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1.
J Asthma ; 61(4): 282-291, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37943507

RESUMO

OBJECTIVE: This scoping review investigated the existing literature and identified the evidence gaps related to diagnosis and management in children aged 2-18 years presenting to hospitals with a co-diagnosis of asthma and community-acquired pneumonia. DATA SOURCES: We designed a scoping review following Arksey and O'Malley's scoping review framework and PRISMA extension for a scoping review. We searched literature using five electronic databases: PubMed, CINAHL, Scopus, Web of Science, and Embase from 2003 to June 2023. RESULTS: A total of 1599 abstracts with titles were screened and 12 abstracts were selected for full review. Separate guidelines including Modified Global Initiative for Asthma (GINA) guidelines; modified Integrated Management of Childhood Illness (IMCI) guidelines; and a consensus guideline developed by the Pediatric Infectious Diseases Society (PIDS) and Infectious Diseases Society of America (IDSA) were used for diagnosing asthma and CAP individually. Chest X-rays were used in 83.3% (10/12) of studies to establish the co-diagnosis of asthma-CAP in children. Variations were observed in using different laboratory investigations across the studies. Infectious etiologies were detected in five (41.7%) studies. In 75% (9/12) of studies, children with asthma-CAP co-diagnosis were treated with antimicrobials, however, bacterial etiology was not reported in 44.4% (4/9) of the studies. CONCLUSIONS: Our scoping review suggests that chest X-rays are commonly used to establish the co-diagnosis of asthma-CAP and antibiotics are often used without laboratory confirmation of a bacterial etiology. Clinical practice guidelines for the management of asthma and pneumonia in children who present with co-diagnosis may standardize clinical care and reduce variation.


Assuntos
Asma , Doenças Transmissíveis , Infecções Comunitárias Adquiridas , Pneumonia , Criança , Humanos , Asma/diagnóstico , Asma/tratamento farmacológico , Pneumonia/diagnóstico , Pneumonia/tratamento farmacológico , Antibacterianos/uso terapêutico , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Doenças Transmissíveis/tratamento farmacológico
2.
Clin Infect Dis ; 76(2): 263-270, 2023 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-36136760

RESUMO

BACKGROUND: Cholera remains a public health threat for low- and middle-income countries, particularly in Asia and Africa. Shanchol™, an inactivated oral cholera vaccine (OCV) is currently in use globally. OCV and oral poliovirus vaccines (OPV) could be administered concomitantly, but the immunogenicity and safety of coadministration among children aged 1-3 years is unknown. METHODS: We undertook an open-label, randomized, controlled, inequality trial in Dhaka city, Bangladesh. Healthy children aged 1-3 years were randomly assigned to 1 of 3 groups: bivalent OPV (bOPV)-alone, OCV-alone, or combined bOPV + OCV and received vaccines on the day of enrollment and 28 days later. Blood samples were collected on the day of enrollment, day 28, and day 56. Serum poliovirus neutralizing antibodies and vibriocidal antibodies against Vibrio cholerae O1 were assessed using microneutralization assays. RESULTS: A total of 579 children aged 1‒3 years were recruited, 193 children per group. More than 90% of the children completed visits at day 56. Few adverse events following immunization were recorded and were equivalent among study arms. On day 28, 60% (90% confidence interval: 53%-67%) and 54% (46%-61%) of participants with co-administration of bOPV + OCV responded to polioviruses type 1 and 3, respectively, compared to 55% (47%-62%) and 46% (38%-53%) in the bOPV-only group. Additionally, >50% of participants showed a ≥4-fold increase in vibriocidal antibody titer responses on day 28, comparable to the responses observed in OCV-only arm. CONCLUSIONS: Co-administration of bOPV and OCV is safe and effective in children aged 1-3 years and can be cost-beneficial. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT03581734).


