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BACKGROUND: The Basic Public Health Service (BPHS), a recently announced free healthcare program, aims to combat the most prevalent Noncommunicable Disease-"Hypertension" (HTN)-and its risk factors on a nationwide scale. In China, there is a rife that HTN less impacts women during their lifetime. We, therefore, aimed to evaluate the sex disparity in hypertension patients with comorbidities among south-west Chinese and the contribution of BPHS to address that concern. METHODS: We have opted for a multistage stratified random sampling method to enroll hypertensive patients of 35 years and older, divided them into BPHS and non-BPHS groups. We assessed the sex disparity in HTN patients with four major comorbidities- Dyslipidemia, Diabetes Mellitus (DM), Cardiovascular Disease (CVD), and Chronic Kidney Disease (CKD), and descriptive data were compiled. Odds ratios from logistic regression models estimated the effectiveness of BPHS in the management of HTN with comorbidities. RESULTS: Among 1521 hypertensive patients,1011(66.5%) were managed in the BPHS group. The proportion of patients who had at least one comorbidity was 70.7% (95% confidence interval [CI]: 66.3-76.8%), patients aged 65 years and older were more likely to have coexisting comorbidities. Participants who received the BPHS showed significant blood pressure (BP) control with two comorbidities (odds ratio [OR] = 2.414, 95% CI: 1.276-4.570), three or more (OR = 5.500, 95%CI: 1.174-25.756). Patients with dyslipidemia and DM also benefited from BPHS in controlling BP (OR = 2.169, 95% CI: 1.430-3.289) and (OR = 2.785, 95%CI: 1.242-6.246), respectively. In certain high-income urban survey centers, there was sex differences in the HTN management provided by BPHS, with men having better BP control rates than women. CONCLUSIONS: Perhaps this is the first study in China to succinctly show the effectiveness and sex disparity regarding "management of hypertensive comorbidities". This supports that the BPHS program plays a pivotal role in controlling BP, therefore should recommend the national healthcare system to give women a foremost priority in BPHS, especially to those from low-socioeconomic and low-scientific literacy regions.
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Diabetes Mellitus , Dislipidemias , Hipertensão , Humanos , Feminino , Masculino , Pressão Sanguínea , China/epidemiologia , Comorbidade , Hipertensão/epidemiologia , Diabetes Mellitus/epidemiologia , Fatores de Risco , Serviços de SaúdeRESUMO
A hyperactive tumour microenvironment (TME) drives unrestricted cancer cell survival, drug resistance, and metastasis in ovarian carcinoma (OC). However, therapeutic targets within the TME for OC remain elusive, and efficient methods to quantify TME activity are still limited. Herein, we employed an integrated bioinformatics approach to determine which immune-related genes (IRGs) modulate the TME and further assess their potential theragnostic (therapeutic + diagnostic) significance in OC progression. Using a robust approach, we developed a predictive risk model to retrospectively examine the clinicopathological parameters of OC patients from The Cancer Genome Atlas (TCGA) database. The validity of the prognostic model was confirmed with data from the International Cancer Genome Consortium (ICGC) cohort. Our approach identified nine IRGs, AKT2, FGF7, FOS, IL27RA, LRP1, OBP2A, PAEP, PDGFRA, and PI3, that form a prognostic model in OC progression, distinguishing patients with significantly better clinical outcomes in the low-risk group. We validated this model as an independent prognostic indicator and demonstrated enhanced prognostic significance when used alongside clinical nomograms for accurate prediction. Elevated LRP1 expression, which indicates poor prognosis in bladder cancer (BLCA), OC, low-grade gliomas (LGG), and glioblastoma (GBM), was also associated with immune infiltration in several other cancers. Significant correlations with immune checkpoint genes (ICGs) highlight the potential importance of LRP1 as a biomarker and therapeutic target. Furthermore, gene set enrichment analysis highlighted LRP1's involvement in metabolism-related pathways, supporting its prognostic and therapeutic relevance also in BLCA, OC, low-grade gliomas (LGG), GBM, kidney cancer, OC, BLCA, kidney renal clear cell carcinoma (KIRC), stomach adenocarcinoma (STAD), and stomach and oesophageal carcinoma (STES). Our study has generated a novel signature of nine IRGs within the TME across cancers, that could serve as potential prognostic predictors and provide a valuable resource to improve the prognosis of OC.
