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PURPOSE: The relationship between body mass index (BMI) and oral disorders remains unclear. This study examined the prevalence and types of dental abnormalities and oral mucosal lesions among female students with obesity attending a Taif University sports centre. MATERIALS AND METHODS: This non-interventional cross-sectional study enrolled female students with high BMI from a university sports facility using a convivence sampling method. The participants were divided into three BMI groups. Data were collected using an interview and by clinical oral examination. Prevalence and oral disorder types and possible mechanisms linking BMI and dental development were evaluated. RESULTS: Ultimately, 86 female students with obesity were analysed. The mean BMI was 42.8 kg/m2, indicating high obesity levels. A weak although statistically significant correlation was observed between age and BMI (r=0.27), indicating that older students had higher BMI. A statistically significant association was observed between BMI and dental abnormalities (p0.05). The dental abnormality prevalence increased with BMI, ranging from 37.5% to 40.7% in the ≤40 and >45 kg/m2 groups, respectively. Most participants (66.3%) had oral mucosal lesions, with the highest prevalence among participants in the 40-45 kg/m2 group (71.4%). CONCLUSION: A statistically significant relationship was observed between BMI and dental abnormalities; obesity may negatively affect oral health.
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Índice de Masa Corporal , Obesidad , Humanos , Femenino , Estudios Transversales , Prevalencia , Adulto Joven , Obesidad/epidemiología , Obesidad/complicaciones , Adulto , Maloclusión/epidemiología , Anomalías Dentarias/epidemiología , Enfermedades de la Boca/epidemiología , AdolescenteRESUMEN
AIM AND OBJECTIVES: Career indecision is a broad term that refers to the uncertainty and difficulty of decision-making regarding future careers among junior professionals. This study aims primarily to estimate the prevalence of career indecisiveness among senior medical students and medical interns in Oman. Secondly, it assesses the association of sociodemographic factors influencing it. Finally, it examines the association between participation in career development activities and career indecision among them during the academic year of 2022-2023. METHODS: A cross-sectional study was conducted using an anonymous self-administered questionnaire in the English language. Unpaired t-test and ANOVA test were used to compare means between groups. A 21-item Career Factors Inventory (CFI) was used to determine the career indecision score. These scores were further classified as low-level (score 27-71) and high-level (score 72-105). Results: The total number of participants was 161. The minimum sample size calculated was 153 participants for 95% confidence intervals. The prevalence of high-level career indecision was 63.4% (95%CI 55.4%-70.8%) among the participants. Participants with one of their parents in healthcare professions and those who did not participate in career development activities had high career indecision scores with P-values of 0.002 and 0.022, respectively. Moreover, participants younger than 25 years of age in comparison to older participants had higher need-for-self-knowledge (NSK) scores (p-value 0.018). CONCLUSION: A high prevalence of high-level career indecision was seen among senior medical students and medical interns in Oman. Few factors were found to be statistically associated with career indecision, especially participation in career development activities. Further studies are recommended to investigate the causality of high-level career indecision among junior professionals in Oman and the contributing factors. Curricular and extra-curricular career development activities and counseling may reduce career indecision.
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Introduction The double burden of malnutrition (DBM) in Pakistan is a rising concern affecting school-going children, marked by coexisting under- and over-nutrition within the same population. Key influences include shifts in dietary habits, socioeconomic status, and lifestyle changes due to rapid urbanization. With a focus on Multan, Pakistan, the study seeks to assess the proportion of underweight and overweight students while identifying the risk factors and sociodemographic characteristics associated with this incidence. The aim is to guide future health interventions addressing this multidimensional health challenge. Materials and methods This study, adopting a descriptive cross-sectional research design, collected data from female teenage students through interviews and anthropometric measurements. A total of 300 participants were randomly selected from a comprehensive school list representing diverse urban and rural settings. Participants' weight and height were measured to calculate their body mass index (BMI), categorizing them into underweight, normal weight, and overweight groups. The relevant risk factors were collected through an interview questionnaire. Collected data were analyzed using IBM SPSS Statistics for Windows, Version 26.0 (Released 2019; IBM Corp., Armonk, New York, United States), with the results stratified according to socioeconomic, dietary, and psychosocial factors and compared across different weight categories. Results The study collected data from 300 students, revealing a correlation between socioeconomic status, dietary habits, and BMI. Parental occupation significantly affected nutritional status, with children of laborers primarily falling within normal and underweight categories. Dietary habits like frequency of fast food and milk or dairy consumption showed notable associations with nutritional status. Psychosocial factors such as peer or teacher comments about weight and outdoor sports participation also influenced the students' nutritional status. However, factors like family income, video game hours, and the presence of pets at home did not show significant associations with nutritional status. Conclusions The study illustrates a multi-faceted association between socioeconomic status, dietary habits, and BMI among schoolchildren in Multan, Pakistan, emphasizing the need for comprehensive interventions.