Assuntos
Vacinas contra Cólera , Cólera , Poliomielite , Poliovirus , Humanos , Criança , Lactente , Pré-Escolar , Bangladesh , Cólera/prevenção & controle , Vacina Antipólio Oral , Vacinas de Produtos Inativados , Administração Oral , Poliomielite/prevenção & controle
3.
J Environ Manage ; 337: 117772, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-36958279

RESUMO

Mangrove forests, some of the most carbon-dense ecosystems on Earth, play an important role in climate change mitigation through storing carbon in the soil. However, increasing anthropogenic pressures and sea level rise are likely to alter mangrove forest structure and functions, including the major source of carbon in mangrove ecosystems - below-ground soil carbon stocks (BSCS). Although estimating soil carbon stocks has been a popular practice in the mangroves, but poorly understood the (I) the linkage between BSCS and key ecosystem drivers (i.e., biotic, abiotic, and functional) and in (II) determining the pathways of how BSCS and multiple forest variables interact along stress gradients. This lack of understanding limits our ability to predict ecosystem carbon dynamics under future changes in climate. Here, we aimed to understand how abiotic factors (such as salinity, canopy gap fraction, nutrients, and soil pH), biotic factors (e.g., structural parameters, canopy packing, and leaf area index, LAI), and forest functional variables (e.g., growth and aboveground biomass stocks, AGB) affect BSCS (i.e., soil organic carbon, SOC, and root carbon, RC) using spatiotemporal data collected from the Sundarbans Mangrove Forest (SMF) in Bangladesh. We observed that BSCS decreased significantly with increasing salinity (e.g., from 70.6 Mg C ha-1 in the low-saline zone to 44.6 Mg C ha-1 in the high-saline zone). In contrast, the availability of several macronutrients (such as nitrogen, phosphorous, and potassium), LAI, species diversity, AGB, and growth showed a significant positive effect on SOC and RC. Stand properties, including tree height, basal area, density, canopy packing, and structural diversity, had a non-significant but positive impact on RC, while tree height and basal area significantly influenced SOC. Pathway analysis showed that salinity affects BSCS variability directly and indirectly by regulating stand structure and restricting nutrients and forest functions, although basal area, nutrients, and LAI directly enhance RC stocks. Our results indicate that an increase in nutrient content, canopy density, species diversity, and leaf area index can enhance BSCS, as they improve forest functions and contribute to a better understanding of the underlying mechanisms.


Assuntos
Ecossistema , Áreas Alagadas , Solo/química , Carbono/análise , Florestas , Biomassa
4.
Molecules ; 28(5)2023 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-36903452

RESUMO

Glycosmis cyanocarpa (Blume) Spreng is a plant in the Rutaceae family and a species in the Glycosmis genus that has received little attention. Therefore, this research aimed to report the chemical and biological analysis of Glycosmis cyanocarpa (Blume) Spreng. The chemical analysis involved the isolation and characterization of secondary metabolites through an extensive chromatographic study, and the structures of these metabolites were elucidated on the basis of a detailed analysis of NMR and HRESIMS spectroscopic data and by comparison with those of related compounds reported in the literature. Different partitions of the crude ethyl acetate (EtOAc) extract were evaluated for antioxidant, cytotoxic, and thrombolytic potentials. In chemical analysis, one new phenyl acetate derivative, namely 3,7,11,15-tetramethylhexadec-2-en-1-yl 2-phenylacetate (1), along with four known compounds N-methyl-3-(methylthio)-N-(2-phenylacetyl) acrylamide (2), penangin (3), ß-Caryophyllene oxide (4), and acyclic diterpene-phytol (5) were isolated for the first time from the stem and leaf of the plant. The ethyl acetate fraction showed significant free radical scavenging activity with an IC50 value of 11.536 µg/mL compared to standard ascorbic acid (4.816 µg/mL). In the thrombolytic assay, the dichloromethane fraction showed the maximum thrombolytic activity of 16.42% but was still insignificant compared to the standard streptokinase (65.98%). Finally, in a brine shrimp lethality bioassay, the LC50 values of dichloromethane, ethyl acetate, and aqueous fractions were found to be 0.687 µg/mL, 0.805 µg/mL, and 0.982 µg/mL which are significant compared to the standard vincristine sulfate of 0.272 µg/mL.


Assuntos
Extratos Vegetais , Rutaceae , Extratos Vegetais/química , Rutaceae/química , Cloreto de Metileno , Antioxidantes/química , Fibrinolíticos/química
5.
BMC Musculoskelet Disord ; 23(1): 333, 2022 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-35395747

