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2.
J Mol Model ; 30(6): 170, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38753123

ABSTRACT

CONTEXT: In the pursuit of novel therapeutic possibilities, repurposing existing drugs has gained prominence as an efficient strategy. The findings from our study highlight the potential of repurposed drugs as promising candidates against receptor for advanced glycation endproducts (RAGE) that offer therapeutic implications in cancer, neurodegenerative conditions and metabolic syndromes. Through careful analyses of binding affinities and interaction patterns, we identified a few promising candidates, ultimately focusing on sertindole and temoporfin. These candidates exhibited exceptional binding affinities, efficacy, and specificity within the RAGE binding pocket. Notably, they displayed a pronounced propensity to interact with the active site of RAGE. Our investigation further revealed that sertindole and temoporfin possess desirable pharmacological properties that highlighted them as attractive candidates for targeted drug development. Overall, our integrated computational approach provides a comprehensive understanding of the interactions between repurposed drugs, sertindole and temoporfin and RAGE that pave the way for future experimental validation and drug development endeavors. METHODS: We present an integrated approach utilizing molecular docking and extensive molecular dynamics (MD) simulations to evaluate the potential of FDA-approved drugs, sourced from DrugBank, against RAGE. To gain deeper insights into the binding mechanisms of the elucidated candidate repurposed drugs, sertindole and temoporfin with RAGE, we conducted extensive all-atom MD simulations, spanning 500 nanoseconds (ns). These simulations elucidated the conformational dynamics and stability of the RAGE-sertindole and RAGE-temoporfin complexes.


Subject(s)
Drug Repositioning , Imidazoles , Indoles , Molecular Docking Simulation , Molecular Dynamics Simulation , Receptor for Advanced Glycation End Products , Receptor for Advanced Glycation End Products/metabolism , Receptor for Advanced Glycation End Products/chemistry , Humans , Indoles/chemistry , Indoles/pharmacology , Imidazoles/chemistry , Imidazoles/pharmacology , Protein Binding , Neoplasms/drug therapy , Neoplasms/metabolism , Metabolic Diseases/drug therapy , Metabolic Diseases/metabolism , Binding Sites
3.
ACS Omega ; 9(14): 16089-16096, 2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38617645

ABSTRACT

Human transferrin (Htf) is vital in maintaining iron within the brain cells; any disruption results in the development of neurodegenerative diseases (NDs) and other related pathologies, especially Alzheimer's disease (AD). Ellagic acid (EA), a naturally occurring phenolic antioxidant, possesses neuroprotective potential and is present in a broad variety of fruits and vegetables. The current work explores the binding mechanism of dietary polyphenol, EA, with Htf by a combination of experimental and computational approaches. Molecular docking studies unveiled the binding of EA to Htf with good affinity. Molecular dynamic (MD) simulation further provided atomistic details of the binding process, demonstrating a stable Htf-EA complex formation without causing substantial alterations to the protein's conformation. Furthermore, fluorescence binding measurements indicated that EA forms a high-affinity interaction with Htf. Isothermal titration calorimetric measurements advocated the spontaneous nature of binding and also revealed the binding process to be exothermic. In conclusion, the study deciphered the binding mechanism of EA with Htf. The results demonstrated that EA binds with Htf with an excellent affinity spontaneously, thereby laying the groundwork for potential applications of EA in the realm of therapeutics for NDs in the context of iron homeostasis.

