Chloroquine(CQ)and hydroxychloroquine(HCQ),originally developed as anti-malarial drugs,have found a new purpose in treating various autoimmune dis-eases due to their immunomodulatory properties.These drugs work throug...Chloroquine(CQ)and hydroxychloroquine(HCQ),originally developed as anti-malarial drugs,have found a new purpose in treating various autoimmune dis-eases due to their immunomodulatory properties.These drugs work through mu-ltiple mechanisms,including inhibiting Toll-like receptor signaling,suppressing antigen presentation,and modulating autophagy.This review article provides a comprehensive analysis of the immunomodulatory effects of CQ and HCQ in several autoimmune diseases such as systemic lupus erythematosus,rheumatoid arthritis,systemic sclerosis,and others.We delve into the intricate mechanisms of action,highlighting the key immune cells involved and discussing the clinical implications of these drugs in managing autoimmune conditions.Our review covers the latest research and clinical trials,offering a comprehensive under-standing of the therapeutic potential of CQ and HCQ in autoimmune diseases.We also discuss the challenges and controversies surrounding the use of these drugs,such as their long-term side effects and the need for personalized treatment approaches.By synthesizing current knowledge and identifying areas for future research,this review aims to provide a valuable resource for healthcare profes-sionals and researchers involved in the management of autoimmune diseases.展开更多
In this editorial,we comment on the article by Sá-Oliveira et al.We focus specifi-cally on the role of platelet-rich fibrin(PRF)in modulating innate immunity to enhance wound repair.The process of wound healing i...In this editorial,we comment on the article by Sá-Oliveira et al.We focus specifi-cally on the role of platelet-rich fibrin(PRF)in modulating innate immunity to enhance wound repair.The process of wound healing is complex and involves a coordinated series of biological events,including inflammation,cell proliferation,and tissue remodeling.The innate immune system is important in the early stages of wound repair,with inflammation being a crucial initial phase in tissue rege-neration.However,the inflammatory response should be regulated,as excessive or dysregulated inflammation can impair healing.Platelet concentrates,specifi-cally PRF,have originated as promising tools to optimize the tissue repair process.PRF is a second-generation platelet concentrate,and the release of growth factors(GFs)plays a determining role in several aspects of wound healing,including promoting cell proliferation,stimulating angiogenesis,and modulating inflam-mation.PRF forms a fibrin matrix that entraps platelets and GFs.This structure allows for their sustained release over time,which is believed to provide a more favorable microenvironment for tissue repair.Recent research by Sá-Oliveira et al has provided valuable evidence supporting the efficacy of PRF in promoting wound healing.Their study,conducted on an animal model,demonstrated that PRF-based dressings were more effective in accelerating wound closure in the early stages of the healing process,enhancing tissue repair,and modulating the inflammatory response.We explore how PRF's unique properties contribute to a more controlled and effective healing process.By examining these findings,we aim to highlight PRF's potential as a promising therapeutic strategy for improved wound management.展开更多
Bronchiectasis is a chronic inflammatory airway disease,and patients often suffer from recurrent airway infections leading to decreased lung function and impaired quality of life.In this study,the effects of supervise...Bronchiectasis is a chronic inflammatory airway disease,and patients often suffer from recurrent airway infections leading to decreased lung function and impaired quality of life.In this study,the effects of supervised pulmonary rehabilitation training on pulmonary function,training compliance,and quality of life in patients with bronchiectasis under home rehabilitation mode are investigated.Ninety stable patients were selected,and the observation group adopted the home-supervised mode of pulmonary rehabilitation training.The results showed that the observation group’s pulmonary function indexes,quality of life,and training adherence were better than those of the control group.The differences were statistically significant(P<0.05).The supervised pulmonary rehabilitation training in home rehabilitation mode can effectively improve patients’pulmonary function and quality of life,and improve training compliance,which has good clinical application value.展开更多
Based on the perspective of caring,this study constructs a whole-cycle management programme for lymphoma patients,and systematically explores the pathway of patients’health management from diagnosis to recovery by in...Based on the perspective of caring,this study constructs a whole-cycle management programme for lymphoma patients,and systematically explores the pathway of patients’health management from diagnosis to recovery by integrating literature analysis,clinical practice research,and multidisciplinary experts’consensus.Focusing on the differentiated needs of patients,the study proposes a dual-track management framework of‘precise diagnosis and treatment standard’and‘humanistic care practice’,and innovatively designs a multidisciplinary collaborative mechanism,an information-based follow-up platform,and a social support network.Through the role of‘care consultant’,the programme connects the medical team with the individual needs of patients,strengthens treatment compliance and improves the quality of life,and provides a theoretical basis and practical reference for the optimization of the whole management mode of lymphoma patients.展开更多
Vascular oxidative stress serves as a pathological foundation for various vascular injury-related diseases,including atherosclerosis,hypertension,restenosis,and abdominal aortic aneurysms.Recent studies have indicated...Vascular oxidative stress serves as a pathological foundation for various vascular injury-related diseases,including atherosclerosis,hypertension,restenosis,and abdominal aortic aneurysms.Recent studies have indicated that intestinal flora-derived metabolites,especially phenylacetylglutamine(PAGln)and phenylacetylglycine(PAGly),may contribute to the promotion of thrombosis,heart failure,and other related conditions.Aucubin(AU),an iridoid glycoside,has been shown to exhibit anti-cardiovascular properties.Nevertheless,the precise role and underlying mechanisms by which AU mitigates PAGly-induced vascular injury remain poorly understood.Our results indicated that PAGln/PAGly promoted oxidative stress in vascular endothelial cells(ECs)and vascular smooth muscle cells(VSMCs)in vitro and in vivo.Network pharmacology suggest that AU may possess the capacity to regulate lipid and atherosclerosis,and reactive oxygen species(ROS)processes.We found that AU penetrated the blood vessels and mitigated oxidative stress induced by PAGln/PAGly.Mechanistically,combining the results from intersection analysis between the targets of AU and vascular diseases and molecular docking,we found that tumor necrosis factor(TNF)may be the potential target of AU.Further DARTS and molecular docking analysis demonstrated that AU bound to recombinant TNF-α,and AU could interact with multiple amino acid residues of TNF-α,including Asn-92 and Phe-144.Additionally,PAGly upregulated the level of soluble TNF-α(sTNF-α)in mouse VSMCs and plasma,and promoted the interaction between sTNF-αand TNF receptor 1(TNFR1),whereas AU inhibited this interaction.Both AU and Infliximab,a specific monoclonal antibody of TNF-α,inhibit TNF-α-induced ROS production.In summary,our results revealed that TNF-αis a cellular target of AU,and the interaction between AU and s TNF-αmay mitigate PAGln/PAGly-induced vascular oxidative stress by inhibiting the interaction of TNF-α-TNFR1.展开更多
