Objective:Whether vortioxetine has a utility as an adjuvant drug in the treatment of bipolar depression remains controversial.This study aimed to validate the efficacy and safety of vortioxetine in bipolar depression....Objective:Whether vortioxetine has a utility as an adjuvant drug in the treatment of bipolar depression remains controversial.This study aimed to validate the efficacy and safety of vortioxetine in bipolar depression.Methods:Patients with bipolarⅡdepression were enrolled in this prospective,two-center,randomized,12-week pilot trial.The main indicator for assessing treatment effectiveness was a Montgomery-Asberg Depression Rating Scale(MADRS)of≥50%.All eligible patients initially received four weeks of lurasidone monotherapy.Patients who responded well continued to receive this kind of monotherapy.However,no-response patients were randomly assigned to either valproate or vortioxetine treatment for eight weeks.By comprehensively comparing the results of MADRS over a period of 4-12 weeks,a systematic analysis was conducted to determine whether vortioxetine could be used as an adjuvant drug for treating bipolar depression.Results:Thirty-seven patients responded to lurasidone monotherapy,and 60 patients were randomly assigned to the valproate or vortioxetine group for eight weeks.After two weeks of combined valproate or vortioxetine treatment,the MADRS score in the vortioxetine group was significantly lower than that in the valproate group.There was no difference in the MADRS scores between the two groups at 8 and 12 weeks.The incidence of side effects did not significantly differ between the valproate and vortioxetine groups.Importantly,three patients in the vortioxetine group appeared to switch to mania or hypomania.Conclusions:This study suggested that lurasidone combination with vortioxetine might have potential benefits to bipolar II depression in the early stage,while disease progression should be monitored closely for the risk of switching to mania.展开更多
Pharmacy clinics,staffed by clinical pharmacists who interact directly with patients,encompass services such as medication reconciliation,education,follow-up visits,and lifestyle guidance.Their primary goal is to enha...Pharmacy clinics,staffed by clinical pharmacists who interact directly with patients,encompass services such as medication reconciliation,education,follow-up visits,and lifestyle guidance.Their primary goal is to enhance patients’quality of life.Numerous studies,both domestic and international,have highlighted the benefits of pharmacy clinics in optimizing drug therapy quality and reducing treatment costs,particularly for long-term medication management in organ transplant recipients and similar patient groups.Despite these benefits,pharmacy clinics are still in the early stages of development in China.There remains a lack of clarity regarding the specific development and service content of pharmacy clinics tailored for transplant patients.Therefore,this study aimed to assess the current status of pharmacy clinic development for transplant patients in China and provide insights to hospitals for advancing and strengthening transplant pharmacy clinic initiatives.展开更多
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
The major aim of stroke therapy is to stimulate brain repair and improve behavioral recovery after cerebral ischemia.One option is to stimulate endogenous neurogenesis in the subventricular zone and direct the newly f...The major aim of stroke therapy is to stimulate brain repair and improve behavioral recovery after cerebral ischemia.One option is to stimulate endogenous neurogenesis in the subventricular zone and direct the newly formed neurons to the damaged area.However,only a small percentage of these neurons survive,and many do not reach the damaged area,possibly because the corpus callosum impedes the migration of subventricular zone-derived stem cells into the lesioned cortex.A second major obstacle to stem cell therapy is the strong inflammatory reaction induced by cerebral ischemia,whereby the associated phagocytic activity of brain macrophages removes both therapeutic cells and/or cell-based drug carriers.To address these issues,neurogenesis was electrically stimulated in the subventricular zone,followed by isolation of proliferating cells,including newly formed neurons,which were subsequently mixed with a nutritional hydrogel.This mixture was then transferred to the stroke cavity of day 14 post-stroke mice.We found that the performance of the treated animals improved in behavioral tests,including novel object,open field,hole board,grooming,and“time-to-feel”adhesive tape tests.Furthermore,immunostaining revealed that the stem cell marker nestin,the neuroepithelial marker Mash1,and the immature neuronal marker doublecortin-positive cells survived in the transplanted area for 2 weeks,possibly due to reduced phagocytic activity and supportive angiogenesis.These results clearly indicate that the transplantation of committed subventricular zone stem cells combined with a protective nutritional gel directly into the infarct cavity after the peak of stroke-induced neuroinflammation represents a feasible approach to improve neurorestoration after cerebral ischemia.展开更多
Background:Diabetic foot,a severe complication of diabetes,is characterized by chronic refractory wounds.Sanhuang Oil,a topical herbal formula,demonstrates significant therapeutic effects including antibacterial,anti-...Background:Diabetic foot,a severe complication of diabetes,is characterized by chronic refractory wounds.Sanhuang Oil,a topical herbal formula,demonstrates significant therapeutic effects including antibacterial,anti-inflammatory,and immunomodulatory activities.However,its active constituents and mechanisms of action against diabetic foot remain to be elucidated.Methods:In this study,the chemical constituents of Sanhuang Oil were identified using UPLC-QE-Orbitrap-MS.Subsequently,the mechanism by which Sanhuang Oil promotes diabetic foot ulcer healing was predicted by integrating network pharmacology and molecular docking.Additionally,diabetic mouse model was established in ICR mice using a combination of a high-fat diet(HFD)and streptozotocin(STZ)chemical induction.A full-thickness skin defect was created on the dorsum of the mice.Wound healing and the healing rate were observed following Sanhuang Oil intervention.The mechanism underlying Sanhuang Oil’s promotion of diabetic ulcer healing was further investigated using transcriptomics and histopathological examination(H&E staining).Results:A total of 97 active ingredients were identified from Sanhuang Oil.Network pharmacology analysis predicted 543 common targets,and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis identified 203 relevant pathways.Molecular docking further confirmed high binding affinity(binding energy≤−5.0 kcal/mol)between specific active components in Sanhuang Oil(e.g.,coptisine,phellodendrine,baicalein)and key targets associated with diabetic foot ulcers(e.g.,EGFR,AKT1,STAT3).In vivo experimental results demonstrated that the wound healing rate was significantly higher in Sanhuang Oil-treated groups compared to the model group(P<0.001).HE staining revealed that the high-dose Sanhuang Oil group exhibited more pronounced epithelial tissue coverage over the wound,reduced inflammatory cell infiltration,and increased collagen deposition and fibroblast proliferation.transcriptomic analysis identified Pdk4,Ttn,Csrp3,Actn2,Myoz2,Tnnc2,Myod1,Myog,Myot,and Myf6 as key regulatory proteins involved in promoting wound healing.Conclusion:Sanhuang Oil promotes wound healing in diabetic ulcer mice,potentially by mitigating inflammation and regulating key targets such as Pdk4 to enhance fibroblast function.These findings provide novel insights into the multi-target,multi-pathway mechanism of Sanhuang Oil for treating diabetic foot ulcers.展开更多
