MicroRNA-137 inhibits pituitary prolactinoma proliferation by targeting AKT2.

PURPOSE: Prolactinoma is the most common type of pituitary adenoma. Most prolactinoma need medical treatment, but some of them are aggressive and require surgery. In previous decades, some miRNAs have been manifested as oncogenes or tumor suppressors. Consequently, miRNAs' abnormal expression involves tumorigenesis, invasion, and metastasis of different types of tumors, including pituitary tumors. The current study aim to explore the aggressiveness-associated miRNAs in prolactinoma and underlying molecular mechanisms based on the bioinformatic analysis and fundamental experiment studies. METHODS: GSE46294 miRNA expression profile from the Gene Expression Omnibus (GEO) database was downloaded. Differentially expressed miRNAs (DEMs) were filtered from this data. Subsequently, the target genes of downregulated miRNAs were analyzed by Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. RT-qPCR, western blot, and CCK-8 assays were used to validate the effect of miR-137 on the proliferation of MMQ cells through AKT2. Finally, the binding site of rat miR-137 to AKT2 were predicted by Targetscan and Bibiserv database, and verified by double luciferase reporter assay. RESULTS: Twenty-four changed DEMs (fourteen upregulated and ten downregulated) were identified. Target genes of downregulated DEMs were classified into three groups by GO terms. KEGG pathway enrichment analysis revealed these target genes enriched in the PI3K-Akt pathway. We also confirmed that miR-137 can target AKT2 and inhibit the proliferation of MMQ cells induced by AKT2. CONCLUSION: MiR-137 suppressed prolactinomas' aggressive behavior by targeting AKT2.

Diversity of sugarcane root-associated endophytic Bacillus and their activities in enhancing plant growth.

AIMS: Plant tissues are the reservoirs of beneficial and harmful microbes that regulates plant growth. In the present study, we investigated the diversity, function and colonization of sugarcane roots associated with Bacillus spp. METHODS AND RESULTS: A total of 20 Bacillus strains were isolated and identified by 16S rRNA gene sequencing, and their genetic diversity was examined by BOX, ERIC, REP, (GTG)5 PCR techniques. Among all Bacillus isolates, 65% showed indole acetic acid-like compounds production, 50% solubilized phosphorus and 25% of the isolates were able to secrete siderophore. Moreover, all 20 Bacillus isolates showed antifungal activity against eight fungal pathogens and 11 of them (55%) antagonized tomato grey mold. Based on the plant growth-promoting traits and antifungal potential, isolate Y8 was selected for root and plant tissue colonization assays and a greenhouse-level sugarcane growth promotion study. Fluorescence microscopy results confirmed that isolate Y8 has a strong ability to colonize in the sugarcane root and leaves, and the root surface association of Y8 was confirmed by scanning electron microscopy. Furthermore, greenhouse experimental results demonstrated that Y8 has a significant effect on enhancing sugarcane biomass and root length. CONCLUSIONS: Endophytic Bacillus strains have growth-promoting properties and anti-fungal ability that can enhance plant fitness in an eco-friendly manner. SIGNIFICANCE AND IMPACT OF THE STUDY: Endophytic Bacillus strains would be a potential alternative to chemical fertilizer as well as a biocontrol agent in the future.

[Comparison on the 10 years risk for ischemic cardiovascular disease among Han, Uygur, Kazak population from Xinjiang Uygur Autonomous Region].