Alcohol-associated liver disease(ALD)is a major global health concern,contributing to liver injury,morbidity,and mortality.Elafibranor(EFN),a dual peroxisome proliferator-activated receptorα/δagonist,has shown promi...Alcohol-associated liver disease(ALD)is a major global health concern,contributing to liver injury,morbidity,and mortality.Elafibranor(EFN),a dual peroxisome proliferator-activated receptorα/δagonist,has shown promise as a therapeutic candidate in preclinical studies.EFN reduces liver fibrosis by inhibiting lipid accumulation,apoptosis,and inflammatory pathways(LPS/TLR4/NF-κB),while enhancing autophagy and antioxidant responses.It also improves intestinal barrier function and modulates gut microbiota,reducing endotoxin-producing bacteria and increasing beneficial species.By strengthening the intestinal barrier and suppressing pro-inflammatory mediators like tumor necrosis factor-alpha and interleukin-6,EFN mitigates hepatic stellate cell activation and fibrogenic signaling.Macrophages play a central role in ALD progression,and EFN’s ability to modulate macrophage activity further highlights its anti-inflammatory properties.This review emphasizes EFN’s dual-targeted approach,addressing both hepatic and intestinal dysfunctions,distinguishing it from conventional ALD treatments.While preclinical results are promising,EFN remains under clinical investigation,with ongoing trials evaluating its safety and efficacy.Future research should focus on elucidating EFN’s molecular mechanisms and advancing its clinical application to establish its therapeutic potential in human populations.EFN represents a novel,comprehensive strategy for ALD management,targeting both liver and gut pathologies.展开更多
Varicocele(VC)is a common cause of male infertility,yet there is a lack of molecular information for VC-associated male infertility.This study investigated alterations in the seminal plasma metabolomic and lipidomic p...Varicocele(VC)is a common cause of male infertility,yet there is a lack of molecular information for VC-associated male infertility.This study investigated alterations in the seminal plasma metabolomic and lipidomic profiles of infertile male VC patients.Twenty infertile males with VC and twenty-three age-matched healthy controls(HCs)were recruited from Peking Union Medical College Hospital(Beijing,China)between October 2019 and April 2021.Untargeted metabolite and lipid profiles from seminal plasma were analyzed using mass spectrometry.Four hundred and seventy-six metabolites and seventeen lipids were significantly different in infertile male VC patients compared to HCs.The top enriched pathways among these significantly different metabolites are protein digestion and absorption,aminoacyl-transfer RNA(tRNA)biosynthesis,and biosynthesis of amino acids.Different key lipid species,including triglyceride(TG),diacylglycerol(DG),ceramides(Cer),and phosphatidylserine(PS),varied betweenVC and HC groups.The distinct metabolites and lipids were moderately correlated.DL-3-phenyllactic acid is a potential diagnostic biomarker for VC-related male infertility(area under the curve[AUC]=0.893),positively correlating with sperm count,concentration,and motility.Furthermore,DL-3-phenyllactic acid is the only metabolite shared by all four comparisons(VC vs HC,VC-induced oligoasthenospermia[OAS]vs VC-induced asthenospermia[AS],OAS vs HC,and AS vs HC).DL-3-phenyllactic acid significantly decreased in OAS than AS.Metabolite-targeting gene analysis revealed carbonic anhydrase 9(CA9)might be the strongest candidate associated with the onset and severity of VC.The seminal plasma metabolite and lipid profiles of infertile males with VC differ significantly from those of HCs.DL-3-phenyllactic acid could be a promising biomarker.展开更多
Aspergillus species produce aflatoxins and raise concerns about food safety in departmental stores and manufacturing mills.To address the risks posed by aflatoxins,and to advise the public on the highest quality rice ...Aspergillus species produce aflatoxins and raise concerns about food safety in departmental stores and manufacturing mills.To address the risks posed by aflatoxins,and to advise the public on the highest quality rice that serves as a nutritious food source,an inquiry following the guidelines outlined in both local and international standards of food safety for the presence of aflatoxins is an essential requirement.Therefore,16 white rice samples were selected randomly from low/high socio-economic departmental stores from 16 different localities.Grind powdered rice filtrate was extracted using chloroform.The filtrate applied on TLC plates and the amount of aflatoxin and moisture contents were determined.In the non-infected rice,moisture content was low(9.08%)whereas high[13.65%>12%(standard>value)]in infected ones.Four out of 8 samples of low-quality rice were contaminated with AFB_(1) and AFB_(2)(ranging from 22.2 to 29.3μg/kg).All the samples except one(22.3μg/kg)from high-quality rice were certified fit despite the contamination with AFB_(1).Furthermore,phylogenetic analysis showed Aspergillus flavus from unfit low(Long grain brown and Brown basmati)and high-quality(Basmati-198)rice whereas A.parasiticus from unfit low-quality Medium-grain brown rice.The presented research proves that the detection of fungi and aflatoxins in rice grains poses a huge risk to the health of consumers.Therefore,it is necessary to check the rice grains before distribution.展开更多
This editorial introduces the potential of targeting macrophage function for diabetic cardiomyopathy(DCM)treatment by dipeptidyl peptidase-4(DPP-4)inhibitors.Zhang et al studied teneligliptin,a DPP-4 inhibitor used fo...This editorial introduces the potential of targeting macrophage function for diabetic cardiomyopathy(DCM)treatment by dipeptidyl peptidase-4(DPP-4)inhibitors.Zhang et al studied teneligliptin,a DPP-4 inhibitor used for diabetes management,and its potential cardioprotective effects in a diabetic mouse model.They suggested teneligliptin administration may reverse established markers of DCM,including cardiac hypertrophy and compromised function.It also inhibited the NLRP3 inflammasome and reduced inflammatory cytokine production in diabetic mice.Macrophages play crucial roles in DCM pathogenesis.Chronic hyperglycemia disturbs the balance between pro-inflammatory(M1)and antiinflammatory(M2)macrophages,favoring a pro-inflammatory state contributing to heart damage.Here,we highlight the potential of DPP-4 inhibitors to modulate macrophage function and promote an anti-inflammatory environment.These compounds may achieve this by elevating glucagon-like peptide-1 levels and potentially inhibiting the NLRP3 inflammasome.Further studies on teneligliptin in combination with other therapies targeting different aspects of DCM could be suggested for developing more effective treatment strategies to improve cardiovascular health in diabetic patients.展开更多
