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1.
Sci Rep ; 14(1): 13177, 2024 06 07.
Article in English | MEDLINE | ID: mdl-38849503

ABSTRACT

Overconsumption of dietary sugar can lead to many negative health effects including the development of Type 2 diabetes, metabolic syndrome, cardiovascular disease, and neurodegenerative disorders. Recently, the human intestinal microbiota, strongly associated with our overall health, has also been known to be affected by diet. However, mechanistic insight into the importance of the human intestinal microbiota and the effects of chronic sugar ingestion has not been possible largely due to the complexity of the human microbiome which contains hundreds of types of organisms. Here, we use an interspecies C. elegans/E. coli system, where E. coli are subjected to high sugar, then consumed by the bacterivore host C. elegans to become the microbiota. This glucose-fed microbiota results in a significant lifespan reduction accompanied by reduced healthspan (locomotion), reduced stress resistance, and changes in behavior and feeding. Lifespan reduction is also accompanied by two potential major contributors: increased intestinal bacterial density and increased concentration of reactive oxygen species. The glucose-fed microbiota accelerated the age-related development of intestinal cell permeability, intestinal distention, and dysregulation of immune effectors. Ultimately, the changes in the intestinal epithelium due to aging with the glucose-fed microbiota results in increased susceptibility to multiple bacterial pathogens. Taken together, our data reveal that chronic ingestion of sugar, such as a Western diet, has profound health effects on the host due to changes in the microbiota and may contribute to the current increased incidence of ailments including inflammatory bowel diseases as well as multiple age-related diseases.


Subject(s)
Caenorhabditis elegans , Escherichia coli , Gastrointestinal Microbiome , Glucose , Intestinal Mucosa , Caenorhabditis elegans/microbiology , Animals , Glucose/metabolism , Intestinal Mucosa/microbiology , Intestinal Mucosa/metabolism , Reactive Oxygen Species/metabolism , Longevity , Disease Susceptibility
2.
J Biomol Struct Dyn ; 42(4): 1858-1874, 2024.
Article in English | MEDLINE | ID: mdl-37129196

ABSTRACT

Coronavirus disease (COVID-19) is an infectious disease caused by the SARS-CoV-2 virus and dexamethasone is a glucocorticoid widely used for its treatment. Dexamethasone is not used in non-severe cases due to its immunosuppressant action. So, considering this, Estrogen and Estetrol were tested for the treatment of COVID-19 as they all possess a common steroid ring and dislike dexamethasone, they are immunoenhancer. Virtual screening of test ligands was performed through molecular docking, MM-GBSA, simulations, in silico ADMET and drug-likeness prediction to identify their potential to inhibit the effects of SARS-CoV-2. Results showed that test ligands possess drug-like properties and they are safe as drug candidates. The protein-ligand interaction study revealed that they bind with the amino acid residues at the active site of the target proteins and the test ligands possess better binding potential than Dexamethasone. With protein Mpro, Estetrol and Estrogen showed docking score of -7.240 and -5.491 kcal/mol, and with protein ACE2, Estetrol and Estrogen showed docking score of -5.269 and -4.732 kcal/mol, respectively. Further, MD Simulation was carried out and most of the interactions of molecular docking are preserved during simulation. The prominent interactions that our test ligands showed during MD Simulation are similar to drugs that possess in vitro anticovid activity as shown in recent studies. Hence, our test ligands possessed potential for anticovid activity and they should be further tested through in vitro and in vivo studies for their activity against COVID-19.Communicated by Ramaswamy H. Sarma.