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Background: Despite deep cultural traditions, incense burning significantly impacts respiratory health. Effects of Arabian bakhour remain unknown in Saudi Arabia's Jazan region with prevalent use. This cross-sectional study addresses this gap by investigating bakhour exposure and respiratory diseases. Methods: This was descriptive cross-sectional study conducted in Jazan area, Saudi Arabia, from October 2023 to March 2024. A total of 1612 participants age more than 18 years, both gender and resident of Jazan Area were included. Those aged less than 18 years were excluded. SPSS v 26 was used for data analysis. Results: The sample (n=1612) had a mean age of 29±11 years and was 63% female. Bakhour use was nearly universal (98%), especially using coal (73%). Higher bakhour frequency significantly associated with increased cough (p<0.01) and dyspnea (p<0.01). Certain bakhour types linked to greater allergic rhinitis prevalence (p<0.01). Regression analysis revealed cough during bakhour use worsened respiratory health (increased respiratory score) by 3.89 times (95% CI 1.13-6.64; p=0.006) while dyspnea increased the score by 7.48 times (95% CI 4.70-10.25; p<0.001). Conclusion: This study provides valuable insights into the association between Bakhour use and respiratory health in the Jazan region. The findings emphasize the need for further research and public health interventions to mitigate potential respiratory risks associated with Bakhour use.
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Background: Optic neuritis is an inflammatory disorder of the optic nerve and is often the initial manifestation of systemic demyelinating diseases such as multiple sclerosis (MS), neuromyelitis optic spectrum disorder (NMOSD), and myelin-oligodendrocyte glycoprotein (MOG) antibody-mediated disease. There are ethnic variations in the etiology of optic neuritis across the world. While multiple sclerosis is common in the West, NMOSD and MOG are more common causes in Asian patients. There is a paucity of reports on the clinical profile of optic neuritis in the Middle East. Objectives: To study the demographic and clinical features of patients with new onset optic neuritis in a main tertiary care center. Methods: A retrospective study of cases with new-onset optic neuritis at a tertiary care center between 2012 and 2022. The clinical and demographic characteristics were obtained from medical records and were summarized using descriptive statistics. Univariate analysis and multivariate analysis to assess the short-term visual outcome. Results: Seventy-one patients with new-onset optic neuritis (70 unilateral and one bilateral) were included in the study. The mean age was 33.3 years, they were predominantly females (73 %), and most of the cases were MS (53 %) followed by idiopathic optic neuritis (42.3 %). Final visual acuity of at least 20/40 was seen in at least 91.5 %. Conclusion: While the clinical profile of patients in this study closely resembles the Optic Neuritis Treatment Trial with a high incidence of MS and a good visual outcome in most patients and a good response to intravenous steroids, there is a significant proportion of idiopathic optic neuritis cases that may need to be better characterized with longer follow up and repeated serum biomarker testing.
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The main objective of this work was to determine the significant physicochemical and bioactive parameters of honeys originating from Iraqi Kurdistan. For this purpose, honey samples (n = 16) were taken directly from Kurdish beekeepers from different places of Dohuk and Erbil Governorate in 2018 and 2022. The following parameters were analyzed: moisture content, electrical conductivity, diastase activity, hydroxymethylfurfural content, pH, free acidity, content of saccharides, total phenolic content, total flavonoid content, color, color intensity and DPPH, FRAP. Another objective of this work was to compare the properties of Kurdistan honeys with the requirements of European Union law and with the honeys of Central Europe. A total of 48 honey samples were included in the comparison. It was detected that the honeys produced in Iraqi Kurdistan met the strict quality criteria set by European law, which is important information for local beekeepers and experts in relation to honey production and an opportunity to set local limits of honey quality. Despite the different climatic and topographical conditions, the available flora, and the different species of bees, the properties of Iraqi Kurdistan honeys were similar to the properties of honeys from the Czech and Slovak Republics.
