The presence of the blood–brain barrier limits the drug concentration in the brain,while low concentrations of antibiotics make it difficult to kill infecting bacteria and tends to induce drug resistance,making the c...The presence of the blood–brain barrier limits the drug concentration in the brain,while low concentrations of antibiotics make it difficult to kill infecting bacteria and tends to induce drug resistance,making the clinical treatment of bacterial meningitis challenging.Herein,a nose-to-brain delivery strategy of small-sized nanozyme has been fabricated for combating bacterial meningitis,to overcome the low drug concentration and drug resistance.This strategy was achieved by a proteinsupported Au nanozyme(ANZ).With a particle size of less than 10 nm,it possesses both glucose oxidase-like and peroxidase-like activities and can generate large amounts of reactive oxygen species through a cascade effect without the addition of external H_(2)O_(2).Benefiting from the cascade catalytic amplification effect generated by its dual enzymelike activities,ANZ shows significant broad-spectrum antibacterial activity without inducing bacterial resistance in vitro.Notably,small-sized ANZ exhibits higher brain entry efficiency and greater accumulation after intranasal administration compared to oral or intravenous administration.In a mouse model of bacterial meningitis,the mice treated with ANZ had lower bacterial loads in the brain and higher survival and clinical behavior scores compared to the classical antibiotic ceftriaxone.Additionally,the meningitis mice exhibited undamaged cognitive and behavioral abilities,indicating the excellent biocompatibility of ANZ.The above results demonstrate that nose-to-brain delivery of ANZ exhibits high intracerebral accumulation,strong antibacterial efficacy and does not lead to bacterial resistance.It holds broad prospects for the treatment of bacterial meningitis.展开更多
Opportunistic viral infections are a well-recognized complication of anti-tumor necrosis factor (TNF) therapy for inflammatory bowel disease (IBD). Cases of severe or atypical varicella zoster virus infection, both pr...Opportunistic viral infections are a well-recognized complication of anti-tumor necrosis factor (TNF) therapy for inflammatory bowel disease (IBD). Cases of severe or atypical varicella zoster virus infection, both primary and latent reactivation, have been described in association with immunosuppression of Crohn's disease (CD) patients. However, central nervous system varicella zoster virus infections have been rarely described, and there are no previous reports of varicella zoster virus meningitis associated with anti-TNF therapy among the CD population. Here, we present the case of a 40-year-old male with severe ileocecal-CD who developed a reactivation of dermatomal herpes zoster after treatment with prednisone and adalimumab. The reactivation presented as debilitating varicella zoster virus meningitis, which was not completely resolved despite aggressive antiviral therapy with prolonged intravenous acyclovir and subsequent oral valacyclovir. This is the first reported case of opportunistic central nervous system varicella zoster infection complicating anti-TNF therapy in the CD population. This paper also reviews the literature on varicella zoster virus infections of immunosuppressed IBD patients and the importance of vaccination prior to initiation of anti-TNF therapy.展开更多
Background:Invasive meningococcal disease is a potentially life-threatening infection caused by Neisseria meningitidis.Vaccination is highly effective in preventing meningitis and reducing its associated complications...Background:Invasive meningococcal disease is a potentially life-threatening infection caused by Neisseria meningitidis.Vaccination is highly effective in preventing meningitis and reducing its associated complications.This study aims to assess the United Arab Emirates(UAE)parents meningitis knowledge and explore vaccination attitudes and practices.Methodology:An observational cross-sectional study was conducted between March and May 2024 across the UAE using convenience sampling through social media,electronic mail,and word of mouth.A 58-item questionnaire collected information regarding demographics,meningitis knowledge,attitudes and practices,and meningococcal vaccination knowledge and practices.Results:Of 443 parents included,more than a third had no knowledge about meningitis.Symptoms and severity were well-recognized overall,but clear gaps were evident regarding complications and meningococcal vaccines.Only 10.38%(46/443)identified themselves as knowledgeable/very knowledgeable regarding meningococcal vaccines.A healthcare provider recommendation was the strongest factor encouraging parents to vaccinate their child.Most vaccine hesitancy was seen regarding side effects.Views and practices regarding the two vaccines aligned closely,with more than four-fifths of participants needing more information and the major reasons for not vaccinating a child being a lack of information or lack of recommendation.Social media and governmental websites were the most common sources for learning more about meningitis,with doctors ranking third.In fact,trust in doctors varied with less than half having moderate or strong trust in their main paediatrician.Multivariate logistic regression revealed that coronavirus disease 2019 vaccination status[adjusted odds ratio(AOR):0.365,95%confidence interval(CI):0.172 to 0.774,P=0.013]and female gender(AOR:2.741,95%CI:1.184 to 6.347,P=0.019)were significant predictors of vaccine hesitancy.Conclusion:Meningococcal vaccine hesitancy is a significant concern,primarily driven by fears of side effects and lack of knowledge and physician recommendation.However,vaccine attitudes were overall positive and highly dependent on physician involvement.There is a need for targeted educational initiatives enhancing meningitis disease awareness and vaccine uptake.展开更多
BACKGROUND Aseptic meningitis is defined as meningeal inflammation caused by various etio-logies with negative cerebrospinal fluid(CSF)bacterial culture.The most common etiologies are viruses[enteroviruses,arboviruses...BACKGROUND Aseptic meningitis is defined as meningeal inflammation caused by various etio-logies with negative cerebrospinal fluid(CSF)bacterial culture.The most common etiologies are viruses[enteroviruses,arboviruses,and herpes simplex virus type 2(HSV-2)].Aseptic meningitis can have various presentations,including sensori-neural deafness.While sensorineural deafness from mumps meningoencephalitis has been reported,cases of HSV-2-induced hearing loss are rare.Herein,we re-port a case of HSV-2-induced meningitis that presented with sudden deafness.CASE SUMMARY A 68-year-old man experienced a profound sudden onset of left-sided hearing loss for one day.Pure-tone audiograms demonstrated sudden left-sided sensorineural hearing loss(thresholds 80-90 dB).After treatment with high-dose steroids for 1 week,he experienced an acute consciousness change with left hemiparesis.The laboratory data showed no significant abnormalities.Brain computed tomography without contrast and magnetic resonance imaging revealed no intracranial hemo-rrhage or obvious brain lesion.The CSF analysis and the Multiplex PCR panels showed HSV-2 positivity.Hence,under the diagnosis of herpes meningoenceph-alitis,acyclovir was prescribed and his symptoms gradually resolved.CONCLUSION This case report further demonstrates that a viral infection could be a cause of sudden sensorineural hearing loss.展开更多