Objective: To compare the 10 years risk for ischemic cardiovascular disease among Han, Uygur, Kazak nationality residents of Xinjiang Uygur Autonomous Region. Methods: From October 2007 to October 2010,14 618 adult (aged ≥35 years) Han (n=5 757),Uygur (n=4 767) and Kazak (n=4 094) residents were selected to join this study through the four-stage stratified cluster sampling method from 7 cities and regions of Xinjiang Uygur Autonomous Region. The 10 years risk for ischemic cardiovascular disease was calculated according to the 10 years ischemic cardiovascular disease risk assessment form modified with Chinese characteristics and compared among the residents of 3 nationalities. Results: (1) There were significant differences in age, body mass index, systolic blood pressure, diastolic blood pressure,fasting blood glucose,triglycerides,total cholesterol,low-density lipoprotein,high-density lipoprotein cholesterol, smoking history, and drinking history among Han, Uygur, Kazak nationality population (all P< 0.001). (2) There were significant differences in 10 years risk for ischemic cardiovascular disease between different gender and age group including 35-39, 40-44, 45-49, 50-54, 55-59, and ≥60 years old between Han, Uygur, Kazak nationality population (all P<0.001). (3) There were significant differences in rates of 10%-20% and>20% of 10 years risk for ischemic cardiovascular disease between different gender in Han, Uygur, Kazak nationality population (P values were 0.013 and <0.001, respectively). There were no significant differences in rates of <5% and 5%-9% of 10 years risk for ischemic cardiovascular disease between different gender in Han,Uygur,Kazak nationality population (all P>0.05).(4) There were significant differences in detection rates of diabetes,hypertension,smoking,hypertriglyceridemia,and obesity in male and female Han,Uygur,Kazak nationality population with 10 years risk for ischemic cardiovascular disease ≥10% (P<0.01 or 0.05). Meanwhile,there was significant difference in detection rates of hypercholesteremia in male Han, Uygur, Kazak nationality adults(P<0.001). There were no significant differences in detection rates of elevated low density lipoprotein cholesterol and reduced high density lipoprotein cholesterol in male and female Han,Uygur,Kazak nationality adults (all P>0.05). Conclusion: There are gender and age differences in the 10 years risk for ischemic cardiovascular disease in ≥35 years old Han,Uygur,Kazak nationality adults from Xinjiang Uygur Autonomous Region.

[Clinical effect of minimally-Invasive surgical-transforaminal lumbar interbody fusion technique associated with percutaneous pedicle screws in micro endoscopy discectomy].

Objective: To evaluate the clinical efficacy between the minimally-Invasive surgical (MIS)-transforaminal lumbar interbody fusion (TLIF) technique associated with percutaneous pedicle screws in micro endoscopy discectomyand MIS-TLIF technique associated with both sides of the lower lumbar spine Wiltse approach in Quadrant channel with treatment of single segment herniation associated with lumbar instability syndrome. Methods: From January 2012 to January 2015, 75 cases that meet the inclusion and exclusion criteria were treated by retrospective study method, which were divided into two groups in Department of Orthopedics, the Affiliated Hospital of Putian University.Experimental group(30 patients) were treated with MIS-TLIF technique associated with percutaneous pedicle screws in microendoscopy discectomy, control group were treated with MIS-TLIF technique associated with both sides of the lower lumbar spine Wiltse approach in Quadrant Chanel.Compare operation time, blood loss, postoperativehospital stay, clinical efficacy, nailing accuracy, fusion rate, postoperative pain scoring of two groups. Results: The blood loss[(102.1±5.5) min vs(103.7±7.7) min, t=-0.586, P>0.05], postoperative blood loss, hospital stay[(44.6±5.2) ml and(57.2±5.3) ml, (7.3±1.6) d and(9.3±1.9) d; t=-5.813, -2.774, P<0.05], JOA score before and after surgery in same group were statistically significant(P<0.05), respectively.Patients of two groups compared with operation time, clinical efficacy, nailing accuracy[group A: 97.5%, group B: 95.7%; χ(2)=3.00, P>0.05.Postoperative 3 month , group A: 96.7%(29/30), group B: 94.3%(33/35; χ(2)=0.79, P>0.05], fusion rate[group A: 96.7%(29/30), group B: 94.3%(33/35), χ(2)=0.79, P>0.05], preoperative JOA score[(20.4±2.4)score and(7.9±1.0), (19.1±2.7)score and(7.8±1.2)score], postoperative JOA score were no statistically significant respectively, P>0.05. JOA score of both groups were statistically significant respectively Before and after operate.Excellent rate: group A; 84.4%(25/30), group B: 80.0%(28/35), χ(2)=0.43, P>0.05. Conclusion: MIS-TLIF technique associated with percutaneous pedicle screws in micro endoscopy discectomy relative to conventional minimally invasive spine surgery had many advantages: minimal damage, operation conveniently, precisely clinical effect, that is a kind of feasible and reliable minimally invasive surgery which is worth promoting.