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Biomarcadores Tumorais , Biologia Computacional , Regulação Neoplásica da Expressão Gênica , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade , Neoplasias Ovarianas , Microambiente Tumoral , Humanos , Feminino , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/mortalidade , Prognóstico , Biologia Computacional/métodos , Microambiente Tumoral/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismoRESUMO
Sustainable urban development is crucial for managing natural resources and mitigating environmental impacts induced by rapid urbanization. This study demonstrates an integrated framework using machine learning-based urban analytics techniques to evaluate spatiotemporal urban expansion in Saudi Arabia (1987-2022) and quantify impacts on leading land, water, and air-related environmental parameters (EPs). Remote sensing and statistical techniques were applied to estimate vegetation health, built-up area, impervious surface, water bodies, soil characteristics, thermal comfort, air pollutants (PM2.5, CH4, CO, NO2, SO2), and nighttime light EPs. Regression assessment and Principal Component Analysis (PCA) were applied to assess the relationships between urban expansion and EPs. The findings highlight the substantial growth of urban areas (0.067%-0.14%), a decline in soil moisture (16%-14%), water bodies (60%-22%), a nationwide increase of PM2.5 (44 µg/m3 to 73 µg/m3) and night light intensity (0.166-9.670) concentrations resulting in significant impacts on land, water, and air quality parameters. PCA showed vegetation cover, soil moisture, thermal comfort, PM2.5, and NO2 are highly impacted by urban expansion compared to other EPs. The results highlight the need for effective and sustainable interventions to mitigate environmental impacts using green innovations and urban development by applying mixed-use development, green space preservation, green building technologies, and implementing renewable energy approaches. The framework recommended for environmental management in this study provides a robust foundation for evidence-based policies and adaptive management practices that balance economic progress and environmental sustainability. It will also help policymakers and urban planners in making informed decisions and promoting resilient urban growth.
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Monitoramento Ambiental , Urbanização , Monitoramento Ambiental/métodos , Arábia Saudita , Dióxido de Nitrogênio , Solo , Material Particulado , Água , CidadesRESUMO
Cyclophilin D (CypD) can stimulate the opening of the membrane permeability transition pore (mPTP) and regulate mitochondrial function. Whole-body knockout of CypD improved high fat diet-induced hepatic steatosis by reducing the excess opening of the mPTP and lipid deposition. However, whether CypD significantly ameliorates nonalcoholic steatohepatitis (NASH) has not been studied. Therefore, we established liver-specific CypD knockout (CypD LKO) mice and fed a HFHC diet to induce NASH. Compared with the wild-type mice, the CypD LKO not only showed improved lipid deposition and insulin resistance by increasing fatty acid oxidation but also displayed ameliorated hepatic inflammation, although the symptoms of fibrosis in the NASH model were not significantly improved. In addition, we used bile duct ligation (BDL) or a 0.1% 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet to induce cholestatic disease and found that CypD LKO had also no significant effect on acute fibrosis. Thus, CypD LKO can inhibit the progression of early NASH by ameliorating steatosis and inflammatory symptoms. These results suggest a new strategy for the treatment of early NASH.
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Fígado Gorduroso/metabolismo , Hepatócitos/metabolismo , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Peptidil-Prolil Isomerase F/deficiência , Peptidil-Prolil Isomerase F/metabolismo , Animais , Ductos Biliares , Colestase/metabolismo , Dieta Hiperlipídica , Teste de Tolerância a Glucose , Inflamação , Metabolismo dos Lipídeos , Lipidômica , Lipídeos/química , Masculino , Camundongos , Camundongos Knockout , Mitocôndrias/metabolismo , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Poro de Transição de Permeabilidade Mitocondrial , RNA-SeqRESUMO
PURPOSE: This review aims to provide a precise perceptive of the insulin-degrading enzyme (IDE) and its relationship to type 2 diabetes (T2D), Alzheimer's disease (AD), obesity, and cardiovascular diseases. The purpose of the current study was to provide clear idea of treating prevalent diseases such as T2D, and AD by molecular pharmacological therapeutics rather than conventional medicinal therapy. METHODS: To achieve the aims, molecular docking was performed using several softwares such as LIGPLOT+, Python, and Protein-Ligand Interaction Profiler with corresponding tools. RESULTS: The IDE is a large zinc-metalloprotease that breakdown numerous pathophysiologically important extracellular substrates, comprising amyloid ß-protein (Aß) and insulin. Recent studies demonstrated that dysregulation of IDE leads to develop AD and T2D. Specifically, IDE regulates circulating insulin in a variety of organs via a degradation-dependent clearance mechanism. IDE is unique because it was subjected to allosteric activation and mediated via an oligomer structure. CONCLUSION: In this review, we summarised the factors that modulate insulin reformation by IDE and interaction of IDE and some recent reports on IDE inhibitors against AD and T2D. We also highlighted the latest signs of progress of the function of IDE and challenges in advancing IDE- targetted therapies against T2D and AD.