Cancer continues to pose a formidable challenge in global health,with conventional treatments such as chemotherapy and radiotherapy often resulting in severe toxicities that significantly degrade patients’quality of ...Cancer continues to pose a formidable challenge in global health,with conventional treatments such as chemotherapy and radiotherapy often resulting in severe toxicities that significantly degrade patients’quality of life and restrict therapeutic outcomes.Addressing this pressing issue,this review presents a thorough and systematic analysis of innovative and emerging strategies designed to minimize the toxicity induced by treatment,while maintaining or even enhancing antitumor efficacy.The focus is on six promising therapeutic approaches:combination therapies utilizing natural bioactive products,molecularly targeted therapies,immunotherapies,nanotechnology-mediated drug delivery systems,adjunct traditional Chinese medicine interventions,and low-dose spatiotemporally concerted regimens.Each approach employs unique mechanisms—such as enhanced targeting precision,immune system activation,tumor microenvironment reprogramming,and multi-component synergistic effects—to mitigate damage to normal tissues and reduce systemic adverse reactions.Despite promising preclinical and clinical advancements,several challenges persist,including drug resistance,high economic costs,a lack of reliable predictive biomarkers,and complexities in clinical translation and regulatory approval.Looking ahead,the incorporation of artificial intelligence,multi-omics profiling,and novel biomimetic nanotechnologies offers unprecedented opportunities for developing highly personalized,low-toxicity treatment frameworks.This review highlights a fundamental shift in oncology towards precision medicine that balances efficacy with safety,demonstrating the transformative potential of these strategies in shaping the future of cancer therapy and enhancing patient care globally.展开更多
Objective:To evaluate laboratory findings that predict bacterial meningitis in emergency service and their diagnostic effectiveness.Methods:This retrospective cohort study analyzed data from patients presenting with m...Objective:To evaluate laboratory findings that predict bacterial meningitis in emergency service and their diagnostic effectiveness.Methods:This retrospective cohort study analyzed data from patients presenting with meningitis symptoms at a referral hospital in Mersin,Turkey,between January 2019 and January 2022.Clinical findings and laboratory results,including leukocyte count,C-reactive protein(CRP),and procalcitonin levels in blood,were examined.Logistic regression,Chi square test,and receiver operating characteristics(ROC)curve analyses assessed the predictive value of these parameters.Results:A total of 199 participants were included in the study;99 patients were diagnosed with meningitis after lumbar puncture and 100 served as controls.Patients with meningitis exhibited significantly higher leukocyte counts(median:11890×10^(3)/μL vs.7905×10^(3)/μL,P<0.001)and CRP levels(median:6.00 mg/dL vs.0.95 mg/dL,P<0.001)compared to controls.Procalcitonin levels were significantly elevated in meningitis patients(median:0.21 ng/mL vs.0.10 ng/mL,P<0.001).Logistic regression identified albumin(OR=0.16,95%CI=0.06-0.40),and CRP(OR=1.18,95%CI=1.08-1.28)as independent predictors of meningitis.ROC analysis for CRP demonstrated a sensitivity of 80.6%and specificity of 70.0%at a cut-off value of 2.23 mg/dL(AUC=0.792).Conclusions:Elevated albumin levels and CRP contents in the blood were significant predictors of meningitis in emergency service.Early identification of predictive markers may aid in timely lumbar puncture and management of atypical cases.展开更多
Objective Pseudomonas aeruginosa(P.aeruginosa)is a prevalent pathogenic bacterium involved in meningitis;however,the virulence factors contributing to this disease remain poorly understood.Methods The virulence of the...Objective Pseudomonas aeruginosa(P.aeruginosa)is a prevalent pathogenic bacterium involved in meningitis;however,the virulence factors contributing to this disease remain poorly understood.Methods The virulence of the P.aeruginosa A584,isolated from meningitis samples,was evaluated by constructing in vitro blood-brain barrier and in vivo systemic infection models.qPCR,whole-genome sequencing,and drug efflux assays of A584 were performed to analyze the virulence factors.Results Genomic sequencing showed that A584 formed a phylogenetic cluster with the reference strains NY7610,DDRC3,Pa58,and Pa124.Its genome includes abundant virulence factors,such as hemolysin,the Type IV secretion system,and pyoverdine.A584 is a multidrug-resistant strain,and its wide-spectrum resistance is associated with enhanced drug efflux.Moreover,this strain caused significantly more severe damage to the blood-brain barrier than the standard strain,PAO1.qPCR assays further revealed the downregulation of the blood-brain barrier-associated proteins Claudin-5 and Occludin by A584.During systemic infection,A584 exhibited a higher capacity of brain colonization than PAO1(37.1×10^(6) CFU/g brain versus 2.5×10^(6) CFU/g brain),leading to higher levels of the proinflammatory factors IL-1βand TNF-α.Conclusion This study sheds light on the virulence factors of P.aeruginosa involved in meningitis.展开更多
Streptococcus suis serotype 2(SS2)is an emerging zoonotic pathogen that causes meningitis in humans and pigs.This pathogen generates substantial economic losses in the swine industry while posing a significant threat ...Streptococcus suis serotype 2(SS2)is an emerging zoonotic pathogen that causes meningitis in humans and pigs.This pathogen generates substantial economic losses in the swine industry while posing a significant threat to public health security.The mechanisms through which SS2 penetrates the brain and induces meningitis remain incompletely understood.This study examines the role and mechanism of SS2 collagenase-like protease(Clp)in facilitating bacterial passage across the blood-brain barrier(BBB).The research demonstrates that SS2 Clp enhanced virulence and tissue colonization while promoting BBB degradation in mice.The Δclp mutant exhibited reduced ability to traverse human brain microvascular endothelial(hCMEC/D3)cell monolayers compared to wild-type SS2,while the addition of recombinant protein rClp increased permeability.Furthermore,rClp significantly enhanced SS2 adhesion to hCMEC/D3,suppressed the expression of intercellular tight junction proteins ZO-1,Occludin,and Claudin-5 independent of its enzyme activity,and triggered hCMEC/D3 apoptosis through cell receptor ligand apoptosis and mitochondrial apoptosis pathways,partially dependent on its enzyme activity,leading to BBB disruption and enhanced permeability.Additionally,Clp enhanced the infiltration of macrophages(F4/80+),monocytes(F4/80-Ly6C+),and neutrophils(Ly6G+)into the brain following SS2 infection.These findings establish that SS2 Clp is essential for bacterial passage across the BBB,offering a theoretical foundation for improved prevention and treatment strategies for SS2-induced meningitis.展开更多
Tuberculous meningitis(TBM),which accounts for 1%-5%of global tuberculosis cases,is a severe neurological infection with a mortality rate of 30%-50%.Its high fatality and disability rates disproportionately affect low...Tuberculous meningitis(TBM),which accounts for 1%-5%of global tuberculosis cases,is a severe neurological infection with a mortality rate of 30%-50%.Its high fatality and disability rates disproportionately affect low-and middle-income regions(e.g.,sub-Saharan Africa and Southeast Asia),threatening the lives of patients and imposing significant psychosocial burdens.Recent studies have highlighted the crucial role of psychosocial factors,including socioeconomic status,disease severity,and social support systems in recovery.However,research gaps persist in developing TBM-specific psychosocial interventions.This narrative review summarizes and organizes the key findings of observational studies,cohort studies,and intervention trials published between 2015 and 2024.Databases including PubMed,Scopus,and Web of Science were searched for terms related to TBM,psychosocial risk factors and mental health interventions.Studies were screened for relevance and quality,focusing on those that examined the psychological and social determinants of mental health outcomes in patients with TBM.展开更多