Targeting Complement Pathways During Cold Ischemia and Reperfusion Prevents Delayed Graft Function.

The complement system plays a critical role in ischemia-reperfusion injury (IRI)-mediated delayed graft function (DGF). To better understand the roles of complement activation pathways in IRI in kidney transplantation, donor kidneys were treated ex vivo with terminal complement pathway (TP) inhibitor, anti-rat C5 mAb 18A10, or complement alternative pathway (AP) inhibitor TT30 for 28 h at 4°C pretransplantation in a syngeneic kidney transplantation rat model. All 18A10- and 67% of TT30-pretreated grafts, but only 16.7% of isotype control-pretreated grafts, survived beyond day 21 (p < 0.01). Inhibitor treatment in the final 45 min of 28-h cold ischemia (CI) similarly improved graft survival. Systemic posttransplant treatment with 18A10 resulted in 60% increased graft survival beyond day 21 (p < 0.01), while no TT30-treated rat survived > 6 days. Our results demonstrate that AP plays a prominent role during CI and that blocking either the AP or, more effectively the TP prevents ischemic injury and subsequent DGF. Multiple complement pathways may be activated and contribute to reperfusion injury; blocking the TP, but not the AP, posttransplant is effective in preventing reperfusion injury and increasing graft survival. These results demonstrate the feasibility of using complement inhibitors for prevention of DGF in humans.

Complement C5 Inhibition Reduces T Cell-Mediated Allograft Vasculopathy Caused by Both Alloantibody and Ischemia Reperfusion Injury in Humanized Mice.

Allograft vasculopathy (AV) is characterized by diffuse stenoses in the vasculature of solid organ transplants. Previously, we developed two humanized models showing that alloantibody and ischemia reperfusion injury (IRI) exacerbated T cell-mediated AV in human arterial xenografts in vivo. Herein we examined a causal role for terminal complement activation in both settings. IRI, in contrast to alloantibody, elicited widespread membrane attack complex (MAC) assembly throughout the vessel wall. Both alloantibody and IRI caused early (24 h) and robust endothelial cell (EC) activation localized to regions of intimal MAC deposition, indicated by increases in nuclear factor kappa B (NF-κB)-inducing kinase, an MAC-dependent activator of noncanonical NF-kB, VCAM-1 expression and Gr-1+ neutrophil infiltration. Endothelial cell activation by alloantibody was inhibited by antimouse C5 mAb, but not by anti-C5a mAb or by control mAb, implicating MAC as the primary target of anti-C5 mAb. Antimouse C5 mAb significantly reduced alloantibody- and IRI-enhanced T cell infiltration and AV-like changes, including neointimal hyperplasia as well as intraluminal thrombosis in a subset of IRI-treated arterial grafts. These results indicate that increased AV lesion formation in response to either alloantibody or IRI is dependent on complement C5 activation and, accordingly, inhibition of this pathway may attenuate AV.

Evaluation of efficacy, safety and tolerability of Ambrisentan in Chinese adults with pulmonary arterial hypertension: a prospective open label cohort study.

