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Neurotrophins, such as nerve growth factor and brain-derived neurotrophic factor, play an essential role in the survival of neurons. However, incorporating better features can increase their therapeutic efficacy in neurodegenerative diseases (NDs). Peptidomimetics, which mimic these neurotrophins, show potential for treating NDs. This study emphasizes the use of peptidomimetics from neurotrophins for treating NDs and their benefits. By improving bioavailability and stability, these molecules can completely transform the therapy for NDs. This in-depth review guides researchers and pharmaceutical developers, providing insight into the changing field of neurodegenerative medicine.
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Indian red scorpion Mesobuthus tamulus is responsible for substantial mortality in India and Sri Lanka; however, no specific diagnostic method is available to detect the venom of this scorpion in envenomed plasma or body fluid. Therefore, we have proposed a novel, simple, and rapid method for detecting M. tamulus venom (MTV) in the plasma of envenomed animals using polyclonal antibodies (PAb) raised against three modified custom peptides representing the antigenic epitopes of K+ (Tamapin) and Na+ (α-neurotoxin) channel toxins, the two major MTV toxins identified by proteomic analysis. The optimum PAb formulation containing PAb 1, 2, and 3 in proportion (1:1:1, w/w/w) acted synergistically, demonstrating significantly higher immunological recognition of MTV than anti-scorpion antivenom (developed against native toxins) and individual antibodies against peptide immunogens. The PAb formulation could detect MTV optimally in envenomed rat plasma (intravenous and subcutaneous routes) at 30-60 min post-injection. The acetonitrile precipitation method developed in this study to augment the MTV detection sensitivity enriched the low molecular mass peptide toxins in envenomed rat plasma, which was ascertained by mass spectrometry analysis. The gold nanoparticles conjugated PAb formulation, characterised by biophysical techniques such as Fourier transform infrared spectroscopy (FTIR) and transmission electron microscopy (TEM), demonstrated their interaction with low molecular mass MTV peptide toxins in envenomed rat plasma. This interaction results in the accumulation of the gold nanoparticles, thus leading to signal change in absorbance spectra that can be discerned within 10 min. From a standard curve of MTV spiked plasma, the quantity of MTV in envenomed rat plasma could be determined by gold nanoparticle-PAb formulation conjugate.
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ETHNOPHARMACOLOGICAL RELEVANCE: Every year, cardiovascular diseases (CVDs) account for about 17.9 million deaths, making them the primary cause of both morbidity and mortality. Conventional drugs, which are often prescribed to treat cardiovascular diseases, are costly and have adverse effects. Consequently, dietary modifications and other medications are needed. Traditional use of Solanum indicum as cardiotonic to treat hypertension and anticoagulant potency has been reported but poorly evaluated scientifically. AIM OF THE STUDY: This study investigated the in vivo anticoagulant activity and mechanism of anticoagulation of quercetin (QC), a bioactive compound isolated from S. indicum (SI) hydroethanolic fruit extract. MATERIALS AND METHODS: Bioassay-guided fractionation (anticoagulant activity) extracted QC from hydroethanolic SI extract. QC was extensively characterized biochemically and pharmacologically. The interaction between QC and thrombin was investigated using spectrofluorometric and isothermal calorimetric methods. Cytotoxicity, antiplatelet, and thrombolytic studies were carried out in vitro. The Swiss albino mice were used to assess the in vivo, anticoagulant, and antithrombotic activities of QC. RESULTS: QC exhibits anticoagulant activity via (i) uncompetitive inhibition of thrombin but not FXa with a Ki value of 33.11 ± 4.2 µM and (ii) a partial inhibition of thrombin-catalyzed platelet aggregation with an IC50 value of 13.2 ± 1.2 µM. The experimental validation of the in silico study's prediction of QC's binding to thrombin was confirmed by spectrofluorometric and isothermal calorimetric analyses. QC was nontoxic to mammalian, non-hemolytic cells and demonstrated thrombolytic activity by activating plasminogen. QC demonstrated in vivo anticoagulant efficacy, preventing k-carrageen-induced thrombus formation in mice's tails. In the acute circulatory stasis paradigm in mice, QC reduces thromboxane B2 (TXB2) and endothelin-1 (ET-1) while increasing nitric oxide synthase (eNOS) and 6-keto prostaglandin F1α (6-keto-PGF1 α). CONCLUSION: Effective in vivo anticoagulant and antithrombotic properties of S. indicum's bioactive component QC point to the plant's potential use as a herbal anticoagulant medication for preventing and treating cardiovascular diseases linked to thrombosis.
