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The Varicella-zoster virus (VZV), classified as a neurotropic member of the Herpesviridae family, exhibits a characteristic pathogenicity, predominantly inducing varicella, commonly known as chickenpox, during the initial infectious phase, and triggering the reactivation of herpes zoster, more commonly recognized as shingles, following its emergence from a latent state. The pathogenesis of VZV-associated neuroinflammation involves a complex interplay between viral replication within sensory ganglia and immune-mediated responses that contribute to tissue damage and dysfunction. Upon primary infection, VZV gains access to sensory ganglia, establishing latent infection within neurons. During reactivation, the virus can spread along sensory nerves, triggering a cascade of inflammatory mediators, chemokines, and immune cell infiltration in the affected neural tissues. The role of both adaptive and innate immune reactions, including the contributions of T and B cells, macrophages, and dendritic cells, in orchestrating the immune-mediated damage in the central nervous system is elucidated. Furthermore, the aberrant activation of the natural defence mechanism, characterised by the dysregulated production of immunomodulatory proteins and chemokines, has been implicated in the pathogenesis of VZV-induced neurological disorders, such as encephalitis, myelitis, and vasculopathy. The intricate balance between protective and detrimental immune responses in the context of VZV infection emphasises the necessity for an exhaustive comprehension of the immunopathogenic mechanisms propelling neuroinflammatory processes. Despite the availability of vaccines and antiviral therapies, VZV-related neurological complications remain a significant concern, particularly in immunocompromised individuals and the elderly. Elucidating these mechanisms might facilitate the emergence of innovative immunomodulatory strategies and targeted therapies aimed at mitigating VZV-induced neuroinflammatory damage and improving clinical outcomes. This comprehensive understanding enhances our grasp of viral pathogenesis and holds promise for pioneering therapeutic strategies designed to mitigate the neurological ramifications of VZV infections.
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Herpesvirus Humano 3 , Humanos , Herpesvirus Humano 3/inmunología , Herpesvirus Humano 3/fisiología , Herpesvirus Humano 3/patogenicidad , Herpes Zóster/virología , Herpes Zóster/inmunología , Infección por el Virus de la Varicela-Zóster/inmunología , Infección por el Virus de la Varicela-Zóster/virología , Enfermedades del Sistema Nervioso/virología , Enfermedades del Sistema Nervioso/inmunología , Enfermedades del Sistema Nervioso/etiología , Animales , Varicela/virología , Varicela/inmunología , Enfermedades Neuroinflamatorias/inmunología , Enfermedades Neuroinflamatorias/virologíaRESUMEN
The capsule is a major virulence factor for Streptococcus pneumoniae which causes global morbidity and mortality. It is already known that there are few conserved genes in the capsular biosynthesis pathway, which are common among all known serotypes, called CpsA, CpsB, CpsC and CpsD. Inhibiting capsular synthesis can render S. pneumoniae defenseless and vulnerable to phagocytosis. The Inhibitory potential of active Zingiber officinale compounds was investigated against the 3D (3-dimensional) structural products of Cps genes using in silico techniques. A 3D compound repository was created and screened for drug-likeness and the qualified compounds were used for molecular docking and dynamic simulation-based experiments using gallic acid for outcome comparison. Cavity-based docking revealed five different cavities in the CpsA, CpsB and CpsD proteins, with gallic acid and selected compounds of Zingiber in a binding affinity range of -6.8 to -8.8 kcal/mol. Gingerenone A, gingerenone B, isogingerenone B and gingerenone C showed the highest binding affinities for CpsA, CpsB and CpsD, respectively. Through the Molegro Virtual Docker re-docking strategy, the highest binding energies (-126.5 kcal/mol) were computed for CpsB with gingerenone A and CpsD with gingerenone B. These findings suggest that gingerenone A, B and C are potential inhibitors of S. pneumoniae-conserved capsule-synthesizing proteins.
