Colorectal cancer(CRC)causes approximately 600000deaths annually and is the third leading cause of cancer mortality worldwide.Despite significant advancements in treatment options,CRC patient survival is still poor ow...Colorectal cancer(CRC)causes approximately 600000deaths annually and is the third leading cause of cancer mortality worldwide.Despite significant advancements in treatment options,CRC patient survival is still poor owing to a lack of effective tools for early diagnosis and a limited capacity for optimal therapeutic decision making.Since there exists a need to find new biomarkers to improve diagnosis of CRC,the research on epigenetic biomarkers for molecular diagnostics encourages the translation of this field from the bench to clinical practice.Epigenetic alterations are thought to hold great promise as tumor biomarkers.In this review,we will primarily focus on recent advances in the study of epigenetic biomarkers for colorectal cancer and discuss epigenetic biomarkers,including DNA methylation,microRNA expression and histone modification,in cancer tissue,stool,plasma,serum,cell lines and xenografts.These studies have improved the chances that epigenetic biomarkers will find a place in the clinical practices of screening,early diagnosis,prognosis,therapy choice and recurrence surveillance for CRC patients.However,these studies have typically been small in size,and evaluation at a larger scale of well-controlled randomized clinical trials is the next step that is necessary to increase the quality of epigenetic biomarkers and ensure their widespread clinical use.展开更多
Therapeutic experiments are commonly performed on laboratory animals to inves-tigate the possible mechanism(s)of action of toxic agents as well as drugs or sub-stances under consideration.The use of toxins in laborato...Therapeutic experiments are commonly performed on laboratory animals to inves-tigate the possible mechanism(s)of action of toxic agents as well as drugs or sub-stances under consideration.The use of toxins in laboratory animal models,including rats,is intended to cause toxicity.This study aimed to investigate different models of hepatotoxicity and nephrotoxicity in laboratory animals to help researchers advance their research goals.The current narrative review used databases such as Medline,Web of Science,Scopus,and Embase and appropriate keywords until June 2021.Nephrotoxicity and hepatotoxicity models derived from some toxic agents such as cisplatin,acetaminophen,doxorubicin,some anticancer drugs,and other materials through various signaling pathways are investigated.To understand the models of renal or hepatotoxicity in laboratory animals,we have provided a list of toxic agents and their toxicity procedures in this review.展开更多
Owing to safety issue and low energy density of liquid lithium-ion batteries(LIBs),all-solid-state lithium metal batteries(ASLMBs)with unique all-solid-state electrolytes(SEs)have attracted wide attentions.This arises...Owing to safety issue and low energy density of liquid lithium-ion batteries(LIBs),all-solid-state lithium metal batteries(ASLMBs)with unique all-solid-state electrolytes(SEs)have attracted wide attentions.This arises mainly from the advantages of the SEs in the suppression of lithium dendrite growth,long cycle life,and broad working temperature range,showing huge potential applications in electronic devices,electric vehicles,smart grids,and biomedical devices.However,SEs suffer from low lithiumion conductivity and low mechanical integrity,slowing down the development of practical ASLMBs.Nanostructure engineering is of great efficiency in tuning the structure and composition of the SEs with improved lithium-ion conductivity and mechanical integrity.Among various available technologies for nanostructure engineering,electrospinning is a promising technique because of its simple operation,cost-effectiveness,and efficient integration with different components.In this review,we will first give a simple description of the electrospinning process.Then,the use of electrospinning technique in the synthesis of various SEs is summarized,for example,organic nanofibrous matrix,organic/inorganic nanofibrous matrix,and inorganic nanofibrous matrix combined with other components.The current development of the advanced architectures of SEs through electrospinning technology is also presented to provide references and ideas for designing high-performance ASLMBs.Finally,an outlook and further challenges in the preparation of advanced SEs for ASLMBs through electrospinning engineering are given.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is the most common subtype of primary liver cancer with varied incidence and epidemiology worldwide.Sorafenib is still a recommended treatment for a large proportion of patients...BACKGROUND Hepatocellular carcinoma(HCC)is the most common subtype of primary liver cancer with varied incidence and epidemiology worldwide.Sorafenib is still a recommended treatment for a large proportion of patients with advanced HCC.Different patterns of treatment responsiveness have been identified in differentiated hepatoblastoma HepG2 cells and metastatic HCC SNU449 cells.AIM To define the long non-codingRNA-microRNA-mRNA(lncRNA-miRNA-mRNA)predicted signatures related to selected hallmarks of cancer(apoptosis,autophagy,cell stress,cell dedifferentiation and invasiveness)in RNAseq studies using Sorafenib-treated HepG2 and SNU449 cells.Various available software analyses allowed us to establish the lncRNA-miRNA-mRNA regulatory axes following treatment in HepG2 and SNU449 cells.METHODS HepG2 and SNU449 cells were treated with Sorafenib(10μmol/L)for 24 hours.Total RNA,including small and long RNA,was extracted with a commercial miRNeasy kit.RNAseq was carried out for the identification of changes in lncRNA-miRNA-mRNA regulatory axes.RESULTS MALAT,THAP9-AS1 and SNGH17 appeared to coordinately regulate miR-374b-3p and miR-769-5p that led to upregulation of SMAD7,TIRARP,TFAP4 and FAXDC2 in HepG2 cells.SNHG12,EPB41 L4A-AS1,LINC01578,SNHG12 and GAS5 interacted with let-7b-3p,miR-195-5p and VEGFA in SNU449 cells.The axes MALAT1/hsamir-374b-3p/SMAD7 and MALAT1/hsa-mir-769-5p/TFAP4 were of high relevance for Sorafenib response in HepG2 cells,whereas PVT1/hsa-miR-195-5p/VEGFA was responsible for the differential response of SNU449 cells to Sorafenib treatment.CONCLUSION Critical lncRNAs acting as sponges of miRNA were identified that regulated mRNA expression,whose proteins mainly increased the antitumor effectiveness of the treatment(SMAD7,TIRARP,TFAP4,FAXDC2 and ADRB2).However,the broad regulatory axis leading to increased VEGFA expression may be related to the side effect of Sorafenib in SNU449 cells.展开更多
Although many causes of Alzheimer’s disease(AD)may exist,both the original amyloid cascade and tau hypotheses posit that abnormal misfolding and accumulation of amyloid-β(Aβ)and tau protein is the central event cau...Although many causes of Alzheimer’s disease(AD)may exist,both the original amyloid cascade and tau hypotheses posit that abnormal misfolding and accumulation of amyloid-β(Aβ)and tau protein is the central event causing the pathology.However,that conclusion could be only partly true,and there is conflicting evidence about the role of both proteins in AD,being able to precede and influence one another.Some researchers argue that these proteins are mere executors rather than primary causes of pathology.Therefore,there have been continuing refinements of both hypotheses,with alternative explanations proposed.Aβand tau proteins may be independently involved in specific neurotoxic pathways;yet there may be other crucial processes going on in early AD.Moreover,accumulating evidence suggests that Aβand tau act synergistically,rather than additively in disease onset(Jeremic et al.,2021,2023a).展开更多