Introduction： The department of emergency medicine （DEM） has a high-risk environment due to its unique and complex workflow. Many high-risk medications are ordered and administered at patients’ bedsides without be...Introduction： The department of emergency medicine （DEM） has a high-risk environment due to its unique and complex workflow. Many high-risk medications are ordered and administered at patients’ bedsides without being checked by a pharmacist first, which may lead to an increase in the incidence of patient medication errors （MEs）. Objective： The current study evaluated the needs of the clinical pharmacy service in the DEM at King Saud University Medical City （KSUMC）, Riyadh, Saudi Arabia. Methods： A cross-sectional retrospective study was conducted between Jan 2016 to Dec 2017 and the documentation of clinical pharmacist interventions was extracted from Esihi database. Results： A total of 2,255 interventions for 862 patients were documented. The recommended interventions were as follows： 645 （dose adjustments）, 108 （therapeutic substitutions）, and 354 interventions （initiating drug therapy）. Adverse drug reactions （ADRs） were reported in 16 patients, and drug interactions were managed in 26 patients. The DEM responded to 713 information inquires and 290 pharmacokinetic consultations. Drug discontinuations included 39 incidents （where unjustified drug prescription occurred）, 37 （where contraindications were involved）, and 19 （where duplicate therapy was involved）. The most common interventions were related to the following drugs： antibiotics （34%）, anticoagulants （15%）, and anticonvulsants （10%）. The acceptance rates for the EM clinical pharmacist recommendations increased from 93.9% in 2016 to 99% in 2017. The most common outcome for interventions was to optimize the therapeutic effects of the drugs that were administered （73%）. Reconciliation was done in 796 patients. Conclusions： The clinical pharmacy service plays a critical role in the management of patients in the emergency department （ED）.展开更多
Dear editor,The recent outbreak of coronavirus disease(COVID-19)has become a major public health issue caused by 2019 novel coronavirus(2019-nCoV).[1]Severe COVID-19 patients may reveal a dysregulated immune response ...Dear editor,The recent outbreak of coronavirus disease(COVID-19)has become a major public health issue caused by 2019 novel coronavirus(2019-nCoV).[1]Severe COVID-19 patients may reveal a dysregulated immune response that allows the development of v iral hyperinfl ammation.[2]In the fight against COVID-19,inflammatory parameters towards illness severity should be identified to improve the prognosis of patients.In this study,we aimed to assess the discriminative ability of several infl ammation indicators in severe COVID-19 infection.展开更多
The population of non-alcoholic fatty liver disease(NAFLD)patients along with relevant advanced liver disease is projected to continue growing,because currently no medications are approved for treatment.Fecal microbio...The population of non-alcoholic fatty liver disease(NAFLD)patients along with relevant advanced liver disease is projected to continue growing,because currently no medications are approved for treatment.Fecal microbiota transplantation(FMT)is believed a novel and promising therapeutic approach based on the concept of the gut-liver axis in liver disease.There has been an increase in the number of pre-clinical and clinical studies evaluating FMT in NAFLD treatment,however,existing findings diverge on its effects.Herein,we briefly summarized the mechanism of FMT for NAFLD treatment,reviewed randomized controlled trials for evaluating its efficacy in NAFLD,and proposed the prospect of future trials on FMT.展开更多
The present study aims to investigate the perceptions and experience of physicians regarding the clinical role of the pharmacists. This is an observational study that was conducted during the period of September 2013 ...The present study aims to investigate the perceptions and experience of physicians regarding the clinical role of the pharmacists. This is an observational study that was conducted during the period of September 2013 through March 2014. A self-administered questionnaire was designed to be distributed by personal interview to the physicians. The questionnaire population consisted of randomly selected physicians practicing in UAE. The questionnaire was piloted by 10 physicians for face and understandability. Demographic data, frequencies and cross tabulation between different variables were calculated. The Chi-square test was used to determine the significance of association between categorical variables (gender, length of medical practice, and specialty) and the perception of physicians. A total of 285 filled questionnaires were returned representing 285 physicians, with a male dominance (65.3%). The average age of the physician screened was 32.4 (SD = 10.38) years with a minimum one year experience and up to 24 years. General practitioners consumed the widest sector (21.8%) followed by cardiologists (15.8%), then internal medicine (10.1%). In the current study, two thirds of the physicians believed that pharmacists could act as a reliable source of general drug information and play an important role in discovering clinical related problems. It was found that the physicians who had fewer years in practice (less than 10 years) and recently graduated had more acceptances to the clinical role of the pharmacist and believed that there should be a clinical pharmacy services in their hospitals (p-value < 0.05). No other statistically significant differences were found from analyzing the data. In conclusion, results suggest that physicians in UAE appear comfortable with pharmacists providing the broad range of services but appear somewhat less comfortable with pharmacists’ provision of direct patient care.展开更多
Alzheimer’s disease is a debilitating,progressive neurodegenerative disorder characterized by the progressive accumulation of abnormal proteins,including amyloid plaques and intracellular tau tangles,primarily within...Alzheimer’s disease is a debilitating,progressive neurodegenerative disorder characterized by the progressive accumulation of abnormal proteins,including amyloid plaques and intracellular tau tangles,primarily within the brain.Lysosomes,crucial intracellular organelles responsible for protein degradation,play a key role in maintaining cellular homeostasis.Some studies have suggested a link between the dysregulation of the lysosomal system and pathogenesis of neurodegenerative diseases,including Alzheimer’s disease.Restoring the normal physiological function of lysosomes hold the potential to reduce the pathological burden and improve the symptoms of Alzheimer’s disease.Currently,the efficacy of drugs in treating Alzheimer’s disease is limited,with major challenges in drug delivery efficiency and targeting.Recently,nanomaterials have gained widespread use in Alzheimer’s disease drug research owing to their favorable physical and chemical properties.This review aims to provide a comprehensive overview of recent advances in using nanomaterials(polymeric nanomaterials,nanoemulsions,and carbon-based nanomaterials)to enhance lysosomal function in treating Alzheimer’s disease.This review also explores new concepts and potential therapeutic strategies for Alzheimer’s disease through the integration of nanomaterials and modulation of lysosomal function.In conclusion,this review emphasizes the potential of nanomaterials in modulating lysosomal function to improve the pathological features of Alzheimer’s disease.The application of nanotechnology to the development of Alzheimer’s disease drugs brings new ideas and approaches for future treatment of this disease.展开更多