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Proteínas Bacterianas , Simulación del Acoplamiento Molecular , Streptococcus pneumoniae , Zingiber officinale , Zingiber officinale/química , Streptococcus pneumoniae/efectos de los fármacos , Streptococcus pneumoniae/metabolismo , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/antagonistas & inhibidores , Simulación por Computador , Cápsulas Bacterianas/metabolismo , Cápsulas Bacterianas/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Simulación de Dinámica Molecular , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/biosíntesis , Ácido Gálico/farmacología , Ácido Gálico/químicaRESUMEN
In most cases, cancer develops due to abnormal cell growth and subsequent tumour formation. Due to significant constraints with current treatments, natural compounds are being explored as potential alternatives. There are now around 30 natural compounds under clinical trials for the treatment of cancer. Tulsi, or Holy Basil, of the genus Ocimum, is one of the most widely available and cost-effective medicinal plants. In India, the tulsi plant has deep religious and medicinal significance. Tulsi essential oil contains a valuable source of bioactive compounds, such as camphor, eucalyptol, eugenol, alpha-bisabolene, beta-bisabolene, and beta-caryophyllene. These compounds are proposed to be responsible for the antimicrobial properties of the leaf extracts. The anticancer effects of tulsi (Ocimum sanctum L.) have earned it the title of "queen of herbs" and "Elixir of Life" in Ayurvedic treatment. Tulsi leaves, which have high concentrations of eugenol, have been shown to have anticancer properties. In a various cancers, eugenol exerts its antitumour effects through a number of different mechanisms. In light of this, the current review focuses on the anticancer benefits of tulsi and its primary phytoconstituent, eugenol, as apotential therapeutic agent against a wide range of cancer types. In recent years, tulsi has gained popularity due to its anticancer properties. In ongoing clinical trials, a number of tulsi plant compounds are being evaluated for their potential anticancer effects. This article discusses anticancer, chemopreventive, and antioxidant effects of tulsi.
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Ocimum sanctum , Plantas Medicinales , Eugenol/farmacología , Eugenol/uso terapéutico , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéuticoRESUMEN
Ticks and tick-borne diseases constitute a substantial hazard to the livestock industry. The rising costs and lack of availability of synthetic chemical acaricides for farmers with limited resources, tick resistance to current acaricides, and residual issues in meat and milk consumed by humans further aggravate the situation. Developing innovative, eco-friendly tick management techniques, such as natural products and commodities, is vital. Similarly, searching for effective and feasible treatments for tick-borne diseases is essential. Flavonoids are a class of natural chemicals with multiple bioactivities, including the inhibition of enzymes. We selected eighty flavonoids having enzyme inhibitory, insecticide, and pesticide properties. Flavonoids' inhibitory effects on the acetylcholinesterase (AChE1) and triose-phosphate isomerase (TIM) proteins of Rhipicephalus microplus were examined utilizing a molecular docking approach. Our research demonstrated that flavonoids interact with the active areas of proteins. Seven flavonoids (methylenebisphloridzin, thearubigin, fortunellin, quercetagetin-7-O-(6-O-caffeoyl-ß-d-glucopyranoside), quercetagetin-7-O-(6-O-p-coumaroyl-ß-glucopyranoside), rutin, and kaempferol 3-neohesperidoside) were the most potent AChE1 inhibitors, while the other three flavonoids (quercetagetin-7-O-(6-O-caffeoyl-ß-d-glucopyranoside), isorhamnetin, and liquiritin) were the potent inhibitors of TIM. These computationally-driven discoveries are beneficial and can be utilized in assessing drug bioavailability in both in vitro and in vivo settings. This knowledge can create new strategies for managing ticks and tick-borne diseases.
