Ischemic retinopathy is a leading cause of blindness:Ischemic retinopathies including diabetic retinopathy(DR),retinopathy of prematurity,and retinal artery and vein occlusion are major causes of visual impairment.Isc...Ischemic retinopathy is a leading cause of blindness:Ischemic retinopathies including diabetic retinopathy(DR),retinopathy of prematurity,and retinal artery and vein occlusion are major causes of visual impairment.Ischemic retinopathy can be acute,such as in central or branch retinal artery occlusion,or chronic,such as with DR(Figure 1).Although the causes of retinopathies are diverse,one pathogenic event shared by these conditions is the myeloid cell response to retinal ischemia(Shahror et al.,2024a).展开更多
Background:Corchorus olitorius L.(Malvaceae)is a green leafy vegetable widely consumed in the Middle East and valued for its rich nutritional content.Its essential oils,an important class of secondary metabolites,are ...Background:Corchorus olitorius L.(Malvaceae)is a green leafy vegetable widely consumed in the Middle East and valued for its rich nutritional content.Its essential oils,an important class of secondary metabolites,are of growing interest for potential use in cosmetics and fragrance industries due to their bioactive properties.Methods:Leaves of C.olitorius cultivated in Egypt were extracted using microwave-assisted hydrodistillation(MAHD)and conventional hydrodistillation(HD).The oils were analyzed by gas chromatography-mass spectrometry(GC-MS)to characterize their chemical profiles.In vitro assays were conducted to evaluate their anti-elastase and anti-collagenase activities,and in silico studies were performed to predict the pharmacokinetic and pharmacodynamic properties of major constituents.Results:GC-MS analysis showed that aldehydes,alkanes,fatty alcohols,fatty acids,and their derivatives were the predominant compound classes in both oils.Notably,oxygenated diterpenes(11.22%)were present exclusively in the MAHD oil,while triterpenoids(16.37%)were found only in the HD oil.The MAHD oil demonstrated stronger In vitro anti-elastase(IC_(50)=42.5μg/mL)and anti-collagenase(IC_(50)=131.5μg/mL)activities compared to the HD oil(IC_(50)=66.7 and 206.8μg/mL,respectively),reflecting an approximate 36.3%improvement in elastase inhibition and 36.4%improvement in collagenase inhibition.In silico docking indicated that the triterpenoidβ-amyrin acetate showed the highest predicted binding affinity for porcine pancreatic elastase(PDB ID:6QEO,ΔG=−8.1 kcal/mol)and collagenase(PDB ID:456C,ΔG=−9.1 kcal/mol)among the major compounds analyzed.Conclusion:These findings demonstrate that MAHD is a greener and more efficient extraction method,yielding oil with enhanced enzyme inhibitory activity compared to conventional HD.The promising anti-elastase and anti-collagenase properties suggest that C.olitorius MAHD oil could serve as a potential candidate for anti-aging cosmetic formulations,following further validation.展开更多
BACKGROUND Crohn’s disease(CD)is a chronic inflammatory bowel disease with unknown etiology.Inflammatory chemical mediators synthesized from arachidonic acid,an n-6 polyunsaturated fatty acid(PUFA),have been shown to...BACKGROUND Crohn’s disease(CD)is a chronic inflammatory bowel disease with unknown etiology.Inflammatory chemical mediators synthesized from arachidonic acid,an n-6 polyunsaturated fatty acid(PUFA),have been shown to activate CD.Additionally,n-3 PUFAs are metabolized by the same enzyme as n-6 PUFAs and known to inhibit the arachidonic acid cascade.Our previous study noted that the presence of erythrocyte membrane fatty acids is a characteristic finding in Japanese CD patients.It was thus speculated that FADS2 gene polymorphisms,which induce PUFA metabolizing enzymes,are involved in the pathogenesis of CD,though no such relationship was found.AIM To investigate the relationship of FADS2 polymorphisms with serum and erythrocyte membrane fatty acid composition ratios,and disease activity.METHODS Using previously reported findings regarding FADS2 genetic polymorphisms,the records of 52 CD patients undergoing treatment at Jikei University Kashiwa Hospital were analyzed.Mutations noted were divided into three groups;wild-type(GG),heterozygous mutants(GA),and homozygous(AA),with the activities of delta-6 and delta-5 desaturases compared using redefined d6d index(rd.d6di)and d5d index(d5di).Additionally,comparisons of serum and erythrocyte membranes for fatty acid composition,and also gene polymorphisms and CD activity index(CDAI)were performed.RESULTS The presence of the rs174538 mutation in FADS2 resulted in reduction of only rd.d6di in the erythrocyte membrane(P<0.01).In contrast,that mutation was found to be associated with d5di induced by FADS1 in serum(P=0.019)as well as the erythrocyte membrane(P<0.0001),and also with reduction in the fatty acid composition of arachidonic acid in both serum(P<0.0001)and the erythrocyte membrane(P<0.01).Regarding disease activity,a positive correlation of CDAI score with rd.d6di in both serum(P<0.05)and the erythrocyte membrane(P<0.05)was found only in the rs174538 wild-type group.In contrast,there was no correction between CDAI and d5di in either serum or erythrocyte membrane samples.CONCLUSION The rs174538 mutation alters the fatty acid profile through strong linkage to the FADS1 gene.In wild-type individuals,rd.d6di was positively correlated with CDAI,suggesting predictive utility of disease severity.展开更多
Nanotechnology has revolutionized drug delivery,particularly through nanoformulations of phytoconstituents,enhancing their therapeutic potential.Despite their broad bioactivities,plant-based compounds often suffer fro...Nanotechnology has revolutionized drug delivery,particularly through nanoformulations of phytoconstituents,enhancing their therapeutic potential.Despite their broad bioactivities,plant-based compounds often suffer from poor bioavailability and stability.Nanoformulations address these limitations by improving solubility,targeted delivery,and controlled release.This approach opens new possibilities for treating chronic diseases like cancer,diabetes,and neurodegenerative disorders.This review aims to examine recent advancements in nanotechnology-based formulation strategies designed to enhance the delivery,stability,and therapeutic efficacy of phytochemicals and also discusses regulatory issues,safety concerns,scalability,and cost-effectiveness.Emphasis was placed on nanoformulation techniques employed for key phytoconstituents such as curcumin,resveratrol,epigallocatechin gallate,and quercetin.The most commonly employed nanocarriers included polymeric nanoparticles,solid lipid nanoparticles,and liposomes.These formulations significantly improved the solubility,stability,and controlled release profiles of phytochemicals.In vitro and in vivo studies demonstrated enhanced anti-inflammatory,anticancer,and antioxidant activities.Moreover,surface-modified and targeted nanoparticles showed promise in increasing site-specific targeting and enhancing bioavailability of the encapsulated compounds.Nanoformulations present a promising strategy for overcoming the pharmacokinetic limitations of phytochemicals.Despite encouraging preclinical results,further studies are needed to address issues related to long-term safety,clinical efficacy,and regulatory approval for successful clinical translation.展开更多
The rapid growth of biomedical data,particularly multi-omics data including genomes,transcriptomics,proteomics,metabolomics,and epigenomics,medical research and clinical decision-making confront both new opportunities...The rapid growth of biomedical data,particularly multi-omics data including genomes,transcriptomics,proteomics,metabolomics,and epigenomics,medical research and clinical decision-making confront both new opportunities and obstacles.The huge and diversified nature of these datasets cannot always be managed using traditional data analysis methods.As a consequence,deep learning has emerged as a strong tool for analysing numerous omics data due to its ability to handle complex and non-linear relationships.This paper explores the fundamental concepts of deep learning and how they are used in multi-omics medical data mining.We demonstrate how autoencoders,variational autoencoders,multimodal models,attention mechanisms,transformers,and graph neural networks enable pattern analysis and recognition across all omics data.Deep learning has been found to be effective in illness classification,biomarker identification,gene network learning,and therapeutic efficacy prediction.We also consider critical problems like as data quality,model explainability,whether findings can be repeated,and computational power requirements.We now consider future elements of combining omics with clinical and imaging data,explainable AI,federated learning,and real-time diagnostics.Overall,this study emphasises the need of collaborating across disciplines to advance deep learning-based multi-omics research for precision medicine and comprehending complicated disorders.展开更多