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Introduction In recent years, the increased use of smartphones has adversely affected students, leading to issues like musculoskeletal pain. Therefore, our objective was to assess the correlation between smartphone addiction and neck and lower back pain. Methodology An observational cross-sectional study was conducted at Al-Baha University, Al-Baha, Saudi Arabia. The Smartphone Addiction Scale Short Version (SAS-SV) was used to measure the level of smartphone addiction while the Nordic Musculoskeletal Questionnaire (NMQ) was utilized to evaluate musculoskeletal pain. Results Smartphone addiction was prevalent in 72% of the participants (n = 293). Significantly, lower back pain was associated with smartphone addiction (p-value = 0.004). However, none of the demographic characteristics were associated with neck or lower back pain (p-value > 0.05). Students in clinical years had a higher risk of neck pain than those in an internship (p-value = 0.048). Conclusion Almost two-thirds of the students were addicted to smartphones, with a significant association with lower back pain. Students addicted to their smartphones had a higher risk of developing lower back pain, while clinical-year students had a higher risk of developing neck pain. It's important to raise awareness about the health and safety dangers linked to smartphones and other devices.
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The aim of this study is to estimate the normal cross-sectional area and diameter of the stellate ganglion (SG) by ultrasound (US) in healthy adults. The study sample included 80 stellate ganglia in 40 participants (15 males, 25 females), mean age 38 years, mean height 162.5 cm, mean weight 67.8 kg, mean body mass index 25.4 kg/m2. Two radiologists separately obtained US images of the bilateral SG. Each participant was scanned 3 times bilaterally to assess for intra-observer reliability. The mean diameter of the SG was 1 mm (range: 0.1-2). The mean CSA of the bilateral SG was 1.3 mm2 (range: 0.6-3.9). The SG diameter positively correlated with age. Our study demonstrates the ability of US to image the SG and estimate its normal diameter and CSA. Knowledge of how to identify and measure the SG during ultrasound-guided procedures would be expected to decrease the risk of associated complications and help establish normal reference values.
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Ganglio Estrellado , Ultrasonografía , Humanos , Masculino , Femenino , Adulto , Ganglio Estrellado/diagnóstico por imagen , Ultrasonografía/métodos , Persona de Mediana Edad , Valores de Referencia , Voluntarios Sanos , Adulto Joven , Reproducibilidad de los Resultados , Variaciones Dependientes del ObservadorRESUMEN
The application of gold nanoparticles (AuNPs) in cancer therapy, particularly targeted therapy of glioblastoma multiforme (GBM), is an up-and-coming field of research that has gained much interest in recent years. GBM is a life-threatening malignant tumour of the brain that currently has a 95 % death rate with an average of 15 months of survival. AuNPs have proven to have wide clinical implications and compelling therapeutic potential in many researches, specifically in GBM treatment. It was found that the reason why AuNPs were highly desired for GBM treatment was due to their unique properties that diversified the applications of AuNPs further to include imaging, diagnosis, and photothermal therapy. These properties include easy synthesis, biocompatibility, and surface functionalization. Various studies also underscored the ability of AuNPs to cross the blood-brain-barrier and selectively target tumour cells while displaying no major safety concerns which resulted in better therapy results. We attempt to bring together some of these studies in this review and provide a comprehensive overview of safety evaluations and current and potential applications of AuNPs in GBM therapy that may result in AuNP-mediated therapy to be the new gold standard for GBM treatment.