Objective:To assess the effects of turmeric extract and its compounds on oxidative stress,inflammation,and apoptosis in acetaminophen-induced liver injury.Methods:HepG2 cells were administered with acetaminophen(40 mM...Objective:To assess the effects of turmeric extract and its compounds on oxidative stress,inflammation,and apoptosis in acetaminophen-induced liver injury.Methods:HepG2 cells were administered with acetaminophen(40 mM)to induce hepatotoxicity,followed by treatment with turmeric extract and its isolated compounds including curcumin,demethoxycurcumin,bis-demethoxycurcumin and ar-turmerone at 5,25,and 125μg/mL.IL-1β,IL-6,and IL-10 levels were quantified with ELISA kits.Further,qRT-PCR was used to analyze the mRNA expression of JNK,Casp-9,and Casp-3.Meanwhile,the levels of nitric oxide and lactate dehydrogenase were analyzed using colorimetric assay.Results:Acetaminophen administration caused an increase in the levels of lactate dehydrogenase,nitric oxide,IL-1β,IL-6,and the mRNA expression of JNK,Casp-9,and Casp-3 in HepG2 cells while reducing IL-10 levels.Treatment with turmeric extract,curcumin,demethoxycurcumin,bis-demethoxycurcumin,and ar-turmerone lowered IL-1β,IL-6,nitric oxide,and lactate dehydrogenase levels,downregulated the mRNA expression of JNK,Casp-9,and Casp-3,and increased IL-10 levels.Conclusions:Turmeric extract and its compounds have significant hepatoprotective activity and could be further explored for the treatment of liver damage.展开更多
Background:An arterial stiffness is an indicator of many cardiovascular diseases.The temporal position of systolic blood pressure(BP)on aorta pulse waveform is assumed to gradually shift on the waveform in response to...Background:An arterial stiffness is an indicator of many cardiovascular diseases.The temporal position of systolic blood pressure(BP)on aorta pulse waveform is assumed to gradually shift on the waveform in response to increasing/decreasing vascular stiffness.The animal model of rats and invasive methods that cannot be used in humans was applied to test the assumption on arterial pulse waveform(APW)of anesthetized rat.The aim of this study was to characterize the temporal movement of diastolic and systolic pressures on the APW of anesthetized rats during increasing/decreasing vascular stiffness.Methods:The right jugular vein of anesthetized normotensive and spontaneously hypertensive rats was cannulated for intravascular administration of vascularly active compounds to alter systolic pressure and vascular stiffness.The left carotid artery was cannulated to detect APW,from which numerous APW parameters were evaluated.Results:During increases/decreases in systolic BP or stiffness,the temporal position of diastolic BP of individual heartbeats di-gitally shifted on the APW between two temporal positions~8–12 ms apart,and the temporal position of systolic BP on the APW did not gradually shift during increases/decreases in vascular stiffness,as expected,but oscillated between constant di-gital,tri-gital,or tetra-gital temporal positions.Conclusions:Introducing new APW parameters,n-gital systolic BP fluctuations on rat APW were found.Fluctuations in n-gital were approximately constant during large changes in systolic pressure despite significant changes in augmentation index and cardiovascular stiffness,which may challenge the assumption of a gradual temporal location of systolic pressure on rat APW under these conditions.展开更多
BACKGROUND In patients with metastatic colorectal cancer,chemotherapy may lead to changes in body composition,including skeletal muscle quantity and quality,and body fat area and distribution.Longitudinal follow-up da...BACKGROUND In patients with metastatic colorectal cancer,chemotherapy may lead to changes in body composition,including skeletal muscle quantity and quality,and body fat area and distribution.Longitudinal follow-up data in a homogeneous population are required to understand these changes better.AIM To comprehensively evaluate changes in body composition and their prognostic value in patients with metastatic colorectal cancer undergoing palliative chemo-therapy.METHODS This retrospective study included patients with recurrent or metastatic colorectal cancer who received palliative chemotherapy between 2008 and 2017.Computed tomography scans were analyzed at multiple time points(before each new chemotherapy regimen and after discontinuing all chemotherapy).Body composition was analyzed from each scan using artificial intelligence software(AID-UTM,iAID Inc.),and its association with survival was evaluated through time-dependent Cox regression to adjust for time-varying effects.RESULTS This analysis included 1805 patients,with a median age at diagnosis of 57 years,and 62%were male.At first-line chemotherapy initiation,4.7%,30.9%,36.5%,and 37.1%of the patients had sarcopenia,myosteatosis,and visceral and subcutaneous obesity,respectively.During treatment,approximately 54.5%of the patients experienced significant changes in body composition,with 9.1%and 19.2%developing new sarcopenia and myosteatosis,respectively.Sarcopenia and myosteatosis were associated with poorer survival outcomes[hazard ratio(HR)for sarcopenia,2.55(95%CI:2.06-3.16,P<0.001;HR for myosteatosis,2.37(95%CI:2.00-2.82),P<0.001].In contrast,visceral and subcutaneous obesity were associated with improved survival[HR for visceral obesity,0.69(95%CI:0.57-0.82),P<0.001;HR for subcutaneous obesity,0.78(95%CI:0.64-0.95),P=0.015],with no negative impacts observed at higher fat levels.These changes correlated with end-of-life survival time.CONCLUSION Abnormalities and body composition changes were frequently observed during palliative chemotherapy for advanced colorectal cancer;myosteatosis was common.Comprehensive body composition assessment offers valuable prognostic insights without requiring additional testing.展开更多
Most Aloe species are used as new food or functional food ingredient.Even though widely known for its health benefits,the anti-inflammatory effects and underlying mechanisms of Aloin(Alo),an anthraquinone compound iso...Most Aloe species are used as new food or functional food ingredient.Even though widely known for its health benefits,the anti-inflammatory effects and underlying mechanisms of Aloin(Alo),an anthraquinone compound isolated from plant species of the genus Aloe,remain unidentified.Here,we investigated the protective effects of Alo against cecal ligation and puncture(CLP)-induced sepsis and microflora in mice.Alo significantly improved CLP-induced sepsis and the survival rate of septic mice,downregulated the expression of proinflammatory factors,and decreased the infiltration of inflammatory cells in tissues.Alo upregulated the proportion of peritoneal macrophages,reduced the number of peritoneal bacteria,decreased the content of short-chain fatty acids and bile acids in the abdominal cavity,and suppressed Toll-like receptor(TLR)-2/4/nuclear factor kappa-B(NF-κB)/NOD-like receptor thermal protein domain associated protein 3(NLRP3)/Caspase-1/3/8 signaling.Furthermore,Alo altered the composition of the microbiome and promoted the growth of Lactobacillus,which showed a stronger anti-inflammatory effect.Whole-genome analysis identified the genes Saa3,Il10,Fpr1,and Eif4a1 associated with the protective effects of Alo in mice with CLP-induced sepsis.Overall,our results provide novel insights into the therapeutic potential and mechanism of action of Alo in the treatment of sepsis.展开更多