RESUMO

BACKGROUND: Knee osteoarthritis was reported as the second most prevalent condition in the national musculoskeletal survey. The purpose of this extended study was to identify risk factors for knee osteoarthritis in Bangladeshi adults. METHODS: This cross-sectional study was conducted in rural and urban areas of Bangladesh using stratified multistage cluster sample of 2000 adults aged 18 years or older recruited at their households. The Modified Community Oriented Program for Control of Rheumatic Disorders (COPCORD) questionnaire was used to collect data. The diagnosis of knee osteoarthritis was made using the decision tree clinical categorization criteria of the American College of Rheumatology. Univariate and multivariate logistic regression analyses were done to identify the risk factors for knee osteoarthritis. RESULTS: A total of 1843 individuals (892 men and 951 women) participated, and 134 had knee osteoarthritis yielding a prevalence of 7.3% (95% confidence interval (CI) 4.9 to 9.6%). The mean (standard deviation) age of the knee osteoarthritis patients was 51.7 (11.2) years. Multivariate logistic regression analysis found a significant association with increasing age (≥38 years OR 8.9, 95% CI 4.8-16.5; ≥58 years OR 13.9, 95% CI 6.9-28.0), low educational level (OR 1.7, 95% CI 1.0-2.7) and overweight (OR 1.9, 95% CI 1.2-2.9) with knee osteoarthritis. Knee osteoarthritis patients had a high likelihood of having work loss preceding 12 months (age and sex-adjusted OR 2.3; 95% CI 1.4-3.8; P < 0.01). CONCLUSIONS: Knee osteoarthritis is a commonly prevalent musculoskeletal problem among Bangladeshi adults having link to work loss. Increasing age, low education and overweight are significant risk factors of knee osteoarthritis.


Assuntos
Osteoartrite do Joelho , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Osteoartrite do Joelho/diagnóstico , Osteoartrite do Joelho/epidemiologia , Osteoartrite do Joelho/etiologia , Sobrepeso/complicações , Prevalência , Fatores de Risco
6.
J Med Virol ; 93(7): 4326-4333, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33710631

RESUMO

Several studies have demonstrated an association between individual zinc status and viral respiratory infections; however, evidence regarding COVID-19 is still missing or insufficient. This study aimed to evaluate the correlation between the prevalence of zinc deficiency and COVID-19 cases and deaths per million population in the Asian and European countries. The COVID-19 data from two different time points, that is, May 30 and June 30, 2020 for the Asian population and May 15 and June 15, 2020 for the European population, were analyzed to determine the correlation with the estimated zinc deficiency for these two continents. The prevalence of zinc deficiency was about two times higher in the Asian population (mean 17.5%) than in the European population (mean 8.9%). A significant positive correlation (p < .05) was observed between the prevalence of zinc deficiency and COVID-19 cases at both time periods for the Asian population. However, the correlation between zinc deficiency prevalence and COVID-19 deaths was not significant in the Asian population. In contrast, a significant but negative correlation (p < .05 for all cases) was observed for zinc deficiency with both COVID-19 cases and deaths per million population at both time periods in the European countries. Considering the direct antiviral properties of zinc, it can be suggested that zinc supplementation may be beneficial for most of the population, especially older people and those who are at risk of COVID-19 infections. In conclusion, there is not enough evidence on the association between individual zinc status and COVID-19 infections and mortality. Therefore, cohort studies and randomized controlled trials are required to test this hypothesis.


Assuntos
COVID-19/epidemiologia , SARS-CoV-2/efeitos dos fármacos , Zinco/deficiência , Antivirais/uso terapêutico , Ásia/epidemiologia , COVID-19/dietoterapia , COVID-19/mortalidade , Suplementos Nutricionais , Europa (Continente)/epidemiologia , Humanos , Prevalência , Estudos Retrospectivos , Zinco/sangue , Zinco/uso terapêutico
7.
Health Qual Life Outcomes ; 18(1): 343, 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33076904

RESUMO

BACKGROUND: This study was focused on translation and cultural adaptation of the English Lequesne Algofunctional index (LAI) into Bengali for patients with primary knee osteoarthritis (OA) and testing reliability and validity of the Bengali version of the LAI. METHODS: This study was carried out in the Department of Rheumatology, BSM Medical University, Dhaka, Bangladesh. Using the forward-backward method the English LAI was translated into Bengali including cultural adaptation. For pretesting, A sample of 40 patients with primary knee osteoarthritis were screened using the Bengali version of LAI. Following the pretest, 130 consecutive patients with symptomatic knee OA completed the interviewer administered Bengali LAI, the validated Bengali version of SF-36, Visual Analogue Scale for Pain, Distance Walked and Activities of Daily Living. For the retest 60 randomly selected patients from the cohort were administered the Bengali LAI 7 days later. An item by item analysis was performed. Internal consistency was assessed by Cronbach's alpha, test-retest reliability by intraclass correlation coefficient (ICC) and Kappa coefficient, construct validity was measured using the Spearman rank correlation coefficient. RESULTS: It took 3.25 ± 0.71 min to complete the Bengali LAI and the mean score was 9.23 ± 4.58. For the Bengali LAI Cronbach's alpha score was 0.88, test-retest reliability assessed by ICC was 0.97. For construct validity, excellent convergent validity was achieved (ρ = 0.93) but the divergent validity was moderate (ρ = 0.43). CONCLUSIONS: The Bengali LAI showed excellent convergent validity, internal consistency and test-retest reliability, only the divergent validity was moderate. So, the Bengali LAI can be applied as a HRQoL assessment tool for primary knee OA patients.