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Acaricidas , Enfermedades de los Bovinos , Rhipicephalus , Enfermedades por Picaduras de Garrapatas , Animales , Humanos , Bovinos , Acetilcolinesterasa/farmacología , Simulación del Acoplamiento Molecular , Triosa-Fosfato Isomerasa , Acaricidas/farmacología , Teoría Funcional de la DensidadRESUMEN
BACKGROUND: Multidrug-resistant tuberculosis (particularly resistant to pyrazinoic acid) is a life-threatening chronic pulmonary disease. Running a marketed regime specifically targets the ribosomal protein subunit-1 (RpsA) and stops trans-translation in the non-mutant bacterium, responsible for the lysis of bacterial cells. However, in the strains of mutant bacteria, this regime has failed in curing TB and killing pathogens, which may only because of the ala438 deletion, which inhibit the binding of pyrazinoic acid to the RpsA active site. Therefore, such cases of tuberculosis need an immediate and effective regime. OBJECTIVE: This study has tried to determine and design such chemotypes that are able to bind to the mutant RpsA protein. METHODS: For these purposes, two phytochemical databases, i.e., NPASS and SANCDB, were virtually screened by a pharmacophore model using an online virtual screening server Pharmit. RESULTS: The model of pharmacophore was developed using the potential inhibitor (zr115) for the mutant of RpsA. Pharmacophore-based virtual screening results into 154 hits from the NPASS database, and 22 hits from the SANCDB database. All the predicted hits were docked in the binding pocket of the mutant RpsA protein. Top-ranked five and two compounds were selected from the NPASS and SANCDB databases respectively. On the basis of binding energies and binding affinities of the compounds, three compounds were selected from the NPASS database and one from the SANCDB database. All compounds were found to be non-toxic and highly active against the mutant pathogen. To further validate the docking results and check the stability of hits, molecular dynamic simulation of three compounds were performed. The MD simulation results showed that all these finally selected compounds have stronger binding interactions, lesser deviation or fluctuations, with greater compactness compared to the reference compound. CONCLUSION: These findings indicate that these compounds could be effective inhibitors for mutant RpsA.
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Simultaneous ipsilateral fractures of the proximal and distal humerus, known as 'floating arm', are rarely seen in adolescents and are considered challenging to manage. Most of the published cases have involved proximal humerus and distal supracondylar fractures. This paper presents a special case of floating arm injury in a 14-year-old boy following a motor vehicle accident that was managed in a well-established trauma center. The injury consisted of displaced proximal humerus and open distal T-condylar intraarticular fractures. The patient was discharged in good condition and regained functionality with no reported complications.
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Interleukin-8 (IL-8) is a chemokine, a type of signaling molecule that has a role in immunological responses and inflammation. In recent years, IL-8 is additionally related to cancer growth and recurrence. Breast cancer growth, progression, and metastatic development are all linked to IL-8. Breast cancer cells are known to develop faster when IL-8 stimulates their proliferation and survival. It can also cause angiogenesis, or the creation of new blood vessels, which is necessary for tumor nutrition and growth. IL-8 and curcumin have been subjects of interest in drug design, particularly in the context of inflammation-related disorders and cancer. This study aims to give an overview of the role of IL-8. Inhibitor-based treatment approaches were being used to target IL-8 with curcumin. Molecular docking method was employed to find a potential interaction to supress competitive inhibition of IL-8 with curcumin. PASS analysis and ADMET characteristics were also being carried out. In the end, IL-8 complexed with curcumin is chosen for MD simulations. Overall, our results showed that during the simulation, the complex stayed comparatively stable. It is also possible to investigate curcumin further as a possible treatment option. The combined results imply that IL-8 and their genetic alterations can be studied in precision cancer therapeutic treatments, utilizing target-driven therapy and early diagnosis.