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Doença de Alzheimer , Diabetes Mellitus Tipo 2 , Insulisina , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/metabolismo , Doença Crônica , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Insulina/metabolismo , Insulisina/química , Insulisina/metabolismo , Insulisina/uso terapêutico , Simulação de Acoplamento MolecularRESUMO
Levees protect floodplain areas from frequent flooding, but they can paradoxically contribute to more severe flood losses. The construction or reinforcement of levees can attract more assets and people in flood-prone area, thereby increasing the potential flood damage when levees eventually fail. Moreover, structural protection measures can generate a sense of complacency, which can reduce preparedness, thereby increasing flood mortality rates. We explore these phenomena in the Jamuna River floodplain in Bangladesh. In this study area, different levels of flood protection have co-existed alongside each other since the 1960s, with a levee being constructed only on the right bank and its maintenance being assured only in certain places. Primary and secondary data on population density, human settlements, and flood fatalities were collected to carry out a comparative analysis of two urban areas and two rural areas with different flood protection levels. We found that the higher the level of flood protection, the higher the increase of population density over the past decades as well as the number of assets exposed to flooding. Our results also show that flood mortality rates associated with the 2017 flooding in Bangladesh were lower in the areas with lower protection level. This empirical analysis of the unintended consequences of structural flood protection is relevant for the making of sustainable policies of disaster risk reduction and adaptation to climate change in rapidly changing environments.
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The response of broiler chickens to 3 levels of sunflower meal and 2 levels of NSP-ase enzyme combination (with and without) was investigated in 3 × 2 factorial arrangement under complete randomized design (CRD). A total of 240 Hubbard broiler chicks were fed on practical mash diets having 2950 kcal of ME and 21% CP from 1 to 42 days of age. The BW gain was not significantly reduced when 25% SFM was added in the diets during 1 to 42 days of age. Supplementation of NSP-ase in broiler diets (day 1-42 overall) demonstrated non-significant differences (p < 0.05) across the treatments in terms of FI and BWG. The difference in feed:gain at 15% or 20% SFM was observed to be non-significant. Replacement of SBM with SFM or inclusion of SFM at higher level (25%) increased/deteriorated FCR. The addition of exogenous NSP-ase showed a significant improvement (p < 0.01) in feed:gain. The improvement was clearly demonstrated when SFM was added to the experimental diet at 15% or even 20%. Supplementation of NSP-ase at the 25% inclusion level could not, however, sustain the beneficial effect, which was possibly due to excessively high dietary CF. No difference was noted across the treatments regarding carcass response. Relative gizzard weight and intestinal weight were observed to be improved in birds consuming higher levels of SFM (p = 0.00). The digestibility of CF was observed to improve when SFM was used at 20% and 25% in the diets. No improvement in the digestibility of CF was observed with NSP-ase supplementation, which meant other factors were clearly involved. Supplementation of NSP-ase improved FCR up to 20% SFM. At 25% SFM, no improvement in the digestibility of CF was observed with NSP-ase supplementation.