Hernandezine(Her),a bisbenzylisoquinoline alkaloid extracted from Thalictrum flavum,is recognized for its range of biological activities inherent to this herbal medicine.Despite its notable properties,the anti-cancer ...Hernandezine(Her),a bisbenzylisoquinoline alkaloid extracted from Thalictrum flavum,is recognized for its range of biological activities inherent to this herbal medicine.Despite its notable properties,the anti-cancer effects of Her have remained largely unexplored.In this study,we elucidated that Her significantly induced cytotoxicity in cancer cells through the activation of apoptosis and necroptosis mechanisms.Furthermore,Her triggered autophagosome formation by activating the AMPK and ATG5 conjugation systems,leading to LC3 lipidation.Our findings revealed that Her caused damage to the mitochondrial membrane,with the damaged mitochondria undergoing mitophagy,as evidenced by the elevated expression of mitophagy markers.Conversely,Her disrupted autophagic flux,demonstrated by the upregulation of p62 and accumulation of autolysosomes,as observed in the RFP-GFP-LC3 reporter assay.Initially,we determined that Her did not prevent the fusion of autophagosomes and lysosomes.However,it inhibited the maturation of cathepsin D and increased lysosomal pH,indicating an impairment of lysosomal function.The use of the early-stage autophagy inhibitor,3-methyladenine(3-MA),did not suppress LC3II,suggesting that Her also induces noncanonical autophagy in autophagosome formation.The application of Bafilomycin A1,an inhibitor of noncanonical autophagy,diminished the recruitment of ATG16L1 and the accumulation of LC3II by Her,thereby augmenting Her-induced cell death.These observations imply that while autophagy initially plays a protective role,the disruption of the autophagic process by Her promotes programmed cell death.This study provides the first evidence of Her’s dual role in inducing apoptosis and necroptosis while also initiating and subsequently impairing autophagy to promote apoptotic cell death.These insights contribute to a deeper understanding of the mechanisms underlying programmed cell death,offering potential avenues for enhancing cancer prevention and therapeutic strategies.展开更多
Esophageal squamous cell carcinoma(ESCC)is a substantial global health burden.Immune escape mechanisms are important in ESCC progression,enabling cancer cells to escape the surveillance of the host immune system.One k...Esophageal squamous cell carcinoma(ESCC)is a substantial global health burden.Immune escape mechanisms are important in ESCC progression,enabling cancer cells to escape the surveillance of the host immune system.One key player in this process is the Aryl Hydrocarbon Receptor(AhR),which influences multiple cellular processes,including proliferation,differentiation,metabolism,and immune regulation.Dysregulated AhR signaling participates in ESCC development by stimulating carcinogenesis,epithelial-mesenchymal transition,and immune escape.Targeting AhR signaling is a potential therapeutic approach for ESCC,with AhR ligands showing efficacy in preclinical studies.Additionally,modification of AhR ligands and combination therapies present new opportunities for therapeutic intervention.This review aims to address the knowledge gap related to the role of AhR signaling in ESCC pathogenesis and immune escape.展开更多
Objective: The human cluster of differentiation(CD)300A, a type-I transmembrane protein with immunoreceptor tyrosine-based inhibitory motifs, was investigated as a potential immune checkpoint for human natural killer(...Objective: The human cluster of differentiation(CD)300A, a type-I transmembrane protein with immunoreceptor tyrosine-based inhibitory motifs, was investigated as a potential immune checkpoint for human natural killer(NK) cells targeting hematologic malignancies(HMs).Methods: We implemented a stimulation system involving the CD300A ligand, phosphatidylserine(PS), exposed to the outer surface of malignant cells. Additionally, we utilized CD300A overexpression, a CD300A blocking system, and a xenotransplantation model to evaluate the impact of CD300A on NK cell efficacy against HMs in in vitro and in vivo settings. Furthermore, we explored the association between CD300A and HM progression in patients.Results: Our findings indicated that PS hampers the function of NK cells. Increased CD300A expression inhibited HM lysis by NK cells. CD300A overexpression shortened the survival of HM-xenografted mice by impairing transplanted NK cells. Blocking PS–CD300A signals with antibodies significantly amplified the expression of lysis function-related proteins and effector cytokines in NK cells, thereby augmenting the ability to lyse HMs. Clinically, heightened CD300A expression correlated with shorter survival and an “exhausted” phenotype of intratumoral NK cells in patients with HMs or solid tumors.Conclusions: These results propose CD300A as a potential target for invigorating NK cell-based treatments against HMs.展开更多
Intermittent fasting can benefit breast cancer patients undergoing chemotherapy or immunotherapy.However,it is still uncertain how to select immunotherapy drugs to combine with intermittent fasting.Herein we observed ...Intermittent fasting can benefit breast cancer patients undergoing chemotherapy or immunotherapy.However,it is still uncertain how to select immunotherapy drugs to combine with intermittent fasting.Herein we observed that two cycles of fasting treatment significantly inhibited breast tumor growth and lung tissue metastasis,as well as prolonged overall survival in mice bearing 4T1 and 4T07 breast cancer.During this process,both the immunosuppressive monocytic-(M-)and granulocytic-(G-)myeloid-derived suppressor cell(MDSC)decreased,accompanied by an increase in interleukin(IL)7R^(+)and granzyme B^(+)T cells in the tumor microenvironment.Interestingly,we observed that Ly6G^(low)G-MDSC sharply decreased after fasting treatment,and the cell surface markers and protein mass spectrometry data showed potential therapeutic targets.Mechanistic investigation revealed that glucose metabolism restriction suppressed the splenic granulocytemonocyte progenitor and the generation of colony-stimulating factors and IL-6,which both contributed to the accumulation of G-MDSC.On the other hand,glucose metabolism restriction can directly induce the apoptosis of Ly6G^(low)G-MDSC,but not Ly6G^(high)subsets.In summary,these results suggest that glucose metabolism restriction induced by fasting treatment attenuates the immune-suppressive milieu and enhances the activation of CD3^(+)T cells,providing potential solutions for enhancing immune-based cancer interventions.展开更多
