Although different studies have associated coronavirus disease 2019(COVID-19)with the occurrence of liver injury,the hepatic injury route during the COVID-19 course is not yet fully understood.In order to better under...Although different studies have associated coronavirus disease 2019(COVID-19)with the occurrence of liver injury,the hepatic injury route during the COVID-19 course is not yet fully understood.In order to better understand the mechanisms of the disease,the human gut microbiota has been the subject of extensive discussion in the context of COVID-19 pathophysiology.However,many questions remain,including the risks of liver injury due to COVID-19 specific populations.Further research in this field could allow the discovery of new personalized treatment strategies aimed at improving the microbiota composition,thereby reducing COVID-19 severity and its complications in different populations.In this article,we discussed basic mechanisms of severe acute respiratory syndrome coronavirus 2 infection and recent evidence on the relationship between COVID-19,the gut microbiome and liver injury as well as proposed recommendations for further research.展开更多
This article seeks to emphasize a simplified approach to phylogeny research using complete mitochondrial genomes alone, while touching upon a number of technological perspectives, such as algorithmic selection, which ...This article seeks to emphasize a simplified approach to phylogeny research using complete mitochondrial genomes alone, while touching upon a number of technological perspectives, such as algorithmic selection, which can help improve accuracy and performance in comparative analysis. My results will show that reliable estimations can be obtained by using mitochondrial markers, even among time-extended taxonomical rankings. Six distinct mammalian groups of taxa were selected for comparison. In all cases, mtDNA models generated reliable phylogeny approximations when compared against other independent data, while rendering exceptional computational performance.展开更多
Nitric oxide(NO)is a gaseous molecule produced by 3 different NO synthase(NOS)isoforms:Neural/brain NOS(nNOS/bNOS,type 1),endothelial NOS(eNOS,type 3)and inducible NOS(type 2).Type 1 and 3 NOS are constitutively expre...Nitric oxide(NO)is a gaseous molecule produced by 3 different NO synthase(NOS)isoforms:Neural/brain NOS(nNOS/bNOS,type 1),endothelial NOS(eNOS,type 3)and inducible NOS(type 2).Type 1 and 3 NOS are constitutively expressed.NO can serve different purposes:As a vasoactive molecule,as a neurotransmitter or as an immunomodulator.It plays a key role in cerebral ischemia/reperfusion injury(CIRI).Hypoxic episodes simulate the production of oxygen free radicals,leading to mitochondrial and phospholipid damage.Upon reperfusion,increased levels of oxygen trigger oxide synthases;whose products are associated with neuronal damage by promoting lipid peroxidation,nitrosylation and excitotoxicity.Molecular pathways in CIRI can be altered by NOS.Neuroprotective effects are observed with eNOS activity.While nNOS interplay is prone to endothelial inflammation,oxidative stress and apoptosis.Therefore,nNOS appears to be detrimental.The interaction between NO and other free radicals develops peroxynitrite;which is a cytotoxic agent.It plays a main role in the likelihood of hemorrhagic events by tissue plasminogen activator(t-PA).Peroxynitrite scavengers are currently being studied as potential targets to prevent hemorrhagic transformation in CIRI.展开更多
The critical role of patient-reported outcome measures(PROMs)in enhancing clinical decision-making and promoting patient-centered care has gained a profound significance in scientific research.PROMs encapsulate a pati...The critical role of patient-reported outcome measures(PROMs)in enhancing clinical decision-making and promoting patient-centered care has gained a profound significance in scientific research.PROMs encapsulate a patient's health status directly from their perspective,encompassing various domains such as symptom severity,functional status,and overall quality of life.By integrating PROMs into routine clinical practice and research,healthcare providers can achieve a more nuanced understanding of patient experiences and tailor treatments accordingly.The deployment of PROMs supports dynamic patient-provider interactions,fostering better patient engagement and adherence to tre-atment plans.Moreover,PROMs are pivotal in clinical settings for monitoring disease progression and treatment efficacy,particularly in chronic and mental health conditions.However,challenges in implementing PROMs include data collection and management,integration into existing health systems,and acceptance by patients and providers.Overcoming these barriers necessitates technological advancements,policy development,and continuous education to enhance the acceptability and effectiveness of PROMs.The paper concludes with recommendations for future research and policy-making aimed at optimizing the use and impact of PROMs across healthcare settings.展开更多
Good afternoon,everyone.I'd like to acknowledge DIA for the invitation.I will spend next 25 minutes to briefly talk about the research in Australia and complementary medicine (CM) there.Most importantly,I'd li...Good afternoon,everyone.I'd like to acknowledge DIA for the invitation.I will spend next 25 minutes to briefly talk about the research in Australia and complementary medicine (CM) there.Most importantly,I'd like to introduce a case that I was involved in the last 10 years,which was about developing a new herbal medicine for vascular dementia (VaD).I would actually highlight the issues in it as well as the experience and lessons.展开更多
Objective To investigate the association between ABO blood types and gestational diabetes mellitus(GDM)risk.Methods A prospective birth cohort study was conducted.ABO blood types were determined using the slide method...Objective To investigate the association between ABO blood types and gestational diabetes mellitus(GDM)risk.Methods A prospective birth cohort study was conducted.ABO blood types were determined using the slide method.GDM diagnosis was based on a 75-g,2-h oral glucose tolerance test(OGTT)according to the criteria of the International Association of Diabetes and Pregnancy Study Groups.Logistic regression was applied to calculate the odds ratios(ORs)and 95%confidence intervals(CIs)between ABO blood types and GDM risk.Results A total of 30,740 pregnant women with a mean age of 31.81 years were enrolled in this study.The ABO blood types distribution was:type O(30.99%),type A(26.58%),type B(32.20%),and type AB(10.23%).GDM was identified in 14.44%of participants.Using blood type O as a reference,GDM risk was not significantly higher for types A(OR=1.05)or B(OR=1.04).However,women with type AB had a 19%increased risk of GDM(OR=1.19,95%CI=1.05–1.34;P<0.05),even after adjusting for various factors.This increased risk for type AB was consistent across subgroup and sensitivity analyses.Conclusion The ABO blood types may influence GDM risk,with type AB associated with a higher risk.Incorporating it—either as a single risk factor or in combination with other known factors—could help identify individuals at risk for GDM before or during early pregnancy.展开更多