Subject(s)
COVID-19 , Estetrol , Humans , Molecular Docking Simulation , COVID-19 Drug Treatment , SARS-CoV-2 , Estrogens , Dexamethasone/pharmacology , Molecular Dynamics Simulation , Protease Inhibitors
3.
bioRxiv ; 2024 Feb 17.
Article in English | MEDLINE | ID: mdl-38106043

ABSTRACT

TIR-domain proteins with enzymatic activity are essential for immunity in plants, animals, and bacteria. However, it is not known how these proteins function in pathogen sensing in animals. We discovered that a TIR-domain protein (TIR-1/SARM1) is strategically expressed on the membranes of a lysosomal sub-compartment, which enables intestinal epithelial cells in the nematode C. elegans to survey for pathogen effector-triggered host damage. We showed that a redox active virulence effector secreted by the bacterial pathogen Pseudomonas aeruginosa alkalinized and condensed a specific subset of lysosomes by inducing intracellular oxidative stress. Concentration of TIR-1/SARM1 on the surface of these organelles triggered its multimerization, which engages its intrinsic NADase activity, to activate the p38 innate immune pathway and protect the host against microbial intoxication. Thus, lysosomal TIR-1/SARM1 is a sensor for oxidative stress induced by pathogenic bacteria to activate metazoan intestinal immunity.

4.
PLoS Pathog ; 19(10): e1011730, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37906605

ABSTRACT

Sphingolipids are required for diverse biological functions and are degraded by specific catabolic enzymes. However, the mechanisms that regulate sphingolipid catabolism are not known. Here we characterize a transcriptional axis that regulates sphingolipid breakdown to control resistance against bacterial infection. From an RNAi screen for transcriptional regulators of pathogen resistance in the nematode C. elegans, we identified the nuclear hormone receptor nhr-66, a ligand-gated transcription factor homologous to human hepatocyte nuclear factor 4. Tandem chromatin immunoprecipitation-sequencing and RNA sequencing experiments revealed that NHR-66 is a transcriptional repressor, which directly targets sphingolipid catabolism genes. Transcriptional de-repression of two sphingolipid catabolic enzymes in nhr-66 loss-of-function mutants drives the breakdown of sphingolipids, which enhances host susceptibility to infection with the bacterial pathogen Pseudomonas aeruginosa. These data define transcriptional control of sphingolipid catabolism in the regulation of cellular sphingolipids, a process that is necessary for pathogen resistance.


Subject(s)
Caenorhabditis elegans Proteins , Caenorhabditis elegans , Animals , Humans , Caenorhabditis elegans/microbiology , Caenorhabditis elegans Proteins/genetics , Caenorhabditis elegans Proteins/metabolism , Transcription Factors/metabolism , Gene Expression Regulation , Sphingolipids/genetics , Sphingolipids/metabolism
5.
Front Mol Neurosci ; 16: 1228980, 2023.
Article in English | MEDLINE | ID: mdl-37680582

ABSTRACT

How neural circuits drive behavior is a central question in neuroscience. Proper execution of motor behavior requires precise coordination of many neurons. Within a motor circuit, individual neurons tend to play discrete roles by promoting or suppressing motor output. How exactly neurons function in specific roles to fine tune motor output is not well understood. In C. elegans, the interneuron RIM plays important yet complex roles in locomotion behavior. Here, we show that RIM both promotes and suppresses distinct features of locomotion behavior to fine tune motor output. This dual function is achieved via the excitation and inhibition of the same motor circuit by electrical and chemical neurotransmission, respectively. Additionally, this bi-directional regulation contributes to motor adaptation in animals placed in novel environments. Our findings reveal that individual neurons within a neural circuit may act in opposing ways to regulate circuit dynamics to fine tune behavioral output.