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Anticoagulantes , Fibrinolíticos , Extractos Vegetales , Agregación Plaquetaria , Quercetina , Solanum , Animales , Quercetina/farmacología , Quercetina/aislamiento & purificación , Ratones , Fibrinolíticos/farmacología , Fibrinolíticos/aislamiento & purificación , Solanum/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Anticoagulantes/farmacología , Anticoagulantes/aislamiento & purificación , Humanos , Agregación Plaquetaria/efectos de los fármacos , Masculino , Plantas Medicinales/química , Trombosis/tratamiento farmacológico , Trombosis/prevención & control , Frutas/química , Trombina , Simulación del Acoplamiento Molecular , Inhibidores de Agregación Plaquetaria/farmacología , Inhibidores de Agregación Plaquetaria/aislamiento & purificación , Coagulación Sanguínea/efectos de los fármacosRESUMEN
The Monocled Cobra (Naja kaouthia), a category one medically significant snake from the Elapidae family, inflicts severe envenomation in South and Southeast Asian countries. N. kaouthia is distributed throughout the eastern and northeastern parts of India, Nepal, Bangladesh, Myanmar, Thailand, Vietnam, Malaysia, and southwestern China. Envenomation by N. kaouthia is a medical emergency, and the primary clinical symptoms are neurotoxicity and localized tissue destruction. Unfortunately, data on the actual magnitude of N. kaouthia envenomation is scarce due to poor record keeping, lack of diagnostic kits, and region-wise well-coordinated epidemiological surveys. The present review highlights the diversity in the composition of N. Kaouthia venom (NKV) across various geographical regions, as revealed through biochemical and proteomic analyses. The qualitative and quantitative differences in the toxin isoforms result in differences in lethality and pathophysiological manifestation that may limit the effectiveness of antivenom therapy. Studies on commercial polyvalent antivenom (PAV) effectiveness against distinct NKV samples have revealed varying toxicity and enzymatic activity neutralization. Additionally, the identification of snake venom's poorly immunogenic toxins by mass spectrometry, quantification of venom-specific antibodies, and implications for antivenom therapy against snakebites are highlighted. Future directions involve clinical studies on NK envenomation where the snake is frequently encountered and the correlation of this data with NKV composition in that region. For more efficient and superior hospital management of NK envenomation, research should enhance the current immunization procedure to boost the development of antibodies against less immunogenic venom components of this snake.
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Antivenenos , Venenos Elapídicos , Mordeduras de Serpientes , Animales , Antivenenos/uso terapéutico , Asia Sudoriental/epidemiología , Mordeduras de Serpientes/tratamiento farmacológico , Humanos , Serpientes VenenosasRESUMEN
The present study evaluates the in-vitro antibiofilm activity against the biofilm formed by Staphylococcus aureus, and the wound-healing efficacy of two different types of rhamnolipids produced by Pseudomonas aeruginosa strain JS29 in S.aureus infected wounds. The biosurfactant production was carried out in a mineral salt medium supplemented with 2 % Glucose and 2 % Glycerol individually and thus were designated as RL-Glu and RL-Gly respectively. 0.5 mg/ml of RL-Glu and RL-Gly demonstrated 90 % growth inhibition of S. aureus while exhibiting bactericidal activity at 4 mg/ml of RL-Glu and 1 mg/ml of RL-Gly. Both types of rhamnolipid cause changes in membrane permeability leading to pathogens' non-viability. 90 % inhibition of biofilm formation by S. aureus was observed at 2 mg/ml of RL-Glu and 0.5 mg/ml of RL-Gly, while 0.5 mg/ml of both rhamnolipid disrupted 90 % of the preformed biofilm. 0.5 mg/ml of RL-Glu and RL-Gly decreases the production of exopolysaccharides and also causes structural alteration. 0.5 mg/ml of RL-Glu and RL-Gly were found to exhibit effective wound healing efficacy in S. aureus infected wounds within 7 days of treatment. Histopathological studies of wound sites revealed efficient wound management by both the rhamnolipid. LCMS and GCMS characterization of the biosurfactant revealed that JS29 produces different rhamnolipid congeners when grown on different carbon sources, thereby influencing the antimicrobial, antibiofilm, and wound healing efficacy of rhamnolipid.
