Magnolol,a compound extracted from Magnolia officinalis,demonstrates potential efficacy in addressing metabolic dysfunction and cardiovascular diseases.Its biological activities encompass anti-inflammatory,antioxidant...Magnolol,a compound extracted from Magnolia officinalis,demonstrates potential efficacy in addressing metabolic dysfunction and cardiovascular diseases.Its biological activities encompass anti-inflammatory,antioxidant,anticoagulant,and anti-diabetic effects.Growth/differentiation factor-15(GDF-15),a member of the transforming growth factorβsuperfamily,is considered a potential therapeutic target for metabolic disorders.This study investigated the impact of magnolol on GDF-15 production and its underlying mechanism.The research examined the pharmacological effect of magnolol on GDF-15 expression in vitro and in vivo,and determined the involvement of endoplasmic reticulum(ER)stress signaling in this process.Luciferase reporter assays,chromatin immunoprecipitation,and in vitro DNA binding assays were employed to examine the regulation of GDF-15 by activating transcription factor 4(ATF4),CCAAT enhancer binding proteinγ(CEBPG),and CCCTC-binding factor(CTCF).The study also investigated the effect of magnolol and ATF4 on the activity of a putative enhancer located in the intron of the GDF-15 gene,as well as the influence of single nucleotide polymorphisms(SNPs)on magnolol and ATF4-induced transcription activity.Results demonstrated that magnolol triggers GDF-15 production in endothelial cells(ECs),hepatoma cell line G2(HepG2)and hepatoma cell line 3B(Hep3B)cell lines,and primary mouse hepatocytes.The cooperative binding of ATF4 and CEBPG upstream of the GDF-15 gene or the E1944285 enhancer located in the intron led to full-power transcription of the GDF-15 gene.SNP alleles were found to impact the magnolol and ATF4-induced transcription activity of GDF-15.In high-fat diet ApoE^(-/-)mice,administration of magnolol induced GDF-15 production and partially suppressed appetite through GDF-15.These findings suggest that magnolol regulates GDF-15 expression through priming of promoter and enhancer activity,indicating its potential as a drug for the treatment of metabolic disorders.展开更多
Recombinant tissue plasminogen activator is commonly used for hematoma evacuation in minimally invasive surgery following intracerebral hemorrhage.However,during minimally invasive surgery,recombinant tissue plasminog...Recombinant tissue plasminogen activator is commonly used for hematoma evacuation in minimally invasive surgery following intracerebral hemorrhage.However,during minimally invasive surgery,recombinant tissue plasminogen activator may come into contact with brain tissue.Therefore,a thorough assessment of its safety is required.In this study,we established a mouse model of intracerebral hemorrhage induced by type VII collagenase.We observed that the administration of recombinant tissue plasminogen activator without hematoma aspiration significantly improved the neurological function of mice with intracerebral hemorrhage,reduced pathological damage,and lowered the levels of apoptosis and autophagy in the tissue surrounding the hematoma.In an in vitro model of intracerebral hemorrhage using primary cortical neurons induced by hemin,the administration of recombinant tissue plasminogen activator suppressed neuronal apoptosis,autophagy,and endoplasmic reticulum stress.Transcriptome sequencing analysis revealed that recombinant tissue plasminogen activator upregulated the phosphoinositide 3-kinase/RAC-alpha serine/threonine-protein kinase/mammalian target of rapamycin pathway in neurons.Moreover,the phosphoinositide 3-kinase inhibitor LY294002 abrogated the neuroprotective effects of recombinant tissue plasminogen activator in inhibiting excessive apoptosis,autophagy,and endoplasmic reticulum stress.Furthermore,to specify the domain of recombinant tissue plasminogen activator responsible for its neuroprotective effects,various inhibitors were used to target distinct domains.It has been revealed that the epidermal growth factor receptor inhibitor AG-1478 reversed the effect of recombinant tissue plasminogen activator on the phosphoinositide 3-kinase/RAC-alpha serine/threonineprotein kinase/mammalian target of rapamycin pathway.These findings suggest that recombinant tissue plasminogen activator exerts a direct neuroprotective effect on neurons following intracerebral hemorrhage,possibly through activation of the phosphoinositide 3-kinase/RAC-alpha serine/threonine-protein kinase/mammalian target of rapamycin pathway.展开更多
BACKGROUND Glomerular endothelial cell(GENC)injury is a characteristic of early-stage diabetic nephropathy(DN),and the investigation of potential therapeutic targets for preventing GENC injury is of clinical importanc...BACKGROUND Glomerular endothelial cell(GENC)injury is a characteristic of early-stage diabetic nephropathy(DN),and the investigation of potential therapeutic targets for preventing GENC injury is of clinical importance.AIM To investigate the role ofβ-arrestin-2 in GENCs under DN conditions.METHODS Eight-week-old C57BL/6J mice were intraperitoneally injected with streptozotocin to induce DN.GENCs were transfected with plasmids containing siRNA-β-arrestin-2,shRNA-activating transcription factor 6(ATF6),pCDNA-β-arrestin-2,or pCDNA-ATF6.Additionally,adeno-associated virus(AAV)containing shRNA-β-arrestin-2 was administered via a tail vein injection in DN mice.RESULTS The upregulation ofβ-arrestin-2 was observed in patients with DN as well as in GENCs from DN mice.Knockdown ofβ-arrestin-2 reduced apoptosis in high glucose-treated GENCs,which was reversed by the overexpression of ATF6.Moreover,overexpression ofβ-arrestin-2 Led to the activation of endoplasmic reticulum(ER)stress and the apoptosis of GENCs which could be mitigated by silencing of ATF6.Furthermore,knockdown ofβ-arrestin-2 by the administration of AAV-shRNA-β-arrestin-2 alleviated renal injury in DN mice.CONCLUSION Knockdown ofβ-arrestin-2 prevents GENC apoptosis by inhibiting ATF6-mediated ER stress in vivo and in vitro.Consequently,β-arrestin-2 may represent a promising therapeutic target for the clinical management of patients with DN.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is a major health challenge with high incidence and poor survival rates in China.Systemic therapies,particularly tyrosine kinase inhibitors(TKIs),are the first-line treatment fo...BACKGROUND Hepatocellular carcinoma(HCC)is a major health challenge with high incidence and poor survival rates in China.Systemic therapies,particularly tyrosine kinase inhibitors(TKIs),are the first-line treatment for advanced HCC,but resistance is common.The Rho GTPase family member Rho GTPase activating protein 12(ARHGAP12),which regulates cell adhesion and invasion,is a potential therapeutic target for overcoming TKI resistance in HCC.However,no studies on the expression of ARHGAP12 in HCC and its role in resistance to TKIs have been reported.AIM To unveil the expression of ARHGAP12 in HCC,its role in TKI resistance and its potential associated pathways.METHODS This study used single-cell RNA sequencing(scRNA-seq)to evaluate ARHGAP12 mRNA levels and explored its mechanisms through enrichment analysis.CellChat was used to investigate focal adhesion(FA)pathway regulation.We integrated bulk RNA data(RNA-seq and microarray),immunohistochemistry and proteomics to analyze ARHGAP12 mRNA and protein levels,correlating with clinical outcomes.We assessed ARHGAP12 expression in TKI-resistant HCC,integrated conventional HCC to explore its mechanism,identified intersecting FA pathway genes with scRNA-seq data and evaluated its response to TKI and immunotherapy.RESULTS ARHGAP12 mRNA was found to be highly expressed in malignant hepatocytes and to regulate FA.In malignant hepatocytes in high-score FA groups,MDK-[integrin alpha 6(ITGA6)+integrinβ-1(ITGB1)]showed specificity in ligand-receptor interactions.ARHGAP12 mRNA and protein were upregulated in bulk RNA,immunohistochemistry and proteomics,and higher expression was associated with a worse prognosis.ARHGAP12 was also found to be a TKI resistance gene that regulated the FA pathway.ITGB1 was identified as a crossover gene in the FA pathway in both scRNA-seq and bulk RNA.High expression of ARHGAP12 was associated with adverse reactions to sorafenib,cabozantinib and regorafenib,but not to immunotherapy.CONCLUSION ARHGAP12 expression is elevated in HCC and TKI-resistant HCC,and its regulatory role in FA may underlie the TKI-resistant phenotype.展开更多