A 35-year-old man(body weight=63 kg)with AIDS complaining fever and headache after having commenced anti-retroviral therapy(ART)for a week was admitted to our hospital.Five lumbar punctures performed during38 days cou...A 35-year-old man(body weight=63 kg)with AIDS complaining fever and headache after having commenced anti-retroviral therapy(ART)for a week was admitted to our hospital.Five lumbar punctures performed during38 days could not confirm a cryptococcal meningitis(CM)based on staining or culture methods for cerebrospinal fluid(CSF).The disease quickly progressed with serious hearing/vision impairment and frequent onset of seizure and coma after being treated with corticosteroids for five days,and then CM was confirmed.Subsequent lumbar puncture showed elevated intracranial pressure as high as 870 mm H2O,even though treated with standard antifungal regimens for CM.His disease was finally controlled by a new triple therapy with amphotericin B(0.7mg?kg-1?day-1,intravenously),flucytosine(100 mg/kg perday,orally in four divided doses),and voriconazole(200mg every 12 hours)and ART containing lamivudine(300 mg/day),stavuding(30 mg,twice a day)and efavirenz(300 mg,orally every night).Although it is rare,negative CSF stain or culture for cryptococci in AIDS patients with CM can persist for a long time.Corticosteroids should be used cautiously when an effective anti-fungal therapy is not administered.Triple therapy with amphotericin B,flucytosine and voriconazole may be selectively applied in severe CM.Voriconazole can be co-administered with efavirenz with modified dosing.展开更多
An upconversion nanoparticle(NaErF_(4)∶Yb/Tm@NaLuF_(4)∶Yb@NaLuF_(4)∶Nd/Yb@NaLuF_(4),noted as UC)was designed,emitting strong red light by 808 nm laser.The mesoporous silica(mSiO_(2))shell co‑doped with chlorin e6(C...An upconversion nanoparticle(NaErF_(4)∶Yb/Tm@NaLuF_(4)∶Yb@NaLuF_(4)∶Nd/Yb@NaLuF_(4),noted as UC)was designed,emitting strong red light by 808 nm laser.The mesoporous silica(mSiO_(2))shell co‑doped with chlorin e6(Ce6)and triethoxy(1H,1H,2H,2H‑nonafluorohexyl)silane(TFS)was coated on the outer layer of UC,and then a layer of HKUST‑1 shell was coated.The obtained nanocomposite UC@Ce6/TFS@mSiO_(2)@HKUST‑1(noted as UCTSH)was used for the synergistic treatment of chemodynamic therapy(CDT)and photodynamic therapy(PDT).Interestingly,the nanostructures can specifically re lease Cu^(2+)in the acidic tumor microenvironment.Cu^(2+)reacts with excess hydrogen peroxide(H_(2)O_(2))in the tumor microenvironment to form cytotoxic hydroxyl radical.Secondly,Ce6,with the action of oxygen‑carrying TFS,selectively produces a large amount of singlet oxygen by 808 nm laser irradiation.UCTSH can enhance the anti‑tumor effects of PDT and CDT by increasing the production level of reactive oxygen species,without causing damage to normal cells.展开更多
BACKGROUND Chemotherapy-induced cardiotoxicity is a significant complication in cancer therapy,limiting treatment efficacy and worsening patient outcomes.Recent studies have implicated the gut microbiome and its key m...BACKGROUND Chemotherapy-induced cardiotoxicity is a significant complication in cancer therapy,limiting treatment efficacy and worsening patient outcomes.Recent studies have implicated the gut microbiome and its key metabolites,such as shortchain fatty acids(SCFAs)and trimethylamine-N-oxide(TMAO),in mediating inflammation,oxidative stress,and cardiac damage.The gut-heart axis is increasingly recognized as a pivotal pathway linking microbiota dysregulation to chemotherapy-related cardiac dysfunction.AIM To systematically review existing evidence on the role of gut microbiome alterations in chemotherapy-induced cardiotoxicity and evaluate emerging microbiome-based therapeutic strategies aimed at mitigating cardiovascular risk in cancer patients.METHODS A systematic literature search was conducted in PubMed,Scopus,and Web of Science for studies published between January 2013 and December 2024.Studies were included if they examined chemotherapy-induced cardiotoxicity in relation to gut microbiota composition,microbial metabolites(e.g.,SCFAs,TMAO),or microbiome-targeted interventions.Selection followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Data extraction focused on microbiota alterations,mechanistic pathways,cardiac outcomes,and quality assessments using standardized risk-of-bias tools.RESULTS Eighteen studies met the inclusion criteria.Chemotherapy was consistently associated with gut dysbiosis characterized by reduced SCFA-producing bacteria and increased TMAO-producing strains.This imbalance contributed to gut barrier disruption,systemic inflammation,and oxidative stress,all of which promote myocardial damage.SCFA depletion weakened anti-inflammatory responses,while elevated TMAO levels exacerbated cardiac fibrosis and dysfunction.Preclinical studies showed promising cardioprotective effects from probiotics,prebiotics,dietary interventions,and fecal microbiota transplantation,though human data remain limited.CONCLUSION Gut microbiome dysregulation plays a crucial role in the development of chemotherapy-induced cardiotoxicity.Altered microbial composition and metabolite production trigger systemic inflammation and cardiac injury.Microbiome-targeted therapies represent a promising preventive and therapeutic approach in cardio-oncology,warranting further clinical validation through well-designed trials.展开更多
Lymphatic vessel networks have been identified in the meninges of mice,non-human primates,and humans[1].Meningeal lymphatic vessels(mLVs),composed of meningeal lymphatic endothelial cells(mLECs),are present in both ze...Lymphatic vessel networks have been identified in the meninges of mice,non-human primates,and humans[1].Meningeal lymphatic vessels(mLVs),composed of meningeal lymphatic endothelial cells(mLECs),are present in both zebrafish and mammals,although their anatomical distributions differ;they reside in the dura mater in mice,but are situated within the meninges in zebrafish[2].Moreover,the lymphatic marker genes expressed in these vessels differ between species[2].展开更多
Bone fractures represent a significant global healthcare burden.Although fractures typically heal on their own,some fail to regenerate properly,leading to nonunion,a condition that causes prolonged disability,morbidit...Bone fractures represent a significant global healthcare burden.Although fractures typically heal on their own,some fail to regenerate properly,leading to nonunion,a condition that causes prolonged disability,morbidity,and mortality.The challenge of treating nonunion fractures is further complicated in patients with underlying bone disorders where systemic and local factors impair bone healing.Traditional treatment approaches,including autografts,allografts,xenografts,and synthetic biomaterials,face limitations such as donor site pain,immune rejection,and insufficient mechanical strength,underscoring the need for alternative strategies.Biologic therapies have emerged as promising tools to enhance bone regeneration by leveraging the body’s natural healing processes.This review explores the critical role of conventional and emerging biologics in fracture healing.We categorize biologic therapies into protein-based treatments,gene and transcript therapies,small molecules,peptides,and cell-based therapies,highlighting their mechanisms of action,advantages,and clinical relevance.Finally,we examine the potential applications of biologics in treating fractures associated with bone disorders such as osteoporosis,osteogenesis imperfecta,rickets,osteomalacia,Paget’s disease,and bone tumors.By integrating biologic therapies with existing biomaterial-based strategies,these innovative approaches have the potential to transform clinical management and improve outcomes for patients with difficult-to-heal fractures.展开更多
