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1.
Immun Ageing ; 21(1): 52, 2024 Aug 02.
Article in English | MEDLINE | ID: mdl-39095841

ABSTRACT

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.

2.
Phytother Res ; 38(6): 2993-3019, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38600725

ABSTRACT

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.


Subject(s)
Catechin , Neurodegenerative Diseases , Phytotherapy , Humans , Neurodegenerative Diseases/drug therapy , Catechin/analogs & derivatives , Catechin/therapeutic use , Catechin/pharmacology , Curcumin/therapeutic use , Curcumin/pharmacology , Quercetin/pharmacology , Quercetin/therapeutic use , Animals , Cannabinoids/therapeutic use , Cannabinoids/pharmacology , Apigenin/pharmacology , Apigenin/therapeutic use , Blood-Brain Barrier/drug effects , Phytochemicals/pharmacology , Phytochemicals/therapeutic use , Plant Extracts/therapeutic use , Plant Extracts/pharmacology
3.
BMC Genomics ; 24(1): 565, 2023 Sep 22.
Article in English | MEDLINE | ID: mdl-37740204

ABSTRACT

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.


Subject(s)
Bacteriocins , Lactobacillus , Humans , Female , Lactobacillus/genetics , Phylogeny , Bacteriocins/genetics , Biological Evolution , Cell Membrane
4.
Crit Rev Microbiol ; 49(2): 256-282, 2023 Mar.
Article in English | MEDLINE | ID: mdl-35312419

ABSTRACT

The vagina endures multifaceted changes from neonatal to menopausal phases due to hormonal flux, metabolite deposition, and microbial colonization. These features have important implications in women's health. Several pre-factors show dynamic characteristics according to the phases that shift the vaginal microbiota from anaerobes to aerobes which is a hallmark of healthy vaginal environment. These factors include oestrogen levels, glycogen deposition, and vaginal microstructure. In the adult phase, Lactobacillus is highly dominant and regulates pH, adherence, aggregation, immune modulation, synthesis of bacteriocins, and biosurfactants (BSs) which are antagonistic to pathogens. Maternal factors are protective by favouring the colonization of lactobacilli in the vagina in the neonatal phase, which diminishes with age. The dominance of lactobacilli and dysbiosis in the adult phase depends on intrinsic and extrinsic factors in women, which vary between ethnicities. Recent developments in probiotics used against vaginal microbiome dysbiosis have shown great promise in restoring the normal microbiota including preventing the loss of beneficial bacteria. However, further in-depth studies are warranted to ensure long-term protection by probiotics. This review highlights various aspects of the vaginal microenvironment in different phases of growth and diverse ethnicities. Furthermore, it discusses future trends for formulating more effective population-specific probiotics and implications of paraprobiotics and postbiotics as effective therapeutics.


Subject(s)
Probiotics , Vaginosis, Bacterial , Adult , Infant, Newborn , Female , Humans , Dysbiosis/microbiology , Vagina/microbiology , Lactobacillus/metabolism , Women's Health , Bacteria , Vaginosis, Bacterial/microbiology
5.
Virol J ; 20(1): 201, 2023 09 01.
Article in English | MEDLINE | ID: mdl-37658381

ABSTRACT

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.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Haplotypes , SARS-CoV-2/genetics , Phylogeny , COVID-19/epidemiology , Mutation
6.
World J Microbiol Biotechnol ; 39(11): 315, 2023 Sep 22.
Article in English | MEDLINE | ID: mdl-37736853

ABSTRACT

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.


Subject(s)
Brevibacillus , Coleoptera , Fermented Foods , Humans , Animals , Glycine max , India , Ethnicity
7.
Cell Mol Life Sci ; 77(7): 1229-1249, 2020 Apr.
Article in English | MEDLINE | ID: mdl-31584128

ABSTRACT

Host-microbe interactions within the gut are fundamental to all higher organisms. Caenorhabditis elegans has been in use as a surrogate model to understand the conserved mechanisms in host-microbe interactions. Morphological and functional similarities of C. elegans gut with the human have allowed the mechanistic investigation of gut microbes and their effects on metabolism, development, reproduction, behavior, pathogenesis, immune responses and lifespan. Recent reports suggest their suitability for functional investigations of human gut bacteria, such as gut microbiota of healthy and diseased individuals. Our knowledge on the gut microbial diversity of C. elegans in their natural environment and the effect of host genetics on their core gut microbiota is important. Caenorhabditis elegans, as a model, is continuously bridging the gap in our understanding the role of genetics, environment, and dietary factors on physiology of the host.


Subject(s)
Caenorhabditis elegans/microbiology , Host-Pathogen Interactions , Models, Animal , Animals , Dysbiosis/microbiology , Gastrointestinal Microbiome , Models, Biological
8.
Cell Mol Life Sci ; 76(3): 473-493, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30317530

ABSTRACT

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.