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Pakistan has a conducive condition for the development of a wide range of scrumptious fruits. As a result, the country grows a diverse assortment of tropical and subtropical fruits; the most prized and top-ranked fruit among all fruits grown in Pakistan is citrus. Citrus is the principal fruit that contributes significantly to Pakistan's export earnings and national income. In this study, the cross-border determinants influencing Pakistan's citrus exports to its topmost 22 trading partners are examined using a gravity model technique. This is the first large study from Pakistan by using gravity model to check the impact of various cross-border factors on citrus fruit export. The analysis is based on a panel dataset covering the years 2003 to 2021. To estimate the results, the study used fixed effect regression with time and country fixed effects. The results signify that per capita income, population, and some regional dummies are positively associated with citrus exports from Pakistan. Citrus price, distance, exchange rate, and other regional dummies are observed to have an adverse effect on citrus exports. Trade agreements between Pakistan and trade partners such as free trade agreements, preferential trade agreements, and SAFTA, have been observed as important determinants of citrus exports. Citrus exporters in Pakistan can also benefit from understanding the factors that influence export markets. By addressing the challenges identified in this study, Pakistan can enhance its citrus exports and boost its agricultural sector.
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Rural and agricultural communities' adaptation to climate change has gained significant attention owing to many countries' vulnerability to climate change risks. A similar trend has been witnessed in South Asia, a highly climate-vulnerable region, where research has grown dramatically considering the agriculture sector's vulnerability to climate-induced disasters. However, little attention has been paid to the adaptation of the livelihoods of rural households. This research, therefore, takes the case of Pakistan to explore livelihood adaptation strategies of rural households to climate change and investigate the factors that expedite or halt the adoption of livelihood diversification strategies. A multistage sampling design is used in this research, where 480 rural households from the Punjab province of Pakistan were selected and interviewed using stratified and random sampling approaches. A multivariate probit (MVP) regression model is employed to analyze the factors affecting households' adoption of livelihood adaptation strategies. The results show that besides adaptation of agronomic operations (agricultural adaptation strategies), rural households in the study area employed a wide range of strategies to adapt their livelihoods to climate change. These strategies include poultry and livestock farming, value addition of farm produce, trading of animals and farm commodities, small businesses (shops, etc.), daily wage labor, horticultural crop farming, and non-farming jobs. The estimates of the MVP model revealed that respondents' education, household size, income, access to a credit facility, access to farm advisory services, and access to climate forecasts have significantly influenced the choice of livelihood adaptation strategies. Based on these findings, this research recommends that the authorities should make efforts to improve farmers' understanding of the adaptation of climate change risks and educate them to adopt multiple livelihood options to improve the resilience of their livelihoods to climate-induced risks. This research has important policy implications for other countries with similar socio-economic features.
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Protein kinases are an attractive therapeutic target for cardiovascular, cancer and neurodegenerative diseases. Cancer cells demand energy generation through aerobic glycolysis, surpassing "oxidative phosphorylation" (OXPHOS) in mitochondria. The pyruvate dehydrogenase kinases (PDKs) have many regulatory roles in energy generation balance by controlling the pyruvate dehydrogenase complex. Overexpression of PDKs is associated with the overall survival of cancer. PDK3, an isoform of PDK is highly expressed in various cancer types, is targeted for inhibition in this study. PDK3 has been shown to binds strongly with a natural compound, thymoquinone (TQ), which is known to exhibit anti-cancer potential. Detailed interaction between the PDK3 and TQ was carried out using spectroscopic and docking methods. The overall changes in the protein's structures after TQ binding were estimated by UV-Vis spectroscopy, circular dichroism and fluorescence binding studies. The kinase activity assay was also carried out to see the kinase inhibitory potential of TQ. The enzyme inhibition assay suggested an excellent inhibitory potential of TQ towards PDK3 (IC50 = 5.49 µM). We observed that TQ forms a stable complex with PDK3 without altering its structure and can be a potent PDK3 inhibitor which may be implicated in cancer therapy after desired clinical validation.