4.
Chem Biol Interact ; 394: 111002, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38604395

ABSTRACT

Lung inflammatory disorders are a major global health burden, impacting millions of people and raising rates of morbidity and death across many demographic groups. An industrial chemical and common environmental contaminant, formaldehyde (FA) presents serious health concerns to the respiratory system, including the onset and aggravation of lung inflammatory disorders. Epidemiological studies have shown significant associations between FA exposure levels and the incidence and severity of several respiratory diseases. FA causes inflammation in the respiratory tract via immunological activation, oxidative stress, and airway remodelling, aggravating pre-existing pulmonary inflammation and compromising lung function. Additionally, FA functions as a respiratory sensitizer, causing allergic responses and hypersensitivity pneumonitis in sensitive people. Understanding the complicated processes behind formaldehyde-induced lung inflammation is critical for directing targeted strategies aimed at minimizing environmental exposures and alleviating the burden of formaldehyde-related lung illnesses on global respiratory health. This abstract explores the intricate relationship between FA exposure and lung inflammatory diseases, including asthma, bronchitis, allergic inflammation, lung injury and pulmonary fibrosis.


Subject(s)
Asthma , Bronchitis , Formaldehyde , Pulmonary Fibrosis , Formaldehyde/toxicity , Formaldehyde/adverse effects , Humans , Asthma/chemically induced , Pulmonary Fibrosis/chemically induced , Bronchitis/chemically induced , Animals , Environmental Exposure/adverse effects , Lung/drug effects , Lung/pathology , Pneumonia/chemically induced , Oxidative Stress/drug effects , Inflammation/chemically induced
5.
Pathol Res Pract ; 257: 155282, 2024 May.
Article in English | MEDLINE | ID: mdl-38608371

ABSTRACT

Cancer is a group of diseases marked by unchecked cell proliferation and the ability for the disease to metastasize to different body areas. Enhancements in treatment and early detection are crucial for improved outcomes. LncRNAs are RNA molecules that encode proteins and have a length of more than 200 nucleotides. LncRNAs are crucial for chromatin architecture, gene regulation, and other cellular activities that impact both normal growth & pathological processes, even though they are unable to code for proteins. LncRNAs have emerged as significant regulators in the study of cancer biology, with a focus on their intricate function in the Notch signaling pathway. The imbalance of this pathway is often linked to a variety of malignancies. Notch signaling is essential for cellular functions like proliferation, differentiation, and death. The cellular response is shaped by these lncRNAs through their modulation of essential Notch pathway constituents such as receptors, ligands, and downstream effectors around it. Furthermore, a variety of cancer types exhibit irregular expression of Notch-related lncRNAs, underscoring their potential use as therapeutic targets and diagnostic markers. Gaining an understanding of the molecular processes behind the interaction between the Notch pathway and lncRNAs will help you better understand the intricate regulatory networks that control the development of cancer. This can open up new possibilities for individualized treatment plans and focused therapeutic interventions. The intricate relationships between lncRNAs & the Notch pathway in cancer are examined in this review.


Subject(s)
Neoplasms , RNA, Long Noncoding , Receptors, Notch , Signal Transduction , Humans , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Neoplasms/genetics , Neoplasms/pathology , Neoplasms/therapy , Neoplasms/metabolism , Receptors, Notch/metabolism , Receptors, Notch/genetics , Signal Transduction/genetics , Gene Expression Regulation, Neoplastic/genetics , Animals
6.
Life Sci ; 345: 122613, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38582393

ABSTRACT

Glioblastoma (GBM) is the most prevalent and deadly primary brain tumor type, with a discouragingly low survival rate and few effective treatments. An important function of the EGFR signalling pathway in the development of GBM is to affect tumor proliferation, persistence, and treatment resistance. Advances in molecular biology in the last several years have shown how important ncRNAs are for controlling a wide range of biological activities, including cancer progression and development. NcRNAs have become important post-transcriptional regulators of gene expression, and they may affect the EGFR pathway by either directly targeting EGFR or by modifying important transcription factors and downstream signalling molecules. The EGFR pathway is aberrantly activated in response to the dysregulation of certain ncRNAs, which has been linked to GBM carcinogenesis, treatment resistance, and unfavourable patient outcomes. We review the literature on miRNAs, circRNAs and lncRNAs that are implicated in the regulation of EGFR signalling in GBM, discussing their mechanisms of action, interactions with the signalling pathway, and implications for GBM therapy. Furthermore, we explore the potential of ncRNA-based strategies to overcome resistance to EGFR-targeted therapies, including the use of ncRNA mimics or inhibitors to modulate the activity of key regulators within the pathway.


