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1.
Front Chem ; 12: 1351669, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38449478

RESUMEN

This study investigates the potential of 2-(4-butylbenzyl)-3-hydroxynaphthalene-1,4-dione (11) and its 12 derivatives as anticancer and biofilm formation inhibitors for methicillin-resistant staphylococcus aureus using in silico methods. The study employed various computational methods, including molecular dynamics simulation molecular docking, density functional theory, and global chemical descriptors, to evaluate the interactions between the compounds and the target proteins. The docking results revealed that compounds 9, 11, 13, and ofloxacin exhibited binding affinities of -7.6, -7.9, -7.5, and -7.8 kcal mol-1, respectively, against peptide methionine sulfoxide reductase msrA/msrB (PDB: 3E0M). Ligand (11) showed better inhibition for methicillin-resistant staphylococcus aureus msrA/msrB enzyme. The complex of the 3E0M-ligand 11 remained highly stable across all tested temperatures (300, 305, 310, and 320 K). Principal Component Analysis (PCA) was employed to evaluate the behavior of the complex at various temperatures (300, 305, 310, and 320 K), demonstrating a total variance of 85%. Convergence was confirmed by the eigenvector's cosine content value of 0.43, consistently displaying low RMSD values, with the minimum observed at 310 K. Furthermore, ligand 11 emerges as the most promising candidate among the compounds examined, showcasing notable potential when considering a combination of in vitro, in vivo, and now in silico data. While the naphthoquinone derivative (11) remains the primary candidate based on comprehensive in silico studies, further analysis using Frontier molecular orbital (FMO) suggests while the Egap value of compound 11 (2.980 eV) and compound 13 (2.975 eV) is lower than ofloxacin (4.369 eV), indicating their potential, so it can be a statement that compound 13 can also be investigated in further research.

2.
MethodsX ; 12: 102537, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38299040

RESUMEN

In exploring nature's potential in addressing liver-related conditions, this study investigates the therapeutic capabilities of flavonoids. Utilizing in silico methodologies, we focus on flavone and its analogs (1-14) to assess their therapeutic potential in treating liver diseases. Molecular change calculations using density functional theory (DFT) were conducted on these compounds, accompanied by an evaluation of each analog's physiochemical and biochemical properties. The study further assesses these flavonoids' binding effectiveness and locations through molecular docking studies against six target proteins associated with human cancer. Tropoflavin and taxifolin served as reference drugs. The structurally modified flavone analogs (1-14) displayed a broad range of binding affinities, ranging from -7.0 to -9.4 kcal mol⁻¹, surpassing the reference drugs. Notably, flavonoid (7) exhibited significantly higher binding affinities with proteins Nrf2 (PDB:1 × 2 J) and DCK (PDB:1 × 2 J) (-9.4 and -8.1 kcal mol⁻¹) compared to tropoflavin (-9.3 and -8.0 kcal mol⁻¹) and taxifolin (-9.4 and -7.1 kcal mol⁻¹), respectively. Molecular dynamics (MD) simulations revealed that the docked complexes had a root mean square deviation (RMSD) value ranging from 0.05 to 0.2 nm and a root mean square fluctuation (RMSF) value between 0.35 and 1.3 nm during perturbation. The study concludes that 5,7-dihydroxyflavone (7) shows substantial promise as a potential therapeutic agent for liver-related conditions. However, further validation through in vitro and in vivo studies is necessary. Key insights from this study include:•Screening of flavanols and their derivatives to determine pharmacological and bioactive properties using ADMET, molinspiration, and pass prediction analysis.•Docking of shortlisted flavone derivatives with proteins having essential functions.•Analysis of the best protein-flavonoid docked complexes using molecular dynamics simulation to determine the flavonoid's efficiency and stability within a system.

3.
Biol Futur ; 74(4): 519-527, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37964139

RESUMEN

The chaperonin TRiC/CCT is cytosolic cylindrical complex of 16 subunits encoded by eight essential genes CCT1-8. It contributes to folding 10% of cellular polypeptides in yeast. The strain carrying substitution point mutation G412E in the equatorial domain of Cct7p resulted in the improper folding of substrates. In this study, the Cct7p mutant exhibited sensitivity to non-optimal growth temperatures and cell wall stressors. Heat shock is known to disrupt cell wall and protein stability in budding yeast. Mitogen-activated protein kinase-mediated cell wall integrity pathway gets activated to compensate the perturbed cell wall. Overexpression of the PKC1 and SLT2 genes of MAPK signaling pathway in mutant rescued the growth and cell division defects. Additionally, the genes of the CWI pathway such as SED1, GFA1, PIR1, and RIM21 are down-regulated. The Cct7p mutant strain (G412E) is unable to withstand the heat stress due to the underlying defects in protein folding and cell wall maintenance. Taken together, our results strongly indicate the interaction between CCT and cell wall integrity pathway.


Asunto(s)
Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas Quinasas Activadas por Mitógenos/genética , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Pared Celular/genética , Pared Celular/metabolismo , Respuesta al Choque Térmico/genética
4.
Biol Trace Elem Res ; 2023 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-37897594