Subject(s)
Gastrointestinal Microbiome/physiology , Computational Biology , Gastrointestinal Microbiome/genetics , Gastrointestinal Microbiome/immunology , Gastrointestinal Tract/microbiology , Humans , Symbiosis
10.
World J Microbiol Biotechnol ; 35(7): 102, 2019 Jun 24.
Article in English | MEDLINE | ID: mdl-31236715

ABSTRACT

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.


Subject(s)
Bacteria/isolation & purification , Biodiversity , Fermentation , Milk/microbiology , Animals , Bacteria/metabolism , DNA, Bacterial/genetics , DNA, Bacterial/isolation & purification , Enterococcus/isolation & purification , Enterococcus/metabolism , Food Handling , Food Microbiology , High-Throughput Nucleotide Sequencing , Lactobacillales , Lactobacillus/isolation & purification , Lactobacillus/metabolism , Lactococcus/isolation & purification , Lactococcus/metabolism , Leuconostoc/isolation & purification , Leuconostoc/metabolism , Metagenomics , Multivariate Analysis , RNA, Ribosomal, 16S/genetics , RNA, Ribosomal, 16S/isolation & purification
11.
J Exp Bot ; 66(9): 2583-93, 2015 May.
Article in English | MEDLINE | ID: mdl-25732534

ABSTRACT

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.


Subject(s)
ATP-Binding Cassette Transporters/physiology , Fusarium/physiology , Mycotoxins/pharmacology , Plant Proteins/physiology , Trichothecenes/pharmacology , Triticum/physiology , ATP-Binding Cassette Transporters/genetics , ATP-Binding Cassette Transporters/metabolism , Chromosome Mapping , Cloning, Molecular , Gene Expression Regulation, Plant , Mycotoxins/metabolism , Phylogeny , Plant Proteins/genetics , Plant Proteins/metabolism , Stress, Physiological , Trichothecenes/metabolism , Triticum/genetics , Triticum/growth & development , Virulence Factors
12.
BMC Plant Biol ; 14: 227, 2014 Aug 20.
Article in English | MEDLINE | ID: mdl-25135116

ABSTRACT

BACKGROUND: Brassinosteroid hormones regulate many aspects of plant growth and development. The membrane receptor BRI1 is a central player in the brassinosteroid signaling cascade. Semi-dwarf 'uzu' barley carries a mutation in a conserved domain of the kinase tail of BRI1 and this mutant allele is recognised for its positive contribution to both yield and lodging resistance. RESULTS: Here we show that uzu barley exhibits enhanced resistance to a range of pathogens. It was due to a combination of preformed, inducible and constitutive defence responses, as determined by a combination of transcriptomic and biochemical studies. Gene expression studies were used to determine that the uzu derivatives are attenuated in downstream brassinosteroid signaling. The reduction of BRI1 RNA levels via virus-induced gene silencing compromised uzu disease resistance. CONCLUSIONS: The pathogen resistance of uzu derivatives may be due to pleiotropic effects of BRI1 or the cascade effects of their repressed BR signaling.


Subject(s)
Disease Resistance/genetics , Hordeum/physiology , Host-Pathogen Interactions/genetics , Brassinosteroids/metabolism , Gene Silencing , Hordeum/virology , Plant Proteins/genetics
13.
Biopolymers ; 101(4): 355-65, 2014 Apr.
Article in English | MEDLINE | ID: mdl-23913788

ABSTRACT

Surface modification of silk fibroin (SF) materials using environmentally friendly and non-hazardous process to tailor them for specific application as biomaterials has drawn a great deal of interest in the field of biomedical research. To further explore this area of research, in this report, polypropylene (PP) grafted muga (Antheraea assama) SF (PP-AASF) suture is developed using plasma treatment and plasma graft polymerization process. For this purpose, AASF is first sterilized in argon (Ar) plasma treatment followed by grafting PP onto its surface. AASF is a non-mulberry variety having superior qualities to mulberry SF and is still unexplored in the context of suture biomaterial. AASF, Ar plasma treated AASF (AASFAr) and PP-AASF are subjected to various characterization techniques for better comparison and the results are attempted to correlate with their observed properties. Excellent mechanical strength, hydrophobicity, antibacterial behavior, and remarkable wound healing activity of PP-AASF over AASF and AASFAr make it a promising candidate for application as sterilized suture biomaterial.


Subject(s)
Anti-Infective Agents/pharmacology , Biocompatible Materials/pharmacology , Plasma Gases/chemistry , Polypropylenes/pharmacology , Silk/pharmacology , Sterilization , Sutures , Animals , Bombyx , Crystallization , Escherichia coli/drug effects , Female , Male , Materials Testing , Mechanical Phenomena , Microbial Sensitivity Tests , Rabbits , Spectrum Analysis, Raman , Tensile Strength , Wound Healing/drug effects , X-Ray Diffraction
14.
Toxicon X ; 23: 100203, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39263685

ABSTRACT

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.