In the present study, we developed a simple, sensitive, precise, and accurate liquid chromatography-tandem mass spectrometric(LC-MS/MS) method and validated such approach for simultaneous determination of flupirtine a...In the present study, we developed a simple, sensitive, precise, and accurate liquid chromatography-tandem mass spectrometric(LC-MS/MS) method and validated such approach for simultaneous determination of flupirtine and its active metabolite D-13223 in human plasma. The flupirtine, D-13223, and stable isotope internal standard(IS) were extracted from plasma samples by liquid-liquid extraction and chromatographed on a C18 column with a mobile phase consisting of acetonitrile–water–ammonia(55:45:0.1, v/v/v) at a flow rate of 0.25 m L/min. Detection was performed on a triple quadrupole tandem mass spectrometer with an electrospray ionization source(ESI) by multiple reaction monitoring(MRM) in positive ion mode. The linear calibration curves were obtained within the concentration range of 10.00–2000.00 ng/m L for flupirtine and 2.00–400.00 ng/m L for D-13223. The intra-and inter-run RSD, calculated from quality control(QC) samples, was less than 9.26% for flupirtine and D-13223. The accuracy was –5.80%–3.31% for flupirtine and D-13223. The extraction recoveries of flupirtine, D-13223, and their IS were all between 88.3%–97.2%. The method was successfully applied to investigate the pharmacokinetic profiles of flupirtine and its active metabolite D-13223 in human plasma following peroral administration of 100 mg flupirtine maleate capsules in healthy male Chinese volunteers.展开更多
Model-informed drug develop⁃ment(MIDD)is the application of a various math⁃ematical,statistical,and biological models to facilitate drug development,decision making and regulatory review.As a quantitative tool,MIDD ap...Model-informed drug develop⁃ment(MIDD)is the application of a various math⁃ematical,statistical,and biological models to facilitate drug development,decision making and regulatory review.As a quantitative tool,MIDD approaches allow an integration of information obtained from non-clinical studies and clinical trials in a drug development program.General understandings of the underlying biology,patho⁃physiology,and pharmacology can also be incor⁃porated into the model.MIDD is centered on knowledge and inferences generated from inte⁃grated models of the physicochemical character⁃istics of a molecule,its disposition in the body,and its mechanism of action,and how the drug might affect a disease from both an efficacy and a safety perspective.MIDD approaches have the potential to significantly streamline drug develop⁃ment,by improving clinical trial efficiency,opti⁃mizing dose and regimen and waive unneces⁃sary clinical studies.This presentation will use cases studies to demonstrate how to apply MIDD in early phase of clinical trials.展开更多
Background:Following the short-term outbreak of coronavirus disease 2019(COVID-19)in December 2022 in China,clinical data on kidney transplant recipients(KTRs)with COVID-19 are lacking.Methods:We conducted a single-ce...Background:Following the short-term outbreak of coronavirus disease 2019(COVID-19)in December 2022 in China,clinical data on kidney transplant recipients(KTRs)with COVID-19 are lacking.Methods:We conducted a single-center retrospective study to describe the clinical features,complications,and mortality rates of hospitalized KTRs infected with COVID-19 between Dec.16,2022 and Jan.31,2023.The patients were followed up until Mar.31,2023.Results:A total of 324 KTRs with COVID-19 were included.The median age was 49 years.The median time between the onset of symptoms and admission was 13 d.Molnupiravir,azvudine,and nirmatrelvir/ritonavir were administered to 67(20.7%),11(3.4%),and 148(45.7%)patients,respectively.Twenty-nine(9.0%)patients were treated with more than one antiviral agent.Forty-eight(14.8%)patients were treated with tocilizumab and 53(16.4%)patients received baricitinib therapy.The acute kidney injury(AKI)occurred in 81(25.0%)patients and 39(12.0%)patients were admitted to intensive care units.Fungal infections were observed in 55(17.0%)patients.Fifty(15.4%)patients lost their graft.The 28-d mortality rate of patients was 9.0%and 42(13.0%)patients died by the end of follow-up.Multivariate Cox regression analysis identified that cerebrovascular disease,AKI incidence,interleukin(IL)-6 level of>6.8 pg/mL,daily dose of corticosteroids of>50 mg,and fungal infection were all associated with an increased risk of death for hospitalized patients.Conclusions:Our findings demonstrate that hospitalized KTRs with COVID-19 are at high risk of mortality.The administration of immunomodulators or the late application of antiviral drugs does not improve patient survival,while higher doses of corticosteroids may increase the death risk.展开更多
Introduction: Prevention of irrational use of medicines may reduce healthcare costs and potentially save lives. Aim: The aim of this study was to assess rational drug prescribing using World Health Organization (WHO) ...Introduction: Prevention of irrational use of medicines may reduce healthcare costs and potentially save lives. Aim: The aim of this study was to assess rational drug prescribing using World Health Organization (WHO) and International Network of Rational Use of Drugs (INRUD) indicators on prescribing in the General Outpatient Department of Kampala International University Teaching Hospital, Ishaka-Bushenyi, Western Uganda. Methodology: The study design was retrospective, descriptive and cross-sectional. A total of 884 prescriptions were selected by systematic sampling using an interval of 27 from 23,868 prescriptions available in the medical records of the General Out-Patient Department (GOPD) of Kampala International University Teaching Hospital (KIUTH) from April, 2016 to March, 2017. The selected samples were analyzed using Microsoft Excel 2013, to assess for conformity with the prescribing indicators. Results: The results showed that the percentage of recording of diagnosis was 90.72% (index of diagnosis—0.91). The average number of drugs per encounter was 2.6 (index of non-polypharmacy—0.77), and the percentage of drugs prescribed with the generic name was 90.21% (index of generics—0.9). Percentages of encounters with antibiotics and injectable drugs prescribed were 61.88% (index of antibiotics—0.48) and 5.43% (index of injectable drugs—1) respectively. Only 78.96% (index of EMSLU—0.79) of the medicines prescribed were from the Essential Medicines Supplies List of Uganda (EMSLU) or Uganda Clinical Guidelines 2016. The index of rational drug prescribing (IRDP) was found to be 4.85. Conclusion: The findings showed that only the percentage of encounters with injectable drugs was in line with WHO/INRUD prescribing indicators. On the over all, the index of rational drug prescribing (IRDP) was poor (observed 4.85 versus optimum 6). The authors recommended continuous sensitization, counselling and education of prescribers in KIUTH in order to achieve rational prescribing.展开更多