Objectives:Breast cancer(BC)is the leading cause of cancer-related mortality in women,largely due to metastasis.This study aims to explore the role of purine nucleoside phosphorylase(PNP),a key enzyme in purine metabo...Objectives:Breast cancer(BC)is the leading cause of cancer-related mortality in women,largely due to metastasis.This study aims to explore the role of purine nucleoside phosphorylase(PNP),a key enzyme in purine metabolism,in the aggressiveness and metastatic behavior of BC.Methods:A comprehensive analysis was performed using in silico transcriptomic data(n=2509 patients),immunohistochemical profiling of BC tissues(n=103),and validation through western blotting in multiple BC cell lines.Gene expression and survival analyses were conducted using Tumor Immune Estimation Resource(TIMER),Gene Expression Profiling Interactive Analysis 2(GEPIA2),and the cBioPortal for cancer genomics(cBioPortal)platforms.Correlations between PNP and key epithelial–mesenchymal transition(EMT)markers,molecular subtypes,tumor grades,and stages were examined.Results:PNP was significantly overexpressed in human epidermal growth factor receptor 2(HER-2)-positive and triple-negative BCs compared to luminal subtypes.High PNP levels were strongly associated with advanced BC stages,high-grade tumors,EMT phenotypes,and poor overall survival.Notably,HER-2 inhibition suppressed PNP expression,while PNP gene silencing induced HER-2 upregulation,revealing a reciprocal regulatory loop.Dual inhibition of PNP and HER-2 resulted in a significant reduction in cell viability compared to HER-2 inhibition alone.Conclusion:Collectively,PNP emerges as a promising biomarker of BC aggressiveness and progression.Its reciprocal interaction with HER-2 underscores its potential as a therapeutic target.Dual targeting of PNP and HER-2 may offer a novel strategy for improving outcomes in aggressive BC subtypes.展开更多
Objective: To analyze the use of all subsidized prescription drugs including their use of drug combination generally accepted as carrying a risk of severe interactions. Methodology: In a cross sectional study, we anal...Objective: To analyze the use of all subsidized prescription drugs including their use of drug combination generally accepted as carrying a risk of severe interactions. Methodology: In a cross sectional study, we analyzed all prescriptions (n = 1014) involving two or more drugs dispensed to the population (age range 4-85 years) from all pharmacies, clinics and hospitals. Data were stratified by age and sex, and frequency of common interacting drugs. Potential drug interactions were classified according to clinical relevance as significance of severity (types A: major, B: moderate, and C: minor) and documented evidence (types 1, 2, 3, and 4). Result and Discussion: The growing use of pharmacological agents means that drug interactions are of increasing interest for public health. Monitoring of potential drug interactions may improve the quality of drug prescribing and dispensing, and it might form a basis for education focused on appropriate prescribing. To make the manifestation of adverse interaction subside, management strategies must be exercised if two interacting drugs have to be taken with each other, involving: adjusting the dose of the object drug;spacing dosing times to avoid the interaction. The pharmacist, along with the prescriber has a duty to ensure that patients are aware of the risk of side effects and a suitable course of action they should take. Conclusion: It is unrealistic to expect clinicians to memorize the thousands of drug-drug interactions and their clinical significance, especially considering the rate of introduction of novel drugs and the escalating appreciation of the importance of pharmacogenomics. Reliable regularly updated decision support systems and information technology are necessary to help avert dangerous drug combinations.展开更多
An ADS （automated dispensing system） was implemented in our hospital pharmacy in 2008 to optimize and secure the medication process. The main objective of this study was to compare the projected and the real ROI （r...An ADS （automated dispensing system） was implemented in our hospital pharmacy in 2008 to optimize and secure the medication process. The main objective of this study was to compare the projected and the real ROI （return on investment）, after seven years of use. ROI was calculated annually （from 2008 to 2015）, by deducting the cost of investment （ADS buying and implementation, maintenance, repairs and ADS upgrade） from the cost saving （drugs stock reduction and decrease of pharmacy staff dedicated to global dispensing）. In 2015, total costs saving （＋$1,141,987） were divided between decreasing drug stock value and reduction of pharmacy staff. Total costs of investment （-$978,656） were acquisition, maintenance, repairs and an unplanned upgrade costs. Finally, the real ROI was ＋$163,331 after seven years of use. In 2008, projected ROI was ＋$410,786. The real payback period has been increased by approximately two years （six years of use, instead of four years as expected）. Despite their cost, ADSs are a worthwhile investment, leading to a ROI within a few years. These economic considerations should be put into perspective with optimization of drugs stock management, greater efficiency of the global dispensing process, securitization of medication process and redeployment of pharmacy staff.展开更多
Meloxicam(MLX) is an anti-inflammatory drug susceptible to variations and crystalline transitions. In compounding pharmacies, the complete crystallographic evaluation of the raw material is not a routine procedure. We...Meloxicam(MLX) is an anti-inflammatory drug susceptible to variations and crystalline transitions. In compounding pharmacies, the complete crystallographic evaluation of the raw material is not a routine procedure. We performed a complete crystallographic characterization of aleatory raw MLX samples from compounding pharmacies. X-ray diffraction indicated the presence of two crystalline forms in one sample. DSC experiments suggested that crystallization, or a crystal transition, occurred differently between samples. The FTIR and ~1H NMR spectra showed characteristic assignments.^(13)C solid-state NMR spectroscopy indicated the presence of more than one phase in a sample from pharmacy B. The Hirshfeld surface analysis, with electrostatic potential projection, allowed complete assignment of the UV spectra in ethanol solution. The polymorph I of meloxicam was more active than polymorph III in an experimental model of acute inflammation in mice. Our results highlighted the need for complete crystallographic characterization and the separation of freely used raw materials in compounding pharmacies,as a routine procedure, to ensure the desired dose/effect.展开更多
Inflammatory bowel disease(IBD)is a chronic inflammatory illness of the intes-tine.While the mechanism underlying the pathogenesis of IBD is not fully under-stood,it is believed that a complex combination of host immu...Inflammatory bowel disease(IBD)is a chronic inflammatory illness of the intes-tine.While the mechanism underlying the pathogenesis of IBD is not fully under-stood,it is believed that a complex combination of host immunological response,environmental exposure,particularly the gut microbiota,and genetic suscept-ibility represents the major determinants.The gut virome is a group of viruses found in great frequency in the gastrointestinal tract of humans.The gut virome varies greatly among individuals and is influenced by factors including lifestyle,diet,health and disease conditions,geography,and urbanization.The majority of research has focused on the significance of gut bacteria in the progression of IBD,although viral populations represent an important component of the microbiome.We conducted this review to highlight the viral communities in the gut and their expected roles in the etiopathogenesis of IBD regarding published research to date.展开更多