Catalase is an enzyme that scavenges hydrogen peroxide in the body and has the role of protecting the organism from oxidative stress. Since catalase activity is associated with various diseases, including diabetes, sk...Catalase is an enzyme that scavenges hydrogen peroxide in the body and has the role of protecting the organism from oxidative stress. Since catalase activity is associated with various diseases, including diabetes, skin diseases like vitiligo, renal failure, and heart failure, it is important to measure its activity. However, it has been difficult to accurately evaluate catalase activity alone, because there are other substances in vivo, such as iron ions, that decompose hydrogen peroxide in addition to catalase. To solve this problem, we conducted a study to develop a method to correctly measure catalase activity from samples containing impurities with hydrogen peroxide removal activity. In this study, catalase inhibitors were added to bovine catalase solution, ferric chloride solution, cell lysates of control cells and experimentally generated catalase knockdown cells (CAT KD), and these mixtures were reacted with hydrogen peroxide to determine the percentage of hydrogen peroxide remaining in the reaction solution after a certain time. The catalase inhibitors used, 3-amino-1H-1,2,4-triazole (3-AT) and sodium azide (NaN3), inhibited the removal of hydrogen peroxide by bovine catalase at a high rate in in-vitro experiments. However, these catalase inhibitors did not inhibit hydrogen peroxide removal in the Fenton reaction of iron ion and hydrogen peroxide in in-vitro experiments. On the other hand, hydrogen peroxide removal by cell lysate was inhibited by the addition of 3-AT or NaN3. The inhibitory effect was equivalent or superior to that of CAT KD cells, in which catalase was experimentally knocked down. These results suggested that 3-AT and NaN3 specifically inhibit hydrogen peroxide removal of catalase. Through these studies, we found that when cell lysate with a catalase inhibitor was mixed with hydrogen peroxide, hydrogen peroxide that was not removed by catalase inhibition remained in the test tube after a certain time, and this residual hydrogen peroxide reflected the hydrogen peroxide removal activity of catalase. By measuring this unremoved hydrogen peroxide, it was possible to evaluate catalase activity from samples containing impurities that have hydrogen peroxide removal properties.展开更多
Hepatocellular carcinoma(HCC),the predominant form of adult liver malignancies,is a global health concern.Its dismal prognosis has prompted recent significant advances in the understanding of its etiology and pathogen...Hepatocellular carcinoma(HCC),the predominant form of adult liver malignancies,is a global health concern.Its dismal prognosis has prompted recent significant advances in the understanding of its etiology and pathogenesis.The deregulation of epigenetic mechanisms,which maintain heritable gene expression changes and chromatin organization,is implicated in the development of multiple cancers,including HCC.This review summarizes the current knowledge of epigenetic mechanisms in the pathogenesis of HCC,with an emphasis on HCC mediated by chronic hepatitis B virus infection.This review also discusses the encouraging outcomes and lessons learnt from epigenetic therapies for hematological and other solid cancers,and highlights the future potential of similar therapies in the treatment of HCC.展开更多
Objective:To evaluate the monogalactosyl diglyceride(MGDG)and digalactosyl diglyceride(DGDG)from Clinacanthus nutans(C.nutans)for their in vitro antiviral activities against herpes simplex virus type 1(HSV-1)and type ...Objective:To evaluate the monogalactosyl diglyceride(MGDG)and digalactosyl diglyceride(DGDG)from Clinacanthus nutans(C.nutans)for their in vitro antiviral activities against herpes simplex virus type 1(HSV-1)and type 2(HSV-2)by plaque reduction assay.Methods:MGDG and DGDG were extracted with chloroform from C.nutans leaves.MGDG and DGDG were separated from chloroform crude extract using column chromatography,characterized by thin layer chromatography and quantified by high performance liquid chromatography.The anti HSV-1 and 2 activity against pre-treatment and posttreatment of the compounds was evaluated using plaque reduction assay.The cytotoxicity of the extract and the compounds on Vero cells were performed by MTT assay.Results:MGDG and DGDG obtained by column chromatography showed identical profiles as standard MGDG and standard DGDG using thin layer chromatography and high performance liquid chromatography.MGDG and DGDG from C.nutans showed 100%inhibition of HSV-1 replication at the post step of infection at noncytotoxic concentration with IC50 values of 36.00 and 40.00 mg/m L,and HSV-2 at 41.00 and 43.20 mg/mL,respectively.Moreover,MGDG and DGDG from C.nutans were demonstrated to have antiherpes simplex activity at the same level as standard synthetic compounds.In contrast,pretreatment of Vero cells with MGDG and DGDG before HSV-1 and HSV-2 infection did not show inhibitory effect against these viruses.MGDG and DGDG exhibited antiviral activity against HSV-1 with selectivity index of 26.00 and 23.00 and HSV-2 of 23.30 and 21.30.Conclusions:MGDG and DGDG from C.nutans,a traditional Thai herbal medicine illustrated inhibitory activity against HSV-1 and HSV-2,probably by inhibiting the late stage of multiplication,suggesting their promising use as anti-HSV agents.展开更多
Low temperature plasma(LTP)technology has shown an outstanding application value in the pharmaceutical filed in recent ten years.This paper reviews the research advances in LTP,including its effects on enhancing or in...Low temperature plasma(LTP)technology has shown an outstanding application value in the pharmaceutical filed in recent ten years.This paper reviews the research advances in LTP,including its effects on enhancing or inhibiting drug activity,its combined use with drugs to treat cancers,its effects on the improvement of drug delivery system,its use in preparation of new inactivated virus vaccines,its use with mass spectrometry for rapid detection of drug quality,and the anti-tumor and sterilization effects of plasma-activated liquids.The paper also analyzes the challenges of LTP in the pharmaceutical filed,hoping to promote related research.展开更多
The increased vascular infl ammation is a key event in the development of atherosclerotic lesions.Antrodia cinnamomea has been shown to promote anticancerogenic activity through decreasing infl ammation.However,the po...The increased vascular infl ammation is a key event in the development of atherosclerotic lesions.Antrodia cinnamomea has been shown to promote anticancerogenic activity through decreasing infl ammation.However,the potential role of A.cinnamomea in cardiovascular diseases remains unexplored.Herein,using carotid arterial ligation models,we found that ethanol extract from A.cinnamomea(EEAC)signifi cantly inhibited neointimal hyperplasia in a dose-dependent manner,accompanied with the reduced expression of activated p65 and infl ammatory cytokines.We also show that EEAC ameliorated TNF-α-induced phosphorylation of p65 and pro-infl ammatory cytokine expression in both vascular smooth muscle cells(VSMCs)and macrophages in vitro.Mechanistically,EEAC suppressed expression levels of intercellular adhesion molecule-1(ICAM-1)and vascular cell adhesion molecule(VCAM-1)in VSMCs,which attenuates the ability of monocytes/macrophages adhesion to VSMCs.Furthermore,the expression level of these adhesion molecules and infi ltration of monocytes/macrophages were also decreased in neointimal VSMCs of arteries pretreated with EEAC.Altogether,our results reveal a novel function of A.cinnamomea in suppressing vascular infl ammation upon ligation injury during neointimal formation,likely through inhibition of infl ammatory cell infi ltration via downregulating the adhesion molecules in VSMCs.Thus,A.cinnamomea may offer a pharmacological therapy to slow down disease progression in patients with vascular injury.展开更多
基金Supported by the Oman Ministry of Higher Education,Research,and Innovation,No.BFP/RGP/HSS/24/015.