RESUMEN

The degradation of the environment due to numerous industrial practices has emerged as a major issue globally, particularly in a country like Bangladesh. The present study dispenses information about heavy metal (Cr, Mn, Fe, Co, Ni, Cu, Zn, Cd, and Pb) contamination in some frequently consumed vegetables, namely, ash pumpkin, potato, bitter gourd, buffalo spinach, snake gourd, and pointed gourd grown in an industrially prone location and their repercussion on consumers' health. Proton-induced X-ray emission (PIXE) technique was used as the major analytical tool to detect heavy metal concentrations. Mean concentration and the range of Cr, Mn, Fe, Co, Ni, Cu, Zn, Cd, and Pb in vegetables were detected (4.81 ± 2.79, 2.43-10.94), (497.57 ± 258.08, 181.24-886.67), (644.49 ± 298.40, 179.56-998.78), (38.88 ± 14.31, 18.88-60.12), (58.11 ± 12.58, 42.55-84.79), (137.24 ± 48.37, 71.99-208.98), (123.31 ± 63.62, 49.97-256.09), (8.09 ± 2.69, 4.29-14.94), and (4.16 ± 2.95, 1.22-9.98) mg/kg (dry weight basis), respectively. An extreme level of heavy metal contamination in vegetable samples was notified regarding the estimated metal pollution index (MPI) and Nemerow pollution index (P) value, which underpinned the health risk values. The estimated hazard index (HI) value stipulated high risk in all varieties of vegetables regardless of age group and cadmium (Cd) was found as the major contributor. Concerning the carcinogenic risk index (CR) for single elements, the value of Co, Ni, and Cr was approximated far above the USEPA threshold risk limit (CR>1E-04). Moreover, total carcinogenic risk (TCR) for all varieties of vegetables exceeded the safety threshold value for both the age group and children, in particular, were found most vulnerable. The outshot of the present study divulged associated health risks for the population group by the heavy metals via dietary intake of vegetables.

5.
Mymensingh Med J ; 32(3): 778-786, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37391974

RESUMEN

Coronary heart disease (CHD) imposes a significant burden on health care systems because of high morbidity and mortality. There is documented evidence that South Asian people develop CHD at a higher rate and at an early age. If the affected individual is 40 years old or below, the tragic consequences are catastrophic. Identifying risk factors could be important for health promotion. The objectives of this study were to determine the frequency of risk factors in young patients with acute myocardial infarction and thus with ischemic heart disease (IHD) aged 40 years and below in our population. It was a descriptive observational study which was carried out at Coronary Care Unit of Rajshahi Medical college Hospital, Rajshahi, Bangladesh in 61 patients from January 2011 to June 2011. All patients who fulfilled the inclusion criteria admitted to coronary care unit (CCU) with a diagnosis of Acute MI were included. Their detailed history was then taken including symptoms at presentation and their risk factors were assessed according to the Framingham Risk Scoring System with the help of history and laboratory investigations. Mean age ±SD of the patients was 36±3.7 year. Most of the patients were male. Smoking was the major risk factor (73.8%) followed by family history of IHD (44.3%). Other risk factors were dyslipidaemia (39.35%), hypertension (37.7%), obesity (11.5%) and diabetes mellitus (8.2%). Majority of the patients were adopted in sedentary lifestyle. 91.8% patient presented with chest pain. Other symptoms were dyspnoea (37.7%), palpitation (59.0%), sweating (77.0%), nausea, vomiting (50.8%) and impaired consciousness (19.7%) etc. Most frequent risk factor for acute myocardial infarction (MI) at young age is smoking followed by family history of MI and dyslipidaemia. Majority of the patients had two or more than two identifiable antecedent risk factors.


Asunto(s)
Infarto del Miocardio , Isquemia Miocárdica , Humanos , Masculino , Adulto Joven , Adulto , Femenino , Bangladesh/epidemiología , Factores de Riesgo , Infarto del Miocardio/epidemiología , Infarto del Miocardio/etiología , Análisis Factorial
6.
ACS Omega ; 8(29): 25817-25831, 2023 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-37521603

RESUMEN

In this study, microwave-assisted Knoevenagel condensation was used to produce two novel series of derivatives (1-6) from benzylidenemalononitrile and ethyl 2-cyano-3-phenylacrylate. The synthesized compounds were characterized using Fourier transform infrared (FT-IR) and 1H NMR spectroscopies. The pharmacodynamics, toxicity profiles, and biological activities of the compounds were evaluated through an in silico study using prediction of activity spectra for substances (PASS) and Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) studies. According to the PASS prediction results, compounds 1-6 showed greater antineoplastic potency for breast cancer than other types of cancer. Molecular docking was employed to investigate the binding mode and interaction sites of the derivatives (1-6) with three human cancer targets (HER2, EGFR, and human FPPS), and the protein-ligand interactions of these derivatives were compared to those reference standards Tyrphostin 1 (AG9) and Tyrphostin 23 (A23). Compound 3 showed a stronger effect on two cell lines (HER2 and FPPS) than the reference drugs. A 20 ns molecular dynamics (MD) simulation was also conducted to examine the ligand's behavior at the active binding site of the modeled protein, utilizing the lowest docking energy obtained from the molecular docking study. Enthalpies (ΔH), Gibbs free energies (ΔG), entropies (ΔS), and frontier molecular orbital parameters (highest occupied molecular orbital-lowest unoccupied molecular orbital (HOMO-LUMO) gap, hardness, and softness) were calculated to confirm the thermodynamic stability of all derivatives. The consistent results obtained from the in silico studies suggest that compound 3 has potential as a new anticancer and antiparasitic drug. Further research is required to validate its efficacy.

7.
Heliyon ; 9(6): e16615, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37313167

RESUMEN

The study identifies potential carcinogenic health risk-zone of Chattogram city for the occurrence of trihalomethanes (THMs) at its water distribution network. The EPANET-THMs simulation model along with an empirical model have been adopted in the study to predict THMs content of supply water of the distribution network of the city's Karnaphuli service area. The empirical model has estimated THMs level of supply water based on influential water quality parameters, and few of these have been used as pre-set values for subsequent EPANET simulation. The simulation (R2= 0.7) shows that THMs' concentrations throughout the network vary from 33 to 486 µg/L. Around 60% of total junctions showed THMs concentrations above 150 µg/L, while that is above 50 µg/L for most (99%) of the junctions. Residual Free chlorine, one of the precursors for the THMs formation in distribution line, has also been simulated by EPANET considering varying applied chlorine dose at the water purification unit and wall (Kw) and bulk (Kb) decay constants. The simulated free residual chlorine peaks are found to be closer to the actual values with chlorine dose of 2 mg/L, and decay constants, Kw = 1 d-1 and Kb = 1 d-1. A mean lifetime total risk of cancer due to the presence of THMs has been found to be very high. Spatial distribution of carcinogenic risk shows that the central zone of the service area is the most vulnerable zone, followed by the western and northern zone. The first ever zone wise risk identification could be used as baseline data for operational and regulatory purposes and may raise awareness among the city's inhabitants. Furthermore, the application of EPANET in combination with an empirical model could be an effective tool for predicting THMs' concentration in water distribution networks in developing countries like Bangladesh to minimize the expenses of measuring THMs.