Subject(s)
Brain Neoplasms , Glioblastoma , MicroRNAs , Humans , ErbB Receptors/metabolism , Glioblastoma/drug therapy , Glioblastoma/genetics , Glioblastoma/metabolism , Signal Transduction , MicroRNAs/metabolism , RNA, Untranslated/genetics , Brain Neoplasms/drug therapy , Brain Neoplasms/genetics , Brain Neoplasms/metabolism
7.
Sci Rep ; 14(1): 7284, 2024 03 27.
Article in English | MEDLINE | ID: mdl-38538618

ABSTRACT

Adherence to scheduled physician screenings for renal function monitoring in patients with chronic kidney disease (CKD) or those at high risk remains suboptimal despite the endorsement of regular screenings by several clinical practice guidelines. Our study aims to assess the effectiveness of a point-of-care CKD screening program led by these pharmacists using the PICCOLO device while recognizing the unique position of community pharmacists in primary care. We conducted an 11-month prospective point-of-care interventional research study in the United Arab Emirates to evaluate the performance of a community pharmacist-led CKD screening program for high-risk patients. Six diverse community pharmacies were selected based on staff availability, patient volume, and their offered range of services. Eligible individuals with risk factors for CKD were identified during medication evaluations. The PICCOLO Comprehensive Metabolic Panel facilitated on-site blood analysis, delivering estimated Glomerular Filtration Rate (eGFR) results within 10 to 15 min. Data also included eGFR categories, demographic information, and insights into lifestyle and health habits collected through a questionnaire. Pharmacists conducted comprehensive medication reviews and offered referrals and lifestyle guidance as part of the program. The study encompassed a total of 400 patients, with an average age of 69 ± 13.4 years within the study cohort. Notably, 38.8% (155 individuals) of the 400 patients were found to have undiagnosed CKD stages 3-5. Univariate logistic regression analysis revealed a significant association between a higher incidence of CKD stages 3-5 and factors such as older age, a history of hypertension, vascular disease, and diabetes mellitus. In the multivariate regression model, age and a history of diabetes mellitus emerged as significant predictors of an elevated risk of CKD. This study sheds light on the viability and impact of CKD screening programs conducted by community pharmacists, particularly in detecting CKD stages 3-5. The findings have implications for healthcare policies, as they can influence the enhancement of early detection and management of CKD. Moreover, these insights may catalyze focused screening initiatives and strengthen collaboration between community pharmacies and healthcare systems to benefit patients at high risk of CKD.


Subject(s)
Diabetes Mellitus , Hypertension , Renal Insufficiency, Chronic , Humans , Middle Aged , Aged , Aged, 80 and over , Pharmacists , Glomerular Filtration Rate , Point-of-Care Systems , Prospective Studies , Hypertension/complications , Hypertension/diagnosis , Hypertension/epidemiology , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/epidemiology , Diabetes Mellitus/epidemiology
8.
Pathol Res Pract ; 256: 155224, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38452584

ABSTRACT

Sepsis, a potentially fatal illness caused by an improper host response to infection, remains a serious problem in the world of healthcare. In recent years, the role of ncRNA has emerged as a pivotal aspect in the intricate landscape of cellular regulation. The exploration of ncRNA-mediated regulatory networks reveals their profound influence on key molecular pathways orchestrating pyroptotic responses during septic conditions. Through a comprehensive analysis of current literature, we navigate the diverse classes of ncRNAs, including miRNAs, lncRNAs, and circRNAs, elucidating their roles as both facilitators and inhibitors in the modulation of pyroptotic processes. Furthermore, we highlight the potential diagnostic and therapeutic implications of targeting these ncRNAs in the context of sepsis, aiming to cover the method for novel and effective strategies to mitigate the devastating consequences of septic pathogenesis. As we unravel the complexities of this regulatory axis, a deeper understanding of the intricate crosstalk between ncRNAs and pyroptosis emerges, offering promising avenues for advancing our approach to sepsis intervention. The intricate pathophysiology of sepsis is examined in this review, which explores the dynamic interaction between ncRNAs and pyroptosis, a highly regulated kind of programmed cell death.