15.
Article in English | MEDLINE | ID: mdl-38231052

ABSTRACT

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.


Subject(s)
Antibodies, Viral , COVID-19 Vaccines , COVID-19 , Immunoglobulin G , SARS-CoV-2 , Severity of Illness Index , Viral Load , Humans , India/epidemiology , COVID-19/immunology , COVID-19/prevention & control , COVID-19/epidemiology , COVID-19/blood , Male , Female , Antibodies, Viral/blood , COVID-19 Vaccines/immunology , Adult , SARS-CoV-2/immunology , Middle Aged , Immunoglobulin G/blood , Young Adult , Vaccination , Adolescent , Aged
16.
Drug Discov Today ; 29(11): 104156, 2024 Sep 02.
Article in English | MEDLINE | ID: mdl-39233307

ABSTRACT

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.

17.
N Biotechnol ; 83: 121-132, 2024 Nov 25.
Article in English | MEDLINE | ID: mdl-39111568

ABSTRACT

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.


Subject(s)
Anti-Inflammatory Agents , Probiotics , Probiotics/pharmacology , Animals , Mice , Humans , HT29 Cells , India , Anti-Inflammatory Agents/pharmacology , Fish Products/microbiology , RAW 264.7 Cells , Fishes/microbiology , Fishes/metabolism , Fermented Foods/microbiology , Fermentation , Lactobacillus plantarum/isolation & purification , Lactobacillus plantarum/metabolism
18.
ACS Omega ; 9(30): 32706-32716, 2024 Jul 30.
Article in English | MEDLINE | ID: mdl-39100358

ABSTRACT

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.

19.
Phytopathology ; 103(12): 1260-7, 2013 Dec.
Article in English | MEDLINE | ID: mdl-23777406

ABSTRACT

Fusarium pathogens are among the most damaging pathogens of cereals. These pathogens have the ability to attack the roots, seedlings, and flowering heads of barley and wheat plants with disease, resulting in yield loss and head blight disease and also resulting in the contamination of grain with mycotoxins harmful to human and animal health. There is increasing evidence that brassinosteroid (BR) hormones play an important role in plant defense against both biotic and abiotic stress agents and this study set out to determine if and how BR might affect Fusarium diseases of barley. Application of the epibrassinolide (epiBL) to heads of 'Lux' barley reduced the severity of Fusarium head blight (FHB) caused by Fusarium culmorum by 86% and reduced the FHB-associated loss in grain weight by 33%. Growth of plants in soil amended with epiBL resulted in a 28 and 35% reduction in Fusarium seedling blight (FSB) symptoms on the Lux and 'Akashinriki' barley, respectively. Microarray analysis was used to determine whether growth in epiBL-amended soil changed the transcriptional profile in stem base tissue during the early stages of FSB development. At 24 and 48 h post F. culmorum inoculation, there were 146 epiBL-responsive transcripts, the majority being from the 48-h time point (n = 118). Real-time reverse-transcription polymerase chain reaction analysis validated the results for eight transcripts, including five defense genes. The results of gene expression studies show that chromatin remodeling, hormonal signaling, photosynthesis, and pathogenesis-related genes are activated in plants as a result of growth in epiBL.


Subject(s)
Brassinosteroids/pharmacology , Disease Resistance , Fusarium/physiology , Hordeum/drug effects , Plant Diseases/prevention & control , Biomass , Gene Expression Profiling , Gene Expression Regulation, Plant , Hordeum/genetics , Hordeum/immunology , Hordeum/physiology , Host-Pathogen Interactions , Inflorescence/drug effects , Inflorescence/genetics , Inflorescence/immunology , Inflorescence/physiology , Oligonucleotide Array Sequence Analysis , Plant Diseases/immunology , Plant Diseases/microbiology , Plant Proteins/genetics , Plant Stems/drug effects , Plant Stems/genetics , Plant Stems/immunology , Plant Stems/physiology , Seedlings/drug effects , Seedlings/genetics , Seedlings/immunology , Seedlings/physiology , Seeds/drug effects , Seeds/genetics , Seeds/immunology , Seeds/physiology , Soil/chemistry , Time Factors
20.
Nanoscale ; 15(43): 17570-17582, 2023 Nov 09.
Article in English | MEDLINE | ID: mdl-37873646

ABSTRACT

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).


Subject(s)
Antineoplastic Agents , Humans , Caco-2 Cells , Antineoplastic Agents/pharmacology , Methotrexate/pharmacology , Cystine , Gold/pharmacology
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