Blood glucose-lowering activity of protocatechuic acid is mediated by inhibiting a-glucosidase

α-Glucosidase inhibitors are effective in controlling postprandial hyperglycemia,which play crucial roles in the management of type 2 diabetes.Protocatechuic acid(PCA)is one of phenolic acids existing not only in various plant foods but also as a major microbial metabolite of dietary anthocyanins in the large colon.The present study investigated the inhibitory mechanism of PCA on a-glucosidase in vitro and examined its effect on postprandial blood glucose levels in vivo.Results from in vitro experiments demonstrated that PCA was a mix-type inhibitor of a-glucosidase.Driven by hydrogen bonds and van der Waals interactions,PCA reversibly bound withα-glucosidase to form a stable a-glucosidase-PCA complex in a spontaneous manner.The computational simulation found that PCA could insert into the active cavity of a-glucosidase and establish hydrogen bonds with catalytic amino acid residues.PCA binding aroused the steric hindrance for substrates to enter active sites and caused the structural changes of interacted catalytic amino acid residues.PCA also exhibited postprandial hypoglycemic capacity in diabetic mice.This study may provide the theoretical basis for the application of PCA as an active ingredient of functional foods in dietary management of diabetes.

CD137 signaling aggravates myocardial ischemia-reperfusion injury by inhibiting mitophagy mediated NLRP3 inflammasome activation

BACKGROUND The inflammatory response caused by the NLRP3 is closely related to the formation of myocardial ischemiareperfusion injury.Costimulatory receptor CD137 and its ligand play a crucial role in regulating the inflammatory immune response in atherosclerosis,which is the fundamental cause of cardiovascular diseases.However,the roles of CD137 signaling in the process of myocardial ischaemia-reperfusion(IR)injury remain unknown.METHODS Genetic ablation was used to determine the functional significance of CD137 in myocardial IR injury.Expression of CD137 was examined by Western-blot,quantitative real-time polymerase chain reaction,and immunohistochemistry in a murine IR model by coronary artery ligation.Even’s blue-TTC staining and echocardiography to evaluate the severity of myocardial IR injury.Furthermore,HL-1 cardiomyocytes treated with agonist-CD137 recombinant protein were used to explore the underlying mechanism in CD137 signaling-induced NLRP3 inflammasome activation in response to hypoxia/reoxygenation or LPS/ATP.RESULTS We demonstrated that CD137 knockout significantly improved cardiac function,accompanied by a markedly reduced NLRP3-mediated inflammatory response and IA/AAR which were reversed by mitophagy inhibitor Mdivi-1.Activating CD137 signaling significantly inhibited mitophagy and provoked NLRP3-mediated inflammatory response in H/R-injured or LPS-primed and ATP-stimulated HL-1 cardiomyocytes,the effects of which could be abolished by either anti-CD137 or mitophagy activator FCCP.Besides,mitochondrial ROS was augmented by activating CD137 signaling through the suppression of mitophagy.CONCLUSIONS Our results reveal that activating CD137 signaling aggravates myocardial IR injury by upregulating NLRP3 inflammasome activation via suppressing mitophagy and promoting mtROS generation.

Porphyromonas gingivalis,a periodontal pathogen,impairs post-infarcted myocardium by inhibiting autophagosome–lysosome fusion

While several previous studies have indicated the link between periodontal disease (PD) and myocardial infarction (MI), theunderlying mechanisms remain unclear. Autophagy, a cellular quality control process that is activated in several diseases, includingheart failure, can be suppressed by Porphyromonas gingivalis (P.g.). However, it is uncertain whether autophagy impairment byperiodontal pathogens stimulates the development of cardiac dysfunction after MI. Thus, this study aimed to investigate therelationship between PD and the development of MI while focusing on the role of autophagy. Neonatal rat cardiomyocytes(NRCMs) and MI model mice were inoculated with wild-type P.g. or gingipain-deficient P.g. to assess the effect of autophagyinhibition by P.g. Wild-type P.g.-inoculated NRCMs had lower cell viability than those inoculated with gingipain-deficient P.g. Thisstudy also revealed that gingipains can cleave vesicle-associated membrane protein 8 (VAMP8), a protein involved in lysosomalsensitive factor attachment protein receptors (SNAREs), at the 47th lysine residue, thereby inhibiting autophagy. Wild-type P.g.-inoculated MI model mice were more susceptible to cardiac rupture, with lower survival rates and autophagy activity thangingipain-deficient P.g.-inoculated MI model mice. After inoculating genetically modified MI model mice (VAMP8-K47A) with wildtype P.g., they exhibited significantly increased autophagy activation compared with the MI model mice inoculated with wild-typeP.g., which suppressed cardiac rupture and enhanced overall survival rates. These findings suggest that gingipains, which arevirulence factors of P.g., impair the infarcted myocardium by cleaving VAMP8 and disrupting autophagy. This study confirms thestrong association between PD and MI and provides new insights into the potential role of autophagy in this relationship.