文摘Chloroquine(CQ)and hydroxychloroquine(HCQ),originally developed as anti-malarial drugs,have found a new purpose in treating various autoimmune dis-eases due to their immunomodulatory properties.These drugs work through mu-ltiple mechanisms,including inhibiting Toll-like receptor signaling,suppressing antigen presentation,and modulating autophagy.This review article provides a comprehensive analysis of the immunomodulatory effects of CQ and HCQ in several autoimmune diseases such as systemic lupus erythematosus,rheumatoid arthritis,systemic sclerosis,and others.We delve into the intricate mechanisms of action,highlighting the key immune cells involved and discussing the clinical implications of these drugs in managing autoimmune conditions.Our review covers the latest research and clinical trials,offering a comprehensive under-standing of the therapeutic potential of CQ and HCQ in autoimmune diseases.We also discuss the challenges and controversies surrounding the use of these drugs,such as their long-term side effects and the need for personalized treatment approaches.By synthesizing current knowledge and identifying areas for future research,this review aims to provide a valuable resource for healthcare profes-sionals and researchers involved in the management of autoimmune diseases.
基金Supported by The Oman Ministry of Higher Education,Research,and Innovation,No.BFP/RGP/HSS/24/015.
文摘In this editorial,we comment on the article by Sá-Oliveira et al.We focus specifi-cally on the role of platelet-rich fibrin(PRF)in modulating innate immunity to enhance wound repair.The process of wound healing is complex and involves a coordinated series of biological events,including inflammation,cell proliferation,and tissue remodeling.The innate immune system is important in the early stages of wound repair,with inflammation being a crucial initial phase in tissue rege-neration.However,the inflammatory response should be regulated,as excessive or dysregulated inflammation can impair healing.Platelet concentrates,specifi-cally PRF,have originated as promising tools to optimize the tissue repair process.PRF is a second-generation platelet concentrate,and the release of growth factors(GFs)plays a determining role in several aspects of wound healing,including promoting cell proliferation,stimulating angiogenesis,and modulating inflam-mation.PRF forms a fibrin matrix that entraps platelets and GFs.This structure allows for their sustained release over time,which is believed to provide a more favorable microenvironment for tissue repair.Recent research by Sá-Oliveira et al has provided valuable evidence supporting the efficacy of PRF in promoting wound healing.Their study,conducted on an animal model,demonstrated that PRF-based dressings were more effective in accelerating wound closure in the early stages of the healing process,enhancing tissue repair,and modulating the inflammatory response.We explore how PRF's unique properties contribute to a more controlled and effective healing process.By examining these findings,we aim to highlight PRF's potential as a promising therapeutic strategy for improved wound management.
文摘Bronchiectasis is a chronic inflammatory airway disease,and patients often suffer from recurrent airway infections leading to decreased lung function and impaired quality of life.In this study,the effects of supervised pulmonary rehabilitation training on pulmonary function,training compliance,and quality of life in patients with bronchiectasis under home rehabilitation mode are investigated.Ninety stable patients were selected,and the observation group adopted the home-supervised mode of pulmonary rehabilitation training.The results showed that the observation group’s pulmonary function indexes,quality of life,and training adherence were better than those of the control group.The differences were statistically significant(P<0.05).The supervised pulmonary rehabilitation training in home rehabilitation mode can effectively improve patients’pulmonary function and quality of life,and improve training compliance,which has good clinical application value.
文摘Based on the perspective of caring,this study constructs a whole-cycle management programme for lymphoma patients,and systematically explores the pathway of patients’health management from diagnosis to recovery by integrating literature analysis,clinical practice research,and multidisciplinary experts’consensus.Focusing on the differentiated needs of patients,the study proposes a dual-track management framework of‘precise diagnosis and treatment standard’and‘humanistic care practice’,and innovatively designs a multidisciplinary collaborative mechanism,an information-based follow-up platform,and a social support network.Through the role of‘care consultant’,the programme connects the medical team with the individual needs of patients,strengthens treatment compliance and improves the quality of life,and provides a theoretical basis and practical reference for the optimization of the whole management mode of lymphoma patients.
基金supported by the National Key Research and Development Program of China(2022YFF1100300)National Natural Science Foundation of China(32272328)+2 种基金Natural Science Foundation of Hebei Province(H2024206177)Hebei Provincial Key Laboratory of Nutrition and Health(2023YDYY-KF05)College Students’Innovative Entrepreneurial Training Plan Program of Hebei Medical University(USIP2023232)。
文摘Vascular oxidative stress serves as a pathological foundation for various vascular injury-related diseases,including atherosclerosis,hypertension,restenosis,and abdominal aortic aneurysms.Recent studies have indicated that intestinal flora-derived metabolites,especially phenylacetylglutamine(PAGln)and phenylacetylglycine(PAGly),may contribute to the promotion of thrombosis,heart failure,and other related conditions.Aucubin(AU),an iridoid glycoside,has been shown to exhibit anti-cardiovascular properties.Nevertheless,the precise role and underlying mechanisms by which AU mitigates PAGly-induced vascular injury remain poorly understood.Our results indicated that PAGln/PAGly promoted oxidative stress in vascular endothelial cells(ECs)and vascular smooth muscle cells(VSMCs)in vitro and in vivo.Network pharmacology suggest that AU may possess the capacity to regulate lipid and atherosclerosis,and reactive oxygen species(ROS)processes.We found that AU penetrated the blood vessels and mitigated oxidative stress induced by PAGln/PAGly.Mechanistically,combining the results from intersection analysis between the targets of AU and vascular diseases and molecular docking,we found that tumor necrosis factor(TNF)may be the potential target of AU.Further DARTS and molecular docking analysis demonstrated that AU bound to recombinant TNF-α,and AU could interact with multiple amino acid residues of TNF-α,including Asn-92 and Phe-144.Additionally,PAGly upregulated the level of soluble TNF-α(sTNF-α)in mouse VSMCs and plasma,and promoted the interaction between sTNF-αand TNF receptor 1(TNFR1),whereas AU inhibited this interaction.Both AU and Infliximab,a specific monoclonal antibody of TNF-α,inhibit TNF-α-induced ROS production.In summary,our results revealed that TNF-αis a cellular target of AU,and the interaction between AU and s TNF-αmay mitigate PAGln/PAGly-induced vascular oxidative stress by inhibiting the interaction of TNF-α-TNFR1.