Subject(s)
MicroRNAs , RNA, Long Noncoding , Sepsis , Humans , Pyroptosis/physiology , RNA, Untranslated/genetics , RNA, Untranslated/metabolism , MicroRNAs/genetics , RNA, Long Noncoding/genetics
9.
Pathol Res Pract ; 256: 155259, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38503004

ABSTRACT

Circular RNAs (circRNAs) have been recognized as key components in the intricate regulatory network of the KRAS pathway across various cancers. The KRAS pathway, a central signalling cascade crucial in tumorigenesis, has gained substantial emphasis as a possible therapeutic target. CircRNAs, a subgroup of non-coding RNAs known for their closed circular arrangement, play diverse roles in gene regulation, contributing to the intricate landscape of cancer biology. This review consolidates existing knowledge on circRNAs within the framework of the KRAS pathway, emphasizing their multifaceted functions in cancer progression. Notable circRNAs, such as Circ_GLG1 and circITGA7, have been identified as pivotal regulators in colorectal cancer (CRC), influencing KRAS expression and the Ras signaling pathway. Aside from their significance in gene regulation, circRNAs contribute to immune evasion, apoptosis, and drug tolerance within KRAS-driven cancers, adding complexity to the intricate interplay. While our comprehension of circRNAs in the KRAS pathway is evolving, challenges such as the diverse landscape of KRAS mutant tumors and the necessity for synergistic combination therapies persist. Integrating cutting-edge technologies, including deep learning-based prediction methods, holds the potential for unveiling disease-associated circRNAs and identifying novel therapeutic targets. Sustained research efforts are crucial to comprehensively unravel the molecular mechanisms governing the intricate interplay between circRNAs and the KRAS pathway, offering insights that could potentially revolutionize cancer diagnostics and treatment strategies.


Subject(s)
Neoplasms , RNA, Circular , Humans , RNA, Circular/metabolism , Proto-Oncogene Proteins p21(ras)/genetics , Proto-Oncogene Proteins p21(ras)/metabolism , Neoplasms/genetics , Neoplastic Processes
10.
Front Pharmacol ; 15: 1348128, 2024.
Article in English | MEDLINE | ID: mdl-38495092

ABSTRACT

Human transferrin (htf) plays a crucial role in regulating the balance of iron within brain cells; any disruption directly contributes to the development of Neurodegenerative Diseases (NDs) and other related pathologies, especially Alzheimer's Disease (AD). In recent times, a transition towards natural compounds is evident to treat diseases and this shift is mainly attributed to their broad therapeutic potential along with minimal side effects. Capsaicin, a natural compound abundantly found in red and chili peppers, possess neuroprotective potential. The current work targets to decipher the interaction mechanism of capsaicin with htf using experimental and computational approaches. Molecular docking analysis revealed that capsaicin occupies the iron binding pocket of htf, with good binding affinity. Further, the binding mechanism was investigated atomistically using Molecular dynamic (MD) simulation approach. The results revealed no significant alterations in the structure of htf implying the stability of the complex. In silico observations were validated by fluorescence binding assay. Capsaicin binds to htf with a binding constant (K) of 3.99 × 106 M-1, implying the stability of the htf-capsaicin complex. This study lays a platform for potential applications of capsaicin in treatment of NDs in terms of iron homeostasis.

