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Objective: To explore the relationship of social support to patients with schizophrenia, family burden with patients' quality of life and family life satisfaction. Methods: Multi-stage stratified cluster random sampling was used to select 358 patients with schizophrenia and 358 patients' family members in Gansu Province who met the inclusion criteria were included. The Social Support Rating Scale, Family Burden Scale, Satisfaction with Life Scale and Quality of Life Scale were used in the survey. AMOS 24.0 was used to explore the pathway of influence of family burden on social support to patients with schizophrenia, patients' quality of life and patients' family life satisfaction. Results: There was a two-by-two significant correlation between patients' access to social support, family burden, patients' life quality and family life satisfaction (P<0.05), and the total score of the social support scale negatively predicted the total score of the life quality scale (β=-0.28, P<0.05) and positively predicted the total score of the life satisfaction scale (β=0.52, P<0.05). Family burden was a full mediator between the social support to the patient and the patient's quality of life, and as a partial mediator between the social support to the patient and the family's life satisfaction. Conclusions: Social support to people with schizophrenia is a significant predictor of their quality of life and family life satisfaction. Family burden mediates the relationship of social support to patients with their quality of life and family life satisfaction. Interventions can focus on increasing social support for the patient and reducing the burden on the patient's family to improve the patient's quality of life and increase the satisfaction of the patient's family.
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Humans , Patient Satisfaction , Quality of Life , Schizophrenia , Family Relations , Social SupportABSTRACT
The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling exert essential regulatory function in microbial-and onco-immunology through the induction of cytokines, primarily type I interferons. Recently, the aberrant and deranged signaling of the cGAS-STING axis is closely implicated in multiple sterile inflammatory diseases, including heart failure, myocardial infarction, cardiac hypertrophy, nonalcoholic fatty liver diseases, aortic aneurysm and dissection, obesity, etc. This is because of the massive loads of damage-associated molecular patterns (mitochondrial DNA, DNA in extracellular vesicles) liberated from recurrent injury to metabolic cellular organelles and tissues, which are sensed by the pathway. Also, the cGAS-STING pathway crosstalk with essential intracellular homeostasis processes like apoptosis, autophagy, and regulate cellular metabolism. Targeting derailed STING signaling has become necessary for chronic inflammatory diseases. Meanwhile, excessive type I interferons signaling impact on cardiovascular and metabolic health remain entirely elusive. In this review, we summarize the intimate connection between the cGAS-STING pathway and cardiovascular and metabolic disorders. We also discuss some potential small molecule inhibitors for the pathway. This review provides insight to stimulate interest in and support future research into understanding this signaling axis in cardiovascular and metabolic tissues and diseases.
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Atrial Ca2+ handling abnormalities, mainly involving the dysfunction of ryanodine receptor (RyR) and sarcoplasmic reticulum Ca2+-ATPase (SERCA), play a role in the pathogenesis of atrial fibrillation (AF). Previously, we found that the expression and function of transient receptor potential vanilloid subtype 4 (TRPV4) are upregulated in a sterile pericarditis (SP) rat model of AF, and oral administration of TRPV4 inhibitor GSK2193874 alleviates AF in this animal model. The aim of this study was to investigate whether oral administration of GSK2193874 could alleviate atrial Ca2+ handling abnormalities in SP rats. A SP rat model of AF was established by daubing sterile talcum powder on both atria of Sprague-Dawley (SD) rats after a pericardiotomy, to simulate the pathogenesis of postoperative atrial fibrillation (POAF). On the 3rd postoperative day, Ca2+ signals of atria were collected in isolated perfused hearts by optical mapping. Ca2+ transient duration (CaD), alternan, and the recovery properties of Ca2+ transient (CaT) were quantified and analyzed. GSK2193874 treatment reversed the abnormal prolongation of time to peak (determined mainly by RyR activity) and CaD (determined mainly by SERCA activity), as well as the regional heterogeneity of CaD in SP rats. Furthermore, GSK2193874 treatment relieved alternan in SP rats, and reduced its incidence of discordant alternan (DIS-ALT). More importantly, GSK2193874 treatment prevented the reduction of the S2/S1 CaT ratio (determined mainly by RyR refractoriness) in SP rats, and decreased its regional heterogeneity. Taken together, oral administration of TRPV4 inhibitor alleviates Ca2+ handling abnormalities in SP rats primarily by blocking the TRPV4-Ca2+-RyR pathway, and thus exerts therapeutic effect on POAF.