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Ração Animal/análise , Galinhas/fisiologia , Dieta/veterinária , Suplementos Nutricionais , Enzimas/administração & dosagem , Helianthus , Fenômenos Fisiológicos da Nutrição Animal , Animais , Digestão/efeitos dos fármacos , Enzimas/metabolismo , Enzimas/farmacologia , SementesRESUMO
Landslides pose a severe threat to people, buildings, and infrastructure. The rugged terrain of the Chattogram Hill Tract region in southeastern Bangladesh frequently experiences landslides, particularly during rainy seasons. This study provides a comparative analysis of innovative machine learning (ML) algorithms used for the purpose of landslide susceptibility (LS) mapping for the Khagrachari district of Bangladesh. The dataset for this study comprises 15 landslide conditioning factors and 127 landslide inventory points. The landslide inventory points included 71 landslide and 56 non-landslide points. Then, the data were split randomly into training data (70%) and testing data (30%). Three ML algorithms, namely random forest (RF), boosted regression trees (BRT), and k-nearest neighbor (KNN), were utilized to evaluate the LS zone. The models were validated using the area under the curve (AUC), overall accuracy, precision, and recall. Based on the AUC value, the BRT model demonstrated the highest performance with a value of 0.95, while the AUC values for RF and KNN were 0.91 and 0.86, respectively. Besides, overall accuracy, precision, and recall values (0.82, 0.81, and 0.86) also indicated BRT as the most effective model. The results showed that maximum rainfall and elevation were the most influential factors for both BRT and RF models. This research provides valuable insight into understanding the LS areas in Khagrachari, aiding in informed decision-making regarding landslide-related concerns in the region, and can be applied to the broader scale to develop effective planning and mitigation strategies for comprehensive disaster management and natural hazard response.
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In this study, different stacking orders of carbon-jute fiber mats were used to fabricate the composites and hybrids. The impact of different stacking orientations on mechanical properties was investigated experimentally. The experimental results were verified by finite element analysis (FEA). In addition, the impact of the fiber orientation on the loading direction was also investigated. Four layers of fabrics were piled to fabricate the composites by hand-layup with the cold press process. A NaCl solution was used to create a corrosive medium (pH 8), and the composites and hybrids were immersed in that medium, and their mechanical properties were compared. In this research, it has been found that the laminates with the stacking sequence of type-C (C/J/J/C) show the best result among other composites. Jute composites where all the fibers are in the loading direction possess a high strain compared with the other composites and hybrids. On the scanning electron microscope (SEM) image, delamination, buckling of fiber, fiber pullout, and voids were observed. In addition, the kinetics of the diffusion mechanism were also investigated, and it was found from the experimental results that the composites and hybrids immersed in pH 8 absorbed water via Fickian diffusion.
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Assessing the quality of fuel is essential to comprehend its impact on the environment and human health. In this study, the evaluation of fuel quality standards at the consumer level was conducted by analyzing the motor fuels in Khulna, Bangladesh. A total of 32 samples of petrol (regular gasoline), and octane (premium gasoline) were collected from the fuel stations in the Khulna City Corporation area and analyzed with an FTIR-Fuel Analyzer. Fuel properties, such as research octane number (RON), motor octane number (MON), ethanol content, olefins content, and oxygen content were analyzed. For petrol, the average RON, MON, olefins, and oxygen content were 95.34, 85.70, 8.23 %v/v, and 0.78 %m/m, respectively, and for octane, they were 96.96, 85.39, 1.25 %v/v, and 0.09 %m/m, respectively. Almost all of these parameters complied with both Bangladesh standard and Euro 5 fuel specifications, and those that did not comply were very close to their standard values. However, benzene concentration, which was not specified in Bangladesh Standard, was the most alarming metric for octane since none of the samples matched the Euro 5 fuel specifications of the maximum concentration of 1 %v/v benzene; on average it was 3.70 %v/v. Although petrol benzene content (average 1.50 %v/v) was not as bad as it was for octane, it was still nowhere near good enough, with only 25% of the samples within the recommended level among the studied sample. This information holds significance in establishing the fuel profile and facilitating the identification of distinct samples linked to adulteration. Therefore, the analysis of motor fuel qualities is essential for maintaining the environment, human health, and the economy of a country.