Background: For the WHO, anemia is a serious public health problem, with an emphasis on deprivation anemia, which has socioeconomic conditions as determining factors for its development. Among nutritional anemias, the...Background: For the WHO, anemia is a serious public health problem, with an emphasis on deprivation anemia, which has socioeconomic conditions as determining factors for its development. Among nutritional anemias, the most relevant is iron deficiency, whose main form of prevention and treatment is supplementation with ferrous sulfate dispensed in the public health system, with the need to periodically check whether the drug has the quality required by regulatory health agencies. Thus, the objective of this study was to analyze the quality of the ferrous sulfate medication, from the same laboratory, and dispensed in a basic health unit (BHU) and a commercial pharmacy (CF). Materials and Methods: An analytical, qualitative and quantitative study of ferrous sulfate heptahydrate (25 mg/mL in 100 mL syrup), carried out on 20 BHU and 10 from CF, both from the same laboratory, but in different batches. Samples were subjected to organoleptic analysis and verification of iron content, pH, volume and density. Data were compared with values recommended by the Brazilian pharmacopoeia 5th edition. Results: Three batches were evaluated: 4659 of from the CF;4574 from the BHU1, and 4576 from the BHU2, stored in accordance with RDC 304/19 of ANVISA. All showed compliance with some organoleptic characteristics;and stable values in pH (3.61 - CF;3.67 - BHU1;3.65 - BHU2), density (1.079 - CF;1.088 - BHU1;1.086 - BHU2) and individual volume (not less than 95% of the declared value). However, it was not possible to detect the odor of herbs;the average volume of batch BHU1 was below the declared value, and the iron content of both BHUs was above the maximum value of pharmacopoeia standards. Conclusion: Samples did not show full compliance with the physical and chemical parameters evaluated, suggesting deviation in the quality of the medication.展开更多
Objective:To assess the effects of turmeric extract and its compounds on oxidative stress,inflammation,and apoptosis in acetaminophen-induced liver injury.Methods:HepG2 cells were administered with acetaminophen(40 mM...Objective:To assess the effects of turmeric extract and its compounds on oxidative stress,inflammation,and apoptosis in acetaminophen-induced liver injury.Methods:HepG2 cells were administered with acetaminophen(40 mM)to induce hepatotoxicity,followed by treatment with turmeric extract and its isolated compounds including curcumin,demethoxycurcumin,bis-demethoxycurcumin and ar-turmerone at 5,25,and 125μg/mL.IL-1β,IL-6,and IL-10 levels were quantified with ELISA kits.Further,qRT-PCR was used to analyze the mRNA expression of JNK,Casp-9,and Casp-3.Meanwhile,the levels of nitric oxide and lactate dehydrogenase were analyzed using colorimetric assay.Results:Acetaminophen administration caused an increase in the levels of lactate dehydrogenase,nitric oxide,IL-1β,IL-6,and the mRNA expression of JNK,Casp-9,and Casp-3 in HepG2 cells while reducing IL-10 levels.Treatment with turmeric extract,curcumin,demethoxycurcumin,bis-demethoxycurcumin,and ar-turmerone lowered IL-1β,IL-6,nitric oxide,and lactate dehydrogenase levels,downregulated the mRNA expression of JNK,Casp-9,and Casp-3,and increased IL-10 levels.Conclusions:Turmeric extract and its compounds have significant hepatoprotective activity and could be further explored for the treatment of liver damage.展开更多
Background:Diabetes and hypertension have been identified as risk factors for HCV complications in previous studies.This has sparked the interest in the field of prevention by identifying at-risk individuals and incre...Background:Diabetes and hypertension have been identified as risk factors for HCV complications in previous studies.This has sparked the interest in the field of prevention by identifying at-risk individuals and increasing investments for screening among pharmacists.The aim of this study was to screen for risk factors,including age,gender,BMI,hypertension,diabetes,and obesity,in Egyptian patients with HCV Methods:A prospective cross-sectional study was carried out from September 2018 to February 2019,with a total of 1,959 medical records collected.By comparing the patients'characteristics,variables related to metabolic risk,and body composition measurements,regression models have been established to determine any confounding factors.Results:The prevalence of HCV antibody was 41.0%in men and 59.0%in women.Among the variables included in the regression analysis,age,BMI,and uncontrolled hypertension were found to have statistically significant associations with diabetes in HCV positive cases(p<0.001).HCV patients>40 years old with high BMI were found to have significant associations with both,diabetes and hypertension(p<0.001).Hypertensive HCV patients were found to have significant associations with gender,age>40,and DM(p<0.001).Conclusion:HCV infection and metabolic disorders have a closed cycle relationship.Reducing the complications of DM has a promising prospective of limiting the complications of HCV .展开更多
The use of traditional herbal drugs derived from natural sources is on the rise due to their minimal side effects and numerous health benefits.However,a major limitation is the lack of standardized knowledge for ident...The use of traditional herbal drugs derived from natural sources is on the rise due to their minimal side effects and numerous health benefits.However,a major limitation is the lack of standardized knowledge for identifying and mapping the quality of these herbal medicines.This article aims to provide practical insights into the application of artificial intelligence for quality-based commercialization of raw herbal drugs.It focuses on feature extraction methods,image processing techniques,and the preparation of herbal images for compatibility with machine learning models.The article discusses commonly used image processing tools such as normalization,slicing,cropping,and augmentation to prepare images for artificial intelligence-based models.It also provides an overview of global herbal image databases and the models employed for herbal plant/drug identification.Readers will gain a comprehensive understanding of the potential application of various machine learning models,including artificial neural networks and convolutional neural networks.The article delves into suitable validation parameters like true positive rates,accuracy,precision,and more for the development of artificial intelligence-based identification and authentication techniques for herbal drugs.This article offers valuable insights and a conclusive platform for the further exploration of artificial intelligence in the field of herbal drugs,paving the way for smarter identification and authentication methods.展开更多
With the continuous development of electronic devices and the information industry towards miniaturization,integration,and high-power consumption,the using of electronic devices will inevitably generate and accumulate...With the continuous development of electronic devices and the information industry towards miniaturization,integration,and high-power consumption,the using of electronic devices will inevitably generate and accumulate heat,which will cause local high temperatures and will seriously reduce their performance,reliability,and lifetime.Therefore,having efficient heat-conducting functional materials is crucial to the normal and stable operation of electrical equipment and microelectronic products.In view of the excellent comprehensive performance of polymer-based thermally conductive materials(including intrinsic polymers and filler-filled polymer-based composites),it has shown great advantages in thermal management applications.In this review,the research status of preparing polymer-based thermally conductive composites and effective strategies to improve their thermal conductivity(TC)are reviewed.Compared with the higher cost and technical support with adjusting the molecular chain structure and cross-linking mode to improve the intrinsic TC of the polymer,introducing suitable fillers into the polymer to build a thermally conductive network or oriented structure can simply and efficiently improve the overall TC.Typical applications of polymer-based composites were discussed with detailed examples in the field of electronic packaging.Challenges and possible solutions to solve the issues are discussed together with the perspectives.This study provides guidance for the future development of polymer-based thermally conductive composites.展开更多
Arsenic,a naturally occurring toxic element,manifests in various chemical forms and is widespread in the environment.Exposure to arsenic is a well-established risk factor for an elevated incidence of various cancers a...Arsenic,a naturally occurring toxic element,manifests in various chemical forms and is widespread in the environment.Exposure to arsenic is a well-established risk factor for an elevated incidence of various cancers and chronic diseases.The crux of arsenic-mediated toxicity lies in its ability to induce oxidative stress,characterized by an unsettling imbalance between oxidants and antioxidants,accompanied by the rampant generation of reactive oxygen species and free radicals.In response to this oxidative turmoil,cells deploy their defensemechanisms,prominently featuring the redox-sensitive transcription factor known as nuclear factor erythroid 2-related factor 2(NRF2).NRF2 stands as a primary guardian against the oxidative harm wrought by arsenic.When oxidative stress activates NRF2,it orchestrates a symphony of downstream antioxidant genes,leading to the activation of pivotal antioxidant enzymes like glutathione-S-transferase,heme oxygenase-1,and NAD(P)H:quinone oxidoreductase 1.This comprehensive review embarks on the intricate and diverse ways by which various arsenicals influence the NRF2 antioxidant pathway and its downstream targets,shedding light on their roles in defending against arsenic exposure toxic effects.It offers valuable insights into targeting NRF2 as a strategy for safeguarding against or treating the harmful and carcinogenic consequences of arsenic exposure.展开更多
