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1.
Zhen Ci Yan Jiu ; 44(11): 805-9, 2019 Nov 25.
Artigo em Chinês | MEDLINE | ID: mdl-31777229

RESUMO

OBJECTIVE: To observe the effect of electroacupuncture (EA) on behavioral changes, and expression of tyrosine hydroxylase (TH), α-synuclein(α-syn), transcription activating factor 6 (ATF6) and transcription factor X box binding protein 1 (XBP-1) in the substantia nigra of Parkinson's disease (PD) rats, so as to explore its mechanisms underlying improvement of motor function. METHODS: Thirty-six male SD rats were randomly divided into control, model and EA groups (n=12 rats in each group). The PD model was established by subcutaneous injection of rotenone (2 mg/kg) at the neck and back, once a day for 28 days. EA (2 Hz, 1 mA) was applied to "Fengfu" (GV16) and bilateral "Taichong" (LR3) for 20 min, once a day for 14 successive days. The voluntary motor behavioral changes (total distance, average speed, total movement time, total rest time in 8 min) were detected by open field tests. The immuno-activity of TH and α-syn in the substantia nigra was detected by immunohistochemistry, and the expression of ATF6 mRNA and XBP-1 mRNA detected by fluorescence real-time quantitative PCR. RESULTS: Following modeling and compared with the control group, the total distance, average speed and total movement time of voluntary movement were significantly decreased (P<0.01), and the total rest time was significantly increased (P<0.01). Moreover, the expression of TH was significantly decreased (P<0.01), and that of α-syn protein, ATF6 mRNA and XBP-1 mRNA significantly increased in the model group in comparison with the control group (P<0.01). After the intervention, the total distance, average speed, and total movement time of voluntary movement in the EA group were considerably higher than those in the model group (P<0.01), and the total rest time was obviously decreased in the EA group (P<0.01). The expression level of TH was significantly increased (P<0.01), and those of α-syn, ATF6 mRNA and XBP-1 mRNA were notably decreased in the EA group compared with the model group (P<0.01). CONCLUSION: EA intervention can improve the locomotor function in PD model rats, which is associated with its functions in up-regulating the expression of TH protein and down-regulating the expression of α-syn protein, and ATF6 mRNA and XBP-1 mRNA in the substantia nigra of mesencephalon.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31769183

RESUMO

Numerous researchers have investigated the associations among methylenetetrahydrofolate reductase gene (MTHFR) C677T polymorphism, homocysteine (Hcy) concentration, and hypertension. However, the results are controversial. Thus, a meta-analysis implementing Mendelian randomization approach was conducted to examine the hypothesis that elevated Hcy concentration plausibly contributes to increased risk of hypertension. Based on several inclusion and exclusion criteria, eligible studies were selected to explore the correlation between MTHFR C677T and hypertension risk, MTHFR C677T and Hcy concentration in hypertension, and Hcy concentration and hypertension, and they were evaluated by odds ratios (ORs), effect size (ES), and standard mean difference with their corresponding 95% confidence intervals (95% CIs), respectively. Moreover, Mendelian randomization was implemented to evaluate the relationship between Hcy and hypertension. Consequently, 14 378 cases and 25 795 controls were involved in this study and the results showed that MTHFR C677T led to an elevated risk of hypertension (for T vs C: OR = 1.27, 95% CI = 1.17-1.37; for TT vs CC: OR = 1.53, 95% CI = 1.30-1.79). Additionally, in hypertensive subjects, the pooled Hcy concentration in individuals of TT genotype was 7.74 µmol/L (95% CI: 5.25-10.23) greater than that in individuals of CC genotype. Moreover, the pooled Hcy concentration in hypertensive was 0.69 µmol/L (95% CI: 0.50-0.87) greater than that in controls. The estimated causal OR associated with hypertension was 1.32 for 5 µmol/L Hcy increment. Via MTHFR C677T polymorphism, the findings in the present study demonstrated that there exists evidence on causal link between Hcy concentration and the risk of hypertension.

