RESUMO
The current study explores the potential function and the underlying mechanisms of endothelial cell-derived R-spondin 3 (RSPO3) neuroprotection against ischemia/reperfusion-induced neuronal cell injury. In both neuronal cells (Neuro-2a) and primary murine cortical neurons, pretreatment with RSPO3 ameliorated oxygen and glucose deprivation (OGD)/re-oxygenation (OGD/R)-induced neuronal cell death and oxidative injury. In neurons RSPO3 activated the Akt, Erk and ß-Catenin signaling cascade, but only Erk inhibitors reversed RSPO3-induced neuroprotection against OGD/R. In mouse embryonic fibroblasts (MEFs) and neuronal cells, RSPO3-induced LGR4-Gab1-Gαi1/3 association was required for Erk activation, and either silencing or knockout of Gαi1 and Gαi3 abolished RSPO3-induced neuroprotection. In mice, middle cerebral artery occlusion (MCAO) increased RSPO3 expression and Erk activation in ischemic penumbra brain tissues. Endothelial knockdown or knockout of RSPO3 inhibited Erk activation in the ischemic penumbra brain tissues and increased MCAO-induced cerebral ischemic injury in mice. Conversely, endothelial overexpression of RSPO3 ameliorated MCAO-induced cerebral ischemic injury. We conclude that RSPO3 activates Gαi1/3-Erk signaling to protect neuronal cells from ischemia/reperfusion injury.
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Isquemia Encefálica , Traumatismo por Reperfusão , Camundongos , Animais , Fibroblastos/metabolismo , Transdução de Sinais , Infarto da Artéria Cerebral Média/genética , Infarto da Artéria Cerebral Média/metabolismo , Oxigênio/metabolismo , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/metabolismo , Células Endoteliais/metabolismo , Neurônios/metabolismo , Isquemia Encefálica/genética , Isquemia Encefálica/metabolismo , Glucose/metabolismo , Apoptose/fisiologiaRESUMO
The present study aimed to explore the potential of artificial intelligence (AI) methodology based on magnetic resonance (MR) images to aid in the management of prostate cancer (PCa). To this end, we reviewed and summarized the studies comparing the diagnostic and predictive performance for PCa between AI and common clinical assessment methods based on MR images and/or clinical characteristics, thereby investigating whether AI methods are generally superior to common clinical assessment methods for the diagnosis and prediction fields of PCa. First, we found that, in the included studies of the present study, AI methods were generally equal to or better than the clinical assessment methods for the risk assessment of PCa, such as risk stratification of prostate lesions and the prediction of therapeutic outcomes or PCa progression. In particular, for the diagnosis of clinically significant PCa, the AI methods achieved a higher summary receiver operator characteristic curve (SROC-AUC) than that of the clinical assessment methods (0.87 vs. 0.82). For the prediction of adverse pathology, the AI methods also achieved a higher SROC-AUC than that of the clinical assessment methods (0.86 vs. 0.75). Second, as revealed by the radiomics quality score (RQS), the studies included in the present study presented a relatively high total average RQS of 15.2 (11.0-20.0). Further, the scores of the individual RQS elements implied that the AI models in these studies were constructed with relatively perfect and standard radiomics processes, but the exact generalizability and clinical practicality of the AI models should be further validated using higher levels of evidence, such as prospective studies and open-testing datasets.
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Inteligência Artificial , Neoplasias da Próstata , Masculino , Humanos , Estudos Prospectivos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Imageamento por Ressonância Magnética/métodos , Próstata/patologiaRESUMO
Background: With dementia significantly increasing hospitalization and disability rates, worldwide aging of the population presents major challenges to public health. The majority of cases of cognitive dysfunction among the elderly, however, are characterized by an identifiable, preventable and treatable vascular component. As such, increased study of preventative methods in the context of dementia is warranted. Traditional Chinese medicine compounds have been reported to be neuroprotective and improve cognitive function via a variety of mechanisms. Shen Ma Yi Zhi granule (SMYZG) is one such collection of compounds that has been proven clinically effective. Pharmacological mechanisms of action, pharmacokinetics and clinical applications of SMYZG have been previously studied using a variety of vascular dementia animal models. SMYZG activates and regulates four main signaling pathways relevant to vascular dementia including the AMPK/PPARα/PGC-1α/UCP2, Nrf2/HO-1, HIF-1/VEGF/Notch, and VEGF/Flk-1/p8 MAPK pathways. Furthermore, SMYZG influences anti-inflammatory and anti-oxidant stress responses, reverses demyelination of brain white matter and vascular endothelium, regulates pericyte function and normalizes mitochondrial metabolism. Neuroprotective effects of SMYZG, as well as those promoting regeneration of vascular endothelium, have also been reported in studies of rat models of vascular dementia. Future research concerning SMYG is warranted for development of vascular dementia preventative management strategies.
