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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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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
Gut microbiota has evolved along with their hosts and is an integral part of the human body. Microbiota acquired at birth develops in parallel as the host develops and maintains its temporal stability and diversity through adulthood until death. Recent developments in genome sequencing technologies, bioinformatics and culturomics have enabled researchers to explore the microbiota and in particular their functions at more detailed level than before. The accumulated evidences suggest that though a part of the microbiota is conserved, the dynamic members vary along the gastrointestinal tract, from infants to elderly, primitive tribes to modern societies and in different health conditions. Though the gut microbiota is dynamic, it performs some basic functions in the immunological, metabolic, structural and neurological landscapes of the human body. Gut microbiota also exerts significant influence on both physical and mental health of an individual. An in-depth understanding of the functioning of gut microbiota has led to some very exciting developments in therapeutics, such as prebiotics, probiotics, drugs and faecal transplantation leading to improved health.
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Microbioma Gastrointestinal/fisiología , Biología Computacional , Microbioma Gastrointestinal/genética , Microbioma Gastrointestinal/inmunología , Tracto Gastrointestinal/microbiología , Humanos , SimbiosisRESUMEN
Preparation of curd vary worldwide due to which its taste, texture and impact on human health also differ. In Assam, curd prepared from raw milk (RMC) is preferred over curd prepared from boiled milk (BMC), a tradition believed to have originated from the Mongoloid customs. Microbial diversity of raw milk (RM), boiled milk (BM), RMC and BMC collected from three farms were investigated by culture dependent and independent techniques. Additionally, metabolite profiles of RMC and BMC were studied by gas chromatography and mass spectroscopy. A total of 59 bacterial isolates were identified from the four different dairy products. In RM, lactic acid bacteria such as Lactococcus, Enterococcus, Lactobacillus and Leuconostoc were obtained along with the environmental bacteria like Bacillus, Staphylococcus, Acetobacter, Chryseobacterium, Streptococcus, Acinetobacter, Kocuria, Klebsiella and Macrococcus. Additionally, Prevotella, Oscillospira, Phascolarctobacterium and Akkermansia were also detected in BM by culture independent technique. In RMC and BMC, Lactococcus, Leuconostoc and Lactobacillus were prevalent. RM and RMC shared Enterococcus, Lactococcus, Streptococcus and Acinetobacter as common bacterial genera. However, no bacterial genus was common in BM and BMC. The correlation analysis revealed that Lactobacillus was negatively correlated to other bacterial genera. Oligotyping analysis revealed that Lactobacillus brevis and L.fermentum were abundant in RMC and BMC, respectively. In metabolomic study, ascorbic acid, dodecanoic acid and hexadecanoic acid were found to be significantly higher in RMC. Presence of different types of probiotics in these curds samples opens a new avenue to understand their effects on human health.
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Bacterias/aislamiento & purificación , Biodiversidad , Fermentación , Leche/microbiología , Animales , Bacterias/metabolismo , ADN Bacteriano/genética , ADN Bacteriano/aislamiento & purificación , Enterococcus/aislamiento & purificación , Enterococcus/metabolismo , Manipulación de Alimentos , Microbiología de Alimentos , Secuenciación de Nucleótidos de Alto Rendimiento , Lactobacillales , Lactobacillus/aislamiento & purificación , Lactobacillus/metabolismo , Lactococcus/aislamiento & purificación , Lactococcus/metabolismo , Leuconostoc/aislamiento & purificación , Leuconostoc/metabolismo , Metagenómica , Análisis Multivariante , ARN Ribosómico 16S/genética , ARN Ribosómico 16S/aislamiento & purificaciónRESUMEN
The mycotoxin deoxynivalenol (DON) acts as a disease virulence factor for Fusarium fungi, and tolerance of DON enhances wheat resistance to Fusarium head blight (FHB) disease. Two variants of an ATP-binding cassette (ABC) family C transporter gene were cloned from DON-treated wheat mRNA, namely TaABCC3.1 and TaABCC3.2. These represent two of three putative genes identified on chromosomes 3A, 3B, and 3D of the wheat genome sequence. Variant TaABCC3.1 represents the DON-responsive transcript previously associated with DON resistance in wheat. PCR-based mapping and in silico sequence analyses located TaABCC3.1 to the short arm of wheat chromosome 3B (not within the FHB resistance quantitative trait locus Fhb1). In silico analyses of microarray data indicated that TaABCC3 genes are expressed in reproductive tissue and roots, and in response to the DON producer Fusarium graminearum. Gene expression studies showed that TaABCC3.1 is activated as part of the early host response to DON and in response to the FHB defence hormone jasmonic acid. Virus-induced gene silencing (VIGS) confirmed that TaABCC3 genes contributed to DON tolerance. VIGS was performed using two independent viral construct applications: one specifically targeted TaABCC3.1 for silencing, while the other targeted this gene and the chromosome 3A homeologue. In both instances, VIGS resulted in more toxin-induced discoloration of spikelets, compared with the DON effects in non-silenced spikelets at 14 d after toxin treatment (≥2.2-fold increase, P<0.05). Silencing by both VIGS constructs enhanced head ripening, and especially so in DON-treated heads. VIGS of TaABCC3 genes also reduced the grain number by more than 28% (P<0.05), both with and without DON treatment, and the effects were greater for the construct that targeted the two homeologues. Hence, DON-responsive TaABCC3 genes warrant further study to determine their potential as disease resistance breeding targets and their function in grain formation and ripening.
