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Transcription initiation is a vital step in the regulation of eukaryotic gene expression. It can be dysregulated in response to various cellular stressors which is associated with numerous human diseases including cancer. Transcription initiation is facilitated via many gene-specific trans-regulatory elements such as transcription factors, activators, and coactivators through their interactions with transcription pre-initiation complex (PIC). These trans-regulatory elements can uniquely facilitate PIC formation (hence, transcription initiation) in response to cellular nutrient stress. Cellular nutrient stress also regulates the activity of other pathways such as target of rapamycin (TOR) pathway. TOR pathway exhibits distinct regulatory mechanisms of transcriptional activation in response to stress. Like TOR pathway, the cell cycle regulatory pathway is also found to be linked to transcriptional regulation in response to cellular stress. Several transcription factors such as p53, C/EBP Homologous Protein (CHOP), activating transcription factor 6 (ATF6α), E2F, transforming growth factor (TGF)-ß, Adenomatous polyposis coli (APC), SMAD, and MYC have been implicated in regulation of transcription of target genes involved in cell cycle progression, apoptosis, and DNA damage repair pathways. Additionally, cellular metabolic and oxidative stressors have been found to regulate the activity of long non-coding RNAs (lncRNA). LncRNA regulates transcription by upregulating or downregulating the transcription regulatory proteins involved in metabolic and cell signaling pathways. Numerous human diseases, triggered by chronic cellular stressors, are associated with abnormal regulation of transcription. Hence, understanding these mechanisms would help unravel the molecular regulatory insights with potential therapeutic interventions. Therefore, here we emphasize the recent advances of regulation of eukaryotic transcription initiation in response to cellular stress.
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Estresse Fisiológico , Humanos , Estresse Fisiológico/genética , Regulação da Expressão Gênica , Iniciação da Transcrição Genética , Animais , Transdução de Sinais , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Serina-Treonina Quinases TOR/genéticaRESUMO
OBJECTIVES: Self-medication with antibiotics (SMA) contributes significantly to the emergence of antimicrobial resistance (AMR), especially in low-income countries including Bangladesh. This study aimed to generate evidence on the self-reported prevalence of antibiotic self-medication and its determinants among indigenous people residing in Bangladesh's Chittagong Hill Tracts (CHT) districts. DESIGN: This study used a cross-sectional design with data collected through a survey using a semi-structured questionnaire. SETTING: This study was conducted from late January to early July 2021; among different indigenous group populations aged 18 years or more olders residing in the three districts of CHT. PARTICIPANTS: A total of 1336 indigenous people residing in Bangladesh's CHT districts were included. PRIMARY OUTCOME AND EXPLANATORY VARIABLES: The primary outcome measure was SMA while explanatory variables were socio-demographic characteristics, health status of participants, and knowledge of antibiotics usage and its side effects. RESULTS: Among the study participants, more males (60.54%) than females (51.57%) reported using antibiotics. The SMA rate was high among individuals with education levels below secondary (over 50%) and those in the low-income group (55.19%). The most common diseases reported were cough, cold and fever, with azithromycin being the most frequently used antibiotic. Levels of education, family income, having a chronic illness and place of residence were found to be the significant predictors of having good knowledge of antibiotic use as found in the ordered logit model. Findings from a logistic regression model revealed that men had 1.6 times higher odds (adjusted OR (AOR) 1.57; 95% CI 1.12 to 2.19) of SMA than women. Participants with ≥US$893 per month family income had lowest odds (AOR 0.14; 95% CI 0.03 to 0.64) of SMA than those who earned Assuntos
Antibacterianos
, Povos Indígenas
, Humanos
, Feminino
, Masculino
, Antibacterianos/uso terapêutico
, Estudos Transversais
, Bangladesh
, Prevalência
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Objective: This study was conducted to validate polymerase chain reaction (PCR) as a confirmatory diagnostic tool to find out the presence and frequency of Streptococcus agalactiae (S. agalactiae) and Streptococcus dysgalactiae (S. dysgalactiae) in mastitic milk samples obtained from dairy cows in the southern region of Bangladesh. Materials and Methods: A total of 196 samples of bovine milk were collected from various dairy farms in the Chattogram metropolitan area of the southern part of Bangladesh. DNA extracted from isolates obtained by culturing California mastitis test (CMT)-positive mastitic milk samples (n = 146) on 5% sheep blood agar was used as a template for PCR. Two sets of specific primers based on the 16S rRNA gene were used to discriminate between S. agalactiae and S. dysgalactiae. Four PCR products were subjected to sequencing, followed by phylogenetic analysis. Results: The PCR analyses revealed that out of the 146 CMT-positive milk samples tested, 29 samples were positive for S. agalactiae (19.86%), while 26 samples were positive for S. dysgalactiae (17.81%). Further sequence analysis of the corresponding PCR products and bioinformatics analysis verified the results. Conclusion: The study proves the efficiency of PCR as a useful diagnostic approach to determine the presence and prevalence of S. agalactiae and S. dysgalactiae in mastitic milk samples obtained from dairy cows.