3.
Chem Commun (Camb) ; 55(91): 13701-13704, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31657390

RESUMO

Partial substitution of Ba by K in the Ba sites of BaGa2Se4 creates a new selenide (K0.38Ba0.81)Ga2Se4 (1), which is crystallized in the noncentrosymmetric space group I4cm, different from the centric structures of all the ternary MI-MIII2-Q4 (MII = divalent Sr, Ba, Pb, Sn, Eu; MIII = trivalent Ga, In; Q = S and Se) chalcogenides. Its 1D structure features {[GaSe2]-}∞ chains, and K/Ba occupying the interchain cavities as the counter cations. Its powder sample demonstrates a second-harmonic generation intensity which is around 0.9 times that of AgGaS2 at 2.1 µm, and a laser-induced damage threshold which is 13.4 times that of AgGaS2. DFT calculations on its electronic structure and optical properties were also performed.

4.
Medicine (Baltimore) ; 98(42): e17591, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31626131

RESUMO

BACKGROUND: Spinal cord ischemia-reperfusion injury (SCII) is a common complication of spinal surgery as well as thoracic and abdominal surgery. Acute cytotoxic edema is the key pathogenic alteration. Therefore, avoiding or decreasing cellular edema has become the major target for SCII treatment. METHODS: The antiedema activity of ginsenoside Rb1 on aquaporin (AQP) 4, nerve growth factor (NGF), and brain-derived neurotrophic factor expression was detected by western blot and real-time polymerase chain reaction under conditions of oxygen-glucose deprivation/reoxygenation (OGD/R) in a rat astrocyte model in vitro. In addition, the cellular membrane permeability of AQP4 overexpressing cells or AQP4 small interfering RNA-transfected cells was detected. RESULTS: Ginsenoside Rb1 significantly prevented OGD/R-induced AQP4 downregulation in rat astrocytes. In addition, ginsenoside Rb1 treatment or AQP4 overexpression in rat astrocytes significantly attenuated the OGD/R-induced increase of cellular membrane permeability. Moreover, ginsenoside Rb1 obviously prevented the OGD/R-induced decrease of NGF and BDNT expression in rat astrocytes. CONCLUSION: These findings demonstrate that ginsenoside Rb1 can relieve spinal cord edema and improve neurological function by increasing AQP4 expression.


Assuntos
Aquaporina 4/genética , Astrócitos/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Ginsenosídeos/farmacologia , Glucose/metabolismo , Oxigênio/metabolismo , Traumatismo por Reperfusão/genética , Animais , Animais Recém-Nascidos , Aquaporina 4/biossíntese , Astrócitos/efeitos dos fármacos , Astrócitos/patologia , Western Blotting , Células Cultivadas , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , RNA/genética , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/patologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Medula Espinal/metabolismo , Medula Espinal/patologia
5.
Metabolism ; 100: 153956, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31394109

RESUMO

To systematically review clinical practice guidelines (CPGs) on diabetes foot and assess the consistency of recommendations, quality of CPGs and to present an evidence-map for explicating research trends and gaps. We performed a literature search on PubMed, Embase, and Web of Science, guideline databases and websites of diabetes society to include the diabetic CPGs. The basic information, recommendations for the diabetic foot, methodological quality and reporting quality of diabetic CPGs were exacted by the Excel. Four researchers evaluated the methodological and reporting quality of diabetic foot CPGs by AGREE II instrument and RIGHT checklist. R3.5.1 software was used to create all bubble plots. A total of 22 diabetic CPGs were included, eight CPGs were from different professional diabetes societies. Recommendations on diabetic foot complications involve Diabetic foot ulcer (DFU), Charcot neuropathy (CN) and Osteomyelitis (OM). Eight DFU diagnostic systems presented in 22 CPGs. According to the recommendations of diabetic CPGs, the treatment of DFU can be summarized in four major items; six recommendations on CN diagnosis and six recommendations on treatment of CN were consistent among studies. However, there were inconsistencies in three OM diagnosis recommendations and four OM treatment recommendations. Some recommendations in CPGs were not very specific and clear, and hence they were not reliable for OM diagnosis and treatment. Once these inconsistencies are resolved, validated, accurate and effective diagnosis and treatment of diabetes foot will lead to reduced costs and adverse complications. The results of this review add to our knowledge and promote the development of trustworthy CPGs on diabetes.