6.
ACS Omega ; 8(21): 18981-18989, 2023 May 30.
Article in English | MEDLINE | ID: mdl-37273637

ABSTRACT

An experiment was conducted to evaluate the effect of the age of a seedling and sources of nutrients on the growth and yield of sweet corn at SKUAST-K during Kharif-2020. The experiment was performed under a factorial arrangement in a randomized complete block design (RCBD) with three replications. Factor A was the age of the seedling with three levels, viz., 12-day-old seedlings, 22-day-old seedlings, and 32-day-old seedlings. Factor B was the source of nutrients with five levels, viz., control, recommended dose of fertilizer (RDF), 1/2 RDF + 12 t ha-1 farmyard manure, 1/2 RDF + 4 t ha-1 vermicompost, and 1/2 RDF + 2 t ha-1 poultry manure. The experiment was tested using variety Sugar-75 with a spacing of 75 × 20 cm2. The findings of this study indicated that the age of the seedling and sources of nutrients extended a significant influence on growth parameters, yield attributes, and yield of sweet corn. Significantly highest values for various growth parameters of sweet corn, viz., plant height, number of functional leaves, leaf area index (LAI), and dry matter accumulation from 30 days after transplanting up to the harvest, were noted by transplanting A2 seedlings (22 day old). A similar trend was observed for yield attributes and yield with higher values with transplanting A2 seedlings (22 day old). Plots fertilized with 1/2 RDF + 2 t ha-1 poultry manure registered a significantly higher plant height, leaf area index (LAI), dry matter accumulation, and number of functional leaves, which eventually resulted in a higher green cob yield and green fodder yield under the same treatment. Overall, this study indicated that among different ages of seedlings, transplanting A2 seedlings (22 day old) outperformed other seedling ages, and plots treated with 1/2 RDF + 2 t ha-1 poultry manure outperformed other treatments; a combination of both proved superior in realizing a higher yield and profitability with a benefit-cost ratio (BCR) of 6.57 under temperate climatic conditions.

7.
Bioorg Chem ; 134: 106449, 2023 05.
Article in English | MEDLINE | ID: mdl-36889200

ABSTRACT

Despite the advancements in the management of Diabetes mellitus, the design and synthesis of drug molecule which ameliorates the hyperglycemia and associated secondary complications in diabetic patients, still remains a challenge. Herein, we report the synthesis, characterization and anti-diabetic evaluation of pyrimidine-thiazolidinedione derivatives. The synthesized compounds were characterized by 1H NMR, 13C NMR, FTIR and Mass Spectroscopic analytical techniques. The in-silico ADME studies depicted that the compounds were within the permissible limits of the Lipinski's rule of five. The compounds 6e and 6m showing the best results in OGTT were evaluated for in-vivo anti-diabetic evaluation in STZ induced diabetic rats. Administration of 6e and 6m for four weeks decreased the blood glucose levels significantly. Compound 6e (4.5 mg/kg p.o.) was the most potent compound of the series. It reduced the level of blood glucose to 145.2 ± 1.35 compared to the standard Pioglitazone (150.2 ± 1.06). Moreover, the 6e and 6m treated group did not show increase in bodyweight. The biochemical estimations showed that the levels of ALT, ASP, ALP, urea, creatinine, blood urea nitrogen, total protein and LDH restored to normal in 6e and 6m treated groups as compared to STZ control group. The histopathological studies supported the results obtained in biochemical estimations. Both the compounds did not show any toxicity. Moreover, the histopathological studies of pancreas, liver, heart and kidney revealed that the structural integrity of these tissues restored to almost normal in 6e and 6m treated groups as compared to STZ control group. Based upon these findings it can be concluded that the pyrimidine-based thiazolidinedione derivatives represent novel anti-diabetic agents with least side effects.


Subject(s)
Diabetes Mellitus, Experimental , Thiazolidinediones , Rats , Animals , Blood Glucose/metabolism , Diabetes Mellitus, Experimental/chemically induced , Diabetes Mellitus, Experimental/drug therapy , Thiazolidinediones/pharmacology , Thiazolidinediones/therapeutic use , Thiazolidinediones/chemistry , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/therapeutic use , Hypoglycemic Agents/chemistry , Pyrimidines/pharmacology , Pyrimidines/therapeutic use
8.
Immunity ; 56(4): 768-782.e9, 2023 04 11.
Article in English | MEDLINE | ID: mdl-36804958

ABSTRACT

Distinguishing infectious pathogens from harmless microorganisms is essential for animal health. The mechanisms used to identify infectious microbes are not fully understood, particularly in metazoan hosts that eat bacteria as their food source. Here, we characterized a non-canonical pattern-recognition system in Caenorhabditis elegans (C. elegans) that assesses the relative threat of virulent Pseudomonas aeruginosa (P. aeruginosa) to activate innate immunity. We discovered that the innate immune response in C. elegans was triggered by phenazine-1-carboxamide (PCN), a toxic metabolite produced by pathogenic strains of P. aeruginosa. We identified the nuclear hormone receptor NHR-86/HNF4 as the PCN sensor in C. elegans and validated that PCN bound to the ligand-binding domain of NHR-86/HNF4. Activation of NHR-86/HNF4 by PCN directly engaged a transcriptional program in intestinal epithelial cells that protected against P. aeruginosa. Thus, a bacterial metabolite is a pattern of pathogenesis surveilled by nematodes to identify a pathogen in its bacterial diet.