文摘Alcohol-associated liver disease(ALD)is a major global health concern,contributing to liver injury,morbidity,and mortality.Elafibranor(EFN),a dual peroxisome proliferator-activated receptorα/δagonist,has shown promise as a therapeutic candidate in preclinical studies.EFN reduces liver fibrosis by inhibiting lipid accumulation,apoptosis,and inflammatory pathways(LPS/TLR4/NF-κB),while enhancing autophagy and antioxidant responses.It also improves intestinal barrier function and modulates gut microbiota,reducing endotoxin-producing bacteria and increasing beneficial species.By strengthening the intestinal barrier and suppressing pro-inflammatory mediators like tumor necrosis factor-alpha and interleukin-6,EFN mitigates hepatic stellate cell activation and fibrogenic signaling.Macrophages play a central role in ALD progression,and EFN’s ability to modulate macrophage activity further highlights its anti-inflammatory properties.This review emphasizes EFN’s dual-targeted approach,addressing both hepatic and intestinal dysfunctions,distinguishing it from conventional ALD treatments.While preclinical results are promising,EFN remains under clinical investigation,with ongoing trials evaluating its safety and efficacy.Future research should focus on elucidating EFN’s molecular mechanisms and advancing its clinical application to establish its therapeutic potential in human populations.EFN represents a novel,comprehensive strategy for ALD management,targeting both liver and gut pathologies.
基金supported by the National Key Research and Development Program of China(No.2018YFE0207300)Beijing Natural Science Foundation(No.M23008)+1 种基金the National High Level Hospital Clinical Research Funding(No.2022-PUMCH-B-124)the National High Level Hospital Clinical Research Funding(No.2022-PUMCH-A-057)。
文摘Varicocele(VC)is a common cause of male infertility,yet there is a lack of molecular information for VC-associated male infertility.This study investigated alterations in the seminal plasma metabolomic and lipidomic profiles of infertile male VC patients.Twenty infertile males with VC and twenty-three age-matched healthy controls(HCs)were recruited from Peking Union Medical College Hospital(Beijing,China)between October 2019 and April 2021.Untargeted metabolite and lipid profiles from seminal plasma were analyzed using mass spectrometry.Four hundred and seventy-six metabolites and seventeen lipids were significantly different in infertile male VC patients compared to HCs.The top enriched pathways among these significantly different metabolites are protein digestion and absorption,aminoacyl-transfer RNA(tRNA)biosynthesis,and biosynthesis of amino acids.Different key lipid species,including triglyceride(TG),diacylglycerol(DG),ceramides(Cer),and phosphatidylserine(PS),varied betweenVC and HC groups.The distinct metabolites and lipids were moderately correlated.DL-3-phenyllactic acid is a potential diagnostic biomarker for VC-related male infertility(area under the curve[AUC]=0.893),positively correlating with sperm count,concentration,and motility.Furthermore,DL-3-phenyllactic acid is the only metabolite shared by all four comparisons(VC vs HC,VC-induced oligoasthenospermia[OAS]vs VC-induced asthenospermia[AS],OAS vs HC,and AS vs HC).DL-3-phenyllactic acid significantly decreased in OAS than AS.Metabolite-targeting gene analysis revealed carbonic anhydrase 9(CA9)might be the strongest candidate associated with the onset and severity of VC.The seminal plasma metabolite and lipid profiles of infertile males with VC differ significantly from those of HCs.DL-3-phenyllactic acid could be a promising biomarker.
基金supported by Princess Nourah bint Abdulrahman University Researchers Supporting Project Number(PNURSP2025R317),Princess Nourah bintAbdulrahman University,Riyadh,Saudi Arabia.
文摘Aspergillus species produce aflatoxins and raise concerns about food safety in departmental stores and manufacturing mills.To address the risks posed by aflatoxins,and to advise the public on the highest quality rice that serves as a nutritious food source,an inquiry following the guidelines outlined in both local and international standards of food safety for the presence of aflatoxins is an essential requirement.Therefore,16 white rice samples were selected randomly from low/high socio-economic departmental stores from 16 different localities.Grind powdered rice filtrate was extracted using chloroform.The filtrate applied on TLC plates and the amount of aflatoxin and moisture contents were determined.In the non-infected rice,moisture content was low(9.08%)whereas high[13.65%>12%(standard>value)]in infected ones.Four out of 8 samples of low-quality rice were contaminated with AFB_(1) and AFB_(2)(ranging from 22.2 to 29.3μg/kg).All the samples except one(22.3μg/kg)from high-quality rice were certified fit despite the contamination with AFB_(1).Furthermore,phylogenetic analysis showed Aspergillus flavus from unfit low(Long grain brown and Brown basmati)and high-quality(Basmati-198)rice whereas A.parasiticus from unfit low-quality Medium-grain brown rice.The presented research proves that the detection of fungi and aflatoxins in rice grains poses a huge risk to the health of consumers.Therefore,it is necessary to check the rice grains before distribution.
文摘This editorial introduces the potential of targeting macrophage function for diabetic cardiomyopathy(DCM)treatment by dipeptidyl peptidase-4(DPP-4)inhibitors.Zhang et al studied teneligliptin,a DPP-4 inhibitor used for diabetes management,and its potential cardioprotective effects in a diabetic mouse model.They suggested teneligliptin administration may reverse established markers of DCM,including cardiac hypertrophy and compromised function.It also inhibited the NLRP3 inflammasome and reduced inflammatory cytokine production in diabetic mice.Macrophages play crucial roles in DCM pathogenesis.Chronic hyperglycemia disturbs the balance between pro-inflammatory(M1)and antiinflammatory(M2)macrophages,favoring a pro-inflammatory state contributing to heart damage.Here,we highlight the potential of DPP-4 inhibitors to modulate macrophage function and promote an anti-inflammatory environment.These compounds may achieve this by elevating glucagon-like peptide-1 levels and potentially inhibiting the NLRP3 inflammasome.Further studies on teneligliptin in combination with other therapies targeting different aspects of DCM could be suggested for developing more effective treatment strategies to improve cardiovascular health in diabetic patients.