6.
Cell Death Dis ; 10(8): 610, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31406109

RESUMO

Muscle LIM protein (MLP, CSRP3) is a key regulator of striated muscle function, and its mutations can lead to both hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) in patients. However, due to lack of human models, mechanisms underlining the pathogenesis of MLP defects remain unclear. In this study, we generated a knockout MLP/CSRP3 human embryonic stem cell (hESC) H9 cell line using CRISPR/Cas9 mediated gene disruption. CSRP3 disruption had no impact on the cardiac differentiation of H9 cells and led to confirmed MLP deficiency in hESC-derived cardiomyocytes (ESC-CMs). MLP-deficient hESC-CMs were found to develop phenotypic features of HCM early after differentiation, such as enlarged cell size, multinucleation, and disorganized sarcomeric ultrastructure. Cellular phenotypes of MLP-deficient hESC-CMs subsequently progressed to mimic heart failure (HF) by 30 days post differentiation, including exhibiting mitochondrial damage, increased ROS generation, and impaired Ca2+ handling. Pharmaceutical treatment with beta agonist, such as isoproterenol, was found to accelerate the manifestation of HCM and HF, consistent with transgenic animal models of MLP deficiency. Furthermore, restoration of Ca2+ homeostasis by verapamil prevented the development of HCM and HF phenotypes, suggesting that elevated intracellular Ca2+ concentration is a central mechanism for pathogenesis of MLP deficiency. In summary, MLP-deficient hESC-CMs recapitulate the pathogenesis of HCM and its progression toward HF, providing an important human model for investigation of CSRP3/MLP-associated disease pathogenesis. More importantly, correction of the autonomous dysfunction of Ca2+ handling was found to be an effective method for treating the in vitro development of cardiomyopathy disease phenotype.

7.
Zhen Ci Yan Jiu ; 44(7): 512-5, 2019 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-31368283

RESUMO

OBJECTIVE: To investigate the therapeutic effect of blade needle therapy for cervicogenic dizziness (CD) and changes of blood flow of vertebral artery in patients with CD. METHODS: A total of 60 patients with CD were equally randomized into medication (16 women and 14 men, 38.9±10.9 years in age) group and blade needle group (17 women and 13 men, 40.1±12.4 years in age). Patients of the blade needle group were treated by performing blade needle stimulation (longitudinal cutting along the musculoaponeurotic layer) to the tender points (attachment points) of the bilateral superior and inferior oblique muscles of the head, major and minor posterior cephalic rectus, about 2/3 of suboccipital nuchal line, and near the cervical processes of C1-C2 segments. The treatment was conducted once every 3 days for 15 days. Patients of the medication group were ordered to take Flunarizine Hydrochloride capsules (10 mg) once every night for 15 days. Transcranial Doppler was used to measure changes of mean blood flow velocities of the left vertebral artery (LVA), right vertebral artery (RVA), and basilar artery (BA) before and after the treatment. The therapeutic effect was assessed according to the Criteria for Diagnosis and Therapeutic Effect Evaluation of Syndromes or Illnesses of Traditional Chinese Medicine (1994) and the Assessment Scale for Symptoms and Function of Cervicogenic Dizziness (2017). RESULTS: Following the treatment, of the two 30 cases in the medication and blade needle groups, 5 (16.7%) and 7 (23.3%) were cured, 16 (53.3%) and 20 (66.7%) were improved in their symptoms, 9 (30.0%) and 3 (10.0%) failed, with the effective rate being 70.0% and 90.0%, respectively. The effective rate of the blade needle was significantly superior to that of the medication (P<0.05). The scores of vertigo, neck-should pain, daily living and work, psychology, social adaptation, and total score of the assessment scale, as well as the average blood flow velocities of LVA, RVA and BA were considerably increased in both groups in comparison with their own pre-treatment (P<0.05), and obviously higher in the blade needle group than in the medication group (P<0.05). CONCLUSION: Blade needle treatment has a good clinical effect in the treatment of CD patients, which is probably associated with its function in increasing blood perfusion of the brain tissue, and thus being worthy of clinical application.