Background:Globally,the use of community pharmacies and pharmacists in the delivery of vaccination services has been hampered by several factors,laws,and regulations that do not support pharmacists to participate in t...Background:Globally,the use of community pharmacies and pharmacists in the delivery of vaccination services has been hampered by several factors,laws,and regulations that do not support pharmacists to participate in the delivery of vaccination services.With the advent of COVID-19 pandemic,many countries have included community pharmacists and pharmacies in vaccination services to improve coverage.This study described the delivery of vaccination services in community pharmacies using the COVID-19 experience and how their involvement impacted vaccination coverage in Nigeria.It also exposed how this experience can be used to support policy revisions to formally recognize pharmacists in immunization delivery.Methods:A descriptive cross-sectional study was conducted among 474 community pharmacists in two southwestern States in Nigeria,using a semi-structured questionnaire.It determines the number of community pharmacists who have been trained in the delivery of vaccination services,the types of vaccination services provided,and vaccines administered in their pharmacies.Data were analyzed with descriptive and inferential statistics and p-value at≤0.05.Results:Response rate was 86.7%.Less than half of the respondents(40.1%)had undergone vaccination training.Of the 129(31.4%)respondents that provide vaccination services,72(55.8%)administer vaccines in their pharmacies.Out of these 72 respondents;45(62.5%)were administering vaccines before their involvement in COVID-19 vaccine administration;57(79.2%)of the health personnel who administer vaccines were pharmacists;60(83.3%)of them administer vaccines on request;22(30.6%)administered COVID-19 vaccines only;and only 7(9.7%)of the respondents had administered over 500 doses of COVID-19 vaccines.Training in vaccination was associated with the vaccination services provided(p<0.05).Respondents suggested government support through legal framework and policy review,training and empowering pharmacists in vaccine administration,and recognition of community pharmacists as PHC providers.展开更多
Objective:The use of stem cells is a promising strategy for seizure treatment owing to their unique characteristics.We investigated the role of endothelial progenitor cells(EPCs)in a pentylenetetrazole(PTZ)-induced ra...Objective:The use of stem cells is a promising strategy for seizure treatment owing to their unique characteristics.We investigated the role of endothelial progenitor cells(EPCs)in a pentylenetetrazole(PTZ)-induced rat seizure model.A selected panel of long noncoding RNAs(lncRNAs),which maintain an elaborate balance in brain neural regulatory networks as well as the autophagy pathway,was also targeted.Methods:The impact of intravenously administered EPCs on PTZ-induced kindling in rats was evaluated by measuring the expression of neuronal damage markers,neurotrophic factors,and relevant lncRNA genes.Rat behavior was assessed using Y-maze test and open field test(OFT).Results:EPCs mitigated seizure associated neurological damage and reversed PTZ-induced working memory and locomotor activity deficits,as evidenced by improved performance in the Y-maze test and OFT.EPC treatment reversed the downregulation of the expression of the lncRNAs Evf2,Pnky,Dlx1,APF,HOTAIR,and FLJ11812.EPCs also boosted vascular endothelial growth factor(VEGF)expression.The ameliorative effect achieved by EPCs was comparable to that produced by valproate.Conclusions:These findings indicate that EPCs ameliorate kindling epileptic seizures and their associated abnormalities and that the effect of EPCs may be mediated via the upregulation of certain regulatory lncRNAs.展开更多
Autoimmune diseases are complex clinical conditions that present significant therapeutic challenges due to their intricate immunological mechanisms.Conventional treatment strategies,such as immunosuppressive drugs and...Autoimmune diseases are complex clinical conditions that present significant therapeutic challenges due to their intricate immunological mechanisms.Conventional treatment strategies,such as immunosuppressive drugs and anti-inflammatory therapies,often demonstrate limited efficacy and are associated with considerable side effects.Recently,mesenchymal stem cells(MSCs)have attracted growing interest as a promising therapeutic approach,owing to their immunomodulatory properties and ability to promote tissue repair.However,the direct application of MSCs faces several limitations,including the risk of immunogenicity and difficulties in large-scale production.In this context MSC-derived exosomes(MSC-Exos),nano-sized extracellular vesicles secreted by MSCs,have emerged as a compelling alternative to cell-based therapies.Enriched with proteins,lipids,and nucleic acids,these exosomes exhibit potent anti-inflammatory and immunomodulatory effects.Their primary mechanisms of action include enhancing the population of regulatory T cells,modulating macrophage polarization,and suppressing proinflammatory cytokines such as interleukin-6 and tumor necrosis factor-α.The therapeutic potential of MSC-Exos extends beyond individual conditions,encompassing a wide range of autoimmune diseases.For instance in Behçet’s disease,they have been shown to regulate vasculitis and inflammatory processes by inhibiting proinflammatory cytokines and promoting endothelial cell regeneration.Moreover,MSC-Exos have demonstrated promising immunomodulatory effects in other autoimmune diseases,including systemic lupus erythematosus,rheumatoid arthritis,and multiple sclerosis.Through mechanisms such as inflammation suppression,vascular repair,and the restoration of immune homeostasis,MSC-Exos represent a versatile and innovative approach to autoimmune disease therapy.This review explored the molecular and therapeutic effects of MSCs and MSC-Exos in autoimmune diseases,with particular emphasis on their clinical potential in Behçet’s disease,systemic lupus erythematosus,rheumatoid arthritis,and multiple sclerosis.展开更多
Objective:To evaluate and compare the quality of life(QoL)in patients with multidrug-resistant(MDR-TB)and drug-sensitive(DS-TB)as well as to investigate factors associated with QoL among MDR-TB patients in real-world ...Objective:To evaluate and compare the quality of life(QoL)in patients with multidrug-resistant(MDR-TB)and drug-sensitive(DS-TB)as well as to investigate factors associated with QoL among MDR-TB patients in real-world scenarios at the Haji Hospital,Surabaya.Methods:We conducted a case-control study from June to December 2024.MDR-TB and DS-TB patients were classified into case and control groups,respectively.We used the World Health Organization’s Quality of Life Brief(WHOQOL-BREF)instrument and Patient Health Questionnaire-9(PHQ-9)to assess QoL and depression levels,respectively.Multivariate analysis was used to analyze factors associated with QoL of patients with MDR-TB.Results:Forty-one patients with MDR-TB and 43 with DS-TB were enrolled in the study.A mean score for all domains(physical,psychological,social relationship,environmental)and total mean score of WHOQOL-BREF was significantly lower in MDR-TB than those with DS-TB(P<0.05).The prevalence of depression and the mean score of PHQ-9 were significantly higher in MDR-TB than in DS-TB(P<0.05).PHQ-9 negatively correlates with the WHOQOL-BREF score(r=-0.502,P<0.05)among MDR-TB patients.MDR-TB patients with depression were significantly associated with low QoL in the physical(OR 3.611;95%CI 2.393-6.951;P=0.029),psychological(OR 1.672;95%CI 1.179-5.941;P=0.021),social relationship(OR 2.586;95%CI 1.611-2.909;P=0.014),and environmental domains(OR 1.926;95%CI 1.047-2.147;P=0.048).Conclusions:MDR-TB patients had worse QoL than DS-TB.Those with depression were associated with low QoL.Strategies that identify and tackle alterations in the QoL for MDR-TB patients are necessary during TB treatment.展开更多
基金supported by the National Institute of Health/National Eye Institute(NIH/NEI)grants(R00 EY029373,R01 EY035658)to AYFKnights Templar Eye Foundation Research Grant to ESIntramural UAMS Hornick and Sturgis grants to AYF and ES respectively。
文摘Ischemic retinopathy is a leading cause of blindness:Ischemic retinopathies including diabetic retinopathy(DR),retinopathy of prematurity,and retinal artery and vein occlusion are major causes of visual impairment.Ischemic retinopathy can be acute,such as in central or branch retinal artery occlusion,or chronic,such as with DR(Figure 1).Although the causes of retinopathies are diverse,one pathogenic event shared by these conditions is the myeloid cell response to retinal ischemia(Shahror et al.,2024a).