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Antibacterianos , Biopelículas , Glucolípidos , Pseudomonas aeruginosa , Staphylococcus aureus , Tensoactivos , Cicatrización de Heridas , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Glucolípidos/farmacología , Staphylococcus aureus/efectos de los fármacos , Tensoactivos/farmacología , Cicatrización de Heridas/efectos de los fármacos , Pseudomonas aeruginosa/efectos de los fármacos , Antibacterianos/farmacología , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Animales , Pruebas de Sensibilidad Microbiana , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/microbiología , Viabilidad Microbiana/efectos de los fármacos , RatonesRESUMEN
The study aimed to isolate and characterize lactic acid bacteria from various traditional fermented fish products from North East India, including Xindol, Hentak, and Ngari, which hold significant dietary importance for the indigenous tribes. Additionally, the study sought to examine their untargeted metabolomic profiles. A total of 43 strains of Bacillus, Priestia, Staphylococcus, Pediococcus, and Lactiplantibacillus were isolated, characterized by 16 S rRNA gene and tested for probiotic properties. Five strains passed pH and bile salt tests with strain dependent antimicrobial activity, which exhibited moderate autoaggregation and hydrophobicity properties. Lactiplantibacillus plantarum MKTJ24 exhibited the highest hydrophobicity (42 %), which was further confirmed by adhesion assay in HT-29 cell lines (100 %). Lactiplantibacillus plantarum MKTJ24 treatment in LPS-stimulated HT-29 cells up-regulated expression of mucin genes compared to LPS-treated cells. Treatment of RAW 264.7 cells with Lactiplantibacillus plantarum MKTJ24 decreased LPS-induced reactive oxygen species (ROS) and nitric oxide (NO) productions. Further, genome analysis of Lactiplantibacillus plantarum MKTJ24 revealed the presence of several probiotic markers and immunomodulatory genes. The genome was found to harbor plantaricin operon involved in bacteriocin production. A pangenome analysis using all the publicly available L. plantarum genomes specifically isolated from fermented fish products identified 120 unique genes in Lactiplantibacillus plantarum MKTJ24. Metabolomic analysis indicated dominance of ascorbic acids, pentafluropropionate, cyclopropaneacetic acid, florobenzylamine, and furanone in Xindol. This study suggests that Lactiplantibacillus plantarum MKTJ24 has potential probiotic and immunomodulatory properties that could be used in processing traditional fermented fish products on an industrial scale to improve their quality and enhance functional properties.