Subject(s)
Caenorhabditis elegans Proteins , Caenorhabditis elegans , Animals , Caenorhabditis elegans Proteins/genetics , Caenorhabditis elegans Proteins/metabolism , Gene Expression Regulation , Receptors, Cytoplasmic and Nuclear/metabolism , Immunity, Innate , Bacteria , Pseudomonas aeruginosa/metabolism
9.
Urol Ann ; 14(3): 252-258, 2022.
Article in English | MEDLINE | ID: mdl-36117794

ABSTRACT

Introduction: Primary obstructive megaureter (POM) is a congenital dilatation of the ureter due to an adynamic segment of vesicoureteric junction obstruction. Surgical intervention is needed if nuclear scan shows obstructive curve. We analyzed our data and outcome of conservative and surgical treatment in such cases at our tertiary care hospital. Materials and Methods: We evaluated all cases of POMs during the study period. Investigations included ultrasonography (USG), voiding cystourethrogram, diethylene pentacetic acid (DTPA) scan, and dimercaptosuccinyle acid scan. In antenatal cases, any pelvic dilatation ≥12 mm after 6 weeks were subjected to reonography. Patients with anterior-posterior pelvic diameter (APPD) ≥12 mm had to undergo DTPA scan to look for DRF and drainage. Follow-up USG was done in all cases of mild-to-moderate hydroureteronephrosis, with APPD <12 at 3 months interval. Results: A total of 270 megaureters were registered and treated during the study period (2008-2019). The total number of patients included was 50 (64 ureters). The mean age of presentation in these 30 children was 21.78 ± 18.1 months (range 1-72 months) and the mean weeks of gestation in antenatal cases at presentation as megaureter was 24 ± 7 weeks (range 13-37 weeks). The mean weight of babies was 2.72 ± 0.7 g. The duration of follow-up ranged from 16 to 1W12 months. The mean APPD on the affected side was 19.99 ± 10.3 mm (range 11-43 mm). The mean ureteric diameter was 1.67 ± 0.33 mm (range 0.78-2.66 cm). The mean split function of patients with POM was 34.88% ± 11.5% on the affected side. Twenty patients (40%) had spontaneous resolution over a mean time period of 24.1 ± 11.1 months. Thirty patients underwent surgical procedures. In three children, HTN was observed over a mean follow-up period of 3 years. Conclusion: The babies with POM need a close follow-up. Surgery is indicated in prolonged t½/Tmax on renal scan, function <40% at the initial scan, or >5% split function deterioration in the subsequent renal scan.

10.
Bioorg Chem ; 126: 105885, 2022 09.
Article in English | MEDLINE | ID: mdl-35636128

ABSTRACT

A series of novel cyanopyrimidine-hydrazone hybrids were synthesized and characterized with various spectroscopic techniques. The synthesized compounds were tested at NCI, USA, on a 60-cell line panel and most of the compounds showed remarkable cytotoxic activity against different cancer cell lines. Compound 5a was found to be the most potent compound of the series and it was further selected for five dose assays wherein it exhibited GI50 value of 0.414 µM and 0.417 µM against HOP-62 and OVCAR-4 cell lines respectively. The in-silico mechanistic studies indicated that these compounds are acting through inhibition of lysine specific demethylase 1 (LSD1) as evident from in to vitro LSD1 inhibition activity of compounds. Among various synthesized derivatives, compound 5a was found to have IC50-value of 0.956 µM. In addition, absorption, distribution, metabolism, excretion and toxicity profile (ADMET) was assessed for these novel derivatives to get an insight on their pharmacokinetic/dynamic attributes which revealed that synthesized compounds showed acceptable metabolic stability in human liver microsomes with minimal inhibition of cytochrome P450s (CYPs). The results indicated that compound 5a could be a promising lead compound for further development as a therapeutic agent for anticancer activity.