8.
Br J Pharmacol ; 180(22): 2898-2915, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37115600

RESUMEN

BACKGROUND AND PURPOSE: Activated fibroblasts deposit fibrotic matrix in chronic kidney disease (CKD) and G-protein coupled receptors (GPCRs) are the most druggable therapeutic targets. Here, we set out to establish a transcriptional profile that identifies activated kidney fibroblasts and the GPCRs that they express. EXPERIMENTAL APPROACH: RNA sequencing and single cell qRT-PCR were performed on mouse kidneys after unilateral ureteral obstruction (UUO). Candidate expression was evaluated in mice with UUO or diabetes or injected with adriamycin or folic acid. Intervention studies were conducted in mice with diabetes or UUO. Correlative histology was performed in human kidney tissue. KEY RESULTS: Transcription factor 21 (Tcf21)+ cells that expressed 2 or 3 of Postn, Acta2 and Pdgfra were highly enriched for fibrogenic genes and were defined as activated kidney fibroblasts. Tcf21+ α-smooth muscle actin (α-SMA)+ interstitial cells accumulated in kidneys of mice with UUO or diabetes or injected with adriamycin or folic acid, whereas renin-angiotensin system blockade attenuated increases in Tcf21 in diabetic mice. Fifty-six GPCRs were up-regulated in single Tcf21+ kidney fibroblasts, the most up-regulated being Adgra2 and S1pr3. Adenosine receptors, Adora2a/2b, were up-regulated in Tcf21+ fibroblasts and the adenosine receptor antagonist, caffeine decreased Tcf21 upregulation and kidney fibrosis in UUO mice. TCF21, ADGRA2, S1PR3 and ADORA2A/2B were each detectable in α-SMA+ interstitial cells in human kidney samples. CONCLUSION AND IMPLICATIONS: Tcf21 is a marker of kidney fibroblasts that are enriched for fibrogenic genes in CKD. Further analysis of the GPCRs expressed by these cells may identify new targets for treating CKD. LINKED ARTICLES: This article is part of a themed issue on Translational Advances in Fibrosis as a Therapeutic Target. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v180.22/issuetoc.


Asunto(s)
Diabetes Mellitus Experimental , Enfermedades Renales , Insuficiencia Renal Crónica , Obstrucción Ureteral , Animales , Humanos , Ratones , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Diabetes Mellitus Experimental/metabolismo , Doxorrubicina/farmacología , Fibroblastos/metabolismo , Fibrosis , Ácido Fólico/metabolismo , Ácido Fólico/farmacología , Ácido Fólico/uso terapéutico , Riñón , Enfermedades Renales/metabolismo , Ratones Endogámicos C57BL , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Insuficiencia Renal Crónica/metabolismo , Factores de Transcripción/metabolismo , Obstrucción Ureteral/metabolismo
9.
Mymensingh Med J ; 32(1): 3-9, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36594292

RESUMEN

Polycystic ovary syndrome (PCOS) is a polygenic and multifactorial condition, regarded as the most common endocrine abnormality of women in reproductive period. It is commonly assumed that insulin resistance, hyperandrogenism and obesity significantly influence the pathophysiological process of PCOS. This study was designed to estimate hormonal parameters in different phenotypes of PCOS. The cross sectional descriptive type of observational study was carried out at Mymensingh Medical College Hospital, Mymensingh, Bangladesh from January 2018 to June 2019. Data were collected from purposively selected 107 patients with PCOS by interview, clinical examination and laboratory investigations using a pretested case record form. Data were analyzed by computer software, SPSS-version 22.0. Hormonal parameters in different phenotypes of PCOS were compared with ANOVA test. Phenotype A was found in highest number (59.8%) followed by phenotype B (14.9%), phenotype D (14.0%) and phenotype C (11.2%). Biochemical hyperandrogenism was observed highest in phenotype A (57.8%) followed by phenotype B (36.4%) and phenotype C (6.1%). Biochemical or clinical hyperandrogenism was not observed among patients of phenotype D. Altered LH:FSH ratio was high in phenotype A (14.1%) and Phenotype B (2.8%). Increased serum prolactin level was found highest in phenotype A (10.3%) and increased serum TSH was found highest in phenotype D (4.7%). Statistically significant difference was observed among levels of serum testosterone of different phenotypes (p<0.001). Hormonal derangements among different phenotypes reflect the severity of reproductive dysfunction and metabolic aberrations. Screening for metabolic risks of diverse phenotypes is important to detect and prevent long term health consequences of PCOS.


Asunto(s)
Hiperandrogenismo , Resistencia a la Insulina , Síndrome del Ovario Poliquístico , Femenino , Humanos , Síndrome del Ovario Poliquístico/complicaciones , Estudios Transversales , Hiperandrogenismo/metabolismo , Fenotipo
10.
Plant Sci ; 326: 111532, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36347336

RESUMEN

Vegetable crops grown under shade nets typically show increased yield and quality. However, little is known about the photosynthetic responses at various CO2 and light levels under nets. This study aimed to determine carbon dioxide (A/Cc) and light (A/I) curves and leaf gas exchange response of bell pepper plants grown under nets at various shade levels. Experiments were conducted in the spring-summer of 2016 and 2018 in Tifton, Georgia (GA), USA, with five shade treatments [0 % (open field), 30 %, 47 %, 63 %, and 80 %]. The A/Cc curves revealed that plants grown at 30 % shade and in the open field had similar carboxylation, electron transport, and triose phosphate utilization rates. The A/I curves showed that gross and net photosynthesis were highest at 30 % shade. The 30 % shade had similar stomatal conductance, intercellular CO2, electron transport rate, and water use efficiency compared to the open field. The A/Cc and A/I curves and the leaf gas exchange parameters explained the intrinsic causes for the higher net photosynthesis at 30 % shade than in open-field bell pepper. The information from A/Cc-curves, A/I-curves, and leaf gas exchange is applicable in modeling photosynthesis and predicting primary productivity for C3 plants in elevated-CO2 and altered-light environments.