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Antiinflamatorios , Probióticos , Probióticos/farmacología , Animales , Ratones , Humanos , Células HT29 , India , Antiinflamatorios/farmacología , Productos Pesqueros/microbiología , Células RAW 264.7 , Peces/microbiología , Peces/metabolismo , Alimentos Fermentados/microbiología , Fermentación , Lactobacillus plantarum/aislamiento & purificación , Lactobacillus plantarum/metabolismoRESUMEN
BACKGROUND: Proteostasis is a critical aging hallmark responsible for removing damaged or misfolded proteins and their aggregates by improving proteasomal degradation through the autophagy-lysosome pathway (ALP) and the ubiquitin-proteasome system (UPS). Research on the impact of heat-killed probiotic bacteria and their structural components on aging hallmarks and innate immune responses is scarce, yet enhancing these effects could potentially delay age-related diseases. RESULTS: This study introduces a novel heat-killed Levilactobacillus brevis strain MKAK9 (HK MKAK9), along with its exopolysaccharide (EPS), demonstrating their ability to extend longevity by improving proteostasis and immune responses in wild-type Caenorhabditis elegans. We elucidate the underlying mechanisms through a comprehensive approach involving mRNA- and small RNA sequencing, proteomic analysis, lifespan assays on loss-of-function mutants, and quantitative RT-PCR. Mechanistically, HK MKAK9 and its EPS resulted in downregulation of the insulin-like signaling pathway in a DAF-16-dependent manner, enhancing protein ubiquitination and subsequent proteasomal degradation through activation of the ALP pathway, which is partially mediated by microRNA mir-243. Importantly, autophagosomes engulf ubiquitinylated proteins, as evidenced by increased expression of the autophagy receptor sqst-3, and subsequently fuse with lysosomes, facilitated by increased levels of the lysosome-associated membrane protein (LAMP) lmp-1, suggesting the formation of autolysosomes for degradation of the selected cargo. Moreover, HK MKAK9 and its EPS activated the p38 MAPK pathway and its downstream SKN-1 transcription factor, which are known to regulate genes involved in innate immune response (thn-1, ilys-1, cnc-2, spp-9, spp-21, clec-47, and clec-266) and antioxidation (sod-3 and gst-44), thereby reducing the accumulation of reactive oxygen species (ROS) at both cellular and mitochondrial levels. Notably, SOD-3 emerged as a transcriptional target of both DAF-16 and SKN-1 transcription factors. CONCLUSION: Our research sets a benchmark for future investigations by demonstrating that heat-killed probiotic and its specific cellular component, EPS, can downregulate the insulin-signaling pathway, potentially improving the autophagy-lysosome pathway (ALP) for degrading ubiquitinylated proteins and promoting organismal longevity. Additionally, we discovered that increased expression of microRNA mir-243 regulates insulin-like signaling and its downstream ALP pathway. Our findings also indicate that postbiotic treatment may bolster antioxidative and innate immune responses, offering a promising avenue for interventions in aging-related diseases.
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Background: The fibrinolytic enzymes from Bacillus sp. are proposed as therapeutics in preventing thrombosis. Computational-based analyses of these enzymes' amino acid composition, basic physiological properties, presence of functional domain and motifs, and secondary and tertiary structure analyses can lead to developing a specific enzyme with improved catalytic activity and other properties that may increase their therapeutic potential. Methods: The nucleotide sequences of fibrinolytic enzymes produced by the genus Bacillus and its corresponding protein sequences were retrieved from the NCBI database and aligned using the PRALINE programme. The varied physiochemical parameters and structural and functional analysis of the enzyme sequences were carried out with the ExPASy-ProtParam tool, MEME server, SOPMA, PDBsum tool, CYS-REC tool, SWISS-MODEL, SAVES servers, TMHMM program, GlobPlot, and peptide cutter software. The assessed in-silico data were compared with the published experimental results for validation. Results: The alignment of sixty fibrinolytic serine protease enzymes (molecular mass 12-86 kDa) sequences showed 49 enzymes possess a conserved domain with a catalytic triad of Asp196, His242, and Ser569. The predicted instability and aliphatic indexes were 1.94-37.77, and 68.9-93.41, respectively, indicating high thermostability. The random coil means value suggested the predominance of this secondary structure in these proteases. A set of 50 amino acid residues representing motif 3 signifies the Peptidase S8/S53 domain that was invariably observed in 56 sequences. Additionally, 28 sequences have transmembrane helices, with two having the most disordered areas, and they pose 25 enzyme cleavage sites. A comparative analysis of the experimental work with the results of in-silico study put forward the characteristics of the enzyme sequences JF739176.1 and MF677779.1 to be considered when creating a potential mutant enzyme as these sequences are stable at high pH with thermostability and to exhibit αß-fibrinogenase activity in both experimental and in-silico studies.