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Benzoquinonas , Neoplasias Pulmonares , Proteínas Serina-Treonina Quinasas , Humanos , Piruvato Deshidrogenasa Quinasa Acetil-Transferidora/química , Neoplasias Pulmonares/tratamiento farmacológico , Fosforilación OxidativaRESUMEN
Millions of people's lives are being devastated by dengue virus (DENV), a severe tropical and subtropical illness spread by mosquitoes and other vectors. Dengue fever may be self-limiting like a common cold or can rapidly progress to catastrophic dengue hemorrhagic fever or dengue shock syndrome. With four distinct dengue serotypes (DENV1-4), each with the potential to contain antibody-boosting complicated mechanisms, developing a dengue vaccine has been an ambitious challenge. Here, we used a computational pan-vaccinomics-based vaccine design strategy (reverse vaccinology) for all 4 DENV serotypes acquired from different regions of the world to develop a new and safe vaccine against DENV. Consequently, only five mapped epitopes from all the 4 serotypes were shown to be extremely effective for the construction of multi-epitope vaccine constructs. The suggested vaccine construct V5 from eight vaccine models was thus classified as an antigenic, non-allergenic, and stable vaccine model. Moreover, molecular docking and molecular dynamics simulation was performed for the V5 vaccine candidate against the HLAs and TRL2 and 4 immunological receptors. Later, the vaccine sequence was transcribed into the cDNA to generate an expression vector for the Escherichia coli K12 strain. Our research suggests that this vaccine design (V5) has promising potential as a dengue vaccine. However, further experimental analysis into the vaccine's efficacy might be required for the V5 proper validation to combat all DENV serotypes.
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Tropomyosin receptor kinase B (TrkB), also known as neurotrophic tyrosine kinase receptor type 2 (NTRK2), is a protein that belongs to the family of receptor tyrosine kinases (RTKs). NTRK2 plays a crucial role in regulating the development and maturation of the central nervous system (CNS) and peripheral nervous system (PNS). Elevated TrkB expression levels observed in different pathological conditions make it a potential target for therapeutic interventions against neurological disorders, including depression, anxiety, Alzheimer's disease, Parkinson's disease, and certain types of cancer. Targeting TrkB using small molecule inhibitors is a promising strategy for the treatment of a variety of neurological disorders. In this research, a systematic virtual screening was carried out on phytoconstituents found in the IMPPAT library to identify compounds potentially inhibiting TrkB. The retrieved compounds from the IMPPAT library were first filtered using Lipinski's rule of five. The compounds were then sorted based on their docking score and ligand efficiency. In addition, PAINS, ADMET, and PASS evaluations were carried out for selecting drug-like compounds. Finally, in interaction analysis, we found two phytoconstituents, Wedelolactone and 3,8-dihydroxy-1-methylanthraquinone-2-carboxylic acid (DMCA), which possessed considerable docking scores and specificity on the TrkB ATP-binding pocket. The selected compounds were further assessed employing molecular dynamics (MD) simulations and essential dynamics. The results revealed that the elucidated compounds bind well with the TrkB binding pocket and lead to fewer conformations fluctuations. This study highlighted using phytoconstituents, Wedelolactone and DMCA as starting leads in developing novel TrkB inhibitors.Communicated by Ramaswamy H. Sarma.
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Neoplasias , Enfermedades del Sistema Nervioso , Humanos , Tropomiosina , Simulación del Acoplamiento Molecular , Simulación de Dinámica MolecularRESUMEN
Introduction Voice is a crucial tool for communication, and voice problems are more likely to occur in professionals who frequently use their voice for work. Teachers, whose profession requires sustained vocal use, are particularly susceptible to occupation-related voice disorders. This study aimed to quantify the prevalence of voice disorders among teachers in Saudi Arabia, with the general population serving as a control group, and to identify associated risk factors. Methods A cross-sectional study was conducted utilizing an online self-administered questionnaire, which was completed by both teachers and the general population in Saudi Arabia. The latter group acted as a control. The questionnaire included sections on sociodemographic data, teaching patterns, symptoms of voice issues, and the Voice Handicap Index-10 (VHI-10) for assessing voice disorders among participants. Results The study included 640 participants, with 438 (68.4%) being teachers, the majority of whom were females (N = 406; 63.4%). The most common voice-related symptoms reported by teachers were hoarseness (N = 210; 37.9%) and dry throat (N = 147; 26.9%). Voice disorders, as determined by the VHI, affected 355 (55.5%) of the teachers. A high VHI score was associated with a diagnosis of voice disorders and GERD. There was no significant difference in the VHI scores between teachers and the general population (p > 0.05). Conclusion Teachers in Saudi Arabia exhibited a higher prevalence of voice disorders compared to the general population. Risk factors, such as smoking, longer teaching experience, and more teaching hours per week, were more common among teachers with voice disorders. Further investigative studies are warranted to elucidate the causal relationships between these variables and voice disorders.