The search for reliable biomarkers to predict metabolic dysfunction-associated steatotic liver disease(MASLD)remains a key research focus.Traditional anthropometric parameters,such as triglycerides,glucose,and waist c...The search for reliable biomarkers to predict metabolic dysfunction-associated steatotic liver disease(MASLD)remains a key research focus.Traditional anthropometric parameters,such as triglycerides,glucose,and waist circumference(WC),have proven to be robust tools for diagnosing,stratifying,and predicting health outcomes.These measures facilitate early detection,personalized treatment strategies,and long-term risk assessment in metabolic health.The triglycerideglucose(TyG)index and related parameters,particularly the TyG-WC index,are gaining recognition as reliable biomarkers for MASLD,with consistently high diagnostic accuracy across diverse populations.The TyG-WC index is associated with MASLD and an increased likelihood of all-cause,cardiovascular,and diabetes-related mortality,highlighting its importance in stratification and patient management.This opinion review summarizes key findings on the TyG-WC index across different MASLD populations and provides nutritional recommendations aimed at reducing this index.The TyG-WC index stands out as a practical and scalable biomarker for identifying and stratifying the risk of MASLD,particularly in resource-limited environments where access to advanced diagnostic tools is restricted.However,before the TyG-WC index can be integrated into routine clinical practice,rigorous,longitudinal studies involving ethnically diverse cohorts must validate its prognostic performance.It should be viewed as a complementary tool within a comprehensive metabolic risk assessment framework,supporting preventive strategies while awaiting formal endorsement in clinical guidelines.展开更多
Cardiolipins(CLs),the mitochondria-specific class of phospholipids,are crucial to energy metabolism,cristae structure,and cell apoptosis.CLs present significant challenges in lipidomics analysis due to their structura...Cardiolipins(CLs),the mitochondria-specific class of phospholipids,are crucial to energy metabolism,cristae structure,and cell apoptosis.CLs present significant challenges in lipidomics analysis due to their structural diversity with up to four fatty acyl side chains.In this study,we developed CLAN(Cardio Lipin ANalysis),a comprehensive computational pipeline designed to improve the accuracy and coverage of cardiolipin identification.CLAN integrates three innovative modules:A cardiolipin identification module that utilizes specific fragmentation rules for precise characterization of CLs and their acyl side chains;a false positives detection module that employs retention time(RT)criteria to reduce false positives;and a prediction module that constructs regression models to identify CLs lacking authentic MS/MS spectra.CLAN achieved better identification accuracy and the highest recall rate for potential CL identification compared to the existing lipid identification tools.Furthermore,we applied CLAN program to an intermittent fasting mouse model,delineating tissue-specific CL alterations across 10 tissues.Every-other-day fasting(EODF)can partially counteract the disruption of the CL atlas across multiple tissues caused by high-fat-high-sugar diet feeding,providing novel insights into mitochondrial lipid metabolism under dietary interventions.Taken together,this work not only advances CL identification methodology but also underscores CLAN's potential in comprehensive analysis of CL atlas in the EODF animal model.CLAN is freely accessible on Git Hub.展开更多
Background The biological mechanisms by which postdiagnosis physical activity improves disease-free survival in colorectal cancer survivors remain incompletely understood.This trial tested the hypothesis that 12 weeks...Background The biological mechanisms by which postdiagnosis physical activity improves disease-free survival in colorectal cancer survivors remain incompletely understood.This trial tested the hypothesis that 12 weeks of moderate-intensity aerobic exercise,when compared with a control group,would change inflammation,circulating tumor cells(CTCs),and circulating tumor DNA(ctDNA)in a manner consistent with an improved cancer prognosis.Methods This trial randomized Stages I–III colorectal cancer survivors to 12 weeks of home-based moderate-intensity aerobic exercise or a waitlist control group.The co-primary endpoints were high-sensitivity C-reactive protein(hs-CRP)and interleukin-6(IL-6),secondary endpoints were soluble tumor necrosis factor-αreceptor 2(sTNFαR2)and CTCs,and the exploratory endpoint was tumor fraction quantified from ctDNA.Results Sixty subjects were randomized(age=60.6±10.8 years,mean±SD;39(65%)females;46(77%)colonic primary tumor),and 59(98%)subjects completed the study.Over 12 weeks,exercise adherence was 92%(95%confidence interval(95%CI):86‒99).Exercise improved submaximal fitness capacity(0.36 metabolic equivalents;95%CI:0.05‒0.67;p=0.025)and objectively measured moderate-to-vigorous-intensity physical activity(34.8%,95%CI:11.3‒63.1;p=0.002)compared to control.Exercise did not change hs-CRP(20.9%,95%CI:−17.1 to 76.2;p=0.32),IL-6(11.4%,95%CI:−7.5 to 34.0;p=0.25),or sTNFαR2(−3.6%,95%CI:−13.7 to 7.7;p=0.52)compared to control.In the subgroup of subjects with elevated baseline hs-CRP(n=35,58.3%),aerobic exercise reduced hs-CRP(−35.5%,95%CI:−55.3 to−3.8;p=0.031).Exercise did not change CTCs(0.59 cells/mL,95%CI:−0.33 to 1.51;p=0.21)or tumor fraction(0.0005,95%CI:−0.0024 to 0.0034;p=0.73).In exploratory analyses,higher aerobic exercise adherence correlated with a reduction in CTCs(ρ=−0.37,95%CI:−0.66 to−0.08;p=0.013).Conclusion Colorectal cancer survivors achieved high adherence to a home-based moderate-intensity aerobic exercise prescription that improved fitness capacity and physical activity but did not reduce inflammation or change tumor endpoints from a liquid biopsy.展开更多
Background:Breast cancer still stands to be the foremost contributor to cancer-related incidence and mortality in women globally accounting for about 14%of all female cancer-related deaths worldwide.This research seek...Background:Breast cancer still stands to be the foremost contributor to cancer-related incidence and mortality in women globally accounting for about 14%of all female cancer-related deaths worldwide.This research seeks to illustrate the mechanisms and clinical findings of natural products against breast cancer treatment.Methodology:Required data for this review article was retrieved employing several readily obtainable search databases,including Web of Science■(Thomson Reuters,USA),PubMed■(U.S.National Library of Medicine,USA),and SciVerse Scopus■(Elsevier Properties S.A.,USA),taking into consideration certain search terms like“breast cancer,”“natural products against breast cancer,”and“Clinically proven natural products in the treatment of breast cancer”and so on.Results:Several natural products,namely Omega-3 fatty acids,dietary isothiocyanates,curcumin,green tea,flaxseed,limonene,and others,were found to modulate crucial pathways in breast cancer cells.These substances suppressed angiogenesis by downregulating the vascular endothelial growth factor(VEGF),promoted apoptosis by activating caspase enzymes,and prevented cell proliferation by controlling cyclin-dependent kinases.Clinical studies demonstrated improved outcomes in patients receiving these natural products with standard treatment procedures.Discussion:The findings underscore the multifaceted functions of natural products in breast cancer therapy,highlighting their potential to increase the efficacy of conventional treatments while reducing adverse effects.Further exploration of synergistic actions and optimal dosages is needed.Conclusion:Clinically proven natural products represent a potential avenue for breast cancer treatment with their mechanistic insights that facilitate their incorporation into treatment regimens.To maximize clinical applications,future inquiries should center on elucidating the full spectrum of these anticancer functions.展开更多