Background:To systematically evaluate the efficacy and safety of activating blood and resolving stasis in patients with IgA nephropathy.Methods:From inception to May 2022,databases including PubMed,Embase,the Cochrane...Background:To systematically evaluate the efficacy and safety of activating blood and resolving stasis in patients with IgA nephropathy.Methods:From inception to May 2022,databases including PubMed,Embase,the Cochrane Library,Web of Science,WanFang database,Chinese Biomedical Database,VIP,and China National Knowledge Infrastructure were searched for randomized controlled trials about enhancing blood circulation and removing stasis for IgA nephropathy.For the articles that satisfied the requirements,quality assessment and meta-analysis were done.Results:Seventeen randomized controlled trials with a total of 1653 patients were included.Meta-analysis showed that activating blood and resolving stasis could increase therapeutic effectiveness(risk ratio(RR)=-0.47,95%confidence interval(CI)(-0.37,-0.2),P=0.0006)and decrease levels of serum creatinine(RR=-0.47,95%CI(-0.37,-0.2),P=0.0006),urea nitrogen(RR=0.85,95%CI(1.44,0.26),P=0.005),24-hour urinary protein quantification(RR=1.6,95%CI(2.44,0.95).P=0.00001),and urine red blood cell count(RR=1.7,95%CI(2.57,0.82),P=0.0001).There was no significant difference between the two groups in terms of security(RR=0.6,95%CI(0.36,1.01),P=0.05).Conclusion:Western medicine combined activating blood and resolving stasis is more efficient than Western medicine therapy alone in treating IgA nephropathy,but it still needs to be supported by additional large-scale,multi-center randomized controlled clinical trials due to the poor quality of the included trials.展开更多
Psoriasis is a chronic autoimmune disease featured by patches on the skin.It is caused by malfunction of immune cells and keratinocytes with inflammation as one of its key features.Apigenin(API)is a natural flavonoid ...Psoriasis is a chronic autoimmune disease featured by patches on the skin.It is caused by malfunction of immune cells and keratinocytes with inflammation as one of its key features.Apigenin(API)is a natural flavonoid with anti-inflammatory and immunoregulatory properties.Therefore,we speculated that API can ameliorate psoriasis,and determined its effect on the development of psoriasis by using imiquimod(IMQ)-induced psoriasis mouse model.Our results showed that API attenuated IMQ-induced phenotypic changes,such as erythema,scaling and epidermal thickening,and improved splenic hyperplasia.Abnormal differentiation of immune cells was restored in API-treated mice.Mechanistically,we revealed that API is a key regulator of signal transducer activator of transcription 3(STAT3).API regulated immune responses by reducing interleukin-23(IL-23)/STAT3/IL-17A axis.Moreover,it suppressed IMQ-caused cell hyperproliferation by inactivating STAT3 through regulation of extracellular signal-regulated kinase 1/2 and nuclear factor-κB(NF-κB)pathway.Furthermore,API reduced expression of inflammatory cytokines through inactivation of NF-κB.Taken together,our study demonstrates that API can ameliorate psoriasis and may be considered as a strategy for psoriasis treatment.展开更多
Enzyme prodrug therapies(EPTs)have been intensively explored as attractive approaches to selective activation of systemically administered benign prodrugs by the exogenous enzymes or enzymes expressed at the desired t...Enzyme prodrug therapies(EPTs)have been intensively explored as attractive approaches to selective activation of systemically administered benign prodrugs by the exogenous enzymes or enzymes expressed at the desired target site,thus achieving localized,site-specific therapeutic effect.Many effective strategies(e.g.,antibody-,viral-,gene-,as well as polymer-directed EPT)have been developed for enzyme localization to locally activate systemically administered benign prodrugs.Nevertheless,intrinsic limitations(e.g.,complex intracellular environment and catalyst instability)make the practical application of EPT strategies a task that presents itself as highly challenging.As a promising alternative to natural enzyme,nanozyme has attracted substantial attention since its discovery in 2007,mainly due to the advantages of robust catalytic activity,high stability,low cost,and facile synthesis.Recently,nanozyme-activated prodrug strategies bring a new opportunity for targeted therapy,referred to as nanozyme-activating prodrug therapies.This review focuses on recently reported nanozyme-activated prodrug strategies,aiming to provide some new insights into the potential applications in site-specific drug synthesis.展开更多
The monoaminotrinitro iron phthalocyanine(FeMATNPc)is used to connect with isonicotinic acid(INA)for amide bonding and axial coordination to synthetic a unique catalyst FeMATNPc-INA,which is loaded in polyacrylonitril...The monoaminotrinitro iron phthalocyanine(FeMATNPc)is used to connect with isonicotinic acid(INA)for amide bonding and axial coordination to synthetic a unique catalyst FeMATNPc-INA,which is loaded in polyacrylonitrile(PAN)nanofibers by electrospinning.The introduction of INA destroys theπ-πconjugated stack structure in phthalocyanine molecules and exposes more active sites.The FeMATNPc-INA structure is characterized by X-ray photoelectron spectroscopy and UV-visible absorption spectrum,and the FeMATNPcINA/PAN structure is characterized by Fourier transform infrared spectroscopy and X-ray diffraction.The FeMATNPc-INA/PAN can effectively activate peroxymonosulfate(PMS)to eliminate carbamazepine(CBZ)within 40 minutes(PMS 1.5 mmol/L)in the dark.The effects of catalyst dosage,PMS concentration,pH and inorganic anion on the degradation of CBZ are investigated.It has been confirmed by electron paramagnetic resonance,gas chromatography–mass spectroscopy and free radical capture experiments that the catalytic system is degraded by·OH,SO4^(·-)and Fe(IV)=O are the major active species,the singlet oxygen(^(1)O_(2))is the secondary active species.The degradation process of CBZ is analyzed by ultra-high performance liquid chromatography-mass spectrometry and the aromatic compounds have been degraded to small molecular acids.展开更多
The effect of enterotoxins is to induce the production of endogenous IF. St. aureus enteropathogenic proteins (enterotoxins) possess an antitumour effect. After intraperitoneal inoculation, they decrease the size and,...The effect of enterotoxins is to induce the production of endogenous IF. St. aureus enteropathogenic proteins (enterotoxins) possess an antitumour effect. After intraperitoneal inoculation, they decrease the size and, in some cases, prevent the development of the human hypernephroma in the cheek pouch of golden hamsters. The effect of enteropathgenic proteims may possibly consist in inducing the production of endogenous immune interferon which activates the host immune system and enhances the rejection of heterologous tumour cells.展开更多
Traumatic brain injury causes gene expression changes in different brain regions. Occurrence and development of traumatic brain injury are closely related, involving expression of three factors, namely cyclooxygenase-...Traumatic brain injury causes gene expression changes in different brain regions. Occurrence and development of traumatic brain injury are closely related, involving expression of three factors, namely cyclooxygenase-2, glutamate receptor-2, and platelet activating factor receptor. However, little is known about the correlation of these three factors and brain neuronal injury. In this study, primary cultured rat hippocampal neurons were subjected to fluid percussion injury according to Scott’s method, with some modifications. RT-PCR and semi-quantitative immunocytochemical staining was used to measure the expression levels of cyclooxygenase-2, glutamate receptor-2, and platelet activating factor receptor. Our results found that cyclooxygenase-2 expression were firstly increased post-injury, and then decreased. Both mRNA and protein expression levels reached peaks at 8 and 12 hours post-injury, respectively. Similar sequential changes in glutamate receptor 2 were observed, with highest levels mRNA and protein expression at 8 and 12 hours post-injury respectively. On the contrary, the expressions of platelet activating factor receptor were firstly decreased post-injury, and then increased. Both mRNA and protein expression levels reached the lowest levels at 8 and 12 hours post-injury, respectively. Totally, our findings suggest that these three factors are involved in occurrence and development of hippocampal neuronal injury.展开更多