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Aims Chronic obstructive pulmonary disease (COPD) is one of the most common causes of death worldwide. This study assesses the level of knowledge about COPD among undergraduate students that makes it different from other respiratory illnesses. Methods A cross-sectional study was conducted among undergraduate students at King Saud bin Abdulaziz University for Health Sciences (KSAU-HS). The Bristol Chronic obstructive pulmonary disease Knowledge Questionnaire (BCKQ) was used to evaluate the knowledge about COPD, epidemiology, symptoms, exercise, smoking, and breathlessness domains. The questionnaire was distributed among the different male colleges. Results There were 304 respondents from five colleges. The overall BCKQ mean score was 15.16±4.52 (maximum 30). The mean score was highest for the Colleges of Pharmacy (18.89±2.17) and Medicine (18.00±3.84), and the College of Science and Health Professions had the lowest score (11.56±5.58). The highest overall means for the different domains (max=5) were for smoking (2.19±1.2), and epidemiology (2.83±1.27), while symptoms of COPD (2.23±1.06) and breathlessness (1.96±1.13) were the lowest among the domains. Conclusions There was a low level of understanding among undergraduate students in general, but the Colleges of Medicine and Pharmacy had better knowledge. On the other hand, the College of Science and Health Professions had a lower score. This indicates some areas for improvement in the education program. Appropriate development in the education program is recommended, such as increasing the awareness of symptoms of COPD and other aspects of the disease.
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Lung cancer is a disease with a high mortality rate and it is the number one cause of cancer death globally. Approximately 12-14% of non-small cell lung cancers are caused by mutations in KRASG12C. The KRASG12C is one of the most prevalent mutants in lung cancer patients. KRAS was first considered undruggable. The sotorasib and adagrasib are the recently approved drugs that selectively target KRASG12C, and offer new treatment approaches to enhance patient outcomes however drug resistance frequently arises. Drug development is a challenging, expensive, and time-consuming process. Recently, machine-learning-based virtual screening are used for the development of new drugs. In this study, we performed machine-learning-based virtual screening followed by molecular docking, all atoms molecular dynamics simulation, and binding energy calculations for the identifications of new inhibitors against the KRASG12C mutant. In this study, four machine learning models including, random forest, k-nearest neighbors, Gaussian naïve Bayes, and support vector machine were used. By using an external dataset and 5-fold cross-validation, the developed models were validated. Among all the models the performance of the random forest (RF) model was best on the train/test dataset and external dataset. The random forest model was further used for the virtual screening of the ZINC15 database, in-house database, Pakistani phytochemicals, and South African Natural Products database. A total of 100 ns MD simulation was performed for the four best docking score complexes as well as the standard compound in complex with KRASG12C. Furthermore, the top four hits revealed greater stability and greater binding affinities for KRASG12C compared to the standard drug. These new hits have the potential to inhibit KRASG12C and may help to prevent KRAS-associated lung cancer. All the datasets used in this study can be freely available at ( https://github.com/Amar-Ajmal/Datasets-for-KRAS ).