Assuntos
Artéria Basilar , Tontura , Pontos de Acupuntura , Adulto , Velocidade do Fluxo Sanguíneo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Artéria Vertebral , Vertigem
8.
J Investig Med ; 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31431469

RESUMO

Hepatocellular Carcinoma (HCC) is one of the most common malignancies in the world, and is well-known for its bad prognosis. Potassium calcium-activated channel subfamily N member 4 (KCNN4) is a type of intermediate conductance calcium-activated potassium channel, and increasing evidence suggests that KCNN4 contributes to the regulation of invasion and metastasis in a number of cancers. However, its clinical significance and biological function remain unclear in the HCC disease process. In this study, the expression levels of KCNN4 in 86 HCC samples were compared with corresponding paracancerous tissues. sh-RNA was used to reduce the expression of KCNN4 in Hep3B HCC cells in vitro; this was confirmed by Real time-PCR and western blotting. Wound healing, transwell assays and high content analysis were performed to investigate the tumor-promoting characteristics of KCNN4 in Hep3B HCC cells. As results, KCNN4 expression was significantly associated with preoperative serum alpha-fetoprotein level (p=0.038) and TNM stage (p=0.039). Additionally, patients with high KCNN4 amplification in HCC tissue exhibited shorter disease-free survival, whereas there was no statistical significance between KCNN4 amplification and overall survival. Wound healing and transwell assays showed that knockdown of KCNN4 expression could reduce migration and invasion abilities of HCC cells. High content analysis result showed that down-regulated KCNN4 could inhibit the ability of HCC cell proliferation. The mitogen-activated protein kinase (MAPK) pathway is active in cell proliferation, differentiation, migration, senescence, and apoptosis. Matrix metallopeptidase 9 and extracellular signal regulated kinase 1/2 (ERK1/2) were important biomarkers of MAPK/ERK pathway, knockdown of KCNN4 reduced the expression of MMP9 and ERK1/2. These findings showed that KCNN4 promotes HCC invasion and metastasis through the MAPK/ERK pathway.

9.
J Mol Cell Cardiol ; 135: 40-51, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31352044

RESUMO

BACKGROUND: Seroepidemiological studies have highlighted a positive relation between CagA-positive Helicobacter pylori (H. pylori), atherosclerosis and related clinic events. However, this link has not been well validated. The present study was designed to explore the role of H. pylori PMSS1 (a CagA-positive strain that can translocate CagA into host cells) and exosomal CagA in the progression of atherosclerosis. METHODS: To evaluate whether H. pylori accelerates or even induces atherosclerosis, H. pylori-infected C57/BL6 mice and ApoE-/- mice were maintained under different dietary conditions. To identify the role of H. pylori-infected gastric epithelial cells-derived exosomes (Hp-GES-EVs) and exosomal CagA in atherosclerosis, ApoE-/- mice were given intravenous or intraperitoneal injections of saline, GES-EVs, Hp-GES-EVs, and recombinant CagA protein (rCagA). FINDINGS: CagA-positive H. pylori PMSS1 infection does not induce but promotes macrophage-derived foam cell formation and augments atherosclerotic plaque growth and instability in two animal models. Meanwhile, circulating Hp-GES-EVs are taken up in aortic plaque, and CagA is secreted in Hp-GES-EVs. Furthermore, the CagA-containing EVs and rCagA exacerbates macrophage-derived foam cell formation and lesion development in vitro and in vivo, recapitulating the pro-atherogenic effects of CagA-positive H. pylori. Mechanistically, CagA suppresses the transcription of cholesterol efflux transporters by downregulating the expression of transcriptional factors PPARγ and LXRα and thus enhances foam cell formation. INTERPRETATION: These results may provide new insights into the role of exosomal CagA in the pathogenesis of CagA-positive H. pylori infection-related atherosclerosis. It is suggested that preventing and eradicating CagA-positive H. pylori infection could reduce the incidence of atherosclerosis and related events.

