexibility and dynamic morphogenetic transition to survive under host niche environmental conditions and to cause virulence. The amino sugar N-acetylglucosamine (GlcNAc) available at the host infection sites, apart from acting as an extremely good carbon and nitrogen source, also induces cellular signalling in this pathogen. In C. albicans, GlcNAc performs multifaceted roles, including GlcNAc scavenging, GlcNAc import and metabolism, morphogenetic transition (yeast-hyphae and white-opaque switch), GlcNAc-induced cell death (GICD), and virulence. Understanding the molecular mechanism(s) involved in GlcNAc-induced cellular processes has become the main focus of many studies. In the current study, we focused on GlcNAc-induced metabolic changes associated with phenotypic changes. Here, we employed gas chromatography-mass spectrometry (GC-MS), which is a high-throughput and sensitive technology, to unveil global metabolomic changes that occur in GlcNAc vs. glucose grown conditions in Candida cells. The morphogenetic transition associated with metabolic changes was analysed by high-resolution field emission scanning electron microscopy (FE-SEM). Metabolite analysis revealed the upregulation of metabolites involved in the glyoxylate pathway, oxidative metabolism, and fatty acid catabolism to probably augment the synthesis of GlcNAc-induced hypha-specific materials. Furthermore, GlcNAc-grown cells showed slightly more sensitivity to amphotericin B treatment. These results all together provide new insights into the development of antifungal therapeutics for the control of candidiasis in humans.

The Ethnopharmacological Properties of Green-Engineered Metallic Nanoparticles against Metabolic Disorders.

Metabolic syndrome is a multifaceted pathophysiologic condition that is largely caused by an imbalance between caloric intake and energy expenditure. The pathogenesis of metabolic syndrome is determined by an individual's genetic/epigenetics and acquired factors. Natural compounds, notably plant extracts, have antioxidant, anti-inflammatory, and insulin-sensitizing properties and are considered to be a viable option for metabolic disorder treatment due to their low risk of side effects. However, the limited solubility, low bioavailability, and instability of these botanicals hinder their performance. These specific limitations have prompted the need for an efficient system that reduces drug degradation and loss, eliminates unwanted side effects, and boosts drug bioavailability, as well as the percentage of the drug deposited in the target areas. The quest for an enhanced (effective) drug delivery system has led to the formation of green-engineered nanoparticles, which has increased the bioavailability, biodistribution, solubility, and stability of plant-based products. The unification of plant extracts and metallic nanoparticles has helped in the development of new therapeutics against metabolic disorders such as obesity, diabetes mellitus, neurodegenerative disorders, non-alcoholic fatty liver, and cancer. The present review outlines the pathophysiology of metabolic diseases and their cures with plant-based nanomedicine.

A Facile Synthesis of Flower-like Iron Oxide Nanoparticles and Its Efficacy Measurements for Antibacterial, Cytotoxicity and Antioxidant Activity.

The objective of this study was to investigate the rhombohedral-structured, flower-like iron oxide (Fe2O3) nanoparticles that were produced using a cost-effective and environmentally friendly coprecipitation process. The structural and morphological characteristics of the synthesized Fe2O3 nanoparticles were analyzed using XRD, UV-Vis, FTIR, SEM, EDX, TEM, and HR-TEM techniques. Furthermore, the cytotoxic effects of Fe2O3 nanoparticles on MCF-7 and HEK-293 cells were evaluated using in vitro cell viability assays, while the antibacterial activity of the nanoparticles against Gram-positive and Gram-negative bacteria (Staphylococcus aureus, Escherichia coli, and Klebsiella pneumoniae) was also tested. The results of our study demonstrated the potential cytotoxic activity of Fe2O3 nanoparticles toward MCF-7 and HEK-293 cell lines. The antioxidant potential of Fe2O3 nanoparticles was evidenced by the 1,1-diphenyl-2-picrylhydrazine (DPPH) and nitric oxide (NO) free radical scavenging assays. In addition, we suggested that Fe2O3 nanoparticles could be used in various antibacterial applications to prevent the spread of different bacterial strains. Based on these findings, we concluded that Fe2O3 nanoparticles have great potential for use in pharmaceutical and biological applications. The effective biocatalytic activity of Fe2O3 nanoparticles recommends its use as one of the best drug treatments for future views against cancer cells, and it is, therefore, recommended for both in vitro and in vivo in the biomedical field.

Biosynthesis and Bioapplications of Nanomaterials from Mushroom Products.

The production of nanoparticles (NPs) from chemical and physical synthesis has ended due to the involvement of toxic byproducts and harsh analytical conditions. Innovation and research in nanoparticle synthesis are derived from biomaterials that have gained attention due to their novel features, such as ease of synthesis, low-cost, eco-friendly approach, and high water solubility. Nanoparticles obtained through macrofungi involve several mushroom species, i.e., Pleurotus spp., Ganoderma spp., Lentinus spp., and Agaricus bisporus. It is well-known that macrofungi possess high nutritional, antimicrobial, anti-cancerous, and immune-modulatory properties. Nanoparticle synthesis via medicinal and edible mushrooms is a striking research field, as macrofungi act as an eco-friendly biofilm that secretes essential enzymes to reduce metal ions. The mushroom-isolated nanoparticles exhibit longer shelf life, higher stability, and increased biological activities. The synthesis mechanisms are still unknown; evidence suggests that fungal flavones and reductases have a significant role. Several macrofungi have been utilized for metal synthesis (such as Ag, Au, Pt, Fe) and non-metal nanoparticles (Cd, Se, etc.). These nanoparticles have found significant applications in advancing industrial and bio-medical ventures. A complete understanding of the synthesis mechanism will help optimize the synthesis protocols and control the shape and size of nanoparticles. This review highlights various aspects of NP production via mushrooms, including its synthesis from mycelium and the fruiting body of macrofungi. Also, we discuss the applications of different technologies in NP high-scale production via mushrooms.