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Animals , Rats , Administration, Oral , Atrial Fibrillation/etiology , Calcium/metabolism , Myocytes, Cardiac/metabolism , Pericarditis/pathology , Rats, Sprague-Dawley , Ryanodine Receptor Calcium Release Channel/pharmacology , Sarcoplasmic Reticulum/pathology , TRPV Cation ChannelsABSTRACT
To establish patient derived xenograft (PDX) model of malignant peritoneal mesothelioma (MPM), and to identify the key characteristics of tumor biology of the model, so as to provide an experiment platform for studying the pathologic mechanisms and new therapeutic strategies for MPM. Surgically excised MPM tumor tissues were inoculated subcutaneously in BALB/c-nu/nu mice for 3 stable passages. In the 4th passage, the subcutaneous tumors were harvested under aseptic conditions, cleaned and made into MPM tumor cell homogenate. Four nude mice (two males and two females) were selected and one male and one female nude mouse were inoculated in the abdominal cavity at the dose of 100 μL, others were inoculated at a dose of 200 μL. The PDX model of MPM was established. The changes of body mass in nude mice were measured regularly, the extent of abdominal and pelvic tumors was judged by experimental peritoneal cancer index (ePCI) score, and the pathologic characteristics of tumors were analyzed. The subcutaneous and abdominal animal models of MPM were successfully established. The subcutaneous tumor model grew into tumor on the 20th day, followed by a slow growth stage between the 20th and 29th day, then a rapid growth stage between the 30th and 57th day. According to the dose of tumor cells (100, 200 μL) and timing (14th and 69th days after grafting), the abdominal tumor model successfully simulated the early and late clinical stages of MPM. The HE staining results of the MPM nude mice model showed that the tumor was epithelial mesothelioma and invaded most of the organs, including liver, spleen, pancreas, mesentery. Immunohistochemical staining for calretinin, cytokeratin 5/6, WT1 and Ki-67 were positive. Whole-genome exon sequencing identified 26 and 36 high frequency gene mutations in tumors derived from the PDX model and clinical sample from patients, including 21 common gene mutations. The PDX model of MPM is established. The model is characterized by highly malignant tumor with rapid growth and high invasiveness.
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Agriculture is the foundation of social development. Under the pressure of population growth, natural disasters, environmental pollution, climate change, and food safety, the interdisciplinary "new agriculture" is becoming an important trend of modern agriculture. In fact, new agriculture is not only the foundation of great health and new energy sources, but is also the cornerstone of national food security, energy security, and biosafety. Hydrogen agronomy focuses mainly on the mechanism of hydrogen gas (H
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Objective:To investigate the molecular mechanism of Buyang Huanwu Tang in improving cerebral vasospasm after subarachnoid hemorrhage. Method:Eighty male Sprague-Dawley rats were randomly divided into sham operation group, model group, Buyang Huanwu Tang low and high dose (13, 26 g·kg-1·d-1) group. According to 10 mL·kg-1, the drug was administered twice a day for 7 days. The subarachnoid hemorrhage model was made by double occipital pool injection method. The neurological function scores of rats in each group were evaluated at 1, 3, 5 and 7 days. The diameter of basilar artery was measured by hematoxylin-eosin (HE)staining. The expressions of phosphp-phosphoinositide 3-kinases(p-PI3K), phosphp-protein kinase B(p-Akt),endothelial nitric oxide synthase(eNOS) and neuronal nitric oxide synthase(nNOS) protein in basilar artery brain tissue were detected by Western blot. The expression of nitric oxide(NO) and endothelin-1(ET-1) in rat cerebrospinal fluid was detected by enzyme-linked immunosorbent assay (ELISA). Result:Compared with sham operation group, the neurological function scores of the model group were significantly decreased (PPPPP-1·d-1) increased the neurological function scores 3 to 5 days after treatment, and the basilar artery diameter was significant increased (PPPPPPPPPConclusion:The protective effect of Buyang Huanwu Tang on cerebral vasospasm after subarachnoid hemorrhage may be related to up-regulation of p-PI3K, p-Akt and eNOS expression in PI3K/Akt/eNOS signaling pathway, thereby increasing NO production.