Protease inhibitor ASP enhances freezing tolerance by inhibiting protein degradation in kumquat

Cold acclimation is a complex biological process leading to the development of freezing tolerance in plants.In this study,we demonstrated that cold-induced expression of protease inhibitor FmASP in a Citrus-relative species kumquat[Fortunella margarita(Lour.)Swingle]contributes to its freezing tolerance by minimizing protein degradation.Firstly,we found that only cold-acclimated kumquat plants,despite extensive leaf cellular damage during freezing,were able to resume their normal growth upon stress relief.To dissect the impact of cold acclimation on this anti-freezing performance,we conducted protein abundance assays and quantitative proteomic analysis of kumquat leaves subjected to cold acclimation(4◦C),freezing treatment(−10◦C)and post-freezing recovery(25◦C).FmASP(Against Serine Protease)and several non-specific proteases were identified as differentially expressed proteins induced by cold acclimation and associated with stable protein abundance throughout the course of low-temperature treatment.FmASP was further characterized as a robust inhibitor of multiple proteases.In addition,heterogeneous expression of FmASP in Arabidopsis confirmed its positive role in freezing tolerance.Finally,we proposed a working model of FmASP and illustrated how this extracellular-localized protease inhibitor protects proteins from degradation,therebymaintaining essential cellular function for post-freezing recovery.These findings revealed the important role of protease inhibition in freezing response and provide insights on how this role may help develop new strategies to enhance plant freezing tolerance.

Three novel dendritic chitosan derivatives for inhibiting acid corrosion of petroleum pipelines

In the process of exploration and development of oil and gas fields, the acidic environment of oil reservoir, production and transport processes cause corrosion of pipelines and equipment, resulting in huge economic losses and production safety risks. Corrosion inhibitors were widely used in oil industry because of simple operation process and economical. In this study, three environmentally friendly corrosion inhibitors were synthesized based on the natural polysaccharide chitosan. Corrosion inhibition of three dendritic chitosan derivatives (We name them BH, CH and DH) on mild steel in 1 mol/L HCl solution with natural ventilation system was evaluated by weight loss experiment, electrochemical analysis and surface morphology characterization. The experimental results showed that when the three dendritic chitosan derivatives added in the corrosive medium were 500 mg L^(−1), the corrosion inhibition efficiencies were all more than 80%. Based on quantum chemical calculation, inhibition mechanisms of three dendritic chitosan derivatives were investigated according to molecular structures. The results showed that the benzene ring, Schiff base and N atom contained in the molecule were the active centers of electron exchange, which were more likely to form a film on the carbon steel surface, thereby slowing or inhibiting corrosion. The results also predicted the corrosion inhibition effect BH > DH > CH, which was consistent with the experimental conclusion.

ZBP1(DAI/DLM-1) promotes osteogenic differentiation while inhibiting adipogenic differentiation in mesenchymal stem cells through a positive feedback loop of Wnt/β-catenin signaling

The lineage specification of mesenchymal stem/stromal cells(MSCs) is tightly regulated by a wide range of factors. Recently, the versatile functions of ZBP1(also known as DAI or DLM-1) have been reported in the blood circulation and immune systems.However, the biological function of ZBP1 during the lineage specification of MSCs is still unknown. In the present study, we found that ZBP1 was upregulated during osteogenesis but downregulated during adipogenesis in mouse bone marrow-derived MSCs(m BMSCs). ZBP1 was highly expressed in osteoblasts but expressed at a relatively low level in marrow adipocytes. Knockdown of ZBP1 inhibited alkaline phosphataseactivity, extracellular matrix mineralization, and osteogenesis-related gene expression in vitro and reduced ectopic bone formation in vivo. Knockdown of ZBP1 also promoted adipogenesis in MSCs in vitro. Conversely, the overexpression of ZBP1 increased the osteogenesis but suppressed the adipogenesis of MSCs. When the expression of ZBP1 was rescued, the osteogenic capacity of ZBP1-depleted m BMSCs was restored at both the molecular and phenotypic levels.Furthermore, we demonstrated that ZBP1, a newly identified target of Wnt/β-catenin signaling, was required for β-catenin translocation into nuclei. Collectively, our results indicate that ZBP1 is a novel regulator of bone and fat transdifferentiation via Wnt/β-catenin signaling.