Background: The present study was undertaken to investigate the patterns of drug and antibiotics prescribing in a teaching hospital in Cairo, Egypt. Aim: to determine the impact of interventions on such trends in an a...Background: The present study was undertaken to investigate the patterns of drug and antibiotics prescribing in a teaching hospital in Cairo, Egypt. Aim: to determine the impact of interventions on such trends in an attempt to rationalize drug use. Method: 1200 prescriptions and patients' records covering the months of January to December, 2011. Prescribing patterns were analyzed using WHO guidelines with regard to prescribing, patient care and health facility indicators. The same parame-ters were again assessed after distributing antibiotic guidelines and holding workshops activities directed towards rational drug use. Results: The number of hospital visits resulting in a prescription was significantly reduced from 94% to 86% (P-value <0.05) and in both cases none of the en-counters contained a generic drug. The average number of drugs per encounter was 2.7 and did not decrease significantly after intervention. A significant reduction was achieved in the number of prescriptions with antibiotics whereas reduction in encounters with injectable drugs was not statis-tically significant. Penicillins was the most commonly prescribed class of antibiotics and amoxicillin was the most frequently prescribed antibiotic. A significant reduction was observed in both en-counters with penicillin and the total of those with antibiotics. Analysis of prescriptions with anti-biotics revealed that penicillins, cephalosporins and erythromycin comprised 94% and 97% of all antibiotics prescribed before and after interventions respectively. Conclusion: The present results clearly indicated that interventions including distribution of antibiotic guidelines and running workshops and seminars on rational drug use to prescribers can lead to significant improvement in prescribing behavior.展开更多
Introduction: There is minimal literature to support the appropriate dosing for the initiation of IV regular insulin therapy in DKA patients. A 0.1 unit/kg bolus followed by 0.1 units/kg/hour or 0.14 units/kg/hour is ...Introduction: There is minimal literature to support the appropriate dosing for the initiation of IV regular insulin therapy in DKA patients. A 0.1 unit/kg bolus followed by 0.1 units/kg/hour or 0.14 units/kg/hour is commonly utilized and recommended in guidelines. Objective: We sought to assess clinical and safety outcomes associated with various insulin infusion starting doses in patients diagnosed with DKA in the emergency department in an effort to help guide prescribing. Methods: A retrospective cohort study was conducted within an academic emergency department and included patients who received continuous infusion regular insulin with an ICD-10 code for DKA between January 2016 and January 2019. A predictive regression model was applied to test if predefined lab values influenced the starting insulin infusion rates. Clinical and safety outcomes were evaluated by starting insulin infusion rate. Data was analyzed based on starting insulin infusion rates. Results: 347 patients met inclusion criteria with 92 (26.5%) patients receiving Conclusion: Glucose levels significantly influenced the insulin starting infusion rate, with no identified differences in adverse effects or clinical outcomes.展开更多
The following article has been retracted due to the investigation of complaints received against it. The Editorial Board found that substantial portions of the text came from other published papers. The scientific com...The following article has been retracted due to the investigation of complaints received against it. The Editorial Board found that substantial portions of the text came from other published papers. The scientific community takes a very strong view on this matter, and the OJAnes treats all unethical behavior such as plagiarism seriously. This paper published in Vol.3 No. 8, 367-373(pages), 2013, has been removed from this site.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
Increasing evidence showed that histone deacetylase 6(HDAC6)dysfunction is directly associated with the onset and progression of various diseases,especially cancers,making the development of HDAC6-targeted anti-tumor ...Increasing evidence showed that histone deacetylase 6(HDAC6)dysfunction is directly associated with the onset and progression of various diseases,especially cancers,making the development of HDAC6-targeted anti-tumor agents a research hotspot.In this study,artificial intelligence(AI)technology and molecular simulation strategies were fully integrated to construct an efficient and precise drug screening pipeline,which combined Voting strategy based on compound-protein interaction(CPI)prediction models,cascade molecular docking,and molecular dynamic(MD)simulations.The biological potential of the screened compounds was further evaluated through enzymatic and cellular activity assays.Among the identified compounds,Cmpd.18 exhibited more potent HDAC6 enzyme inhibitory activity(IC_(50)=5.41 nM)than that of tubastatin A(TubA)(IC_(50)=15.11 nM),along with a favorable subtype selectivity profile(selectivity index z 117.23 for HDAC1),which was further verified by the Western blot analysis.Additionally,Cmpd.18 induced G2/M phase arrest and promoted apoptosis in HCT-116 cells,exerting desirable antiproliferative activity(IC_(50)=2.59 mM).Furthermore,based on long-term MD simulation trajectory,the key residues facilitating Cmpd.18's binding were identified by decomposition free energy analysis,thereby elucidating its binding mechanism.Moreover,the representative conformation analysis also indicated that Cmpd.18 could stably bind to the active pocket in an effective conformation,thus demonstrating the potential for in-depth research of the 2-(2-phenoxyethyl)pyridazin-3(2H)-one scaffold.展开更多
Polyphenols,a diverse group of naturally occurring compounds found in plants,have garnered significant attention for their potential therapeutic properties in treating neurodegenerative diseases(NDs).The Wnt/β-cateni...Polyphenols,a diverse group of naturally occurring compounds found in plants,have garnered significant attention for their potential therapeutic properties in treating neurodegenerative diseases(NDs).The Wnt/β-catenin(WβC)signaling pathway,a crucial player in neurogenesis,neuronal survival,and synaptic plasticity,is involved in several cellular mechanisms related to NDs.Dysregulation of this pathway is a hallmark in the development of various NDs.This study explores multiple polyphenolic compounds,such as flavonoids,stilbenes,lignans,and phenolic acids,and their potential to protect the nervous system.It provides a comprehensive analysis of their effects on the WβC pathway,elucidating their modes of action.The study highlights the dual function of polyphenols in regulating and protecting the nervous system,providing reassurance about the research benefits.This review provides a comprehensive analysis of the results obtained from both in vitro studies and in vivo research,shedding light on how these substances influence the various components of the pathway.The focus is mainly on the molecular mechanisms that allow polyphenols to reduce oxidative stress,inflammation,and apoptotic processes,ultimately improving the function and survival of neurons.This study aims to offer a thorough understanding of the potential of polyphenols in targeting the WβC signaling pathway,which could lead to the development of innovative therapeutic options for NDs.展开更多
基金partially supported by the Construction Fund of Key Medical Disciplines of Hangzhou(No.OO2020491)the National Key Research and Development Program of China(No.2023YFC2506200)+4 种基金the Zhejiang Provincial Key Research and Development Program(No.2021C03107)the Research Project of Jinan Microecological Biomedicine Shandong Laboratory(No.JNL-2023001B)the Leading Talent of Scientific and Technological Innovation-“Ten Thousand Talents Program”of Zhejiang Province(No.2021R52016)the Innovation Team for Precision Diagnosis and Treatment of Major Brain Diseases(No.2020R01001)the Chinese Medical Education Association(No.2022KTZ004).