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OBJECTIVES: The SOCS1 gene is frequently mutated in primary Diffuse Large B-Cell Lymphoma (DLBCL) patients and is associated with a reduced survival rate. Using various computational techniques, the current study aims to identify Single Nucleotide Polymorphisms (SNPs) in the SOCS1 gene that are associated with the mortality rate of DLBCL patients. This study also evaluates the effects of SNPs on the structural instability of the SOCS1 protein in DLBCL patient. METHODS: The cBioPortal webserver was used for mutations and determining how the SNP mutations affect the SOCS1 protein with various algorithms (PolyPhen-2.0, Provean, PhD-SNPg, SNPs&GO, SIFT, FATHMM, Predict SNP and SNAP). Five webservers (I-Mutant 2.0, MUpro, mCSM, DUET and SDM) were used for protein instability and the conserved status and were also predicted through different tools (ConSurf, Expasy, SOMPA). Lastly, MD simulations were run on the two chosen mutations (S116N and V128G) using GROMACS 5.0.1 to study how the mutations change the structure of SOCS1. RESULTS: Among the 93 SOCS1 mutations detected in DLBCL patients, nine mutations were found to have a detrimental effect (damaging/deleterious/pathogenic/altered) on the SOCS1 protein. All the nine selected mutations are in the conserved region and four are on the extended strand site, four on the random coil site and one on the alpha helix position of the secondary protein structure. After anticipating the structural effects of these nine mutations, two were chosen (S116N and V128G) based on mutational frequency, location within the protein, structural effect (primary, secondary and tertiary) on stability and conservation status within the SOCS1 protein. The simulation of a 50 ns time interval revealed that the Rg value of S116N (2.17 nm) is higher than that of WT (1.98 nm), indicating a loss of structural compactness. In the case of the RMSD value, this mutated type (V128G) shows more deviation (1.54 nm) in comparison to the wild-type (2.14 nm) and another mutant type (S116N) (2.12 nm). The average RMSF values of wild-type and mutant types (V128G and S116N) were 0.88 nm, 0.49 nm, and 0.93 nm, respectively. The RMSF result shows that the mutant V128G structure is more stable than the wild-type and mutant S116N structures. CONCLUSION: Based on all these computational predictions, this study finds that certain mutations, particularly S116N, have a destabilising and robust effect on the SOCS1 protein. These results can be used to learn more about the importance of SOCS1 mutations in DLBCL patients and to develop new ways to treat DLBCL.
Assuntos
Linfoma Difuso de Grandes Células B , Proteínas Supressoras da Sinalização de Citocina , Humanos , Proteína 1 Supressora da Sinalização de Citocina/genética , Mutação , Proteínas Supressoras da Sinalização de Citocina/genética , Taxa de Mutação , Linfoma Difuso de Grandes Células B/genética , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Background: Self-medication is a global phenomenon and a potential contributor to negative health consequences on human health including emergence of antibiotic drug resistance globally. Objective: The primary objective of this study was to estimate the prevalence and determinants of self-medication in Thimphu, Bhutan and Chattogram, Bangladesh, two neighbouring South Asian country. Methodology: A community-based cross-sectional study was conducted in the city of Thimphu, Bhutan and Chattogram, Bangladesh. A pre-tested and semi-structured questionnaire was used to collect information on socio-demographic characteristics, health status and self-medication practices in the previous year. Results: Out of the 998 recruited participants, 61.8% (170/275) from Thimphu and 41.5% (300/723) from Chattogram reported self-medication practices in last year of interview. In Thimphu, eye/ear infection (90.9%), fever (84.9%), headache (80.5%) and cough and cold (78.2%) were the major illnesses reported for self-medication, whereas in Chattogram people mostly self-medicated for skin disorder (74.4%), diarrhoeal illness (59.1%) and eye/ear infection (48.1%). Knowledge on side-effects of the drugs taken for self-medication was comparatively higher in Thimphu than in Chattogram. Both in Thimphu and Chattogram, higher odds of self-medication were found for common illnesses with adjusted OR 7.8; 95% CI 3.3-18.4 and adjusted OR 2.0; 95% CI 1.4-2.8, respectively in Thimphu and Chattogram. Conclusion: Self-medication was found to be substantially high in both the cities, however, rate of self-medication was higher in Thimphu compared to Chattogram. Knowledge and awareness raising about harmful effect of self-medication and effective regulation over selling of prescription medication in pharmacies should be strengthened in both countries.