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Objective:To explore the effect of aerobic exercise on behavioral function in rats with cerebral small vessel disease and its mechanism. Methods:Eight-week-old male Sprague-Dawley rats were randomly divided into sham group (n = 16), model group (n = 16) and swimming group (n = 16). The model was developed with bilateral common carotid artery ligation. They were assessed with burrowing test after four weeks of swimming exercise. The levels of brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) protein in hippocampus were detected with Western blotting. The development of dendrites and synaptic spines in hippocampal neurons was observed with Golgi staining. The expression of Ki67, doublecortin (DCX) and Neun in hippocampal dentate gyrus was detected with immunofluorescence. Results:Compared with the model group, the burrowing ability improved in the swimming group (P < 0.05), with increase of levels of BDNF and TrkB in hippocampus (P < 0.05), Ki67/DCX and Neun positive cells in hippocampal dentate gyrus (P < 0.05), and extension of dendrites and length of synaptic spine in hippocampal neurons (P < 0.05). Conclusion:Aerobic exercise may promote the proliferation and differentiation of hippocampal neurons through BDNF/TrkB signaling pathway, expression of Ki67/DCX and Neun and development of hippocampal neurons, to improve behavioral function in rats with cerebral small vessel disease.
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Objective: To investigate the metabolic stability, the main CYP450 enzymes phenotypes and metabolites of Diosbulbin B based on in vitro metabolism model. Methods: For metabolic stability study, UPLC-MS/MS was used to detect the remaining Diosbulbin B content in the incubation solution after being incubated with human and rat liver microsomes, respectively. Ten recombinant human CYP450 enzymes (1A1, 1A2, 1B1, 2A13, 2A6, 2B6, 2D6, 2C9, 2C19, 3A4) were used for identifying the metabolic enzyme phenotypes of Diosbulbin B. Moreover, the major metabolic enzyme phenotype for the metabolism of Diosbulbin B was confirmed and verified by the rat isolated hepatic perfusion model. The metabolites of Diosbulbin B in human and rat liver microsomes were determined by LC-MS/MS. Results: The metabolic percentage of Diosbulbin B in human and rat liver microsomes were 37% and 59%, respectively. Its half-lives t1/2 in human and rat liver microsomes were 97.4 and 52.3 min, respectively. The intrinsic clearance rates CLint in human and rat livers were 8.23 and 23.9 mL/(min•kg), and liver clearance CLh in human and rat livers were 5.89 and 16.8 mL/(min•kg). It can be found that the metabolic rate of Diosbulbin B in rat liver microsomes was faster than in human liver microsomes. There were five CYP enzymes, including 3A4, 2C19, 2C9, 1A13 and 1A1, related to the metabolism of Diosbulbin B, especially CYP3A4. The hepatic perfusion experimental results showed that the metabolism of Diosbulbin B was inhibited by ketoconazole, and the inhibitory effect was enhanced along with the increasing dosage of ketoconazole, which confirmed that CYP3A4 played an important role in metabolism of Diosbulbin B. There was one metabolite (M1) of Diosbulbin B has been found in both human and rat liver microsomes incubation. Conclusion: The metabolic rate of Diosbulbin B in rat liver microsomes was faster than human liver microsomes. The CYP3A4 plays a leading role in the metabolism of Diosbulbin B. And a demethylated metabolite of Diosbulbin B was appeared in both human and rat liver microsomes incubation.
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Objective To study operative treatment of severe tibial pilon fracture.Methods Between March 2010 and September 2016,29 patients with severe pilon fracture received operative treatment and complete follow-up at Department of Orthopaedic Surgery,Maternal and Child Care Service Centre of Guangzhou Nansha District.They were 24 men and 5 women,aged from 23 to 62 years (average,40.3 years).According to AO/OTA classification,9 cases were type C1,12 type C2 and 8 type C3.There were 6 open and 23 closed fractures.Of them,27 were complicated with fibular fracture.Open reduction and intenal fixation was conducted in 22 cases and limited internal fixation combined with external fixation in 7.Results This cohort was followed up for an average of 15 months (from 12 to 25 mouths).All the fractures obtained union after an average of 16 weeks (from 8 to 28 weeks),but the union in 5 cases was delayed.According to American Orthopaedic Foot and Ankle Society (AOFAS) criteria for ankle and hind foot,16 cases were rated as excellent,9 as good,3 as fair,one as poor,yielding an excellent to good rate of 86.2％.The main complications included superficial necrosis of wound skin in 3 cases,which were cured by skin flap repair after wound treatment,and superficial and deep infection both in 2 cases,which were cured by dressing change.Conclusions Severe tibial pilon fractures should be treated according to their different types and severities of soft tissue injury,using different operative methods and timing.