10.
Int Immunopharmacol ; 74: 105701, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31228817

RESUMO

Synovitis is an aseptic inflammation that leads to joint effusion, pain and swelling. As one of the main drivers of pathogenesis in osteoarthritis (OA), the presence of synovitis contributes to pain, incidence and progression of OA. In our previous study, DC32 [(9α,12α-dihydroartemisinyl) bis(2'-chlorocinnmate)], a dihydroartemisinin derivative, was found to have an antirheumatic ability via immunosuppression, but the effect of DC32 on synovitis has not been fully illuminated. In this study, we chose to evaluate the effect and mechanism of DC32 on attenuating synovial inflammation. Fibroblast-like synoviocytes (FLSs) of papain-induced OA rats were isolated and cultured. And DC32 significantly inhibited the invasion and migration of cultured OA-FLSs, as well as the transcription of IL-6, IL-1ß, CXCL12 and CX3CL1 in cultured OA-FLSs measured by qPCR. DC32 remarkably inhibited the activation of ERK and NF-κB pathway, increased the expression of Nrf2 and HO-1 in cultured OA-FLSs detected by western blot. DC32 inhibited the degradation and phosphorylation of IκBα which further prevented the phosphorylation of NF-κB p65 and the effect of DC32 could be relieved by siRNA for Nrf2. In papain-induced OA mice, DC32 significantly alleviated papain-induced mechanical allodynia, knee joint swelling and infiltration of inflammatory cell in synovium. DC32 upregulated the mRNA expression of Type II collagen and aggrecan, and downregulated the mRNA expression of MMP2, MMP3, MMP13 and ADAMTS-5 in the knee joints of papain-induced OA mice measured by qPCR. The level of TNF-α in the serum and secretion of TNF-α in the knee joints were also reduced by DC32 in papain-induced OA mice. In conclusion, DC32 inhibited the inflammatory response in osteoarthritic synovium through regulating Nrf2/NF-κB pathway and attenuated OA. In this way, DC32 may be a potential agent in the treatment of OA.

11.
Cell Death Dis ; 10(7): 487, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31221990

RESUMO

Endothelium (EC) is a key component of blood-brain barrier (BBB), and has an important position in the neurovascular unit. Its dysfunction and death after cerebral ischemic/reperfusion (I/R) injury not only promote evolution of neuroinflammation and brain edema, but also increase the risk of intracerebral hemorrhage of thrombolytic therapies. However, the mechanism and specific interventions of EC death after I/R injury are poorly understood. Here we showed that necroptosis was a mechanism underlying EC death, which promoted BBB breakdown after I/R injury. Treatment of rats with receptor interacting protein kinase 1 (RIPK1)-inhibitor, necrostatin-1 reduced endothelial necroptosis and BBB leakage. We furthermore showed that perivascular M1-like microglia-induced endothelial necroptosis leading to BBB disruption requires tumor necrosis factor-α (TNF-α) secreted by M1 type microglia and its receptor, TNF receptor 1 (TNFR1), on endothelium as the primary mediators of these effects. More importantly, anti-TNFα (infliximab, a potent clinically used drug) treatment significantly ameliorate endothelial necroptosis, BBB destruction and improve stroke outcomes. Our data identify a previously unexplored role for endothelial necroptosis in BBB disruption and suggest infliximab might serve as a potential drug for stroke therapy.

12.
Anat Sci Educ ; 2019 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-31022327

RESUMO

Postmortem human brain donation is crucial to both anatomy education and research. The China Human Brain Banking Consortium was established recently to foster brain donation in China. The purpose of this study was to gain information about the public perception of and attitudes toward brain donation and to identify factors that may impact the willingness to participate in brain donation among the Chinese people. A specifically designed questionnaire was delivered to community residents in Changsha (the capital city of Hunan province) with a total of 1,249 completed forms returned and statistically analyzed. The majority of the participants considered that brain donation would help medical research and education, and 32.0% of respondents agreed that the brain donation would help change the traditional Chinese funeral belief in keeping the body intact after death. However, participants aged over 60 years old were less supportive of this concept. Among all participants, 63.7% stated that they were not knowledgeable about brain donation, while 26.4% explicitly expressed a willingness to participate in brain donation. Age, gender, monthly household income, and knowledge about brain donation significantly affected the willingness. Compared with other age groups, a higher proportion of participants aged over 60 years old preferred to be informed by a medical college. To promote brain donation in China, especially among the elderly, better communication of its medical benefits and a reinterpretation of the Confucius view of the human body should be provided. Efforts are also needed to provide appropriate forums and sources of brain donation information to targeted communities and society in general.