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Transportadoras de Casetes de Unión a ATP/fisiología , Fusarium/fisiología , Micotoxinas/farmacología , Proteínas de Plantas/fisiología , Tricotecenos/farmacología , Triticum/fisiología , Transportadoras de Casetes de Unión a ATP/genética , Transportadoras de Casetes de Unión a ATP/metabolismo , Mapeo Cromosómico , Clonación Molecular , Regulación de la Expresión Génica de las Plantas , Micotoxinas/metabolismo , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estrés Fisiológico , Tricotecenos/metabolismo , Triticum/genética , Triticum/crecimiento & desarrollo , Factores de VirulenciaRESUMEN
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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Hydrogels have emerged as a potential tool for enhancing bioavailability and regulating the controlled release of therapeutic agents. Owing to its excellent biocompatibility, silk sericin-based hydrogels have garnered interest in biomedical applications. This study focuses on synthesizing a soft hydrogel by blending silk sericin (SS) and polycaprolactone (PCL) at room temperature. The physicochemical characteristics of the hydrogels have been estimated by different analytical techniques such as UV-visible spectroscopy, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and scanning electron microscopy (SEM). The rheological studies demonstrate the non-Newtonian behavior of the hydrogels. Further, the porosity analysis indicates a commendable absorption capacity of the hydrogels. The swelling degree of the hydrogels has been checked in both distilled water and buffer solutions of different pHs (2-10). Moreover, the drug release profile of the hydrogels, using diclofenac sodium (DS) as a model drug, has revealed a substantial release of approximately 67% within the first 130 min with a drug encapsulation efficiency of 60.32%. Moreover, both the empty and the drug-loaded hydrogels have shown antibacterial properties against Gram-positive and Gram-negative bacteria, with the drug-loaded hydrogels displaying enhanced effectiveness. Additionally, the prepared hydrogels are biodegradable, demonstrating their future prospects in biomedical applications.
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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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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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Monitoring therapeutic drugs and their elimination is crucial because they may cause severe side effects on the human body. Methotrexate (MTX) is a widely used anti-cancer drug, which is highly expensive, and the detection of unwanted overdoses of MTX using traditional procedures is time-consuming and involves complex instrumentation. In this work, we have developed a nanocomposite material using phosphorene, cystine, and gold (Ph-Cys-Au) that shows excellent optical properties. This nanocomposite can be used as an optical sensing platform for the detection of MTX in the range 0-260 µM. The synthesized sensing platform is very sensitive, selective, and cost-effective for the detection of MTX. Ph-Cys-Au can effectively detect MTX in aqueous media with a limit of detection (LOD) of about 0.0266 nM (for a linear range of 0-140 µM) and 0.0077 nM (for a linear range of 160-260 µM). The nanocomposite is equally selective for real samples, such as human blood serum (HBS) and artificial urine (AU) with a LOD of 0.0914 nM and 0.0734 nM, respectively. We have also determined the limit of quantification (LOQ); the LOQ values for the aqueous media were 0.0807 nM (for a linear range of 0-140 µM) and 0.0234 nM (for a linear range of 160-260 µM), whereas, the values for HBS and AU were around 0.2771 nM and 0.2226 nM, respectively. Moreover, the nanocomposite also provides a feasible platform for cytotoxicity screening in cancerous cells (Caco-2 cell lines) and non-cancerous cells (L-929 cell lines).