基金Egyptian Science and Technology and Innovation Fund(STIFA)for the support of the study through grant No.46667 entitled“Sustainability of Lab Capacities of the Center of Drug Discovery Research and Development”.
文摘Background:Corchorus olitorius L.(Malvaceae)is a green leafy vegetable widely consumed in the Middle East and valued for its rich nutritional content.Its essential oils,an important class of secondary metabolites,are of growing interest for potential use in cosmetics and fragrance industries due to their bioactive properties.Methods:Leaves of C.olitorius cultivated in Egypt were extracted using microwave-assisted hydrodistillation(MAHD)and conventional hydrodistillation(HD).The oils were analyzed by gas chromatography-mass spectrometry(GC-MS)to characterize their chemical profiles.In vitro assays were conducted to evaluate their anti-elastase and anti-collagenase activities,and in silico studies were performed to predict the pharmacokinetic and pharmacodynamic properties of major constituents.Results:GC-MS analysis showed that aldehydes,alkanes,fatty alcohols,fatty acids,and their derivatives were the predominant compound classes in both oils.Notably,oxygenated diterpenes(11.22%)were present exclusively in the MAHD oil,while triterpenoids(16.37%)were found only in the HD oil.The MAHD oil demonstrated stronger In vitro anti-elastase(IC_(50)=42.5μg/mL)and anti-collagenase(IC_(50)=131.5μg/mL)activities compared to the HD oil(IC_(50)=66.7 and 206.8μg/mL,respectively),reflecting an approximate 36.3%improvement in elastase inhibition and 36.4%improvement in collagenase inhibition.In silico docking indicated that the triterpenoidβ-amyrin acetate showed the highest predicted binding affinity for porcine pancreatic elastase(PDB ID:6QEO,ΔG=−8.1 kcal/mol)and collagenase(PDB ID:456C,ΔG=−9.1 kcal/mol)among the major compounds analyzed.Conclusion:These findings demonstrate that MAHD is a greener and more efficient extraction method,yielding oil with enhanced enzyme inhibitory activity compared to conventional HD.The promising anti-elastase and anti-collagenase properties suggest that C.olitorius MAHD oil could serve as a potential candidate for anti-aging cosmetic formulations,following further validation.
文摘BACKGROUND Crohn’s disease(CD)is a chronic inflammatory bowel disease with unknown etiology.Inflammatory chemical mediators synthesized from arachidonic acid,an n-6 polyunsaturated fatty acid(PUFA),have been shown to activate CD.Additionally,n-3 PUFAs are metabolized by the same enzyme as n-6 PUFAs and known to inhibit the arachidonic acid cascade.Our previous study noted that the presence of erythrocyte membrane fatty acids is a characteristic finding in Japanese CD patients.It was thus speculated that FADS2 gene polymorphisms,which induce PUFA metabolizing enzymes,are involved in the pathogenesis of CD,though no such relationship was found.AIM To investigate the relationship of FADS2 polymorphisms with serum and erythrocyte membrane fatty acid composition ratios,and disease activity.METHODS Using previously reported findings regarding FADS2 genetic polymorphisms,the records of 52 CD patients undergoing treatment at Jikei University Kashiwa Hospital were analyzed.Mutations noted were divided into three groups;wild-type(GG),heterozygous mutants(GA),and homozygous(AA),with the activities of delta-6 and delta-5 desaturases compared using redefined d6d index(rd.d6di)and d5d index(d5di).Additionally,comparisons of serum and erythrocyte membranes for fatty acid composition,and also gene polymorphisms and CD activity index(CDAI)were performed.RESULTS The presence of the rs174538 mutation in FADS2 resulted in reduction of only rd.d6di in the erythrocyte membrane(P<0.01).In contrast,that mutation was found to be associated with d5di induced by FADS1 in serum(P=0.019)as well as the erythrocyte membrane(P<0.0001),and also with reduction in the fatty acid composition of arachidonic acid in both serum(P<0.0001)and the erythrocyte membrane(P<0.01).Regarding disease activity,a positive correlation of CDAI score with rd.d6di in both serum(P<0.05)and the erythrocyte membrane(P<0.05)was found only in the rs174538 wild-type group.In contrast,there was no correction between CDAI and d5di in either serum or erythrocyte membrane samples.CONCLUSION The rs174538 mutation alters the fatty acid profile through strong linkage to the FADS1 gene.In wild-type individuals,rd.d6di was positively correlated with CDAI,suggesting predictive utility of disease severity.
文摘Nanotechnology has revolutionized drug delivery,particularly through nanoformulations of phytoconstituents,enhancing their therapeutic potential.Despite their broad bioactivities,plant-based compounds often suffer from poor bioavailability and stability.Nanoformulations address these limitations by improving solubility,targeted delivery,and controlled release.This approach opens new possibilities for treating chronic diseases like cancer,diabetes,and neurodegenerative disorders.This review aims to examine recent advancements in nanotechnology-based formulation strategies designed to enhance the delivery,stability,and therapeutic efficacy of phytochemicals and also discusses regulatory issues,safety concerns,scalability,and cost-effectiveness.Emphasis was placed on nanoformulation techniques employed for key phytoconstituents such as curcumin,resveratrol,epigallocatechin gallate,and quercetin.The most commonly employed nanocarriers included polymeric nanoparticles,solid lipid nanoparticles,and liposomes.These formulations significantly improved the solubility,stability,and controlled release profiles of phytochemicals.In vitro and in vivo studies demonstrated enhanced anti-inflammatory,anticancer,and antioxidant activities.Moreover,surface-modified and targeted nanoparticles showed promise in increasing site-specific targeting and enhancing bioavailability of the encapsulated compounds.Nanoformulations present a promising strategy for overcoming the pharmacokinetic limitations of phytochemicals.Despite encouraging preclinical results,further studies are needed to address issues related to long-term safety,clinical efficacy,and regulatory approval for successful clinical translation.