AIM To study the effects of Radix Salviae Militiorrhiza (RSM), other blood-activating and stasis-eliminating Chinese herbs on hemodynamics of portal hypertension.METHODS Portal pressure of cirrhotic dogs after chronic...AIM To study the effects of Radix Salviae Militiorrhiza (RSM), other blood-activating and stasis-eliminating Chinese herbs on hemodynamics of portal hypertension.METHODS Portal pressure of cirrhotic dogs after chronic common bile duct ligation was measured directly; portal blood flow in patients with liver cirrhosis were detected by ultrasound Doppler.RESULTS After administration of RSM and Radix Angelicae Sinensis (RAS) by intravenous infusion in cirrhosis dogs, the portal venous pressure (Ppv), wedge hepatic venous pressure (WHVP), hepatic venous pressure gradient (HVPG), were significantly decreased (P＜0.05-0.01), but the mean arterial pressure (MAP), and the heart rate (HR) remained unchanged. When nifedipine was used, Ppv, WHVP, MAP and HR were significantly decreased (P＜0.05), and the MVPG unchanged (P＞0.05). After administration of RSM, RSM+nifedipine and RSM+Hirudin+Nifedpin for 10-12 weeks, the diameter of portal vein (Dpv), spleen vein (Dsv), the portal venous flow (Qpv) and splenic venous flow (Qsv) in patients with hepatic cirrhosis were significantly lowered (P＜0.05-0.01), and the effect of RAS was weaker.CONCLUSIONS The efficacy of decreasing Ppv by Chinese herbs-RSM, RAS, etc. as compared with nifedipine, demonstrated that the Chinese herbs were slower in action than that of nifedipine, but more long-lasting and without side effects. Hence, long-term administration of Chinese herbs, would be more beneficial.展开更多
In order to increase the absorption of laser energy and improve the weld appearance in laser welding of Al alloy, 1.8 mm- 6013 Al alloy plate was welded by activating flux CO2 laser welding. Activating flux includes o...In order to increase the absorption of laser energy and improve the weld appearance in laser welding of Al alloy, 1.8 mm- 6013 Al alloy plate was welded by activating flux CO2 laser welding. Activating flux includes oxide and fluoride, which was coated on the workpiece surface before welding. The experimental results show that the activating flux can effectively improve the absorption of CO2 laser energy and increase the amount of the molten base metal. The improvement on the absorption of laser energy by oxide activating flux is greater than that by fluoride activating flux or two-component activating flux, but the slag detachability made from both the single activating flux and two-activating flux is poor. The gas pore sensitivity with oxide activating flux is much higher than that with fluoride activating flux in CO2 laser welding of 6013 Al alloy.展开更多
AIM:To investigate the dynamic changes and significance of platelet activating factor receptor (PAF-R) mRNA and protein in pancreatic tissues of rats with severe acute pancreatitis (SAP) and effects of BN52021 (Ginkgo...AIM:To investigate the dynamic changes and significance of platelet activating factor receptor (PAF-R) mRNA and protein in pancreatic tissues of rats with severe acute pancreatitis (SAP) and effects of BN52021 (Ginkgolide B). METHODS:Wistar male rats were randomly assigned to the negative control group (NC group),SAP model group (SAP group),and BN52051-remedy group (BN group),and each of the groups was divided into 6 subgroups at different time points after operation (1 h,2 h,3 h,6 h,12 h,and 24 h) (n=10 in each). PT-PCR and Western blot methods were used to detect PAF-RmRNA and protein expression in pancreatic tissues of rats respectively. Pathological examination of pancreatic tissues was performed and the serum amylase change was detected. RESULTS:Serum amylase and pathological results showed the that SAP model was successfully prepared,BN52021 was able to decrease serum amylase,and the pathological ratings in BN group at 3 h,6 h,and 12 h significantly decreased compared with those in the SAP group (8.85 ± 0.39 vs 5.95 ± 0.19,9.15 ± 0.55 vs 5.55 ± 0.36,10.10 ± 0.65 vs 6.72 ± 0.30,P < 0.05). The result of PAF-mRNA showed dynamic changes in SAP and BN groups,which increased gradually in early stage,reached a peak at 3 h (0.71 ± 0.14 vs 0.54 ± 0.14,0.69 ± 0.13 vs 0.59 ± 0.04,P < 0.05),and decreased gradually later. There were significant differences at each time point except 1 h and 2 h,when compared with those in the NC group (0.71 ± 0.14 or 0.69 ± 0.13 vs 0.47 ± 0.10,0.38 ± 0.08 or 0.59 ± 0.04 vs 0.47 ± 0.09,0.25 ± 0.07 or 0.29 ± 0.05 vs 0.46 ± 0.10,0.20 ± 0.06 or 0.20± 0.04 vs 0.43 ± 0.09,P < 0.05),whereas there was no significant difference between BN and SAP groups at each time point. The result of PAF-R protein showed that the change of PAF-R protein in the SAP group and the BN group was consistent with that of PAF-R mRNA. There were significant differences at each time point except 1 h,when compared with those in the NC group (0.90 ± 0.02 or 0.80 ± 0.05 vs 0.48 ± 0.02,1.69 ± 0.06 or 1.58 ± 0.02 vs 0.48 ± 0.03,1.12 ± 0.10 or 0.98 ± 0.03 vs 0.49 ± 0.09,1.04 ± 0.14 or 0.87 ± 0.02 vs 0.52 ± 0.08,0.97 ± 0.16 or 0.90 ± 0.05 vs 0.49 ± 0.10,P < 0.05),whereas there was no significant difference between the BN group and the SAP group. CONCLUSION:PAF-R plays an important role in occurrence and development of SAP. BN52021 exerts biological effects through competitively inhibiting the binding of increased both PAF and PAF-R expression rather than through decreasing PAF-R expression in pancreatic tissues.展开更多
OBJECTIVE: To investigate the effects of tonifying Qi and activating blood circulation(SQABC), a method in Traditional Chinese Medicine(TCM), on end-point events in patients with myocardial infarction(MI) in this retr...OBJECTIVE: To investigate the effects of tonifying Qi and activating blood circulation(SQABC), a method in Traditional Chinese Medicine(TCM), on end-point events in patients with myocardial infarction(MI) in this retrospective cohort study.METHODS: Clinical data were obtained from the medical records of patients with acute MI(AMI),both during hospitalization and follow-up, and included general demographic information(age, gender, and contact information), TCM regimens used,and end-point events.RESULTS: A total of 1596 patients with AMI were enrolled to this study, but data of only 1210 casesare accessible till follow-up. We classified the patients based on the exposure levels of SQABC.When comparing the results between all exposure and non-exposure groups, significant differences were identified, both during hospitalization and follow-ups. During hospitalization, cardiac death(4.40% vs 21.55%, P < 0.05) and cardiac shock(3.04% vs 11.62%, P < 0.05) were significantly lower in the exposure group than the non-exposure group. Similarly, during the follow-up, cardiac death(12.04% vs 20.49%, P < 0.05), acute heart failure(7.27% vs 11.81%, P < 0.05), composite endpoint of reinfarction and stroke(9.11% vs 15.28%,P < 0.05), and rehospitalization due to angina(25.49% vs 34.38%, P < 0.05) were significantly lower in the exposure group than the non-exposure group.CONCLUSION: Our findings suggest that SQABC can significantly benefits the subjects in the management of high-risk AMI in them.展开更多
OBJECTIVE: To evaluate the anti-platelet aggregation effects of extracts from 31 Traditional Chinese Medicines(TCM) with the property of activating blood and resolving stasis in terms of TCM theory.METHODS: The 31 TCM...OBJECTIVE: To evaluate the anti-platelet aggregation effects of extracts from 31 Traditional Chinese Medicines(TCM) with the property of activating blood and resolving stasis in terms of TCM theory.METHODS: The 31 TCMs extracts were prepared using water, 90% ethanol and ethyl acetate., and the effects on anti-platelet aggregation were tested on a platelet aggregation analyzer in vitro with adenosine 5'-diphosphate, bovine thrombin and arachi-donic acid(AA) as aggregation inducers, respectively. Aspirin was the positive control.RESULTS: Lots of the tested TCMs had inhibitory effects with concentration-dependent manner on platelet aggregations induced by various agonists.Especially, some of the TCMs such as Chuanxiong(Rhizoma Chuanxiong), Yanhusuo(Rhizoma Corydalis Yanhusuo) and Danshen(Radix Salviae Miltiorrhizae) showed good anti-platelet aggregation effect similar or higher than that in positive control group.CONCLUSION: The study provided scientific references that several TCMs such as Chuanxiong(Rhizoma Chuanxiong), Yanhusuo(Rhizoma Corydalis Yanhusuo) and Danshen(Radix Salviae Miltiorrhizae),possess the property of anti-platelet aggregation.展开更多