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High blood pressure (BP) and dyslipidemia are major risk factors for cardiovascular disease mortality. The systemic immune-inflammation index (SII) has been suggested as a predictive tool to identify those at risk for chronic diseases, however, its use for predicting high BP and dyslipidemia has not been thoroughly investigated. This study aimed to examine the association between SII and high BP as well as lipid markers. Retrospective hospital data from a large cohort (nâ =â 3895) of Saudi adults agedâ ≥18 years were analyzed. Lipid markers (cholesterol, high-density lipoprotein, low-density lipoprotein [LDL]), systolic BP, and diastolic BP measures were extracted. When the sample was divided into quartiles of SII, cholesterol, triglycerides, and LDL were higher in those with a higher SII than in those with a lower SII (Pâ <â .01). After adjusting for potential confounders, higher SII was significantly associated with higher odds of hypertension (odds ratio: 1.12, 95% confidence interval: 1.04-1.21) and elevated LDL (odds ratio: 1.07, 95% CI: 1.02-1.14), but not with elevated cholesterol. Across quartiles of SII, there was a significant trend between higher SII and the odds of hypertension in people with diabetes and those agedâ ≥65 years. The SII could be an economical predictive measure for identifying individuals at risk of hypertension and some aspects of dyslipidemia. Longitudinal studies are needed to confirm this relationship.
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Presión Sanguínea , Dislipidemias , Hipertensión , Inflamación , Humanos , Estudios Retrospectivos , Masculino , Dislipidemias/sangre , Dislipidemias/epidemiología , Dislipidemias/inmunología , Femenino , Persona de Mediana Edad , Hipertensión/epidemiología , Hipertensión/sangre , Hipertensión/inmunología , Adulto , Inflamación/sangre , Inflamación/inmunología , Anciano , Presión Sanguínea/fisiología , Arabia Saudita/epidemiología , Factores de Riesgo , Biomarcadores/sangre , Triglicéridos/sangreRESUMEN
Sleeve gastrectomy (SG) is a type of procedure called bariatric surgery that provides large weight loss and has a positive impact on diseases associated with obesity. However, it has brought several complications that have an impact on those undergoing surgery, which are classified into intraoperative and postoperative issues. The study's goal is to assess the Saudi Arabian population's awareness of SG consequences. This study assessed the general population's knowledge in Saudi Arabia in 2023 using a cross-sectional approach. The total number of participants was 1,013, the majority of whom were individuals between the ages of 18 and 25 (471, 46%), and females (692, 68%). A total of 692 (68%) participants showed awareness of BMI; in addition, 987 (97%) were aware of gastric sleeve surgery, and 538 (53%) understood its indications correctly. Regarding SG complications, approximately 821 (81%) of participants showed awareness. There were significant associations between knowledge of gastric sleeve surgery and residence in the northern region of Saudi Arabia. In conclusion, our study indicated that the general population is aware of the complications of gastric sleeve surgery, but it found a deficiency in their knowledge about BMI.
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BACKGROUND: Leishmaniasis is a deadly protozoan parasitic disease and a significant health problem in underdeveloped and developing countries. The global spread of the parasite, coupled with the emergence of drug resistance and severe side effects associated with existing treatments, has necessitated the identification of new and potential drugs. OBJECTIVE: This study aimed to identify promising compounds for the treatment of leishmaniasis by targeting two essential enzymes of Leishmania donovani: trypanothione reductase (Try-R) and trypanothione synthetase (Try-S). METHODS: High-throughput virtual and in vitro screening of in-house and commercial databases was conducted. A pharmacophore model with seven features was developed and validated using the Guner-Henery method. The pharmacophore-based virtual screening yielded 690 hits, which were further filtered through Lipinski's rule, ADMET analysis, and molecular docking against Try-R and Try-S. Molecular dynamics studies were performed on selected compounds, and in vitro experiments were conducted to evaluate their activity against the promastigote and amastigote forms of L. donovani. RESULTS: The virtual screening and subsequent analysis identified 33 promising compounds. Molecular dynamics studies of two compounds (comp-1 and comp-2) demonstrated stable binding interactions with the target enzymes and high affinity. In vitro experiments revealed that 13 compounds exhibited moderate activity against both the promastigote (IC50, 41 µM-76 µM) and the amastigote (IC50, 44 µM-72 µM) forms of L. donovani. Compounds 1 and 2 showed the highest percent inhibition and the lowest IC50 values. CONCLUSION: The identified compounds demonstrated significant inhibitory activity against Leishmania donovani and stable interactions with target enzymes. These findings suggest that the compounds could serve as promising leads for developing new treatments for leishmaniasis.