文摘Objective:Whether vortioxetine has a utility as an adjuvant drug in the treatment of bipolar depression remains controversial.This study aimed to validate the efficacy and safety of vortioxetine in bipolar depression.Methods:Patients with bipolarⅡdepression were enrolled in this prospective,two-center,randomized,12-week pilot trial.The main indicator for assessing treatment effectiveness was a Montgomery-Asberg Depression Rating Scale(MADRS)of≥50%.All eligible patients initially received four weeks of lurasidone monotherapy.Patients who responded well continued to receive this kind of monotherapy.However,no-response patients were randomly assigned to either valproate or vortioxetine treatment for eight weeks.By comprehensively comparing the results of MADRS over a period of 4-12 weeks,a systematic analysis was conducted to determine whether vortioxetine could be used as an adjuvant drug for treating bipolar depression.Results:Thirty-seven patients responded to lurasidone monotherapy,and 60 patients were randomly assigned to the valproate or vortioxetine group for eight weeks.After two weeks of combined valproate or vortioxetine treatment,the MADRS score in the vortioxetine group was significantly lower than that in the valproate group.There was no difference in the MADRS scores between the two groups at 8 and 12 weeks.The incidence of side effects did not significantly differ between the valproate and vortioxetine groups.Importantly,three patients in the vortioxetine group appeared to switch to mania or hypomania.Conclusions:This study suggested that lurasidone combination with vortioxetine might have potential benefits to bipolar II depression in the early stage,while disease progression should be monitored closely for the risk of switching to mania.
文摘Pharmacy clinics,staffed by clinical pharmacists who interact directly with patients,encompass services such as medication reconciliation,education,follow-up visits,and lifestyle guidance.Their primary goal is to enhance patients’quality of life.Numerous studies,both domestic and international,have highlighted the benefits of pharmacy clinics in optimizing drug therapy quality and reducing treatment costs,particularly for long-term medication management in organ transplant recipients and similar patient groups.Despite these benefits,pharmacy clinics are still in the early stages of development in China.There remains a lack of clarity regarding the specific development and service content of pharmacy clinics tailored for transplant patients.Therefore,this study aimed to assess the current status of pharmacy clinic development for transplant patients in China and provide insights to hospitals for advancing and strengthening transplant pharmacy clinic initiatives.
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supported by European Union Funding Programme,PNRR,No. 760058(to DMH)the UEFISCDI Project,No. PN-III-P4-IDPCE-2020-059(to APW)
文摘The major aim of stroke therapy is to stimulate brain repair and improve behavioral recovery after cerebral ischemia.One option is to stimulate endogenous neurogenesis in the subventricular zone and direct the newly formed neurons to the damaged area.However,only a small percentage of these neurons survive,and many do not reach the damaged area,possibly because the corpus callosum impedes the migration of subventricular zone-derived stem cells into the lesioned cortex.A second major obstacle to stem cell therapy is the strong inflammatory reaction induced by cerebral ischemia,whereby the associated phagocytic activity of brain macrophages removes both therapeutic cells and/or cell-based drug carriers.To address these issues,neurogenesis was electrically stimulated in the subventricular zone,followed by isolation of proliferating cells,including newly formed neurons,which were subsequently mixed with a nutritional hydrogel.This mixture was then transferred to the stroke cavity of day 14 post-stroke mice.We found that the performance of the treated animals improved in behavioral tests,including novel object,open field,hole board,grooming,and“time-to-feel”adhesive tape tests.Furthermore,immunostaining revealed that the stem cell marker nestin,the neuroepithelial marker Mash1,and the immature neuronal marker doublecortin-positive cells survived in the transplanted area for 2 weeks,possibly due to reduced phagocytic activity and supportive angiogenesis.These results clearly indicate that the transplantation of committed subventricular zone stem cells combined with a protective nutritional gel directly into the infarct cavity after the peak of stroke-induced neuroinflammation represents a feasible approach to improve neurorestoration after cerebral ischemia.
基金supported by the Natural Science Foundation of Hubei Provincial Department of Education(D20232101)Shandong Second Medical University 2024 Affiliated Hospital(Teaching Hospital)Scientific Research Development Fund Project(2024FYQ026)+3 种基金the innovative Research Programme of Xiangyang No.1 People’s Hospital(XYY2023ZY01)Faculty Development Grants of Xiangyang No.1 People’s Hospital Affiliated to Hubei University of Medicine(XYY2023D05)Joint supported by Hubei Provincial Natural Science Foundation and Xiangyang of China(2025AFD091)Traditional Chinese Medicine Scientific Research Project of Hubei Provincial Administration of Traditional Chinese Medicine(ZY2025D019).
文摘Background:Diabetic foot,a severe complication of diabetes,is characterized by chronic refractory wounds.Sanhuang Oil,a topical herbal formula,demonstrates significant therapeutic effects including antibacterial,anti-inflammatory,and immunomodulatory activities.However,its active constituents and mechanisms of action against diabetic foot remain to be elucidated.Methods:In this study,the chemical constituents of Sanhuang Oil were identified using UPLC-QE-Orbitrap-MS.Subsequently,the mechanism by which Sanhuang Oil promotes diabetic foot ulcer healing was predicted by integrating network pharmacology and molecular docking.Additionally,diabetic mouse model was established in ICR mice using a combination of a high-fat diet(HFD)and streptozotocin(STZ)chemical induction.A full-thickness skin defect was created on the dorsum of the mice.Wound healing and the healing rate were observed following Sanhuang Oil intervention.The mechanism underlying Sanhuang Oil’s promotion of diabetic ulcer healing was further investigated using transcriptomics and histopathological examination(H&E staining).Results:A total of 97 active ingredients were identified from Sanhuang Oil.Network pharmacology analysis predicted 543 common targets,and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis identified 203 relevant pathways.Molecular docking further confirmed high binding affinity(binding energy≤−5.0 kcal/mol)between specific active components in Sanhuang Oil(e.g.,coptisine,phellodendrine,baicalein)and key targets associated with diabetic foot ulcers(e.g.,EGFR,AKT1,STAT3).In vivo experimental results demonstrated that the wound healing rate was significantly higher in Sanhuang Oil-treated groups compared to the model group(P<0.001).HE staining revealed that the high-dose Sanhuang Oil group exhibited more pronounced epithelial tissue coverage over the wound,reduced inflammatory cell infiltration,and increased collagen deposition and fibroblast proliferation.transcriptomic analysis identified Pdk4,Ttn,Csrp3,Actn2,Myoz2,Tnnc2,Myod1,Myog,Myot,and Myf6 as key regulatory proteins involved in promoting wound healing.Conclusion:Sanhuang Oil promotes wound healing in diabetic ulcer mice,potentially by mitigating inflammation and regulating key targets such as Pdk4 to enhance fibroblast function.These findings provide novel insights into the multi-target,multi-pathway mechanism of Sanhuang Oil for treating diabetic foot ulcers.