Assuntos
Osteoartrite do Joelho/psicologia , Qualidade de Vida , Inquéritos e Questionários/normas , Idoso , Bangladesh , Estudos de Coortes , Comparação Transcultural , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Traduções
8.
BMC Cardiovasc Disord ; 19(1): 42, 2019 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-30791868

RESUMO

BACKGROUND: Although the link between elevated uric acid and metabolic syndrome has been reported in some studies; the relationship of serum uric acid (SUA) with lipid profile has not well studied or little is known so far. This study was conducted to assess the relationship between SUA and lipid profile among the general adults in Bangladesh. METHODS: In total, 280 blood samples were collected from general adult participants (male, n = 150 and female, n = 130) and analyzed for serum lipid profile (TC, TG, HDL and LDL) and SUA levels. The study subjects were divided by quartiles based on SUA levels (Q1: ≤225 µmol/L, Q2: 226-285 µmol/L, Q3: 286-340 µmol/L and Q4: > 340 µmol/L). Linear regression modeling was used to evaluate the relationship between SUA and lipid levels. RESULTS: The prevalence of hyperuricemia was 9.2% in males and 10.4% in females. The mean level of SUA was significantly higher in male (317 ± 90 µmol/L) than in the female (255 ± 65 µmol/L) subjects (p < 0.001). An increasing trend for elevated lipid profile was observed in both gender with increasing levels of SUA in the quartiles (p < 0.05). In regression analysis, a significant positive correlation was found between SUA and TG, TC and LDL (p < 0.01) while an inverse correlation was observed between SUA and HDL (p < 0.01). After adjusting for potential confounders, lipid profile was linearly associated with SUA levels (p < 0.01 for trend). CONCLUSIONS: Present study showed a significant positive relationship for SUA with TG, TC and LDL levels, and an inverse relationship for SUA with HDL. Early prevention of hyperuricemia and dyslipidemia may be helpful to reduce the incidence of associated cardiovascular diseases.


Assuntos
Doenças Cardiovasculares/sangue , Dislipidemias/sangue , Hiperuricemia/sangue , Lipídeos/sangue , Ácido Úrico/sangue , Adulto , Bangladesh/epidemiologia , Biomarcadores/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Estudos Transversais , Dislipidemias/diagnóstico , Dislipidemias/epidemiologia , Feminino , Humanos , Hiperuricemia/diagnóstico , Hiperuricemia/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Medição de Risco , Fatores de Risco , Regulação para Cima , Adulto Jovem
9.
Environ Monit Assess ; 191(9): 575, 2019 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-31422469

RESUMO

Industrial effluents are one of the foremost concerns relating to the anthropogenic environmental pollution. The effluents from the tanning and textile industries in Dhaka, Bangladesh, were characterized chemically and physicochemically with multivariate statistical techniques. The concentrations of heavy metals viz., Pb, Cd, Cr, Mn, Fe, Ni, Cu, and Zn were determined by atomic absorption spectrometer while concentrations of anions viz., F-, Cl-, NO2-, NO3-, and SO42- were measured by ion chromatograph. The physicochemical parameters viz., temperature, pH, electrical conductivity (EC), salinity, turbidity, dissolved oxygen (DO), and biological oxygen demand (BOD) were measured by a multiparameter meter while total suspended solids (TSS) and total dissolved solids (TDS) were measured gravimetrically. This study showed that effluents from both industries demonstrated high levels of TSS, TDS, EC, and heavy metals. Tannery effluents have lower pH and DO, and higher BOD, Cl-, SO42-, and Cr concentrations while textile dyeing effluents have higher pH, NO2-, and NO3- concentrations, compared to the standard limits promulgated by the Bangladesh government. Multivariate statistical techniques such as cluster analysis and principal component analysis along with the correlation matrices showed significant association among the measured parameters and identified pollution sources as well as effluent types in the study area which could be linked to the processes used in textile dying and tanning industries. This study will be useful for identifying pollutants emanating from the two industries and will guide future industrial aquatic studies where multiple industrial runoffs are concerned.


