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1.
Mol Divers ; 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38758508

RESUMO

In the contemporary landscape, anxiety and seizures stand as major areas of concern, prompting researchers to explore potential drugs against them. While numerous drugs have shown the potential to treat these two neurological conditions, certain adverse effects emphasize the need for development of safer alternatives. This study seeks to employ an in silico approach to evaluate natural compounds, particularly curcumins, as potential inhibitors of GABA-AT to mitigate anxiety and seizures. The proposed methodology includes generating a compound library, minimizing energy, conducting molecular docking using AutoDock, molecular dynamics simulations using Amber, and MM-GBSA calculations. Remarkably, CMPD50 and CMPD88 exhibited promising binding affinities of - 9.0 kcal/mol and - 9.1 kcal/mol with chains A and C of GABA-AT, respectively. Further, MM-GBSA calculations revealed binding free energies of - 10.88 kcal/mol and - 10.72 kcal/mol in CMPD50 and CMPD88, respectively. ADME analysis showed that these compounds contain drug-likeness properties and might be considered as potential drug candidates. The findings from this study will have practical applications in the field of drug discovery for the development of safer and effective drugs for treatment of anxiety and seizures. Overall, this study will lay the groundwork for providing valuable insights into the potential therapeutic effects of curcumins in alleviating anxiety and seizures, establishing a computational framework for future experimental validation.

2.
Nicotine Tob Res ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38715337

RESUMO

INTRODUCTION: Under the current policy landscapes, the lifetime health and economic burden of smokeless tobacco (ST) products, consumed by over 297 million ST users in South Asia, is unknown. The aim of this study was to estimate the lifetime health effects and costs attributable to current and future ST use in Bangladesh, India, and Pakistan where the majority of ST users live. AIMS AND METHODS: We developed a Markov-based state-transition model (ASTRAMOD) to predict the lifetime costs of treatment of four diseases (oral, pharyngeal, esophageal cancers, and stroke) and disability-adjusted life years (DALYs), attributable to the current and future use of ST under existing ST policy scenario. Country-specific Global Adult Tobacco Surveys, life tables, and meta-analyses of South Asian and South East Asian studies were used to populate the model. A probabilistic sensitivity analysis evaluated the uncertainty in model predictions. RESULTS: If there were no change in the current ST policies, the lifetime ST-attributable treatment costs would be over US$19 billion in India, over US$1.5 billion in Bangladesh, and over US$3 billion in Pakistan. For all countries, the attributable costs are higher for younger cohorts with costs declining with increasing age for those over 50. The model predicted that a typical 15-year-old male adoloscent would gain 0.07-0.18 life years, avert 0.07-0.19 DALYs, and generate a cost-savings of US$7-21 on healthcare spending if ST policies were changed to eliminate ST use. CONCLUSIONS: Policy interventions aimed at decreasing the uptake of ST and increasing quitting success have the potential to substantially decrease the economic and health burden of ST. IMPLICATIONS: This study provides the most comprehensive estimates of the lifetime health and economic burden of ST by 5-year age and sex cohorts. This is also the first study that highlights the scale of health and economic burden of ST in Bangladesh, India, and Pakistan if there were no changes in the current ST policies. Policymakers and practitioners can use the reported data to justify their decisions to improve current ST policies and practices in their country. Researchers can use the ASTRAMOD methodology to estimate the impact of future ST policy changes.

4.
World J Surg ; 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38658165

RESUMO

BACKGROUND: Excess and prolonged axillary drainage is a frequent nuisance following axillary lymph node dissection (ALND) in breast cancer patients. No consensus exists about the best method to prevent this consistently and reliably. Tranexamic acid (TA) has been found to reduce the amount and duration of drainage, but the reduction is not optimal. We hypothesized that systemic administration of TA along with the topical application of hemocoagulase (H) to the axillary dissection bed may decrease the cumulative axillary drain output and shorten the requirement of drainage after ALND as compared to placebo. PATIENT AND METHODS: Seventy women undergoing ALND for breast carcinoma were randomized into two groups, the intervention (TA + H) group and the control (C) group. The cumulative drain output (primary objective), duration of drainage, incidence of seroma formation after drain removal, number of seroma aspirations required, volume of seroma aspirated, and incidence of surgical site infection (SSI) were compared. RESULTS: The mean cumulative output in the TA + H group was significantly lower than the C group (290 ± 200 mL vs. 552 ± 369 mL, p < 0.001). Axillary drains were removed significantly earlier in the TA + H group (6.6 ± 2.2 vs. 11.7 ± 6.0 days, p < 0.001), but the incidence of seroma formation (p = 0.34), number of aspirations required (p = 0.33), volume of seroma aspirated (p = 0.47), and the incidence of SSI (p = 0.07) were similar. CONCLUSIONS: Perioperative systemic administration of tranexamic acid along with topical application of H to the axillary dissection bed is effective in reducing cumulative axillary drain output after ALND. This strategy may also facilitate earlier removal of suction drains.