Background:Sudden sensorineural hearing loss(SSNHL),often associated with tinnitus,significantly impacts individuals'quality of life.Current treatments,such as free drugs via intravenous or intratympanic(IT)admini...Background:Sudden sensorineural hearing loss(SSNHL),often associated with tinnitus,significantly impacts individuals'quality of life.Current treatments,such as free drugs via intravenous or intratympanic(IT)administration of dexamethasone(DEX)and lidocaine,face limitations like low bioavailability and rapid drug clearance.To address these challenges,we developed a local co-delivery system combining DEX microcrystals(DEX MCs)and lidocaine-loaded poly(lactic-co-glycolic acid)(PLGA)non-spherical microparticles(LPNMs)for sustained drug release in the inner ear.Methods:DEX MCs and LPNMs were prepared using the traditional precipitation technique and double emulsion-solvent evaporation,respectively.After characterizing physicochemical properties and drug release kinetics,they were dispersed in sodium hyaluronate solution for IT injection,then in vivo pharmacokinetics and biocompatibility in guinea pigs were studied.Results:DEX MCs exhibited stable dissolution,while LPNMs provided sustained lidocaine release,reducing potential side effects.In vivo studies in guinea pigs demonstrated prolonged drug retention in the perilymph and improved pharmacokinetics.Histological evaluation confirmed the good biocompatibility of this combined delivery system,with no significant inner ear damage observed.Conclusion:This co-delivery system can be used as a depot for delivering both DEX and lidocaine to the inner ear and offers a promising approach for the synergistic treatment of SSNHL associated with tinnitus.展开更多
ObjectiveTo develop a sustained-release codelivery system for intratympanic administration of dexamethasone(DEX)and lipoic acid(LA).MethodsDEX microcrystals(MCs)were prepared via precipitation,while LA-loaded porous P...ObjectiveTo develop a sustained-release codelivery system for intratympanic administration of dexamethasone(DEX)and lipoic acid(LA).MethodsDEX microcrystals(MCs)were prepared via precipitation,while LA-loaded porous PLGA microspheres(LPMPs)were fabricated using a double emulsion–solvent evaporation method.DEX MCs were physically perfused into LPMPs via negative pressure to form a combined system(DEX MCs+LPMPs).Physicochemical properties,in vitro drug release,pharmacokinetics,and biocompatibility were evaluated.Guinea pigs were used for intratympanic injections of DEX MCs,LPMPs,or DEX MCs+LPMPs.ResultsThe DEX MCs+LPMPs system enabled simultaneous release of both drugs,with DEX exhibiting superior pharmacokinetics(sustained perilymph concentrations up to 7 days)compared to DEX MCs alone.LA release from LPMPs demonstrated prolonged kinetics without burst release.SEM confirmed DEX MCs were localized within/on LPMPs and adhered to the round window membrane(RWM).Histological analysis revealed normal cochlear morphology and no inflammatory response,confirming biocompatibility.ConclusionsThis novel codelivery system combining microcrystals and porous microspheres achieves sustained dual-drug release,enhances therapeutic efficacy,and offers a promising strategy for managing hearing loss via intratympanic administration.展开更多
Background Bovine mastitis is one of the main causes of reduced production in dairy cows.The infection of the mammary gland is mainly caused by the bacterium Staphylococcus aureus,whose resistant strains make the trea...Background Bovine mastitis is one of the main causes of reduced production in dairy cows.The infection of the mammary gland is mainly caused by the bacterium Staphylococcus aureus,whose resistant strains make the treatment of mastitis with conventional antibiotics very difficult and result in high losses.Therefore,it is impor-tant to develop novel therapeutic agents to overcome the resistance of mastitis-causing strains.In this study,novel selenium-tellurium based nanoparticles(SeTeNPs)were synthesized and characterized.Their antibacterial activity and biocompatibility were evaluated both in vitro and in vivo using a bovine model.A total of 10 heifers were divided into experimental and control groups(5 animals each).After intramammary infection with methicillin resistant S.aureus(MRSA)and the development of clinical signs of mastitis,a dose of SeTeNPs was administered to all quarters in the experimental group.Results Based on in vitro tests,the concentration of 149.70 mg/L and 263.95 mg/L of Se and Te,respectively,was used for application into the mammary gland.Three days after SeTeNPs administration,MRSA counts in the experimental group showed a significant reduction(P<0.01)compared to the control group.The inhibitory effect observed within the in vitro experiments was thus confirmed,resulting in the suppression of infection in ani-mals.Moreover,the superior biocompatibility of SeTeNPs in the organism was demonstrated,as the nanoparticles did not significantly alter the inflammatory response or histopathology at the site of application,i.e.,mammary gland,compared to the control group(P>0.05).Additionally,the metabolic profile of the blood plasma as well as the histology of the main organs remained unaffected,indicating that the nanoparticles had no adverse effects on the organism.Conclusions Our findings suggest that SeTeNPs can be used as a promising treatment for bovine mastitis in the pres-ence of resistant bacteria.However,the current study is limited by its small sample size,making it primarily a proof of the concept for the efficacy of intramammary-applied SeTeNPs.Therefore,further research with a larger sample size is needed to validate these results.展开更多
基金Supported by National Natural Science Foundation of China,No.81071651 and No.81372622the Program for Zhejiang Leading Team of ST innovation,No.2012R10046-03+3 种基金Major State Basic Research Development Program,No.2010CB834303National High Technology Research and Development Program of China,No.2012AA02A601Major Projects in Zhejiang Province,No.2012C13014-1the Fundamental Research Funds for the Central Universities,No.2012FZA7020
文摘Colorectal cancer(CRC)causes approximately 600000deaths annually and is the third leading cause of cancer mortality worldwide.Despite significant advancements in treatment options,CRC patient survival is still poor owing to a lack of effective tools for early diagnosis and a limited capacity for optimal therapeutic decision making.Since there exists a need to find new biomarkers to improve diagnosis of CRC,the research on epigenetic biomarkers for molecular diagnostics encourages the translation of this field from the bench to clinical practice.Epigenetic alterations are thought to hold great promise as tumor biomarkers.In this review,we will primarily focus on recent advances in the study of epigenetic biomarkers for colorectal cancer and discuss epigenetic biomarkers,including DNA methylation,microRNA expression and histone modification,in cancer tissue,stool,plasma,serum,cell lines and xenografts.These studies have improved the chances that epigenetic biomarkers will find a place in the clinical practices of screening,early diagnosis,prognosis,therapy choice and recurrence surveillance for CRC patients.However,these studies have typically been small in size,and evaluation at a larger scale of well-controlled randomized clinical trials is the next step that is necessary to increase the quality of epigenetic biomarkers and ensure their widespread clinical use.