Assuntos
Monitoramento Ambiental/métodos , Resíduos Industriais/análise , Curtume , Indústria Têxtil , Poluentes Químicos da Água/análise , Ânions/análise , Ânions/química , Bangladesh , Metais Pesados/análise , Metais Pesados/química , Análise Multivariada , Poluentes Químicos da Água/química
11.
BMC Public Health ; 18(1): 58, 2017 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-28743284

RESUMO

BACKGROUND: Hypertension is a global health issue and is currently increasing at rapid pace in South Asian countries including Bangladesh. Although, some studies on hypertension have been conducted in Bangladesh, there is a lack of scientific evidence in the adult student population that was missing from the previous and recent national cross-sectional studies. Moreover, the specific risk factors of hypertension in the Bangladeshi adults still need to be investigated. This study was conducted to estimate hypertension prevalence among adult students in Bangladesh and to test the hypothesis of Luke et al. (Hypertension 43:555-560, 2004) that basal metabolic rate (BMR) and blood pressure are positively associated independent of body size. METHOD: The data was collected on 184 adult university students (118 female and 66 male) in Dhaka, Bangladesh. Anthropometric, BMR details and an average of at least two blood pressure measurements were obtained. Hypertension was defined by a systolic blood pressure (SBP) ≥ 140 mmHg and/or, diastolic blood pressure (DBP) ≥ 90 mmHg. RESULTS: Overall, 6.5% of participants had hypertension with significantly (p < 0.001) higher prevalence in male (12.1%) than in the female (3.4%) students. Age and BMI showed positive and significant correlation with hypertension among the students. When adjusted for body mass index (BMI), as well as other potentially confounding variables such as age, sex, smoking status and degree of urbanization, BMR was positively correlated with SBP and DBP (p < 0.001). Thus, higher BMR is associated with SBP and DBP; this is opposite the well documented inverse relationship between physical activity and blood pressure. If the influence of BMR on blood pressure is confirmed, the systematically elevated BMR might be an important predictor that can explain relatively high blood pressure and hypertension in humans. CONCLUSION: This study reports the prevalence and associated risk factors of hypertension in the Bangladeshi adult students. The study also showed a positive association between BMR and blood pressure among the participants. A large scale longitudinal study across the country is needed to find out the underlying causes of hypertension in the Bangladeshi adults. In addition, comprehensive and integrated intervention programs focusing on modifiable risk factors are recommended to make awareness and prevent hypertension.


Assuntos
Metabolismo Basal/fisiologia , Pressão Sanguínea/fisiologia , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Adolescente , Adulto , Bangladesh/epidemiologia , Estudos Transversais , Feminino , Humanos , Índia , Estudos Longitudinais , Masculino , Prevalência , Fatores de Risco , Estudantes , Adulto Jovem
12.
Lancet ; 382(9909): 2027-37, 2013 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-24268604

RESUMO

By disaggregating gains in child health in Bangladesh over the past several decades, significant improvements in gender and socioeconomic inequities have been revealed. With the use of a social determinants of health approach, key features of the country's development experience can be identified that help explain its unexpected health trajectory. The systematic equity orientation of health and socioeconomic development in Bangladesh, and the implementation attributes of scale, speed, and selectivity, have been important drivers of health improvement. Despite this impressive pro-equity trajectory, there remain significant residual inequities in survival of girls and lower wealth quintiles as well as a host of new health and development challenges such as urbanisation, chronic disease, and climate change. Further progress in sustaining and enhancing equity-oriented achievements in health hinges on stronger governance and longer-term systems thinking regarding how to effectively promote inclusive and equitable development within and beyond the health system.