Sugarcane bagasse(SCB)is a promising natural fiber for bio-based composites,but its high moisture absorption and poor interfacial adhesion with polymer matrices limit mechanical performance.While chemical treatments h...Sugarcane bagasse(SCB)is a promising natural fiber for bio-based composites,but its high moisture absorption and poor interfacial adhesion with polymer matrices limit mechanical performance.While chemical treatments have been extensively explored,limited research has addressed how thermal treatment alone alters the surface properties and reinforcing behavior of SCB fibers.This study aims to fill that gap by investigating the effects of heat treatment on SCB fiber structure and its performance in starch/poly(vinyl alcohol)(PVA)composites.Characterization techniques including Fourier transform infrared spectroscopy(FTIR),X-ray diffraction(XRD),X-ray photoelectron spectroscopy(XPS),and scanning electron microscopy(SEM)were employed to analyze changes in fiber morphology,surface chemistry,and crystallinity.Mechanical properties were assessed via tensile,flexural,and impact testing,and moisture absorption was also evaluated.Composites reinforced with SCB fibers treated at 200○C exhibited significantly superior mechanical properties compared to those prepared with untreated or differently treated fibers.The tensile,flexural,and impact performance of the composites were 15.13,19.37 MPa,and 7.28 J/m,respectively.Composites treated at this temperature also retained better mechanical properties after exposure to humidity.These findings demonstrate that heat treatment is a simple and sustainable method to improve the durability and mechanical performance of nature fiber-reinforced composites,expanding their potential for environmentally friendly material applications.展开更多
The increasing global demand for energy,coupled with concerns about environmental sustainability,has underscored the need for a transition toward renewable energy sources.A well-structured teaching program under the f...The increasing global demand for energy,coupled with concerns about environmental sustainability,has underscored the need for a transition toward renewable energy sources.A well-structured teaching program under the framework of sustainable development in renewable energy seeks to give students the information,abilities,and critical thinking needed to solve energy-related problems sustainably.This research proposes AI-powered personalized learning,innovative real-time integration of diverse data,and adaptive teaching strategies to enhance student understanding regarding renewable energy concepts.The sheep flock-optimized innovative recurrent neural network(SFO-IRNN)will recommend relevant topics and resources based on students’performance.Renewable energy teaching data from assessmethments are combined with real-time IoT-based renewable energy data.This dataset contains renewable energy education using AI-driven teaching methods and internet-based learning.The data was preprocessed by handling missing values and min-max scaling.The data features were extracted using Fourier Transform(FT).Further application of 10-fold cross-validation will increase the reliability of the model as it can evaluate its performance metrics like accuracy,F1-score,recall,and precision on different subsets of student data,which improves its robustness and prevents overfitting.The findings showed that the proposed method is significantly better,which ensures that the students have a deeper theoretical and practical understanding of renewable energy technologies.In addition,integrating real-time IoT data from renewable energy sources gives students a chance to do live simulations and problems that would enhance analytical thinking and hands-on learning.The research shows that AI provides context-aware guidance on sustainable energy infrastructure,enhancing interactive and personalized learning.展开更多
Density(p),speed of sound(u),viscosity(η),and refractive index(n_(D))were measured for pure acetonitrile,trichloroethene,and tetrachloroethene,as well as their binary mixtures at temperatures T=(293.15,298.15,303.15)...Density(p),speed of sound(u),viscosity(η),and refractive index(n_(D))were measured for pure acetonitrile,trichloroethene,and tetrachloroethene,as well as their binary mixtures at temperatures T=(293.15,298.15,303.15)K and at ambient pressure(81.5 kPa).From the experimental data,excess molar volume(V_(m)~E),thermal expansion coefficients(α),deviations in isentropic compressibility(Δκ_(S)),viscosity(Δ_η),and refractive index(Δn_(D))were calculated.These values were then correlated using the Redlich-Kister polynomial equation,with fitting coefficients and standard deviations determined.Additionally,the Prigogine-Flory-Patterson(PFP)theory and the Extended Real Associated Solution(ERAS)model were employed to correlate the excess molar volume,while the Perturbed Chain Statistical Associating Fluid Theory(PC-SAFT)was used to predict the density of mixtures.展开更多
BACKGROUND Aloe vera has been used as a traditional herbal therapy for wound management and dermatological conditions worldwide for thousands of years.Scientific evidence has confirmed that acemannan,the bioactive com...BACKGROUND Aloe vera has been used as a traditional herbal therapy for wound management and dermatological conditions worldwide for thousands of years.Scientific evidence has confirmed that acemannan,the bioactive compound in aloe vera gel,exhibits significant anti-inflammatory and immunomodulatory properties that enhance tissue regeneration.This case report describes the successful application of an innovative acemannan-enriched glycolipid sphere dressing derived from aloe vera gel in diabetic foot ulcer(DFU)treatment,which achieved a clinically remarkable outcome.CASE SUMMARY An 80-year-old female patient with a 20-year history of type 2 diabetes mellitus experienced recurrent diabetic foot pain for 15 years.She had multiple hospitalizations due to acute infections and poorly controlled hyperglycemia.Long-term treatments included metformin and gliclazide.Upon presentation,she had a nonhealing wound on her left dorsal foot,diagnosed as a severe DFU(Texas classification:Grade II,stage D).She declined amputation and opted for conservative treatment.The medical team applied an acemannan-enriched glycolipid sphere dressing five times daily to the left calf and foot,avoiding the wound area.Frequency was reduced to three times daily after scab formation.Weight-bearing on the injured foot was avoided.Through in-person and online consultations,the team managed her lifestyle and diet,emphasizing natural foods.After 5 months,the DFU healed without significant scarring or functional loss.No recurrence was observed during the 2-year follow-up.Acemannan-enriched glycolipid sphere dressings promote DFU healing.This suggests the potential of these dressings for treating other refractory wounds.展开更多
Background Resistance to traditional intense chemotherapy and high invasiveness are characteristics of head and neck squamous cell cancer(HNSCC).Numerous human disorders are linked to N6-methyladenosine(m6A)modificati...Background Resistance to traditional intense chemotherapy and high invasiveness are characteristics of head and neck squamous cell cancer(HNSCC).Numerous human disorders are linked to N6-methyladenosine(m6A)modification of RNA,and the genetic changes in m6A regulatory genes in HNSCC are not well-understood.There is also a pressing need to find efficient targets and inhibitors for the treatment of HNSCC.This investigation examined the RNA m6A alteration in HNSCC and found putative IGFBP3 inhibitors for potential use.Methods We examined m6A regulator gene expression data from the public Gene Expression Omnibus(GEO)database in both normal tissues and patient HNSCC.For bioinformatics analysis,the R package and additional tools,including the m6A2Target database,Gene Ontology(GO)functional and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses,Gene Expression Profiling Interactive Analysis(GEPIA),and Human Protein Atlas,were used to examine the molecular mechanisms and prognostic impact for regulators that are distinctly expressed.Furthermore,TCMBank molecules were employed for virtual screening to find possible inhibitors.Results Out of the 151 differentially expressed genes(DEGs)found in the chosen datasets,insulin-like growth factor 2 mRNA-binding protein 3(IGF2BP3)was the m6A regulator that was elevated in HNSCC.The GO and KEGG analyses revealed that the target genes of IGF2BP3 were mostly enriched in several pathways and activities linked to cancer.In patients with HNSCC,IGF2BP3 showed an effective predictive effect by GEPIA analysis.Virtual screening yielded four traditional Chinese medicine ingredients as putative IGF2BP3 inhibitors for additional research.Discussion This work learned the role and prognostic effect of IGF2BP3 in HNSCC;meanwhile,the potential inhibitors of IGF2BP3 were identified for further study.展开更多