5.
Chem Biodivers ; : e202302080, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38578653

RESUMO

Numerous chemical pesticides were employed for a long time to manage pests, but their uncontrolled application harmed the health and the environment. Accurately quantifying pesticide residues is essential for risk evaluation and regulatory purposes. Numerous analytical methods have been developed and utilized to achieve sensitive and specific detection of pesticides in intricate sampl es like water, soil, food, and air. Electrochemical sensors based on amperometry, potentiometry, or impedance spectroscopy offer portable, rapid, and sensitive detection suitable for on-site analysis. This study examines the potential of electrochemical sensors for the accurate evaluation of various effects of pesticides. Emphasizing the use of Graphene (GR), Graphene Oxide (GO), Reduced Graphene Oxide (rGO), and Graphdiyne composites, the study highlights their enhanced performance in pesticide sensing by stating the account of many actual sensors that have been made for specific pesticides. Computational studies provide valuable insights into the adsorption kinetics, binding energies, and electronic properties of pesticide-graphene complexes, guiding the design and optimization of graphene-based sensors with improved performance. Furthermore, the discussion extends to the emerging field of biopesticides. While the GR/GO/rGO based sensors hold immense future prospects, and their existing limitations have also been discussed, which need to be solved with future research.

6.
Mol Nutr Food Res ; 68(8): e2400087, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38581346

RESUMO

SCOPE: Dietary isothiocyanate (ITC) exposure from cruciferous vegetable (CV) intake may improve non-muscle invasive bladder cancer (NMIBC) prognosis. This study aims to investigate whether genetic variations in key ITC-metabolizing/functioning genes modify the associations between dietary ITC exposure and NMIBC prognosis outcomes. METHODS AND RESULTS: In the Bladder Cancer Epidemiology, Wellness, and Lifestyle Study (Be-Well Study), a prospective cohort of 1472 incident NMIBC patients, dietary ITC exposure is assessed by self-reported CV intake and measured in plasma ITC-albumin adducts. Using Cox proportional hazards regression models, stratified by single nucleotide polymorphisms (SNPs) in nine key ITC-metabolizing/functioning genes, it is calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for recurrence and progression. The rs15561 in N-acetyltransferase 1 (NAT1) is alter the association between CV intake and progression risk. Multiple SNPs in nuclear factor E2-related factor 2 (NRF2) and nuclear factor kappa B (NFκB) are modify the associations between plasma ITC-albumin adduct level and progression risk (pint < 0.05). No significant association is observed with recurrence risk. Overall, >80% study participants are present with at least one protective genotype per gene, showing an average 65% reduction in progression risk with high dietary ITC exposure. CONCLUSION: Despite that genetic variations in ITC-metabolizing/functioning genes may modify the effect of dietary ITCs on NMIBC prognosis, dietary recommendation of CV consumption may help improve NMIBC survivorship.


Assuntos
Dieta , Isotiocianatos , Polimorfismo de Nucleotídeo Único , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Masculino , Feminino , Isotiocianatos/farmacologia , Isotiocianatos/administração & dosagem , Pessoa de Meia-Idade , Prognóstico , Idoso , Estudos Prospectivos , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Arilamina N-Acetiltransferase/genética , Neoplasias não Músculo Invasivas da Bexiga
7.
Urology ; 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38663585