文摘Introduction： The department of emergency medicine （DEM） has a high-risk environment due to its unique and complex workflow. Many high-risk medications are ordered and administered at patients’ bedsides without being checked by a pharmacist first, which may lead to an increase in the incidence of patient medication errors （MEs）. Objective： The current study evaluated the needs of the clinical pharmacy service in the DEM at King Saud University Medical City （KSUMC）, Riyadh, Saudi Arabia. Methods： A cross-sectional retrospective study was conducted between Jan 2016 to Dec 2017 and the documentation of clinical pharmacist interventions was extracted from Esihi database. Results： A total of 2,255 interventions for 862 patients were documented. The recommended interventions were as follows： 645 （dose adjustments）, 108 （therapeutic substitutions）, and 354 interventions （initiating drug therapy）. Adverse drug reactions （ADRs） were reported in 16 patients, and drug interactions were managed in 26 patients. The DEM responded to 713 information inquires and 290 pharmacokinetic consultations. Drug discontinuations included 39 incidents （where unjustified drug prescription occurred）, 37 （where contraindications were involved）, and 19 （where duplicate therapy was involved）. The most common interventions were related to the following drugs： antibiotics （34%）, anticoagulants （15%）, and anticonvulsants （10%）. The acceptance rates for the EM clinical pharmacist recommendations increased from 93.9% in 2016 to 99% in 2017. The most common outcome for interventions was to optimize the therapeutic effects of the drugs that were administered （73%）. Reconciliation was done in 796 patients. Conclusions： The clinical pharmacy service plays a critical role in the management of patients in the emergency department （ED）.
文摘Dear editor,The recent outbreak of coronavirus disease(COVID-19)has become a major public health issue caused by 2019 novel coronavirus(2019-nCoV).[1]Severe COVID-19 patients may reveal a dysregulated immune response that allows the development of v iral hyperinfl ammation.[2]In the fight against COVID-19,inflammatory parameters towards illness severity should be identified to improve the prognosis of patients.In this study,we aimed to assess the discriminative ability of several infl ammation indicators in severe COVID-19 infection.
基金the National Natural Science Foundation of China,No.82104525the Natural Science Foundation of the Jiangsu Higher Education Institutions of China,No.21KJB360009Health Commission of Zhejiang Province Scientific Research Foundation,No.2024KY247.
文摘The population of non-alcoholic fatty liver disease(NAFLD)patients along with relevant advanced liver disease is projected to continue growing,because currently no medications are approved for treatment.Fecal microbiota transplantation(FMT)is believed a novel and promising therapeutic approach based on the concept of the gut-liver axis in liver disease.There has been an increase in the number of pre-clinical and clinical studies evaluating FMT in NAFLD treatment,however,existing findings diverge on its effects.Herein,we briefly summarized the mechanism of FMT for NAFLD treatment,reviewed randomized controlled trials for evaluating its efficacy in NAFLD,and proposed the prospect of future trials on FMT.
文摘The present study aims to investigate the perceptions and experience of physicians regarding the clinical role of the pharmacists. This is an observational study that was conducted during the period of September 2013 through March 2014. A self-administered questionnaire was designed to be distributed by personal interview to the physicians. The questionnaire population consisted of randomly selected physicians practicing in UAE. The questionnaire was piloted by 10 physicians for face and understandability. Demographic data, frequencies and cross tabulation between different variables were calculated. The Chi-square test was used to determine the significance of association between categorical variables (gender, length of medical practice, and specialty) and the perception of physicians. A total of 285 filled questionnaires were returned representing 285 physicians, with a male dominance (65.3%). The average age of the physician screened was 32.4 (SD = 10.38) years with a minimum one year experience and up to 24 years. General practitioners consumed the widest sector (21.8%) followed by cardiologists (15.8%), then internal medicine (10.1%). In the current study, two thirds of the physicians believed that pharmacists could act as a reliable source of general drug information and play an important role in discovering clinical related problems. It was found that the physicians who had fewer years in practice (less than 10 years) and recently graduated had more acceptances to the clinical role of the pharmacist and believed that there should be a clinical pharmacy services in their hospitals (p-value < 0.05). No other statistically significant differences were found from analyzing the data. In conclusion, results suggest that physicians in UAE appear comfortable with pharmacists providing the broad range of services but appear somewhat less comfortable with pharmacists’ provision of direct patient care.
基金supported by the Natural Science Foundation of Shanghai,No.22ZR147750Science and Technology Innovation Action Plan of Shanghai Science and Technology Commission,No.23Y11906600Shanghai Changzheng Hospital Innovative Clinical Research Project,No.2020YLCYJ-Y02(all to YY).
文摘Alzheimer’s disease is a debilitating,progressive neurodegenerative disorder characterized by the progressive accumulation of abnormal proteins,including amyloid plaques and intracellular tau tangles,primarily within the brain.Lysosomes,crucial intracellular organelles responsible for protein degradation,play a key role in maintaining cellular homeostasis.Some studies have suggested a link between the dysregulation of the lysosomal system and pathogenesis of neurodegenerative diseases,including Alzheimer’s disease.Restoring the normal physiological function of lysosomes hold the potential to reduce the pathological burden and improve the symptoms of Alzheimer’s disease.Currently,the efficacy of drugs in treating Alzheimer’s disease is limited,with major challenges in drug delivery efficiency and targeting.Recently,nanomaterials have gained widespread use in Alzheimer’s disease drug research owing to their favorable physical and chemical properties.This review aims to provide a comprehensive overview of recent advances in using nanomaterials(polymeric nanomaterials,nanoemulsions,and carbon-based nanomaterials)to enhance lysosomal function in treating Alzheimer’s disease.This review also explores new concepts and potential therapeutic strategies for Alzheimer’s disease through the integration of nanomaterials and modulation of lysosomal function.In conclusion,this review emphasizes the potential of nanomaterials in modulating lysosomal function to improve the pathological features of Alzheimer’s disease.The application of nanotechnology to the development of Alzheimer’s disease drugs brings new ideas and approaches for future treatment of this disease.