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Antineoplásicos , Humanos , Células CACO-2 , Antineoplásicos/farmacología , Metotrexato/farmacología , Cistina , Oro/farmacologíaRESUMEN
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
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
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
Neurodegenerative disorders (ND), associated with the progressive loss of neurons, oxidative stress-mediated production of reactive oxygen species (ROS), and mitochondrial dysfunction, can be treated with synthetic peptides possessing innate neurotrophic effects and neuroprotective activity. Computational analysis of two small synthetic peptides (trideca-neuropeptide, TNP; heptadeca-neuropeptide, HNP) developed from the nerve growth factors from snake venoms predicted their significant interaction with the human TrkA receptor (TrkA). In silico results were validated by an in vitro binding study of the FITC-conjugated custom peptides to rat pheochromocytoma PC-12 cell TrkA receptors. Pre-treatment of PC-12 cells with TNP and HNP induced neuritogenesis and significantly reduced the paraquat (PT)-induced cellular toxicity, the release of lactate dehydrogenase from the cell cytoplasm, production of intracellular ROS, restored the level of antioxidants, prevented alteration of mitochondrial transmembrane potential (ΔΨm) and adenosine triphosphate (ATP) production, and inhibited cellular apoptosis. These peptides lack in vitro cytotoxicity, haemolytic activity, and platelet-modulating properties and do not interfere with the blood coagulation system. Functional proteomic analyses demonstrated the reversal of PT-induced upregulated and downregulated metabolic pathway genes in PC-12 cells that were pre-treated with HNP and revealed the metabolic pathways regulated by HNP to induce neuritogenesis and confer protection against PT-induced neuronal damage in PC-12. The quantitative RT-PCR analysis confirmed that the PT-induced increased and decreased expression of critical pro-apoptotic and anti-apoptotic genes had been restored in the PC-12 cells pre-treated with the custom peptides. A network gene expression profile was proposed to elucidate the molecular interactions among the regulatory proteins for HNP to salvage the PT-induced damage. Taken together, our results show how the peptides can rescue PT-induced oxidative stress, mitochondrial dysfunction, and cellular death and suggest new opportunities for developing neuroprotective drugs.
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Neoplasias de las Glándulas Suprarrenales , Feocromocitoma , Ratas , Humanos , Animales , Especies Reactivas de Oxígeno/metabolismo , Paraquat/farmacología , Feocromocitoma/tratamiento farmacológico , Feocromocitoma/genética , Proteómica , Apoptosis , Estrés Oxidativo , Venenos de Serpiente/metabolismo , Venenos de Serpiente/farmacologíaRESUMEN
It is known that alcoholic beverages alter the human gut microbiome. This study focused on the potential impact of non-ethanolic ingredients in whisky on the gut bacteriome. A pilot study was carried out on 15 whisky drinkers, 5 rice beer drinkers, and 9 non-drinkers to determine the effect of alcoholic beverages on the host microbiome and metabolome. Additionally, a mouse model was used to assess the differential impact of three whisky brands (each with an equal ethanol concentration). The results indicate that the non-ethanolic components have an impact on the gut microbiome, as well as on the metabolites in blood and feces. The amount of Prevotella copri, a typical core Indian gut bacterium, decreased in both the human and mouse groups of whisky type 1, but an increase in abundance of Helicobacteriaceae (p = 0.01) was noticed in both groups. Additionally, the alcohol-treated cohorts had lower levels of short-chain fatty acids (SCFAs), specifically butyric acid, and higher amounts of lipids and stress marker IL1-ß than the untreated groups (p = 0.04-0.01). Furthermore, two compounds, ethanal/acetaldehyde (found in all the whisky samples) and arabitol (unique to whisky type 1), were tested in the mice. Similar to the human subjects, the whisky type 1 treated mouse cohort and the arabitol-treated group showed decreased levels of Prevotella copri (p = 0.01) in their gut. The results showed that non-ethanolic compounds have a significant impact on host gut bacterial diversity and metabolite composition, which has a further vital impact on host health. Our work further emphasizes the need to study the impact of non-ethanolic ingredients of alcoholic beverages on host health.
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The gut microbiome has a tremendous influence on human physiology, including the nervous system. During fetal development, the initial colonization of the microbiome coincides with the development of the nervous system in a timely, coordinated manner. Emerging studies suggest an active involvement of the microbiome and its metabolic by-products in regulating early brain development. However, any disruption during this early developmental process can negatively impact brain functionality, leading to a range of neurodevelopment and neuropsychiatric disorders (NPD). In this review, we summarize recent evidence as to how the gut microbiome can influence the process of early human brain development and its association with major neurodevelopmental psychiatric disorders such as autism spectrum disorders, attention-deficit hyperactivity disorder, and schizophrenia. Further, we discuss how gut microbiome alterations can also play a role in inducing drug resistance in the affected individuals. We propose a model that establishes a direct link of microbiome dysbiosis with the exacerbated inflammatory state, leading to functional brain deficits associated with NPD. Based on the existing research, we discuss a framework whereby early diet intervention can boost mental wellness in the affected subjects and call for further research for a better understanding of mechanisms that govern the gut-brain axis may lead to novel approaches to the study of the pathophysiology and treatment of neuropsychiatric disorders.