13.
J Asian Nat Prod Res ; : 1-9, 2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-31012734

RESUMO

A series of novel parthenolide-thiazolidinedione hybrids have been synthesized via a click chemistry-mediated coupling between parthenolide and thiazolidinedione, and evaluated for their cytotoxic activities. The results indicated that all the hybrids showed moderate cytotoxic effects on human cancer cell lines, including human erythroleukemia cell line (HEL), prostate (PC3), and breast (MDA-MB-231) by MTT assay. In particular, compound VI-6 exhibited the best cytotoxic activities against the MDA-MB-231 cells with IC50 value of 2.07 µM, which was about eight times more active than that of the original compound (PTL). These interesting results might be used to develop novel lead scaffolds for potential anticancer agents.

14.
Stem Cell Res ; 36: 101414, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30870686

RESUMO

Marfan syndrome (MFS) is a heritable connective tissue disease caused by mutations in FBN1, encoding the extracellular matrix protein fibrillin-1. In this study, we generated human induced pluripotent stem cells (iPSCs) from dermal fibroblasts of an MFS patient with the p. E2130K (c. 6388G > A) mutation. The generated hiPSC line had a normal karyotype, showed robust expression of pluripotency markers and was able to differentiate into all three germ layers in vivo. This cell line can provide a platform for understanding the pathogenic mechanisms of MFS related to FBN1 mutations. Resource table.

15.
Zhongguo Zhong Yao Za Zhi ; 44(1): 88-94, 2019 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-30868817

RESUMO

Eleven flavonoids were isolated from the twigs of Broussonetia papyrifera by column chromatography over silica gel,ODS,MCI gel,and Sephadex LH-20,as well as RP-HPLC.Their structures were identified by spectroscopic methods including NMR,MS,UV,and IR as broupapyrin A(1),5,7,3',4'-tetrahydroxy-3-methoxy-8-geranylflavone(2),8-prenylquercetin-3-methyl ether(3),broussonol D(4),broussoflavonol B(5),uralenol(6),broussonol E(7),8-(1,1-dimethylallyl)-5'-(3-methylbut-2-enyl)-3',4',5,7-tetrahydroxyflanvonol(8),broussoflavonol E(9),4,2',4'-trihydroxychalcone(10),and butein(11).Compound 1 is a new isoprenylated flavonol.Compounds 3,6,10,and 11 were obtained from the genus Broussonetia for the first time,and 4 and 7 were firstly discovered in B.papyrifera.Compounds 1-5 and 7-9 showed significant inhibitory effects on PTP1 B with IC50 values ranging from(0.83±0.30) to(4.66±0.83) µmol·L-1.


Assuntos
Broussonetia/química , Flavonoides/farmacologia , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Cromatografia Líquida de Alta Pressão , Flavonoides/isolamento & purificação , Espectroscopia de Ressonância Magnética , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia
16.
Sci Rep ; 9(1): 938, 2019 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-30700734

RESUMO

Haliotid herpesvirus-1 (HaHV-1) is the viral agent causative of abalone viral ganglioneuritis, a disease that has severely affected gastropod aquaculture. Although limited, the sequence similarity between HaHV-1 and Ostreid herpesvirus-1 supported the assignment of both viruses to Malacoherpesviridae, a Herpesvirales family distantly related with other viruses. In this study, we reported the first transcriptional data of HaHV-1, obtained from an experimental infection of Haliotis diversicolor supertexta. We also sequenced the genome draft of the Chinese HaHV-1 variant isolated in 2003 (HaHV-1-CN2003) by PacBio technology. Analysis of 13 million reads obtained from 3 RNA samples at 60 hours post injection (hpi) allowed the prediction of 51 new ORFs for a total of 117 viral genes and the identification of 207 variations from the reference genome, consisting in 135 Single Nucleotide Polymorphisms (SNPs) and 72 Insertions or Deletions (InDels). The pairing of genomic and transcriptomic data supported the identification of 60 additional SNPs, representing viral transcriptional variability and preferentially grouped in hotspots. The expression analysis of HaHV-1 ORFs revealed one putative secreted protein, two putative capsid proteins and a possible viral capsid protease as the most expressed genes and demonstrated highly synchronized viral expression patterns of the 3 infected animals at 60 hpi. Quantitative reverse transcription data of 37 viral genes supported the burst of viral transcription at 30 and 60 hpi during the 72 hours of the infection experiment, and allowed the distinction between early and late viral genes.