文摘In the present study, we developed a simple, sensitive, precise, and accurate liquid chromatography-tandem mass spectrometric(LC-MS/MS) method and validated such approach for simultaneous determination of flupirtine and its active metabolite D-13223 in human plasma. The flupirtine, D-13223, and stable isotope internal standard(IS) were extracted from plasma samples by liquid-liquid extraction and chromatographed on a C18 column with a mobile phase consisting of acetonitrile–water–ammonia(55:45:0.1, v/v/v) at a flow rate of 0.25 m L/min. Detection was performed on a triple quadrupole tandem mass spectrometer with an electrospray ionization source(ESI) by multiple reaction monitoring(MRM) in positive ion mode. The linear calibration curves were obtained within the concentration range of 10.00–2000.00 ng/m L for flupirtine and 2.00–400.00 ng/m L for D-13223. The intra-and inter-run RSD, calculated from quality control(QC) samples, was less than 9.26% for flupirtine and D-13223. The accuracy was –5.80%–3.31% for flupirtine and D-13223. The extraction recoveries of flupirtine, D-13223, and their IS were all between 88.3%–97.2%. The method was successfully applied to investigate the pharmacokinetic profiles of flupirtine and its active metabolite D-13223 in human plasma following peroral administration of 100 mg flupirtine maleate capsules in healthy male Chinese volunteers.
文摘Model-informed drug develop⁃ment(MIDD)is the application of a various math⁃ematical,statistical,and biological models to facilitate drug development,decision making and regulatory review.As a quantitative tool,MIDD approaches allow an integration of information obtained from non-clinical studies and clinical trials in a drug development program.General understandings of the underlying biology,patho⁃physiology,and pharmacology can also be incor⁃porated into the model.MIDD is centered on knowledge and inferences generated from inte⁃grated models of the physicochemical character⁃istics of a molecule,its disposition in the body,and its mechanism of action,and how the drug might affect a disease from both an efficacy and a safety perspective.MIDD approaches have the potential to significantly streamline drug develop⁃ment,by improving clinical trial efficiency,opti⁃mizing dose and regimen and waive unneces⁃sary clinical studies.This presentation will use cases studies to demonstrate how to apply MIDD in early phase of clinical trials.
基金supported by the National Natural Science Foundation of China(No.2022YFC82200842)the Zhejiang Provincial Natural Science Foundation of China(No.LQ22H050004).
文摘Background:Following the short-term outbreak of coronavirus disease 2019(COVID-19)in December 2022 in China,clinical data on kidney transplant recipients(KTRs)with COVID-19 are lacking.Methods:We conducted a single-center retrospective study to describe the clinical features,complications,and mortality rates of hospitalized KTRs infected with COVID-19 between Dec.16,2022 and Jan.31,2023.The patients were followed up until Mar.31,2023.Results:A total of 324 KTRs with COVID-19 were included.The median age was 49 years.The median time between the onset of symptoms and admission was 13 d.Molnupiravir,azvudine,and nirmatrelvir/ritonavir were administered to 67(20.7%),11(3.4%),and 148(45.7%)patients,respectively.Twenty-nine(9.0%)patients were treated with more than one antiviral agent.Forty-eight(14.8%)patients were treated with tocilizumab and 53(16.4%)patients received baricitinib therapy.The acute kidney injury(AKI)occurred in 81(25.0%)patients and 39(12.0%)patients were admitted to intensive care units.Fungal infections were observed in 55(17.0%)patients.Fifty(15.4%)patients lost their graft.The 28-d mortality rate of patients was 9.0%and 42(13.0%)patients died by the end of follow-up.Multivariate Cox regression analysis identified that cerebrovascular disease,AKI incidence,interleukin(IL)-6 level of>6.8 pg/mL,daily dose of corticosteroids of>50 mg,and fungal infection were all associated with an increased risk of death for hospitalized patients.Conclusions:Our findings demonstrate that hospitalized KTRs with COVID-19 are at high risk of mortality.The administration of immunomodulators or the late application of antiviral drugs does not improve patient survival,while higher doses of corticosteroids may increase the death risk.
文摘Introduction: Prevention of irrational use of medicines may reduce healthcare costs and potentially save lives. Aim: The aim of this study was to assess rational drug prescribing using World Health Organization (WHO) and International Network of Rational Use of Drugs (INRUD) indicators on prescribing in the General Outpatient Department of Kampala International University Teaching Hospital, Ishaka-Bushenyi, Western Uganda. Methodology: The study design was retrospective, descriptive and cross-sectional. A total of 884 prescriptions were selected by systematic sampling using an interval of 27 from 23,868 prescriptions available in the medical records of the General Out-Patient Department (GOPD) of Kampala International University Teaching Hospital (KIUTH) from April, 2016 to March, 2017. The selected samples were analyzed using Microsoft Excel 2013, to assess for conformity with the prescribing indicators. Results: The results showed that the percentage of recording of diagnosis was 90.72% (index of diagnosis—0.91). The average number of drugs per encounter was 2.6 (index of non-polypharmacy—0.77), and the percentage of drugs prescribed with the generic name was 90.21% (index of generics—0.9). Percentages of encounters with antibiotics and injectable drugs prescribed were 61.88% (index of antibiotics—0.48) and 5.43% (index of injectable drugs—1) respectively. Only 78.96% (index of EMSLU—0.79) of the medicines prescribed were from the Essential Medicines Supplies List of Uganda (EMSLU) or Uganda Clinical Guidelines 2016. The index of rational drug prescribing (IRDP) was found to be 4.85. Conclusion: The findings showed that only the percentage of encounters with injectable drugs was in line with WHO/INRUD prescribing indicators. On the over all, the index of rational drug prescribing (IRDP) was poor (observed 4.85 versus optimum 6). The authors recommended continuous sensitization, counselling and education of prescribers in KIUTH in order to achieve rational prescribing.