Subject(s)
Antineoplastic Agents , Hydrazones , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cell Proliferation , Drug Design , Drug Screening Assays, Antitumor , Histone Demethylases , Humans , Hydrazones/chemistry , Lysine/pharmacology , Molecular Docking Simulation , Molecular Structure , Structure-Activity Relationship
11.
Sci Rep ; 11(1): 11291, 2021 05 28.
Article in English | MEDLINE | ID: mdl-34050209

ABSTRACT

Lung cancer is genetically diverse and a major health burden. Non-small cell lung cancer (NSCLC) accounts for 80% of total lung cancer cases and 20% cases are Small cell lung cancer (SCLC). The present case-control association study focused on the cost effective high throughput genotyping using Agena MassARRAY matrix-assisted laser desorption/ionization-time of flight, mass spectrometry (MALDI-TOF) platform to analyze the genetic association of candidate genetic variants. We performed multiplex PCR and genotyped twelve single nucleotide polymorphisms (SNPs) in 723 samples (162 NSCLC cases and 592 healthy controls). These genetic variants were selected from literature for their association with various cancers worldwide and this is the first study from the region to examine these critically important genetic variants. With prospective case-control association study design, twelve variants from ten genes were evaluated. Amongst these six variants, TCF21 (rs12190287), ERCC1 (rs2298881, 11615), ERCC5 (rs751402), ARNTL (rs4757151), BRIP1 (rs4986764) showed significant association with NSCLC risk (p ≤ 0.003) in Jammu and Kashmir population. In-silico findings of these genetic variants showed remarkable functional roles that needs in-vitro validations. It is further anticipated that such case control studies will help us in understanding the missing heritability of non-small cell lung cancer.


Subject(s)
Carcinoma, Non-Small-Cell Lung/genetics , Gene Expression Profiling/methods , Alleles , Asian People , Case-Control Studies , Gene Expression/genetics , Gene Frequency/genetics , Genetic Association Studies/methods , Genetic Predisposition to Disease/genetics , Genetic Variation/genetics , Genotype , Humans , India/epidemiology , Lung Neoplasms/genetics , Polymorphism, Single Nucleotide/genetics , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods , Transcriptome/genetics
12.
Elife ; 102021 05 12.
Article in English | MEDLINE | ID: mdl-33978570

ABSTRACT

The model organism Caenorhabditis elegans mounts transcriptional defense responses against intestinal bacterial infections that elicit overlapping starvation and infection responses, the regulation of which is not well understood. Direct comparison of C. elegans that were starved or infected with Staphylococcus aureus revealed a large infection-specific transcriptional signature, which was almost completely abrogated by deletion of transcription factor hlh-30/TFEB, except for six genes including a flavin-containing monooxygenase (FMO) gene, fmo-2/FMO5. Deletion of fmo-2/FMO5 severely compromised infection survival, thus identifying the first FMO with innate immunity functions in animals. Moreover, fmo-2/FMO5 induction required the nuclear hormone receptor, NHR-49/PPAR-α, which controlled host defense cell non-autonomously. These findings reveal an infection-specific host response to S. aureus, identify HLH-30/TFEB as its main regulator, reveal FMOs as important innate immunity effectors in animals, and identify the mechanism of FMO regulation through NHR-49/PPAR-α during S. aureus infection, with implications for host defense and inflammation in higher organisms.


Subject(s)
Caenorhabditis elegans/immunology , Immunity, Innate , Oxygenases/metabolism , Animals , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism , Basic Helix-Loop-Helix Transcription Factors/metabolism , Caenorhabditis elegans/enzymology , Caenorhabditis elegans/genetics , Caenorhabditis elegans/microbiology , Caenorhabditis elegans Proteins/metabolism , Food Deprivation , Oxygenases/genetics , PPAR alpha/metabolism , Receptors, Cytoplasmic and Nuclear/metabolism , Staphylococcal Infections/immunology , Staphylococcus aureus/physiology
14.
Sci Rep ; 10(1): 22144, 2020 Dec 17.
Article in English | MEDLINE | ID: mdl-33335154