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Neoplasias Encefálicas , Glioblastoma , Oro , Nanopartículas del Metal , Glioblastoma/tratamiento farmacológico , Glioblastoma/terapia , Oro/química , Oro/administración & dosificación , Humanos , Nanopartículas del Metal/administración & dosificación , Nanopartículas del Metal/química , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/terapia , Animales , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/efectos de los fármacosRESUMEN
Introduction: In diabetes mellitus (DM) patients, obtaining a good night's sleep is crucial for maintaining body caloric intake, controlling insulin levels, and reducing the likelihood of engaging in unhealthy behavior. Patients with poor sleep quality may experience impaired glycemia, playing a significant role in the development of chronic complications. This study aims to explore the effects of DM complications on sleep quality among Saudi Arabian patients. Patient and Methods: This is a cross-sectional study conducted among patients with diabetes. A self-administered, validated questionnaire translated into Arabic was distributed among diabetic patients using an online survey. The questionnaire includes sociodemographic characteristics (i.e. age, gender, marital status, etc.), the medical history of the patients, and a questionnaire about sleep quality. Results: Out of 4171 patients involved, 52.7% were females and 27.7% were aged between 40 and 60 years old. The prevalence of patients with perceived poor sleep quality was 24.1%. Significant predictors of poor sleep quality were the gender female, having social stressors, comorbid sleep disorders, associated comorbidities, increasing HbA1c levels, being overweight/obese, and diabetes complications. Furthermore, sleep disturbance, taking sleep medications, daytime sleepiness, and having bad dreams during sleep were also identified as prognostic factors for poor sleep quality. Conclusion: The subjective poor sleep quality of patients with diabetes was 24.1%. Poor sleep quality was significantly demonstrated by females who were having social stressors, comorbid sleep disorders, comorbidities, uncontrolled HbA1c levels, elevated BMI levels, and complications of diabetes. However, regular physical activity and adequate sleep were estimated to be the protective factors against poor sleep quality. Further research is needed to establish the effect of sleep quality among patients with DM.
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Misfolding and aggregation of transthyretin (TTR) is associated with numerous ATTR amyloidosis. TTR aggregates extracted from ATTR patients consist of not only full-length TTR, but also N-terminally truncated TTR fragments that can be produced by proteolytic cleavage, suggesting the presence of multiple misfolding pathways. Here, we report mechanistic studies of an early stage of TTR aggregation to probe the oligomerization process for the full-length as well as N-terminally truncated TTR. Our kinetic analyses using size exclusion chromatography revealed that amyloidogenic monomers dissociated from wild-type (WT) as well as pathogenic variants (V30M and L55P) form misfolded dimers, which self-assemble into oligomers, precursors of fibril formation. Dimeric interfaces in the full-length misfolded oligomers were investigated by examining the effect of single-point mutations on the two ß-strands (F and H). The single-point mutations on the two ß-strands (E92P on strand F and T119W on strand H) inhibited the dimerization of misfolded monomers, while the TTR variants can still form native dimers through the same F and H strands. These results suggest that the two strands are involved in intermolecular associations for both native and misfolded dimers, but detailed intermolecular interactions are different in the two forms of dimers. In the presence of a proteolytic enzyme, TTR aggregation is greatly accelerated. The two mutations on the two ß-strands, however, inhibited TTR aggregation even in the presence of a proteolytic enzyme, trypsin. These results suggest that the two ß-strands (F and H) play a critical role in aggregation of the N-terminally truncated TTR as well.
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Prealbúmina , Pliegue de Proteína , Multimerización de Proteína , Prealbúmina/química , Prealbúmina/genética , Prealbúmina/metabolismo , Humanos , Mutación Puntual , Cinética , Neuropatías Amiloides Familiares/metabolismo , Neuropatías Amiloides Familiares/genética , Amiloide/química , Amiloide/metabolismoRESUMEN
Epilepsy is a common neurological disease characterized by the recurrent, paroxysmal, and unprovoked seizures. It has been shown that hyperuricemia enhances and associated with the development and progression of epilepsy through induction of inflammation and oxidative stress. In addition, uric acid is released within the brain and contributes in the development of neuronal hyperexcitability and epileptic seizure. Brain uric acid acts as damage associated molecular pattern (DAMP) activates the immune response and induce the development of neuroinflammation. Therefore, inhibition of xanthine oxidase by allopurinol may reduce hyperuricemia-induced epileptic seizure and associated oxidative stress and inflammation. However, the underlying mechanism of allopurinol in the epilepsy was not fully elucidated. Therefore, this review aims to revise from published articles the link between hyperuricemia and epilepsy, and how allopurinol inhibits the development of epileptic seizure.