文摘Background: The present study was undertaken to investigate the patterns of drug and antibiotics prescribing in a teaching hospital in Cairo, Egypt. Aim: to determine the impact of interventions on such trends in an attempt to rationalize drug use. Method: 1200 prescriptions and patients' records covering the months of January to December, 2011. Prescribing patterns were analyzed using WHO guidelines with regard to prescribing, patient care and health facility indicators. The same parame-ters were again assessed after distributing antibiotic guidelines and holding workshops activities directed towards rational drug use. Results: The number of hospital visits resulting in a prescription was significantly reduced from 94% to 86% (P-value <0.05) and in both cases none of the en-counters contained a generic drug. The average number of drugs per encounter was 2.7 and did not decrease significantly after intervention. A significant reduction was achieved in the number of prescriptions with antibiotics whereas reduction in encounters with injectable drugs was not statis-tically significant. Penicillins was the most commonly prescribed class of antibiotics and amoxicillin was the most frequently prescribed antibiotic. A significant reduction was observed in both en-counters with penicillin and the total of those with antibiotics. Analysis of prescriptions with anti-biotics revealed that penicillins, cephalosporins and erythromycin comprised 94% and 97% of all antibiotics prescribed before and after interventions respectively. Conclusion: The present results clearly indicated that interventions including distribution of antibiotic guidelines and running workshops and seminars on rational drug use to prescribers can lead to significant improvement in prescribing behavior.
文摘Introduction: There is minimal literature to support the appropriate dosing for the initiation of IV regular insulin therapy in DKA patients. A 0.1 unit/kg bolus followed by 0.1 units/kg/hour or 0.14 units/kg/hour is commonly utilized and recommended in guidelines. Objective: We sought to assess clinical and safety outcomes associated with various insulin infusion starting doses in patients diagnosed with DKA in the emergency department in an effort to help guide prescribing. Methods: A retrospective cohort study was conducted within an academic emergency department and included patients who received continuous infusion regular insulin with an ICD-10 code for DKA between January 2016 and January 2019. A predictive regression model was applied to test if predefined lab values influenced the starting insulin infusion rates. Clinical and safety outcomes were evaluated by starting insulin infusion rate. Data was analyzed based on starting insulin infusion rates. Results: 347 patients met inclusion criteria with 92 (26.5%) patients receiving Conclusion: Glucose levels significantly influenced the insulin starting infusion rate, with no identified differences in adverse effects or clinical outcomes.
文摘The following article has been retracted due to the investigation of complaints received against it. The Editorial Board found that substantial portions of the text came from other published papers. The scientific community takes a very strong view on this matter, and the OJAnes treats all unethical behavior such as plagiarism seriously. This paper published in Vol.3 No. 8, 367-373(pages), 2013, has been removed from this site.
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 .
基金funded by Central Guidance on Local Science and Technology Development Fund of Hebei Province,China(Grant No.:226Z2605G)the Key Project from Hebei Provincial Department of Science and Technology,China(Grant No.:21372601D)+6 种基金Graduate Student Innovation Grant Program of Hebei Medical University,China(Grant No.:XCXZZB202303)Science Research Project of Hebei Education Department,China(Grant Nos.:BJ2025046,and CYZD202501)Program for Young Scientists in the Field of Natural Science of Hebei Medical University,China(Program Nos.:CYCZ2023010,CYCZ2023011,CYQD2021011,CYQD2021015 and CYQD2023012)Traditional Chinese Medicine Administration Project of Hebei Province,China(Project No.:2025427)National Natural Science Foundation of China(Grant No.:32100771)the Hebei Provincial Medical Science Research Project Plan,China(Project Nos.:20240241 and 20220200)Shijiazhuang Science and Technology Bureau,China(Grant Nos.:241200487A,and 07202204).
文摘Increasing evidence showed that histone deacetylase 6(HDAC6)dysfunction is directly associated with the onset and progression of various diseases,especially cancers,making the development of HDAC6-targeted anti-tumor agents a research hotspot.In this study,artificial intelligence(AI)technology and molecular simulation strategies were fully integrated to construct an efficient and precise drug screening pipeline,which combined Voting strategy based on compound-protein interaction(CPI)prediction models,cascade molecular docking,and molecular dynamic(MD)simulations.The biological potential of the screened compounds was further evaluated through enzymatic and cellular activity assays.Among the identified compounds,Cmpd.18 exhibited more potent HDAC6 enzyme inhibitory activity(IC_(50)=5.41 nM)than that of tubastatin A(TubA)(IC_(50)=15.11 nM),along with a favorable subtype selectivity profile(selectivity index z 117.23 for HDAC1),which was further verified by the Western blot analysis.Additionally,Cmpd.18 induced G2/M phase arrest and promoted apoptosis in HCT-116 cells,exerting desirable antiproliferative activity(IC_(50)=2.59 mM).Furthermore,based on long-term MD simulation trajectory,the key residues facilitating Cmpd.18's binding were identified by decomposition free energy analysis,thereby elucidating its binding mechanism.Moreover,the representative conformation analysis also indicated that Cmpd.18 could stably bind to the active pocket in an effective conformation,thus demonstrating the potential for in-depth research of the 2-(2-phenoxyethyl)pyridazin-3(2H)-one scaffold.
基金financially supporting this work through the Large Research Group Project under Grant no.R.G.P.2/509/45
文摘Polyphenols,a diverse group of naturally occurring compounds found in plants,have garnered significant attention for their potential therapeutic properties in treating neurodegenerative diseases(NDs).The Wnt/β-catenin(WβC)signaling pathway,a crucial player in neurogenesis,neuronal survival,and synaptic plasticity,is involved in several cellular mechanisms related to NDs.Dysregulation of this pathway is a hallmark in the development of various NDs.This study explores multiple polyphenolic compounds,such as flavonoids,stilbenes,lignans,and phenolic acids,and their potential to protect the nervous system.It provides a comprehensive analysis of their effects on the WβC pathway,elucidating their modes of action.The study highlights the dual function of polyphenols in regulating and protecting the nervous system,providing reassurance about the research benefits.This review provides a comprehensive analysis of the results obtained from both in vitro studies and in vivo research,shedding light on how these substances influence the various components of the pathway.The focus is mainly on the molecular mechanisms that allow polyphenols to reduce oxidative stress,inflammation,and apoptotic processes,ultimately improving the function and survival of neurons.This study aims to offer a thorough understanding of the potential of polyphenols in targeting the WβC signaling pathway,which could lead to the development of innovative therapeutic options for NDs.