Molecular mechanisms of inhibiting glucosyltransferases for biofilm formation in Streptococcus mutans

Glucosyltransferases(Gtfs)play critical roles in the etiology and pathogenesis of Streptococcus mutans(S.mutans)-mediated dental caries including early childhood caries.Gtfs enhance the biofilm formation and promotes colonization of cariogenic bacteria by generating biofilm extracellular polysaccharides(EPSs),the key virulence property in the cariogenic process.Therefore,Gtfs have become an appealing target for effective therapeutic interventions that inhibit cariogenic biofilms.Importantly,targeting Gtfs selectively impairs the S.mutans virulence without affecting S.mutans existence or the existence of other species in the oral cavity.Over the past decade,numerous Gtfs inhibitory molecules have been identified,mainly including natural and synthetic compounds and their derivatives,antibodies,and metal ions.These therapeutic agents exert their inhibitory role in inhibiting the expression gtf genes and the activities and secretion of Gtfs enzymes with a wide range of sensitivity and effectiveness.Understanding molecular mechanisms of inhibiting Gtfs will contribute to instructing drug combination strategies,which is more effective for inhibiting Gtfs than one drug or class of drugs.This review highlights our current understanding of Gtfs activities and their potential utility,and discusses challenges and opportunities for future exploration of Gtfs as a therapeutic target.

Transcriptomic and metabolomic analyses reveal that melatonin promotes melon root development under copper stress by inhibiting jasmonic acid biosynthesis

Melatonin has been shown to alleviate the effects of abiotic stress and to regulate plant development.Copper,a common heavy metal and soil pollutant,can suppress plant growth and development.In this work,we explored the protective effects of exogenous melatonin on lateral root formation in response to copper stress using melon seeds subjected to three germination treatments:CK1(control),CK2(300μmol/L CuSO4),and MT3(300μmol/L melatonin+300μmol/L CuSO4).Melatonin pretreatment increased the antioxidant enzyme activities and root vigor,and decreased the proline and malondialdehyde(MDA)contents in the roots of copper-stressed melon seedlings.We then used transcriptomic and metabolomic analyses to explore the mechanisms by which exogenous melatonin protects against copper stress.There were 70 significant differentially expressed genes(DEGs)(28 upregulated,42 downregulated)and 318 significantly differentially expressed metabolites(DEMs)(168 upregulated,150 downregulated)between the MT3 and CK2 treatments.Melatonin pretreatment altered the expression of genes related to redox and cell wall formation processes.In addition,we found that members of the AP2/ERF,BBR/BPC,GRAS,and HD-ZIP transcription factor families may have vital roles in lateral root development.Melatonin also increased the level of Glutathione(GSH),which chelates excess Cu^(2+).The combined transcriptomic and metabolomic analysis revealed DEGs and DEMs involved in jasmonic acid(JA)biosynthesis,including four lipoxygenase-related genes and two metabolites(linoleic acid and lecithin)related to melatonin’s alleviation effect on copper toxicity.This research elucidated the molecular mechanisms of melatonin’s protective effects in copper-stressed melon.

miR-4651 inhibits cell proliferation of gingival mesenchymal stem cells by inhibiting HMGA2 under nifedipine treatment

Drug-induced gingival overgrowth(DIGO) is recognized as a side effect of nifedipine(NIF);however, the underlying molecular mechanisms remain unknown. In this study, we found that overexpressed mi R-4651 inhibits cell proliferation and induces G0/G1-phase arrest in gingival mesenchymal stem cells(GMSCs) with or without NIF treatment. Furthermore, sequential window acquisition of all theoretical mass spectra(SWATH-MS) analysis, bioinformatics analysis, and dual-luciferase report assay results confirmed that high-mobility group AT-hook 2(HMGA2) is the downstream target gene of mi R-4651. Overexpression of HMGA2 enhanced GMSC proliferation and accelerated the cell cycle with or without NIF treatment. The present study demonstrates that mi R-4651 inhibits the proliferation of GMSCs and arrests the cell cycle at the G0/G1 phase by upregulating cyclin D and CDK2 while downregulating cyclin E through inhibition of HMGA2 under NIF stimulation. These findings reveal a novel mechanism regulating DIGO progression and suggest the potential of mi R-4651 and HMGA2 as therapeutic targets.