文摘The rapid growth of biomedical data,particularly multi-omics data including genomes,transcriptomics,proteomics,metabolomics,and epigenomics,medical research and clinical decision-making confront both new opportunities and obstacles.The huge and diversified nature of these datasets cannot always be managed using traditional data analysis methods.As a consequence,deep learning has emerged as a strong tool for analysing numerous omics data due to its ability to handle complex and non-linear relationships.This paper explores the fundamental concepts of deep learning and how they are used in multi-omics medical data mining.We demonstrate how autoencoders,variational autoencoders,multimodal models,attention mechanisms,transformers,and graph neural networks enable pattern analysis and recognition across all omics data.Deep learning has been found to be effective in illness classification,biomarker identification,gene network learning,and therapeutic efficacy prediction.We also consider critical problems like as data quality,model explainability,whether findings can be repeated,and computational power requirements.We now consider future elements of combining omics with clinical and imaging data,explainable AI,federated learning,and real-time diagnostics.Overall,this study emphasises the need of collaborating across disciplines to advance deep learning-based multi-omics research for precision medicine and comprehending complicated disorders.
基金funded by Al Jalila Foundation-Research Grant(AJF2023-078)to SSMS.
文摘Objectives:Breast cancer(BC)is the leading cause of cancer-related mortality in women,largely due to metastasis.This study aims to explore the role of purine nucleoside phosphorylase(PNP),a key enzyme in purine metabolism,in the aggressiveness and metastatic behavior of BC.Methods:A comprehensive analysis was performed using in silico transcriptomic data(n=2509 patients),immunohistochemical profiling of BC tissues(n=103),and validation through western blotting in multiple BC cell lines.Gene expression and survival analyses were conducted using Tumor Immune Estimation Resource(TIMER),Gene Expression Profiling Interactive Analysis 2(GEPIA2),and the cBioPortal for cancer genomics(cBioPortal)platforms.Correlations between PNP and key epithelial–mesenchymal transition(EMT)markers,molecular subtypes,tumor grades,and stages were examined.Results:PNP was significantly overexpressed in human epidermal growth factor receptor 2(HER-2)-positive and triple-negative BCs compared to luminal subtypes.High PNP levels were strongly associated with advanced BC stages,high-grade tumors,EMT phenotypes,and poor overall survival.Notably,HER-2 inhibition suppressed PNP expression,while PNP gene silencing induced HER-2 upregulation,revealing a reciprocal regulatory loop.Dual inhibition of PNP and HER-2 resulted in a significant reduction in cell viability compared to HER-2 inhibition alone.Conclusion:Collectively,PNP emerges as a promising biomarker of BC aggressiveness and progression.Its reciprocal interaction with HER-2 underscores its potential as a therapeutic target.Dual targeting of PNP and HER-2 may offer a novel strategy for improving outcomes in aggressive BC subtypes.
文摘Objective: To analyze the use of all subsidized prescription drugs including their use of drug combination generally accepted as carrying a risk of severe interactions. Methodology: In a cross sectional study, we analyzed all prescriptions (n = 1014) involving two or more drugs dispensed to the population (age range 4-85 years) from all pharmacies, clinics and hospitals. Data were stratified by age and sex, and frequency of common interacting drugs. Potential drug interactions were classified according to clinical relevance as significance of severity (types A: major, B: moderate, and C: minor) and documented evidence (types 1, 2, 3, and 4). Result and Discussion: The growing use of pharmacological agents means that drug interactions are of increasing interest for public health. Monitoring of potential drug interactions may improve the quality of drug prescribing and dispensing, and it might form a basis for education focused on appropriate prescribing. To make the manifestation of adverse interaction subside, management strategies must be exercised if two interacting drugs have to be taken with each other, involving: adjusting the dose of the object drug;spacing dosing times to avoid the interaction. The pharmacist, along with the prescriber has a duty to ensure that patients are aware of the risk of side effects and a suitable course of action they should take. Conclusion: It is unrealistic to expect clinicians to memorize the thousands of drug-drug interactions and their clinical significance, especially considering the rate of introduction of novel drugs and the escalating appreciation of the importance of pharmacogenomics. Reliable regularly updated decision support systems and information technology are necessary to help avert dangerous drug combinations.
文摘An ADS （automated dispensing system） was implemented in our hospital pharmacy in 2008 to optimize and secure the medication process. The main objective of this study was to compare the projected and the real ROI （return on investment）, after seven years of use. ROI was calculated annually （from 2008 to 2015）, by deducting the cost of investment （ADS buying and implementation, maintenance, repairs and ADS upgrade） from the cost saving （drugs stock reduction and decrease of pharmacy staff dedicated to global dispensing）. In 2015, total costs saving （＋$1,141,987） were divided between decreasing drug stock value and reduction of pharmacy staff. Total costs of investment （-$978,656） were acquisition, maintenance, repairs and an unplanned upgrade costs. Finally, the real ROI was ＋$163,331 after seven years of use. In 2008, projected ROI was ＋$410,786. The real payback period has been increased by approximately two years （six years of use, instead of four years as expected）. Despite their cost, ADSs are a worthwhile investment, leading to a ROI within a few years. These economic considerations should be put into perspective with optimization of drugs stock management, greater efficiency of the global dispensing process, securitization of medication process and redeployment of pharmacy staff.
基金Fundacao de Amparo a Pesquisa do Estado de Minas Gerais project APQ-01083-11Conselho Nacional de Desenvolvimento Cientifico e Tecnologico grant 245914/2012-9+1 种基金Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior grant PNPD 1648694Pro-Reitoria de Pesquisa/UFMG IE 27/2010 for financial support
文摘Meloxicam(MLX) is an anti-inflammatory drug susceptible to variations and crystalline transitions. In compounding pharmacies, the complete crystallographic evaluation of the raw material is not a routine procedure. We performed a complete crystallographic characterization of aleatory raw MLX samples from compounding pharmacies. X-ray diffraction indicated the presence of two crystalline forms in one sample. DSC experiments suggested that crystallization, or a crystal transition, occurred differently between samples. The FTIR and ~1H NMR spectra showed characteristic assignments.^(13)C solid-state NMR spectroscopy indicated the presence of more than one phase in a sample from pharmacy B. The Hirshfeld surface analysis, with electrostatic potential projection, allowed complete assignment of the UV spectra in ethanol solution. The polymorph I of meloxicam was more active than polymorph III in an experimental model of acute inflammation in mice. Our results highlighted the need for complete crystallographic characterization and the separation of freely used raw materials in compounding pharmacies,as a routine procedure, to ensure the desired dose/effect.
文摘Inflammatory bowel disease(IBD)is a chronic inflammatory illness of the intes-tine.While the mechanism underlying the pathogenesis of IBD is not fully under-stood,it is believed that a complex combination of host immunological response,environmental exposure,particularly the gut microbiota,and genetic suscept-ibility represents the major determinants.The gut virome is a group of viruses found in great frequency in the gastrointestinal tract of humans.The gut virome varies greatly among individuals and is influenced by factors including lifestyle,diet,health and disease conditions,geography,and urbanization.The majority of research has focused on the significance of gut bacteria in the progression of IBD,although viral populations represent an important component of the microbiome.We conducted this review to highlight the viral communities in the gut and their expected roles in the etiopathogenesis of IBD regarding published research to date.