基金This work was supported by JSPS KAKENHI(Nos.20K10449 and 23K09645)。
文摘Hernandezine(Her),a bisbenzylisoquinoline alkaloid extracted from Thalictrum flavum,is recognized for its range of biological activities inherent to this herbal medicine.Despite its notable properties,the anti-cancer effects of Her have remained largely unexplored.In this study,we elucidated that Her significantly induced cytotoxicity in cancer cells through the activation of apoptosis and necroptosis mechanisms.Furthermore,Her triggered autophagosome formation by activating the AMPK and ATG5 conjugation systems,leading to LC3 lipidation.Our findings revealed that Her caused damage to the mitochondrial membrane,with the damaged mitochondria undergoing mitophagy,as evidenced by the elevated expression of mitophagy markers.Conversely,Her disrupted autophagic flux,demonstrated by the upregulation of p62 and accumulation of autolysosomes,as observed in the RFP-GFP-LC3 reporter assay.Initially,we determined that Her did not prevent the fusion of autophagosomes and lysosomes.However,it inhibited the maturation of cathepsin D and increased lysosomal pH,indicating an impairment of lysosomal function.The use of the early-stage autophagy inhibitor,3-methyladenine(3-MA),did not suppress LC3II,suggesting that Her also induces noncanonical autophagy in autophagosome formation.The application of Bafilomycin A1,an inhibitor of noncanonical autophagy,diminished the recruitment of ATG16L1 and the accumulation of LC3II by Her,thereby augmenting Her-induced cell death.These observations imply that while autophagy initially plays a protective role,the disruption of the autophagic process by Her promotes programmed cell death.This study provides the first evidence of Her’s dual role in inducing apoptosis and necroptosis while also initiating and subsequently impairing autophagy to promote apoptotic cell death.These insights contribute to a deeper understanding of the mechanisms underlying programmed cell death,offering potential avenues for enhancing cancer prevention and therapeutic strategies.
文摘Esophageal squamous cell carcinoma(ESCC)is a substantial global health burden.Immune escape mechanisms are important in ESCC progression,enabling cancer cells to escape the surveillance of the host immune system.One key player in this process is the Aryl Hydrocarbon Receptor(AhR),which influences multiple cellular processes,including proliferation,differentiation,metabolism,and immune regulation.Dysregulated AhR signaling participates in ESCC development by stimulating carcinogenesis,epithelial-mesenchymal transition,and immune escape.Targeting AhR signaling is a potential therapeutic approach for ESCC,with AhR ligands showing efficacy in preclinical studies.Additionally,modification of AhR ligands and combination therapies present new opportunities for therapeutic intervention.This review aims to address the knowledge gap related to the role of AhR signaling in ESCC pathogenesis and immune escape.
基金supported by the National Key R&D Program of China (2019YFA0508502/3 and 2021YFC2300604)the Natural Science Foundation of China (Reference numbers 82388201, 82241216, and 32270963)+1 种基金the Research Funds of Center for Advanced Interdisciplinary Science and Biomedicine of IHM (QYZD20220008)the Anhui Key Research and Development Plan (Reference number 2023z04020011)。
文摘Objective: The human cluster of differentiation(CD)300A, a type-I transmembrane protein with immunoreceptor tyrosine-based inhibitory motifs, was investigated as a potential immune checkpoint for human natural killer(NK) cells targeting hematologic malignancies(HMs).Methods: We implemented a stimulation system involving the CD300A ligand, phosphatidylserine(PS), exposed to the outer surface of malignant cells. Additionally, we utilized CD300A overexpression, a CD300A blocking system, and a xenotransplantation model to evaluate the impact of CD300A on NK cell efficacy against HMs in in vitro and in vivo settings. Furthermore, we explored the association between CD300A and HM progression in patients.Results: Our findings indicated that PS hampers the function of NK cells. Increased CD300A expression inhibited HM lysis by NK cells. CD300A overexpression shortened the survival of HM-xenografted mice by impairing transplanted NK cells. Blocking PS–CD300A signals with antibodies significantly amplified the expression of lysis function-related proteins and effector cytokines in NK cells, thereby augmenting the ability to lyse HMs. Clinically, heightened CD300A expression correlated with shorter survival and an “exhausted” phenotype of intratumoral NK cells in patients with HMs or solid tumors.Conclusions: These results propose CD300A as a potential target for invigorating NK cell-based treatments against HMs.
基金supported by the Postdoctoral Research Funds of Hebei Medical University(30705010016-3759)Natural Science Foundation of China(32272328)+4 种基金Natural Science Foundation of Hebei Province(B2022321001)National Key Research Project of Hebei Province(20375502D)Postdoctoral Research Project of Hebei Province(B2022003031)Science and Technology Research Program of Hebei Provincial Colleges(QN2023229)Hebei Provincial Key Laboratory of Nutrition and Health(2023YDYY-KF05)。
文摘Intermittent fasting can benefit breast cancer patients undergoing chemotherapy or immunotherapy.However,it is still uncertain how to select immunotherapy drugs to combine with intermittent fasting.Herein we observed that two cycles of fasting treatment significantly inhibited breast tumor growth and lung tissue metastasis,as well as prolonged overall survival in mice bearing 4T1 and 4T07 breast cancer.During this process,both the immunosuppressive monocytic-(M-)and granulocytic-(G-)myeloid-derived suppressor cell(MDSC)decreased,accompanied by an increase in interleukin(IL)7R^(+)and granzyme B^(+)T cells in the tumor microenvironment.Interestingly,we observed that Ly6G^(low)G-MDSC sharply decreased after fasting treatment,and the cell surface markers and protein mass spectrometry data showed potential therapeutic targets.Mechanistic investigation revealed that glucose metabolism restriction suppressed the splenic granulocytemonocyte progenitor and the generation of colony-stimulating factors and IL-6,which both contributed to the accumulation of G-MDSC.On the other hand,glucose metabolism restriction can directly induce the apoptosis of Ly6G^(low)G-MDSC,but not Ly6G^(high)subsets.In summary,these results suggest that glucose metabolism restriction induced by fasting treatment attenuates the immune-suppressive milieu and enhances the activation of CD3^(+)T cells,providing potential solutions for enhancing immune-based cancer interventions.