11.
Clin Med Insights Endocrinol Diabetes ; 17: 11795514241235514, 2024.
Article in English | MEDLINE | ID: mdl-38495947

ABSTRACT

Background: The use of ChatGPT and artificial intelligence (AI) in the management of metabolic and endocrine disorders presents both significant opportunities and notable risks. Objectives: To investigate the benefits and risks associated with the application of ChatGPT in managing diabetes and metabolic illnesses by exploring the perspectives of endocrinologists and diabetologists. Methods and materials: The study employed a qualitative research approach. A semi-structured in-depth interview guide was developed. A convenience sample of 25 endocrinologists and diabetologists was enrolled and interviewed. All interviews were audiotaped and verbatim transcribed; then, thematic analysis was used to determine the themes in the data. Results: The findings of the thematic analysis resulted in 19 codes and 9 major themes regarding the benefits of implementing AI and ChatGPT in managing diabetes and metabolic illnesses. Moreover, the extracted risks of implementing AI and ChatGPT in managing diabetes and metabolic illnesses were categorized into 7 themes and 14 codes. The benefits of heightened diagnostic precision, tailored treatment, and efficient resource utilization have potential to improve patient results. Concurrently, the identification of potential challenges, such as data security concerns and the need for AI that can be explained, enables stakeholders to proactively tackle these issues. Conclusions: Regulatory frameworks must evolve to keep pace with the rapid adoption of AI in healthcare. Sustained attention to ethical considerations, including obtaining patient consent, safeguarding data privacy, ensuring accountability, and promoting fairness, remains critical. Despite its potential impact on the human aspect of healthcare, AI will remain an integral component of patient-centered care. Striking a balance between AI-assisted decision-making and human expertise is essential to uphold trust and provide comprehensive patient care.


Regulatory frameworks must evolve to keep pace with the rapid adoption of AI in healthcare. Sustained attention to ethical considerations, including obtaining patient consent, safeguarding data privacy, ensuring accountability, and promoting fairness, remains critical. Despite its potential impact on the human aspect of healthcare, AI will remain an integral component of patient-centered care. The use of ChatGPT in the management of metabolic and endocrine disorders presents both significant opportunities and notable risks. The benefits of heightened diagnostic precision, tailored treatment, and efficient resource utilization have potential to improve patient results. Concurrently, the identification of potential challenges, such as data security concerns and the need for AI that can be explained, enables stakeholders to proactively tackle these issues. Regulatory frameworks must evolve to keep pace with the rapid adoption of AI in healthcare. Sustained attention to ethical considerations, including obtaining patient consent, safeguarding data privacy, ensuring accountability, and promoting fairness, remains critical. Despite its potential impact on the human aspect of healthcare, AI will remain an integral component of patient-centered care. Striking a balance between AI-assisted decision-making and human expertise is essential to uphold trust and provide comprehensive patient care.

12.
Noncoding RNA Res ; 9(2): 277-287, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38505309

ABSTRACT

The intricate molecular landscape of cancer pathogenesis continues to captivate researchers worldwide, with Circular RNAs (circRNAs) emerging as pivotal players in the dynamic regulation of biological functions. The study investigates the elusive link between circRNAs and the Transforming Growth Factor-ß (TGF-ß) signalling pathway, exploring their collective influence on cancer progression and metastasis. Our comprehensive investigation begins by profiling circRNA expression patterns in diverse cancer types, revealing a repertoire of circRNAs intricately linked to the TGF-ß pathway. Through integrated bioinformatics analyses and functional experiments, we elucidate the specific circRNA-mRNA interactions that modulate TGF-ß signalling, unveiling the regulatory controls governing this crucial pathway. Furthermore, we provide compelling evidence of the impact of circRNA-mediated TGF-ß modulation on key cellular processes, including epithelial-mesenchymal transition (EMT), migration, and cell proliferation. In addition to their mechanistic roles, circRNAs have shown promise as diagnostic and prognostic biomarkers, as well as potential molecular targets for cancer therapy. Their ability to modulate critical pathways, such as the TGF-ß signalling axis, underscores their significance in cancer biology and clinical applications. The intricate interplay between circRNAs and TGF-ß is dissected, uncovering novel regulatory circuits that contribute to the complexity of cancer biology. This review unravels a previously unexplored dimension of carcinogenesis, emphasizing the crucial role of circRNAs in shaping the TGF-ß signalling landscape.