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BACKGROUND: Arthroscopic reconstruction for treatment of avulsion fracture at the tibial insertion of the knee posterior cruciate ligament (PCL) can minimize surgical trauma to the largest degree. However, its implants have relatively poor stability; therefore, functional exercise cannot be performed in the early stages after surgery, which is inconducive to knee function recovery. It is extremely challenging to perform traditional open reduction with internal fixation to repair avulsion fractures at the tibial insertion of the knee PCL. Often, the crushed bones cannot be firmly fixed, leading to a poor repair effect. OBJECTIVE: To design a new inverted "L"-shaped incision in the popliteal fossa through which bone plates were inserted to fix the crushed bones and to reconstruct PCL tension, facilitating knee function recovery; to compare the therapeutic effects of this new fixation and reconstruction method, and arthroscopic reconstruction for treating avulsion fracture at the tibial insertion of the knee PCL. METHODS: A prospective, single-center, non-randomized controlled trial. One hundred and eighty patients (knees) with avulsion fracture at the tibial insertion of the knee PCL will be assigned to two groups based on treatment methods: arthroscopic reconstruction group (n = 90;fracture fixation and repair under the arthroscope) and new method group (n = 90; bone plates will be inserted through an "L"-shaped incision in the popliteal fossa to fix the crushed bones and reconstruct PCL tension). After surgery, these patients will be followed up for 6 weeks, 6 months, and 12 months. RESULTS AND CONCLUSION: The primary outcome measure is the excellent and good rate of knee function recovery at 12 months after surgery as evaluated by Lysholm Knee Scoring Scale score (Herein referred to as Lysholm score). The secondary outcome measures are the excellent and good rate of knee function recovery before surgery, 6 weeks and 6 months after surgery; Lysholm score before surgery, 6 weeks, 6 months and 12 months after surgery; Hospital for Special Surgery (HSS) knee score, Visual Analogue Scale (VAS) score, posterior drawer test negative rate, X-ray morphology of the knee before surgery, and 6 weeks, 6 months, and 12 months after surgery and; incidence of adverse events at 6 weeks, 6 months and 12 months after surgery. Results of a preliminary study involving 62 patients (knees) with avulsion fracture at the tibial insertion of the knee PCL showed that posterior drawer test negative rate and Lysholm score were significantly higher in the new method group compared to the arthroscopic reconstruction group (P < 0.05) at 3 months after surgery. This study will be performed to compare the therapeutic effects of bone plate insertion through an "L"-shaped incision made in the popliteal fossa to fix the crushed bones and to reconstruct PCL tension, and traditional fracture fixation and repair under the arthroscope to treat avulsion fracture at the tibial insertion of the knee PCL. We believe that the former method will be superior to the latter one because it can fix the avulsion fracture more firmly, facilitating knee function recovery. This study was approved by Medical Ethics Committee of Cangzhou Central Hospital of China (approval No. 2017-120-01). This study will be performed in strict accordance with the Declaration of Helsinki formulated by the World Medical Association. Participants provided signed informed consent prior to participation in the study. This study was designed in December 2017. Patient recruitment and data collection will begin in April 2018. Patient recruitment will end in June 2019. Data analysis will be performed in August 2020. The study will be completed in October 2020. Results will be disseminated through presentations at scientific meetings and/or by publication in a peer-reviewed journal. This trial was registered with the Chinese Clinical Trial Registry (registration number:ChiCTR1800015026). The version of this study protocol is (1.0).
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OBJECTIVE:To systematically review the efficacy and safety of intrathecal injection of vancomycin combined with dexamethasone in the treatment of intracranial infection,and to provide evidence-based reference in the clinic. METHODS:Re-trieved from PubMed,Medline,CJFD,VIP,Wanfang databases,randomized controlled trials(RCTs)about intrathecal injection of vancomycin combined with dexamethasone in the treatment of intracranial infection were collected. Two reviewers independently screened literature,extracted data and assessed the risk of bias of included studies according to Cochrane system review manual 5.0.1. Then Meta-analysis was conducted by Rev Man 5.2 statistical software. RESULTS:Total of 8 RCTs were included,involv-ing 543 patients. Meta-analysis showed that,compared with intravenous dripping of ceftriaxone or vancomycin,intrathecal injec-tion of vancomycin combined with dexamethasone could significantly increase response rate [RR=1.18,95%CI(1.11,1.26),P<0.001] and bacterial clearance rate of CSF[RR=1.13,95%CI(1.01,1.27),P<0.001] of intracranial infection patients,shortened treatment time [SMD=-1.60,95%CI(-1.89,-1.30),P<0.001],reduce the incidence of ADR [RR=0.48,95%CI(0.32,0.73), P<0.001]. At the same time,it also could improve changes of intracranial pressure[SMD=-1.78,95% CI(-2.10,-1.47),P<0.001],changes of protein quantitation of CSF[SMD=-0.18,95%CI(-0.25,-0.11),P<0.001] and changes of glucose quantita-tion of CSF[SMD=1.77,95%CI(0.91,2.63),P<0.001],with statistical significance. CONCLUSIONS:Intrathecal injection of van-comycin combined with dexamethasone shows good clinical efficacy for intracranial infection,improves bacterial clearance rate, shortens treatment duration,significantly lowers intracranial pressure and protein quantitation,improves glucose quantitation of cere-brospinal fluid,with good safety.