AIM： Platelet-activating factor （PAF） is a pro-inflammatory and angiogenic lipid mediator. Here we aimed to investigate levels of PAF, lyso-PAF （the PAF precursor）, phospholipase A2 （PLA2, the enzymatic activity...AIM： Platelet-activating factor （PAF） is a pro-inflammatory and angiogenic lipid mediator. Here we aimed to investigate levels of PAF, lyso-PAF （the PAF precursor）, phospholipase A2 （PLA2, the enzymatic activity generating lyso-PAF）, acetylhydrolase activity （AHA, the PAF degrading enzyme） and PAF receptor （PAF-R） transcripts in cirrhotic liver and hepatocellular carcinoma （HCC）. METHODS： Twenty-nine patients with HCC were enrolled in this study. Cirrhosis was present in fourteen patients and seven had no liver disease. Tissue PAF levels were investigated by a platelet-aggregation assay. Lyso- PAF was assessed after its chemical acetylation into PAR AHA was determined by degradation of [^3H]-PAE PLA2 levels were assessed by EIA. PAF-R transcripts were investigated using RT-PCR. RESULTS： Elevated amounts of PAF and PAF-R transcripts 1 （leukocyte-type） were found in cirrhotic tissues as compared with non-cirrhotic ones. Higher amounts of PAF and PAF-R transcripts 1 and 2 （tissue-type） were found in HCC tissues as compared with non-tumor tissues. PLA2, lyso-PAF and AHA levels were not changed in cirrhotic tissues and HCC. CONCLUSION： While the role of PAF is currently unknown in liver physiology, this study suggests its potential involvement in the inflammatory network found in the cirrhotic liver and in the angiogenic response during HCC.展开更多
To explore the effect of Buyang Huanwu Decoction (BHD) on platelet activating factor (PAF) content in arterial blood pre- and post-arterial thrombosis in rats, male Wistar rats were randomly divided into 3 groups, the...To explore the effect of Buyang Huanwu Decoction (BHD) on platelet activating factor (PAF) content in arterial blood pre- and post-arterial thrombosis in rats, male Wistar rats were randomly divided into 3 groups, the medicine group treated with BHD, the control group with dexamethasone liquid, and the blank group with distilled water. Oral administration was given for 14 consecutive days, once daily. Model of arterial thrombosis was established in the animals 2 hours after final medication, the blood content of PAF, dry weight (DW) and occlusion time (OT) of thrombus, and dry weight of thrombus/body weight (TW/BW) ratio were observed. Results indicated that BHD could markedly lower the arterial blood content of PAF after thrombosis, increase the OT of thrombus, reduce the dry weight of thrombus and the TW/BW ratio (P展开更多
Dementia is a clinical syndrome that affects approximately 47 million people worldwide and is characterized by progressive and irreversible decline of cognitive,behavioral and sesorimotor functions.Alzheimer’s diseas...Dementia is a clinical syndrome that affects approximately 47 million people worldwide and is characterized by progressive and irreversible decline of cognitive,behavioral and sesorimotor functions.Alzheimer’s disease(AD)accounts for approximately 60–80%of all cases of dementia,and neuropathologically is characterized by extracellular deposits of insoluble amyloid-β(Aβ)and intracellular aggregates of hyperphosphorylated tau.Significantly,although for a long time it was believed that the extracellular accumulation of Aβwas the culprit of the symptoms observed in these patients,more recent studies have shown that cognitive decline in people suffering this disease is associated with soluble Aβ-induced synaptic dysfunction instead of the formation of insoluble Aβ-containing extracellular plaques.These observations are translationally relevant because soluble Aβ-induced synaptic dysfunction is an early event in AD that precedes neuronal death,and thus is amenable to therapeutic interventions to prevent cognitive decline before the progression to irreversible brain damage.The plasminogen activating(PA)system is an enzymatic cascade that triggers the degradation of fibrin by catalyzing the conversion of plasminogen into plasmin via two serine proteinases:tissue-type plasminogen activator(tPA)and urokinase-type plasminogen activator(uPA).Experimental evidence reported over the last three decades has shown that tPA and uPA play a role in the pathogenesis of AD.However,these studies have focused on the ability of these plasminogen activators to trigger plasmin-induced cleavage of insoluble Aβ-containing extracellular plaques.In contrast,recent evidence indicates that activity-dependent release of uPA from the presynaptic terminal of cerebral cortical neurons protects the synapse from the deleterious effects of soluble Aβvia a mechanism that does not require plasmin generation or the cleavage of Aβfibrils.Below we discuss the role of the PA system in the pathogenesis of AD and the translational relevance of data published to this date.展开更多
OBJECTIVE: To evaluate the effect of decoction prepared with Yang-activating and stasis-eliminating medicinals from Traditional Chinese Medicine(TCM) on the intestinal mucosal permeability in rats with ulcerative coli...OBJECTIVE: To evaluate the effect of decoction prepared with Yang-activating and stasis-eliminating medicinals from Traditional Chinese Medicine(TCM) on the intestinal mucosal permeability in rats with ulcerative colitis induced by dextran sulfate sodium(DSS).METHODS: Totally 55 male Wistar rats(body weight of 170-190 g) were randomly divided into the blank group(n = 10) and the model duplication group(n = 45). The blank group was not intervened, while the other was modeled with 5% dextran sulfate sodium by gavaging in a dosage of4 m L per day to induce ulcerative colitis, a total of7 days. Then, the model rats were divided into model blank group, mesalazine group and TCM group,and each group was consisted of 15 rats. They were given retention enema 10 min with normal saline,mesalazine enema(0.036 g/m L), and Yang-activating and stasis-eliminating decoction [0.54 g/m L of a decoction boiled by Puhuang(Pollen Typhae), Xiebai(Bulbus Allii Macrostemonis) and Wulingzhi(Faeces Trogopteri)] for 10 days respectively. Afterwards,all of the rats were evaluated by disease activity index(DAI), histological changes of distal colon, expression of occludin protein and ultrastructure of intestinal epithelial cells. Furthermore, ratio of lactulose to mannitol(L/M) discharged in urine was evaluated.RESULTS: Comparing the results between TCM and model control groups, scores of DAI and histological lesions decreased significantly(P = 0.000 <0.01), ultrastructures of intestinal epithelial cells and tight junctions were more complete. The expression of occludin protein(P = 0.001 < 0.01) increased while the L/M value decreased significantly(P = 0.000 < 0.01) in TCM group. There was no statistical difference between the TCM and mesalazine groups in results of each item(P > 0.05).CONCLUSION: The decoction prepared with Yang-activating and stasis-eliminating TCM medicianls can restore intestinal mucosal epithelial cells and tight junctions the model rats with ulcerative colitis; it can reduce histological lesions and protect the permeability of intestinal mucosa barrier in the rats as well.展开更多
AIM： To evaluate the changes in hepatic platelet activating factor （PAF） and its receptors and their effect on portal pressure of cirrhotic rats induced by CCh. METHODS： A model of liver cirrhosis was replicated i...AIM： To evaluate the changes in hepatic platelet activating factor （PAF） and its receptors and their effect on portal pressure of cirrhotic rats induced by CCh. METHODS： A model of liver cirrhosis was replicated in rats by intra-peritoneal injection of CCh for 8 wk. We determined the effect of hepatic PAF and its receptor level on portal and arterial pressure by EIA, saturation binding and RT-PCR technique. RESULTS： Compared to control rats, cirrhotic rats had higher hepatic PAF levels and output as well as higher plasma PAF levels （P〈0.01, P〈0.01, P〈0.05, respectively）. Both hepatic PAF receptor mRNA levels and PAF binding were nearly 3-fold greater in cirrhotic rats （P〈0.01）. Portal injection of PAF （1 g/kg WT） increased the portal pressure by 22% and 33% in control and cirrhotic rats, respectively. In contrast, the arterial pressure was decreased in the both groups （54% in control rats and 42% in cirrhotic rats）. Injection of the PAF antagonist BN52021 （5 mg/kg WT） decreased the portal pressure by 16% in cirrhotic rats but had no effect in the control rats. CONCLUSION： The upregulation of the PAF system contributes to hepatic hemodynamic and metabolic abnormalities in drrhosis, and the increased release of PAF into the circulation has impacts on the systemic hemodynamics.展开更多
基金supported by the National Natural Science Foundation of China(Nos.82171552 and 82170479)the Natural Science Foundation of Shanghai Ctiy(No.21ZR1457500)the Science and Technology Bureau of Shanghai Putuo District(No.ptkwws202102).