17.
Acta Crystallogr C Struct Chem ; 75(Pt 2): 213-220, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30720461

RESUMO

For the first time, a new langbeinite-type phosphate, namely potassium terbium tantalum tris(phosphate), K2Tb1.5Ta0.5(PO4)3, has been prepared successfully using a high-temperature flux method and has been structurally characterized by single-crystal X-ray diffraction. The results show that its structure can be described as a three-dimensional open framework of [Tb1.5Ta0.5(PO4)3]∞ interconnected by K+ ions. The TbIII and TaV cations in the structure are disordered and occupy the same crystallographic sites. The IR spectrum, the UV-Vis spectrum, the morphology and the Eu3+-activated photoluminescence spectroscopic properties were studied. A series of Eu3+-doped phosphors, i.e. K2Tb1.5-xTa0.5(PO4)3:xEu3+ (x = 0.01, 0.03, 0.05, 0.07, 0.10), were prepared via a solid-state reaction and the photoluminescence properties were studied. The results show that under near-UV excitation, the luminescence colour can be tuned from green through yellow to red by simply adjusting the Eu3+ concentration from 0 to 0.1, because of the efficient Tb3+→Eu3+ energy-transfer mechanism.

18.
Stem Cell Res Ther ; 10(1): 18, 2019 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-30635041

RESUMO

BACKGROUND: Mesenchymal stem/stromal cells (MSCs) have been widely used to treat various inflammatory diseases. The immunomodulatory capabilities of MSCs are usually licensed by inflammatory cytokines and may vary depending on the levels and the types of inflammatory cytokines. However, how the inflammatory microenvironment affects the fate of MSCs remains elusive. Here we characterized the molecular mechanism underlying the apoptosis of mouse MSCs triggered by the synergistic action of IFNγ and TNFα. METHODS: We isolated and expanded MSCs by flushing the femoral and tibial bone marrow of wild-type, iNOS-/-, and Fas-/- mice. BM-MSCs were treated with IFNγ and TNFα in vitro, and cell viability was evaluated by a CCK-8 kit. Apoptosis was assessed by Annexin V/propidium iodide-stained flow cytometry. Expression of genes related to apoptosis and endoplasmic reticulum (ER) stress was measured by reverse transcription-polymerase chain reaction (RT-PCR). Apoptosis and autophagy-related proteins were examined by Western blot analysis. RESULTS: IFNγ and TNFα synergistically trigger apoptosis of mouse BM-MSCs. The two cytokines were shown to stimulate the expression of inducible nitric oxide synthase (iNOS) and consequently the generation of nitric oxide (NO), which is required for the apoptosis of mouse BM-MSCs. The two cytokines similarly induced apoptosis in Fas-/- BM-MSCs. iNOS and NO were shown to upregulate Fas in mouse MSCs and sensitize them to Fas agonist-induced apoptosis. Moreover, NO stimulated by IFNγ/TNFα impairs autophagy, which aggravates ER stress and promotes apoptosis. CONCLUSIONS: IFNγ/TNFα-induced apoptosis in mouse MSCs is mediated by NO. Our findings shed new light on cytokine-induced apoptosis of MSCs and have implications in MSC-based therapy of inflammatory diseases.