Identification of Prognostic Biomarkers for Suppressing Tumorigenesis and Metastasis of Hepatocellular Carcinoma through Transcriptome Analysis.

Cancer is one of the deadliest diseases developed through tumorigenesis and could be fatal if it reaches the metastatic phase. The novelty of the present investigation is to explore the prognostic biomarkers in hepatocellular carcinoma (HCC) that could develop glioblastoma multiforme (GBM) due to metastasis. The analysis was conducted using RNA-seq datasets for both HCC (PRJNA494560 and PRJNA347513) and GBM (PRJNA494560 and PRJNA414787) from Gene Expression Omnibus (GEO). This study identified 13 hub genes found to be overexpressed in both GBM and HCC. A promoter methylation study showed these genes to be hypomethylated. Validation through genetic alteration and missense mutations resulted in chromosomal instability, leading to improper chromosome segregation, causing aneuploidy. A 13-gene predictive model was obtained and validated using a KM plot. These hub genes could be prognostic biomarkers and potential therapeutic targets, inhibition of which could suppress tumorigenesis and metastasis.

Demystifying the Role of Prognostic Biomarkers in Breast Cancer through Integrated Transcriptome and Pathway Enrichment Analyses.

Breast cancer (BC) is the most commonly diagnosed cancer and the leading cause of death in women. Researchers have discovered an increasing number of molecular targets for BC prognosis and therapy. However, it is still urgent to identify new biomarkers. Therefore, we evaluated biomarkers that may contribute to the diagnosis and treatment of BC. We searched TCGA datasets and identified differentially expressed genes (DEGs) by comparing tumor (100 samples) and non-tumor (100 samples) tissues using the Deseq2 package. Pathway and functional enrichment analysis of the DEGs was performed using the DAVID (Database for Annotation, Visualization, and Integrated Discovery) database. The protein-protein interaction (PPI) network was identified using the STRING database and visualized through Cytoscape software. Hub gene analysis of the PPI network was completed using cytohubba plugins. The associations between the identified genes and overall survival (OS) were analyzed using a Kaplan-Meier plot. Finally, we have identified hub genes at the transcriptome level. A total of 824 DEGs were identified, which were mostly enriched in cell proliferation, signal transduction, and cell division. The PPI network comprised 822 nodes and 12,145 edges. Elevated expression of the five hub genes AURKA, BUB1B, CCNA2, CCNB2, and PBK are related to poor OS in breast cancer patients. A promoter methylation study showed these genes to be hypomethylated. Validation through genetic alteration and missense mutations resulted in chromosomal instability, leading to improper chromosome segregation causing aneuploidy. The enriched functions and pathways included the cell cycle, oocyte meiosis, and the p53 signaling pathway. The identified five hub genes in breast cancer have the potential to become useful targets for the diagnosis and treatment of breast cancer.

Heavy Metal Contamination in the Aquatic Ecosystem: Toxicity and Its Remediation Using Eco-Friendly Approaches.

Urbanization and industrialization are responsible for environmental contamination in the air, water, and soil. These activities also generate large amounts of heavy metal ions in the environment, and these contaminants cause various types of health issues in humans and other animals. Hexavalent chromium, lead, and cadmium are toxic heavy metal ions that come into the environment through several industrial processes, such as tanning, electroplating, coal mining, agricultural activities, the steel industry, and chrome plating. Several physical and chemical methods are generally used for the heavy metal decontamination of wastewater. These methods have some disadvantages, including the generation of secondary toxic sludge and high operational costs. Hence, there is a need to develop a cost-effective and eco-friendly method for the removal of heavy metal ions from polluted areas. Biological methods are generally considered eco-friendly and cost-effective. This review focuses on heavy metal contamination, its toxicity, and eco-friendly approaches for the removal of heavy metals from contaminated sites.

Inter and intracellular mitochondrial transfer: Future of mitochondrial transplant therapy in Parkinson's disease.

Parkinson's disease (PD) is marked by the gradual degeneration of dopaminergic neurons and the intracellular build-up of Lewy bodies rich in α-synuclein protein. This impairs various aspects of the mitochondria including the generation of ROS, biogenesis, dynamics, mitophagy etc. Mitochondrial dynamics are regulated through the inter and intracellular movement which impairs mitochondrial trafficking within and between cells. This inter and intracellular mitochondrial movement plays a significant role in maintaining neuronal dynamics in terms of energy and growth. Kinesin, dynein, myosin, Mitochondrial rho GTPase (Miro), and TRAK facilitate the retrograde and anterograde movement of mitochondria. Enzymes such as Kinases along with Calcium (Ca2+), Adenosine triphosphate (ATP) and the genes PINK1 and Parkin are also involved. Extracellular vesicles, gap junctions, and tunneling nanotubes control intercellular movement. The knowledge and understanding of these proteins, enzymes, molecules, and movements have led to the development of mitochondrial transplant as a therapeutic approach for various disorders involving mitochondrial dysfunction such as stroke, ischemia and PD. A better understanding of these pathways plays a crucial role in establishing extracellular mitochondrial transplant therapy for reverting the pathology of PD. Currently, techniques such as mitochondrial coculture, mitopunch and mitoception are being utilized in the pre-clinical stages and should be further explored for translational value. This review highlights how intercellular and intracellular mitochondrial dynamics are affected during mitochondrial dysfunction in PD. The field of mitochondrial transplant therapy in PD is underlined in particular due to recent developments and the potential that it holds in the near future.