文摘Magnolol,a compound extracted from Magnolia officinalis,demonstrates potential efficacy in addressing metabolic dysfunction and cardiovascular diseases.Its biological activities encompass anti-inflammatory,antioxidant,anticoagulant,and anti-diabetic effects.Growth/differentiation factor-15(GDF-15),a member of the transforming growth factorβsuperfamily,is considered a potential therapeutic target for metabolic disorders.This study investigated the impact of magnolol on GDF-15 production and its underlying mechanism.The research examined the pharmacological effect of magnolol on GDF-15 expression in vitro and in vivo,and determined the involvement of endoplasmic reticulum(ER)stress signaling in this process.Luciferase reporter assays,chromatin immunoprecipitation,and in vitro DNA binding assays were employed to examine the regulation of GDF-15 by activating transcription factor 4(ATF4),CCAAT enhancer binding proteinγ(CEBPG),and CCCTC-binding factor(CTCF).The study also investigated the effect of magnolol and ATF4 on the activity of a putative enhancer located in the intron of the GDF-15 gene,as well as the influence of single nucleotide polymorphisms(SNPs)on magnolol and ATF4-induced transcription activity.Results demonstrated that magnolol triggers GDF-15 production in endothelial cells(ECs),hepatoma cell line G2(HepG2)and hepatoma cell line 3B(Hep3B)cell lines,and primary mouse hepatocytes.The cooperative binding of ATF4 and CEBPG upstream of the GDF-15 gene or the E1944285 enhancer located in the intron led to full-power transcription of the GDF-15 gene.SNP alleles were found to impact the magnolol and ATF4-induced transcription activity of GDF-15.In high-fat diet ApoE^(-/-)mice,administration of magnolol induced GDF-15 production and partially suppressed appetite through GDF-15.These findings suggest that magnolol regulates GDF-15 expression through priming of promoter and enhancer activity,indicating its potential as a drug for the treatment of metabolic disorders.
基金supported by the National Natural Science Foundation of China,Nos.92148206,82071330(both to ZT)a grant from the Major Program of Hubei Province,No.2023BAA005(to ZT)+1 种基金a grant from the Key Research and Discovery Program of Hubei Province,No.2021BCA109(to ZT)the Research Foundation of Tongji Hospital,No.2022B37(to PZ)。
文摘Recombinant tissue plasminogen activator is commonly used for hematoma evacuation in minimally invasive surgery following intracerebral hemorrhage.However,during minimally invasive surgery,recombinant tissue plasminogen activator may come into contact with brain tissue.Therefore,a thorough assessment of its safety is required.In this study,we established a mouse model of intracerebral hemorrhage induced by type VII collagenase.We observed that the administration of recombinant tissue plasminogen activator without hematoma aspiration significantly improved the neurological function of mice with intracerebral hemorrhage,reduced pathological damage,and lowered the levels of apoptosis and autophagy in the tissue surrounding the hematoma.In an in vitro model of intracerebral hemorrhage using primary cortical neurons induced by hemin,the administration of recombinant tissue plasminogen activator suppressed neuronal apoptosis,autophagy,and endoplasmic reticulum stress.Transcriptome sequencing analysis revealed that recombinant tissue plasminogen activator upregulated the phosphoinositide 3-kinase/RAC-alpha serine/threonine-protein kinase/mammalian target of rapamycin pathway in neurons.Moreover,the phosphoinositide 3-kinase inhibitor LY294002 abrogated the neuroprotective effects of recombinant tissue plasminogen activator in inhibiting excessive apoptosis,autophagy,and endoplasmic reticulum stress.Furthermore,to specify the domain of recombinant tissue plasminogen activator responsible for its neuroprotective effects,various inhibitors were used to target distinct domains.It has been revealed that the epidermal growth factor receptor inhibitor AG-1478 reversed the effect of recombinant tissue plasminogen activator on the phosphoinositide 3-kinase/RAC-alpha serine/threonineprotein kinase/mammalian target of rapamycin pathway.These findings suggest that recombinant tissue plasminogen activator exerts a direct neuroprotective effect on neurons following intracerebral hemorrhage,possibly through activation of the phosphoinositide 3-kinase/RAC-alpha serine/threonine-protein kinase/mammalian target of rapamycin pathway.
基金Supported by Key Research and Development Program of Shandong Province,No.2021CXGC011101Special Fund for Taishan Scholars Project,No.tsqn202211324+2 种基金National Natural Science Foundation of China,No.81900669Natural Science Foundation of Shandong Province,China,No.ZR2018PH007the Multidisciplinary Innovation Center for Nephrology of the Second Hospital of Shandong University.
文摘BACKGROUND Glomerular endothelial cell(GENC)injury is a characteristic of early-stage diabetic nephropathy(DN),and the investigation of potential therapeutic targets for preventing GENC injury is of clinical importance.AIM To investigate the role ofβ-arrestin-2 in GENCs under DN conditions.METHODS Eight-week-old C57BL/6J mice were intraperitoneally injected with streptozotocin to induce DN.GENCs were transfected with plasmids containing siRNA-β-arrestin-2,shRNA-activating transcription factor 6(ATF6),pCDNA-β-arrestin-2,or pCDNA-ATF6.Additionally,adeno-associated virus(AAV)containing shRNA-β-arrestin-2 was administered via a tail vein injection in DN mice.RESULTS The upregulation ofβ-arrestin-2 was observed in patients with DN as well as in GENCs from DN mice.Knockdown ofβ-arrestin-2 reduced apoptosis in high glucose-treated GENCs,which was reversed by the overexpression of ATF6.Moreover,overexpression ofβ-arrestin-2 Led to the activation of endoplasmic reticulum(ER)stress and the apoptosis of GENCs which could be mitigated by silencing of ATF6.Furthermore,knockdown ofβ-arrestin-2 by the administration of AAV-shRNA-β-arrestin-2 alleviated renal injury in DN mice.CONCLUSION Knockdown ofβ-arrestin-2 prevents GENC apoptosis by inhibiting ATF6-mediated ER stress in vivo and in vitro.Consequently,β-arrestin-2 may represent a promising therapeutic target for the clinical management of patients with DN.
基金Supported by National Natural Science Foundation of China,No.82260581Guangxi Zhuang Autonomous Region Health Committee Scientific Research Project,No.Z20201147+3 种基金Guangxi Medical University Education and Teaching Reform Project,No.2021XJGA02Undergraduate Teaching Reform Project of Guangxi Higher Education,No.2023JGB163Guangxi Medical University Teacher Teaching Ability Development Project,No.2202JFA20China Undergraduate Innovation and Entrepreneurship Training Program,No.S202310598170.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is a major health challenge with high incidence and poor survival rates in China.Systemic therapies,particularly tyrosine kinase inhibitors(TKIs),are the first-line treatment for advanced HCC,but resistance is common.The Rho GTPase family member Rho GTPase activating protein 12(ARHGAP12),which regulates cell adhesion and invasion,is a potential therapeutic target for overcoming TKI resistance in HCC.However,no studies on the expression of ARHGAP12 in HCC and its role in resistance to TKIs have been reported.AIM To unveil the expression of ARHGAP12 in HCC,its role in TKI resistance and its potential associated pathways.METHODS This study used single-cell RNA sequencing(scRNA-seq)to evaluate ARHGAP12 mRNA levels and explored its mechanisms through enrichment analysis.CellChat was used to investigate focal adhesion(FA)pathway regulation.We integrated bulk RNA data(RNA-seq and microarray),immunohistochemistry and proteomics to analyze ARHGAP12 mRNA and protein levels,correlating with clinical outcomes.We assessed ARHGAP12 expression in TKI-resistant HCC,integrated conventional HCC to explore its mechanism,identified intersecting FA pathway genes with scRNA-seq data and evaluated its response to TKI and immunotherapy.RESULTS ARHGAP12 mRNA was found to be highly expressed in malignant hepatocytes and to regulate FA.In malignant hepatocytes in high-score FA groups,MDK-[integrin alpha 6(ITGA6)+integrinβ-1(ITGB1)]showed specificity in ligand-receptor interactions.ARHGAP12 mRNA and protein were upregulated in bulk RNA,immunohistochemistry and proteomics,and higher expression was associated with a worse prognosis.ARHGAP12 was also found to be a TKI resistance gene that regulated the FA pathway.ITGB1 was identified as a crossover gene in the FA pathway in both scRNA-seq and bulk RNA.High expression of ARHGAP12 was associated with adverse reactions to sorafenib,cabozantinib and regorafenib,but not to immunotherapy.CONCLUSION ARHGAP12 expression is elevated in HCC and TKI-resistant HCC,and its regulatory role in FA may underlie the TKI-resistant phenotype.