14.
J Multidiscip Healthc ; 17: 1251-1263, 2024.
Article in English | MEDLINE | ID: mdl-38524860

ABSTRACT

Background: Several studies indicate a correlation between consanguinity and genetic disorders, congenital malformations, harm to reproductive health, and increased child mortality. Objective: To assess students' knowledge and attitudes about risks and prevention of consanguineous marriage. Methods: Demographic details of the participants and data on knowledge and attitudes concerning the risks and prevention of consanguineous marriage were obtained using an online self-administered questionnaire. The factors associated with good knowledge and attitude toward consanguineous marriage were investigated by logistic regression analysis. Results: A total of 667 participants enrolled in the study. The average knowledge score about consanguineous marriage risk and prevention was 78.6% with a 95% confidence interval (CI) [77.3, 79.8], and the average attitude was 79.7% with a 95% confidence interval (CI) [79, 80.6]. A better knowledge score was observed in older participants (OR 1.01; 95% CI 1.004-1.024), females (OR 1.69; 95% CI 1.48-1.94), participants with parental history of consanguinity (OR 1.33; 95% CI 1.17-1.52), participants with family history of consanguineous marriage (OR 5.18; 95% CI 2.19-7.10), and participants with family history of inherited disease (OR 1.52; 95% CI 1.25-1.86). Conclusion: In general, the overall level of knowledge and attitudes toward consanguineous marriage risk and prevention was good among university students. To efficiently control and manage the adverse health impacts associated with consanguineous marriage, there is an urgent need to develop and implement evidence-based counseling and screening programs for consanguineous marriage that would significantly reduce the number of at-risk marriages.

15.
Risk Manag Healthc Policy ; 17: 663-675, 2024.
Article in English | MEDLINE | ID: mdl-38528943

ABSTRACT

Background: p-Phenylenediamine (PPD) has been used over the past five decades as a primary precursor in the production of oxidative hair dyes. Numerous health dangers are associated with the short- and long-term use of PPD, raising concerns about its safety. For instance, mounting data suggests that PPD is linked to dermatitis and allergy cases. Objective: To quantify the PPD content in hair dyes by measuring the PPD concentration after mixing the ingredients of commercial hair dyes. Methods: A total of 290 permanent hair dyes were tested. RP-HPLC-DAD analysis was performed to determine and quantify the PPD content. Results: The estimated mean of the PPD limit was 0.89 (95% CI [0.81-0.96]). Of the 290 tested hair dyes, 7.2% (n = 21) exceeded the recommended PPD concentration after mixing. Significantly more hair dyes manufactured in India and China had a PPD content exceeding 2% after mixing compared to dyes from other regions (P = 0.001). Moreover, hair dyes manufactured in India and the UAE were more likely to have incomplete descriptions of the conditions of use and warnings on the label (P = 0.002). Conclusion: The effectiveness of the current regulations relevant to these products should be reevaluated. Moreover, through the use of good manufacturing procedures (GMPs), research, and the reporting of adverse reactions, hair dyes should be subjected to better control and monitoring in terms of their safety and quality.