BACKGROUND Extracellular vesicles derived from mesenchymal stromal cells(MSC-EVs)can be used for anti-aging therapy and treating various aging-related diseases.However,the clinical application of MSC-EVs is still limi...BACKGROUND Extracellular vesicles derived from mesenchymal stromal cells(MSC-EVs)can be used for anti-aging therapy and treating various aging-related diseases.However,the clinical application of MSC-EVs is still limited,mainly due to insufficient in-formation on the preparation process,quality,and mechanism of action of MSC-EVs.To study the biological effects of MSC-EVs in regulating cellular senescence.METHODS In this study,we developed a clinical-grade production process for MSC-EVs and defined the release criteria for products suitable for human use.To support the clinical use of our product as a therapeutic agent,we performed efficacy assays to evaluate the anti-aging capacity of MSC-EVs in vitro and in vivo.RESULTS The functional analysis results revealed that MSC-EVs significantly reduced the levels of senescence-associatedβ-galactosidase,matrix metallopeptidase 1,P21,and interleukin-1βand increased the level of collagen I in a naturally aged cell model of human dermal fibroblasts.Similarly,treatment with MSC-EVs effectively improved D-gal-induced subacute aging in mice,aging-related histopathological changes,oxidative stress,and aging-related gene expression.CONCLUSION These findings indicate that MSC-EVs can partially alleviate D-gal-induced senescence by reducing oxidative stress and regulating metabolism.Overall,these findings strongly suggest that MSC-EVs hold promise for aging therapy.展开更多
China’s annual Central Economic Work Conference(CEWC),held on December 11 and 12,2024,signaled the government’s determination to sustain economic growth and expand high-level opening up.Against the backdrop of risin...China’s annual Central Economic Work Conference(CEWC),held on December 11 and 12,2024,signaled the government’s determination to sustain economic growth and expand high-level opening up.Against the backdrop of rising global economic uncertainty,stabilizing the economy and promoting highquality development not only represent a practical need for the country to achieve key goals on its socioeconomic agenda and make steady progress on the Chinese path to modernization,but will also help enhance economic resilience against external headwinds and contribute more to the global economy.展开更多
Mesenchymal stem cells are highly regarded for their potential in tissue repair and regenerative medicine due to their multipotency and self-renewal abilities.Recently,mesenchymal stem cells have been redefined as“me...Mesenchymal stem cells are highly regarded for their potential in tissue repair and regenerative medicine due to their multipotency and self-renewal abilities.Recently,mesenchymal stem cells have been redefined as“medical signaling cells,”with their primary biological effects mediated through exosome secretion.These exosomes,which contain lipids,proteins,RNA,and metabolites,are crucial in regulating various biological processes and enhancing regenerative therapies.Exosomes replicate the effects of their parent cells while offering benefits such as reduced side effects,low immunogenicity,excellent biocompatibility,and high drug-loading capacity.Dental stem cells,including those from apical papilla,gingiva,dental pulp,and other sources,are key contributors to exosome-mediated regenerative effects,such as tumor cell apoptosis,neuroprotection,angiogenesis,osteogenesis,and immune modulation.Despite their promise,clinical application of exosomes is limited by challenges in isolation techniques.Current methods face issues of complexity,inefficiency,and insufficient purity,hindering detailed analysis.Recent advancements,such as micro-electromechanical systems,alternating current electroosmosis,and serum-free three-dimensional cell cultures,have improved exosome isolation efficacy.This review synthesizes nearly 200 studies on dental stem cell-derived exosomes,highlighting their potential in treating a wide range of conditions,including periodontal diseases,cancer,neurodegenerative disorders,diabetes,and more.Optimized isolation methods offer a path forward for overcoming current limitations and advancing the clinical use of exosome-based therapies.展开更多
BACKGROUND Bile cast nephropathy(BCN)is suspected in the setting of liver disease and hyperbilirubinemia and is characterized by the formation of tubular bile casts and acute tubular injury.While postmortem studies re...BACKGROUND Bile cast nephropathy(BCN)is suspected in the setting of liver disease and hyperbilirubinemia and is characterized by the formation of tubular bile casts and acute tubular injury.While postmortem studies reveal a high prevalence of BCN,little is known about this orphan acute kidney injury syndrome.AIM To address this knowledge gap,we performed a systematic review of case reports and case series of BCN,focusing on risk factors,diagnostic criteria,clinical presentation,kidney biopsy findings,severity,treatment approaches,and outcomes.METHODS Electronic databases were searched to identify eligible studies of patients with possible,probable,or definite BCN,using pre-established criteria.Relevant variables were extracted and analyzed.We explored the impact of serum total bilirubin levels and alcoholic liver disease on BCN severity and outcomes by stratifying cases into total bilirubin tertiles and alcoholic vs non-alcoholic liver disease.Univariate and multivariable logistic regression analyses were used to examine factors associated with the composite outcome of dialysis requirement or death.RESULTS Sixty-seven case reports and six case series(involving 2 patients each)met the inclusion criteria,totaling 79 cases of BCN.The mean age was 48.3 years,and 83.5%were men.The most common cause of liver disease was drug-induced injury(30.4%),followed by infection(18.9%)and alcoholism(12.7%).BCN diagnosis was deemed definite,probable,and possible in 65.8%,32.9%,and 1.3%of cases,respectively.Levels of serum creatinine,dialysis requirement,and renal recovery did not differ among the total bilirubin tertile groups.However,both initial and peak serum creatinine were significantly higher in the alcoholic liver disease group compared to the non-alcoholic group(P=0.011 and P=0.012,respectively).There was also a non-significant trend toward a higher incidence of dialysis requirement or death in the alcoholic liver disease group(80%vs 52%,P=0.098).Finally,higher initial serum creatinine(per 1 mg/dL increase)was independently associated with dialysis requirement or death(adjusted odds ratio 1.291,95%confidence interval:1.032-1.615,P=0.025).CONCLUSION BCN is a common and potentially serious cause of acute kidney injury in patients with liver disease.The degree of hyperbilirubinemia does not appear to correlate with BCN severity or outcomes.However,in alcoholic liver disease,BCN is associated with a greater rise in serum creatinine and a trend toward worse outcomes compared to non-alcoholic liver disease.Serum creatinine may be a valuable predictor of BCN prognosis.Further studies are needed to develop non-invasive diagnostic tools and establish effective treatments for BCN.展开更多