Novel antibacterial strategies such as antibacterial photodynamic therapy(aPDT)and photothermal therapy(PTT)have gained significant attention,however,relying on a single-treatment approach still faces challenges of in...Novel antibacterial strategies such as antibacterial photodynamic therapy(aPDT)and photothermal therapy(PTT)have gained significant attention,however,relying on a single-treatment approach still faces challenges of insufficient therapeutic efficiency and the potential for drug resistance.In this study,a multimodal synergistic antibacterial nanoplatform by coupling a carbon monoxide(CO)donor(4-(3-hydroxy-4-oxo-4H-chromen-2-yl)benzoic acid(4-BA))with carbon dots(CDs)is developed,referred to as CDs-CO,which integrates multiple antibacterial modes of aPDT,PTT,and gas therapy.This nanoplatform is designed for highly efficient antibacterial action with a low risk of inducing drug resistance.CDs are engineered to possess tailored functions,including deep-red light-triggered heat and singlet oxygen(^(1)O_(2))production.After modification with 4-BA and exposure to 660 nm laser irradiation,CDs-CO exhibits favorable photothermal conversion efficiency(η=52.7%),robust ^(1)O_(2) generation,and ^(1)O_(2)-activated CO release.Antibacterial experiments demonstrated the excellent sterilization effects of CDs-CO against both Escherichia coli(E.coli)and Staphylococcus aureus(S.aureus),underscoring the enhanced antibacterial efficiency of this multimodal nanoplatform.This study offers a rational approach for designing multimodal synergistic antibacterial platforms,highlighting their potential for effectively treating bacterial infections.展开更多
Cardiovascular disease remains the leading global cause of mortality,projected to increase by 73.4%from 2025 to 2050 despite declining age-standardized rates.Contemporary interventions,such as percutaneous coronary in...Cardiovascular disease remains the leading global cause of mortality,projected to increase by 73.4%from 2025 to 2050 despite declining age-standardized rates.Contemporary interventions,such as percutaneous coronary intervention and statins,reduce major adverse cardiovascular events(MACE)by 25%-30%,yet a 20%five-year MACE risk persists in high-risk cohorts.These approaches,histor-ically focused on luminal stenosis,fail to address systemic atherogenesis drivers like endothelial dysfunction and inflammation.Specifically,dietary linoleic acid restriction(<5 g/day)reduces oxidized low-density lipoprotein by approximately 15%by limiting peroxidation-prone bisallylic bonds,mitigating arterial inflam-mation,a key atherogenic trigger.Enhanced external counterpulsation,through pulsatile shear stress,enhances nitric oxide-mediated coronary perfusion,alle-viating angina in approximately 70%of refractory cases unresponsive to revascu-larization.Nanoparticle-facilitated chelation targets atherosclerotic plaques with precision,reducing calcium content by up to 30%in preclinical models,offering a novel avenue for lesion reversal.These innovations collectively address residual risk by tackling root causes,oxidative stress,endothelial dysfunction,and plaque instability,potentially halving MACE rates with widespread adoption.Despite promising preliminary data,gaps remain in long-term safety and scalability.Robust clinical trials are needed to validate these approaches,which collectively aim to transform cardiovascular disease management by prioritizing prevention and vascular restoration,potentially reducing coronary events to a public health rarity.展开更多
Metal-organic frameworks(MOFs)with high porosity,specific surface area,and unique topologies are highly regarded for their applications in photocatalysis,medical treatment,and environmental pollutant degradation.Howev...Metal-organic frameworks(MOFs)with high porosity,specific surface area,and unique topologies are highly regarded for their applications in photocatalysis,medical treatment,and environmental pollutant degradation.However,due to the limitations of the tumor microenvironment(TME),traditional MOFs have limited efficacy in this environment.This paper designs multi-metal oxide-based heterostructure POMOFs nanoreactors with a nesting doll-like structure.This new structure not only exhibits therapeutic effects in TME but also utilizes ultrasound(US)to enhance the release of reactive oxygen species(ROS)for CDT&SDT co-therapy,becoming an effective sound sensitizer for destroying tumor cells.In summary,our study proposes an idea for constructing multi-metal oxide-based heterostructure MOFs nanoreactors material with a nesting doll-like structure to enhance ROS release and synergistically treat tumor diseases.展开更多
Despite remarkable advances in nanomedicine,localized delivery of advanced cancer therapeutics remains underexploited.Advanced therapies based on biopharmaceuticals,immunotherapy,or gene therapy have revolutionized on...Despite remarkable advances in nanomedicine,localized delivery of advanced cancer therapeutics remains underexploited.Advanced therapies based on biopharmaceuticals,immunotherapy,or gene therapy have revolutionized oncology.Yet,their systemic administration is often associated with limitations such as poor sitespecific accumulation,instability,and systemic toxicity.Hydrogels/macrogels offer the ability to encapsulate,protect,and release biomolecules in situ with sustained and stimulus-responsive profiles,addressing key translational gaps.This review provides a focused synthesis of the last five years of hydrogel-based research for cancer therapy,with emphasis on peptides,antibodies,immunotherapeutic agents,and gene delivery systems.We discuss design principles,release mechanisms,and clinical translation challenges,highlighting structure-function relationships and comparative performance across therapeutic classes.By integrating mechanistic insights with recent breakthroughs,we outline how next-generation hydrogels can synergize with personalized medicine and combination therapies to redefine localized cancer treatment.This work explores the fundamental aspects and provides examples of hydrogel-based delivery for the advanced treatment of cancer.The review summarizes the dynamic landscape of hydrogel research of the last 5 years,showcasing their potential systems for the precise delivery of biomolecules.Specifically,we explore the multidimensional role of hydrogels in the sustained and localized release of antibodies,immunotherapeutic agents,and genes as next-generation platforms for localized cancer treatment.This review aims to critically evaluate the mechanisms and applications of these systems in order to assess their potential to transform medical interventions and advance patient care.展开更多
In recent years,multidisciplinary treatment strategies have profoundly improved drug responses and survival outcomes of breast cancer(BC)patients.However,there is an urgent need for novel therapies for BC patients who...In recent years,multidisciplinary treatment strategies have profoundly improved drug responses and survival outcomes of breast cancer(BC)patients.However,there is an urgent need for novel therapies for BC patients who are heavily treated or develop resistance to conventional treatment regimens.Radionuclide therapy(RT)and targeted radionuclide therapy(TRT)have emerged as paradigm-shifting therapeutic approaches for BC,which enable functions of both imaging and localised treatment.They utilise radionuclides that can selectively bind to biomarkers overexpressing on BC cells,allowing precise delivery and localised tumour irradiation.Moreover,several types of radionuclides possess‘cross-fire’effects that result in the eradication of neighbouring tumour cells lacking the biomarker expression.In the current review,we summarise the potential biomarkers for the development of RT and TRT that can be employed in the treatment of BC,including receptor markers of ER,PR and HER2,together with other markers of Trop2,PD-1,EGFR,GRPR and PSMA.展开更多