RESUMO

OBJECTIVE: To evaluate the long-term effectiveness and consequences of augmentation cystoplasty in adult patients with small capacity bladder due to genitourinary tuberculosis (GUTB). METHODS: After approval of the institutional ethical committee, we retrospectively analyzed the database of adult patients with small capacity bladder due to GUTB treated by augmentation cystoplasty from January 2010 to December 2022 at our center. The patients were followed up at 6 weeks postoperatively, then every 3 months for first year and 6 months in second year, and then annually. Patients were assessed for symptoms, renal function, blood biochemistry levels, and ultrasound KUB at each follow-up visit. RESULTS: A total of 40 patients underwent augmentation cystoplasty were included. All patients underwent augmentation cystoplasty either with ileum (n = 35) or sigmoid colon (n = 5). On long-term follow-up, there was statistically significant improvement in bladder capacity, decrease in voiding frequency (P = .00), decrease in eGFR (P = .02) and increase in serum creatinine (P = .02). Significant complications were wound infection 4 (10%), intestinal obstruction 1(2.5%), urinary tract infection 6 (15%), bladder stone 2 (5%), mucus retention 3 (7.5%), hypocalcemia with metabolic acidosis 2 (5%) and need of intermittent catheterization in 11 (27.5%) patients. CONCLUSION: Multidrug therapy with judicious reconstructive surgery is the optimal treatment modality for GUTB with cicatrization sequelae. In GUTB, augmentation cystoplasty is a safe procedure and strict long-term follow-up is needed to prevent complications.

8.
Curr Res Food Sci ; 8: 100705, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38435279

RESUMO

Pea protein isolate (PPI)-based active films were prepared by incorporating 0.5 %, 1.0 %, or 2.0 % of oregano essential oil (OEO), either in the form of micro-emulsion (MOEO) or nano-emulsion (NOEO). The particle size and polydispersity index of OEO droplets were 2755.00 nm and 0.63 for MOEO, and 256.30 nm and 0.20 for NOEO. The surface and cross-sectional SEM results revealed the presence of holes and internal pores within the film upon the addition of OEO. The molecular interaction between PPI and OEO was confirmed by FTIR. The addition of OEO significantly increased film thickness, decreased water contact angle, and imparted a more yellow color. At a low concentration (0.5 %), the addition of OEO significantly improved the water vapor barrier and mechanical properties of the film. However, at higher concentrations, these film properties were significantly weakened. Additionally, the film antimicrobial properties were assessed after OEO addition. In vitro inhibition zone results indicated that a 2.0 % addition of OEO significantly suppressed the growth of three Salmonella strains [Salmonella Typhimurium (ATCC14028), Salmonella Infantis 94-1, and Salmonella Enteritidis PT-30]. Application of pea protein-based film with 2.0 % OEO on chicken breast demonstrated significant reduction in microbial count. Our results further showed that reducing the particle size of OEO from micrometer-scale to nanometer-scale in the PPI film matrix did not significantly alter film properties or antimicrobial activities. The study demonstrated that the antibacterial film based on pea protein and OEO is an innovative food packing material for prohibiting bacteria growth on poultry products.

9.
Nat Commun ; 15(1): 2803, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38555305

RESUMO

Myeloid derived suppressor cells (MDSCs) are key regulators of immune responses and correlate with poor outcomes in hematologic malignancies. Here, we identify that MDSC mitochondrial fitness controls the efficacy of doxorubicin chemotherapy in a preclinical lymphoma model. Mechanistically, we show that triggering STAT3 signaling via ß2-adrenergic receptor (ß2-AR) activation leads to improved MDSC function through metabolic reprograming, marked by sustained mitochondrial respiration and higher ATP generation which reduces AMPK signaling, altering energy metabolism. Furthermore, induced STAT3 signaling in MDSCs enhances glutamine consumption via the TCA cycle. Metabolized glutamine generates itaconate which downregulates mitochondrial reactive oxygen species via regulation of Nrf2 and the oxidative stress response, enhancing MDSC survival. Using ß2-AR blockade, we target the STAT3 pathway and ATP and itaconate metabolism, disrupting ATP generation by the electron transport chain and decreasing itaconate generation causing diminished MDSC mitochondrial fitness. This disruption increases the response to doxorubicin and could be tested clinically.