The Tourism Industry plays a critical role in economic growth on the international scene but is equally responsible for contributing to greenhouse gas emissions and energy demand.The research analyzed the global trend...The Tourism Industry plays a critical role in economic growth on the international scene but is equally responsible for contributing to greenhouse gas emissions and energy demand.The research analyzed the global trends of energy consumption(EC)within this industry concerning environmental performance,limits,and prospects of sustained expan-sion.It includes 300 tourism-related businesses across different global economic regions.Key tourism factors include EC,greenhouse gas emissions,renewable energy(RE)use,tourism’s Gross Domestic Product(GDP)contribution,and energy efficiency.Statistical methods such as regression and panel data analysis assess the impact of tourism GDP,carbon emissions and RE.The regression analysis,including linear regression and panel data regression,to assess the influence of factors such as tourism GDP,carbon emissions,RE share,and energy efficiency improvements,providing a data-driven approach to understanding EC in tourism.The findings reveal regional differences,with developed regions consuming more energy per capita,while developing markets show progress in energy-efficient practices.The findings of the linear regression analysis show tourism GDP contribution(β=4,200).The outcomes of the panel data regression analysis show the t-statistic values of carbon emissions(t=5.64).The Difference-in-Differences analysis indicates that tourist GDP is greater in developed regions(β=4,100)compared to developing regions(β=3,500).Carbon emissions(β=4,800)are greater,although RE(β=4,200)and energy efficiency(β=2,500)increase more in developing nations.The research emphasizes expanding use of RE in tourism infrastructure,especially in ecotourism and green hotels.展开更多
BACKGROUND The adoption of telehealth services surged after the coronavirus disease 2019 pandemic,revolutionizing traditional healthcare delivery models.Amazon Clinic's recent nationwide launch marks a significant...BACKGROUND The adoption of telehealth services surged after the coronavirus disease 2019 pandemic,revolutionizing traditional healthcare delivery models.Amazon Clinic's recent nationwide launch marks a significant milestone in this trend.This study aims to offer a strengths,weaknesses,opportunities,and threats(SWOT)analysis of Amazon Clinic and compare its features with leading virtual healthcare platforms.AIM To evaluate Amazon Clinic's telehealth services through a SWOT analysis and compare its features with other leading virtual healthcare platforms.METHODS The initial search terms included were,amazon clinic odds ratio(OR)amwell OR Teladoc OR Walmart virtual health service OR CVS minute clinic OR CirrusMD OR brightside health,from 2000 to 2023.This search yielded 111 articles,from which duplicates were removed,and unrelated titles were filtered out.Eight articles were retained for a final review,including comparative studies,usability research,retrospective analyses,observational studies,and review articles.The data was organized and analyzed using Rayyan software and summarized in a table and PRISMA flowcharts.RESULTS The review included eight articles focusing on various aspects of telehealth.Comparative studies highlighted differences between Teladoc and traditional physician offices,noting lower diagnostic imaging orders and antibiotic prescriptions for Teladoc.User demographics for Teladoc showed younger,less engaged patients.Usability studies emphasized the importance of website design for telemedicine adoption.Tele-mental health platforms like Brightside showed superior outcomes in treating depression compared to traditional methods.Telemedicine for specialized fields like skin reconstruction demonstrated cost efficiency and reduced waiting times.The SWOT analysis identified Amazon Clinic's strengths,such as its vast consumer base and transparent pricing,and weaknesses like the lack of pediatric care.Opportunities included potential partnerships and service expansions,while threats involved competition and regulatory challenges.CONCLUSION Amazon Clinic's entry into the telehealth sector represents a significant development with various strengths and opportunities.However,it faces challenges from established healthcare providers and regulatory landscapes.The future success of Amazon Clinic will depend on strategic collaborations,addressing service gaps,and navigating competition and regulations.Telemedicine's impact will hinge on its ability to effectively leverage these opportunities and overcome inherent challenges in the ever-evolving healthcare landscape.展开更多
Osteoarthritis(OA)is a chronic joint disease characterized by cartilage degradation,synovial inflammation,and subchondral bone remodelling.Despite its increasing prevalence,effective diagnostic,disease-limiting,and th...Osteoarthritis(OA)is a chronic joint disease characterized by cartilage degradation,synovial inflammation,and subchondral bone remodelling.Despite its increasing prevalence,effective diagnostic,disease-limiting,and therapeutic strategies remain unattainable.Recent studies have recognized the involvement of microRNA-155(miR-155)in the pathogenesis of OA and most of its risk factors while also identifying the antidiabetic drug metformin as a potential modulator of disease progression.MiR-155,a key endogenous regulator of the immune system,mechano-transduction,and multiple genetic pathways,interacts with OA targets of cellular energetic and circadian homeostasis,promoting systemic and local articular inflammation,cartilage matrix degradation,and chondrocyte apoptosis.Metformin,widely used for type 2 diabetes,has demonstrated anti-inflammatory,anti-oxidative,and chondroprotective properties in OA,mainly through its activation of adenosine monophosphate-activated protein kinase and inhibition of nuclear factor kappa-B signalling.Enthrallingly,metformin targets the same cellular pathways as miR-155 with emerging evidence also suggesting miR-155 expression modulation,indicating synergistic,potentially disease-modifying effects in OA.This review highlights the central role of miR-155 in OA pathophysiology and its potential as a biomarker for disease diagnosis and progression.MiR-155 targeting-through microRNA therapeutics(mimics/antagomiRs)and/or metformin-could pave the way for innovative treatments,including novel articular delivery systems and cell-based therapies.展开更多
Although the etiology of inflammatory bowel disease (IBD) remains unclear,compromised epithelial barrier integrity is believed to promote susceptibility toIBD and be associated with disease severity, suggesting that i...Although the etiology of inflammatory bowel disease (IBD) remains unclear,compromised epithelial barrier integrity is believed to promote susceptibility toIBD and be associated with disease severity, suggesting that improving gut barrierintegrity may palliate or treat IBD. Such a notion gets support from the clinicalfindings that mucosal healing in IBD patients is associated with improvedprognosis, and reduced risk of relapse or colitis-associated cancer. It thereforebecomes critical to understand the intracellular signals that regulate mucosalhealing and gut barrier integrity. Focal adhesion kinase (FAK) is a non-receptortyrosine kinase that critically modulates epithelial cell growth and mobility andhas been associated with carcinogenesis. However, studies also suggest that FAKactivation may promote mucosal healing under conditions of colitis, which shouldreduce the risk of colitis-associated cancer. These findings highlight a potentiallytransformative role for FAK in the context of IBD. Understanding the molecularmechanisms by which FAK influences gut barrier repair and mucosal integritycould offer novel therapeutic avenues for treating IBD and preventing its longtermcomplications. This review focuses on the potential role of FAK in promotingcolitis-associated mucosal healing and the underlying molecular mechanismsdriving these processes, offering critical insights into IBD pathogenesis and therapy.展开更多