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Objective:To assess trend of clinical features,diagnosis,treatments and outcomes for in-hospital patients of acute ST-segment elevation myocardial infarction (STEMI) in Hebei province from 2001 to 2011.Methods:Our research was based on the information of China PEACE retrospective acute myocardial infarction (AMI) study.We conducted an analysis from 8 hospitals in Hebei province including 1 third class hospital and 7 second class hospitals for STEMI patients who were diagnosed,treated and discharged in those hospitals in 2001,2006 and 2011.The clinical features,process of diagnosis and treatment and outcomes were summarized.Results:A total of 832 medical records were enrolled.During 2001 to 2011,the mean age for in-hospital STEMI patients was increased as 63.5 years in 2001,65.0 years in 2006 and 66.0 years in 2011,P=0.0097;female ratio was similar as 30.1％ in 2001,30.7％ in 2006 and 30.3％ in 2011,P=0.9846;the ratio for cardiovascular risk factors were elevated as 69.9％ in 2001,87.1％ in 2006 and 87.0％ in 2011,P＜0.0010.In patients without documented contraindications,reperfusion rate was similar,P=0.8990 and primary percutaneous coronary intervention (PCI) conduction rate was similar.The following drug therapies were increased:aspirin (P＜0.0001),clopidogrel (P＜0.0001),β-blockers (P=0.0172),statins (P＜0.0001) and ACEI/ARB (P=0.0008).In 2001,2006 and 2011,the 7-day in-hospital mortality,the ratio of death and gave-up treatment were similar,P=0.5854 and P=0.3516 respectively.Conclusion:During 2001 to 2011,the onset age and the prevalence of cardiovascular risk factors were increased in STEMI patients in Hebei province;drug therapy for secondary prevention of coronary artery disease was elevated by years while the reperfusion rate was similar and 7-day mortality was similar.
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Objective:To assess trend of clinical features,diagnosis,treatments and outcomes for in-hospital patients of acute ST-segment elevation myocardial infarction (STEMI) in Hebei province from 2001 to 2011.Methods:Our research was based on the information of China PEACE retrospective acute myocardial infarction (AMI) study.We conducted an analysis from 8 hospitals in Hebei province including 1 third class hospital and 7 second class hospitals for STEMI patients who were diagnosed,treated and discharged in those hospitals in 2001,2006 and 2011.The clinical features,process of diagnosis and treatment and outcomes were summarized.Results:A total of 832 medical records were enrolled.During 2001 to 2011,the mean age for in-hospital STEMI patients was increased as 63.5 years in 2001,65.0 years in 2006 and 66.0 years in 2011,P=0.0097;female ratio was similar as 30.1％ in 2001,30.7％ in 2006 and 30.3％ in 2011,P=0.9846;the ratio for cardiovascular risk factors were elevated as 69.9％ in 2001,87.1％ in 2006 and 87.0％ in 2011,P＜0.0010.In patients without documented contraindications,reperfusion rate was similar,P=0.8990 and primary percutaneous coronary intervention (PCI) conduction rate was similar.The following drug therapies were increased:aspirin (P＜0.0001),clopidogrel (P＜0.0001),β-blockers (P=0.0172),statins (P＜0.0001) and ACEI/ARB (P=0.0008).In 2001,2006 and 2011,the 7-day in-hospital mortality,the ratio of death and gave-up treatment were similar,P=0.5854 and P=0.3516 respectively.Conclusion:During 2001 to 2011,the onset age and the prevalence of cardiovascular risk factors were increased in STEMI patients in Hebei province;drug therapy for secondary prevention of coronary artery disease was elevated by years while the reperfusion rate was similar and 7-day mortality was similar.