Asunto(s)
Capsicum , Dióxido de Carbono , Dióxido de Carbono/fisiología , Luz , Fotosíntesis/fisiología , Hojas de la Planta/fisiología , Plantas
11.
Braz. j. biol ; 832023.
Artículo en Inglés | LILACS-Express | LILACS, VETINDEX | ID: biblio-1469239

RESUMEN

Abstract Dengue fever (DF) is increasingly recognized as one of the worlds major mosquito borne diseases and causes significant morbidity and mortality in tropical and subtropical countries. Dengue fever is endemic in most part of Pakistan and continues to be a public health concern. Knowledge, attitude and practices can play an important role in management of the disease. Current study was aimed to determine the level of knowledge, attitude and practices regarding dengue fever among health practitioners, to study the level of knowledge and attitude with preventive practices for dengue fever. A cross sectional study was carried out in medical practitioners of the four districts of Malakand region during October to November 2019. A pre-structured questionnaire was used to collect data from medical practitioners. Data was analyzed using Graph Pad version 5. Significant value was considered when less than 0.05 (at 95% confidence of interval). The results revealed that most of participants have seen dengue vector (62%), the media being the most quoted source of information. Nearly 81.2% participants were aware from transmission of dengue fever is by mosquito bite. Practices based upon preventive measures were found to be predominantly focused towards prevention of mosquito bites rather than elimination of breeding places. Although the knowledge regarding DF and mosquito control measure was quite high among the medical practitioners but this knowledge was not put into practice. Further studies are required to aware the people about dengue and its vector in order to get prevention and control.


Resumo A dengue (DF) é cada vez mais reconhecida como uma das principais doenças transmitidas por mosquitos do mundo e causa significativa morbidade e mortalidade em países tropicais e subtropicais. A dengue é endêmica na maior parte do Paquistão e continua a ser um problema de saúde pública. Conhecimento, atitude e práticas podem desempenhar papel importante no manejo da doença. O presente estudo teve como objetivo determinar o nível de conhecimento, atitude e práticas em relação à dengue entre os profissionais de saúde, para estudar o nível de conhecimento e atitude com as práticas preventivas da dengue. Um estudo transversal foi realizado com médicos dos quatro distritos da região de Malakand de outubro a novembro de 2019. Um questionário pré-estruturado foi usado para coletar dados de médicos. Os dados foram analisados no Graph Pad versão 5. Valor significativo foi considerado quando menor que 0,05 (com intervalo de confiança de 95%). Os resultados revelaram que a maioria dos participantes já viu o vetor da dengue (62%), sendo a mídia a fonte de informação mais citada. Quase 81,2% dos participantes sabiam que a transmissão da dengue é por picada de mosquito. Constatou-se que as práticas baseadas em medidas preventivas se concentravam predominantemente na prevenção de picadas de mosquitos, e não na eliminação de criadouros. Embora o conhecimento sobre DF e medidas de controle de mosquitos fosse bastante elevado entre os médicos, esse conhecimento não foi colocado em prática. Mais estudos são necessários para conscientizar a população sobre a dengue e seu vetor, a fim de se obter prevenção e controle.

12.
Bull Math Biol ; 84(12): 145, 2022 11 09.
Artículo en Inglés | MEDLINE | ID: mdl-36350426

RESUMEN

It is well known that the FitzHugh-Nagumo model is one of the simplified forms of the four-variable Hodgkin-Huxley model that can reflect most of the significant phenomena of nerve cell action potential. However, this model cannot capture the irregular action potentials of sufficiently large periods in a one-parameter family of solutions. Motivated by this, we propose a modified FitzHugh-Nagumo reaction-diffusion system by changing its recovery kinetics. First, we investigate the parameter regime to know the existence of the wavetrains. Second, we conceive the occurrence of Eckhaus bifurcations of solutions that divide the solution region into two parts. The essential spectra at different grid points explore the occurrence of bifurcations of the waves. We find that the wavetrains of sufficiently large periods cross the stability boundary. This characteristic phenomenon is absent in the standard FitzHugh-Nagumo model. Finally, we observe a reasonable agreement between the direct PDE simulations and the solutions in the traveling wave ODEs. Furthermore, the model exhibits spiral wave for monotone and non-monotone cases that agrees with the waves observed in cellular activity.


Asunto(s)
Conceptos Matemáticos , Modelos Biológicos , Potenciales de Acción/fisiología , Neuronas , Difusión
13.
Mol Metab ; 66: 101641, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36396031