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Since the hypothesis of Dr. Elie Metchnikoff on lactobacilli-mediated healthy aging, several microbes have been reported to extend the lifespan with different features of healthy aging. However, a microbe affecting diverse features of healthy aging is of choice for broader acceptance and marketability as a next-generation probiotic. We employed Caenorhabditis elegans as a model to understand the potential of Lactobacillus plantarum JBC5 (LPJBC5), isolated from fermented food sample on longevity and healthy aging as well as their underlying mechanisms. Firstly, LPJBC5 enhanced the mean lifespan of C. elegans by 27.81% compared with control (untreated). LPBC5-induced longevity was accompanied with better aging-associated biomarkers, such as physical functions, fat, and lipofuscin accumulation. Lifespan assay on mutant worms and gene expression studies indicated that LPJBC5-mediated longevity was due to upregulation of the skinhead-1 (skn-1) gene activated through p38 MAPK signaling cascade. Secondly, the activated transcription factor SKN-1 upregulated the expression of antioxidative, thermo-tolerant, and anti-pathogenic genes. In support, LPJBC5 conferred resistance against abiotic and biotic stresses such as oxidative, heat, and pathogen. LPJBC5 upregulated the expression of intestinal tight junction protein ZOO-1 and improved gut integrity. Thirdly, LPJBC5 improved the learning and memory of worms trained on LPJBC5 compared with naive worms. The results showed upregulation of genes involved in serotonin signaling (ser-1, mod-1, and tph-1) in LPJBC5-fed worms compared with control, suggesting that serotonin-signaling was essential for LPJBC5-mediated improved cognitive function. Fourthly, LPJBC5 decreased the fat accumulation in worms by reducing the expression of genes encoding key substrates and enzymes of fat metabolism (i.e., fat-5 and fat-7). Lastly, LPJBC5 reduced the production of reactive oxygen species and improved mitochondrial function, thereby reducing apoptosis in worms. The capability of a single bacterium on pro-longevity and the features of healthy aging, including enhancement of gut integrity and cognitive functions, makes it an ideal candidate for promotion as a next-generation probiotic.
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Cold atmospheric pressure (CAP) plasma has a profound effect on protein-protein interactions. In this work, we have highlighted the deactivation of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) spike protein by CAP plasma treatment. Complete deactivation of spike protein binding to the human ACE2 protein was observed within an exposure time of 5 minutes which is correlated to the higher concentration of hydrogen peroxide formation due to the interaction with the reactive oxygen species present in the plasma. On the other hand, we have established that CAP plasma is also capable of degrading RNA of SARS-CoV-2 virus which is also linked to hydrogen peroxide concentration. The reactive oxygen species is produced in the plasma by using noble gases such as helium, in the absence of any other chemicals. Therefore, it is a green process with no chemical waste generated and highly advantageous from the environmental safety prospects. Results of this work could be useful in designing plasma-based disinfection systems over those based on environmentally hazardous chemical-based disinfection and biomedical applications.
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Ethnicity, geography, and dietary habits are known to have dominant roles in modulating the gut microbiota. Two major ethnic groups Ahom and Bodo in the north-east of India consume traditionally prepared rice beer which contains various microbes and substances that promote the growth of such microbes, known as prebiotics. This study aimed to understand the effect of traditionally prepared rice beer on gut microbiota. A total of 134 (67 from each group) volunteers including non-drinkers and drinkers from three locations were recruited. Fecal and blood samples were collected to study fecal bacterial and metabolite profiles and biochemical markers, respectively. Amplicon 16S rRNA gene sequencing (region V3-V4) by next-generation sequencing showed similar alpha and beta diversities in both the ethnic groups. However, with rice beer consumption the abundance of Firmicutes, Bacteroidetes, Fusobacteria phyla was higher in the drinkers (p < 0.05) of Ahom whereas only Firmicutes were higher in Bodo ethnic group. At the genus level, the bacterial abundance of Faecalibacterium and Roseburia were lower in the drinkers (p < 0.05) of both communities. Gas chromatography-mass spectrometry for the detection of fecal metabolites also revealed lower butyric acid in the feces of drinkers (p < 0.05). This study showed the effects of traditionally prepared rice beer on human gut microbiota and fecal metabolites. Further research is required to understand their effect on health.
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Global research is focused on understanding the factors affecting human gut microbiota vis-à-vis health. Brooks et al. [PLoS Biol. (2018) 16, e2006842] has reported a group of microbial taxa that vary across ethnicity in the USA (AGP and HMP data sets). Ethnicity-specific microbial signatures will aid in developing therapeutics for targeted microbiota modulation.