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OBJECTIVE@#To study the effect of hGC-MSCs from human gastric cancer tissue on cell proliferation, invasion and epithelial-mesenchymal transition in tumor tissue of gastric cancer tumor-bearing mice.@*METHODS@#BABL/c nude mice were selected as experimental animals and gastric cancer tumor-bearing mice model were established by subcutaneous injection of gastric cancer cells, randomly divided into different intervention groups. hGC-MSCs group were given different amounts of gastric cancer cells for subcutaneous injection, PBS group was given equal volume of PBS for subcutaneous injection. Then tumor tissue volume were determined, tumor-bearing mice were killed and tumor tissues were collected, mRNA expression of proliferation, invasion, EMT-related molecules were determined.@*RESULTS@#4, 8, 12, 16, 20 d after intervention, tumor tissue volume of hGC-MSCs group were significantly higher than those of PBS group and the more the number of hGC-MSCs, the higher the tumor tissue volume; mRNA contents of Ki-67, PCNA, Bcl-2, MMP-2, MMP-7, MMP-9, MMP-14, N-cadherin, vimentin, Snail and Twist in tumor tissue of hGC-MSCs group were higher than those of PBS group, and mRNA contents of Bax, TIMP1, TIMP2 and E-cadherin were lower than those of PBS group.@*CONCLUSION@#hGC-MSCs from human gastric cancer tissue can promote the tumor growth in gastric cancer tumor-bearing mice, and the molecular mechanism includes promoting cell proliferation, invasion and epithelial-mesenchymal transition.
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Objective To study the effect of hGC-MSCs from human gastric cancer tissue on cell proliferation, invasion and epithelial-mesenchymal transition in tumor tissue of gastric cancer tumor-bearing mice. Methods BABL/c nude mice were selected as experimental animals and gastric cancer tumor-bearing mice model were established by subcutaneous injection of gastric cancer cells, randomly divided into different intervention groups. hGC-MSCs group were given different amounts of gastric cancer cells for subcutaneous injection, PBS group was given equal volume of PBS for subcutaneous injection. Then tumor tissue volume were determined, tumor-bearing mice were killed and tumor tissues were collected, mRNA expression of proliferation, invasion, EMT-related molecules were determined. Results 4, 8, 12, 16, 20 d after intervention, tumor tissue volume of hGC-MSCs group were significantly higher than those of PBS group and the more the number of hGC-MSCs, the higher the tumor tissue volume; mRNA contents of Ki-67, PCNA, Bcl-2, MMP-2, MMP-7, MMP-9, MMP-14, N-cadherin, vimentin, Snail and Twist in tumor tissue of hGC-MSCs group were higher than those of PBS group, and mRNA contents of Bax, TIMP1, TIMP2 and E-cadherin were lower than those of PBS group. Conclusion hGC-MSCs from human gastric cancer tissue can promote the tumor growth in gastric cancer tumor-bearing mice, and the molecular mechanism includes promoting cell proliferation, invasion and epithelial-mesenchymal transition.
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This study was aimed to establish an experimental mouse model of combined transgenic inhibition of both multifunctional Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and inward rectifier potassium current (Ik1), and to observe whether the specific inhibition of both CaMKII and Ik1 can bring about any effects on cardiac remodeling. Mice were divided into 4 groups: wild type (WT), CaMKII inhibited (AC3-I), Ik1 inhibited (Kir2.1-AAA) and combined inhibition of both CaMKII and Ik1 (AC3-I+Kir2.1-AAA). Mice in each group received electrocardiogram (ECG) and echocardiography examination. ECG in the condition of isoproterenol (ISO) injection was also checked. The whole cell patch clamp technique was used to measure Ik1 and the transient outward potassium current (Ito) from enzymatically isolated myocytes of left ventricle. In the condition of basal status, no significant changes of heart rate, PR interval and QRS interval were observed. No mouse showed ventricular arrhythmias in all of the 4 groups. After ISO injection, each group presented no significant ventricular arrhythmias either. The indexes measured by M-mode (motion-mode) and two-dimensional echocardiography had no significant differences among the four groups. Ik1 in AC3-I group was significantly higher than those in other three groups (P < 0.01) because of the results brought about by CaMKII inhibition. Among the latter three groups, both Kir2.1-AAA group and AC3-I+Kir2.1-AAA group had a significant reduced Ik1 compared with that of WT group, which was due to the Ik1 inhibition (P < 0.01). Ito in AC3-I group was higher than that of the other three groups (P < 0.01), but there were no significant differences in Ito among WT, Kir2.1-AAA and AC3-I+Kir2.1-AAA groups. Thus, combined transgenic myocardial CaMKII and Ik1 inhibition eliminated the up-regulation of Ik1 in CaMKII inhibited mice, and had no effects on cardiac remodeling including heart structure and function as well as arrhythmias at the basic and ISO conditions. The results of this study may provide a basis for the further investigation of combined inhibition of CaMKII and Ik1 in pathogenic cardiac remodeling.