As PEGylated liposomes have witnessed remarkable advancements in drug delivery,their immunogenicity has emerged as a notable challenge.In this study,we discovered that a simple pre-injection of folic acid(FA)effective...As PEGylated liposomes have witnessed remarkable advancements in drug delivery,their immunogenicity has emerged as a notable challenge.In this study,we discovered that a simple pre-injection of folic acid(FA)effectively mitigated the immunogenicity of PEGylated liposomes and enhanced their in vivo performance by tolerating splenic marginal zone B cells.FA specifically inhibited the internalization of PEGylated liposomes by splenic marginal zone B cells,thereby reducing splenic lymphocyte proliferation and specific IgM secretion.This modulation alleviated Ig M-mediated accelerated blood clearance and adverse accumulation of the PEGylated liposomes in the skin.These findings provide new insights into the immunomodulatory effects of FA and promising avenues to enhance the efficacy and safety of PEGylated liposomal nanomedicines.展开更多
基金the Italian Ministry of Health-Ricerca Corrente 2022Saveetha Institute of Medical and Technical Sciences for supporting this study
文摘Although different studies have associated coronavirus disease 2019(COVID-19)with the occurrence of liver injury,the hepatic injury route during the COVID-19 course is not yet fully understood.In order to better understand the mechanisms of the disease,the human gut microbiota has been the subject of extensive discussion in the context of COVID-19 pathophysiology.However,many questions remain,including the risks of liver injury due to COVID-19 specific populations.Further research in this field could allow the discovery of new personalized treatment strategies aimed at improving the microbiota composition,thereby reducing COVID-19 severity and its complications in different populations.In this article,we discussed basic mechanisms of severe acute respiratory syndrome coronavirus 2 infection and recent evidence on the relationship between COVID-19,the gut microbiome and liver injury as well as proposed recommendations for further research.
文摘This article seeks to emphasize a simplified approach to phylogeny research using complete mitochondrial genomes alone, while touching upon a number of technological perspectives, such as algorithmic selection, which can help improve accuracy and performance in comparative analysis. My results will show that reliable estimations can be obtained by using mitochondrial markers, even among time-extended taxonomical rankings. Six distinct mammalian groups of taxa were selected for comparison. In all cases, mtDNA models generated reliable phylogeny approximations when compared against other independent data, while rendering exceptional computational performance.
文摘Nitric oxide(NO)is a gaseous molecule produced by 3 different NO synthase(NOS)isoforms:Neural/brain NOS(nNOS/bNOS,type 1),endothelial NOS(eNOS,type 3)and inducible NOS(type 2).Type 1 and 3 NOS are constitutively expressed.NO can serve different purposes:As a vasoactive molecule,as a neurotransmitter or as an immunomodulator.It plays a key role in cerebral ischemia/reperfusion injury(CIRI).Hypoxic episodes simulate the production of oxygen free radicals,leading to mitochondrial and phospholipid damage.Upon reperfusion,increased levels of oxygen trigger oxide synthases;whose products are associated with neuronal damage by promoting lipid peroxidation,nitrosylation and excitotoxicity.Molecular pathways in CIRI can be altered by NOS.Neuroprotective effects are observed with eNOS activity.While nNOS interplay is prone to endothelial inflammation,oxidative stress and apoptosis.Therefore,nNOS appears to be detrimental.The interaction between NO and other free radicals develops peroxynitrite;which is a cytotoxic agent.It plays a main role in the likelihood of hemorrhagic events by tissue plasminogen activator(t-PA).Peroxynitrite scavengers are currently being studied as potential targets to prevent hemorrhagic transformation in CIRI.
文摘The critical role of patient-reported outcome measures(PROMs)in enhancing clinical decision-making and promoting patient-centered care has gained a profound significance in scientific research.PROMs encapsulate a patient's health status directly from their perspective,encompassing various domains such as symptom severity,functional status,and overall quality of life.By integrating PROMs into routine clinical practice and research,healthcare providers can achieve a more nuanced understanding of patient experiences and tailor treatments accordingly.The deployment of PROMs supports dynamic patient-provider interactions,fostering better patient engagement and adherence to tre-atment plans.Moreover,PROMs are pivotal in clinical settings for monitoring disease progression and treatment efficacy,particularly in chronic and mental health conditions.However,challenges in implementing PROMs include data collection and management,integration into existing health systems,and acceptance by patients and providers.Overcoming these barriers necessitates technological advancements,policy development,and continuous education to enhance the acceptability and effectiveness of PROMs.The paper concludes with recommendations for future research and policy-making aimed at optimizing the use and impact of PROMs across healthcare settings.
文摘Good afternoon,everyone.I'd like to acknowledge DIA for the invitation.I will spend next 25 minutes to briefly talk about the research in Australia and complementary medicine (CM) there.Most importantly,I'd like to introduce a case that I was involved in the last 10 years,which was about developing a new herbal medicine for vascular dementia (VaD).I would actually highlight the issues in it as well as the experience and lessons.
基金supported by the Capital’s Funds for Health Improvement and Research(No.2024-2G-2118)the National Key Research and Development Program of China(2016YFC1000101)+2 种基金the Leading Talents in the Construction Project of High-Level Public Health Technical Talents in Beijing(2022-1-003)the“Green Seedling”Youth Program by the Beijing Hospitals Authority(QML20231402)the Young Elite Scientist Sponsorship Program by the Beijing Association for Science and Technology(BYESS2022200)。
文摘Objective To investigate the association between ABO blood types and gestational diabetes mellitus(GDM)risk.Methods A prospective birth cohort study was conducted.ABO blood types were determined using the slide method.GDM diagnosis was based on a 75-g,2-h oral glucose tolerance test(OGTT)according to the criteria of the International Association of Diabetes and Pregnancy Study Groups.Logistic regression was applied to calculate the odds ratios(ORs)and 95%confidence intervals(CIs)between ABO blood types and GDM risk.Results A total of 30,740 pregnant women with a mean age of 31.81 years were enrolled in this study.The ABO blood types distribution was:type O(30.99%),type A(26.58%),type B(32.20%),and type AB(10.23%).GDM was identified in 14.44%of participants.Using blood type O as a reference,GDM risk was not significantly higher for types A(OR=1.05)or B(OR=1.04).However,women with type AB had a 19%increased risk of GDM(OR=1.19,95%CI=1.05–1.34;P<0.05),even after adjusting for various factors.This increased risk for type AB was consistent across subgroup and sensitivity analyses.Conclusion The ABO blood types may influence GDM risk,with type AB associated with a higher risk.Incorporating it—either as a single risk factor or in combination with other known factors—could help identify individuals at risk for GDM before or during early pregnancy.