Assuntos
Neoplasias Hematológicas , Células Supressoras Mieloides , Succinatos , Humanos , Glutamina/metabolismo , Neoplasias Hematológicas/metabolismo , Trifosfato de Adenosina/metabolismo , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Doxorrubicina/metabolismo
10.
Int J Biol Macromol ; 265(Pt 2): 131050, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38522708

RESUMO

In this study, the folding of G-quadruplex (G4) from the telomeric DNA sequences having loop nucleobases of different chemical natures, numbers, and arrangements in 10 mM and 100 mM KCl salt conditions mimicking the cancerous and normal KCl salt microenvironments have been investigated. The data suggest that the structure and stability of the G4 are highly dependent on the KCl salt concentration. In general, the conformational flexibility of the folded G4 is higher in KCl salt relevant to cancer than in the normal case for any loop arrangements with the same number of nucleobases. The stability of the G4 decreases with the increase in the number of loop nucleobases for both salt conditions. However, the decrease in the stability of G4 having adenine in the loop region is significantly higher than the case of thymine, particularly more prominent in the KCl salt relevant to the cancer. The topology of the folded G4 and its stability also depend delicately on the permutation of the nucleobases in the loop and the salt concentrations for a particular sequence. The findings indicate that the structure and stability of G4 are noticeably different in KCl salt relevant to physiological and cancer conditions.


Assuntos
Quadruplex G , Neoplasias , Timina , Adenina
12.
Front Immunol ; 15: 1334769, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38312842

RESUMO

Background: Stimulator of Interferon Genes (STING) is a dsDNA sensor that triggers type I inflammatory responses. Recent data from our group and others support the therapeutic efficacy of STING agonists applied intratumorally or systemically in a range of murine tumor models, with treatment benefits associated with tumor vascular normalization and improved immune cell recruitment and function within the tumor microenvironment (TME). However, such interventions are rarely curative and STING agonism coordinately upregulates expression of immunoregulatory interferon-stimulated genes (ISGs) including Arg2, Cox2, Isg15, Nos2, and Pdl1 that may limit treatment benefits. We hypothesized that combined treatment of melanoma-bearing mice with STING agonist ADU-S100 together with antagonists of regulatory ISGs would result in improved control of tumor growth vs. treatment with ADU-S100 alone. Methods: Mice bearing either B16 (BRAFWTPTENWT) or BPR20 (BRAFV600EPTEN-/-) melanomas were treated with STING agonist ADU-S100 plus various inhibitors of ARG2, COX2, NOS2, PD-L1, or ISG15. Tumor growth control and changes in the TME were evaluated for combination treatment vs ADU-S100 monotherapy by tumor area measurements and flow cytometry/transcriptional profiling, respectively. Results: In the B16 melanoma model, we noted improved antitumor efficacy only when ADU-S100 was combined with neutralizing/blocking antibodies against PD-L1 or ISG15, but not inhibitors of ARG2, COX2, or NOS2. Conversely, in the BPR20 melanoma model, improved tumor growth control vs. ADU-S100 monotherapy was only observed when combining ADU-S100 with ARG2i, COX2i, and NOS2i, but not anti-PD-L1 or anti-ISG15. Immune changes in the TME associated with improved treatment outcomes were subtle but included increases in proinflammatory innate immune cells and activated CD8+CD69+ T cells and varied between the two tumor models. Conclusions: These data suggest contextual differences in the relative contributions of individual regulatory ISGs that serve to operationally limit the anti-tumor efficacy of STING agonists which should be considered in future design of novel combination protocols for optimal treatment benefit.


Assuntos
Antígeno B7-H1 , Melanoma Experimental , Camundongos , Animais , Proteínas Proto-Oncogênicas B-raf , Ciclo-Oxigenase 2 , Linhagem Celular Tumoral , Interferons , Microambiente Tumoral
13.
J Phycol ; 60(2): 387-408, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38342971

RESUMO

Five cyanobacterial strains exhibiting Nostoc-like morphology were sampled from the biodiversity hotspots of the northeast region of India and characterized using a polyphasic approach. Molecular and phylogenetic analysis using the 16S rRNA gene indicated that the strains belonged to the genera Amazonocrinis and Dendronalium. In the present investigation, the 16S rRNA gene phylogeny clearly demarcated two separate clades of Amazonocrinis. The strain MEG8-PS clustered along with Amazonocrinis nigriterrae CENA67, which is the type strain of the genus. The other three strains ASM11-PS, RAN-4C-PS, and NP-KLS-5A-PS clustered in a different clade that was phylogenetically distinct from the Amazonocrinis sensu stricto clade. Interestingly, while the 16S rRNA gene phylogeny exhibited two separate clusters, the 16S-23S ITS region analysis did not provide strong support for the phylogenetic observation. Subsequent analyses raised questions regarding the resolving power of the 16S-23S ITS region at the genera level and the associated complexities in cyanobacterial taxonomy. Through this study, we describe a novel genus Ahomia to accommodate the members clustering outside the Amazonocrinis sensu stricto clade. In addition, we describe five novel species, Ahomia kamrupensis, Ahomia purpurea, Ahomia soli, Amazonocrinis meghalayensis, and Dendronalium spirale, in accordance with the International Code of Nomenclature for algae, fungi, and plants (ICN). Apart from further enriching the genera Amazonocrinis and Dendronalium, the current study helps to resolve the taxonomic complexities revolving around the genus Amazonocrinis and aims to attract researchers to the continued exploration of the tropical and subtropical cyanobacteria for interesting taxa and lineages.