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IL-35 is a recently discovered protein made up of IL-12α and IL-27ß chains. It is encoded by IL12A and EBI3 genes. Interest in researching IL-35 has significantly increased in recent years, as evidenced by numerous scientific publications. Diabetes is on the rise globally, causing more illness and death in developing countries. The International Diabetes Federation (IDF) reports that diabetes is increasingly affecting children and teenagers, with varying rates across different regions. Therefore, scientists seek new diabetes treatments despite the growth of drug research. Recent research aims to emphasize IL-35 as a critical regulator of diabetes, especially type 1 and autoimmune diabetes. This review provides an overview of recent research on IL-35 and its link to diabetes and its associated complications. Studies suggest that IL-35 can offer protection against type-1 diabetes and autoimmune diabetes by regulating macrophage polarization, T-cell-related cytokines, and regulatory B cells (Bregs). This review will hopefully assist biomedical scientists in exploring the potential role of IL-35-mediated immunotherapy in treating diabetes. However, further research is necessary to determine the exact mechanism and plan clinical trials.
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Diabetes Mellitus Tipo 1 , Inmunoterapia , Interleucinas , Humanos , Diabetes Mellitus Tipo 1/inmunología , Diabetes Mellitus Tipo 1/terapia , Inmunoterapia/métodos , Interleucinas/inmunología , Interleucinas/genética , Interleucinas/metabolismo , Animales , Linfocitos B Reguladores/inmunología , Macrófagos/inmunología , Macrófagos/metabolismoRESUMEN
Neurodegenerative disorders (NDs) are among the most common causes of death across the globe. NDs are characterized by progressive damage to CNS neurons, leading to defects in specific brain functions such as memory, cognition, and movement. The most common NDs are Parkinson's, Alzheimer's, Huntington's, and amyotrophic lateral sclerosis (ALS). Despite extensive research, no therapeutics or medications against NDs have been proven to be effective. The current treatment of NDs involving symptom-based targeting of the disease pathogenesis has certain limitations, such as drug resistance, adverse side effects, poor blood-brain barrier permeability, and poor bioavailability of drugs. Some studies have shown that plant-derived natural compounds hold tremendous promise for treating and preventing NDs. Therefore, the primary objective of this review article is to critically analyze the properties and potency of some of the most studied phytomedicines, such as quercetin, curcumin, epigallocatechin gallate (EGCG), apigenin, and cannabinoids, and highlight their advantages and limitations for developing next-generation alternative treatments against NDs. Further extensive research on pre-clinical and clinical studies for developing plant-based drugs against NDs from bench to bedside is warranted.
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Catequina , Enfermedades Neurodegenerativas , Fitoterapia , Humanos , Enfermedades Neurodegenerativas/tratamiento farmacológico , Catequina/análogos & derivados , Catequina/uso terapéutico , Catequina/farmacología , Curcumina/uso terapéutico , Curcumina/farmacología , Quercetina/farmacología , Quercetina/uso terapéutico , Animales , Cannabinoides/uso terapéutico , Cannabinoides/farmacología , Apigenina/farmacología , Apigenina/uso terapéutico , Barrera Hematoencefálica/efectos de los fármacos , Fitoquímicos/farmacología , Fitoquímicos/uso terapéutico , Extractos Vegetales/uso terapéutico , Extractos Vegetales/farmacologíaRESUMEN
BACKGROUND: As per the recommendation of the United States Food and Drug Administration, more research is needed to determine the antibody titer against COVID-19 vaccination. OBJECTIVE: The study aimed to understand the relationship between the antibody titer to the demographics, infection severity, and cycle threshold (CT) values of confirmed COVID-19 patients. METHODS: Initially, we obtained consent from 185 populations and included sixty RT-PCRpositive COVID-19 patients from Kamrup District in the Northeast State of Assam, India. The vaccination status was recorded and tested for the level of serum immunoglobulin (IgG). The CT values, gender, and clinical symptoms-based scoring (CSBS) correlated with their IgG value. RESULTS: Around 48% of participants gained an antibody titer more than the threshold value and showed CT values between 18-25. Moreover, the maximum distributed score above the average was found between the CT values 18-25. CONCLUSION: The IgG titer value differs significantly amongst the vaccinated population, which may depend upon their genetic and demographic variability.