RESUMEN

OBJECTIVES: Glucagon-like peptide-1 receptor (GLP-1R) agonists reduce the rates of major cardiovascular events, including myocardial infarction in people with type 2 diabetes, and decrease infarct size while preserving ventricular function in preclinical studies. Nevertheless, the precise cellular sites of GLP-1R expression that mediate the cardioprotective actions of GLP-1 in the setting of ischemic cardiac injury are uncertain. METHODS: Publicly available single cell RNA sequencing (scRNA-seq) datasets on mouse and human heart cells were analyzed for Glp1r/GLP1R expression. Fluorescent activated cell sorting was used to localize Glp1r expression in cell populations from the mouse heart. The importance of endothelial and hematopoietic cells for the cardioprotective response to liraglutide in the setting of acute myocardial infarction (MI) was determined by inactivating the Glp1r in Tie2+ cell populations. Cardiac gene expression profiles regulated by liraglutide were examined using RNA-seq to interrogate mouse atria and both infarcted and non-infarcted ventricular tissue after acute coronary artery ligation. RESULTS: In mice, cardiac Glp1r mRNA transcripts were exclusively detected in endocardial cells by scRNA-seq. In contrast, analysis of human heart by scRNA-seq localized GLP1R mRNA transcripts to populations of atrial and ventricular cardiomyocytes. Moreover, very low levels of GIPR, GCGR and GLP2R mRNA transcripts were detected in the human heart. Cell sorting and RNA analyses detected cardiac Glp1r expression in endothelial cells (ECs) within the atria and ventricle in the ischemic and non-ischemic mouse heart. Transcriptional responses to liraglutide administration were not evident in wild type mouse ventricles following acute MI, however liraglutide differentially regulated genes important for inflammation, cardiac repair, cell proliferation, and angiogenesis in the left atrium, while reducing circulating levels of IL-6 and KC/GRO within hours of acute MI. Inactivation of the Glp1r within the Tie2+ cell expression domain encompassing ECs revealed normal cardiac structure and function, glucose homeostasis and body weight in Glp1rTie2-/- mice. Nevertheless, the cardioprotective actions of liraglutide to reduce infarct size, augment ejection fraction, and improve survival after experimental myocardial infarction (MI), were attenuated in Glp1rTie2-/- mice. CONCLUSIONS: These findings identify the importance of the murine Tie2+ endothelial cell GLP-1R as a target for the cardioprotective actions of GLP-1R agonists and support the importance of the atrial and ventricular endocardial GLP-1R as key sites of GLP-1 action in the ischemic mouse heart. Hitherto unexplored species-specific differences in cardiac GLP-1R expression challenge the exclusive use of mouse models for understanding the mechanisms of GLP-1 action in the normal and ischemic human heart.


Asunto(s)
Fibrilación Atrial , Receptor del Péptido 1 Similar al Glucagón , Liraglutida , Infarto del Miocardio , Animales , Humanos , Ratones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Células Endoteliales/metabolismo , Péptido 1 Similar al Glucagón/metabolismo , Receptor del Péptido 1 Similar al Glucagón/efectos de los fármacos , Receptor del Péptido 1 Similar al Glucagón/metabolismo , Liraglutida/farmacología , Infarto del Miocardio/tratamiento farmacológico , ARN Mensajero , Modelos Animales de Enfermedad , Receptor TIE-2/metabolismo
14.
Braz. j. biol ; 82: 1-8, 2022. map, tab
Artículo en Inglés | LILACS, VETINDEX | ID: biblio-1468577

RESUMEN

Present study was conducted among school children to recognize the prevalence of IPIs in rural communities of district Dir Lower, Pakistan. A sum of 324 samples of stool were collected (210 boys and 114 girls). Used direct smear method and formol ether sedimentation concentration technique for processing the samples. The result shows that 82% (n=266) were found infected comprised 64.8% male and 35.1% females. Children of the age group 10 to 12 years were found extremely infected 94.2% while 4-6 year age group were having minimum ratio of infection 72%. Current study shows mono parasitism in 50.6% of the students while 22.2% were infected with 2 species and 7.40% were infected with three species of parasites. Seven species of intestinal parasites were reported include Ascaris lumbricoid in male (n=122) 58.0% and in female (n=65) 57.0% followed by Hook worm (n=88) 41.9% and (n=44) 38.5%; Tania saginata (n=44) 20.9% and (n=24) 21.0%; Entrobius vermicularis (n=32) 15.2% and (n=16) 14.0%; Trichuris trichura (n=25) 11.9% and (n=22) 19.2%; Hymenolepis nana (n=24) 11.4% and (n=18) 15.7% and Entameoba histolytica (n=16) 7.61% and (n=14) 12.2% in male and females respectively. The study indicates that most occurring intestinal parasite in the current study were Ascaris lumbricoides 58.0% (n=122) followed by hookworms 41.9% (n=88). Male students were more infected than females in the present study.


O presente estudo foi conduzido entre crianças em idade escolar para reconhecer a prevalência de IPIs em comunidades rurais do distrito de Dir Lower, Paquistão. Foram coletadas 324 amostras de fezes (210 meninos e 114 meninas). Método de esfregaço direto usado e técnica de concentração de sedimentação de formol éter para processar as amostras. O resultado mostra que 82% (n = 266) dos infectados eram 64,8% do sexo masculino e 35,1% do feminino. Crianças da faixa etária de 10 a 12 anos foram encontradas extremamente infectadas 94,2%, enquanto a faixa etária de 4 a 6 anos apresentava proporção mínima de infecção de 72%. O estudo atual mostra monoparasitismo em 50,6% dos alunos, enquanto 22,2% estavam infectados com 2 espécies e 7,40% estavam infectados com três espécies de parasitas. Sete espécies de parasitas intestinais foram relatadas incluindo Ascaris lumbricoid em machos (n = 122) 58,0% e em fêmeas (n = 65) 57,0% seguido por anzol (n = 88) 41,9% e (n = 44) 38,5%; Tania saginata (n = 44) 20,9% e (n = 24) 21,0%; Entrobius vermicularis (n = 32) 15,2% e (n = 16) 14,0%; Trichuris trichura (n = 25) 11,9% e (n = 22) 19,2%; Hymenolepis nana (n = 24) 11,4% e (n = 18) 15,7% e Entameoba histolytica (n = 16) 7,61% e (n = 14) 12,2% em homens e mulheres, respectivamente. O estudo indica que os parasitas intestinais que mais ocorreram no presente estudo foram Ascaris lumbricoides 58,0% (n = 122), seguidos por ancilóstomos 41,9% (n = 88). Estudantes do sexo masculino foram mais infectados do que do sexo feminino no presente estudo.