BACKGROUND: Although several new drugs have been approved in recent years, pulmonary arterial hypertension (PAH) remains a rapidly progressive disease with a poor prognosis. Ambrisentan, a selective endothelin type A antagonist, has been approved for treatment of PAH. This open label study assessed the efficacy and safety of ambrisentan in Chinese subjects with PAH. METHODS: Eligible patients with PAH (World Health Organisation [WHO] functional class [FC] II orIII) were enrolled and received Ambrisentan (5 mg) once daily for a 12-week preliminary evaluation period, and a 12-week dose-adjustment period (dose titration to 10 mgallowed). Endpoints included: change from baseline in 6-Minute Walk Distance (6-MWD), N-Terminal Pro B-Type Natriuretic Peptide (NT-pro-BNP), WHO FC, Borg Dyspnoea Index (BDI), clinical worsening of PAH and incidences of adverse events (AE). RESULTS: One hundred thirty-three subjects (85 % women, mean age: 36 years) with PAH (WHOFC II or III) were enrolled and received ambrisentan (5 mg) once daily for a 12-week preliminary evaluation period, and a 12-week dose-adjustment period. Mean (SD) duration of drug exposure was 161.7 (27.13) days. Ambrisentan (average daily dose of 6.27 mg) significantly improved exercise capacity (6MWD) from baseline (mean: 377.1 m [m]) at week 12 (+53.6 m, p < 0.001) (primary endpoint). Improvement in exercise capacity was noted as early as week 4, and was sustained up to week 24 (+ 64.4 m, p < 0.001). NT-pro-BNP plasma levels decreased significantly (p < 0.001) at week 12 (-861.4 ng/L) and week 24 (-806 ng/L) from baseline (mean: 1600.7 ng/L). The WHO FC showed improvements for 44 subjects at week 12 and 51 subjects at week 24. BDI scores decreased significantly at week 12 (-0.3, p < 0.001) and week 24 (-0.2, p = 0.003) from baseline (mean: 2.5). Four patients died during the study (sudden cardiac death [n = 2], cerebral haemorrhage [n = 1], cardiac failure [n = 1]). Drug related adverse events occurred in 34.3 % of subjects; peripheral oedema (11.2 %) and flushing (8.2 %) occurred most frequently. CONCLUSION: Ambrisentan (5 and 10 mg, orally) significantly improved the exercise capacity in Chinese PAH subjects with a safety profile similar to that observed in global studies. TRIAL REGISTRATION: NCT No. (ClinicalTrials.gov): NCT01808313 ; Registration date (first time): February 28, 2013.

Genetic polymorphisms of serum amyloid A1 and coronary artery disease risk.

Serum amyloid A (SAA) protein is not only an inflammatory factor but also an apolipoprotein that can replace apolipoprotein A1 (apoA1) as the major apolipoprotein of high-density lipoprotein cholesterol (HDL-C). However, the relationship between genetic polymorphisms of SAA and coronary artery disease (CAD) remains unclear. A total of four single nucleotide polymorphisms (rs12218, rs4638289, rs7131332, and rs11603089) of the SAA gene were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in two independent case-control studies, one of the Han population (1416 CAD patients and 1373 control subjects) and the other of the Uygur population (588 CAD patients and 529 control subjects). We found that the rs12218 CC genotype was more frequent among the CAD patients than among the controls in both the Han (8.3% vs. 4.8%, P < 0.001) and Uygur populations (15.5% vs. 11.3%, P < 0.05). After adjustments for confounding factors, such as sex, age, smoking, drinking, hypertension, diabetes, and serum levels of triglycerides, total cholesterol, HDL, and plasma SAA, the differences remained significant in the Han (CC vs. CT+TT, P < 0.001, OR = 3.863, 95% CI: 1.755-12.477) and Uygur groups (CC vs. CT+TT, P = 0.031, OR = 3.022, 95% CI: 1.033-8.840). Genetic polymorphisms in SAA1 are associated with CAD in the Han and Uygur populations in western China.

Prevalence of diabetes and impaired fasting glucose in Uygur children of Xinjiang, China.

This study was designed to estimate the prevalence of diabetes and impaired fasting glucose (IFG) in Xinjiang children in western China. Data were obtained from the Chun-Miao Project, a community-based, cross-sectional study designed to investigate the prevalence and risk factors of diabetes in children of the Chinese Uygur population in Xinjiang from February 2010 to May 2012. A total of 3644 children completed the survey and measurements of fasting glucose. Diabetes and IFG were defined using American Diabetes Association 2009 criteria. Overall, 0.7% of the 3644 Uygur children had IFG and 0.1% had diabetes. In the newborn to 8-year-old group, the prevalence of diabetes and IFG was 0.6 and 1.1%, respectively. In the 9-13-year-old group, the prevalence of diabetes and IFG was 0.1 and 0.7%, respectively. There was no evidence of IFG or diabetes in the 14-17-year-old group. Logistic regression analysis suggested that overweight and obesity were independent risk factors of diabetes in Uygur children of Xinjiang. The prevalence of diabetes and IFG in Uygur children was lower than that reported previously in children of other ethnicities in China.