文摘Background:To systematically evaluate the efficacy and safety of activating blood and resolving stasis in patients with IgA nephropathy.Methods:From inception to May 2022,databases including PubMed,Embase,the Cochrane Library,Web of Science,WanFang database,Chinese Biomedical Database,VIP,and China National Knowledge Infrastructure were searched for randomized controlled trials about enhancing blood circulation and removing stasis for IgA nephropathy.For the articles that satisfied the requirements,quality assessment and meta-analysis were done.Results:Seventeen randomized controlled trials with a total of 1653 patients were included.Meta-analysis showed that activating blood and resolving stasis could increase therapeutic effectiveness(risk ratio(RR)=-0.47,95%confidence interval(CI)(-0.37,-0.2),P=0.0006)and decrease levels of serum creatinine(RR=-0.47,95%CI(-0.37,-0.2),P=0.0006),urea nitrogen(RR=0.85,95%CI(1.44,0.26),P=0.005),24-hour urinary protein quantification(RR=1.6,95%CI(2.44,0.95).P=0.00001),and urine red blood cell count(RR=1.7,95%CI(2.57,0.82),P=0.0001).There was no significant difference between the two groups in terms of security(RR=0.6,95%CI(0.36,1.01),P=0.05).Conclusion:Western medicine combined activating blood and resolving stasis is more efficient than Western medicine therapy alone in treating IgA nephropathy,but it still needs to be supported by additional large-scale,multi-center randomized controlled clinical trials due to the poor quality of the included trials.
基金supported by the National Natural Science Foundation of China(NSFC)(81973316,82173807)the China Postdoctoral Science Foundation(2020M681914)+1 种基金the Fund from Tianjin Municipal Health Commission(ZC200093)the Open Fund of Tianjin Central Hospital of Obstetrics and Gynecology/Tianjin Key Laboratory of human development and reproductive regulation(2021XHY01)。
文摘Psoriasis is a chronic autoimmune disease featured by patches on the skin.It is caused by malfunction of immune cells and keratinocytes with inflammation as one of its key features.Apigenin(API)is a natural flavonoid with anti-inflammatory and immunoregulatory properties.Therefore,we speculated that API can ameliorate psoriasis,and determined its effect on the development of psoriasis by using imiquimod(IMQ)-induced psoriasis mouse model.Our results showed that API attenuated IMQ-induced phenotypic changes,such as erythema,scaling and epidermal thickening,and improved splenic hyperplasia.Abnormal differentiation of immune cells was restored in API-treated mice.Mechanistically,we revealed that API is a key regulator of signal transducer activator of transcription 3(STAT3).API regulated immune responses by reducing interleukin-23(IL-23)/STAT3/IL-17A axis.Moreover,it suppressed IMQ-caused cell hyperproliferation by inactivating STAT3 through regulation of extracellular signal-regulated kinase 1/2 and nuclear factor-κB(NF-κB)pathway.Furthermore,API reduced expression of inflammatory cytokines through inactivation of NF-κB.Taken together,our study demonstrates that API can ameliorate psoriasis and may be considered as a strategy for psoriasis treatment.
基金financially supported by the Shandong Provincial Natural Science Foundation of China(No.ZR2021QC088).
文摘Enzyme prodrug therapies(EPTs)have been intensively explored as attractive approaches to selective activation of systemically administered benign prodrugs by the exogenous enzymes or enzymes expressed at the desired target site,thus achieving localized,site-specific therapeutic effect.Many effective strategies(e.g.,antibody-,viral-,gene-,as well as polymer-directed EPT)have been developed for enzyme localization to locally activate systemically administered benign prodrugs.Nevertheless,intrinsic limitations(e.g.,complex intracellular environment and catalyst instability)make the practical application of EPT strategies a task that presents itself as highly challenging.As a promising alternative to natural enzyme,nanozyme has attracted substantial attention since its discovery in 2007,mainly due to the advantages of robust catalytic activity,high stability,low cost,and facile synthesis.Recently,nanozyme-activated prodrug strategies bring a new opportunity for targeted therapy,referred to as nanozyme-activating prodrug therapies.This review focuses on recently reported nanozyme-activated prodrug strategies,aiming to provide some new insights into the potential applications in site-specific drug synthesis.
基金supported by National Natural Science Foundation of China (No.22006136)。
文摘The monoaminotrinitro iron phthalocyanine(FeMATNPc)is used to connect with isonicotinic acid(INA)for amide bonding and axial coordination to synthetic a unique catalyst FeMATNPc-INA,which is loaded in polyacrylonitrile(PAN)nanofibers by electrospinning.The introduction of INA destroys theπ-πconjugated stack structure in phthalocyanine molecules and exposes more active sites.The FeMATNPc-INA structure is characterized by X-ray photoelectron spectroscopy and UV-visible absorption spectrum,and the FeMATNPcINA/PAN structure is characterized by Fourier transform infrared spectroscopy and X-ray diffraction.The FeMATNPc-INA/PAN can effectively activate peroxymonosulfate(PMS)to eliminate carbamazepine(CBZ)within 40 minutes(PMS 1.5 mmol/L)in the dark.The effects of catalyst dosage,PMS concentration,pH and inorganic anion on the degradation of CBZ are investigated.It has been confirmed by electron paramagnetic resonance,gas chromatography–mass spectroscopy and free radical capture experiments that the catalytic system is degraded by·OH,SO4^(·-)and Fe(IV)=O are the major active species,the singlet oxygen(^(1)O_(2))is the secondary active species.The degradation process of CBZ is analyzed by ultra-high performance liquid chromatography-mass spectrometry and the aromatic compounds have been degraded to small molecular acids.
文摘The effect of enterotoxins is to induce the production of endogenous IF. St. aureus enteropathogenic proteins (enterotoxins) possess an antitumour effect. After intraperitoneal inoculation, they decrease the size and, in some cases, prevent the development of the human hypernephroma in the cheek pouch of golden hamsters. The effect of enteropathgenic proteims may possibly consist in inducing the production of endogenous immune interferon which activates the host immune system and enhances the rejection of heterologous tumour cells.
基金supported by the National Natural Science Foundation of China,No.30471934
文摘Traumatic brain injury causes gene expression changes in different brain regions. Occurrence and development of traumatic brain injury are closely related, involving expression of three factors, namely cyclooxygenase-2, glutamate receptor-2, and platelet activating factor receptor. However, little is known about the correlation of these three factors and brain neuronal injury. In this study, primary cultured rat hippocampal neurons were subjected to fluid percussion injury according to Scott’s method, with some modifications. RT-PCR and semi-quantitative immunocytochemical staining was used to measure the expression levels of cyclooxygenase-2, glutamate receptor-2, and platelet activating factor receptor. Our results found that cyclooxygenase-2 expression were firstly increased post-injury, and then decreased. Both mRNA and protein expression levels reached peaks at 8 and 12 hours post-injury, respectively. Similar sequential changes in glutamate receptor 2 were observed, with highest levels mRNA and protein expression at 8 and 12 hours post-injury respectively. On the contrary, the expressions of platelet activating factor receptor were firstly decreased post-injury, and then increased. Both mRNA and protein expression levels reached the lowest levels at 8 and 12 hours post-injury, respectively. Totally, our findings suggest that these three factors are involved in occurrence and development of hippocampal neuronal injury.