文摘Catalase is an enzyme that scavenges hydrogen peroxide in the body and has the role of protecting the organism from oxidative stress. Since catalase activity is associated with various diseases, including diabetes, skin diseases like vitiligo, renal failure, and heart failure, it is important to measure its activity. However, it has been difficult to accurately evaluate catalase activity alone, because there are other substances in vivo, such as iron ions, that decompose hydrogen peroxide in addition to catalase. To solve this problem, we conducted a study to develop a method to correctly measure catalase activity from samples containing impurities with hydrogen peroxide removal activity. In this study, catalase inhibitors were added to bovine catalase solution, ferric chloride solution, cell lysates of control cells and experimentally generated catalase knockdown cells (CAT KD), and these mixtures were reacted with hydrogen peroxide to determine the percentage of hydrogen peroxide remaining in the reaction solution after a certain time. The catalase inhibitors used, 3-amino-1H-1,2,4-triazole (3-AT) and sodium azide (NaN3), inhibited the removal of hydrogen peroxide by bovine catalase at a high rate in in-vitro experiments. However, these catalase inhibitors did not inhibit hydrogen peroxide removal in the Fenton reaction of iron ion and hydrogen peroxide in in-vitro experiments. On the other hand, hydrogen peroxide removal by cell lysate was inhibited by the addition of 3-AT or NaN3. The inhibitory effect was equivalent or superior to that of CAT KD cells, in which catalase was experimentally knocked down. These results suggested that 3-AT and NaN3 specifically inhibit hydrogen peroxide removal of catalase. Through these studies, we found that when cell lysate with a catalase inhibitor was mixed with hydrogen peroxide, hydrogen peroxide that was not removed by catalase inhibition remained in the test tube after a certain time, and this residual hydrogen peroxide reflected the hydrogen peroxide removal activity of catalase. By measuring this unremoved hydrogen peroxide, it was possible to evaluate catalase activity from samples containing impurities that have hydrogen peroxide removal properties.
文摘Hepatocellular carcinoma(HCC),the predominant form of adult liver malignancies,is a global health concern.Its dismal prognosis has prompted recent significant advances in the understanding of its etiology and pathogenesis.The deregulation of epigenetic mechanisms,which maintain heritable gene expression changes and chromatin organization,is implicated in the development of multiple cancers,including HCC.This review summarizes the current knowledge of epigenetic mechanisms in the pathogenesis of HCC,with an emphasis on HCC mediated by chronic hepatitis B virus infection.This review also discusses the encouraging outcomes and lessons learnt from epigenetic therapies for hematological and other solid cancers,and highlights the future potential of similar therapies in the treatment of HCC.
基金Supported by Department of Medical SciencesMinistry of Public Health,Thailand(Grant No.RMSc-3Nk-RD-27-2011)
文摘Objective:To evaluate the monogalactosyl diglyceride(MGDG)and digalactosyl diglyceride(DGDG)from Clinacanthus nutans(C.nutans)for their in vitro antiviral activities against herpes simplex virus type 1(HSV-1)and type 2(HSV-2)by plaque reduction assay.Methods:MGDG and DGDG were extracted with chloroform from C.nutans leaves.MGDG and DGDG were separated from chloroform crude extract using column chromatography,characterized by thin layer chromatography and quantified by high performance liquid chromatography.The anti HSV-1 and 2 activity against pre-treatment and posttreatment of the compounds was evaluated using plaque reduction assay.The cytotoxicity of the extract and the compounds on Vero cells were performed by MTT assay.Results:MGDG and DGDG obtained by column chromatography showed identical profiles as standard MGDG and standard DGDG using thin layer chromatography and high performance liquid chromatography.MGDG and DGDG from C.nutans showed 100%inhibition of HSV-1 replication at the post step of infection at noncytotoxic concentration with IC50 values of 36.00 and 40.00 mg/m L,and HSV-2 at 41.00 and 43.20 mg/mL,respectively.Moreover,MGDG and DGDG from C.nutans were demonstrated to have antiherpes simplex activity at the same level as standard synthetic compounds.In contrast,pretreatment of Vero cells with MGDG and DGDG before HSV-1 and HSV-2 infection did not show inhibitory effect against these viruses.MGDG and DGDG exhibited antiviral activity against HSV-1 with selectivity index of 26.00 and 23.00 and HSV-2 of 23.30 and 21.30.Conclusions:MGDG and DGDG from C.nutans,a traditional Thai herbal medicine illustrated inhibitory activity against HSV-1 and HSV-2,probably by inhibiting the late stage of multiplication,suggesting their promising use as anti-HSV agents.
基金supported by the National Natural Science Foundation of China(Grant No.51677146)Project of Independent Innovative Experiment for Postgraduates in Medicine in Xi’an Jiaotong University(Grant No.JSCX-2018-014)the Special Scientific Research Project Funds of Shaanxi Province(Grant No.18JK1102).
文摘Low temperature plasma(LTP)technology has shown an outstanding application value in the pharmaceutical filed in recent ten years.This paper reviews the research advances in LTP,including its effects on enhancing or inhibiting drug activity,its combined use with drugs to treat cancers,its effects on the improvement of drug delivery system,its use in preparation of new inactivated virus vaccines,its use with mass spectrometry for rapid detection of drug quality,and the anti-tumor and sterilization effects of plasma-activated liquids.The paper also analyzes the challenges of LTP in the pharmaceutical filed,hoping to promote related research.
基金This work was supported by the National Key Research Project of China(2019YFC1606400)Major Public Welfare Projects in Henan Province(201300110200)+4 种基金National Key Research Project of Hebei Province(20375502D)Natural Science Foundation of Hebei Province(H2019206212)High-level Talent Funding Project of Hebei Province(A201905006)Fund of National R&D Center for Edible Fungus Processing Technology,Henan University(20200109)the Open Fund from Beijing Advanced Innovation Center for Food Nutrition and Human Health(20182025).
文摘The increased vascular infl ammation is a key event in the development of atherosclerotic lesions.Antrodia cinnamomea has been shown to promote anticancerogenic activity through decreasing infl ammation.However,the potential role of A.cinnamomea in cardiovascular diseases remains unexplored.Herein,using carotid arterial ligation models,we found that ethanol extract from A.cinnamomea(EEAC)signifi cantly inhibited neointimal hyperplasia in a dose-dependent manner,accompanied with the reduced expression of activated p65 and infl ammatory cytokines.We also show that EEAC ameliorated TNF-α-induced phosphorylation of p65 and pro-infl ammatory cytokine expression in both vascular smooth muscle cells(VSMCs)and macrophages in vitro.Mechanistically,EEAC suppressed expression levels of intercellular adhesion molecule-1(ICAM-1)and vascular cell adhesion molecule(VCAM-1)in VSMCs,which attenuates the ability of monocytes/macrophages adhesion to VSMCs.Furthermore,the expression level of these adhesion molecules and infi ltration of monocytes/macrophages were also decreased in neointimal VSMCs of arteries pretreated with EEAC.Altogether,our results reveal a novel function of A.cinnamomea in suppressing vascular infl ammation upon ligation injury during neointimal formation,likely through inhibition of infl ammatory cell infi ltration via downregulating the adhesion molecules in VSMCs.Thus,A.cinnamomea may offer a pharmacological therapy to slow down disease progression in patients with vascular injury.