Diagnostic efficacy of lung ultrasound in cardiogenic pulmonary edema: a systematic review and meta-analysis.

OBJECTIVE: This meta-analysis was performed to evaluate the diagnostic efficacy of lung ultrasound (LUS) in cardiogenic pulmonary edema. MATERIALS AND METHODS: An electronic search of databases, including MEDLINE, Embase, PubMed, and Web of Science, was performed to collect clinical studies on ultrasound diagnosis of cardiogenic pulmonary edema from inception to 23 March 2023. The number of patients with true-positive, true-negative, false-positive, and false-negative cardiogenic pulmonary edema diagnosed by LUS was collected, and the R package was used to analyze the diagnostic efficacy of LUS. RESULTS: Nine pieces of literature were finally included with 2,097 participants, including 1,047 patients with cardiogenic heart failure. Across the nine included papers, the pooled sensitivity of LUS in the included studies was 0.92 (95% CI: 0.84, 0.97) with a maximum sensitivity of 0.99 (95% CI: 0.96 to 1.00) and a minimum of 0.59 (95% CI: 0.50, 0.68). The pooled specificity of the included studies was 0.87 (95% CI: 0. 82, 0.91) with a maximum specificity of 0.93 (95% CI: 0.90-0.95) and a minimum of 0.80 (95% CI: 0.67, 0.89). The pooled AUC was 0.93 (95% CI: 0.84 to 0.97), suggesting a high diagnostic value of LUS in cardiogenic pulmonary edema. CONCLUSIONS: Lung ultrasound offers a good diagnostic efficacy for cardiogenic pulmonary edema. Further standardization of the examination method is required to provide a reference for the clinical use of LUS.

[Analysis of clinical characteristics of 35 inflammasomopathies cases].

Objective: To summarize the clinical characteristics of inflammasomopathies, enhance the recognition of those diseases, and help to establish the early diagnosis. Methods: The clinical manifestations including fever, rash, systems involvement as well as laboratory results and genotypic characteristics of 35 children with inflammasomopathies diagnosed by the Department of Pediatrics, Peking Union Medical College Hospital, from January 1, 2008 to December 31, 2020 were analyzed retrospectively. Results: A total of 35 cases of inflammasomopathies were diagnosed, and 20 of them were boys while 15 were girls. Inflammasomopathies patients have early onset, the age of onset as well as diagnostic age were 1 (0,7) and 7 (3,12), respectively. Among those patients, 10 had familial mediterranean fever, 3 had mevalonate kinase deficiency, 15 cases had NLRP3 gene associated autoinflammatory disease, 4 cases had NLRP12-associated autoinflammatory disease, 2 cases had familial cold autoinflammatory syndrome 3, and 1 case had familial cold autoinflammatory syndrome 4. A total of 34 cases (97%) showed recurrent fever, 27 cases (77%) had skin rashes, while 11 cases (31%), 10 cases (29%), and 8 cases (23%) were presented with lymphadenopathy, hepatosplenomegaly and growth retardation, respectively. In terms of systemic involvement, there were 18 cases (51%), 12 cases (34%), 8 cases (23%), and 5 cases (14%) with skeletal, neurological, auditory, and renal involvement, respectively. Central nervous system involvement was seen only in NLRP3 gene associtated autoinflammatory diseases (12 cases), sensorineural deafness was seen in NLRP3 gene associtated autoinflammatory diseases (6 cases) and NLRP12 gene associated autoinflammatory diseases (2 cases), and abdominal pain was observed in familial Mediterranean fever (5 cases), mevalonate kinase deficiency (1 case) and NLRP12 gene related autoinflammatory diseases (1 case). In the acute inflammatory phase, the acute phase reactants (erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)) of 35 cases (100%) were significantly increased. There were 21 cases received ferritin examination, and only 4 cases (19%) showed an increase of it. In terms of autoantibodies, among all 35 patients, 4 cases (11%) were positive for antinuclear antibodies (ANA). Conclusions: Fever, skin rash, and skeletal manifestations are the most common clinical features, accompanied with increased CRP and ESR, and negative results of autoantibodies such as ANA. The clinical manifestations of those diseases are complex and diverse, and it is prone to delayed diagnosis and treatment.