Regenerative medicine is a promising therapeutic avenue for previously incurable diseases.As the risk of chronic and degenerative diseases significantly increases with age,the elderly population represents a major coh...Regenerative medicine is a promising therapeutic avenue for previously incurable diseases.As the risk of chronic and degenerative diseases significantly increases with age,the elderly population represents a major cohort for stem cell-based therapies.However,the regenerative potential of stem cells significantly decreases with advanced age and deteriorating health status of the donor.Therefore,the efficacy of autologous stem cell therapy is significantly compromised in older patients.To overcome these limitations,alternative strategies have been used to restore the age-and disease-depleted function of stem cells.These methods aim to restore the therapeutic efficacy of aged stem cells for autologous use.This article explores the effect of donor age and health status on the regenerative potential of stem cells.It further highlights the limitations of stem cell-based therapy for autologous treatment in the elderly.A comprehensive insight into the potential strategies to address the“age”and“disease”compromised regenerative potential of autologous stem cells is also presented.The information provided here serves as a valuable resource for physicians and patients for optimization of stem cellbased autologous therapy for aged patients.展开更多
基金financially supported by the National Natural Science Foundation of China(No.32172855)Fundamental Research Funds for the Central Universities(Nos.2632024ZD07,2632024TD02)the Open Project of Jiangsu Provincial Science and Technology Resources(Clinical Resources)Coordination Service Platform(No.TC2023B001)。
文摘The presence of the blood–brain barrier limits the drug concentration in the brain,while low concentrations of antibiotics make it difficult to kill infecting bacteria and tends to induce drug resistance,making the clinical treatment of bacterial meningitis challenging.Herein,a nose-to-brain delivery strategy of small-sized nanozyme has been fabricated for combating bacterial meningitis,to overcome the low drug concentration and drug resistance.This strategy was achieved by a proteinsupported Au nanozyme(ANZ).With a particle size of less than 10 nm,it possesses both glucose oxidase-like and peroxidase-like activities and can generate large amounts of reactive oxygen species through a cascade effect without the addition of external H_(2)O_(2).Benefiting from the cascade catalytic amplification effect generated by its dual enzymelike activities,ANZ shows significant broad-spectrum antibacterial activity without inducing bacterial resistance in vitro.Notably,small-sized ANZ exhibits higher brain entry efficiency and greater accumulation after intranasal administration compared to oral or intravenous administration.In a mouse model of bacterial meningitis,the mice treated with ANZ had lower bacterial loads in the brain and higher survival and clinical behavior scores compared to the classical antibiotic ceftriaxone.Additionally,the meningitis mice exhibited undamaged cognitive and behavioral abilities,indicating the excellent biocompatibility of ANZ.The above results demonstrate that nose-to-brain delivery of ANZ exhibits high intracerebral accumulation,strong antibacterial efficacy and does not lead to bacterial resistance.It holds broad prospects for the treatment of bacterial meningitis.
文摘Opportunistic viral infections are a well-recognized complication of anti-tumor necrosis factor (TNF) therapy for inflammatory bowel disease (IBD). Cases of severe or atypical varicella zoster virus infection, both primary and latent reactivation, have been described in association with immunosuppression of Crohn's disease (CD) patients. However, central nervous system varicella zoster virus infections have been rarely described, and there are no previous reports of varicella zoster virus meningitis associated with anti-TNF therapy among the CD population. Here, we present the case of a 40-year-old male with severe ileocecal-CD who developed a reactivation of dermatomal herpes zoster after treatment with prednisone and adalimumab. The reactivation presented as debilitating varicella zoster virus meningitis, which was not completely resolved despite aggressive antiviral therapy with prolonged intravenous acyclovir and subsequent oral valacyclovir. This is the first reported case of opportunistic central nervous system varicella zoster infection complicating anti-TNF therapy in the CD population. This paper also reviews the literature on varicella zoster virus infections of immunosuppressed IBD patients and the importance of vaccination prior to initiation of anti-TNF therapy.
文摘Background:Invasive meningococcal disease is a potentially life-threatening infection caused by Neisseria meningitidis.Vaccination is highly effective in preventing meningitis and reducing its associated complications.This study aims to assess the United Arab Emirates(UAE)parents meningitis knowledge and explore vaccination attitudes and practices.Methodology:An observational cross-sectional study was conducted between March and May 2024 across the UAE using convenience sampling through social media,electronic mail,and word of mouth.A 58-item questionnaire collected information regarding demographics,meningitis knowledge,attitudes and practices,and meningococcal vaccination knowledge and practices.Results:Of 443 parents included,more than a third had no knowledge about meningitis.Symptoms and severity were well-recognized overall,but clear gaps were evident regarding complications and meningococcal vaccines.Only 10.38%(46/443)identified themselves as knowledgeable/very knowledgeable regarding meningococcal vaccines.A healthcare provider recommendation was the strongest factor encouraging parents to vaccinate their child.Most vaccine hesitancy was seen regarding side effects.Views and practices regarding the two vaccines aligned closely,with more than four-fifths of participants needing more information and the major reasons for not vaccinating a child being a lack of information or lack of recommendation.Social media and governmental websites were the most common sources for learning more about meningitis,with doctors ranking third.In fact,trust in doctors varied with less than half having moderate or strong trust in their main paediatrician.Multivariate logistic regression revealed that coronavirus disease 2019 vaccination status[adjusted odds ratio(AOR):0.365,95%confidence interval(CI):0.172 to 0.774,P=0.013]and female gender(AOR:2.741,95%CI:1.184 to 6.347,P=0.019)were significant predictors of vaccine hesitancy.Conclusion:Meningococcal vaccine hesitancy is a significant concern,primarily driven by fears of side effects and lack of knowledge and physician recommendation.However,vaccine attitudes were overall positive and highly dependent on physician involvement.There is a need for targeted educational initiatives enhancing meningitis disease awareness and vaccine uptake.
文摘BACKGROUND Aseptic meningitis is defined as meningeal inflammation caused by various etio-logies with negative cerebrospinal fluid(CSF)bacterial culture.The most common etiologies are viruses[enteroviruses,arboviruses,and herpes simplex virus type 2(HSV-2)].Aseptic meningitis can have various presentations,including sensori-neural deafness.While sensorineural deafness from mumps meningoencephalitis has been reported,cases of HSV-2-induced hearing loss are rare.Herein,we re-port a case of HSV-2-induced meningitis that presented with sudden deafness.CASE SUMMARY A 68-year-old man experienced a profound sudden onset of left-sided hearing loss for one day.Pure-tone audiograms demonstrated sudden left-sided sensorineural hearing loss(thresholds 80-90 dB).After treatment with high-dose steroids for 1 week,he experienced an acute consciousness change with left hemiparesis.The laboratory data showed no significant abnormalities.Brain computed tomography without contrast and magnetic resonance imaging revealed no intracranial hemo-rrhage or obvious brain lesion.The CSF analysis and the Multiplex PCR panels showed HSV-2 positivity.Hence,under the diagnosis of herpes meningoenceph-alitis,acyclovir was prescribed and his symptoms gradually resolved.CONCLUSION This case report further demonstrates that a viral infection could be a cause of sudden sensorineural hearing loss.