Assuntos
Mortalidade da Criança/tendências , Proteção da Criança/tendências , Bangladesh , Criança , Pré-Escolar , Desenvolvimento Econômico/tendências , Serviços de Planejamento Familiar/tendências , Feminino , Disparidades em Assistência à Saúde/tendências , Humanos , Programas de Imunização/tendências , Lactente , Masculino , Avaliação de Resultados em Cuidados de Saúde , Pobreza/prevenção & controle , Pobreza/tendências , Características de Residência/estatística & dados numéricos , Distribuição por Sexo , Fatores Socioeconômicos , Apoio ao Desenvolvimento de Recursos Humanos/tendências , Cobertura Universal do Seguro de Saúde/tendências , Saúde da Mulher/tendências
13.
BMC Biotechnol ; 14: 78, 2014 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-25141858

RESUMO

BACKGROUND: With the accelerating development of bioscience, the problem of research cost has become important. We previously devised and developed a novel concept microarray with manageable volumes (MMV) using a soft gel. It demonstrated the great potential of the MMV technology with the examples of 1024-parallel-cell culture and PCR experiments. However, its full potential failed to be expressed, owing to the nature of the material used for the MMV chip. RESULTS: In the present study, by developing plastic-based MMVs and associated technologies, we introduced novel technologies such as C2D2P (in which the cells in each well are converted from DNA to protein in 1024-parallel), NGS-non-dependent microbiome analysis, and other powerful applications. CONCLUSIONS: The reborn MMV-microarray technology has proven to be highly efficient and cost-effective (with approximately 100-fold cost reduction) and enables us to realize hitherto unattainable technologies.


Assuntos
Análise em Microsséries/instrumentação , Análise em Microsséries/métodos , Microbiota , Análise em Microsséries/economia , Reação em Cadeia da Polimerase , Reprodutibilidade dos Testes
14.
Trends Mol Med ; 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38890027

RESUMO

An effective HIV-1 vaccine is still not available, and most vaccine efficacy trials conducted over the years resulted in no significant overall protection. Here we highlight several insights gained from these trials as well as emerging questions that may be important for further guidance to advance current research directions.

15.
Biochem Biophys Rep ; 38: 101727, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38766381

RESUMO

Background and aim: N-acetyl-p-benzoquinoneimine (NAPQI), a toxic byproduct of paracetamol (Acetaminophen, APAP), can accumulate and cause liver damage by depleting glutathione and forming protein adducts in the mitochondria. These adducts disrupt the respiratory chain, increasing superoxide production and reducing ATP. The goal of this study was to provide computational proof that succinate dehydrogenase (SDH), a subunit of complex II in the mitochondrial respiratory chain, is a favorable binding partner for NAPQI in this regard. Method: Molecular docking, molecular dynamics simulation, protein-protein interaction networks (PPI), and KEGG metabolic pathway analysis were employed to identify binding characteristics, interaction partners, and their associations with metabolic pathways. A lipid membrane was added to the experimental apparatus to mimic the natural cellular environment of SDH. This modification made it possible to develop a context for investigating the role and interactions of SDH within a cellular ecosystem that was more realistic and biologically relevant. Result: The molecular binding affinity score for APAP and NAPQI with SDH was predicted -6.5 and -6.7 kcal/mol, respectively. Furthermore, RMSD, RMSF, and Rog from the molecular dynamics simulations study revealed that NAPQI has slightly higher stability and compactness compared to APAP at 100 ns timeframe with mitochondrial SDH. Conclusion: This study serves to predict the mechanistic process of paracetamol toxicity by using different computational approaches. In addition, this study will provide information about the drug target against APAP hepatotoxicity.

16.
mBio ; 15(4): e0268623, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38470051

RESUMO

The envelope glycoprotein (Env) trimer on the surface of human immunodeficiency virus type I (HIV-1) mediates viral entry into host CD4+ T cells and is the sole target of neutralizing antibodies. Broadly neutralizing antibodies (bnAbs) that target gp120 V3-glycan of HIV-1 Env trimer are potent and block the entry of diverse HIV-1 strains. Most V3-glycan bnAbs interact, to a different extent, with a glycan attached to N332, but Asn at this position is not absolutely conserved or required for HIV-1 entry based on the prevalence of N332 in different circulating HIV-1 strains from diverse clades. Here, we studied the effects of amino acid changes at position 332 of HIV-1AD8 Envs on HIV-1 sensitivity to antibodies, cold exposure, and soluble CD4. We further investigated how these changes affect Env function and HIV-1 infectivity in vitro. Our results suggest robust tolerability of HIV-1AD8 Env N332 to changes, with specific changes that resulted in extended exposure of gp120 V3 loop, which is typically concealed in most primary HIV-1 isolates. Viral evolution leading to Asn at position 332 of HIVAD8 Envs is supported by the selection advantage of high levels of cell-cell fusion, transmission, and infectivity with high levels of cell surface expression and slightly higher gp120 shedding than most N332 variants. Thus, tolerance of HIV-1AD8 Envs to different amino acids at position 332 provides increased flexibility to respond to changing conditions/environments and evade the immune system. Modeling studies of the distance between N332 glycan and specific bnAbs were in agreement with N332 glycan dependency on bnAb neutralization. Overall, our studies provide insights into the contribution of specific amino acids at position 332 to Env antigenicity, stability on ice, and conformational states. IMPORTANCE: Glycan attached to amino acid asparagine at position 332 of HIV-1 envelope glycoproteins is a main target of a subset of broadly neutralizing antibodies that block HIV-1 infection. Here, we defined the contribution of different amino acids at this position to Env antigenicity, stability on ice, and conformational states.