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Alopurinol , Epilepsia , Hiperuricemia , Hiperuricemia/tratamiento farmacológico , Alopurinol/farmacología , Alopurinol/uso terapéutico , Humanos , Epilepsia/tratamiento farmacológico , Epilepsia/metabolismo , Animales , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología , Ácido Úrico/metabolismo , Xantina Oxidasa/metabolismo , Xantina Oxidasa/antagonistas & inhibidores , Encéfalo/metabolismo , Encéfalo/efectos de los fármacosRESUMEN
CONTEXT: A computational representation was used to model the doping and nanomodification of ZnO nanoparticles incorporated in Au/Fe nanocomposite. Au/Fe nanostructure was geometrically and discussed to investigate its electronic properties such electronic band structure and PDOS spectra. Moreover, the ZnO interacted with Au/Fe system was illustrated concerning the modified properties present on the surface of the nanocomposite as it may behave different attribution of band gap evaluated after ZnO modification included. Molecular dynamic simulation of the whole nano system was studied to predict the system stability concerning temperature and energy parameters during 100 ps simulation time. The most effective models under investigation were evaluated using adsorption annealing computations associated with the adsorption energy surface. A highly stable energetic adsorption system was anticipated by the periodic adsorption-annealing calculation. METHODS: Au and Fe pure metals nanostructures were studied as a separate molecule with (0 0 1) plane surface for optimum energy minimization. Dmol3 module in/materials studio software was utilized for this protocol. The designed Au/Fe layers for nanostructure building material was computationally optimized, where DFT level was considered involving generalized gradient approximation (GGA) with Perdew-Burke-Ernzerh (PBE) exchange functional. In the computations of the structure matrix simulation, the global orbital cutoff was selected. To address the weak quantification of the standard DFT functionals, Tkatchenko-Schefer (TS) (DFT + D) was utilized to precisely correct the pairwise dispersion of the functionals. The electrical parameters were interpreted using the reciprocal space of the ultrasoft pseudopotential representation. To overcome the issues of self-electron interaction, the nonlocal hybrid functional with PBE0 method was utilized to calculate the electronic properties of the studied systems. The computations generated are predicated on a particular trajectory of the gamma k-point band energy interpolations proposed in this examination. An investigation into the position of adsorption came after geometric optimization. Adsorbed on an optimized Au/Fe surface, ZnO nanostructure was computationally explored using the Dmol3 simulation software.
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OBJECTIVE: This study aimed to investigate the status of antimicrobial-resistant strains of Staphylococcus aureus in Pakistan, their association in terms of co-occurrence with the biofilm-forming genes, resistance profiling and associated discrepancies in diagnostic methods. METHODOLOGY: A total of 384 milk samples from bovine was collected by using convenient sampling technique and were initially screened for subclinical mastitis, further preceded by isolation and confirmation of S. aureus. The S. aureus isolates were subjected to evaluation of antimicrobial resistance by phenotypic identification using Kirby-Bauer disc diffusion method, while the genotypic estimation was done by polymerase chain reaction to declare isolates as methicillin, beta-lactam, vancomycin, tetracycline, and aminoglycoside resistant S. aureus (MRSA, BRSA, VRSA, TRSA, and ARSA), respectively. RESULTS: The current study revealed an overall prevalence of subclinical mastitis and S. aureus to be 59.11% and 46.69%, respectively. On a phenotypic basis, the prevalence of MRSA, BRSA, VRSA, TRSA, and ARSA was found to be 44.33%, 58.49%, 20.75%, 35.84%, and 30.18%, respectively. The results of PCR analysis showed that 46.80% of the tested isolates were declared as MRSA, 37.09% as BRSA, and 36.36% as VRSA, while the occurrence of TRSA and ARSA was observed in 26.31% and 18.75%, respectively. The current study also reported the existence of biofilm-producing genes (icaA and icaD) in 49.06% and 40.57% isolates, respectively. Lastly, this study also reported a high incidence of discrepancies for both genotypic and phenotypic identification methods of resistance evaluation, with the highest discrepancy ratio for the accA-aphD gene, followed by tetK, vanB, blaZ, and mecA genes. CONCLUSION: The study concluded that different antibiotic resistance strains of S. aureus are prevalent in study districts with high potential to transmit between human populations. The study also determined that there are multiple resistance determinants and mechanisms that are responsible for the silencing and expression of antibiotic resistance genes.