文摘Sugarcane bagasse(SCB)is a promising natural fiber for bio-based composites,but its high moisture absorption and poor interfacial adhesion with polymer matrices limit mechanical performance.While chemical treatments have been extensively explored,limited research has addressed how thermal treatment alone alters the surface properties and reinforcing behavior of SCB fibers.This study aims to fill that gap by investigating the effects of heat treatment on SCB fiber structure and its performance in starch/poly(vinyl alcohol)(PVA)composites.Characterization techniques including Fourier transform infrared spectroscopy(FTIR),X-ray diffraction(XRD),X-ray photoelectron spectroscopy(XPS),and scanning electron microscopy(SEM)were employed to analyze changes in fiber morphology,surface chemistry,and crystallinity.Mechanical properties were assessed via tensile,flexural,and impact testing,and moisture absorption was also evaluated.Composites reinforced with SCB fibers treated at 200○C exhibited significantly superior mechanical properties compared to those prepared with untreated or differently treated fibers.The tensile,flexural,and impact performance of the composites were 15.13,19.37 MPa,and 7.28 J/m,respectively.Composites treated at this temperature also retained better mechanical properties after exposure to humidity.These findings demonstrate that heat treatment is a simple and sustainable method to improve the durability and mechanical performance of nature fiber-reinforced composites,expanding their potential for environmentally friendly material applications.
文摘The increasing global demand for energy,coupled with concerns about environmental sustainability,has underscored the need for a transition toward renewable energy sources.A well-structured teaching program under the framework of sustainable development in renewable energy seeks to give students the information,abilities,and critical thinking needed to solve energy-related problems sustainably.This research proposes AI-powered personalized learning,innovative real-time integration of diverse data,and adaptive teaching strategies to enhance student understanding regarding renewable energy concepts.The sheep flock-optimized innovative recurrent neural network(SFO-IRNN)will recommend relevant topics and resources based on students’performance.Renewable energy teaching data from assessmethments are combined with real-time IoT-based renewable energy data.This dataset contains renewable energy education using AI-driven teaching methods and internet-based learning.The data was preprocessed by handling missing values and min-max scaling.The data features were extracted using Fourier Transform(FT).Further application of 10-fold cross-validation will increase the reliability of the model as it can evaluate its performance metrics like accuracy,F1-score,recall,and precision on different subsets of student data,which improves its robustness and prevents overfitting.The findings showed that the proposed method is significantly better,which ensures that the students have a deeper theoretical and practical understanding of renewable energy technologies.In addition,integrating real-time IoT data from renewable energy sources gives students a chance to do live simulations and problems that would enhance analytical thinking and hands-on learning.The research shows that AI provides context-aware guidance on sustainable energy infrastructure,enhancing interactive and personalized learning.
基金Bu-Ali Sina University for providing financial support for conducting this study。
文摘Density(p),speed of sound(u),viscosity(η),and refractive index(n_(D))were measured for pure acetonitrile,trichloroethene,and tetrachloroethene,as well as their binary mixtures at temperatures T=(293.15,298.15,303.15)K and at ambient pressure(81.5 kPa).From the experimental data,excess molar volume(V_(m)~E),thermal expansion coefficients(α),deviations in isentropic compressibility(Δκ_(S)),viscosity(Δ_η),and refractive index(Δn_(D))were calculated.These values were then correlated using the Redlich-Kister polynomial equation,with fitting coefficients and standard deviations determined.Additionally,the Prigogine-Flory-Patterson(PFP)theory and the Extended Real Associated Solution(ERAS)model were employed to correlate the excess molar volume,while the Perturbed Chain Statistical Associating Fluid Theory(PC-SAFT)was used to predict the density of mixtures.
文摘BACKGROUND Aloe vera has been used as a traditional herbal therapy for wound management and dermatological conditions worldwide for thousands of years.Scientific evidence has confirmed that acemannan,the bioactive compound in aloe vera gel,exhibits significant anti-inflammatory and immunomodulatory properties that enhance tissue regeneration.This case report describes the successful application of an innovative acemannan-enriched glycolipid sphere dressing derived from aloe vera gel in diabetic foot ulcer(DFU)treatment,which achieved a clinically remarkable outcome.CASE SUMMARY An 80-year-old female patient with a 20-year history of type 2 diabetes mellitus experienced recurrent diabetic foot pain for 15 years.She had multiple hospitalizations due to acute infections and poorly controlled hyperglycemia.Long-term treatments included metformin and gliclazide.Upon presentation,she had a nonhealing wound on her left dorsal foot,diagnosed as a severe DFU(Texas classification:Grade II,stage D).She declined amputation and opted for conservative treatment.The medical team applied an acemannan-enriched glycolipid sphere dressing five times daily to the left calf and foot,avoiding the wound area.Frequency was reduced to three times daily after scab formation.Weight-bearing on the injured foot was avoided.Through in-person and online consultations,the team managed her lifestyle and diet,emphasizing natural foods.After 5 months,the DFU healed without significant scarring or functional loss.No recurrence was observed during the 2-year follow-up.Acemannan-enriched glycolipid sphere dressings promote DFU healing.This suggests the potential of these dressings for treating other refractory wounds.
基金National Natural Science Foundation of China(22307109),Natural Science Foundation of Henan Province(222300420510)Key Research Project Plan for Higher Education Institutions in Henan Province(23A350013)the Tackle Key Problems in Science and Technology Project of Henan Province,China(242102311226,242102310417).
文摘Background Resistance to traditional intense chemotherapy and high invasiveness are characteristics of head and neck squamous cell cancer(HNSCC).Numerous human disorders are linked to N6-methyladenosine(m6A)modification of RNA,and the genetic changes in m6A regulatory genes in HNSCC are not well-understood.There is also a pressing need to find efficient targets and inhibitors for the treatment of HNSCC.This investigation examined the RNA m6A alteration in HNSCC and found putative IGFBP3 inhibitors for potential use.Methods We examined m6A regulator gene expression data from the public Gene Expression Omnibus(GEO)database in both normal tissues and patient HNSCC.For bioinformatics analysis,the R package and additional tools,including the m6A2Target database,Gene Ontology(GO)functional and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses,Gene Expression Profiling Interactive Analysis(GEPIA),and Human Protein Atlas,were used to examine the molecular mechanisms and prognostic impact for regulators that are distinctly expressed.Furthermore,TCMBank molecules were employed for virtual screening to find possible inhibitors.Results Out of the 151 differentially expressed genes(DEGs)found in the chosen datasets,insulin-like growth factor 2 mRNA-binding protein 3(IGF2BP3)was the m6A regulator that was elevated in HNSCC.The GO and KEGG analyses revealed that the target genes of IGF2BP3 were mostly enriched in several pathways and activities linked to cancer.In patients with HNSCC,IGF2BP3 showed an effective predictive effect by GEPIA analysis.Virtual screening yielded four traditional Chinese medicine ingredients as putative IGF2BP3 inhibitors for additional research.Discussion This work learned the role and prognostic effect of IGF2BP3 in HNSCC;meanwhile,the potential inhibitors of IGF2BP3 were identified for further study.