16.
Exp Gerontol ; 188: 112389, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38432575

ABSTRACT

Aging-related diseases (ARDs) are a major global health concern, and the development of effective therapies is urgently needed. Kaempferol, a flavonoid found in several plants, has emerged as a promising candidate for ameliorating ARDs. This comprehensive review examines Kaempferol's chemical properties, safety profile, and pharmacokinetics, and highlights its potential therapeutic utility against ARDs. Kaempferol's therapeutic potential is underpinned by its distinctive chemical structure, which confers antioxidative and anti-inflammatory properties. Kaempferol counteracts reactive oxygen species (ROS) and modulates crucial cellular pathways, thereby combating oxidative stress and inflammation, hallmarks of ARDs. Kaempferol's low toxicity and wide safety margins, as demonstrated by preclinical and clinical studies, further substantiate its therapeutic potential. Compelling evidence supports Kaempferol's substantial potential in addressing ARDs through several mechanisms, notably anti-inflammatory, antioxidant, and anti-apoptotic actions. Kaempferol exhibits a versatile neuroprotective effect by modulating various proinflammatory signaling pathways, including NF-kB, p38MAPK, AKT, and the ß-catenin cascade. Additionally, it hinders the formation and aggregation of beta-amyloid protein and regulates brain-derived neurotrophic factors. In terms of its anticancer potential, kaempferol acts through diverse pathways, inducing apoptosis, arresting the cell cycle at the G2/M phase, suppressing epithelial-mesenchymal transition (EMT)-related markers, and affecting the phosphoinositide 3-kinase/protein kinase B signaling pathways. Subsequent studies should focus on refining dosage regimens, exploring innovative delivery systems, and conducting comprehensive clinical trials to translate these findings into effective therapeutic applications.


Subject(s)
Kaempferols , Respiratory Distress Syndrome , Humans , Kaempferols/pharmacology , Kaempferols/therapeutic use , Kaempferols/chemistry , Phosphatidylinositol 3-Kinases , Antioxidants/pharmacology , Antioxidants/therapeutic use , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Aging , Respiratory Distress Syndrome/drug therapy
17.
Saudi Pharm J ; 32(3): 101965, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38313821

ABSTRACT

Objectives: To assess the characteristics of patients with heart failure with reduced ejection fraction (HFrEF) and heart failure with mid-range ejection fraction (HFmrEF), as well as the current application of guideline-directed medical therapy (GDMT) in Palestine. Methods: This retrospective cohort study involved a population of heart failure (HF) patients who visited cardiology clinics at An-Najah National University Hospital and the National Hospital, Palestine. The primary outcome measures of interest were the proportions of patients prescribed guideline-based cardiovascular medications (GBCMs), such as angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin II receptor blockers (ARBs), ß-blockers, and mineralocorticoid receptor antagonists (MRAs), and the corresponding optimized doses at ≥ 50 % of targets and the reasons underlying the non-prescription of GDMT. Results: A total of 70.5%, 56.6%, and 88.6% of patients were on ACEIs/ARBs, MRAs, and ß-blockers, respectively. Of all patients, 38.7% were on the triple GDMT regimen. Conclusion: Less than half the patients received the triple combination treatment. Age, diabetes mellitus, chronic renal disease, and admission to the hospital for HF all had significant independent relationships with the reduced utilization and inadequate dosage of GDMT.

18.
Diabetes Metab Syndr Obes ; 17: 545-561, 2024.
Article in English | MEDLINE | ID: mdl-38327733

ABSTRACT

Background: Non-alcoholic fatty liver disease (NAFLD) is a common disease and has been increasing in recent years. To date, no FDA-approved drug specifically targets NAFLD. Methods: The terms "Non-alcoholic Fatty Liver Disease" and "NAFLD" were used in a search of ClinicalTrials.gov on August 24, 2023. Two evaluators independently examined the trials using predetermined eligibility criteria. Studies had to be interventional, NAFLD focused, in Phase IV, and completed to be eligible for this review. Results: The ClinicalTrials.gov database was searched for trials examining pharmacotherapeutics in NAFLD. The search revealed 1364 trials, with 31 meeting the inclusion criteria. Out of these, 19 were finalized for evaluation. The dominant intervention model was Parallel. The most prevalent studies were in Korea (26.3%) and China (21.1%). The most common intervention was metformin (12.1%), with others like Exenatide and Pioglitazone accounting for 9.1%. Conclusion: Therapeutics used to manage NAFLD are limited. However, various medications offer potential benefits. Further investigations are definitely warranted.