miR-140-3p enhanced the osteo/odontogenic differentiation of DPSCs via inhibiting KMT5B under hypoxia condition

Human dental pulp stem cells(DPSCs)have emerged as an important source of stem cells in the tissue engineering,and hypoxia will change various innate characteristics of DPSCs and then affect dental tissue regeneration.Nevertheless,little is known about the complicated molecular mechanisms.In this study,we aimed to investigate the influence and mechanism of miR-140-3p on DPSCs under hypoxia condition.Hypoxia was induced in DPSCs by Cobalt chloride(CoCl_(2))treatment.The osteo/dentinogenic differentiation capacity of DPSCs was assessed by alkaline phosphatase(ALP)activity,Alizarin Red S staining and main osteo/dentinogenic markers.A luciferase reporter gene assay was performed to verify the downstream target gene of miR-140-3p.This research exhibited that miR-140-3p promoted osteo/dentinogenic differentiation of DPSCs under normoxia environment.Furthermore,miR-140-3p rescued the CoCl_(2)-induced decreased osteo/odontogenic differentiation potentials in DPSCs.Besides,we investigated that miR-140-3p directly targeted lysine methyltransferase 5B(KMT5B).Surprisingly,we found inhibition of KMT5B obviously enhanced osteo/dentinogenic differentiation of DPSCs both under normoxia and hypoxia conditions.In conclusion,our study revealed the role and mechanism of miR-140-3p for regulating osteo/dentinogenic differentiation of DPSCs under hypoxia,and discovered that miR-140-3p and KMT5B might be important targets for DPSC-mediated tooth or bone tissue regeneration.

Inducing α-synuclein compaction: a new strategy for inhibiting α-synuclein aggregation?

Proteins might misfold during translation and folding or even once they are in their native states, due to stochastic fluctuations, destabilizing mutations or cellular stress. Aberrant protein species are usually detected and either refolded or cleared by the protein quality control machinery (Ciechanover and Kwon, 2015). When misfolded protein conformers cannot be degraded, they tend to self-assemble to form aggregates, a characteristic of many neurodegenerative diseases.

LsAP2 regulates leaf morphology by inhibiting CIN-like TCP transcription factors and repressing LsKAN2 in lettuce

Leaf size and flatness directly affect photosynthesis and are closely related to agricultural yield.The final leaf size and shape are coordinately determined by cell proliferation,differentiation,and expansion during leaf development.Lettuce(Lactuca sativa L.)is one of the most important leafy vegetables worldwide,and lettuce leaves vary in shape and size.However,the molecular mechanisms of leaf development in lettuce are largely unknown.In this study,we showed that the lettuce APETALA2(LsAP2)gene regulates leaf morphology.LsAP2 encodes a transcriptional repressor that contains the conserved EAR motif,which mediates interactions with the TOPLESS/TOPLESS-RELATED(JPL/TPR)corepressors.Overexpression of LsAP2 led to small and crinkly leaves,and many bulges were seen on the surface of the leaf blade.LsAP2 physically interacted with the CINCINNATA(CIN)-like TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTOR(TCP)transcription factors and inhibited their transcriptional activation activity.RNA sequencing analysis showed that LsAP2 affected the expression of auxin-and polarity-related genes.In addition,LsAP2 directly repressed the abaxial identity gene KANAD12(LsKAN2).Together,these results indicate that LsAP2 regulates leaf morphology by inhibiting CIN-like TCP transcription factors and repressing LsKAN2,and our work provides insights into the regulatory mechanisms of leaf development in lettuce.

CONDITIONED MEDIUM OF HUMAN NASOPHARYNGEAL CARCINOMA EPITHELIOID CELL LINE CNE_(1) CONTAINED THE ACTIVITIES OF TRANSFORMED GROWTH-INHIBITING FACTORS