基金Supported by the Ministry of Science and Technology of China,No.2021YFA1101502。
文摘BACKGROUND Extracellular vesicles derived from mesenchymal stromal cells(MSC-EVs)can be used for anti-aging therapy and treating various aging-related diseases.However,the clinical application of MSC-EVs is still limited,mainly due to insufficient in-formation on the preparation process,quality,and mechanism of action of MSC-EVs.To study the biological effects of MSC-EVs in regulating cellular senescence.METHODS In this study,we developed a clinical-grade production process for MSC-EVs and defined the release criteria for products suitable for human use.To support the clinical use of our product as a therapeutic agent,we performed efficacy assays to evaluate the anti-aging capacity of MSC-EVs in vitro and in vivo.RESULTS The functional analysis results revealed that MSC-EVs significantly reduced the levels of senescence-associatedβ-galactosidase,matrix metallopeptidase 1,P21,and interleukin-1βand increased the level of collagen I in a naturally aged cell model of human dermal fibroblasts.Similarly,treatment with MSC-EVs effectively improved D-gal-induced subacute aging in mice,aging-related histopathological changes,oxidative stress,and aging-related gene expression.CONCLUSION These findings indicate that MSC-EVs can partially alleviate D-gal-induced senescence by reducing oxidative stress and regulating metabolism.Overall,these findings strongly suggest that MSC-EVs hold promise for aging therapy.
文摘China’s annual Central Economic Work Conference(CEWC),held on December 11 and 12,2024,signaled the government’s determination to sustain economic growth and expand high-level opening up.Against the backdrop of rising global economic uncertainty,stabilizing the economy and promoting highquality development not only represent a practical need for the country to achieve key goals on its socioeconomic agenda and make steady progress on the Chinese path to modernization,but will also help enhance economic resilience against external headwinds and contribute more to the global economy.
文摘Mesenchymal stem cells are highly regarded for their potential in tissue repair and regenerative medicine due to their multipotency and self-renewal abilities.Recently,mesenchymal stem cells have been redefined as“medical signaling cells,”with their primary biological effects mediated through exosome secretion.These exosomes,which contain lipids,proteins,RNA,and metabolites,are crucial in regulating various biological processes and enhancing regenerative therapies.Exosomes replicate the effects of their parent cells while offering benefits such as reduced side effects,low immunogenicity,excellent biocompatibility,and high drug-loading capacity.Dental stem cells,including those from apical papilla,gingiva,dental pulp,and other sources,are key contributors to exosome-mediated regenerative effects,such as tumor cell apoptosis,neuroprotection,angiogenesis,osteogenesis,and immune modulation.Despite their promise,clinical application of exosomes is limited by challenges in isolation techniques.Current methods face issues of complexity,inefficiency,and insufficient purity,hindering detailed analysis.Recent advancements,such as micro-electromechanical systems,alternating current electroosmosis,and serum-free three-dimensional cell cultures,have improved exosome isolation efficacy.This review synthesizes nearly 200 studies on dental stem cell-derived exosomes,highlighting their potential in treating a wide range of conditions,including periodontal diseases,cancer,neurodegenerative disorders,diabetes,and more.Optimized isolation methods offer a path forward for overcoming current limitations and advancing the clinical use of exosome-based therapies.
文摘BACKGROUND Bile cast nephropathy(BCN)is suspected in the setting of liver disease and hyperbilirubinemia and is characterized by the formation of tubular bile casts and acute tubular injury.While postmortem studies reveal a high prevalence of BCN,little is known about this orphan acute kidney injury syndrome.AIM To address this knowledge gap,we performed a systematic review of case reports and case series of BCN,focusing on risk factors,diagnostic criteria,clinical presentation,kidney biopsy findings,severity,treatment approaches,and outcomes.METHODS Electronic databases were searched to identify eligible studies of patients with possible,probable,or definite BCN,using pre-established criteria.Relevant variables were extracted and analyzed.We explored the impact of serum total bilirubin levels and alcoholic liver disease on BCN severity and outcomes by stratifying cases into total bilirubin tertiles and alcoholic vs non-alcoholic liver disease.Univariate and multivariable logistic regression analyses were used to examine factors associated with the composite outcome of dialysis requirement or death.RESULTS Sixty-seven case reports and six case series(involving 2 patients each)met the inclusion criteria,totaling 79 cases of BCN.The mean age was 48.3 years,and 83.5%were men.The most common cause of liver disease was drug-induced injury(30.4%),followed by infection(18.9%)and alcoholism(12.7%).BCN diagnosis was deemed definite,probable,and possible in 65.8%,32.9%,and 1.3%of cases,respectively.Levels of serum creatinine,dialysis requirement,and renal recovery did not differ among the total bilirubin tertile groups.However,both initial and peak serum creatinine were significantly higher in the alcoholic liver disease group compared to the non-alcoholic group(P=0.011 and P=0.012,respectively).There was also a non-significant trend toward a higher incidence of dialysis requirement or death in the alcoholic liver disease group(80%vs 52%,P=0.098).Finally,higher initial serum creatinine(per 1 mg/dL increase)was independently associated with dialysis requirement or death(adjusted odds ratio 1.291,95%confidence interval:1.032-1.615,P=0.025).CONCLUSION BCN is a common and potentially serious cause of acute kidney injury in patients with liver disease.The degree of hyperbilirubinemia does not appear to correlate with BCN severity or outcomes.However,in alcoholic liver disease,BCN is associated with a greater rise in serum creatinine and a trend toward worse outcomes compared to non-alcoholic liver disease.Serum creatinine may be a valuable predictor of BCN prognosis.Further studies are needed to develop non-invasive diagnostic tools and establish effective treatments for BCN.