文摘AIM To study the effects of Radix Salviae Militiorrhiza (RSM), other blood-activating and stasis-eliminating Chinese herbs on hemodynamics of portal hypertension.METHODS Portal pressure of cirrhotic dogs after chronic common bile duct ligation was measured directly; portal blood flow in patients with liver cirrhosis were detected by ultrasound Doppler.RESULTS After administration of RSM and Radix Angelicae Sinensis (RAS) by intravenous infusion in cirrhosis dogs, the portal venous pressure (Ppv), wedge hepatic venous pressure (WHVP), hepatic venous pressure gradient (HVPG), were significantly decreased (P＜0.05-0.01), but the mean arterial pressure (MAP), and the heart rate (HR) remained unchanged. When nifedipine was used, Ppv, WHVP, MAP and HR were significantly decreased (P＜0.05), and the MVPG unchanged (P＞0.05). After administration of RSM, RSM+nifedipine and RSM+Hirudin+Nifedpin for 10-12 weeks, the diameter of portal vein (Dpv), spleen vein (Dsv), the portal venous flow (Qpv) and splenic venous flow (Qsv) in patients with hepatic cirrhosis were significantly lowered (P＜0.05-0.01), and the effect of RAS was weaker.CONCLUSIONS The efficacy of decreasing Ppv by Chinese herbs-RSM, RAS, etc. as compared with nifedipine, demonstrated that the Chinese herbs were slower in action than that of nifedipine, but more long-lasting and without side effects. Hence, long-term administration of Chinese herbs, would be more beneficial.
基金supported by State Key Laboratory of Advanced Welding and Joining, Harbin Institute of Technology, China
文摘In order to increase the absorption of laser energy and improve the weld appearance in laser welding of Al alloy, 1.8 mm- 6013 Al alloy plate was welded by activating flux CO2 laser welding. Activating flux includes oxide and fluoride, which was coated on the workpiece surface before welding. The experimental results show that the activating flux can effectively improve the absorption of CO2 laser energy and increase the amount of the molten base metal. The improvement on the absorption of laser energy by oxide activating flux is greater than that by fluoride activating flux or two-component activating flux, but the slag detachability made from both the single activating flux and two-activating flux is poor. The gas pore sensitivity with oxide activating flux is much higher than that with fluoride activating flux in CO2 laser welding of 6013 Al alloy.
基金the National Natural Science Foundation of China, No. 30300465
文摘AIM:To investigate the dynamic changes and significance of platelet activating factor receptor (PAF-R) mRNA and protein in pancreatic tissues of rats with severe acute pancreatitis (SAP) and effects of BN52021 (Ginkgolide B). METHODS:Wistar male rats were randomly assigned to the negative control group (NC group),SAP model group (SAP group),and BN52051-remedy group (BN group),and each of the groups was divided into 6 subgroups at different time points after operation (1 h,2 h,3 h,6 h,12 h,and 24 h) (n=10 in each). PT-PCR and Western blot methods were used to detect PAF-RmRNA and protein expression in pancreatic tissues of rats respectively. Pathological examination of pancreatic tissues was performed and the serum amylase change was detected. RESULTS:Serum amylase and pathological results showed the that SAP model was successfully prepared,BN52021 was able to decrease serum amylase,and the pathological ratings in BN group at 3 h,6 h,and 12 h significantly decreased compared with those in the SAP group (8.85 ± 0.39 vs 5.95 ± 0.19,9.15 ± 0.55 vs 5.55 ± 0.36,10.10 ± 0.65 vs 6.72 ± 0.30,P < 0.05). The result of PAF-mRNA showed dynamic changes in SAP and BN groups,which increased gradually in early stage,reached a peak at 3 h (0.71 ± 0.14 vs 0.54 ± 0.14,0.69 ± 0.13 vs 0.59 ± 0.04,P < 0.05),and decreased gradually later. There were significant differences at each time point except 1 h and 2 h,when compared with those in the NC group (0.71 ± 0.14 or 0.69 ± 0.13 vs 0.47 ± 0.10,0.38 ± 0.08 or 0.59 ± 0.04 vs 0.47 ± 0.09,0.25 ± 0.07 or 0.29 ± 0.05 vs 0.46 ± 0.10,0.20 ± 0.06 or 0.20± 0.04 vs 0.43 ± 0.09,P < 0.05),whereas there was no significant difference between BN and SAP groups at each time point. The result of PAF-R protein showed that the change of PAF-R protein in the SAP group and the BN group was consistent with that of PAF-R mRNA. There were significant differences at each time point except 1 h,when compared with those in the NC group (0.90 ± 0.02 or 0.80 ± 0.05 vs 0.48 ± 0.02,1.69 ± 0.06 or 1.58 ± 0.02 vs 0.48 ± 0.03,1.12 ± 0.10 or 0.98 ± 0.03 vs 0.49 ± 0.09,1.04 ± 0.14 or 0.87 ± 0.02 vs 0.52 ± 0.08,0.97 ± 0.16 or 0.90 ± 0.05 vs 0.49 ± 0.10,P < 0.05),whereas there was no significant difference between the BN group and the SAP group. CONCLUSION:PAF-R plays an important role in occurrence and development of SAP. BN52021 exerts biological effects through competitively inhibiting the binding of increased both PAF and PAF-R expression rather than through decreasing PAF-R expression in pancreatic tissues.
基金Supported by National Natural Science Foundation-funded Project:the Method of Establishing End Point Index Based on Principal Component Analysis Combined with Frequency Statistics for Evaluating TCM Efficacy(No.81373827)
文摘OBJECTIVE: To investigate the effects of tonifying Qi and activating blood circulation(SQABC), a method in Traditional Chinese Medicine(TCM), on end-point events in patients with myocardial infarction(MI) in this retrospective cohort study.METHODS: Clinical data were obtained from the medical records of patients with acute MI(AMI),both during hospitalization and follow-up, and included general demographic information(age, gender, and contact information), TCM regimens used,and end-point events.RESULTS: A total of 1596 patients with AMI were enrolled to this study, but data of only 1210 casesare accessible till follow-up. We classified the patients based on the exposure levels of SQABC.When comparing the results between all exposure and non-exposure groups, significant differences were identified, both during hospitalization and follow-ups. During hospitalization, cardiac death(4.40% vs 21.55%, P < 0.05) and cardiac shock(3.04% vs 11.62%, P < 0.05) were significantly lower in the exposure group than the non-exposure group. Similarly, during the follow-up, cardiac death(12.04% vs 20.49%, P < 0.05), acute heart failure(7.27% vs 11.81%, P < 0.05), composite endpoint of reinfarction and stroke(9.11% vs 15.28%,P < 0.05), and rehospitalization due to angina(25.49% vs 34.38%, P < 0.05) were significantly lower in the exposure group than the non-exposure group.CONCLUSION: Our findings suggest that SQABC can significantly benefits the subjects in the management of high-risk AMI in them.
基金the National Natural Science Foundation of China(Magnetic Nanoparticles-based Cell Affinity Capillary Electrochromatography and Its Applications,No.21275169Screening of Bioactive Compounds From Typical Huoxue Huayu Medicine by Platelet Based Capillary Electrochromatography,No.81202886)+1 种基金the Fundamental Research Funds for the Central Universities(Study on the Quality Control Method for the Animal Glue Medicine,No.CQDXWL-2012-028)the Chongqing Postdoctoral Funds(No.RC20120027)
文摘OBJECTIVE: To evaluate the anti-platelet aggregation effects of extracts from 31 Traditional Chinese Medicines(TCM) with the property of activating blood and resolving stasis in terms of TCM theory.METHODS: The 31 TCMs extracts were prepared using water, 90% ethanol and ethyl acetate., and the effects on anti-platelet aggregation were tested on a platelet aggregation analyzer in vitro with adenosine 5'-diphosphate, bovine thrombin and arachi-donic acid(AA) as aggregation inducers, respectively. Aspirin was the positive control.RESULTS: Lots of the tested TCMs had inhibitory effects with concentration-dependent manner on platelet aggregations induced by various agonists.Especially, some of the TCMs such as Chuanxiong(Rhizoma Chuanxiong), Yanhusuo(Rhizoma Corydalis Yanhusuo) and Danshen(Radix Salviae Miltiorrhizae) showed good anti-platelet aggregation effect similar or higher than that in positive control group.CONCLUSION: The study provided scientific references that several TCMs such as Chuanxiong(Rhizoma Chuanxiong), Yanhusuo(Rhizoma Corydalis Yanhusuo) and Danshen(Radix Salviae Miltiorrhizae),possess the property of anti-platelet aggregation.