ABSTRACT

This paper demonstrates how secondary electron energy spectroscopy (SEES) performed inside a scanning electron microscope (SEM) can be used to map sample atomic number and acquire bulk valence band density of states (DOS) information at low primary beam voltages. The technique uses an electron energy analyser attachment to detect small changes in the shape of the scattered secondary electron (SE) spectrum and extract out fine structure features from it. Close agreement between experimental and theoretical bulk valance band DOS distributions was obtained for six different test samples, where the normalised root mean square deviation ranged from 2.7 to 6.7%. High accuracy levels of this kind do not appear to have been reported before. The results presented in this paper point towards SEES becoming a quantitative material analysis companion tool for low voltage scanning electron microscopy (LVSEM) and providing new applications for Scanning Auger Microscopy (SAM) instruments.

15.
3 Biotech ; 10(9): 410, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32904533

ABSTRACT

Various Genome-wide association studies (GWAS) have reported the association of variant rs2494938 with lung cancer. However, genetic association of LRFN2 genetic variation with non-small cell lung cancer (NSCLC) in North Indian population remained unexplored. We conducted a case-control association study using TaqMan-based chemistry in which a total of 619 individuals, 189 NSCLC cases and 430 controls, were genotyped to explore the association of rs2494938 genetic variant of the LRFN2 gene with NSCLC patients from North India. The allele 'G' (risk allele) of the genetic variant rs2494938 was significantly associated with the NSCLC [OR = 1.51 (1.18-1.93 at 95% CI); p value = 0.0009]. Genetic association was also explored by applying different genetic models (Dominant, Additive). These results suggest that rs2494938 polymorphism of the LRFN2 gene is a risk factor in the North Indian populations to develop NSCLC. The LD (Linkage Disequilibrium) plot demonstrates the variant and its LD SNPs (r 2 > 0.8) and the variant has direct regulatory effect, which could affect the overall physiology of the gene. These findings could be used as diagnostic and prognostic markers in clinical studies of lung cancer patients in North Indian population groups. The present study also provides an important evidence on the genetic etiology of NSCLC in North Indian populations and further expounds GWAS findings on the role of LRFN2 in lung cancer risk. This study provides the holistic view about the non-small cell lung cancer in Jammu and Kashmir, North Indian population and it can be a hallmark of cancer if verified on a very large sample size (cohort).

16.
Egypt Heart J ; 72(1): 48, 2020 Aug 05.
Article in English | MEDLINE | ID: mdl-32757079

ABSTRACT

BACKGROUND: Although rare, the possibility of encountering an anomalous coronary artery is a reality. The outcome of such a procedure is greatly influenced by the awareness of the operator about the anatomical variations and the technique required. CASE PRESENTATION: A 50-year-old female patient presented with chest pain. On evaluation, she was found to have an inferior wall myocardial infarction. Left coronary angiography showed non-obstructive disease in the left anterior descending (LAD) and left circumflex artery (LCX). The right coronary artery could not be hooked despite multiple attempts and catheter changes. A non-specific aortic angiogram revealed anomalous origin of the right coronary artery (RCA) above the sinotubular junction on the left side. RCA was hooked with the AL-2 diagnostic catheter, and the percutaneous coronary intervention (PCI) procedure was completed via the same diagnostic catheter. CONCLUSION: In a life-threatening difficult situation like acute coronary syndrome with anomalous origin of coronary arteries, PCI can be done using a diagnostic catheter.

17.
Curr Opin Neurobiol ; 62: 1-9, 2020 06.
Article in English | MEDLINE | ID: mdl-31790812

ABSTRACT

Interplay between the nervous and immune systems is critical for homeostasis, and its dysfunction underlies pathologies such as multiple sclerosis, autism, leukemia, and inflammation. The nematode Caenorhabditis elegans provides an opportunity to define evolutionarily conserved mechanisms of regulation of host innate immunity and inflammation in a genetically tractable whole-animal system. In the past few years, the C. elegans nervous system has emerged as an integral part of host defense against pathogens, acting through diverse mechanisms to repress or induce protective transcriptional responses to infection in distal tissues. In this review, we discuss current knowledge of the mechanisms through which the C. elegans nervous system controls the expression of host defense genes in the intestinal epithelium. Although still incomplete, the insights derived from such work have broad implications for neural regulation of epithelial function at mucosal barriers in higher organisms in health and disease.