Modulation of retinoid signalling through NGF-induced nuclear export of NGFI-B.

The retinoid-X receptor (RXR) regulates multiple hormonal pathways through heterodimerization with nuclear receptors such as the all-trans retinoic acid receptor (RAR). The orphan nuclear receptor NGFI-B (also called Nur77) can heterodimerize with RXR. Here we show that nerve growth factor (NGF) induces the phosphorylation of Ser 105 of NGFI-B in PC12 phaeochromocytoma cells, resulting in translocation of the NGFI-B-RXR heterodimer complex out of the nucleus using nuclear export signals within NGFI-B. As a consequence of the redistribution of RXR, the transcriptional activity of RXR-RAR is reduced. NGFI-B-mediated nuclear export of receptors may serve as a mechanism for crosstalk between NGF and retinoid pathways.

[Clinical characteristics of 25 patients with type â interferonopathies].

Objective: To summarize the clinical characteristics of type I interferonopathies and provide clues for early identification and diagnosis. Methods: Clinical data of 20 patients admitted to Department of Pediatrics, Peking Union Medical College Hospital and 5 patients admitted to Department of Rheumatology and Immunology, Shenzhen Children's Hospital from January 2016 to September 2021 were retrospectively analyzed. The data included gene results, clinical manifestations and auxiliary examination results. Results: Of the 25 cases, 12 were males and 13 were females. Age of onset ranged from 1 day to 11 years. And 84% of them had the onset before the age of 3 years. The cases consisted of 14 cases of Aicardi-Goutières syndrome (AGS), 6 cases of adenosine deaminase 2 deficiency (DADA2), 3 cases of stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy (SAVI), and 2 cases of Spondyloenchondrodysplasia with immune dysregulation (SPENCDI). Eighteen patients (72%) experienced neurologic disorder, among whom 16 (64%) showed intracranial calcification, 11 (44%) had dystonia, 10 (40%) had leukodystrophy, 6 (24%) had epilepsy, 5 (20%) had brain atrophy and 5 (20%) had early-onset cerebrovascular events. Skin involvement occurred in 15 cases (60%), among whom 8 cases (32%) had chilblain-like rash, 4 cases (16%) had livedo reticularis, 3 cases (12%) had erythema, 2 cases (8%) had erythema nodosum and 2 cases (8%) had Raynaud's phenomenon. In addition, 12 cases (48%) had positive autoimmune antibodies, 10 cases (40%) manifested as developmental retardation, 8 cases (32%) experienced lung interstitial lesions, and 7 cases (28%) demonstrated thyroid dysfunction. And 1 died (4%) at 11 years of age. Conclusions: Type Ⅰinterferonopathies can involve multiple organs, and share the characteristics of systemic inflammatory and autoimmune diseases. The early-onset neurological symptoms (early-onset cerebrovascular events, intracranial calcification, leukodystrophy and cerebral atrophy), rashes (chilblain-like rash, livedo reticularis and erythema), positive autoimmune antibodies, developmental delay, interstitial lung disease and thyroid dysfunction may indicate type Ⅰ interferonopathies.

Acidic fibroblast growth factor in the developing rat embryo.