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BACKGROUND: Brown fat is known to provide non-shivering thermogenesis through mitochondrial uncoupling mediated by uncoupling protein 1 (UCP1). Non-shivering is not dependent on UCP2, UCP4, and BMCP1/UCP5 genes, which are distinct from UCP1 in a way that they are not constitutive uncouplers. Although they are susceptible to free fatty acid and free radical activation, their functioning has a significant impact on the performance of neurons. METHODOLOGY: Using subject-specific keywords (Adipose tissue; Adipocytes; Mitochondria; Obesity; Thermogenesis; UCP's in Neurodegeneration; Alzheimer's disease; Parkinson's disease), research articles and reviews were retrieved from Web of Science, ScienceDirect, Google Scholar, and PubMed. This article includespublications published between 2018 and 2023. The drugs that upregulate UCP1 are included in the study while the drugs that do not impact UCP1 are were not included. RESULTS: Neuronal UCPs have a direct impact on synaptic plasticity, neurodegenerative processes, and neurotransmission, by modulating calcium flux, mitochondrial biogenesis, local temperature, and free radical generation. Numerous significant advances in the study of neuronal UCPs and neuroprotection are still to be made. Identification of the tissue-dependent effects of UCPs is essential first. Pharmacologically targeting neuronal UCPs is a key strategy for preventing both neurodegenerative diseases and physiological aging. Given that UCP2 has activities that are tissue-specific, it will be essential to develop treatments without harmful side effects. The triggering of UCPs by CoQ, an essential cofactor, produces nigral mitochondrial uncoupling, reduces MPTP-induced toxicity, and may even decrease the course of Parkinson's disease, according to early indications. CONCLUSION: Herein, we explore the potential of UCP1 as a therapeutic target for treating obesity, neurodegenerative diseases as well as a potential activator of both synthetic and natural drugs. A deeper knowledge of synaptic signaling and neurodegeneration may pave the way to new discoveries regarding the functioning and controlling of these genes.
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Tecido Adiposo Marrom , Doenças Neurodegenerativas , Obesidade , Termogênese , Proteína Desacopladora 1 , Humanos , Termogênese/efeitos dos fármacos , Obesidade/tratamento farmacológico , Doenças Neurodegenerativas/tratamento farmacológico , Proteína Desacopladora 1/metabolismo , Proteína Desacopladora 1/genética , Animais , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Marrom/metabolismo , Mitocôndrias/efeitos dos fármacos , Epigênese Genética/efeitos dos fármacos , Produtos Biológicos/farmacologiaRESUMO
SARS-CoV-2 is a highly contagious pathogen that predominantly caused the COVID-19 pandemic. The persistent effects of COVID-19 are defined as an inflammatory or host response to the virus that begins four weeks after initial infection and persists for an undetermined length of time. Chronic effects are more harmful than acute ones thus, this review explored the long-term effects of the virus on various human organs, including the pulmonary, cardiovascular, and neurological, reproductive, gastrointestinal, musculoskeletal, endocrine, and lymphoid systems and found that SARS-CoV-2 adversely affects these organs of older adults. Regarding diagnosis, the RT-PCR is a gold standard method of diagnosing COVID-19; however, it requires specialized equipment and personnel for performing assays and a long time for results production. Therefore, to overcome these limitations, artificial intelligence employed in imaging and microfluidics technologies is the most promising in diagnosing COVID-19. Pharmacological and non-pharmacological strategies are the most effective treatment for reducing the persistent impacts of COVID-19 by providing immunity to post-COVID-19 patients by reducing cytokine release syndrome, improving the T cell response, and increasing the circulation of activated natural killer and CD8 T cells in blood and tissues, which ultimately reduces fever, nausea, fatigue, and muscle weakness and pain. Vaccines such as inactivated viral, live attenuated viral, protein subunit, viral vectored, mRNA, DNA, or nanoparticle vaccines significantly reduce the adverse long-term virus effects in post-COVID-19 patients; however, no vaccine was reported to provide lifetime protection against COVID-19; consequently, protective measures such as physical separation, mask use, and hand cleansing are promising strategies. This review provides a comprehensive knowledge of the persistent effects of COVID-19 on people of varying ages, as well as diagnosis, treatment, vaccination, and future preventative measures against the spread of SARS-CoV-2.