19.
FASEB J ; 33(4): 4947-4961, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30653356

RESUMO

Angiogenesis is a crucial defense response to hypoxia that regulates the process of raising the promise of long-term neurologic recovery during the management of stroke. A high expression of antiangiogenic factors leads to the loss of neovascularization capacity in pathologic conditions. We have previously documented an impairment of the cerebral vessel perfusion and neovascularization in the cortex neighboring the stroke-induced lesion, which was accompanied by an activation of semaphorin 3E (Sema3E)/PlexinD1 after ischemic stroke. In this study, we employed micro-optical sectioning tomography to fully investigate the details of the vascular pattern, including the capillaries. We found that after transient middle cerebral artery occlusion, inhibiting PlexinD1 signaling led to an organized recovery of the vascular network in the ischemic area. We then further explored the possible mechanisms. In vivo, Sema3E substantially decreased dynamic delta-like 4 (DLL4) expression. In cultured brain microvascular endothelial cells, Sema3E down-regulated DLL4 expression via inhibiting Ras-related C3 botulinum toxin substrate 1-induced JNK phosphorylation. At the microcosmic level, Sema3E/PlexinD1 signaling promoted F-actin disassembly and focal adhesion reduction by activating the small guanosine triphosphatase Ras homolog family member J by releasing RhoGEF Tuba from direct binding to PlexinD1, thus mediating endothelial cell motility and filopodia retraction. Our study reveals that Sema3E/PlexinD1 signaling, which suppressed endothelial DLL4 expression, cell motility, and filopodia formation, is expected to be a novel druggable target for angiogenesis during poststroke progression.-Zhou, Y.-F., Chen, A.-Q., Wu, J.-H., Mao, L., Xia, Y.-P., Jin, H.-J., He, Q.-W., Miao, Q. R., Yue, Z.-Y., Liu, X.-L., Huang, M., Li, Y.-N., Hu, B. Sema3E/PlexinD1 signaling inhibits postischemic angiogenesis by regulating endothelial DLL4 and filopodia formation in a rat model of ischemic stroke.

20.
EBioMedicine ; 39: 95-108, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30579864

RESUMO

BACKGROUND: Neointimal hyperplasia is a prominent pathological event during in-stent restenosis. Phenotype switching of vascular smooth muscle cells (VSMCs) from a differentiated/contractile to a dedifferentiated/synthetic phenotype, accompanied by migration and proliferation of VSMCs play an important role in neointimal hyperplasia. However, the molecular mechanisms underlying phenotype switching of VSMCs have yet to be fully understood. METHODS: The mouse carotid artery ligation model was established to evaluate Sema3A expression and its role during neointimal hyperplasia in vivo. Bioinformatics analysis, chromatin immunoprecipitation (ChIP) assays and promoter-luciferase reporter assays were used to examine regulatory mechanism of Sema3A expression. SiRNA transfection and lentivirus infection were performed to regulate Sema3A expression. EdU assays, Wound-healing scratch experiments and Transwell migration assays were used to assess VSMC proliferation and migration. FINDINGS: In this study, we found that semaphorin-3A (Sema3A) was significantly downregulated in VSMCs during neointimal hyperplasia after vascular injury in mice and in human atherosclerotic plaques. Meanwhile, Sema3A was transcriptionally downregulated by PDGF-BB via p53 in VSMCs. Furthermore, we found that overexpression of Sema3A inhibited VSMC proliferation and migration, as well as increasing differentiated gene expression. Mechanistically, Sema3A increased the NRP1-plexin-A1 complex and decreased the NRP1-PDGFRß complex, thus inhibiting phosphorylation of PDGFRß. Moreover, we found that overexpression of Sema3A suppressed neointimal hyperplasia after vascular injury in vivo. INTERPRETATION: These results suggest that local delivery of Sema3A may act as a novel therapeutic option to prevent in-stent restenosis.


Assuntos
Aterosclerose/genética , Neointima/prevenção & controle , Semaforina-3A/genética , Lesões do Sistema Vascular/genética , Animais , Aterosclerose/metabolismo , Becaplermina/metabolismo , Movimento Celular , Proliferação de Células , Modelos Animais de Doenças , Regulação para Baixo , Humanos , Camundongos , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/metabolismo , Neointima/genética , Neointima/metabolismo , Semaforina-3A/metabolismo , Transdução de Sinais , Transcrição Genética , Lesões do Sistema Vascular/metabolismo
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