The hormone defined serum free conditioned medium (SFCM) of human nasopharyngeal carcinoma epithelioid cell line (CNE1) was assayed by both the 3H-thymidine incorporation test and the soft agar test. It was found that the SFCM stimulated the growth of long-term serum-free cultured CNE4 cells in ac-cordence with the fact that the growth rate of long-term serum-free cultured CNE1 cells was directly proportional to the plating density. Alternatively 5% SFCM inhibited the growth of short-term serum-free cultured CNE4 cells by 51% in which the indicator cell remained the responsiveness state of growing in the serum-supplemented medium to the effector of interest. Furthermore, SFCM resulted in the inhibition of anchorage-independent growth of CNE4 cells and A431 cells. Also in soft agar test. SFCM reduced the colony formation of NRK(?),9F cells in the presence of EGF or EGF plus TGF-β. These finding suggested that CNE4 secreted autocrine growth stimulating factor(s) and growth inhibiting factor(s) in the

Mechanisms of a Synthetic Retinoid in Inhibiting Tumor-Repopulating Cells

Recently we have synthesized a novel small retinoid molecule WYC-209 that can effectively inhibit proliferation of malignant murine melanoma tumor-repopulating cells(TRCs).The molecule can induce 100%TRCs apoptosis at 10μM concentration.However,how WYC-209 induces TRCs apoptosis is still elusive.Here we demonstrate that WYC-209 at>6μM concentration started to induce TRCs apoptosis primarily via the caspase 3 pathway by releasing cytochrome c from mitochondria.Interestingly,we found that at concentrations<6μM WYC-209 induced TRCs to elevate dormancy marker COUP TF1 but induced no changes in apoptosis marker P53.Furthermore,proliferation markers Ki67 and PCNA decreased with the increase of WYC-209 concentrations,suggesting that low concentrations of WYC-209 inhibit TRCs growth by inducing cell dormancy instead of causing apoptosis.In addition,TRC traction forces were almost abolished when WYC-209 concentration was at 5μM,preceding the initiation of apoptosis.Our findings demonstrate that inhibition of TRCs by anti-cancer molecule WYC-209 is concentration-dependent and WYC-209 inhibits cellular force generation of the tumor-repopulating cells before inducing apoptosis.

Irisin Attenuates Osteoarthritis by Inhibiting Apoptosis of Osteocytes Through Activating Erk Signaling Pathway

Osteoarthritis(OA)is an inflammatory disease involving the joints that is prevalent in the global aging population.The purpose of this study is to determine whether irisin can attenuate osteoarthritis(OA)progression in anterior cruciate ligament transection(ACLT)mice models and the mechanism of irisin therapy effect on OA by increase the resistance of apoptosis in MLO-Y4 cells induced by mechanical stretch in vitro.Methods For in vivo study,3-month-old male C57BL/6 J mice were randomized to three groups,sham-operated,anterior cruciate ligament transection(ACLT)-operated treated with vehicle,and ACLT-operated treated with irisin by intraperitoneal injection once a week.Cartilage erosion was observed by HE staining.Osteoarthritis Research Society International(OARSI)scores were evaluated according to the safranin O stai-ning.The microstructure of tibia cortical bone,trabecular bone,and subchondral bone was analyzed by micro-CT and the bone histomorphometry has been administrated including mineral apposition rate(MAR).Edu staining and cck-8 were used for the detection of the proliferation of MLO-Y4 cells.For mechanical stress,cells were seeded on the collagen-I coated chamber subjected with a peak biaxial stretch of 20%at 1 Hz for 16 hours to induce apoptosis.Flow cytometry was used for the detection of apoptosis and cell cycle.TUNNEL was used for staining the apoptotic cells and rt-PCR was applied for quantifying the expression of mRNA such as Bax,Bcl-2,SOST,c-myc,Opg.Western blot was utilized to confirm the mechanism of how irisin decrease the osteocyte apoptosis.Results In vivo,irisin can attenuate articular cartilage degeneration.Irisin maintains the proportion of hyaline cartilage and calcified cartilage and keep fewer cartilage erosions in ACLT-operated mice.For immunohistochemical(IHC)staining,irisin reduced the expression of caspase3,Bax and matrix metalloproteinase-13 in both cartilage and subchondral bone.Irisin-treated ACLT group shows higher Trabecular number(Tb.N)and bone volume fraction(BV/TV)compared to the vehicle-treated ACLT group.In vitro, irisin significantly increased the proliferation of MLO-Y4 cells detected by Edu and Ki67 staining,and irisin can protect the cells from both mechanical stretchinduced apoptosis detected by FITC-PI flow cytometry and maintain the cell activity by regulating the expression of Bax,Bcl-2,and c-myc.Transcriptome sequencing shows that irisin significantly activates the MAPK signaling pathway and we confirm the result by western blot:irisin effectively activates the Erk signaling pathway through phosphorylation and has a certain activation effect on p38 signaling pathway,no activation was observed for FAK signaling pathway.Conclusions Irisin can attenuate the progression of OA by decrease the apoptosis of osteocyte,which can improve the microarchitecture of subchondral bone.Erk pathway activation plays an important role in reducing the apoptosis of osteocyte.