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Animals , Mice , Arrhythmias, Cardiac , Brugada Syndrome , Calcium-Calmodulin-Dependent Protein Kinase Type 2 , Physiology , Cardiac Conduction System Disease , Disease Models, Animal , Electrocardiography , Heart , Physiology , Heart Conduction System , Congenital Abnormalities , Heart Ventricles , Isoproterenol , Mice, Transgenic , Patch-Clamp Techniques , Potassium Channels, Inwardly Rectifying , Physiology , Up-Regulation , Ventricular RemodelingABSTRACT
This study was aimed to investigate the effects of blockade of Ca(2+) activated channel KCa3.1 and voltage-gated potassium channel Kv1.3 of the monocytes/macrophages on inflammatory monocyte chemotaxis. Chemotaxis assay was used to test the inflammatory Ly-6C(hi) monocyte chemotaxis caused by the monocytes/macrophages. The proliferation of monocytes/macrophages was detected by cell counting kit-8 (CCK8). Enzyme-linked immunosorbent assay (ELISA) was applied to detect the C-C motif ligand 7 (CCL7) in cultured media. The results showed that the recruitment of Ly-6C(hi) monocyte induced by monocytes/macrophages was suppressed by the potent Kv1.3 blocker Stichodactyla helianthus neurotoxin (ShK) or the specific KCa3.1 inhibitor TRAM-34. Meanwhile, the proliferation of monocytes/macrophages was significantly inhibited by ShK. The response of Ly-6C(hi) monocyte pretreated with ShK or TRAM-34 to CCL2 was declined. These results suggest that KCa3.1 and Kv1.3 may play an important role in monocytes/macrophages' proliferation and migration.
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Humans , Cell Movement , Cell Proliferation , Cnidarian Venoms , Pharmacology , Enzyme-Linked Immunosorbent Assay , Physiology , Macrophages , Cell Biology , Monocytes , Cell Biology , Protein Structure, Tertiary , Pyrazoles , Pharmacology , Small-Conductance Calcium-Activated Potassium Channels , PhysiologyABSTRACT
<p><b>OBJECTIVE</b>To explore the inflammatory cascade mechanism through Toll like receptor 2 (TLR2) pathway after cerebral ischemia/reperfusion, and to study molecular mechanisms of Guanmaitong (GMT) Tablet for protecting brain damage.</p><p><b>METHODS</b>We used bolt-line method to block/release the middle cerebral artery, causing cerebral ischemia/reperfusion (I/R) injury model. GMT Tablet was given by gastrogavage. Rats were then divided into the high dose GMT group (1200 mg/kg), the middle dose GMT group (600 mg/kg), the low dose GMT group (300 mg/kg), the positive control group (Tanakan, 20 mg/kg). Their right brain tissues were fixed in 10% neutral formalin. TLR2 expressions were detected by immunofluorescence staining. The total protein was extracted from right brain tissues by ultrasonica- tion. Expression levels of extracellular regulated protein kinases (ERK), phospho-extracellular regulated protein kinases (p-ERK), p38-mitogen activated protein kinases (p-ERK), phospho-p38-mitogen activated protein kinases [p-p38-MAPKs(p-p38)] were assessed by Western blot. Abdominal aortic blood was withdrawn. IL-6 and IL-1β levels were detected by ELISA in brain tissues and serum.</p><p><b>RESULTS</b>Compared with the sham-oepration group, expression levels of TLR2, ERK, p-ERK, p38, p-p38 protein were up-regulated (P < 0.05, P < 0.01), and contents of IL-6 and IL-1β in brain tissues and serum were increased in the model group (P < 0.01). Expression levels of TLR2, ERK, p-ERK, p38, p-p38 were down-regulated (P < 0.05, P < 0.01), and contents of IL-6 and IL-1β were reduced in brain tissues and serum in middle and high dose GMT groups (P < 0.05, P < 0.01).</p><p><b>CONCLUSIONS</b>TLR2 pathway was involved in cerebral I/R injury. GMT protected neurons by down-regulating protein expressions of TLR2, ERK, p-ERK, p38, p-p38 and contents of IL-1β and IL-6.</p>
Subject(s)