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Obesity initiates numerous diseases like cardiovascular, metabolic, and type 2 diabetes, and obesity is a vital cause of death worldwide. Plants are necessary to the source of life. Several drug compounds isolated from plants are called phytochemicals which are safe, effective drug moieties to treat several diseases. Berberine chloride is a dual topoisomerase I and II inhibitor, that exhibited potent antitumor activities against several malignancies. However, the effect of Berberine on mitochondria remains unknown. The focus of this study was to determine the role of Berberine on mitochondrial uncoupling protein (UCP1), ATP production, and cytotoxic effect of HEK293T cell at a time and dose-dependent manner analysis by CCK8 assay. The upregulation of mitochondrial UCP1 gene expression reduces adipocyte content by initiating thermogenesis. In this study, berberine chloride significantly up-regulates UCP1 gene expression in brown adipocytes. AT 10 µM concentration of Berberine 48 h treatment demonstrated significant cell death. The decreased level of ATP production leads to mitochondrial uncoupling. Initiate thermogenesis reducing fat droplets in adipocytes. The first time, we used molecular docking and dynamic of Berberine with UCP1 gene in this study and revealed therapeutic potential of Berberine via modulation of mitochondrial UCP1 gene. Further investigation will reveal new insight into mechanisms to treat metabolic-related diseases.Communicated by Ramaswamy H. Sarma.
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Berberina , Diabetes Mellitus Tipo 2 , Humanos , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismo , Simulação de Acoplamento Molecular , Berberina/farmacologia , Berberina/metabolismo , Cloretos , Tecido Adiposo Marrom/metabolismo , DNA Topoisomerases Tipo I/metabolismo , DNA Topoisomerases Tipo I/farmacologia , Diabetes Mellitus Tipo 2/metabolismo , Células HEK293 , Mitocôndrias/genética , Mitocôndrias/metabolismo , Adipócitos Marrons/metabolismo , Plantas/metabolismo , Trifosfato de Adenosina/metabolismo , Obesidade/genéticaRESUMO
Infectious Spleen and Kidney Necrosis Virus (ISKNV) is linked to severe infections that cause significant financial losses in global aquaculture. ISKNV enters the host cell through its major capsid protein (MCP), and the resulting infection can lead to mass mortality of fish. Even though several drugs and vaccines are at various stages of clinical testing, none are currently available. Thus, we sought to assess the potential of seaweed compounds to block viral entrance by inhibiting the MCP. The Seaweed Metabolite Database (1110 compounds) was assessed for potential antiviral activity against ISKNV using high throughput virtual screening. Forty compounds with docking scores of ≥8.0 kcal/mol were screened further. The inhibitory molecules BC012, BC014, BS032, and RC009 were predicted by the docking and MD techniques to bind the MCP protein significantly with binding affinities of -9.2, -9.2, -9.9, and -9.4 kcal/mol, respectively. Also, ADMET characteristics of the compounds indicated drug-likeness. According to this study, marine seaweed compounds may operate as viral entrance inhibitors. For their efficacy to be established, in-vitro and in-vivo testing is required.
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Background: Liver ischemia/reperfusion (I/R) injury is a complex and multifactorial pathophysiological process. It is well recognized that the membrane permeability transition pore (mPTP) opening of mitochondria plays a crucial role in cell death after I/R injury. Cyclophilin D (CypD) is a critical positive regulator of mPTP. However, the effect of CypD on the pathogenesis of liver I/R injury and whether CypD is a potential therapeutic target are still unclear. Methods: We constructed liver-specific CypD knockout and AAV8-peptidyl prolyl isomerase F (PPIF) overexpression mice. Then, a 70% liver I/R injury model was established in mice, with 90 min of ischemia and 6 h of reperfusion. The liver function was detected by the level of serum glutamic pyruvic transaminase (alanine transaminase) and glutamic oxaloacetic transaminase (aspartate aminotransferase), the liver damage score and degree of necrosis were measured by hematoxylin and eosin (H&E) staining of liver tissues. Reactive oxygen species (ROS) staining, apoptosis, and autophagy-related molecules were used to detect apoptosis and autophagy during liver I/R. Results: The liver-specific knockout of CypD alleviated necrosis and dysfunction in liver I/R injury, by reducing the excessive production of ROS, and inhibiting cell apoptosis and autophagy. On the contrary, overexpression of CypD exacerbated I/R-induced liver damage. Conclusion: We found that the downregulation of CypD expression alleviated liver I/R injury by reducing apoptosis and autophagy through caspase-3/Beclin1 crosstalk; in contrast, the upregulation of CypD expression aggravated liver I/R injury. Therefore, interfering with the expression of CypD seems to be a promising treatment for liver I/R injury.