Inhibiting Effects of S.acus Linnaeus Extracts on GLT-82 Tumor Cell Lines

Hailong S.acus Linnaeus was chosen as the experimental material in the experiments and changes of cell morphology, forming rate of clone and changes of division index were conducted to identify the inhibiting effects of Hailong extract on human tumor cell lines (GLT 82). Four days after medication, most of the cells changed their normal morphology of tumor cells and became round, broken and even broke into pieces. The inhibiting rates could reach 75.1% on the fourth day. The division index reduced strongly and the clone could not form or the forming rate was very low. With the extract concentration increasing and the time prolonging, the inhibiting effect increased. These results indicate that Hailong has striking anti tumor effects and will have a perfect future in the fields of treatment and prevention of cancer.

Acupuncture and moxibustion for the prevention of contrast induced nephropathy in diabetic rats by inhibiting Notch signaling pathway

Objective Apoptosis is recognized as an important mechanism in contrast-induced nephropathy(CIN).Acupuncture and moxibustion,the auxiliary treatment in China,are effective interventions for cell apoptosis in many ischemic diseases.In our previous study,we found acupuncture and moxibustion could prevent CIN.The objective of this research is to study the mechanism of acupuncture and moxibustion on tubular epithelial cell apoptosis in diabetic CIN rats.

Comment on“Breviscapine alleviates nonalcoholic steatohepatitis by inhibiting TGF-β-activated kinase 1-dependent signaling”

The article by Lan et al.[1],published on 30 October 2021 in Hepatology,showed the relationship between the natural flavonoid compound breviscapine and nonalcoholic steatohepatitis(NASH).The researchers demonstrated that breviscapine might be a novel therapeutic candidate for the treatment of NASH.It can be proven that breviscapine prevents metabolic stress-induced NASH progression through direct inhibition of the TGF-β-activated Kinase 1(TAK1)signaling pathway.

Cyclosporin A impairs dendritic cell migration by regulating chemokine receptor expression and inhibiting cyclooxygenase-2 expression

Migration of dendritic cells (DCs) into tissues and secondary lymphoid organs plays a crucial role in the initiation of innate and adaptive immunity. In this article, we show that cyclosporin A (CsA) impairs the migration of DCs both in vitro and in vivo. Exposure of DCs to clinical concentrations of CsA neither induces apoptosis nor alters development but does impair cytokine secretion, chemokine receptor expression, and migration. In vitro, CsA impairs the migration of mouse bone marrow-derived DCs toward macrophage inflammatory protein-3beta (MIP-3beta) and induces them to retain responsiveness to MIP-1alpha after lipopolysaccharide (LPS)-stimulated DC maturation, while in vivo administration of CsA inhibits the migration of DCs out of skin and into the secondary lymphoid organs. CsA impairs chemokine receptor and cyclooxygenase-2 (COX-2) expression normally triggered in LPS-stimulated DCs; administration of exogenous prostaglandin E2 (PGE2) reverses the effects of CsA on chemokine receptor expression and DC migration. Inhibition of nuclear factor-kappaB (NF-κB) and mitogen-activated protein kinase (MAPK) pathway signaling by CsA may be responsible for the CsA-mediated effects on the regulation of chemokine receptor and cyclooxygenase-2 (COX-2) expression. Impairment of DC migration due to inhibition of PGE2 production and regulation of chemokine receptor expression may contribute, in part, to CsA-mediated immunosuppression.

Acupoint Catgut Embedding attenuates immune-inflammatory response in hippocampus of vascular dementia rats by inhibiting TLR4/My D88 signaling pathway

Acupoint Catgut Embedding(ACE)has been proposed as a beneficial treatment for vascular dementia(VaD),but the underlying mechanisms are still unclear.The present study investigated whether ACE alleviates cognitive impairment by suppressing TLR4/MyD88 signaling pathway,which triggers immune-inflammatory responses in the hippocampus.V aD was established by 4-VO in male SD rats.Eight days after the operation,rats were treated with ACE once a week for 3 consecutive weeks.'T ransmission electron microscopy was used to observe the ultrastructure of nerve cells in the hippocampal area before and after ACE treatment.