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Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , Inmunoglobulina G , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Carga Viral , Humanos , India/epidemiología , COVID-19/inmunología , COVID-19/prevención & control , COVID-19/epidemiología , COVID-19/sangre , Masculino , Femenino , Anticuerpos Antivirales/sangre , Vacunas contra la COVID-19/inmunología , Adulto , SARS-CoV-2/inmunología , Persona de Mediana Edad , Inmunoglobulina G/sangre , Adulto Joven , Vacunación , Adolescente , AncianoRESUMEN
IMPORTANCE: Our study investigated how a traditional drink called Apong, made from fermented rice, affects the gut and health of the Mishing community in India. We compared two groups of people who drink Apong to a group of people who do not drink it. To accomplish this, we studied the gut bacteria, fecal metabolites, and blood samples of the participants. It was found that the people who drank Apong had higher blood pressure but lower blood sugar and protein levels than people who did not drink it. We also found that the gut microbiome composition of people who drank Apong was different from those who did not drink it. Moreover, people who drank Apong had lower levels of isovaleric acid in their feces. Overall, this study shows that a traditional drink like Apong can affect the gut bacteria of a community.
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Microbioma Gastrointestinal , Hipertensión , Humanos , Bacterias , Bebidas Fermentadas , Heces/microbiologíaRESUMEN
To understand the mechanism underlying the evolution of SARS-CoV-2 in a population, we sequenced 92 viral genomes from Assam, India. Analysis of these and database sequences revealed a complete selective sweep of a haplotype in Assam carrying 13 pre-existing variants, including a high leap in frequency of a variant on ORF8, which is involved in immune evasion. A comparative study between sequences of same lineage and similar time frames in and outside Assam showed that 10 of the 13 pre-existing variants had a frequency ranging from 96 to 99%, and the remaining 3 had a low frequency outside Assam. Using a phylogenetic approach to infer sequential occurrences of variants we found that the variant Phe120del on ORF8, which had a low frequency (1.75%) outside Assam, is at the base of the phylogenetic tree of variants and became totally fixed (100%) in Assam population. Based on this observation, we inferred that the variant on ORF8 had a selective advantage, so it carried the haplotype to reach the100% frequency. The haplotype also carried 32 pre-existing variants at a frequency from 1.00 to 80.00% outside Assam. Those of these variants that are more closely linked to the S-protein locus, which often carries advantageous mutations and is tightly linked to the ORF8 locus, retained higher frequencies, while the less tightly linked variants showed lower frequencies, likely due to recombination among co- circulating variants in Assam. The ratios of non-synonymous substitutions to synonymous substitutions suggested that some genes such as those coding for the S-protein and non-structural proteins underwent positive selection while others were subject to purifying selection during their evolution in Assam. Furthermore, we observed negative correlation of the Ct value of qRT-PCR of the patients with abundant ORF6 transcripts, suggesting that ORF6 can be used as a marker for estimating viral titer. In conclusion, our in-depth analysis of SARS-CoV-2 genomes in a regional population reveals the mechanism and dynamics of viral evolution.