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Antibacterianos , Mastitis Bovina , Leche , Infecciones Estafilocócicas , Staphylococcus aureus , Bovinos , Staphylococcus aureus/genética , Staphylococcus aureus/efectos de los fármacos , Animales , Infecciones Estafilocócicas/microbiología , Antibacterianos/farmacología , Femenino , Mastitis Bovina/microbiología , Leche/microbiología , Biopelículas , Pakistán/epidemiología , Pruebas de Sensibilidad Microbiana , Staphylococcus aureus Resistente a Meticilina/genética , Farmacorresistencia Bacteriana Múltiple/genética , Farmacorresistencia Bacteriana/genética , GenotipoRESUMEN
Parkinson's disease (PD) is a neurodegenerative disorder of the brain and is manifested by motor and non-motor symptoms because of degenerative changes in dopaminergic neurons of the substantia nigra. PD neuropathology is associated with mitochondrial dysfunction, oxidative damage and apoptosis. Thus, the modulation of mitochondrial dysfunction, oxidative damage and apoptosis by growth factors could be a novel boulevard in the management of PD. Brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin receptor kinase type B (TrkB) are chiefly involved in PD neuropathology. BDNF promotes the survival of dopaminergic neurons in the substantia nigra and enhances the functional activity of striatal neurons. Deficiency of the TrkB receptor triggers degeneration of dopaminergic neurons and accumulation of α-Syn in the substantia nigra. As well, BDNF/TrkB signalling is reduced in the early phase of PD neuropathology. Targeting of BDNF/TrkB signalling by specific activators may attenuate PD neuropathology. Thus, this review aimed to discuss the potential role of BDNF/TrkB activators against PD. In conclusion, BDNF/TrkB signalling is decreased in PD and linked with disease severity and long-term complications. Activation of BDNF/TrkB by specific activators may attenuate PD neuropathology.
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Factor Neurotrófico Derivado del Encéfalo , Enfermedad de Parkinson , Receptor trkB , Transducción de Señal , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Humanos , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/patología , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/genética , Receptor trkB/metabolismo , Animales , Glicoproteínas de Membrana/metabolismo , Neuronas Dopaminérgicas/metabolismo , Neuronas Dopaminérgicas/patologíaRESUMEN
The discovery of novel therapeutic agents with potent anticancer activity remains a critical challenge in drug development. Natural products, particularly bioactive phytoconstituents derived from plants, have emerged as promising sources for anticancer drug discovery. In this study, we used virtual screening techniques to explore the potential of bioactive phytoconstituents as inhibitors of fibroblast growth factor receptor 1 (FGFR1), a key signaling protein implicated in cancer progression. We used virtual screening techniques to analyze phytoconstituents extracted from the IMPPAT 2.0 database. Our primary objective was to discover promising inhibitors of FGFR1. To ensure the selection of promising candidates, we initially filtered the molecules based on their physicochemical properties. Subsequently, we performed binding affinity calculations, PAINS, ADMET, and PASS filters to identify nontoxic and highly effective hits. Through this screening process, one phytocompound, namely Mundulone, emerged as a potential lead. This compound demonstrated an appreciable affinity for FGFR1 and exhibited specific interactions with the ATP-binding site residues. To gain further insights into the conformational dynamics of Mundulone and the reference FGFR1 inhibitor, Lenvatinib, we conducted time-evolution analyses employing 200 ns molecular dynamics simulations (MDS) and essential dynamics. These analyses provided valuable information regarding the dynamic behavior and stability of the compounds in complexes with FGFR1. Overall, the findings indicate that Mundulone exhibits promising binding affinity, specific interactions, and favorable drug profiles, making it a promising lead candidate. Further experimental analysis will be necessary to confirm its effectiveness and safety profiles for therapeutic advancement in the cancer field.Communicated by Ramaswamy H. Sarma.