Subject(s)
Caenorhabditis elegans , Animals , Caenorhabditis elegans Proteins , Immunity, Innate , Nervous System
18.
Mol Cell ; 74(5): 864-865, 2019 06 06.
Article in English | MEDLINE | ID: mdl-31173721

ABSTRACT

Dietary restriction (DR) extends lifespan in multiple animal species, but the underlying molecular mechanisms remain poorly understood. A recent study published in Cell Metabolism by Wu et al. (2019) shows that DR represses an evolutionarily conserved p38 MAPK pathway involved in innate immunity, leading to diminished expression of p38 MAPK-regulated genes and extended lifespan.


Subject(s)
Immunity, Innate , Longevity , Animals , Nutritional Status
19.
BMC Cancer ; 19(1): 493, 2019 May 24.
Article in English | MEDLINE | ID: mdl-31126249

ABSTRACT

BACKGROUND: Telomere genetics has recently been emerged as an important field in molecular oncology. Various genome-wide association studies in different population groups have revealed that polymorphisms in Telomere maintenance gene (TERT) gene located on 5p15.33 is associated with susceptibility to leukemia and lung cancer risk. However, association of TERT with leukemia and lung cancer risk in north Indian population groups is still unknown. This study observed the association between genetic variant rs2853677 of TERT and leukemia and lung cancer in the state of Jammu and Kashmir, India. METHODS: A total of 781 subjects, out of which 381 cases (203 leukemic patients and 178 non-small cell lung cancer patients NSCLC) and 400 healthy controls were recruited for the study. Genetic variant rs2853677of TERT was detected using the real-time and Taqman Chemistry. Hardy-Weinberg Equilibrium was assessed using the chi square test. The allele and genotype- specific risks were estimated as odds ratio with 95% confidence interval. RESULTS: We observed that variant rs2853677 was strongly associated with lung cancer and leukemia risk with an odds ratio (OR) =1.8 (1.03-3.2 at 95% CI); p value (adjusted) = 0.03; odds ratio (OR) =2.9 (1.4-5.5.at 95% CI); p value (adjusted) = 0.002, respectively. CONCLUSION: The results of this study suggested that rs2853677 of TERT signifies association in multiple cancers and suggests that it can become potential marker for diagnosis of non-small cell lung cancer and leukemia. The study will provide an insight in understanding the genetic etiology and highlights the role of telomere-associated pathways in non-small cell lung cancer and leukemia. However, it would be quite interesting to explore the contribution of this variant in other cancers as well.


Subject(s)
Carcinoma, Non-Small-Cell Lung/genetics , Leukemia/genetics , Lung Neoplasms/genetics , Telomerase/genetics , Adult , Aged , Biomarkers, Tumor/genetics , Carcinoma, Non-Small-Cell Lung/blood , Case-Control Studies , Chi-Square Distribution , Female , Gene Frequency , Genetic Predisposition to Disease , Genome-Wide Association Study , Genotype , Humans , India , Leukemia/blood , Lung Neoplasms/blood , Male , Middle Aged , Odds Ratio , Polymorphism, Single Nucleotide
20.
Public Health Action ; 8(2): 85-90, 2018 Jun 21.
Article in English | MEDLINE | ID: mdl-29946525

ABSTRACT

Setting: Karachi, Pakistan. Objective: To assess the effectiveness of a community-based integrated approach in changing women's behaviour regarding contraceptive use. Design: The Sukh Initiative is a multipronged approach with door-to-door services using community health workers to provide quality family planning/reproductive health services at both public and private facilities and a 24/7 family planning helpline service that provides youth skill-based education. Methods: Retrospective pre- and post-intervention data using samples of 5140 and 3810 women, respectively. Results: The contraceptive prevalence rate increased by 10.7%, from 42.3% at baseline to 53.0% mid-intervention, with an increase in use of modern contraceptive methods of 9.2%. A significant association was found between door-to-door counselling and the use of contraceptive methods (OR 3.4, 95%CL 2.9-4.1) and access to public and private facilities for modern contraceptives (OR 2.4, 95%CL 2.0-3.0). However, support group meetings and 24/7 helpline use did not show any association with use of contraceptive method. Conclusion: The study helped to increase access to and choice of family planning services through a community-based approach that successfully reduced unmet needs and improved continuity in contraceptive use.