文摘Cancer continues to pose a formidable challenge in global health,with conventional treatments such as chemotherapy and radiotherapy often resulting in severe toxicities that significantly degrade patients’quality of life and restrict therapeutic outcomes.Addressing this pressing issue,this review presents a thorough and systematic analysis of innovative and emerging strategies designed to minimize the toxicity induced by treatment,while maintaining or even enhancing antitumor efficacy.The focus is on six promising therapeutic approaches:combination therapies utilizing natural bioactive products,molecularly targeted therapies,immunotherapies,nanotechnology-mediated drug delivery systems,adjunct traditional Chinese medicine interventions,and low-dose spatiotemporally concerted regimens.Each approach employs unique mechanisms—such as enhanced targeting precision,immune system activation,tumor microenvironment reprogramming,and multi-component synergistic effects—to mitigate damage to normal tissues and reduce systemic adverse reactions.Despite promising preclinical and clinical advancements,several challenges persist,including drug resistance,high economic costs,a lack of reliable predictive biomarkers,and complexities in clinical translation and regulatory approval.Looking ahead,the incorporation of artificial intelligence,multi-omics profiling,and novel biomimetic nanotechnologies offers unprecedented opportunities for developing highly personalized,low-toxicity treatment frameworks.This review highlights a fundamental shift in oncology towards precision medicine that balances efficacy with safety,demonstrating the transformative potential of these strategies in shaping the future of cancer therapy and enhancing patient care globally.
文摘Objective:To evaluate laboratory findings that predict bacterial meningitis in emergency service and their diagnostic effectiveness.Methods:This retrospective cohort study analyzed data from patients presenting with meningitis symptoms at a referral hospital in Mersin,Turkey,between January 2019 and January 2022.Clinical findings and laboratory results,including leukocyte count,C-reactive protein(CRP),and procalcitonin levels in blood,were examined.Logistic regression,Chi square test,and receiver operating characteristics(ROC)curve analyses assessed the predictive value of these parameters.Results:A total of 199 participants were included in the study;99 patients were diagnosed with meningitis after lumbar puncture and 100 served as controls.Patients with meningitis exhibited significantly higher leukocyte counts(median:11890×10^(3)/μL vs.7905×10^(3)/μL,P<0.001)and CRP levels(median:6.00 mg/dL vs.0.95 mg/dL,P<0.001)compared to controls.Procalcitonin levels were significantly elevated in meningitis patients(median:0.21 ng/mL vs.0.10 ng/mL,P<0.001).Logistic regression identified albumin(OR=0.16,95%CI=0.06-0.40),and CRP(OR=1.18,95%CI=1.08-1.28)as independent predictors of meningitis.ROC analysis for CRP demonstrated a sensitivity of 80.6%and specificity of 70.0%at a cut-off value of 2.23 mg/dL(AUC=0.792).Conclusions:Elevated albumin levels and CRP contents in the blood were significant predictors of meningitis in emergency service.Early identification of predictive markers may aid in timely lumbar puncture and management of atypical cases.
基金supported by National Natural Science Foundation of China,China(32170102)Natural Science Foundation of Tianjin(21JCYBJC01420)the Fundamental Research Funds for the Central Universities(63233050)。
文摘Objective Pseudomonas aeruginosa(P.aeruginosa)is a prevalent pathogenic bacterium involved in meningitis;however,the virulence factors contributing to this disease remain poorly understood.Methods The virulence of the P.aeruginosa A584,isolated from meningitis samples,was evaluated by constructing in vitro blood-brain barrier and in vivo systemic infection models.qPCR,whole-genome sequencing,and drug efflux assays of A584 were performed to analyze the virulence factors.Results Genomic sequencing showed that A584 formed a phylogenetic cluster with the reference strains NY7610,DDRC3,Pa58,and Pa124.Its genome includes abundant virulence factors,such as hemolysin,the Type IV secretion system,and pyoverdine.A584 is a multidrug-resistant strain,and its wide-spectrum resistance is associated with enhanced drug efflux.Moreover,this strain caused significantly more severe damage to the blood-brain barrier than the standard strain,PAO1.qPCR assays further revealed the downregulation of the blood-brain barrier-associated proteins Claudin-5 and Occludin by A584.During systemic infection,A584 exhibited a higher capacity of brain colonization than PAO1(37.1×10^(6) CFU/g brain versus 2.5×10^(6) CFU/g brain),leading to higher levels of the proinflammatory factors IL-1βand TNF-α.Conclusion This study sheds light on the virulence factors of P.aeruginosa involved in meningitis.
基金supported by the National Key Research and Development Program of China(2021FYD1800405)the National Natural Science Foundation of China(32072823).
文摘Streptococcus suis serotype 2(SS2)is an emerging zoonotic pathogen that causes meningitis in humans and pigs.This pathogen generates substantial economic losses in the swine industry while posing a significant threat to public health security.The mechanisms through which SS2 penetrates the brain and induces meningitis remain incompletely understood.This study examines the role and mechanism of SS2 collagenase-like protease(Clp)in facilitating bacterial passage across the blood-brain barrier(BBB).The research demonstrates that SS2 Clp enhanced virulence and tissue colonization while promoting BBB degradation in mice.The Δclp mutant exhibited reduced ability to traverse human brain microvascular endothelial(hCMEC/D3)cell monolayers compared to wild-type SS2,while the addition of recombinant protein rClp increased permeability.Furthermore,rClp significantly enhanced SS2 adhesion to hCMEC/D3,suppressed the expression of intercellular tight junction proteins ZO-1,Occludin,and Claudin-5 independent of its enzyme activity,and triggered hCMEC/D3 apoptosis through cell receptor ligand apoptosis and mitochondrial apoptosis pathways,partially dependent on its enzyme activity,leading to BBB disruption and enhanced permeability.Additionally,Clp enhanced the infiltration of macrophages(F4/80+),monocytes(F4/80-Ly6C+),and neutrophils(Ly6G+)into the brain following SS2 infection.These findings establish that SS2 Clp is essential for bacterial passage across the BBB,offering a theoretical foundation for improved prevention and treatment strategies for SS2-induced meningitis.
文摘Tuberculous meningitis(TBM),which accounts for 1%-5%of global tuberculosis cases,is a severe neurological infection with a mortality rate of 30%-50%.Its high fatality and disability rates disproportionately affect low-and middle-income regions(e.g.,sub-Saharan Africa and Southeast Asia),threatening the lives of patients and imposing significant psychosocial burdens.Recent studies have highlighted the crucial role of psychosocial factors,including socioeconomic status,disease severity,and social support systems in recovery.However,research gaps persist in developing TBM-specific psychosocial interventions.This narrative review summarizes and organizes the key findings of observational studies,cohort studies,and intervention trials published between 2015 and 2024.Databases including PubMed,Scopus,and Web of Science were searched for terms related to TBM,psychosocial risk factors and mental health interventions.Studies were screened for relevance and quality,focusing on those that examined the psychological and social determinants of mental health outcomes in patients with TBM.
文摘A 35-year-old man(body weight=63 kg)with AIDS complaining fever and headache after having commenced anti-retroviral therapy(ART)for a week was admitted to our hospital.Five lumbar punctures performed during38 days could not confirm a cryptococcal meningitis(CM)based on staining or culture methods for cerebrospinal fluid(CSF).The disease quickly progressed with serious hearing/vision impairment and frequent onset of seizure and coma after being treated with corticosteroids for five days,and then CM was confirmed.Subsequent lumbar puncture showed elevated intracranial pressure as high as 870 mm H2O,even though treated with standard antifungal regimens for CM.His disease was finally controlled by a new triple therapy with amphotericin B(0.7mg?kg-1?day-1,intravenously),flucytosine(100 mg/kg perday,orally in four divided doses),and voriconazole(200mg every 12 hours)and ART containing lamivudine(300 mg/day),stavuding(30 mg,twice a day)and efavirenz(300 mg,orally every night).Although it is rare,negative CSF stain or culture for cryptococci in AIDS patients with CM can persist for a long time.Corticosteroids should be used cautiously when an effective anti-fungal therapy is not administered.Triple therapy with amphotericin B,flucytosine and voriconazole may be selectively applied in severe CM.Voriconazole can be co-administered with efavirenz with modified dosing.