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Traumatic brain injury (TBI) is a serious global public health problem. Survivors of TBI often suffer from long-term disability, which puts a heavy burden on society and families. Unfortunately, up to now, there is no efficacious treatment for TBI patients in clinical practice. As a reducing gas, hydrogen has been shown to be neuroprotective in multiple cerebral disease models; however, its efficacy in TBI remains controversial. In this review, we will focus on the results of hydrogen in experimental TBI, elaborate the potential mechanisms, and put forward for future researches based on our current understanding and views.
Assuntos
Lesões Encefálicas Traumáticas , Hidrogênio , HumanosRESUMO
OBJECTIVE: To investigate the effects and underlying mechanisms of Panax quinquefolium saponin (PQS) on energy deficiency in hypoxia-reperfusion (H/R) induced cardiomyocytes. METHODS: The H/R injury involved hypoxia for 3 h and then reperfusion for 2 h. Cardiomyocytes recruited from neonatal rat ventricular myocytes (NRVMs) were randomly divided into control, H/R, H/R+compound C (C.C), H/R+PQS, and H/R+C. C+PQS groups. BrdU assay, lactase dehydrogenase (LDH) leakage and early apoptosis rate were evaluated to assess cell damages. Contents of high energy phosphate compounds were conducted to detect the energy production. Protein expression levels of adenosine monophosphate-activated protein kinase a (AMPKα), glucose transporter 4 (GLUT4), phosphate fructose kinase 2 (PFK2), fatty acid translocase/cluster of differentiation 36 (FAT/CD36), and acetyl CoA carboxylase 2 (ACC2) in the regulatory pathways were measured by Western blotting. Immunofluorescence staining of GLUT4 and FAT/CD36 was used to observe the mobilization of metabolic transporters. RESULTS: PQS (50 mg/L) pretreatment significantly alleviated H/R-induced inhibition of NRVMs viability, up-regulation of LDH leakage, acceleration of early apoptosis, and reduction of energy production (P<0.05). Compared with the H/R group, up-regulated expression of AMPKα, GLUT4, PFK2, FAT/CD36 and ACC2 were observed, and more GLUT4 and FAT/CD36 expressions were detected on the membrane in the H/R+PQS group (P<0.05). These effects of PQS on H/R-induced NRVMs were eliminated in the H/R+C.C+PQS group (P<0.05). CONCLUSION: PQS has prominent advantages in protecting NRVMs from H/R-induced cell damages and energy metabolic disorders, by activation of AMPKα-mediated GLUT4-PFK2 and FAT/CD36-ACC2 pathways.