Animals , Rats , Blotting, Western , Brain Ischemia , Metabolism , Cerebral Infarction , Down-Regulation , Drugs, Chinese Herbal , Therapeutic Uses , Interleukin-1beta , Interleukin-6 , Rats, Sprague-Dawley , Reperfusion Injury , Tablets , Toll-Like Receptor 2 , Metabolism , Up-Regulation , p38 Mitogen-Activated Protein Kinases , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To investigate the mechanism that the formulas for activating blood and resolving stasis can regulate hemopoietic stem cell to produce new blood.</p><p><b>METHOD</b>Rats were established animal model of acute cerebral infarction by referencing Olivette' method. They were randomly divided into model group, the group of the high, middle, low dose of the formulas for activating blood and resolving stasis. Each group and then wasrandomly divided into subgroups by 1, 3, 7, 14, 28 d. Xuesaitong capsule was formulated into 20, 40, 60 g x L(-1) with normal saline. The rats were given gavage drugs once a day until the experient ended, and the model group was administrated by intragastrical perfusion of normal saline. ELISA was used to detect the expression of SCF in peripheral blood and bone marrow among different groups at different time points. Flow cytometry was used to observe the changes of CD117 in blood and bone marrow.</p><p><b>RESULT</b>The CD117+ HSC and SCF concentration in peripheral blood and bone marrow of model group were increasing during 1-14 d,there was a peak on the 14th day, then the expression was reducing. CD117+ HSC and SCF concentration rising trend in the group of the high, middle dose of the formulas for activating blood and resolving stasis was preceded model group (P < 0.05).</p><p><b>CONCLUSION</b>Activating blood and resolving stasis can regulate hemopoietic stem cell to produce new blood, and it is through the regulation of CD117+ HSC number to achieve the purpose.</p>
Subject(s)
Animals , Humans , Male , Rats , Bone Marrow Cells , Metabolism , Capsules , Cerebral Infarction , Blood , Drug Therapy , Genetics , Metabolism , Chemistry, Pharmaceutical , Drugs, Chinese Herbal , Hematopoietic Stem Cells , Metabolism , Proto-Oncogene Proteins c-kit , Genetics , Metabolism , Rats, Sprague-Dawley , Stem Cell Factor , Genetics , MetabolismABSTRACT
In early 2011, the serious outbreak of porcine pseudorabies virus (PRV) infection suddenly recurred in Henan and neighboring Provinces. To investigate the etiology of massive infection with PRV, 16 800 serum samples, 905 porcine epidemic diarrhea virus (PEDV) back-feeding tissues, and 56 PR gene deleted live vaccines were colleted from January 2011 to May 2013 to detect PRV field infection using a PRV gE antibody test kit. The gE and TK genes of 11 new epidemic PRV strains were sequenced by PCR, and their molecular characteristics were analyzed. Moreover, virus titer determination, protective test against PRV, and vaccine potency testing were performed. The results showed that the detection rate of PRV field infection-positive pig farms was 68.06%, and the overall positive rate of PRV field infection in serum was 38.47%; the positive rates in breeding sows, breeding boars, reserve pigs, and commercial pigs were 40.12%, 30.88%, 54.67%, and 26.52%, respectively. The new epidemic strains were in the same evolutionary branch and belonged to the virulent strain group. Compared with the classical PRV strain, the virulence of new epidemic strains changed a little. The length of gE gene was 1 787 bp, and the length of TK gene was 963 bp. The nucleotide homologies of gE and TK genes to Chinese reference strains were 98.2%-99.8% and 98.90%-99.6%, respectively, and the amino acid homologies were 97.1%-99.8% and 97.5%-99.4%, respectively. Commercial vaccine had a 100% protective effect against the new epidemic strains. The positive rate of PRV field infection was 0% in vaccine and 40.44% in back-feeding tissues. The results confirmed that PRV field infection rates were rising sharply among pigs in Henan and neighboring Provinces after 2011. The main virulence genes of new epidemic PRV strains did not change significantly over the years. PR gene deleted live vaccines had no PRV field infection and could completely resist the attack of new strains. The virus carriage of breeding boars and reserve pigs and the serious PRV field infection in PEDV back-feeding tissues were the main causative factors for massive infection with PRV and epidemic outbreak in Henan and neighboring Provinces from 2011 to 2013.