文摘Background: For the WHO, anemia is a serious public health problem, with an emphasis on deprivation anemia, which has socioeconomic conditions as determining factors for its development. Among nutritional anemias, the most relevant is iron deficiency, whose main form of prevention and treatment is supplementation with ferrous sulfate dispensed in the public health system, with the need to periodically check whether the drug has the quality required by regulatory health agencies. Thus, the objective of this study was to analyze the quality of the ferrous sulfate medication, from the same laboratory, and dispensed in a basic health unit (BHU) and a commercial pharmacy (CF). Materials and Methods: An analytical, qualitative and quantitative study of ferrous sulfate heptahydrate (25 mg/mL in 100 mL syrup), carried out on 20 BHU and 10 from CF, both from the same laboratory, but in different batches. Samples were subjected to organoleptic analysis and verification of iron content, pH, volume and density. Data were compared with values recommended by the Brazilian pharmacopoeia 5th edition. Results: Three batches were evaluated: 4659 of from the CF;4574 from the BHU1, and 4576 from the BHU2, stored in accordance with RDC 304/19 of ANVISA. All showed compliance with some organoleptic characteristics;and stable values in pH (3.61 - CF;3.67 - BHU1;3.65 - BHU2), density (1.079 - CF;1.088 - BHU1;1.086 - BHU2) and individual volume (not less than 95% of the declared value). However, it was not possible to detect the odor of herbs;the average volume of batch BHU1 was below the declared value, and the iron content of both BHUs was above the maximum value of pharmacopoeia standards. Conclusion: Samples did not show full compliance with the physical and chemical parameters evaluated, suggesting deviation in the quality of the medication.
基金funded by Maranatha Christian University,Bandung,Indonesia for Productive Lecturer Research under grant number:011/SK/ADD/UKM/IV/2024.
文摘Objective:To assess the effects of turmeric extract and its compounds on oxidative stress,inflammation,and apoptosis in acetaminophen-induced liver injury.Methods:HepG2 cells were administered with acetaminophen(40 mM)to induce hepatotoxicity,followed by treatment with turmeric extract and its isolated compounds including curcumin,demethoxycurcumin,bis-demethoxycurcumin and ar-turmerone at 5,25,and 125μg/mL.IL-1β,IL-6,and IL-10 levels were quantified with ELISA kits.Further,qRT-PCR was used to analyze the mRNA expression of JNK,Casp-9,and Casp-3.Meanwhile,the levels of nitric oxide and lactate dehydrogenase were analyzed using colorimetric assay.Results:Acetaminophen administration caused an increase in the levels of lactate dehydrogenase,nitric oxide,IL-1β,IL-6,and the mRNA expression of JNK,Casp-9,and Casp-3 in HepG2 cells while reducing IL-10 levels.Treatment with turmeric extract,curcumin,demethoxycurcumin,bis-demethoxycurcumin,and ar-turmerone lowered IL-1β,IL-6,nitric oxide,and lactate dehydrogenase levels,downregulated the mRNA expression of JNK,Casp-9,and Casp-3,and increased IL-10 levels.Conclusions:Turmeric extract and its compounds have significant hepatoprotective activity and could be further explored for the treatment of liver damage.
文摘Background:Diabetes and hypertension have been identified as risk factors for HCV complications in previous studies.This has sparked the interest in the field of prevention by identifying at-risk individuals and increasing investments for screening among pharmacists.The aim of this study was to screen for risk factors,including age,gender,BMI,hypertension,diabetes,and obesity,in Egyptian patients with HCV Methods:A prospective cross-sectional study was carried out from September 2018 to February 2019,with a total of 1,959 medical records collected.By comparing the patients'characteristics,variables related to metabolic risk,and body composition measurements,regression models have been established to determine any confounding factors.Results:The prevalence of HCV antibody was 41.0%in men and 59.0%in women.Among the variables included in the regression analysis,age,BMI,and uncontrolled hypertension were found to have statistically significant associations with diabetes in HCV positive cases(p<0.001).HCV patients>40 years old with high BMI were found to have significant associations with both,diabetes and hypertension(p<0.001).Hypertensive HCV patients were found to have significant associations with gender,age>40,and DM(p<0.001).Conclusion:HCV infection and metabolic disorders have a closed cycle relationship.Reducing the complications of DM has a promising prospective of limiting the complications of HCV .
文摘The use of traditional herbal drugs derived from natural sources is on the rise due to their minimal side effects and numerous health benefits.However,a major limitation is the lack of standardized knowledge for identifying and mapping the quality of these herbal medicines.This article aims to provide practical insights into the application of artificial intelligence for quality-based commercialization of raw herbal drugs.It focuses on feature extraction methods,image processing techniques,and the preparation of herbal images for compatibility with machine learning models.The article discusses commonly used image processing tools such as normalization,slicing,cropping,and augmentation to prepare images for artificial intelligence-based models.It also provides an overview of global herbal image databases and the models employed for herbal plant/drug identification.Readers will gain a comprehensive understanding of the potential application of various machine learning models,including artificial neural networks and convolutional neural networks.The article delves into suitable validation parameters like true positive rates,accuracy,precision,and more for the development of artificial intelligence-based identification and authentication techniques for herbal drugs.This article offers valuable insights and a conclusive platform for the further exploration of artificial intelligence in the field of herbal drugs,paving the way for smarter identification and authentication methods.
基金We acknowledge the Henan Young Backbone Teachers Foundation(No.2021GGJS135)。
文摘With the continuous development of electronic devices and the information industry towards miniaturization,integration,and high-power consumption,the using of electronic devices will inevitably generate and accumulate heat,which will cause local high temperatures and will seriously reduce their performance,reliability,and lifetime.Therefore,having efficient heat-conducting functional materials is crucial to the normal and stable operation of electrical equipment and microelectronic products.In view of the excellent comprehensive performance of polymer-based thermally conductive materials(including intrinsic polymers and filler-filled polymer-based composites),it has shown great advantages in thermal management applications.In this review,the research status of preparing polymer-based thermally conductive composites and effective strategies to improve their thermal conductivity(TC)are reviewed.Compared with the higher cost and technical support with adjusting the molecular chain structure and cross-linking mode to improve the intrinsic TC of the polymer,introducing suitable fillers into the polymer to build a thermally conductive network or oriented structure can simply and efficiently improve the overall TC.Typical applications of polymer-based composites were discussed with detailed examples in the field of electronic packaging.Challenges and possible solutions to solve the issues are discussed together with the perspectives.This study provides guidance for the future development of polymer-based thermally conductive composites.
基金supported by the Natural Sciences and Engineering Research Council of Canada(NSERC)Discovery Grant[RGPIN 250139]to A.O.S.E.