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COVID-19 , SARS-CoV-2 , Humanos , Haplotipos , SARS-CoV-2/genética , Filogenia , COVID-19/epidemiología , MutaciónRESUMEN
The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a highly infectious positive RNA virus, has spread from its epicenter to other countries with increased mortality and morbidity. Its expansion has hampered humankind's social, economic, and health realms to a large extent. Globally, investigations are underway to understand the complex pathophysiology of coronavirus disease (COVID-19) induced by SARS-CoV-2. Though numerous therapeutic strategies have been introduced to combat COVID-19, none are fully proven or comprehensive, as several key issues and challenges remain unresolved. At present, natural products have gained significant momentum in treating metabolic disorders. Mushrooms have often proved to be the precursor of various therapeutic molecules or drug prototypes. The plentiful bioactive macromolecules in edible mushrooms, like polysaccharides, proteins, and other secondary metabolites (such as flavonoids, polyphenols, etc.), have been used to treat multiple diseases, including viral infections, by traditional healers and the medical fraternity. Some edible mushrooms with a high proportion of therapeutic molecules are known as medicinal mushrooms. In this review, an attempt has been made to highlight the exploration of bioactive molecules in mushrooms to combat the various pathophysiological complications of COVID-19. This review presents an in-depth and critical analysis of the current therapies against COVID-19 versus the potential of natural anti-infective, antiviral, anti-inflammatory, and antithrombotic products derived from a wide range of easily sourced mushrooms and their bioactive molecules.
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The vaginal microenvironment of healthy women has a predominance of Lactobacillus crispatus, L. iners, L. gasseri, and L. jensenii. The genomic repertoire of the strains of each of the species associated with the key attributes thereby regulating a healthy vaginal environment needs a substantial understanding.We studied all available human strains of the four lactobacilli across different countries, isolated from vaginal and urinal sources through phylogenetic and pangenomic approaches. The findings showed that L. iners has the highest retention of core genes, and L. crispatus has more gene gain in the evolutionary stratum. Interestingly, L. gasseri and L. jensenii demonstrated major population-specific gene-cluster gain/loss associated with bacteriocin synthesis, iron chelating, adherence, zinc and ATP binding proteins, and hydrolase activity. Gene ontology enrichment analysis revealed that L. crispatus strains showed greater enrichment of functions related to plasma membrane integrity, biosurfactant, hydrogen peroxide synthesis, and iron sequestration as an ancestral derived core function, while bacteriocin and organic acid biosynthesis are strain-specific accessory enriched functions. L. jensenii showed greater enrichment of functions related to adherence, aggregation, and exopolysaccharide synthesis. Notably, the key functionalities are heterogeneously enriched in some specific strains of L. iners and L. gasseri.This study shed light on the genomic features and their variability that provides advantageous attributes to predominant vaginal Lactobacillus species maintaining vaginal homeostasis. These findings evoke the need to consider region-specific candidate strains of Lactobacillus to formulate prophylactic measures against vaginal dysbiosis for women's health.
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Bacteriocinas , Lactobacillus , Humanos , Femenino , Lactobacillus/genética , Filogenia , Bacteriocinas/genética , Evolución Biológica , Membrana CelularRESUMEN
Preparation of traditionally fermented soybeans varies across ethnicities with distinct tastes, flavour, and nutritional values. The fermented soybean varieties Hawaijar, Bekang, and Akhone of north-east India are associated with diverse ethnic groups from Manipur, Mizoram, and Nagaland, respectively. These varieties differ in substrate and traditional practice that exerts differential bacterial-metabolite profile, which needs an in-depth analysis i. Culture-dependent and independent techniques investigated the bacterial diversity of the fermented soybean varieties. Gas chromatography and mass spectroscopy (GC-MS) studied these varieties' metabolite profiles. The common dominant bacterial genera detected in Hawaijar, Bekang, and Akhone were Bacillus, Ignatzschinaria, and Corynebacterium, with the presence of Brevibacillus and Staphylococcus exclusively in Hawaijar and Oceanobacillus in Bekang and Akhone. The metabolite analysis identified a higher abundance of essential amino acids, amino and nucleotide sugars, and vitamins in Hawaijar, short-chain fatty acids in Bekang, polyunsaturated fatty acids in Akhone and Hawaijar, and prebiotics in Akhone. The bacteria-metabolite correlation analysis predicted four distinct bacterial clusters associated with the differential synthesis of the functional metabolites. While B. subtilis is ubiquitous, cluster-1 comprised B. thermoamylovorans/B. amyloliquefaciens, cluster-2 comprised B. tropicus, cluster-3 comprised B. megaterium/B. borstelensis, and cluster-4 comprised B. rugosus. To the best of our knowledge, this is the first comparative study on traditional fermented soybean varieties of north-east India linking bacterial-metabolite profiles which may help in designing starters for desired functionalities in the future.