文摘Therapeutic experiments are commonly performed on laboratory animals to inves-tigate the possible mechanism(s)of action of toxic agents as well as drugs or sub-stances under consideration.The use of toxins in laboratory animal models,including rats,is intended to cause toxicity.This study aimed to investigate different models of hepatotoxicity and nephrotoxicity in laboratory animals to help researchers advance their research goals.The current narrative review used databases such as Medline,Web of Science,Scopus,and Embase and appropriate keywords until June 2021.Nephrotoxicity and hepatotoxicity models derived from some toxic agents such as cisplatin,acetaminophen,doxorubicin,some anticancer drugs,and other materials through various signaling pathways are investigated.To understand the models of renal or hepatotoxicity in laboratory animals,we have provided a list of toxic agents and their toxicity procedures in this review.
基金financially supported by the National Key Research and Development Project of China for Demonstration of Integrated Utilization of Solid Waste in Distinctive Convergent Areas of Southeast Light Industry Building Materials(2019YFC1904500)the National Natural Science Foundation of China(Grant No.81770222)+4 种基金the Social Development Industry University Research Cooperation Project from the Department of Science and Technology in Fujian(2018Y4002)support by the Award Program for Fujian Minjiang Scholar Professorshipsupport from the Australian Research Grants Council(DP130104648)support from the NSERC Discovery Grant(NSERC RGPIN-2020-04463)McGill Start-Up Grant。
文摘Owing to safety issue and low energy density of liquid lithium-ion batteries(LIBs),all-solid-state lithium metal batteries(ASLMBs)with unique all-solid-state electrolytes(SEs)have attracted wide attentions.This arises mainly from the advantages of the SEs in the suppression of lithium dendrite growth,long cycle life,and broad working temperature range,showing huge potential applications in electronic devices,electric vehicles,smart grids,and biomedical devices.However,SEs suffer from low lithiumion conductivity and low mechanical integrity,slowing down the development of practical ASLMBs.Nanostructure engineering is of great efficiency in tuning the structure and composition of the SEs with improved lithium-ion conductivity and mechanical integrity.Among various available technologies for nanostructure engineering,electrospinning is a promising technique because of its simple operation,cost-effectiveness,and efficient integration with different components.In this review,we will first give a simple description of the electrospinning process.Then,the use of electrospinning technique in the synthesis of various SEs is summarized,for example,organic nanofibrous matrix,organic/inorganic nanofibrous matrix,and inorganic nanofibrous matrix combined with other components.The current development of the advanced architectures of SEs through electrospinning technology is also presented to provide references and ideas for designing high-performance ASLMBs.Finally,an outlook and further challenges in the preparation of advanced SEs for ASLMBs through electrospinning engineering are given.
基金Supported by Instituto de Salud Carlos III(ISCiii),No.PI19/01266 and No.PI22/00857Consejería de Salud y Familias(Junta de Andalucía),No.PI-0216-2020 and No.PIP-0215-2020Biomedical Research Network Center for Liver and Digestive Diseases(CIBERehd)founded by the ISCIII and co-financed by European Regional Development Fund“A way to achieve Europe”ERDF.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is the most common subtype of primary liver cancer with varied incidence and epidemiology worldwide.Sorafenib is still a recommended treatment for a large proportion of patients with advanced HCC.Different patterns of treatment responsiveness have been identified in differentiated hepatoblastoma HepG2 cells and metastatic HCC SNU449 cells.AIM To define the long non-codingRNA-microRNA-mRNA(lncRNA-miRNA-mRNA)predicted signatures related to selected hallmarks of cancer(apoptosis,autophagy,cell stress,cell dedifferentiation and invasiveness)in RNAseq studies using Sorafenib-treated HepG2 and SNU449 cells.Various available software analyses allowed us to establish the lncRNA-miRNA-mRNA regulatory axes following treatment in HepG2 and SNU449 cells.METHODS HepG2 and SNU449 cells were treated with Sorafenib(10μmol/L)for 24 hours.Total RNA,including small and long RNA,was extracted with a commercial miRNeasy kit.RNAseq was carried out for the identification of changes in lncRNA-miRNA-mRNA regulatory axes.RESULTS MALAT,THAP9-AS1 and SNGH17 appeared to coordinately regulate miR-374b-3p and miR-769-5p that led to upregulation of SMAD7,TIRARP,TFAP4 and FAXDC2 in HepG2 cells.SNHG12,EPB41 L4A-AS1,LINC01578,SNHG12 and GAS5 interacted with let-7b-3p,miR-195-5p and VEGFA in SNU449 cells.The axes MALAT1/hsamir-374b-3p/SMAD7 and MALAT1/hsa-mir-769-5p/TFAP4 were of high relevance for Sorafenib response in HepG2 cells,whereas PVT1/hsa-miR-195-5p/VEGFA was responsible for the differential response of SNU449 cells to Sorafenib treatment.CONCLUSION Critical lncRNAs acting as sponges of miRNA were identified that regulated mRNA expression,whose proteins mainly increased the antitumor effectiveness of the treatment(SMAD7,TIRARP,TFAP4,FAXDC2 and ADRB2).However,the broad regulatory axis leading to increased VEGFA expression may be related to the side effect of Sorafenib in SNU449 cells.
基金supported by grants PID2020-115823-GB100 funded by MCIN/AEI/10.13039/501100011033SBPLY/21/180501/000150 funded by JCCM/ERDF-A way of making Europe+1 种基金2022-GRIN-34354 grant by UCLM/ERDF intramural funding to LJDJDNL.DJ held a predoctoral fellowship granted by UCLM/ESF“Plan Propio de Investigación.”。
文摘Although many causes of Alzheimer’s disease(AD)may exist,both the original amyloid cascade and tau hypotheses posit that abnormal misfolding and accumulation of amyloid-β(Aβ)and tau protein is the central event causing the pathology.However,that conclusion could be only partly true,and there is conflicting evidence about the role of both proteins in AD,being able to precede and influence one another.Some researchers argue that these proteins are mere executors rather than primary causes of pathology.Therefore,there have been continuing refinements of both hypotheses,with alternative explanations proposed.Aβand tau proteins may be independently involved in specific neurotoxic pathways;yet there may be other crucial processes going on in early AD.Moreover,accumulating evidence suggests that Aβand tau act synergistically,rather than additively in disease onset(Jeremic et al.,2021,2023a).