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Background: Escherichia coli is one of the serious pathogens causing various infections in the animal field, such as neonatal calf diarrhea, which is responsible for mortality associated with diarrhea during the first days of life. Aim: Current work is aimed at designing an effective and safe multiepitope vaccine candidate against E. coli infection in calves based on the fimbrial protein K99 of Enterotoxigenic E. coli (ETEC) and Immuno-informatics. Methods: A conserved sequence of K99 protein was generated, and then highly antigenic, nonallergic, and overlapped epitopes were used to construct a multiepitope vaccine. Five THL, six MHC II, and four beta cell epitopes were targeted to create the candidate. The candidate vaccine was produced utilizing 15 epitopes and three types of linkers, two types of untranslated region (UTR) human hemoglobin subunit beta (HBB), UTR beta-globin (Rabb), and RpfE protein as an immunomodulation adjuvant. Results: Immuno-informatics analysis of the constructed protein showed that the protein was antigenic (antigenic score of 0.8841), stable, nonallergen, and soluble. Furthermore, the Immuno-informatics and physiochemical analysis of the constructed protein showed a stable, nonallergic, soluble, hydrophilic, and acidic PI (isoelectric point). of 9.34. Docking of the candidate vaccine with the toll-like receptor TLR3 was performed, and results showed a strong interaction between the immune receptor and the vaccine. Finally, the expression efficiency of the construct in E. coli was estimated via computational cloning of the vaccine sequence into Pet28a. Conclusion: Results of immunoinformatics and in silico approaches reveal that the designed vaccine is antigenic, stable, and able to bind to the immune cell receptors. Our results interpret the proposed multiepitope mRNA vaccine as a good preventive option against E. coli infection in calves.
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Enfermedades de los Bovinos , Biología Computacional , Escherichia coli Enterotoxigénica , Infecciones por Escherichia coli , Vacunas contra Escherichia coli , Animales , Bovinos , Escherichia coli Enterotoxigénica/inmunología , Infecciones por Escherichia coli/veterinaria , Infecciones por Escherichia coli/prevención & control , Infecciones por Escherichia coli/inmunología , Vacunas contra Escherichia coli/inmunología , Enfermedades de los Bovinos/prevención & control , Enfermedades de los Bovinos/inmunología , Enfermedades de los Bovinos/microbiología , Epítopos/inmunología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Modelos Moleculares , InmunoinformáticaRESUMEN
Integrin-linked kinase (ILK), a ß1-integrin cytoplasmic domain interacting protein, supports multi-protein complex formation. ILK-1 is involved in neurodegenerative diseases by promoting neuro-inflammation. On the other hand, its overexpression induces epithelial-mesenchymal transition (EMT), which is a major hallmark of cancer and activates various factors associated with a tumorigenic phenotype. Thus, ILK-1 is considered as an attractive therapeutic target. We investigated the binding affinity and ILK-1 inhibitory potential of noscapine (NP) using spectroscopic and docking approaches followed by enzyme inhibition activity. A strong binding affinity of NP was measured for the ILK-1 with estimated Ksv (M-1) values of 1.9 × 105, 3.6 × 105, and 4.0 × 105 and ∆G0 values (kcal/mol) -6.19554, -7.8557 and -8.51976 at 298 K, 303 K, and 305 K, respectively. NP binds to ILK-1 with a docking score of -6.6 kcal/mol and forms strong interactions with active-site pocket residues (Lys220, Arg323, and Asp339). The binding constant for the interaction of NP to ILK-1 was 1.04 × 105 M-1, suggesting strong affinity and excellent ILK-1 inhibitory potential (IC50 of â¼5.23µM). Conformational dynamics of ILK-1 were also studied in the presence of NP. We propose that NP presumably inhibits ILK-1-mediated phosphorylation of various downstream signalling pathways that are involved in cancer cell survival and neuroinflammation.