Assuntos
Comportamento Exploratório , Nostoc , Filogenia , RNA Ribossômico 16S/genética , DNA Bacteriano/genética , Técnicas de Tipagem Bacteriana , Análise de Sequência de DNA , Nostoc/genética , Biodiversidade , Índia
14.
J Photochem Photobiol B ; 252: 112866, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38364711

RESUMO

Cyanobacteria are photosynthetic organisms and challenged by large number of stresses, especially by ultraviolet radiation (UVR). UVR primarily impacts lipids, proteins, DNA, photosynthetic performance, which lowers the fitness and production of cyanobacteria. UVR has a catastrophic effect on cyanobacterial cells and eventually leads to cell death. UVR tolerance in the Synechocystis was poorly studied. Therefore, we irradiated Synechocystis sp. PCC 6803 to varying hours of photosynthetically active radiations (PAR), PAR + UV-A (PA), and PAR + UV-A + UV-B (PAB) for 48 h. To study the tolerance of Synechocystis sp. PCC 6803 against different UVR. The study shows that Chl a and total carotenoids content increased up to 36 h in PAR and PA, after 36 h a decrease was observed. PC increased up to 4-fold in 48 h of PA irradiation compared to 12 h. Maximum increase in ROS was observed under 48 h PAB i.e., 5.8-fold. Flowcytometry (FCM) based analysis shows that 25% of cells do not give fluorescence of Chl a and H2DCFH. In case of cell viability 10% cells were found to be non-viable in 48 h of PAB irradiance compared to 12 h. From the above study it was found that FCM-based approaches would provide a better understanding of the variations that occurred within the Synechocystis cells compared to fluorescence microscopy-based methods.


Assuntos
Synechocystis , Raios Ultravioleta , Fotossíntese/efeitos da radiação , Microscopia de Fluorescência
15.
Gastroenterology ; 166(4): 620-630, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38176661

RESUMO

BACKGROUND & AIMS: Current international guidelines recommend duodenal biopsies to confirm the diagnosis of celiac disease in adult patients. However, growing evidence suggests that immunoglobulin A (IgA) anti-tissue transglutaminase (tTg) antibody levels ≥10 times the upper limit of normal (ULN) can accurately predict celiac disease, eliminating the need for biopsy. We performed a systematic review and meta-analysis to evaluate the accuracy of the no-biopsy approach to confirm the diagnosis of celiac disease in adults. METHODS: We systematically searched MEDLINE, EMBASE, Cochrane Library, and Web of Science from January 1998 to October 2023 for studies reporting the sensitivity and specificity of IgA-tTG ≥10×ULN against duodenal biopsies (Marsh grade ≥2) in adults with suspected celiac disease. We used a bivariate random effects model to calculate the summary estimates of sensitivity, specificity, and positive and negative likelihood ratios. The positive and negative likelihood ratios were used to calculate the positive predictive value of the no-biopsy approach across different pretest probabilities of celiac disease. The methodological quality of the included studies was evaluated using the QUADAS-2 tool. This study was registered with PROSPERO, number CRD42023398812. RESULTS: A total of 18 studies comprising 12,103 participants from 15 countries were included. The pooled prevalence of biopsy-proven celiac disease in the included studies was 62% (95% confidence interval [CI], 40%-83%). The proportion of patients with IgA-tTG ≥10×ULN was 32% (95% CI, 24%-40%). The summary sensitivity of IgA-tTG ≥10×ULN was 51% (95% CI, 42%-60%), and the summary specificity was 100% (95% CI, 98%-100%). The area under the summary receiver operating characteristic curve was 0.83 (95% CI, 0.77 - 0.89). The positive predictive value of the no-biopsy approach to identify patients with celiac disease was 65%, 88%, 95%, and 99% if celiac disease prevalence was 1%, 4%, 10%, and 40%, respectively. Between-study heterogeneity was moderate (I2 =30.3%), and additional sensitivity analyses did not significantly alter our findings. Only 1 study had a low risk of bias across all domains. CONCLUSION: The results of this meta-analysis suggest that selected adult patients with IgA-tTG ≥10×ULN and a moderate to high pretest probability of celiac disease could be diagnosed without undergoing invasive endoscopy and duodenal biopsy.