基金funded by Maranatha Christian University,Bandung,Indonesia for Productive Lecturer Research under grant number:011/SK/ADD/UKM/IV/2024.
文摘Objective:To assess the effects of turmeric extract and its compounds on oxidative stress,inflammation,and apoptosis in acetaminophen-induced liver injury.Methods:HepG2 cells were administered with acetaminophen(40 mM)to induce hepatotoxicity,followed by treatment with turmeric extract and its isolated compounds including curcumin,demethoxycurcumin,bis-demethoxycurcumin and ar-turmerone at 5,25,and 125μg/mL.IL-1β,IL-6,and IL-10 levels were quantified with ELISA kits.Further,qRT-PCR was used to analyze the mRNA expression of JNK,Casp-9,and Casp-3.Meanwhile,the levels of nitric oxide and lactate dehydrogenase were analyzed using colorimetric assay.Results:Acetaminophen administration caused an increase in the levels of lactate dehydrogenase,nitric oxide,IL-1β,IL-6,and the mRNA expression of JNK,Casp-9,and Casp-3 in HepG2 cells while reducing IL-10 levels.Treatment with turmeric extract,curcumin,demethoxycurcumin,bis-demethoxycurcumin,and ar-turmerone lowered IL-1β,IL-6,nitric oxide,and lactate dehydrogenase levels,downregulated the mRNA expression of JNK,Casp-9,and Casp-3,and increased IL-10 levels.Conclusions:Turmeric extract and its compounds have significant hepatoprotective activity and could be further explored for the treatment of liver damage.
基金supported by funding from ERA4Health:InterHeart 2025 to L.Tomasova and the VEGA Grant Agency of the Slovak Republic(grant number 2/0138/25 to A.Misak and 2/0066/23 to L.Tomasova).
文摘Background:An arterial stiffness is an indicator of many cardiovascular diseases.The temporal position of systolic blood pressure(BP)on aorta pulse waveform is assumed to gradually shift on the waveform in response to increasing/decreasing vascular stiffness.The animal model of rats and invasive methods that cannot be used in humans was applied to test the assumption on arterial pulse waveform(APW)of anesthetized rat.The aim of this study was to characterize the temporal movement of diastolic and systolic pressures on the APW of anesthetized rats during increasing/decreasing vascular stiffness.Methods:The right jugular vein of anesthetized normotensive and spontaneously hypertensive rats was cannulated for intravascular administration of vascularly active compounds to alter systolic pressure and vascular stiffness.The left carotid artery was cannulated to detect APW,from which numerous APW parameters were evaluated.Results:During increases/decreases in systolic BP or stiffness,the temporal position of diastolic BP of individual heartbeats di-gitally shifted on the APW between two temporal positions~8–12 ms apart,and the temporal position of systolic BP on the APW did not gradually shift during increases/decreases in vascular stiffness,as expected,but oscillated between constant di-gital,tri-gital,or tetra-gital temporal positions.Conclusions:Introducing new APW parameters,n-gital systolic BP fluctuations on rat APW were found.Fluctuations in n-gital were approximately constant during large changes in systolic pressure despite significant changes in augmentation index and cardiovascular stiffness,which may challenge the assumption of a gradual temporal location of systolic pressure on rat APW under these conditions.
基金Supported by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute,by the Ministry of Health&Welfare,Republic of Korea,No.RS-2018-KH049509the 2022 Cancer Research Support Project from the Korea Foundation for Cancer Research,No.CB-2022-A-3.
文摘BACKGROUND In patients with metastatic colorectal cancer,chemotherapy may lead to changes in body composition,including skeletal muscle quantity and quality,and body fat area and distribution.Longitudinal follow-up data in a homogeneous population are required to understand these changes better.AIM To comprehensively evaluate changes in body composition and their prognostic value in patients with metastatic colorectal cancer undergoing palliative chemo-therapy.METHODS This retrospective study included patients with recurrent or metastatic colorectal cancer who received palliative chemotherapy between 2008 and 2017.Computed tomography scans were analyzed at multiple time points(before each new chemotherapy regimen and after discontinuing all chemotherapy).Body composition was analyzed from each scan using artificial intelligence software(AID-UTM,iAID Inc.),and its association with survival was evaluated through time-dependent Cox regression to adjust for time-varying effects.RESULTS This analysis included 1805 patients,with a median age at diagnosis of 57 years,and 62%were male.At first-line chemotherapy initiation,4.7%,30.9%,36.5%,and 37.1%of the patients had sarcopenia,myosteatosis,and visceral and subcutaneous obesity,respectively.During treatment,approximately 54.5%of the patients experienced significant changes in body composition,with 9.1%and 19.2%developing new sarcopenia and myosteatosis,respectively.Sarcopenia and myosteatosis were associated with poorer survival outcomes[hazard ratio(HR)for sarcopenia,2.55(95%CI:2.06-3.16,P<0.001;HR for myosteatosis,2.37(95%CI:2.00-2.82),P<0.001].In contrast,visceral and subcutaneous obesity were associated with improved survival[HR for visceral obesity,0.69(95%CI:0.57-0.82),P<0.001;HR for subcutaneous obesity,0.78(95%CI:0.64-0.95),P=0.015],with no negative impacts observed at higher fat levels.These changes correlated with end-of-life survival time.CONCLUSION Abnormalities and body composition changes were frequently observed during palliative chemotherapy for advanced colorectal cancer;myosteatosis was common.Comprehensive body composition assessment offers valuable prognostic insights without requiring additional testing.
基金supported by the National Natural Science Foundation of China(81803547)the Natural Science Foundation of Fujian Province,China(2021J01204)Fujian Provincial Regional Development Project(2021N3005)。
文摘Most Aloe species are used as new food or functional food ingredient.Even though widely known for its health benefits,the anti-inflammatory effects and underlying mechanisms of Aloin(Alo),an anthraquinone compound isolated from plant species of the genus Aloe,remain unidentified.Here,we investigated the protective effects of Alo against cecal ligation and puncture(CLP)-induced sepsis and microflora in mice.Alo significantly improved CLP-induced sepsis and the survival rate of septic mice,downregulated the expression of proinflammatory factors,and decreased the infiltration of inflammatory cells in tissues.Alo upregulated the proportion of peritoneal macrophages,reduced the number of peritoneal bacteria,decreased the content of short-chain fatty acids and bile acids in the abdominal cavity,and suppressed Toll-like receptor(TLR)-2/4/nuclear factor kappa-B(NF-κB)/NOD-like receptor thermal protein domain associated protein 3(NLRP3)/Caspase-1/3/8 signaling.Furthermore,Alo altered the composition of the microbiome and promoted the growth of Lactobacillus,which showed a stronger anti-inflammatory effect.Whole-genome analysis identified the genes Saa3,Il10,Fpr1,and Eif4a1 associated with the protective effects of Alo in mice with CLP-induced sepsis.Overall,our results provide novel insights into the therapeutic potential and mechanism of action of Alo in the treatment of sepsis.