文摘AIM： Platelet-activating factor （PAF） is a pro-inflammatory and angiogenic lipid mediator. Here we aimed to investigate levels of PAF, lyso-PAF （the PAF precursor）, phospholipase A2 （PLA2, the enzymatic activity generating lyso-PAF）, acetylhydrolase activity （AHA, the PAF degrading enzyme） and PAF receptor （PAF-R） transcripts in cirrhotic liver and hepatocellular carcinoma （HCC）. METHODS： Twenty-nine patients with HCC were enrolled in this study. Cirrhosis was present in fourteen patients and seven had no liver disease. Tissue PAF levels were investigated by a platelet-aggregation assay. Lyso- PAF was assessed after its chemical acetylation into PAR AHA was determined by degradation of [^3H]-PAE PLA2 levels were assessed by EIA. PAF-R transcripts were investigated using RT-PCR. RESULTS： Elevated amounts of PAF and PAF-R transcripts 1 （leukocyte-type） were found in cirrhotic tissues as compared with non-cirrhotic ones. Higher amounts of PAF and PAF-R transcripts 1 and 2 （tissue-type） were found in HCC tissues as compared with non-tumor tissues. PLA2, lyso-PAF and AHA levels were not changed in cirrhotic tissues and HCC. CONCLUSION： While the role of PAF is currently unknown in liver physiology, this study suggests its potential involvement in the inflammatory network found in the cirrhotic liver and in the angiogenic response during HCC.
文摘To explore the effect of Buyang Huanwu Decoction (BHD) on platelet activating factor (PAF) content in arterial blood pre- and post-arterial thrombosis in rats, male Wistar rats were randomly divided into 3 groups, the medicine group treated with BHD, the control group with dexamethasone liquid, and the blank group with distilled water. Oral administration was given for 14 consecutive days, once daily. Model of arterial thrombosis was established in the animals 2 hours after final medication, the blood content of PAF, dry weight (DW) and occlusion time (OT) of thrombus, and dry weight of thrombus/body weight (TW/BW) ratio were observed. Results indicated that BHD could markedly lower the arterial blood content of PAF after thrombosis, increase the OT of thrombus, reduce the dry weight of thrombus and the TW/BW ratio (P
基金This work was supported in part by National Institutes of Health Grant NS-NS091201(to MY)and VA MERIT Award IO1BX003441(to MY).
文摘Dementia is a clinical syndrome that affects approximately 47 million people worldwide and is characterized by progressive and irreversible decline of cognitive,behavioral and sesorimotor functions.Alzheimer’s disease(AD)accounts for approximately 60–80%of all cases of dementia,and neuropathologically is characterized by extracellular deposits of insoluble amyloid-β(Aβ)and intracellular aggregates of hyperphosphorylated tau.Significantly,although for a long time it was believed that the extracellular accumulation of Aβwas the culprit of the symptoms observed in these patients,more recent studies have shown that cognitive decline in people suffering this disease is associated with soluble Aβ-induced synaptic dysfunction instead of the formation of insoluble Aβ-containing extracellular plaques.These observations are translationally relevant because soluble Aβ-induced synaptic dysfunction is an early event in AD that precedes neuronal death,and thus is amenable to therapeutic interventions to prevent cognitive decline before the progression to irreversible brain damage.The plasminogen activating(PA)system is an enzymatic cascade that triggers the degradation of fibrin by catalyzing the conversion of plasminogen into plasmin via two serine proteinases:tissue-type plasminogen activator(tPA)and urokinase-type plasminogen activator(uPA).Experimental evidence reported over the last three decades has shown that tPA and uPA play a role in the pathogenesis of AD.However,these studies have focused on the ability of these plasminogen activators to trigger plasmin-induced cleavage of insoluble Aβ-containing extracellular plaques.In contrast,recent evidence indicates that activity-dependent release of uPA from the presynaptic terminal of cerebral cortical neurons protects the synapse from the deleterious effects of soluble Aβvia a mechanism that does not require plasmin generation or the cleavage of Aβfibrils.Below we discuss the role of the PA system in the pathogenesis of AD and the translational relevance of data published to this date.
基金Supported by National Natural Science Foundation of China Project:the Effect and Mechanism of Ulcerative Colitis Rats in the Intestinal Barrier Permeability by Huayutongyang Formula(No.81373848)
文摘OBJECTIVE: To evaluate the effect of decoction prepared with Yang-activating and stasis-eliminating medicinals from Traditional Chinese Medicine(TCM) on the intestinal mucosal permeability in rats with ulcerative colitis induced by dextran sulfate sodium(DSS).METHODS: Totally 55 male Wistar rats(body weight of 170-190 g) were randomly divided into the blank group(n = 10) and the model duplication group(n = 45). The blank group was not intervened, while the other was modeled with 5% dextran sulfate sodium by gavaging in a dosage of4 m L per day to induce ulcerative colitis, a total of7 days. Then, the model rats were divided into model blank group, mesalazine group and TCM group,and each group was consisted of 15 rats. They were given retention enema 10 min with normal saline,mesalazine enema(0.036 g/m L), and Yang-activating and stasis-eliminating decoction [0.54 g/m L of a decoction boiled by Puhuang(Pollen Typhae), Xiebai(Bulbus Allii Macrostemonis) and Wulingzhi(Faeces Trogopteri)] for 10 days respectively. Afterwards,all of the rats were evaluated by disease activity index(DAI), histological changes of distal colon, expression of occludin protein and ultrastructure of intestinal epithelial cells. Furthermore, ratio of lactulose to mannitol(L/M) discharged in urine was evaluated.RESULTS: Comparing the results between TCM and model control groups, scores of DAI and histological lesions decreased significantly(P = 0.000 <0.01), ultrastructures of intestinal epithelial cells and tight junctions were more complete. The expression of occludin protein(P = 0.001 < 0.01) increased while the L/M value decreased significantly(P = 0.000 < 0.01) in TCM group. There was no statistical difference between the TCM and mesalazine groups in results of each item(P > 0.05).CONCLUSION: The decoction prepared with Yang-activating and stasis-eliminating TCM medicianls can restore intestinal mucosal epithelial cells and tight junctions the model rats with ulcerative colitis; it can reduce histological lesions and protect the permeability of intestinal mucosa barrier in the rats as well.
基金Supported by the Key Scientific and Technological Research Foundation of the National 863 Program,No.2003AA208106Medical Outstandard Foundation of Army,No.04J020
文摘AIM： To evaluate the changes in hepatic platelet activating factor （PAF） and its receptors and their effect on portal pressure of cirrhotic rats induced by CCh. METHODS： A model of liver cirrhosis was replicated in rats by intra-peritoneal injection of CCh for 8 wk. We determined the effect of hepatic PAF and its receptor level on portal and arterial pressure by EIA, saturation binding and RT-PCR technique. RESULTS： Compared to control rats, cirrhotic rats had higher hepatic PAF levels and output as well as higher plasma PAF levels （P〈0.01, P〈0.01, P〈0.05, respectively）. Both hepatic PAF receptor mRNA levels and PAF binding were nearly 3-fold greater in cirrhotic rats （P〈0.01）. Portal injection of PAF （1 g/kg WT） increased the portal pressure by 22% and 33% in control and cirrhotic rats, respectively. In contrast, the arterial pressure was decreased in the both groups （54% in control rats and 42% in cirrhotic rats）. Injection of the PAF antagonist BN52021 （5 mg/kg WT） decreased the portal pressure by 16% in cirrhotic rats but had no effect in the control rats. CONCLUSION： The upregulation of the PAF system contributes to hepatic hemodynamic and metabolic abnormalities in drrhosis, and the increased release of PAF into the circulation has impacts on the systemic hemodynamics.