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BACKGROUND: In developing countries like Bangladesh, self-medication has become a predicament associated with health risks and clinical complications. To date, no studies have been conducted on the practice of self-medication among the indigenous population living in Chittagong Hill Tract (CHT). OBJECTIVES: This study was aimed to determine the prevalence of self-medication and analyzing the factors associated with it among the indigenous population in CHT. METHODS: This cross-sectional study was conducted from late October to early December 2020; among different indigenous group populations residing in the three districts of CHT aged 18 or more. A pre-tested and semi-structured questionnaire was developed to collect data on socio-demographic characteristics, health status, frequency of self-medication, reasons for self-medication in last one year, as well as other variables. Multivariate logistic regression was performed to assess associated factors with self-medication. RESULTS: A total of 1350 people from different indigenous populations were interviewed, among whom 49.9% practiced self-medication. The rate of self-prescribed antibiotics usage (80.9%) was significantly higher compared to other drugs. Self-prescribed medications were mostly used for diarrhea and food poisoning (60.6%), cough, cold and fever (51.4%), and headache (51.4%). A common source of self-prescribed medicines was community or retail pharmacy and the most reported reason for self-prescribed medication was the long-distance of healthcare facilities from home. CONCLUSION: The prevalence of self-medication is substantially high among indigenous people and the effect is alarming. Particular concern is the misuse of antibiotics and analgesic drugs. Increasing awareness among the population of the negative effect of self-medication and implementation of proper policies and actions are urgently needed to prevent self-medication among indigenous population in Bangladesh.
Assuntos
Antibacterianos , Automedicação , Bangladesh/epidemiologia , Estudos Transversais , Humanos , Fatores de RiscoRESUMO
The incorporation of waste materials generated in many industries has been actively advocated for in the construction industry, since they have the capacity to lessen the pollution on dumpsites, mitigate environmental resource consumption, and establish a sustainable environment. This research has been conducted to determine the influence of different rice husk ash (RHA) concentrations on the fresh and mechanical properties of high-strength concrete. RHA was employed to partially replace the cement at 5%, 10%, 15%, and 20% by weight. Fresh properties, such as slump, compacting factor, density, and surface absorption, were determined. In contrast, its mechanical properties, such as compressive strength, splitting tensile strength and flexural strength, were assessed after 7, 28, and 60 days. In addition, the microstructural evaluation, initial surface absorption test, = environmental impact, and cost-benefit analysis were evaluated. The results show that the incorporation of RHA reduces the workability of fresh mixes, while enhancing their compressive, splitting, and flexural strength up to 7.16%, 7.03%, and 3.82%, respectively. Moreover, incorporating 10% of RHA provides the highest compressive strength, splitting tensile, and flexural strength, with an improved initial surface absorption and microstructural evaluation and greater eco-strength efficiencies. Finally, a relatively lower CO2-eq (equivalent to kg CO2) per MPa for RHA concrete indicates the significant positive impact due to the reduced Global Warming Potential (GWP). Thus, the current findings demonstrated that RHA can be used in the concrete industry as a possible revenue source for developing sustainable concretes with high performance.