文摘The search for reliable biomarkers to predict metabolic dysfunction-associated steatotic liver disease(MASLD)remains a key research focus.Traditional anthropometric parameters,such as triglycerides,glucose,and waist circumference(WC),have proven to be robust tools for diagnosing,stratifying,and predicting health outcomes.These measures facilitate early detection,personalized treatment strategies,and long-term risk assessment in metabolic health.The triglycerideglucose(TyG)index and related parameters,particularly the TyG-WC index,are gaining recognition as reliable biomarkers for MASLD,with consistently high diagnostic accuracy across diverse populations.The TyG-WC index is associated with MASLD and an increased likelihood of all-cause,cardiovascular,and diabetes-related mortality,highlighting its importance in stratification and patient management.This opinion review summarizes key findings on the TyG-WC index across different MASLD populations and provides nutritional recommendations aimed at reducing this index.The TyG-WC index stands out as a practical and scalable biomarker for identifying and stratifying the risk of MASLD,particularly in resource-limited environments where access to advanced diagnostic tools is restricted.However,before the TyG-WC index can be integrated into routine clinical practice,rigorous,longitudinal studies involving ethnically diverse cohorts must validate its prognostic performance.It should be viewed as a complementary tool within a comprehensive metabolic risk assessment framework,supporting preventive strategies while awaiting formal endorsement in clinical guidelines.
基金supported by grants from the National Key Research and Development Program of China(No.2022YFE0205800)the National Natural Science Foundation of China(No.21974114)+5 种基金Major Science and Technology Special Project of Fujian Province(No.2022YZ036012)the Fundamental Research Funds for the Central Universities(No.20720220003)Project“111”sponsored by the State Bureau of Foreign Experts and Ministry of Education of China(No.BP0618017)to S.-H.LinNatural Science Foundation of Fujian Province of China(No.2022J01330)Natural Science Foundation of Xiamen City of China(No.3502Z20227208)the China Scholarship Council(No.202308350047)to J.Zeng。
文摘Cardiolipins(CLs),the mitochondria-specific class of phospholipids,are crucial to energy metabolism,cristae structure,and cell apoptosis.CLs present significant challenges in lipidomics analysis due to their structural diversity with up to four fatty acyl side chains.In this study,we developed CLAN(Cardio Lipin ANalysis),a comprehensive computational pipeline designed to improve the accuracy and coverage of cardiolipin identification.CLAN integrates three innovative modules:A cardiolipin identification module that utilizes specific fragmentation rules for precise characterization of CLs and their acyl side chains;a false positives detection module that employs retention time(RT)criteria to reduce false positives;and a prediction module that constructs regression models to identify CLs lacking authentic MS/MS spectra.CLAN achieved better identification accuracy and the highest recall rate for potential CL identification compared to the existing lipid identification tools.Furthermore,we applied CLAN program to an intermittent fasting mouse model,delineating tissue-specific CL alterations across 10 tissues.Every-other-day fasting(EODF)can partially counteract the disruption of the CL atlas across multiple tissues caused by high-fat-high-sugar diet feeding,providing novel insights into mitochondrial lipid metabolism under dietary interventions.Taken together,this work not only advances CL identification methodology but also underscores CLAN's potential in comprehensive analysis of CL atlas in the EODF animal model.CLAN is freely accessible on Git Hub.
基金supported by the National Cancer Institute of the National Institutes of Health under Award Number R00CA218603
文摘Background The biological mechanisms by which postdiagnosis physical activity improves disease-free survival in colorectal cancer survivors remain incompletely understood.This trial tested the hypothesis that 12 weeks of moderate-intensity aerobic exercise,when compared with a control group,would change inflammation,circulating tumor cells(CTCs),and circulating tumor DNA(ctDNA)in a manner consistent with an improved cancer prognosis.Methods This trial randomized Stages I–III colorectal cancer survivors to 12 weeks of home-based moderate-intensity aerobic exercise or a waitlist control group.The co-primary endpoints were high-sensitivity C-reactive protein(hs-CRP)and interleukin-6(IL-6),secondary endpoints were soluble tumor necrosis factor-αreceptor 2(sTNFαR2)and CTCs,and the exploratory endpoint was tumor fraction quantified from ctDNA.Results Sixty subjects were randomized(age=60.6±10.8 years,mean±SD;39(65%)females;46(77%)colonic primary tumor),and 59(98%)subjects completed the study.Over 12 weeks,exercise adherence was 92%(95%confidence interval(95%CI):86‒99).Exercise improved submaximal fitness capacity(0.36 metabolic equivalents;95%CI:0.05‒0.67;p=0.025)and objectively measured moderate-to-vigorous-intensity physical activity(34.8%,95%CI:11.3‒63.1;p=0.002)compared to control.Exercise did not change hs-CRP(20.9%,95%CI:−17.1 to 76.2;p=0.32),IL-6(11.4%,95%CI:−7.5 to 34.0;p=0.25),or sTNFαR2(−3.6%,95%CI:−13.7 to 7.7;p=0.52)compared to control.In the subgroup of subjects with elevated baseline hs-CRP(n=35,58.3%),aerobic exercise reduced hs-CRP(−35.5%,95%CI:−55.3 to−3.8;p=0.031).Exercise did not change CTCs(0.59 cells/mL,95%CI:−0.33 to 1.51;p=0.21)or tumor fraction(0.0005,95%CI:−0.0024 to 0.0034;p=0.73).In exploratory analyses,higher aerobic exercise adherence correlated with a reduction in CTCs(ρ=−0.37,95%CI:−0.66 to−0.08;p=0.013).Conclusion Colorectal cancer survivors achieved high adherence to a home-based moderate-intensity aerobic exercise prescription that improved fitness capacity and physical activity but did not reduce inflammation or change tumor endpoints from a liquid biopsy.
文摘Background:Breast cancer still stands to be the foremost contributor to cancer-related incidence and mortality in women globally accounting for about 14%of all female cancer-related deaths worldwide.This research seeks to illustrate the mechanisms and clinical findings of natural products against breast cancer treatment.Methodology:Required data for this review article was retrieved employing several readily obtainable search databases,including Web of Science■(Thomson Reuters,USA),PubMed■(U.S.National Library of Medicine,USA),and SciVerse Scopus■(Elsevier Properties S.A.,USA),taking into consideration certain search terms like“breast cancer,”“natural products against breast cancer,”and“Clinically proven natural products in the treatment of breast cancer”and so on.Results:Several natural products,namely Omega-3 fatty acids,dietary isothiocyanates,curcumin,green tea,flaxseed,limonene,and others,were found to modulate crucial pathways in breast cancer cells.These substances suppressed angiogenesis by downregulating the vascular endothelial growth factor(VEGF),promoted apoptosis by activating caspase enzymes,and prevented cell proliferation by controlling cyclin-dependent kinases.Clinical studies demonstrated improved outcomes in patients receiving these natural products with standard treatment procedures.Discussion:The findings underscore the multifaceted functions of natural products in breast cancer therapy,highlighting their potential to increase the efficacy of conventional treatments while reducing adverse effects.Further exploration of synergistic actions and optimal dosages is needed.Conclusion:Clinically proven natural products represent a potential avenue for breast cancer treatment with their mechanistic insights that facilitate their incorporation into treatment regimens.To maximize clinical applications,future inquiries should center on elucidating the full spectrum of these anticancer functions.