Compared to basic fibroblast growth factor (bFGF), a widely distributed, broad spectrum mitogen and mesoderm inducer, acidic fibroblast growth factor (aFGF) is reported to have an essentially neural distribution and to be undetectable in the early embryo. In the present investigation, we used immunoblotting and immunochemistry to assess the cellular and tissue distributions of aFGF and bFGF in 11-20-d rat embryos. Immunoblotting of crude and heparin-bound embryo extracts revealed faint bands at the expected 17-18-kD and predominant bands at an apparent molecular mass of 26 to 28-kD (despite reducing conditions) using multiple specific antibodies for aFGF and bFGF. Pretreatment with 8 M urea yielded 18-20-kD aFGF and bFGF and some 24-26-kD bFGF. Immunoreactivity for both aFGF and bFGF was positive and similar in the cytoplasm, nuclei, and extracellular matrix of cells of neuroectodermal and mesodermal origin, while it was negative in endoderm-derived cells. The distribution of immunoreactive aFGF and bFGF also showed changes during development that were associated with the process of cellular and tissue differentiation. For example, intensity and extent of immunoreactivity for both peptides progressively increased in the middle layer of the spinal cord with increasing differentiation of the neural cells. The immunostaining patterns were very similar for aFGF and bFGF for each organ and at each stage. In conclusion, high molecular mass forms of immunoreactive aFGF and bFGF are present in the rat embryo. Acidic FGF and bFGF are both widely distributed in tissues of neuroectodermal and mesodermal origin, and their distribution was very similar.

Requirement for generation of H2O2 for platelet-derived growth factor signal transduction.

Stimulation of rat vascular smooth muscle cells (VSMCs) by platelet-derived growth factor (PDGF) transiently increased the intracellular concentration of hydrogen peroxide (H2O2). This increase could be blunted by increasing the intracellular concentration of the scavenging enzyme catalase or by the chemical antioxidant N-acetylcysteine. The response of VSMCs to PDGF, which includes tyrosine phosphorylation, mitogen-activated protein kinase stimulation, DNA synthesis, and chemotaxis, was inhibited when the growth factor-stimulated rise in H2O2 concentration was blocked. These results suggest that H2O2 may act as a signal-transducing molecule, and they suggest a potential mechanism for the cardioprotective effects of antioxidants.

Perindopril inhibits myocardial apoptosis in mice with acute myocardial infarction through TLR4/NF-κB pathway.

OBJECTIVE: To explore the anti-apoptotic effect of perindopril on myocardial cells in mice with acute myocardial infarction (AMI). MATERIALS AND METHODS: A total of 48 mice were randomly divided into 4 groups before intervention, namely sham operation group (Sham group, n=12), AMI group (n=12), 1.5 mg/kg perindopril treatment group (Perindopril group, n=12), and 1.5 mg/kg perindopril treatment and Toll-like receptor-4 (TLR4) knockout group (TLR4-/-Perindopril group, n=12). Mice in the control group and AMI group were gavaged with normal saline, and those in the Perindopril group and TLR4-/-Perindopril group were gavaged with perindopril for 7 d. On the 4th day after drug administration, mice in the AMI group, Perindopril group and TLR4-/-Perindopril group were subjected to the ligation of the anterior descending coronary artery to induce AMI, and those in the Sham group underwent the same operation, but had a loose knot at the anterior descending coronary artery. At 24 h after the above operation, color echocardiography was performed on mice to observe changes in cardiac function. Then, the mice were sacrificed. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP)-biotin nick end labeling (TUNEL) assay was carried out to determine myocardial apoptosis. Immunohistochemistry and Western blotting technique were employed to detect the protein expression levels of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), TLR4 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p50 in infarction zones. The messenger ribonucleic acid (mRNA) expression levels of TLR4 and NF-κB p50 in infarction zones were measured via Reverse Transcription-Polymerase Chain Reaction (RT-PCR). RESULTS: Perindopril could significantly reduce the number of apoptotic myocardial cells after AMI. Mouse echocardiography showed that ejection fraction (EF), left ventricular fractional shortening (FS), left ventricular end-systolic diameter (LVESD) and left ventricular end-diastolic diameter (LVEDD) of AMI mice in the Perindopril groups were markedly superior to those in the AMI group. AMI mice in the Perindopril group had decreased expression levels of Bax protein and TLR4 and NF-κB p50 mRNA and protein, as well as the Bax/Bcl-2 ratio. Knockout of TLR4 attenuated the effect of perindopril in alleviating myocardial apoptosis after AMI. CONCLUSIONS: Perindopril inhibits myocardial apoptosis in mice with AMI through the TLR4/NF-κB pathway.