Contexte : Des enquêtes avant et après intervention ont été réalisées à Karachi, Pakistan.Objectif : Evaluer l'efficacité d'une approche intégrée à base communautaire afin de modifier le comportement des femmes en matière d'utilisation de la contraception.Schéma : La Sukh Initiative est une approche multiple avec des services de porte-à-porte par des travailleurs de santé communautaire, la fourniture de services de qualité en matière de planification familiale/santé reproductive, à la fois dans des structures publiques et privées, offrant une disponibilité 24/7 d'une assistance téléphonique en planification familiale et engager les jeunes pour les guider grâce à une éducation basée sur les compétences de vie.Méthodes : On a utilisé les données rétrospectives des enquêtes avant et après l'intervention, avec un échantillon de respectivement 5141 et 3861 femmes.Résultats : Le taux de prévalence contraceptive a augmenté de 10,7% par rapport au taux initial (42,3% contre 53,0% à mi-parcours), avec une augmentation du taux d'utilisation des méthodes contraceptifs modernes de 9,2%. Des associations significatives ont été constatées entre le conseil en porte-à-porte et l'utilisation de méthodes contraceptives (OR 3,4 ; niveau de confiance à 95% 2,9­4,1), et l'accès aux structures publiques et privées pour des contraceptifs modernes (OR 2,4 ; niveau de confiance à 95% 2,0­3,0). Les réunions de groupes de soutien et l'assistance téléphonique 24/7 n'ont cependant pas mis en évidence d'association avec l'utilisation d'une méthode contraceptive.Conclusion : L'étude actuelle a contribué à augmenter l'accès aux services de planification familiale et le choix des méthodes grâce à une approche à base communautaire qui a réduit avec succès les besoins non satisfaits et amélioré la continuité de l'utilisation de contraceptifs.


Marco de Referencia: En Karachi, Paquistán, se llevaron a cabo encuestas antes y después de una intervención.Objetivo: Evaluar la eficacia de una estrategia comunitaria integrada, encaminada a modificar el comportamiento de las mujeres con respecto a la utilización de los anticonceptivos.Diseño: La iniciativa Sukh consiste en un enfoque en varios frentes, que comporta servicios puerta a puerta a cargo de agentes de salud comunitarios, provisión de servicios de planificación familiar y salud reproductiva de gran calidad en establecimientos del sector público y el sector privado, con asistencia telefónica permanente en materia de planificación familiar y búsqueda de la participación de los jóvenes en tutorías de preparación para la vida activa.Método: Se realizó un análisis retrospectivo de los datos de una encuesta anterior a la intervención realizada a 5141 mujeres y de 3861 mujeres en una encuesta posterior a la misma.Resultados: La tasa de prevalencia de utilización de anticonceptivos aumentó hasta un 10,7% con respecto al valor inicial (42,3% contra 53,0% en mitad del período), con un aumento de 9,2% del recurso a los métodos modernos de anticoncepción. Se observó una asociación significativa del asesoramiento puerta a puerta con el uso de métodos anticonceptivos (OR 3,4; nivel de confianza a 95% 2,9­4,1) y el recurso a los servicios de establecimientos públicos y privados para la utilización de métodos anticonceptivos modernos (OR 2,4; nivel de confianza a 95% 2,0­3,0). Sin embargo, las reuniones en grupos de apoyo y la asistencia telefónica permanente no exhibieron ninguna correlación.Conclusión: Según el estudio realizado, se aumentó el acceso a los servicios de planificación familiar y la decisión de acudir a ellos, gracias a una estrategia comunitaria que logró reducir las necesidades insatisfechas y reforzar la continuidad de la utilización de los anticonceptivos.

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