文摘An upconversion nanoparticle(NaErF_(4)∶Yb/Tm@NaLuF_(4)∶Yb@NaLuF_(4)∶Nd/Yb@NaLuF_(4),noted as UC)was designed,emitting strong red light by 808 nm laser.The mesoporous silica(mSiO_(2))shell co‑doped with chlorin e6(Ce6)and triethoxy(1H,1H,2H,2H‑nonafluorohexyl)silane(TFS)was coated on the outer layer of UC,and then a layer of HKUST‑1 shell was coated.The obtained nanocomposite UC@Ce6/TFS@mSiO_(2)@HKUST‑1(noted as UCTSH)was used for the synergistic treatment of chemodynamic therapy(CDT)and photodynamic therapy(PDT).Interestingly,the nanostructures can specifically re lease Cu^(2+)in the acidic tumor microenvironment.Cu^(2+)reacts with excess hydrogen peroxide(H_(2)O_(2))in the tumor microenvironment to form cytotoxic hydroxyl radical.Secondly,Ce6,with the action of oxygen‑carrying TFS,selectively produces a large amount of singlet oxygen by 808 nm laser irradiation.UCTSH can enhance the anti‑tumor effects of PDT and CDT by increasing the production level of reactive oxygen species,without causing damage to normal cells.
文摘BACKGROUND Chemotherapy-induced cardiotoxicity is a significant complication in cancer therapy,limiting treatment efficacy and worsening patient outcomes.Recent studies have implicated the gut microbiome and its key metabolites,such as shortchain fatty acids(SCFAs)and trimethylamine-N-oxide(TMAO),in mediating inflammation,oxidative stress,and cardiac damage.The gut-heart axis is increasingly recognized as a pivotal pathway linking microbiota dysregulation to chemotherapy-related cardiac dysfunction.AIM To systematically review existing evidence on the role of gut microbiome alterations in chemotherapy-induced cardiotoxicity and evaluate emerging microbiome-based therapeutic strategies aimed at mitigating cardiovascular risk in cancer patients.METHODS A systematic literature search was conducted in PubMed,Scopus,and Web of Science for studies published between January 2013 and December 2024.Studies were included if they examined chemotherapy-induced cardiotoxicity in relation to gut microbiota composition,microbial metabolites(e.g.,SCFAs,TMAO),or microbiome-targeted interventions.Selection followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Data extraction focused on microbiota alterations,mechanistic pathways,cardiac outcomes,and quality assessments using standardized risk-of-bias tools.RESULTS Eighteen studies met the inclusion criteria.Chemotherapy was consistently associated with gut dysbiosis characterized by reduced SCFA-producing bacteria and increased TMAO-producing strains.This imbalance contributed to gut barrier disruption,systemic inflammation,and oxidative stress,all of which promote myocardial damage.SCFA depletion weakened anti-inflammatory responses,while elevated TMAO levels exacerbated cardiac fibrosis and dysfunction.Preclinical studies showed promising cardioprotective effects from probiotics,prebiotics,dietary interventions,and fecal microbiota transplantation,though human data remain limited.CONCLUSION Gut microbiome dysregulation plays a crucial role in the development of chemotherapy-induced cardiotoxicity.Altered microbial composition and metabolite production trigger systemic inflammation and cardiac injury.Microbiome-targeted therapies represent a promising preventive and therapeutic approach in cardio-oncology,warranting further clinical validation through well-designed trials.
基金supported by the National Natural Science Foundation of China(32220103006 and 82271524).
文摘Lymphatic vessel networks have been identified in the meninges of mice,non-human primates,and humans[1].Meningeal lymphatic vessels(mLVs),composed of meningeal lymphatic endothelial cells(mLECs),are present in both zebrafish and mammals,although their anatomical distributions differ;they reside in the dura mater in mice,but are situated within the meninges in zebrafish[2].Moreover,the lymphatic marker genes expressed in these vessels differ between species[2].
基金performed as part of the cmRNAbone project funded by the European Union’s Horizon 2020 research and innovation program under the Grant Agreement No 874790。
文摘Bone fractures represent a significant global healthcare burden.Although fractures typically heal on their own,some fail to regenerate properly,leading to nonunion,a condition that causes prolonged disability,morbidity,and mortality.The challenge of treating nonunion fractures is further complicated in patients with underlying bone disorders where systemic and local factors impair bone healing.Traditional treatment approaches,including autografts,allografts,xenografts,and synthetic biomaterials,face limitations such as donor site pain,immune rejection,and insufficient mechanical strength,underscoring the need for alternative strategies.Biologic therapies have emerged as promising tools to enhance bone regeneration by leveraging the body’s natural healing processes.This review explores the critical role of conventional and emerging biologics in fracture healing.We categorize biologic therapies into protein-based treatments,gene and transcript therapies,small molecules,peptides,and cell-based therapies,highlighting their mechanisms of action,advantages,and clinical relevance.Finally,we examine the potential applications of biologics in treating fractures associated with bone disorders such as osteoporosis,osteogenesis imperfecta,rickets,osteomalacia,Paget’s disease,and bone tumors.By integrating biologic therapies with existing biomaterial-based strategies,these innovative approaches have the potential to transform clinical management and improve outcomes for patients with difficult-to-heal fractures.
基金supported by the National Natural Science Foundation of China(No.52173126)China Postdoctoral Science Foundation(No.2024M751152).
文摘Novel antibacterial strategies such as antibacterial photodynamic therapy(aPDT)and photothermal therapy(PTT)have gained significant attention,however,relying on a single-treatment approach still faces challenges of insufficient therapeutic efficiency and the potential for drug resistance.In this study,a multimodal synergistic antibacterial nanoplatform by coupling a carbon monoxide(CO)donor(4-(3-hydroxy-4-oxo-4H-chromen-2-yl)benzoic acid(4-BA))with carbon dots(CDs)is developed,referred to as CDs-CO,which integrates multiple antibacterial modes of aPDT,PTT,and gas therapy.This nanoplatform is designed for highly efficient antibacterial action with a low risk of inducing drug resistance.CDs are engineered to possess tailored functions,including deep-red light-triggered heat and singlet oxygen(^(1)O_(2))production.After modification with 4-BA and exposure to 660 nm laser irradiation,CDs-CO exhibits favorable photothermal conversion efficiency(η=52.7%),robust ^(1)O_(2) generation,and ^(1)O_(2)-activated CO release.Antibacterial experiments demonstrated the excellent sterilization effects of CDs-CO against both Escherichia coli(E.coli)and Staphylococcus aureus(S.aureus),underscoring the enhanced antibacterial efficiency of this multimodal nanoplatform.This study offers a rational approach for designing multimodal synergistic antibacterial platforms,highlighting their potential for effectively treating bacterial infections.