Asunto(s)
Masculino , Femenino , Humanos , Preescolar , Niño , Ascaris , Entamoeba , Hymenolepis , Parásitos/patogenicidad , Taenia saginata , Trichuris
15.
Braz. j. biol ; 82: 1-10, 2022. tab
Artículo en Inglés | LILACS, VETINDEX | ID: biblio-1468579

RESUMEN

Vegetables eating raw are a leading source of transmission of infective forms of pathogenic internal parasites among human beings. This research was conducted from April to October, 2017 to assess the parasitic contamination of vegetables sold at main vegetable markets in districts Lower Dir and Peshawar, Pakistan. Eight hundred specimens of different vegetables were purchased and soaked in physiological saline solution, shaken with a mechanical shaker for 20 minutes and processed by sedimentation concentration method. Results revealed that only 19.7% (n=158/800) of the vegetables were found to be contaminated with single or multiple parasite species. Ascaris lumbricoides (the large round worm) 12.3% (n=99/800) was the most commonly detected pathogen and Taenia saginata (the beef tapeworm) 1.62% (n=13/800) was the least frequently detected one. Interestingly, significant p value (p>0.05 at 95%CI) between the number of examined and contaminated for all the variables studied including education status of the vendors, markets location, type of vegetables, means of display, washed before display, washing source of water and market type. The findings of this study evidenced that consumption of raw vegetables possesses great risk of getting parasitic infections in Lower Dir and Peshawar districts, Pakistan. Instructing the sellers and the public about parasitic disease transfer and their hygiene can reduce the infection rate of parasites of human origin.


Os vegetais crus são a principal fonte de transmissão de formas infecciosas de parasitas internos patogênicos entre os seres humanos. Esta pesquisa foi realizada de abril a outubro de 2017 para avaliar a contaminação parasitária de vegetais vendidos nos principais mercados de vegetais nos distritos de Lower Dir e Peshawar, Paquistão. Oitocentos exemplares de diferentes vegetais foram adquiridos e embebidos em solução salina fisiológica, agitados em agitador mecânico por 20 minutos e processados pelo método de concentração por sedimentação. Os resultados revelaram que apenas 19,7% (n = 158/800) das hortaliças estavam contaminadas com uma ou várias espécies de parasitas. Ascaris lumbricoides (o verme redondo grande) 12,3% (n = 99/800) foi o patógeno mais comumente detectado e Taenia saginata (a tênia da carne) 1,62% (n = 13/800) foi o menos freqüentemente detectado. Curiosamente, valor de p significativo (p> 0,05 em IC de 95%) entre o número de examinados e contaminados para todas as variáveis estudadas incluindo escolaridade dos vendedores, localização dos mercados, tipo de vegetais, meios de exposição, lavado antes da exposição, fonte de lavagem de água e tipo de mercado. Os resultados deste estudo evidenciaram que o consumo de vegetais crus possui grande risco de contrair infecções parasitárias nos distritos de Lower Dir e Peshawar, no Paquistão. Instruir os vendedores e o público sobre a transferência de doenças parasitárias e sua higiene pode reduzir a taxa de infecção de parasitas de origem humana.


Asunto(s)
Ascaris lumbricoides/patogenicidad , Helmintos , Plantas/parasitología , Taenia saginata/patogenicidad
16.
Braz. j. biol ; 822022.
Artículo en Inglés | LILACS-Express | LILACS, VETINDEX | ID: biblio-1468764

RESUMEN

Abstract Present study was conducted among school children to recognize the prevalence of IPIs in rural communities of district Dir Lower, Pakistan. A sum of 324 samples of stool were collected (210 boys and 114 girls). Used direct smear method and formol ether sedimentation concentration technique for processing the samples. The result shows that 82% (n=266) were found infected comprised 64.8% male and 35.1% females. Children of the age group 10 to 12 years were found extremely infected 94.2% while 4-6 year age group were having minimum ratio of infection 72%. Current study shows mono parasitism in 50.6% of the students while 22.2% were infected with 2 species and 7.40% were infected with three species of parasites. Seven species of intestinal parasites were reported include Ascaris lumbricoid in male (n=122) 58.0% and in female (n=65) 57.0% followed by Hook worm (n=88) 41.9% and (n=44) 38.5%; Tania saginata (n=44) 20.9% and (n=24) 21.0%; Entrobius vermicularis (n=32) 15.2% and (n=16) 14.0%; Trichuris trichura (n=25) 11.9% and (n=22) 19.2%; Hymenolepis nana (n=24) 11.4% and (n=18) 15.7% and Entameoba histolytica (n=16) 7.61% and (n=14) 12.2% in male and females respectively. The study indicates that most occurring intestinal parasite in the current study were Ascaris lumbricoides 58.0% (n=122) followed by hookworms 41.9% (n=88). Male students were more infected than females in the present study.


Resumo O presente estudo foi conduzido entre crianças em idade escolar para reconhecer a prevalência de IPIs em comunidades rurais do distrito de Dir Lower, Paquistão. Foram coletadas 324 amostras de fezes (210 meninos e 114 meninas). Método de esfregaço direto usado e técnica de concentração de sedimentação de formol éter para processar as amostras. O resultado mostra que 82% (n = 266) dos infectados eram 64,8% do sexo masculino e 35,1% do feminino. Crianças da faixa etária de 10 a 12 anos foram encontradas extremamente infectadas 94,2%, enquanto a faixa etária de 4 a 6 anos apresentava proporção mínima de infecção de 72%. O estudo atual mostra monoparasitismo em 50,6% dos alunos, enquanto 22,2% estavam infectados com 2 espécies e 7,40% estavam infectados com três espécies de parasitas. Sete espécies de parasitas intestinais foram relatadas incluindo Ascaris lumbricoid em machos (n = 122) 58,0% e em fêmeas (n = 65) 57,0% seguido por anzol (n = 88) 41,9% e (n = 44) 38,5%; Tania saginata (n = 44) 20,9% e (n = 24) 21,0%; Entrobius vermicularis (n = 32) 15,2% e (n = 16) 14,0%; Trichuris trichura (n = 25) 11,9% e (n = 22) 19,2%; Hymenolepis nana (n = 24) 11,4% e (n = 18) 15,7% e Entameoba histolytica (n = 16) 7,61% e (n = 14) 12,2% em homens e mulheres, respectivamente. O estudo indica que os parasitas intestinais que mais ocorreram no presente estudo foram Ascaris lumbricoides 58,0% (n = 122), seguidos por ancilóstomos 41,9% (n = 88). Estudantes do sexo masculino foram mais infectados do que do sexo feminino no presente estudo.