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Brevibacillus , Escarabajos , Alimentos Fermentados , Humanos , Animales , Glycine max , India , EtnicidadRESUMEN
Indian Red Scorpion (Mesobuthus tamulus) stings are a neglected public health problem in tropical and sub-tropical countries, including India. The drawbacks of conventional therapies using commercial anti-scorpion antivenom (ASA) and α1-adrenoreceptor antagonists (AAA) have prompted us to search for an adequate formulation to improve treatment against M. tamulus stings. Novel therapeutic drug formulations (TDF) of low doses of commercial ASA, AAA, and ascorbic acid have remarkably improved in neutralising the in vivo toxic effects of M. tamulus venom (MTV) tested in Caenorhabditis elegans and Wistar strain albino rats in vivo models. The neutralisation of MTV-induced production of free radicals, alteration of the mitochondrial transmembrane potential, and upregulated expression of genes involved in apoptosis, detoxification, and stress response in C. elegans by TDF surpassed the same effect shown by individual components of the TDF. Further, TDF efficiently neutralized the MTV-induced increase in blood glucose level within 30 to 60 min post-treatment, organ tissue damage, necrosis, and pulmonary oedema in Wistar rats, indicating its clinical application for effecting treating M. tamulus envenomation. This study demonstrates for the first time that C. elegans can be a model organism for screening the neutralization potency of the drug molecules against a neurotoxic scorpion venom.
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Mordeduras y Picaduras , Caenorhabditis elegans , Ratas , Animales , Ratas Wistar , Ponzoñas , EscorpionesRESUMEN
Recent studies on genetically susceptible individuals and animal models revealed the potential role of the intestinal microbiota in the pathogenesis of type 1 diabetes (T1D) through complex interactions with the immune system. T1D incidence has been increasing exponentially with modern lifestyle altering normal microbiota composition, causing dysbiosis characterized by an imbalance in the gut microbial community. Dysbiosis has been suggested to be a potential contributing factor in T1D. Moreover, several studies have shown the potential role of probiotics in regulating T1D through various mechanisms. Current T1D therapies target curative measures; however, preventive therapeutics are yet to be proven. This review highlights immune microbiota interaction and the immense role of probiotics and postbiotics as important immunological interventions for reducing the risk of T1D.
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Diabetes Mellitus Tipo 1 , Microbioma Gastrointestinal , Microbiota , Probióticos , Animales , Diabetes Mellitus Tipo 1/prevención & control , Disbiosis , Probióticos/uso terapéuticoRESUMEN
Crude petroleum oil spillage is becoming a global concern for environmental pollution and poses a severe threat to flora and fauna. Bioremediation is considered a clean, eco-friendly, and cost-effective process to achieve success among the several technologies adopted to mitigate fossil fuel pollution. However, due to the hydrophobic and recalcitrant nature of the oily components, they are not readily bioavailable to the biological components for the remediation process. In the last decade, nanoparticle-based restoration of oil-contaminated, owing to several attractive properties, has gained significant momentum. Thus, intertwining nano- and bioremediation can lead to a suitable technology termed 'nanobioremediation' expected to nullify bioremediation's drawbacks. Furthermore, artificial intelligence (AI), an advanced and sophisticated technique that utilizes digital brains or software to perform different tasks, may radically transfer the bioremediation process to develop an efficient, faster, robust, and more accurate method for rehabilitating oil-contaminated systems. The present review outlines the critical issues associated with the conventional bioremediation process. It analyses the significance of the nanobioremediation process in combination with AI to overcome such drawbacks of a traditional approach for efficiently remedying crude petroleum oil-contaminated sites.