基金Tianjin Natural Science Foundation for Jingjinji Collaboration,Grant/Award Number:23JCZXJC00240Hebei Natural Science Foundation,Grant/Award Number:H2023201903+2 种基金Beijing Natural Science Foundation,Grant/Award Number:J230006Capital's Funds for Health Improvement and Research,Grant/Award Number:CFH:2022-2-5072CAMS Innovation Fund for Medical Sciences,Grant/Award Number:2021-I2M-1-052。
文摘Background:Sudden sensorineural hearing loss(SSNHL),often associated with tinnitus,significantly impacts individuals'quality of life.Current treatments,such as free drugs via intravenous or intratympanic(IT)administration of dexamethasone(DEX)and lidocaine,face limitations like low bioavailability and rapid drug clearance.To address these challenges,we developed a local co-delivery system combining DEX microcrystals(DEX MCs)and lidocaine-loaded poly(lactic-co-glycolic acid)(PLGA)non-spherical microparticles(LPNMs)for sustained drug release in the inner ear.Methods:DEX MCs and LPNMs were prepared using the traditional precipitation technique and double emulsion-solvent evaporation,respectively.After characterizing physicochemical properties and drug release kinetics,they were dispersed in sodium hyaluronate solution for IT injection,then in vivo pharmacokinetics and biocompatibility in guinea pigs were studied.Results:DEX MCs exhibited stable dissolution,while LPNMs provided sustained lidocaine release,reducing potential side effects.In vivo studies in guinea pigs demonstrated prolonged drug retention in the perilymph and improved pharmacokinetics.Histological evaluation confirmed the good biocompatibility of this combined delivery system,with no significant inner ear damage observed.Conclusion:This co-delivery system can be used as a depot for delivering both DEX and lidocaine to the inner ear and offers a promising approach for the synergistic treatment of SSNHL associated with tinnitus.
基金supported by Capital’s Funds for Health Improvement and Research(CFH:2022-2-5072)the Tianjin Natural Science Foundation for Jingjinji Collaboration(23JCZXJC00240)+1 种基金Beijing Natural Science Foundation(J230006)the CAMS Innovation Fund for Medical Science(2021-I2M-1-052).
文摘ObjectiveTo develop a sustained-release codelivery system for intratympanic administration of dexamethasone(DEX)and lipoic acid(LA).MethodsDEX microcrystals(MCs)were prepared via precipitation,while LA-loaded porous PLGA microspheres(LPMPs)were fabricated using a double emulsion–solvent evaporation method.DEX MCs were physically perfused into LPMPs via negative pressure to form a combined system(DEX MCs+LPMPs).Physicochemical properties,in vitro drug release,pharmacokinetics,and biocompatibility were evaluated.Guinea pigs were used for intratympanic injections of DEX MCs,LPMPs,or DEX MCs+LPMPs.ResultsThe DEX MCs+LPMPs system enabled simultaneous release of both drugs,with DEX exhibiting superior pharmacokinetics(sustained perilymph concentrations up to 7 days)compared to DEX MCs alone.LA release from LPMPs demonstrated prolonged kinetics without burst release.SEM confirmed DEX MCs were localized within/on LPMPs and adhered to the round window membrane(RWM).Histological analysis revealed normal cochlear morphology and no inflammatory response,confirming biocompatibility.ConclusionsThis novel codelivery system combining microcrystals and porous microspheres achieves sustained dual-drug release,enhances therapeutic efficacy,and offers a promising strategy for managing hearing loss via intratympanic administration.
基金Financial support from ERDF “Multidisciplinary research to increase application potential of nanomaterials in agricultural practice” (No.CZ.02.1.01/0.0/0.0/16_025/0007314)the assistance provided by the Research Infrastructure Nano Envi Cz, supported by the Ministry of Education, Youth and Sports of the Czech Republic under Project No. LM2018124+4 种基金Czech Nano Lab Research Infrastructure supported by MEYS CR (LM2023051)Grant Agency of Gregor Johann Mendel (C-MNG-23–002)further supported by the Ministry of Agriculture of the Czech Republic by Grant RO0523Internal Grant Agency of University of Veterinary Sciences Brno (223/2024/FVHE)the National Institute of Virology and Bacteriology project (Programme EXCELES, Project ID No. LX22NPO5103)-Funded by the European Union-Next Generation EU.
文摘Background Bovine mastitis is one of the main causes of reduced production in dairy cows.The infection of the mammary gland is mainly caused by the bacterium Staphylococcus aureus,whose resistant strains make the treatment of mastitis with conventional antibiotics very difficult and result in high losses.Therefore,it is impor-tant to develop novel therapeutic agents to overcome the resistance of mastitis-causing strains.In this study,novel selenium-tellurium based nanoparticles(SeTeNPs)were synthesized and characterized.Their antibacterial activity and biocompatibility were evaluated both in vitro and in vivo using a bovine model.A total of 10 heifers were divided into experimental and control groups(5 animals each).After intramammary infection with methicillin resistant S.aureus(MRSA)and the development of clinical signs of mastitis,a dose of SeTeNPs was administered to all quarters in the experimental group.Results Based on in vitro tests,the concentration of 149.70 mg/L and 263.95 mg/L of Se and Te,respectively,was used for application into the mammary gland.Three days after SeTeNPs administration,MRSA counts in the experimental group showed a significant reduction(P<0.01)compared to the control group.The inhibitory effect observed within the in vitro experiments was thus confirmed,resulting in the suppression of infection in ani-mals.Moreover,the superior biocompatibility of SeTeNPs in the organism was demonstrated,as the nanoparticles did not significantly alter the inflammatory response or histopathology at the site of application,i.e.,mammary gland,compared to the control group(P>0.05).Additionally,the metabolic profile of the blood plasma as well as the histology of the main organs remained unaffected,indicating that the nanoparticles had no adverse effects on the organism.Conclusions Our findings suggest that SeTeNPs can be used as a promising treatment for bovine mastitis in the pres-ence of resistant bacteria.However,the current study is limited by its small sample size,making it primarily a proof of the concept for the efficacy of intramammary-applied SeTeNPs.Therefore,further research with a larger sample size is needed to validate these results.