Assuntos
Infecções por HIV , Soropositividade para HIV , HIV-1 , Humanos , Aminoácidos , Anticorpos Neutralizantes , Anticorpos Amplamente Neutralizantes , Produtos do Gene env do Vírus da Imunodeficiência Humana , Glicoproteínas , Anticorpos Anti-HIV , Proteína gp120 do Envelope de HIV/genética , Gelo , Polissacarídeos
17.
Pathol Res Pract ; 254: 155097, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38277745

RESUMO

Exosomes are nanometric membrane vesicles of late endosomal origin that are released by most, if not all, cell types as a sophisticated means of intercellular communication. They play an essential role in the movement of materials and information between cells, transport a variety of proteins, lipids, RNA, and other vital data, and over time, they become an essential part of the drug delivery system and a marker for the early detection of many diseases. Dendritic cells have generated interest in cancer immunotherapy due to their ability to initiate and modify effective immune responses. Apart from their cytokine release and direct interactions with other cell types, DCs also emit nanovesicles, such as exosomes, that contribute to their overall activity. Numerous studies have demonstrated exosomes to mediate and regulate immune responses against cancers. Dendritic cell-derived exosomes (DCs) have attracted a lot of attention as immunotherapeutic anti-cancer treatments since it was found that they contain functional MHC-peptide complexes along with a variety of other immune-stimulating components that together enable immune cell-dependent tumor rejection. By enhancing tumor and immunosuppressive immune cells or changing a pro-inflammatory milieu to inhibit tumor advancement, exosomes generated from dendritic cells can initiate and support tumor growth. This study reviewed the immunogenicity of dendritic cell-derived exosomes and strategies for expanding their immunogenic potential as novel and effective anti-cancer therapies.


Assuntos
Exossomos , Neoplasias , Humanos , Exossomos/genética , Células Dendríticas , Neoplasias/patologia , Imunidade , Imunoterapia
18.
Biomed Pharmacother ; 174: 116438, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38513594

RESUMO

The mitogen-activated protein kinase (MAPK) signaling pathway, particularly the p38 MAPK and ERK1/2, has been implicated in the pathogenesis of Parkinson's disease (PD). Recent studies have shown that MAPK signaling pathway can influence the expression of matrix metalloproteinase 9 (MMP-9), known for its involvement in various physiological and pathological processes, including neurodegenerative diseases. This study explores the modulation of MMP-9 expression via the MAPK/ERK signaling cascade and its potential therapeutic implications in the context of PD-associated motor dysfunction. Here, tolperisone hydrochloride (TL), a muscle relaxant that blocks voltage-gated sodium and calcium channels, was used as a treatment to observe its effect on MAPK signaling and MMP-9 expression. Rotenone (RT) exposure in mice resulted in a significant reduction in substantia nigra and primary motor cortex neurons, which were further evidenced by impairments in motor function. When TL was administered, neuron count was restored (89.0 ± 4.78 vs 117.0 ± 4.46/mm2), and most of the motor dysfunction was alleviated. Mechanistically, TL reduced the protein expression of phospho-p38MAPK (1.06 fold vs 1.00 fold) and phospho-ERK1/2 (1.16 fold vs 1.02 fold), leading to the inhibition of MAPK signaling, as well as reduced MMP-9 concentrations (2.76 ± 0.10 vs 1.94 ± 0.10 ng/mL) in the process of rescuing RT-induced neuronal cell death and motor dysfunction. Computational analysis further revealed TL's potential inhibitory properties against MMP-9 along with N and L-type calcium channels. These findings shed light on TL's neuroprotective effects via MMP-9 inhibition and MAPK signaling downregulation, offering potential therapeutic avenues for PD-associated motor dysfunction.