17.
Braz. j. biol ; 822022.
Artículo en Inglés | LILACS-Express | LILACS, VETINDEX | ID: biblio-1468766

RESUMEN

Abstract Vegetables eating raw are a leading source of transmission of infective forms of pathogenic internal parasites among human beings. This research was conducted from April to October, 2017 to assess the parasitic contamination of vegetables sold at main vegetable markets in districts Lower Dir and Peshawar, Pakistan. Eight hundred specimens of different vegetables were purchased and soaked in physiological saline solution, shaken with a mechanical shaker for 20 minutes and processed by sedimentation concentration method. Results revealed that only 19.7% (n=158/800) of the vegetables were found to be contaminated with single or multiple parasite species. Ascaris lumbricoides (the large round worm) 12.3% (n=99/800) was the most commonly detected pathogen and Taenia saginata (the beef tapeworm) 1.62% (n=13/800) was the least frequently detected one. Interestingly, significant p value (p>0.05 at 95%CI) between the number of examined and contaminated for all the variables studied including education status of the vendors, markets location, type of vegetables, means of display, washed before display, washing source of water and market type. The findings of this study evidenced that consumption of raw vegetables possesses great risk of getting parasitic infections in Lower Dir and Peshawar districts, Pakistan. Instructing the sellers and the public about parasitic disease transfer and their hygiene can reduce the infection rate of parasites of human origin.


Resumo Os vegetais crus são a principal fonte de transmissão de formas infecciosas de parasitas internos patogênicos entre os seres humanos. Esta pesquisa foi realizada de abril a outubro de 2017 para avaliar a contaminação parasitária de vegetais vendidos nos principais mercados de vegetais nos distritos de Lower Dir e Peshawar, Paquistão. Oitocentos exemplares de diferentes vegetais foram adquiridos e embebidos em solução salina fisiológica, agitados em agitador mecânico por 20 minutos e processados pelo método de concentração por sedimentação. Os resultados revelaram que apenas 19,7% (n = 158/800) das hortaliças estavam contaminadas com uma ou várias espécies de parasitas. Ascaris lumbricoides (o verme redondo grande) 12,3% (n = 99/800) foi o patógeno mais comumente detectado e Taenia saginata (a tênia da carne) 1,62% (n = 13/800) foi o menos freqüentemente detectado. Curiosamente, valor de p significativo (p> 0,05 em IC de 95%) entre o número de examinados e contaminados para todas as variáveis estudadas incluindo escolaridade dos vendedores, localização dos mercados, tipo de vegetais, meios de exposição, lavado antes da exposição, fonte de lavagem de água e tipo de mercado. Os resultados deste estudo evidenciaram que o consumo de vegetais crus possui grande risco de contrair infecções parasitárias nos distritos de Lower Dir e Peshawar, no Paquistão. Instruir os vendedores e o público sobre a transferência de doenças parasitárias e sua higiene pode reduzir a taxa de infecção de parasitas de origem humana.

18.
Braz. j. biol ; 82: e243150, 2022. tab, graf
Artículo en Inglés | LILACS, VETINDEX | ID: biblio-1339334

RESUMEN

Present study was conducted among school children to recognize the prevalence of IPIs in rural communities of district Dir Lower, Pakistan. A sum of 324 samples of stool were collected (210 boys and 114 girls). Used direct smear method and formol ether sedimentation concentration technique for processing the samples. The result shows that 82% (n=266) were found infected comprised 64.8% male and 35.1% females. Children of the age group 10 to 12 years were found extremely infected 94.2% while 4-6 year age group were having minimum ratio of infection 72%. Current study shows mono parasitism in 50.6% of the students while 22.2% were infected with 2 species and 7.40% were infected with three species of parasites. Seven species of intestinal parasites were reported include Ascaris lumbricoid in male (n=122) 58.0% and in female (n=65) 57.0% followed by Hook worm (n=88) 41.9% and (n=44) 38.5%; Tania saginata (n=44) 20.9% and (n=24) 21.0%; Entrobius vermicularis (n=32) 15.2% and (n=16) 14.0%; Trichuris trichura (n=25) 11.9% and (n=22) 19.2%; Hymenolepis nana (n=24) 11.4% and (n=18) 15.7% and Entameoba histolytica (n=16) 7.61% and (n=14) 12.2% in male and females respectively. The study indicates that most occurring intestinal parasite in the current study were Ascaris lumbricoides 58.0% (n=122) followed by hookworms 41.9% (n=88). Male students were more infected than females in the present study.


O presente estudo foi conduzido entre crianças em idade escolar para reconhecer a prevalência de IPIs em comunidades rurais do distrito de Dir Lower, Paquistão. Foram coletadas 324 amostras de fezes (210 meninos e 114 meninas). Método de esfregaço direto usado e técnica de concentração de sedimentação de formol éter para processar as amostras. O resultado mostra que 82% (n = 266) dos infectados eram 64,8% do sexo masculino e 35,1% do feminino. Crianças da faixa etária de 10 a 12 anos foram encontradas extremamente infectadas 94,2%, enquanto a faixa etária de 4 a 6 anos apresentava proporção mínima de infecção de 72%. O estudo atual mostra monoparasitismo em 50,6% dos alunos, enquanto 22,2% estavam infectados com 2 espécies e 7,40% estavam infectados com três espécies de parasitas. Sete espécies de parasitas intestinais foram relatadas incluindo Ascaris lumbricoid em machos (n = 122) 58,0% e em fêmeas (n = 65) 57,0% seguido por anzol (n = 88) 41,9% e (n = 44) 38,5%; Tania saginata (n = 44) 20,9% e (n = 24) 21,0%; Entrobius vermicularis (n = 32) 15,2% e (n = 16) 14,0%; Trichuris trichura (n = 25) 11,9% e (n = 22) 19,2%; Hymenolepis nana (n = 24) 11,4% e (n = 18) 15,7% e Entameoba histolytica (n = 16) 7,61% e (n = 14) 12,2% em homens e mulheres, respectivamente. O estudo indica que os parasitas intestinais que mais ocorreram no presente estudo foram Ascaris lumbricoides 58,0% (n = 122), seguidos por ancilóstomos 41,9% (n = 88). Estudantes do sexo masculino foram mais infectados do que do sexo feminino no presente estudo.