文摘Arsenic,a naturally occurring toxic element,manifests in various chemical forms and is widespread in the environment.Exposure to arsenic is a well-established risk factor for an elevated incidence of various cancers and chronic diseases.The crux of arsenic-mediated toxicity lies in its ability to induce oxidative stress,characterized by an unsettling imbalance between oxidants and antioxidants,accompanied by the rampant generation of reactive oxygen species and free radicals.In response to this oxidative turmoil,cells deploy their defensemechanisms,prominently featuring the redox-sensitive transcription factor known as nuclear factor erythroid 2-related factor 2(NRF2).NRF2 stands as a primary guardian against the oxidative harm wrought by arsenic.When oxidative stress activates NRF2,it orchestrates a symphony of downstream antioxidant genes,leading to the activation of pivotal antioxidant enzymes like glutathione-S-transferase,heme oxygenase-1,and NAD(P)H:quinone oxidoreductase 1.This comprehensive review embarks on the intricate and diverse ways by which various arsenicals influence the NRF2 antioxidant pathway and its downstream targets,shedding light on their roles in defending against arsenic exposure toxic effects.It offers valuable insights into targeting NRF2 as a strategy for safeguarding against or treating the harmful and carcinogenic consequences of arsenic exposure.
文摘Background:Globally,the use of community pharmacies and pharmacists in the delivery of vaccination services has been hampered by several factors,laws,and regulations that do not support pharmacists to participate in the delivery of vaccination services.With the advent of COVID-19 pandemic,many countries have included community pharmacists and pharmacies in vaccination services to improve coverage.This study described the delivery of vaccination services in community pharmacies using the COVID-19 experience and how their involvement impacted vaccination coverage in Nigeria.It also exposed how this experience can be used to support policy revisions to formally recognize pharmacists in immunization delivery.Methods:A descriptive cross-sectional study was conducted among 474 community pharmacists in two southwestern States in Nigeria,using a semi-structured questionnaire.It determines the number of community pharmacists who have been trained in the delivery of vaccination services,the types of vaccination services provided,and vaccines administered in their pharmacies.Data were analyzed with descriptive and inferential statistics and p-value at≤0.05.Results:Response rate was 86.7%.Less than half of the respondents(40.1%)had undergone vaccination training.Of the 129(31.4%)respondents that provide vaccination services,72(55.8%)administer vaccines in their pharmacies.Out of these 72 respondents;45(62.5%)were administering vaccines before their involvement in COVID-19 vaccine administration;57(79.2%)of the health personnel who administer vaccines were pharmacists;60(83.3%)of them administer vaccines on request;22(30.6%)administered COVID-19 vaccines only;and only 7(9.7%)of the respondents had administered over 500 doses of COVID-19 vaccines.Training in vaccination was associated with the vaccination services provided(p<0.05).Respondents suggested government support through legal framework and policy review,training and empowering pharmacists in vaccine administration,and recognition of community pharmacists as PHC providers.
基金Open access funding provided by The Science,Technology&Innovation Funding Authority(STDF)in coop eration with The Egyptian Knowledge Bank(EKB).
文摘Objective:The use of stem cells is a promising strategy for seizure treatment owing to their unique characteristics.We investigated the role of endothelial progenitor cells(EPCs)in a pentylenetetrazole(PTZ)-induced rat seizure model.A selected panel of long noncoding RNAs(lncRNAs),which maintain an elaborate balance in brain neural regulatory networks as well as the autophagy pathway,was also targeted.Methods:The impact of intravenously administered EPCs on PTZ-induced kindling in rats was evaluated by measuring the expression of neuronal damage markers,neurotrophic factors,and relevant lncRNA genes.Rat behavior was assessed using Y-maze test and open field test(OFT).Results:EPCs mitigated seizure associated neurological damage and reversed PTZ-induced working memory and locomotor activity deficits,as evidenced by improved performance in the Y-maze test and OFT.EPC treatment reversed the downregulation of the expression of the lncRNAs Evf2,Pnky,Dlx1,APF,HOTAIR,and FLJ11812.EPCs also boosted vascular endothelial growth factor(VEGF)expression.The ameliorative effect achieved by EPCs was comparable to that produced by valproate.Conclusions:These findings indicate that EPCs ameliorate kindling epileptic seizures and their associated abnormalities and that the effect of EPCs may be mediated via the upregulation of certain regulatory lncRNAs.
文摘Autoimmune diseases are complex clinical conditions that present significant therapeutic challenges due to their intricate immunological mechanisms.Conventional treatment strategies,such as immunosuppressive drugs and anti-inflammatory therapies,often demonstrate limited efficacy and are associated with considerable side effects.Recently,mesenchymal stem cells(MSCs)have attracted growing interest as a promising therapeutic approach,owing to their immunomodulatory properties and ability to promote tissue repair.However,the direct application of MSCs faces several limitations,including the risk of immunogenicity and difficulties in large-scale production.In this context MSC-derived exosomes(MSC-Exos),nano-sized extracellular vesicles secreted by MSCs,have emerged as a compelling alternative to cell-based therapies.Enriched with proteins,lipids,and nucleic acids,these exosomes exhibit potent anti-inflammatory and immunomodulatory effects.Their primary mechanisms of action include enhancing the population of regulatory T cells,modulating macrophage polarization,and suppressing proinflammatory cytokines such as interleukin-6 and tumor necrosis factor-α.The therapeutic potential of MSC-Exos extends beyond individual conditions,encompassing a wide range of autoimmune diseases.For instance in Behçet’s disease,they have been shown to regulate vasculitis and inflammatory processes by inhibiting proinflammatory cytokines and promoting endothelial cell regeneration.Moreover,MSC-Exos have demonstrated promising immunomodulatory effects in other autoimmune diseases,including systemic lupus erythematosus,rheumatoid arthritis,and multiple sclerosis.Through mechanisms such as inflammation suppression,vascular repair,and the restoration of immune homeostasis,MSC-Exos represent a versatile and innovative approach to autoimmune disease therapy.This review explored the molecular and therapeutic effects of MSCs and MSC-Exos in autoimmune diseases,with particular emphasis on their clinical potential in Behçet’s disease,systemic lupus erythematosus,rheumatoid arthritis,and multiple sclerosis.
文摘Objective:To evaluate and compare the quality of life(QoL)in patients with multidrug-resistant(MDR-TB)and drug-sensitive(DS-TB)as well as to investigate factors associated with QoL among MDR-TB patients in real-world scenarios at the Haji Hospital,Surabaya.Methods:We conducted a case-control study from June to December 2024.MDR-TB and DS-TB patients were classified into case and control groups,respectively.We used the World Health Organization’s Quality of Life Brief(WHOQOL-BREF)instrument and Patient Health Questionnaire-9(PHQ-9)to assess QoL and depression levels,respectively.Multivariate analysis was used to analyze factors associated with QoL of patients with MDR-TB.Results:Forty-one patients with MDR-TB and 43 with DS-TB were enrolled in the study.A mean score for all domains(physical,psychological,social relationship,environmental)and total mean score of WHOQOL-BREF was significantly lower in MDR-TB than those with DS-TB(P<0.05).The prevalence of depression and the mean score of PHQ-9 were significantly higher in MDR-TB than in DS-TB(P<0.05).PHQ-9 negatively correlates with the WHOQOL-BREF score(r=-0.502,P<0.05)among MDR-TB patients.MDR-TB patients with depression were significantly associated with low QoL in the physical(OR 3.611;95%CI 2.393-6.951;P=0.029),psychological(OR 1.672;95%CI 1.179-5.941;P=0.021),social relationship(OR 2.586;95%CI 1.611-2.909;P=0.014),and environmental domains(OR 1.926;95%CI 1.047-2.147;P=0.048).Conclusions:MDR-TB patients had worse QoL than DS-TB.Those with depression were associated with low QoL.Strategies that identify and tackle alterations in the QoL for MDR-TB patients are necessary during TB treatment.