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Sortilin (SORT1) is a multifunctional protein intricately involved in atherogenesis, coronary artery disease (CAD), and various neurological disorders. It has materialized as a potential pharmacological target for therapeutic development due to its diverse biological roles in pathological processes. Despite its central role under these conditions, effective therapeutic strategies targeting SORT1 remain challenging. In this study, we introduce a drug repurposing strategy guided by structural insights to identify potent SORT1 inhibitors with broad therapeutic potential. Our approach combines molecular docking, virtual screening, and molecular dynamics (MD) simulations, enabling the systematic evaluation of 3648 FDA-approved drugs for their potential to modulate SORT1. The investigation reveals a subset of repurposed drugs exhibiting highly favorable binding profiles and stable interactions within the binding site of SORT1. Notably, two hits, ergotamine and digitoxin, were carefully chosen based on their drug profiles and subjected to analyze their interactions with SORT1 and stability assessment via all-atom MD simulations spanning 300 ns (ns). The structural analyses uncover the complex binding interactions between these identified compounds and SORT1, offering essential mechanistic insights. Additionally, we explore the clinical implications of repurposing these compounds as potential therapeutic agents, emphasizing their significance in addressing atherogenesis, CAD, and neurological disorders. Overall, this study highlights the efficacy of structure-guided drug repurposing and provides a solid foundation for future research endeavors aimed at the development of effective therapies targeting SORT1 under diverse pathological conditions.
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Metastatic cancer is a leading cause of death in cancer patients worldwide. While circulating hybrid cells (CHCs) are implicated in metastatic spread, studies documenting their tissue origin remain sparse, with limited candidate approaches using one-two markers. Utilizing high-throughput single-cell and spatial transcriptomics, we identified tumor hybrid cells (THCs) co-expressing epithelial and macrophage markers and expressing a distinct transcriptome. Rarely, normal tissue showed these cells (NHCs), but their transcriptome was easily distinguishable from THCs. THCs with unique transcriptomes were observed in breast and colon cancers, suggesting this to be a generalizable phenomenon across cancer types. This study establishes a framework for HC identification in large datasets, providing compelling evidence for their tissue residence and offering comprehensive transcriptomic characterization. Furthermore, it sheds light on their differential function and identifies pathways that could explain their newly acquired invasive capabilities. THCs should be considered as potential therapeutic targets.
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OBJECTIVE: The current body of research on utilizing botulinum toxin (BTX) to manage temporomandibular disorders (TMDs) has not yet yielded definitive conclusions. The primary objective of this study was to determine the effectiveness of BTX in pain reduction for TMDs compared to placebo and other treatments. The secondary outcomes evaluated were adverse events, maximum mouth opening, bruxism events, and maximum occlusal force. MATERIALS AND METHODS: A literature search was performed on PubMed, Dimension Publication, Scopus, and Google Scholar. The RoB 2 tool was used for quality assessment. The mean differences in pain scores were estimated to measure the effect of BTX on pain reduction. For adverse events, the risk ratio for the incidence of side effects was calculated. RESULTS: Two hundred and sixty non-duplicate articles were identified; however, only 14 RCTS were included in this review. The total study population included 395 patients. The overall risk of bias showed a low to moderate quality of evidence. Results from 6 studies were reported only narratively; four studies were used for meta-analysis on pain reduction, and five were used for meta-analysis on adverse events. The control used in the meta-analysis was placebo injections. Results of the meta-analysis for pain reduction were statistically insignificant for the BTX group with mean differences at MD = -1.71 (95% CI, -2.87 to -0.5) at one month, -1.53 (95% CI, -2.80 to -0.27) at three months, and -1.33 (95% CI, -2.74 to 0.77) at six months. This showed that BTX treatment was not significantly better than placebo for a reduction in pain scores at 1, 3, and 6 months. Regarding safety, the placebo group showed a relative risk of 1.34 (95%CI, 0.48-6.78) and 1.17 (95%CI, 0.54-3.88) at 1 and 3 months respectively. However, the risks were not statistically significant. There was also no difference in the effectiveness of BTX compared to placebo and other treatments for maximum mouth opening, bruxism events, and maximum occlusal force. CONCLUSION: BTX was not associated with better outcomes in terms of pain reduction, adverse events, maximum mouth opening, bruxism events, and maximum occlusal force. More high-quality RCTs are needed to better understand this topic.