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Counts for SARS-CoV-2 associated infections and fatalities are on the rise globally even in regions which contained the spread momentarily. The pattern of infections has been found to be controlled by the distinctive selection pressures exerted by fluctuating environmental nature and hosts. A total of 410 whole-genome sequences submitted by the South Asian countries were retrieved from the GISAID database and analyzed to assess the impact and pattern of mutations in this region. Most common and frequent mutations in the South Asian countries are 241C > T, 3037C > T, 14408C > T, and 23403A > G and about 85% SNPs are localized in ORF1ab, spike protein, and nucleocapsid. Among the identified mutations, the proportion of missense type (54.17%) was highest, followed by the synonymous (41.66%) and the non-coding types (4.17%). While analyzing transmission source in terms of geolocation, the largest clustered group from the South Asian countries was based on the G-clade (D614G) (81.7%; 335/410 samples), tracing the inception and transmission of SARS-CoV-2 infections in the South Asian countries from European regions. Phylogenetic analysis also revealed that the South Asian strains are highly related to the South American and European strains. We found that G-clade mutations are more prevalent (96.19%) in the samples of Bangladesh which were also prevalent in the European isolates. Surprisingly, one missense mutation (1163A > T) in ORF1ab gene became dominant only in Bangladesh (78.8%), which led to debates regarding effects on the pathogenicity and transmissibility of the virus. Overall, the findings of this study highlight the frequently mutated SARS-CoV-2 variants among the COVID-19 patients in the South Asian countries which might ease containment of the disease in this region through investigating the virulence reducing factors as the identified mutations are strongly correlated with low infection and mortality rate.
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OBJECTIVES: This study aimed to analyze the epidemiological and clinical characteristics of COVID-19 cases and investigate risk factors including comorbidities and age in relation with the clinical aftermath of COVID-19 in ICU admitted cases in Bangladesh. METHODS: In this retrospective study, epidemiological and clinical characteristics, complications, laboratory results, and clinical management of the patients were studied from data obtained from 168 individuals diagnosed with an advanced prognosis of COVID-19 admitted in two hospitals in Bangladesh. RESULTS: Individuals in the study sample contracted COVID-19 through community transmission. 56.5% (n = 95) cases died in intensive care units (ICU) during the study period. The median age was 56 years and 79.2% (n = 134) were male. Typical clinical manifestation included Acute respiratory distress syndrome (ARDS) related complications (79.2%), fever (54.2%) and cough (25.6%) while diabetes mellitus (52.4%), hypertension (41.1%) and heart diseases (16.7%) were the conventional comorbidities. Clinical outcomes were detrimental due to comorbidities rather than age and comorbid individuals over 50 were at more risk. In the sample, oxygen saturation was low (< 95% SpO2) in 135 patients (80.4%) and 158 (93.4%) patients received supplemental oxygen. Identical biochemical parameters were found in both deceased and surviving cases. Administration of antiviral drug Remdesivir and the glucocorticoid, Dexamethasone increased the proportion of surviving patients slightly. CONCLUSIONS: Susceptibility to developing critical illness due to COVID-19 was found more in comorbid males. These atypical patients require more clinical attention from the prospect of controlling mortality rate in Bangladesh.
Assuntos
COVID-19/terapia , Estado Terminal , Gerenciamento Clínico , Unidades de Terapia Intensiva , Bangladesh/epidemiologia , COVID-19/epidemiologia , Comorbidade , Feminino , Humanos , Masculino , Avaliação de Resultados em Cuidados de Saúde , Respiração Artificial , Estudos Retrospectivos , SARS-CoV-2RESUMO
BACKGROUND AND AIMS: Diabetes mellitus is highly prevalent among critical cases of coronavirus disease 2019 (COVID-19) with poor outcomes. This study aimed to describe the clinical characteristics and outcomes of COVID-19 patients with diabetes, admitted in the intensive care unit (ICU) of the southern region of Bangladesh. METHODS: Epidemiological, clinical, laboratory, treatments, complications, and clinical outcomes data were extracted from electronic medical records of 168 COVID-19 patients admitted into ICU of two COVID-19 dedicated hospitals of Chattogram, Bangladesh and compared between diabetes (n = 88) and non-diabetes (n = 80) groups. RESULTS: The prevalence of diabetes was high among 51-70 years old patients. All the diabetic patients had at least one other comorbidity, with a significantly higher incidence of hypertension (53.4% vs 27.5%, P < 0.05). Prevalence of male patients (74/88; 84.1%) was slightly higher among diabetic patients than the non-diabetic patients (60/80; 75%). Even though not significant, Kaplan-Meier survival curve showed that COVID-19 patients with diabetes had a shorter overall survival time than those without diabetes. In subgroup analysis, diabetic patients were classified into insulin-requiring and non-insulin-requiring groups based on their requirement of insulin during the stay in ICU. COVID-19 infected diabetic patients requiring insulin have high risk of disease progression and shorter survival time than the non-insulin required group. CONCLUSIONS: Diabetes is an independent risk factor for the poor prognosis of COVID-19. More attention should be paid to the prevention and prompt treatment of diabetic patients, to maintain good glycaemic control especially those who require insulin therapy.