Assuntos
Doença Celíaca , Adulto , Humanos , Doença Celíaca/diagnóstico , Doença Celíaca/epidemiologia , Transglutaminases , Proteína 2 Glutamina gama-Glutamiltransferase , Imunoglobulina A , Proteínas de Ligação ao GTP , Biópsia , Sensibilidade e Especificidade , Autoanticorpos
16.
Nicotine Tob Res ; 26(3): 342-352, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-37422916

RESUMO

INTRODUCTION: Tobacco is a well-established risk factor for cancer, but its association with other morbidities needs consideration. The low-income and middle-income countries (LMICs) with unprecedented demographic transformation lack evidence on tobacco use and its impact on cognitive health. AIMS AND METHODS: Using a propensity score matching approach, we utilized data from the Longitudinal Ageing Study of India. Study employed 1:1 nearest neighbor matching with the replacement methodology. We estimated the odds of the poor cognitive score and tobacco use among older adults based on five different models for ever tobacco user, former tobacco user, current tobacco user, current smokers, and current smokeless tobacco users with reference to never tobacco users. RESULTS: The estimated average treatment effect for the treated and the untreated group has shown a higher likelihood of cognitive decline among ever (OR -0.26; 95%CI -0.43 to -0.09), current (OR -0.28; 95%CI -0.45 to -0.10), and former (OR -0.53; 95%CI -0.87 to -0.19) tobacco users compared to never tobacco users. The finding further suggests the odds of lower cognitive scores among older adults who were smokers (OR -0.53; 95%CI -0.87 to -0.19) and smokeless tobacco users (OR -0.22; 95%CI -0.43 to -0.01) as compared to never tobacco users. CONCLUSIONS: Interventions designed to prevent the incidence of cognitive impairment should focus on limiting the use of tobacco. Strategies under the tobacco-free generation initiative should be amplified in order to prevent future generations from productivity loss, premature ageing and to promote healthy aging. IMPLICATIONS: Evidence of a definitive association between tobacco consumption and cognition among older adults is sporadic in LMICs. Though tobacco is a risk factor for various diseases including cancer, the extent of its impact on cognitive health among the older population is limited. This study contributes to the existing literature by highlighting poor cognitive outcomes among older adults who smoke tobacco and/or consume smokeless tobacco as compared to never-tobacco users. Our findings emphasize the need to accelerate programmes related to tobacco-free generation in LMICs to reach a higher quality of life and healthy aging in pursuit of achieving the sustainable development goal of "good health and well-being."


Assuntos
Neoplasias , Tabaco sem Fumaça , Humanos , Idoso , Pontuação de Propensão , Qualidade de Vida , Uso de Tabaco/epidemiologia , Cognição
17.
Ann Rheum Dis ; 83(4): 488-498, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38123919

RESUMO

OBJECTIVES: Cytotoxic T cells and natural killer (NK) cells are central effector cells in cancer and infections. Their effector response is regulated by activating and inhibitory receptors. The regulation of these cells in systemic autoimmune diseases such as systemic sclerosis (SSc) is less defined. METHODS: We conducted ex vivo analysis of affected skin and blood samples from 4 SSc patient cohorts (a total of 165 SSc vs 80 healthy individuals) using single-cell transcriptomics, flow cytometry and multiplex immunofluorescence staining. We further analysed the effects of costimulatory modulation in functional assays, and in a severely affected SSc patient who was treated on compassionate use with a novel anti-CD3/CD7 immunotoxin treatment. RESULTS: Here, we show that SSc-affected skin contains elevated numbers of proliferating T cells, cytotoxic T cells and NK cells. These cells selectively express the costimulatory molecule CD7 in association with cytotoxic, proinflammatory and profibrotic genes, especially in recent-onset and severe disease. We demonstrate that CD7 regulates the cytolytic activity of T cells and NK cells and that selective depletion of CD7+ cells prevents cytotoxic cell-induced fibroblast contraction and inhibits their profibrotic phenotype. Finally, anti-CD3/CD7 directed depletive treatment eliminated CD7+ skin cells and stabilised disease manifestations in a severely affected SSc patient. CONCLUSION: Together, the findings imply costimulatory molecules as key regulators of cytotoxicity-driven pathology in systemic autoimmune disease, yielding CD7 as a novel target for selective depletion of pathogenic cells.