文摘The Tourism Industry plays a critical role in economic growth on the international scene but is equally responsible for contributing to greenhouse gas emissions and energy demand.The research analyzed the global trends of energy consumption(EC)within this industry concerning environmental performance,limits,and prospects of sustained expan-sion.It includes 300 tourism-related businesses across different global economic regions.Key tourism factors include EC,greenhouse gas emissions,renewable energy(RE)use,tourism’s Gross Domestic Product(GDP)contribution,and energy efficiency.Statistical methods such as regression and panel data analysis assess the impact of tourism GDP,carbon emissions and RE.The regression analysis,including linear regression and panel data regression,to assess the influence of factors such as tourism GDP,carbon emissions,RE share,and energy efficiency improvements,providing a data-driven approach to understanding EC in tourism.The findings reveal regional differences,with developed regions consuming more energy per capita,while developing markets show progress in energy-efficient practices.The findings of the linear regression analysis show tourism GDP contribution(β=4,200).The outcomes of the panel data regression analysis show the t-statistic values of carbon emissions(t=5.64).The Difference-in-Differences analysis indicates that tourist GDP is greater in developed regions(β=4,100)compared to developing regions(β=3,500).Carbon emissions(β=4,800)are greater,although RE(β=4,200)and energy efficiency(β=2,500)increase more in developing nations.The research emphasizes expanding use of RE in tourism infrastructure,especially in ecotourism and green hotels.
文摘BACKGROUND The adoption of telehealth services surged after the coronavirus disease 2019 pandemic,revolutionizing traditional healthcare delivery models.Amazon Clinic's recent nationwide launch marks a significant milestone in this trend.This study aims to offer a strengths,weaknesses,opportunities,and threats(SWOT)analysis of Amazon Clinic and compare its features with leading virtual healthcare platforms.AIM To evaluate Amazon Clinic's telehealth services through a SWOT analysis and compare its features with other leading virtual healthcare platforms.METHODS The initial search terms included were,amazon clinic odds ratio(OR)amwell OR Teladoc OR Walmart virtual health service OR CVS minute clinic OR CirrusMD OR brightside health,from 2000 to 2023.This search yielded 111 articles,from which duplicates were removed,and unrelated titles were filtered out.Eight articles were retained for a final review,including comparative studies,usability research,retrospective analyses,observational studies,and review articles.The data was organized and analyzed using Rayyan software and summarized in a table and PRISMA flowcharts.RESULTS The review included eight articles focusing on various aspects of telehealth.Comparative studies highlighted differences between Teladoc and traditional physician offices,noting lower diagnostic imaging orders and antibiotic prescriptions for Teladoc.User demographics for Teladoc showed younger,less engaged patients.Usability studies emphasized the importance of website design for telemedicine adoption.Tele-mental health platforms like Brightside showed superior outcomes in treating depression compared to traditional methods.Telemedicine for specialized fields like skin reconstruction demonstrated cost efficiency and reduced waiting times.The SWOT analysis identified Amazon Clinic's strengths,such as its vast consumer base and transparent pricing,and weaknesses like the lack of pediatric care.Opportunities included potential partnerships and service expansions,while threats involved competition and regulatory challenges.CONCLUSION Amazon Clinic's entry into the telehealth sector represents a significant development with various strengths and opportunities.However,it faces challenges from established healthcare providers and regulatory landscapes.The future success of Amazon Clinic will depend on strategic collaborations,addressing service gaps,and navigating competition and regulations.Telemedicine's impact will hinge on its ability to effectively leverage these opportunities and overcome inherent challenges in the ever-evolving healthcare landscape.
文摘Osteoarthritis(OA)is a chronic joint disease characterized by cartilage degradation,synovial inflammation,and subchondral bone remodelling.Despite its increasing prevalence,effective diagnostic,disease-limiting,and therapeutic strategies remain unattainable.Recent studies have recognized the involvement of microRNA-155(miR-155)in the pathogenesis of OA and most of its risk factors while also identifying the antidiabetic drug metformin as a potential modulator of disease progression.MiR-155,a key endogenous regulator of the immune system,mechano-transduction,and multiple genetic pathways,interacts with OA targets of cellular energetic and circadian homeostasis,promoting systemic and local articular inflammation,cartilage matrix degradation,and chondrocyte apoptosis.Metformin,widely used for type 2 diabetes,has demonstrated anti-inflammatory,anti-oxidative,and chondroprotective properties in OA,mainly through its activation of adenosine monophosphate-activated protein kinase and inhibition of nuclear factor kappa-B signalling.Enthrallingly,metformin targets the same cellular pathways as miR-155 with emerging evidence also suggesting miR-155 expression modulation,indicating synergistic,potentially disease-modifying effects in OA.This review highlights the central role of miR-155 in OA pathophysiology and its potential as a biomarker for disease diagnosis and progression.MiR-155 targeting-through microRNA therapeutics(mimics/antagomiRs)and/or metformin-could pave the way for innovative treatments,including novel articular delivery systems and cell-based therapies.
文摘Although the etiology of inflammatory bowel disease (IBD) remains unclear,compromised epithelial barrier integrity is believed to promote susceptibility toIBD and be associated with disease severity, suggesting that improving gut barrierintegrity may palliate or treat IBD. Such a notion gets support from the clinicalfindings that mucosal healing in IBD patients is associated with improvedprognosis, and reduced risk of relapse or colitis-associated cancer. It thereforebecomes critical to understand the intracellular signals that regulate mucosalhealing and gut barrier integrity. Focal adhesion kinase (FAK) is a non-receptortyrosine kinase that critically modulates epithelial cell growth and mobility andhas been associated with carcinogenesis. However, studies also suggest that FAKactivation may promote mucosal healing under conditions of colitis, which shouldreduce the risk of colitis-associated cancer. These findings highlight a potentiallytransformative role for FAK in the context of IBD. Understanding the molecularmechanisms by which FAK influences gut barrier repair and mucosal integritycould offer novel therapeutic avenues for treating IBD and preventing its longtermcomplications. This review focuses on the potential role of FAK in promotingcolitis-associated mucosal healing and the underlying molecular mechanismsdriving these processes, offering critical insights into IBD pathogenesis and therapy.
基金supported by the National Natural Science Foundation of China(Nos.82373817 and 82003659)Shanghai Natural Science Foundation(No.23ZR1477500)Pudong Health Bureau of Shanghai(No.YC-2023-0401)。
文摘As PEGylated liposomes have witnessed remarkable advancements in drug delivery,their immunogenicity has emerged as a notable challenge.In this study,we discovered that a simple pre-injection of folic acid(FA)effectively mitigated the immunogenicity of PEGylated liposomes and enhanced their in vivo performance by tolerating splenic marginal zone B cells.FA specifically inhibited the internalization of PEGylated liposomes by splenic marginal zone B cells,thereby reducing splenic lymphocyte proliferation and specific IgM secretion.This modulation alleviated Ig M-mediated accelerated blood clearance and adverse accumulation of the PEGylated liposomes in the skin.These findings provide new insights into the immunomodulatory effects of FA and promising avenues to enhance the efficacy and safety of PEGylated liposomal nanomedicines.