Assuntos
COVID-19/epidemiologia , COVID-19/terapia , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/terapia , Unidades de Terapia Intensiva/tendências , Admissão do Paciente/tendências , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bangladesh/epidemiologia , COVID-19/diagnóstico , Criança , Estudos de Coortes , Diabetes Mellitus/diagnóstico , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Hipertensão/terapia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Averrhoa bilimbi, Gymnema sylvestre and Capsicum frutescens are medicinal plants commonly used as traditional medicine for the treatment of various diseases. The present study was designed to investigate the antioxidant activities of Ethanolic extract of A. bilimbi, G. sylvestre and C. frutescens. MATERIALS AND METHODS: The antioxidant activity of the extracts were evaluated using total phenolic and flavonoid contents, ferric reducing power and the free radical scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH). RESULTS: Total phenolic and flavonoid contents were higher in G. sylvestre (53.63636 ± 0.454545 mg/g gallic acid equivalent) and C. frutescens (26.66667 ± 2.081666 mg/g quercetin equivalent) respectively. Reducing power of the crude ethanol extracts increased with the concentrations of the extracts and all the extracts showed moderate free radical scavenging activity against DPPH. The plant extract displayed moderate phenolic and flavonoid contents compared to gallic acid and quercetin equivalent respectively, whereas also exhibited significant scavenging of DPPH radical and reducing power compared with ascorbic acid as standard. CONCLUSION: Our study suggests that G. sylvestre has significant antioxidant activity. The antioxidant compound of this plant might be a therapeutic candidate against oxidative stress related diseases. Different sub-fraction of A. bilimbi and C. frutescens should be studied further to assess the effect. Further study is necessary for isolation and characterization of the active antioxidant agents for better treatment.
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PURPOSE: Streptococcus sanguinis is a Gram-positive, facultative aerobic bacterium that is a member of the viridans streptococcus group. It is found in human mouths in dental plaque, which accounts for both dental cavities and bacterial endocarditis, and which entails a mortality rate of 25%. Although a range of remedial mediators have been found to control this organism, the effectiveness of agents such as penicillin, amoxicillin, trimethoprim-sulfamethoxazole, and erythromycin, was observed. The emphasis of this investigation was on finding substitute and efficient remedial approaches for the total destruction of this bacterium. MATERIALS AND METHODS: In this computational study, various databases and online software were used to ascertain some specific targets of S. sanguinis. Particularly, the Kyoto Encyclopedia of Genes and Genomes databases were applied to determine human nonhomologous proteins, as well as the metabolic pathways involved with those proteins. Different software such as Phyre2, CastP, DoGSiteScorer, the Protein Function Predictor server, and STRING were utilized to evaluate the probable active drug binding site with its known function and protein-protein interaction. RESULTS: In this study, among 218 essential proteins of this pathogenic bacterium, 81 nonhomologous proteins were accrued, and 15 proteins that are unique in several metabolic pathways of S. sanguinis were isolated through metabolic pathway analysis. Furthermore, four essentially membrane-bound unique proteins that are involved in distinct metabolic pathways were revealed by this research. Active sites and druggable pockets of these selected proteins were investigated with bioinformatic techniques. In addition, this study also mentions the activity of those proteins, as well as their interactions with the other proteins. CONCLUSION: Our findings helped to identify the type of protein to be considered as an efficient drug target. This study will pave the way for researchers to develop and discover more effective and specific therapeutic agents against S. sanguinis.
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Bovine collagen alpha-1 is a naturally occurring extracellular matrix protein found in tendons and other connective tissues. It plays a vital role in cell growth, differentiation, attachment, and migration. Recent findings have established that collagen alpha-1 is involved in osteogenesis imperfecta phenotype in cattle but deep information about other members of this large family is not available so far. So with a view to finding a new edge and attempt to figure out a correlation among the well attributed Bovine alpha-1 collagen sequences are executed and analyzed. To do so, comparative analysis among the 28 members of collagen family has been carried out using Computational tools. Consequently, based on the physico-chemical, secondary structural, functional and phylogenetic classifications, we have selected collagen 12, 14 and 20 as targets for pathological conditions. These proteins belong to the FACIT family and significantly showed low glycine and proline content, high instability and aliphatic index. Moreover, FACIT family collagens contain multiple triple helical domains and being members of the FACIT family, bovine collagen 12, 14, 20 do not form fibrils by themselves but they are associated to collagen 1 associated fibrils. These collagen molecules might be crucial candidates to detect and understand the process of matrix remodeling in diseases especially in the arena of cellular compartments.