Assuntos
Escleroderma Sistêmico , Linfócitos T , Humanos , Antígenos CD7/metabolismo , Células Matadoras Naturais
19.
Photochem Photobiol Sci ; 23(2): 285-302, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38143251

RESUMO

Environmental variation has a significant impact on how organisms, including cyanobacteria, respond physiologically and biochemically. Salinity and ultraviolet radiation (UVR)-induced variations in the photopigments of the rice-field cyanobacterium Nostochopsis lobatus HKAR-21 and its photosynthetic performance was studied. We observed that excessive energy dissipation after UVR is mostly caused by Non-Photochemical Quenching (NPQ), whereas photochemical quenching is important for preventing photoinhibition. These findings suggest that ROS production may play an important role in the UVR-induced injury. To reduce ROS-induced oxidative stress, Nostochopsis lobatus HKAR-21 induces the effective antioxidant systems, which includes different antioxidant compounds like carotenoids and enzymes such as superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX). The study indicates that Nostochopsis lobatus HKAR-21 exposed to photosynthetically active radiation + UV-A + UV-B (PAB) and PAB + NaCl (PABN) had significantly reduced photosynthetic efficiency. Furthermore, maximum ROS was detected in PAB exposed cyanobacterial cells. The induction of lipid peroxidation (LPO) has been investigated to evaluate the impact of UVR on the cyanobacterial membrane in addition to enzymatic defensive systems. The maximal LPO level was found in PABN treated cells. Based on the findings of this research, it was concluded that salinity and UVR had collegial effects on the major macromolecular components of the rice-field cyanobacterium Nostochopsis lobatus HKAR-21.


Assuntos
Cianobactérias , Oryza , Raios Ultravioleta , Antioxidantes/farmacologia , Oryza/efeitos da radiação , Cloreto de Sódio/farmacologia , Espécies Reativas de Oxigênio , Cianobactérias/metabolismo , Fotossíntese/efeitos da radiação , Superóxido Dismutase/metabolismo
20.
BMJ Open ; 13(12): e067875, 2023 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-38070918

RESUMO

OBJECTIVE: Tobacco use begins at an early age and typically leads to a long-term addiction. The age of initiation for tobacco use is not well studied in South Asia, where 22% of tobacco smokers and 81% of smokeless tobacco (SLT) users reside. METHODS: Data from the nationally representative Global Adult Tobacco Surveys in India, Bangladesh and Pakistan were analysed to examine patterns of initiation among smokers and smokeless tobacco users. RESULTS: Data on 94 651 individuals were analysed, of which 13 396 reported were ever daily smokers and 17 684 were ever SLT users. The proportion of individuals initiating tobacco use before the age of 15 years has increased over time. The rates of SLT initiation among those aged 15-24 years increased markedly in Bangladesh (by 7.8%) and Pakistan (by 37.7%) between 1983 and 1999-2000. Among males, the increase in SLT initiation was higher in individuals aged below 15 years compared with other age groups in India and Bangladesh. Smoking initiation among females aged below 15 years has also significantly increased in India over time. Compared with the initiation of tobacco smoking before the age of 15 years, a greater increase in the proportion of SLT users was observed in urban areas. CONCLUSION: Our findings indicate that the proportion of youth initiating tobacco (both smoking and smokeless) before the age of 15 years has increased over time in all three countries. Moreover, variations in age at initiation for different types of tobacco products across countries, and by rurality, were noticeable. Younger youths (aged up to 15 years) should therefore be a priority population for tobacco control interventions. Strategies such as raising the legal age of tobacco sale and use to 21 years, and, other measures under WHO Framework Convention on Tobacco Control (FCTC), may prevent underage use and avert lifelong addiction to tobacco products.


Assuntos
Uso de Tabaco , Adolescente , Adulto , Feminino , Humanos , Masculino , Bangladesh/epidemiologia , Estudos Transversais , Índia/epidemiologia , Paquistão/epidemiologia , Uso de Tabaco/epidemiologia
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