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INTRODUCTION: Chronic severe aortic regurgitation (AR) has a poor long-term prognosis, especially among old-age patients. Considering their advancing age, the surgical approach of aortic valve replacement may not always be the best alternative modality of treatment in such patients. Therefore, this study's primary goal was to provide an initial summary of the medium- and short-term clinical effectiveness of transcatheter aortic valve replacement (TAVR) guided by accurate multi-detector computed tomography (MDCT) measurements in patients with severe and chronic AR, especially in elderly patients. METHODS: The study enrolled retrospectively and prospectively patients diagnosed with severe AR who eventually underwent TAVR procedure from January 2019 to September 2022 at Fuwai cardiovascular Hospital, Beijing. Baseline information, MDCT measurements, anatomical classification, perioperative, and 1-year follow-up outcomes were collected and analyzed. Based on a novel anatomical categorization and dual anchoring theory, patients were divided into four categories according to the level of anchoring area. Type 1, 2, and 3 patients (with at least two anchoring regions) will receive TAVR with a transcatheter heart valve (THV), but Type 4 patients (with zero or one anchoring location) will be deemed unsuitable for TAVR and will instead receive medical care (retrospectively enrolled patients who already underwent TAVR are an exception). RESULTS: The mean age of the 37 patients with severe chronic AR was 73.1 ± 8.7 years, and 23 patients (62.2%) were male. The American Association of Thoracic Surgeons' score was 8.6 ± 2.1%. The MDCT anatomical classification included 17 cases of type 1 (45.9%), 3 cases of type 2 (8.1%), 13 cases of type 3 (35.1%), and 4 cases of Type 4 (10.8%). The VitaFlow valve (MicroPort, Shanghai, China) was implanted in 19 patients (51.3%), while the Venus A valve (Venus MedTech, Hangzhou, China) was implanted in 18 patients (48.6%). Immediate TAVR procedural and device success rates were 86.5% and 67.6%, respectively, while eight cases (21.6%) required THV-in-THV implantation, and nine cases (24.3%) required permanent pacemaker implantation. Univariate regression analysis revealed that the major factors affecting TAVR device failure were sinotubular junction diameter, THV type, and MDCT anatomical classification (p < 0.05). Compared with the baseline, the left ventricular ejection fraction gradually increased, while the left ventricular end-diastolic diameter remained small, and the N-terminal-pro hormone B-type natriuretic peptide level significantly decreased within one year. CONCLUSION: According to the results of our study, TAVR with a self-expanding THV is safe and feasible for patients with chronic severe AR, particularly for those who meet the criteria for the appropriate MDCT anatomical classification with intact dual aortic anchors, and it has a significant clinical effect for at least a year.
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With numerous countermeasures, the number of deaths in the construction industry is still higher compared to other industries. Personal Protective Equipment (PPE) is constantly being improved to avoid these accidents, although workers intentionally or unintentionally forget to use such safety measures. It is challenging to manually run a safety check as the number of co-workers on a site can be large; however, it is a prime duty of the authority to provide maximum protection to the workers on the working site. From these motivations, we have created a computer vision (CV) based automatic PPE detection system that detects various types of PPE. This study also created a novel dataset named CHVG (four colored hardhats, vest, safety glass) containing eight different classes, including four colored hardhats, vest, safety glass, person body, and person head. The dataset contains 1,699 images and corresponding annotations of these eight classes. For the detection algorithm, this study has used the You Only Look Once (YOLO) family's anchor-free architecture, YOLOX, which yields better performance than the other object detection models within a satisfactory time interval. Moreover, this study found that the YOLOX-m model yields the highest mean average precision (mAP) than the other three versions of the YOLOX.
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BACKGROUND: Obesity, fatty liver, type 2 diabetes, and Non-alcoholic fatty liver disease (NAFLD) are all metabolic diseases caused by excess food consumption. Existing drug molecules had negative side effects and caused other diseases to develop (Orlistat causes angioedema, and menstrual irregularities; megestrol acetate causes hypertension, and insomnia). By enhancing lipid consumption and increasing nonshivering thermogenesis, targeting mitochondrial uncoupling protein-1 (UCP1) expression in adipocytes could be an auspicious treatment strategy against obesity or metabolic disorders associated with obesity. METHODS: We used previously produced UCP1-A-GFP reporter cell lines in this investigation to find new pharmacological compounds against obesity or metabolic syndrome, which we then tested in cellular analysis, cytotoxicity, mitochondrial function, mitochondrial DNA quantification, mitochondrial ATP production, and in-silico models. RESULTS: Baicalein was discovered to play a critical role in obesity prevention via altering mitochondrial function. Baicalein lowers ATP generation while increasing considerable UCP1 gene expression in brown adipocytes. As a result, cellular thermogenesis is boosted. The HEK293T cell line is harmless by baicalein. The investigation by the in-silico study revealed drug-protein interaction and UCP1 binding. Thus, our research clarifies baicalein's therapeutic role in metabolic and obesity-related illnesses via modulating mitochondrial activity (Supplementary Fig. 2). CONCLUSIONS: Further studies are required in both murine and human models to understand the full mechanism of action by mitochondrial modulation. Drug development investigation also requires to development of a precise formulation.