文摘Cardiovascular disease remains the leading global cause of mortality,projected to increase by 73.4%from 2025 to 2050 despite declining age-standardized rates.Contemporary interventions,such as percutaneous coronary intervention and statins,reduce major adverse cardiovascular events(MACE)by 25%-30%,yet a 20%five-year MACE risk persists in high-risk cohorts.These approaches,histor-ically focused on luminal stenosis,fail to address systemic atherogenesis drivers like endothelial dysfunction and inflammation.Specifically,dietary linoleic acid restriction(<5 g/day)reduces oxidized low-density lipoprotein by approximately 15%by limiting peroxidation-prone bisallylic bonds,mitigating arterial inflam-mation,a key atherogenic trigger.Enhanced external counterpulsation,through pulsatile shear stress,enhances nitric oxide-mediated coronary perfusion,alle-viating angina in approximately 70%of refractory cases unresponsive to revascu-larization.Nanoparticle-facilitated chelation targets atherosclerotic plaques with precision,reducing calcium content by up to 30%in preclinical models,offering a novel avenue for lesion reversal.These innovations collectively address residual risk by tackling root causes,oxidative stress,endothelial dysfunction,and plaque instability,potentially halving MACE rates with widespread adoption.Despite promising preliminary data,gaps remain in long-term safety and scalability.Robust clinical trials are needed to validate these approaches,which collectively aim to transform cardiovascular disease management by prioritizing prevention and vascular restoration,potentially reducing coronary events to a public health rarity.
基金funded by the National Natural Science Foundation of China(Nos.52372264,32271609and 52473109)+2 种基金The Natural Science Foundation of Heilongjiang Province of China(No.LH2023B002)The Fundamental Research Funds for the Central Universities(No.2572023CT12)Undergraduate Training Programs for Innovations by NEFU(No.202310225565)。
文摘Metal-organic frameworks(MOFs)with high porosity,specific surface area,and unique topologies are highly regarded for their applications in photocatalysis,medical treatment,and environmental pollutant degradation.However,due to the limitations of the tumor microenvironment(TME),traditional MOFs have limited efficacy in this environment.This paper designs multi-metal oxide-based heterostructure POMOFs nanoreactors with a nesting doll-like structure.This new structure not only exhibits therapeutic effects in TME but also utilizes ultrasound(US)to enhance the release of reactive oxygen species(ROS)for CDT&SDT co-therapy,becoming an effective sound sensitizer for destroying tumor cells.In summary,our study proposes an idea for constructing multi-metal oxide-based heterostructure MOFs nanoreactors material with a nesting doll-like structure to enhance ROS release and synergistically treat tumor diseases.
基金supported by the Vall d’Hebron Research Institute(PI23/01345)the Networking Research Centre on Bioengineering,Biomaterials,and Nanomedicine(CIBER-BBN),which is financed by the Instituto de Salud Carlos III(ISCIII)with assistance from the European Regional Development Fund(ERDF)+4 种基金supported by ANID FONDECYT REGULAR(Chile)through project No.1250634,and FOVI230019 granted to Esteban Duran-LaraDiana Rafael was supported by Marie Skłodowska-Curie Actions(MSCA-PF ID 101107735),“La Caixa Foundation”(LCF/BQ/PR24/12050008),and ISCIII(PI24/00745)Fernanda Andrade was granted by the Fundación Científica de la Asociación Española Contra el Cáncer(FCAECC Refs.INVES211530DASI and SNRGS247164DASI)“La Caixa Foundation”(HR24-00927).Júlia German-Cortés was granted by the 791 FAECC(PRDBA258393GERM)The authors also thank the denomination of Consolidated group from Generalitat de Catalunya(2021 SGR 01173)granted to the CB-DDT group。
文摘Despite remarkable advances in nanomedicine,localized delivery of advanced cancer therapeutics remains underexploited.Advanced therapies based on biopharmaceuticals,immunotherapy,or gene therapy have revolutionized oncology.Yet,their systemic administration is often associated with limitations such as poor sitespecific accumulation,instability,and systemic toxicity.Hydrogels/macrogels offer the ability to encapsulate,protect,and release biomolecules in situ with sustained and stimulus-responsive profiles,addressing key translational gaps.This review provides a focused synthesis of the last five years of hydrogel-based research for cancer therapy,with emphasis on peptides,antibodies,immunotherapeutic agents,and gene delivery systems.We discuss design principles,release mechanisms,and clinical translation challenges,highlighting structure-function relationships and comparative performance across therapeutic classes.By integrating mechanistic insights with recent breakthroughs,we outline how next-generation hydrogels can synergize with personalized medicine and combination therapies to redefine localized cancer treatment.This work explores the fundamental aspects and provides examples of hydrogel-based delivery for the advanced treatment of cancer.The review summarizes the dynamic landscape of hydrogel research of the last 5 years,showcasing their potential systems for the precise delivery of biomolecules.Specifically,we explore the multidimensional role of hydrogels in the sustained and localized release of antibodies,immunotherapeutic agents,and genes as next-generation platforms for localized cancer treatment.This review aims to critically evaluate the mechanisms and applications of these systems in order to assess their potential to transform medical interventions and advance patient care.
基金Noncommunicable Chronic Diseases-National Science and Technology Major Project,Grant/Award Number:2023ZD0502200National Natural Science Foundation of China,Grant/Award Number:82103010+2 种基金Cultivation Project of Medical Oncology Key Foundation of Cancer HospitalChinese Academy of Medical Sciences,Grant/Award Number:CICAMS-MOCP2022004Joint Innovative Fund of Beijing Natural Science Foundation and Changping District,Grant/Award Number:L234004。
文摘In recent years,multidisciplinary treatment strategies have profoundly improved drug responses and survival outcomes of breast cancer(BC)patients.However,there is an urgent need for novel therapies for BC patients who are heavily treated or develop resistance to conventional treatment regimens.Radionuclide therapy(RT)and targeted radionuclide therapy(TRT)have emerged as paradigm-shifting therapeutic approaches for BC,which enable functions of both imaging and localised treatment.They utilise radionuclides that can selectively bind to biomarkers overexpressing on BC cells,allowing precise delivery and localised tumour irradiation.Moreover,several types of radionuclides possess‘cross-fire’effects that result in the eradication of neighbouring tumour cells lacking the biomarker expression.In the current review,we summarise the potential biomarkers for the development of RT and TRT that can be employed in the treatment of BC,including receptor markers of ER,PR and HER2,together with other markers of Trop2,PD-1,EGFR,GRPR and PSMA.
文摘Regenerative medicine is a promising therapeutic avenue for previously incurable diseases.As the risk of chronic and degenerative diseases significantly increases with age,the elderly population represents a major cohort for stem cell-based therapies.However,the regenerative potential of stem cells significantly decreases with advanced age and deteriorating health status of the donor.Therefore,the efficacy of autologous stem cell therapy is significantly compromised in older patients.To overcome these limitations,alternative strategies have been used to restore the age-and disease-depleted function of stem cells.These methods aim to restore the therapeutic efficacy of aged stem cells for autologous use.This article explores the effect of donor age and health status on the regenerative potential of stem cells.It further highlights the limitations of stem cell-based therapy for autologous treatment in the elderly.A comprehensive insight into the potential strategies to address the“age”and“disease”compromised regenerative potential of autologous stem cells is also presented.The information provided here serves as a valuable resource for physicians and patients for optimization of stem cellbased autologous therapy for aged patients.