Asunto(s)
Animales , Masculino , Femenino , Niño , Parásitos , Parasitosis Intestinales/epidemiología , Pakistán/epidemiología , Instituciones Académicas , Prevalencia , Heces
19.
Braz. j. biol ; 82: e242614, 2022. tab
Artículo en Inglés | LILACS, VETINDEX | ID: biblio-1350297

RESUMEN

Vegetables eating raw are a leading source of transmission of infective forms of pathogenic internal parasites among human beings. This research was conducted from April to October, 2017 to assess the parasitic contamination of vegetables sold at main vegetable markets in districts Lower Dir and Peshawar, Pakistan. Eight hundred specimens of different vegetables were purchased and soaked in physiological saline solution, shaken with a mechanical shaker for 20 minutes and processed by sedimentation concentration method. Results revealed that only 19.7% (n=158/800) of the vegetables were found to be contaminated with single or multiple parasite species. Ascaris lumbricoides (the large round worm) 12.3% (n=99/800) was the most commonly detected pathogen and Taenia saginata (the beef tapeworm) 1.62% (n=13/800) was the least frequently detected one. Interestingly, significant p value (p>0.05 at 95%CI) between the number of examined and contaminated for all the variables studied including education status of the vendors, markets location, type of vegetables, means of display, washed before display, washing source of water and market type. The findings of this study evidenced that consumption of raw vegetables possesses great risk of getting parasitic infections in Lower Dir and Peshawar districts, Pakistan. Instructing the sellers and the public about parasitic disease transfer and their hygiene can reduce the infection rate of parasites of human origin.


Os vegetais crus são a principal fonte de transmissão de formas infecciosas de parasitas internos patogênicos entre os seres humanos. Esta pesquisa foi realizada de abril a outubro de 2017 para avaliar a contaminação parasitária de vegetais vendidos nos principais mercados de vegetais nos distritos de Lower Dir e Peshawar, Paquistão. Oitocentos exemplares de diferentes vegetais foram adquiridos e embebidos em solução salina fisiológica, agitados em agitador mecânico por 20 minutos e processados pelo método de concentração por sedimentação. Os resultados revelaram que apenas 19,7% (n = 158/800) das hortaliças estavam contaminadas com uma ou várias espécies de parasitas. Ascaris lumbricoides (o verme redondo grande) 12,3% (n = 99/800) foi o patógeno mais comumente detectado e Taenia saginata (a tênia da carne) 1,62% (n = 13/800) foi o menos freqüentemente detectado. Curiosamente, valor de p significativo (p> 0,05 em IC de 95%) entre o número de examinados e contaminados para todas as variáveis estudadas incluindo escolaridade dos vendedores, localização dos mercados, tipo de vegetais, meios de exposição, lavado antes da exposição, fonte de lavagem de água e tipo de mercado. Os resultados deste estudo evidenciaram que o consumo de vegetais crus possui grande risco de contrair infecções parasitárias nos distritos de Lower Dir e Peshawar, no Paquistão. Instruir os vendedores e o público sobre a transferência de doenças parasitárias e sua higiene pode reduzir a taxa de infecção de parasitas de origem humana.


Asunto(s)
Humanos , Animales , Parásitos , Verduras/parasitología , Contaminación de Alimentos/análisis , Nematodos , Pakistán , Salud Pública , Parasitología de Alimentos
20.
Biotechnol Lett ; 43(9): 1735-1745, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34047865

RESUMEN

OBJECTIVE: To study the effect of the mutation in conserved G412E in Cct7p subunit of CCT complex on its cellular fate. RESULTS: TriC/CCT is a dynamic multimeric protein that assists in protein folding in an energy-dependent manner. A point mutation in the ATP binding pocket in the equatorial domain of the Cct7p subunit delays the doubling time. The cell size was twice the wild type, and the formation of protein aggregates suggests disturbed folding of the proteins. Upon growing in stressful conditions of arsenous acid and cadmium chloride, the mutant was lethal in As3+ but grew well in Cd2+ with 10.5 µg cadmium uptake mg-1 compared to the wild type. The increased expression of vacuole transporters YCF1 and BPT1 by ten-fold and two-fold in mutant indicates the metal transportation to the vacuole. CONCLUSION: CCT complex was vulnerable to the mutation in G412E in the Cct7p subunit of protein folding molecular machinery. Interestingly, already stressed cells provided robustness against oxidative stress and cadmium sequestration in the vacuole.


Asunto(s)
Transportadoras de Casetes de Unión a ATP/genética , Cloruro de Cadmio/farmacología , Chaperoninas/genética , Mutación Puntual , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/crecimiento & desarrollo , Arsenitos/farmacología , Arsenitos/uso terapéutico , Arsenitos/toxicidad , Chaperoninas/química , Perfilación de la Expresión Génica , Regulación Fúngica de la Expresión Génica/efectos de los fármacos , Viabilidad Microbiana/efectos de los fármacos , Modelos Moleculares , Conformación Proteica , Pliegue de Proteína , Saccharomyces cerevisiae/efectos de los fármacos , Saccharomyces cerevisiae/genética
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