Assuntos
Inibidores de Metaloproteinases de Matriz , Doença de Parkinson , Tolperisona , Animais , Masculino , Camundongos , Regulação para Baixo/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Metaloproteinase 9 da Matriz/metabolismo , Inibidores de Metaloproteinases de Matriz/farmacologia , Camundongos Endogâmicos C57BL , Atividade Motora/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Rotenona/farmacologia , Tolperisona/farmacocinética , Tolperisona/uso terapêutico
19.
Cureus ; 16(4): e59395, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38707172

RESUMO

Rheumatoid arthritis (RA) is the most common inflammatory polyarthritis in Bangladesh. Bangladesh Rheumatology Society (BRS) proposes these management recommendations to treat the considerable burden of RA in the resource-constrained situation based on the best current evidence combined with societal challenges and opportunities. BRS formed a task force (TF) comprising four rheumatologists. The TF searched for all available literature, including updated American College of Rheumatology (ACR), European Alliance of Associations for Rheumatology (EULAR), and Asia-Pacific League of Associations for Rheumatology (APLAR) and several other guidelines, and systematic literature reviews until October 2023, and then a steering committee was formed, which included rheumatologists and internists. We followed the EULAR standard operating procedures to categorize levels of evidence and grading of recommendations. This recommendation has two parts -- general (diagnosis of RA, nomenclature of disease-modifying anti-rheumatic drugs [DMARDs], disease activity indices) and management portion. The TF agreed on four overarching principles and 12 recommendations. Overarching principles deal with early diagnosis and disease activity monitoring. Recommendations 1-5 discuss using glucocorticoids, NSAIDs, and conventional synthetic DMARDs (csDMARD). Recommendations 6-9 stretch the use of targeted synthetic DMARDs (tsDMARDs) and biological DMARDs (bDMARDs). The suggested DMARD therapy includes initiation with methotrexate (MTX) or another csDMARD (in case of contraindication to MTX) in the first phase and the addition of a tsDMARD in the second phase, switching to an alternative tsDMARDs or bDMARDs in the subsequent phases. The TF included the Padua prediction score for the thromboembolism risk estimation. Recommendations 10-12 cover infection screening, vaccination, and DMARD tapering. Bangladesh has a higher prevalence of RA. This recommendation will serve as a tool to treat this high burden of patients with RA scientifically and more effectively.

20.
PLoS One ; 19(4): e0300878, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38635835

RESUMO

Saltwater intrusion in the coastal areas of Bangladesh is a prevalent phenomenon. However, it is not conducive to activities such as irrigation, navigation, fish spawning and shelter, and industrial usage. The present study analyzed 45 water samples collected from 15 locations in coastal areas during three seasons: monsoon, pre-monsoon, and post-monsoon. The aim was to comprehend the seasonal variation in physicochemical parameters, including water temperature, pH, electrical conductivity (EC), salinity, total dissolved solids (TDS), hardness, and concentrations of Na+, K+, Mg2+, Ca2+, Fe2+, HCO3-, PO43-, SO42-, and Cl-. Additionally, parameters essential for agriculture, such as soluble sodium percentage (SSP), sodium absorption ratio (SAR), magnesium absorption ratio (MAR), residual sodium carbonate (RSC), Kelly's ratio (KR), and permeability index (PI), were examined. Their respective values were found to be 63%, 16.83 mg/L, 34.92 mg/L, 145.44 mg/L, 1.28 mg/L, and 89.29%. The integrated water quality index was determined using entropy theory and principal component analysis (PCA). The resulting entropy water quality index (EWQI) and SAR of 49.56% and 63%, respectively, indicated that the samples are suitable for drinking but unsuitable for irrigation. These findings can assist policymakers in implementing the Bangladesh Deltaplan-2100, focusing on sustainable land management, fish cultivation, agricultural production, environmental preservation, water resource management, and environmental protection in the deltaic areas of Bangladesh. This research contributes to a deeper understanding of seasonal variations in the hydrochemistry and water quality of coastal rivers, aiding in the comprehension of salinity intrusion origins, mechanisms, and causes.


Assuntos
Água Potável , Água Subterrânea , Poluentes Químicos da Água , Qualidade da Água , Monitoramento Ambiental/métodos , Rios , Bangladesh , Sódio/análise , Poluentes Químicos da Água/análise , Água Subterrânea/análise , Água Potável/análise , Índia
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