19.
J Biomol Struct Dyn ; : 1-11, 2024 Feb 19.
Article in English | MEDLINE | ID: mdl-38373093

ABSTRACT

Neurodegenerative diseases such as Alzheimer's disease (AD) pose a significant global health challenge that requires the exploration of innovative therapeutic strategies. Triggering receptor expressed on myeloid cells-2 (TREM2) is one of the critical proteins involved in immune regulation and neuroinflammation. It has emerged as a promising therapeutic target to develop treatments for neurodegenerative disorders like AD. Here, we employed a comprehensive virtual screening approach to identify potential small molecule inhibitors among FDA-approved drugs for TREM2. The docking study reveals significant binding affinity, ranging from -7.8 kcal/mol to -8.5 kcal/mol, for the elucidated hits against TREM2, accompanied by several crucial interactions. Among the repurposed drugs identified in the initial screening, Carpipramine, Clocapramine, and Pimozide stood out due to their notable binding potential and favorable drug profiling. Further, we conducted molecular dynamics (MD) simulations on the selected molecules that probed their structural dynamics and stability within the TREM2 binding pocket. The structural parameters and hydrogen bond dynamics remained remarkably stable throughout the simulated trajectories. Furthermore, we performed principal component analysis (PCA) and constructed free energy landscapes (FELs) to gain deeper insights into ligand binding and conformational flexibility of TREM2. The findings revealed that the elucidated molecules, Carpipramine, Clocapramine, and Pimozide, exhibited an exceptional fit within the binding pocket of TREM2 with remarkable stability and interaction patterns throughout the 500 ns simulation window. Interestingly, these molecules possessed a spectrum of anti-neurodegenerative properties and favorable drug profiles, which suggest their potential as promising drug candidates for repurposing in the treatment of AD.Communicated by Ramaswamy H. Sarma.

20.
Saudi Pharm J ; 32(4): 101987, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38405042

ABSTRACT

Background: The escalating worldwide concerns for mental health, significantly amplified by the COVID-19 pandemic, necessitates understanding the impact on vulnerable populations, such as university students. This study aims to investigate the prevalence and implications of depression, anxiety, and stress among university students in the United Arab Emirates (UAE) using the Depression, Anxiety, and Stress Scale-21 Items (DASS-21). Methods: This study utilized convenience sampling to investigate the mental health of undergraduates in UAE universities using a bilingual DASS-21 questionnaire via Google Forms. Analysis was conducted using SPSS version 29.0, employing descriptive statistics, Chi-squared tests, Mann-Whitney tests, Kruskal-Wallis tests, and Multinomial Logistic Regression to analyze relationships between sociodemographic variables and mental health scores. Results: The study examined 332 students, with most female participants (81 %, n = 269) and individuals aged 18-20 (89.8 %, n = 298). It revealed higher mean DASS scores among females: Depression (M = 15.80, p = 0.030), Anxiety (M = 17.63, p < 0.001), and Stress (M = 22.61, p < 0.001). Fourth-year students exhibited the highest DASS scores for depression (M = 30.33, p = 0.002), anxiety (M = 21.33, p = 0.002), and stress (M = 27.00, p = 0.005). Younger participants aged 18-20 had an odds ratio (OR) of 4.925 for depression, indicating they were approximately five times more likely to experience depression. Conclusions: This study reveals gender, age, and academic-year variations in depression, anxiety, and stress among UAE university students. Specifically, our findings indicate higher levels of anxiety and stress among females and reveal academic-year and age-related patterns in mental health conditions. University support services in the UAE should better address student needs, including counseling focused on high school to university transition challenges.

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