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Adipócitos Marrons , Diabetes Mellitus Tipo 2 , Humanos , Camundongos , Animais , Adipócitos Marrons/metabolismo , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismo , Tecido Adiposo Marrom/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Células HEK293 , Mitocôndrias , Obesidade/metabolismo , Trifosfato de Adenosina/metabolismo , Proteínas Mitocondriais/metabolismoRESUMO
OBJECTIVES: To examine the prevalence of and risk factors associated with tobacco smoking in the Gambia. DESIGN: A nationwide cross-sectional study. SETTING: The Gambia. PARTICIPANTS: The study participants were both women and men aged between 15 and 49 years old. We included 16,066 men and women in our final analysis. DATA ANALYSIS: We analysed data from the Gambia Demographic and Health Survey (DHS), 2019-2020. DHS collected nationally stratified data from local government areas and rural-urban areas. The outcome variable was the prevalence of tobacco smoking. Descriptive analysis, prevalence and logistic regression methods were used to analyse data to identify the potential determinants of tobacco smoking. RESULTS: The response rate was 93%. The prevalence of current tobacco smoking was 9.92% in the Gambia in 2019-2020, of which, 81% of the consumers smoked tobacco daily. Men (19.3%) smoked tobacco much higher than women (0.65%) (p<0.001). People aged 40-49 years, with lower education, and manual workers were the most prevalent group of smoking in the Gambia (p<0.001).Men were 33 times more likely to smoke tobacco than women. The chance of consuming smoked tobacco increased with the increase of age (adjusted OR (AOR) 9.08, 95% CI 5.08 to 16.22 among adults aged 40-49 years, p<0.001). The strength of association was the highest among primary educated individuals (AOR 5.35, 95% CI 3.35 to 8.54).Manual workers (AOR 2.73) and people from the poorest households (AOR 1.86) were the risk groups for smoking. However, place of residency and region were insignificantly associated with smoking in the Gambia. CONCLUSIONS: Men, older people, manual workers, individuals with lower education and lower wealth status were the vulnerable groups to tobacco smoking in the Gambia. Government should intensify awareness programmes on the harmful effects of smoking, and introduce proper cessation support services among tobacco smoking users prioritising these risk groups.
Assuntos
Fumar , Fumar Tabaco , Adolescente , Adulto , Idoso , Estudos Transversais , Feminino , Gâmbia/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fumar/epidemiologia , Fatores Socioeconômicos , Fumar Tabaco/epidemiologia , Adulto JovemRESUMO
Scientists have discovered many ways to treat bacteria, viruses, and parasites in aquaculture; however, there is still an impossibility in finding a permanent solution for all types of diseases. In that case, the CRISPR-Cas genome-editing technique can be the potential solution to preventing diseases for aquaculture sustainability. CRISPR-Cas is cheaper, easier, and more precise than the other existing genome-editing technologies and can be used as a new disease treatment tool to solve the far-reaching challenges in aquaculture. This technique may now be employed in novel ways, such as modifying a single nucleotide base or tagging a location in the DNA with a fluorescent protein. This review paper provides an informative discussion on adopting CRISPR technology in aquaculture disease management. Starting with the basic knowledge of CRISPR technology and phages, this study highlights the development of RNA-guided immunity to combat the Chilodonella protozoan group and nervous necrosis virus (NNV) in marine finfish. Additionally, we highlight the immunological application of CRISPR-Cas against bacterial diseases in channel catfish and the white spot syndrome virus (WSSV) in shrimp. In addition, the review summarizes a synthesis of bioinformatics tools used for CRISPR-Cas sgRNA design, and acceptable solutions are discussed, considering the limitations.