Assuntos
Miócitos Cardíacos , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Apoptose , Homeostase , Hipóxia , Redes e Vias Metabólicas , Miócitos Cardíacos/metabolismo , Ratos , Reperfusão , SaponinasRESUMO
OBJECTIVE: To investigate the long-term therapeutic effects of the Chinese medicine Jiannao Yizhi Formula (, JYF) in the treatment of Alzheimer's disease (AD). METHODS: Sixty mild-to-moderate AD participants were recruited and randomly allocated to the treatment (30 with JYF) and the control groups (30 with donepezil) for 6 months with the random numbers. The primary outcomes were scores of Alzheimer's Disease Rating Scale-Cognitive (ADAS-Cog) and Chinese Medicine Symptom Scale (CM-SS). The secondary outcomes were scores of Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Activities of Daily Living (ADL). Safety assessments were conducted at baseline and the 6th month of treatment. Serum levels of acetylcholine (Ach), amyloid-ß protein 42 (Aß42), and the microtubule-associated protein tau (Tau) were also determined by enzyme-liked immunosorbent assay. RESULTS: Fifty-one participants were included in the final analyses (JYF n=27; donepezil n=24). Compared with baseline, both JYF and donepezil increased the MoCA and MMSE scores and decreased the ADAS-Cog and CM-SS scores (P<0.05 or P<0.01). Both drugs increased the serum levels of Ach and decreased the serum levels of Aß42 and Tau (all P<0.05). There was no significant difference in these variables between the two groups, which showed that JYF was not inferior to donepezil. No obviously significant changes were observed in the ADL. No severe adverse events were observed in both groups. CONCLUSION: The effect and safety of JYF for the treatment of AD were not inferior to those of donepezil.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Donepezila/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa , Idoso , Idoso de 80 Anos ou mais , Alpinia , Atenção/efeitos dos fármacos , Biomarcadores/sangue , Inibidores da Colinesterase/uso terapêutico , Cognição/efeitos dos fármacos , Função Executiva/efeitos dos fármacos , Feminino , Humanos , Masculino , Memória/efeitos dos fármacos , Pessoa de Meia-Idade , Extratos Vegetais , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: To assess the effect and safety of Huannao Yicong Formula (, HYF) in the treatment of patients with mild-to-moderate Alzheimer's disease (AD). METHODS: Sixty patients with mild-tomoderate AD were evenly randomized into HYF group and donepezil group with the random number method. Patients in the HYF group took 5 g of HYF granules twice daily and 5 mg placebo of donepezil once daily. Patients in the donepezil group took 5 mg donepezil once daily and 5 g placebo of HYF granules twice daily. The intervention lasted for 6 months. Clinical researchers, participants and statisticians were blinded to the treatment assignment throughout the study. The primary outcomes were scores of Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and Chinese Medicine Symptom Scale (CM-SS). The secondary outcomes were scores of Montreal Cognitive Assessment (MoCA) test and Mini-Mental State Exam (MMSE). The serum levels of acetylcholinesterase (AchE) and amyloid-ß protein 42 (Aß42) were detected with enzymelinked immunosorbent assay kits. The scale assessments were conducted at baseline, the 3rd and 6th months of treatment, respectively. Biochemistry tests were conducted at baseline and the 6th month of treatment. RESULTS: A total of 52 patients completed the trial, 28 in HYF group and 24 in donepezil group. Compared with the baseline, HYF and donepezil signifificantly decreased the total scores of ADAS-Cog and CM-SS, and signifificantly increased the scores of MoCA and MMSE after 6-month treatment (all P<0.01). Both treatments remarkably reduced the serum levels of AchE and Aß42 (both P<0.05). The CM-SS total effective rate of HYF was signifificantly higher than donepezil [75.00% (21/28) vs. 54.17% (13/24), P<0.05]. No severe adverse events were observed in both groups. CONCLUSION: HYF is effective and safe for improving the cognitive function in mildto-moderate AD patients. [Trial registration: Chinese Clinical Trial Registry (Reg No. ChiCTR-IOR-17011746)].
Assuntos
Doença de Alzheimer/tratamento farmacológico , Donepezila/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Acetilcolinesterase/sangue , Doença de Alzheimer/sangue , Doença de Alzheimer/fisiopatologia , Peptídeos beta-Amiloides/sangue , Cognição , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
OBJECTIVE: To observe the effects of Huannao Yicong Formula (, HYF) on learning and memory and it's regulating effect on γ-secretase related anterior pharynx defective 1 (APH-1), presenilin enhancer-2 (PEN-2) signaling pathway, so as to discuss and further clarify the mechanism of HYF on Alzheimer's disease. METHODS: Sixty APP/PS1 transgenic mice, randomly allocated into 4 groups, the model group, the donepezil group (0.65 mg/kg), HYF low-dose group (HYF-L, 5.46 g/kg) and HYF high-dose group (HYF-H, 10.92 g/kg), 15 for each group. Another 15 C57BL/6J mice with the same age and same genetic background were allocated into the control group, proper dosage of drugs or distilled water were given by intragastric administration once daily for 12 weeks. After 12 weeks of administration, the learning and memory abilities of mice in each group was evaluated by the morris water maze test, amyloid precursor protein (APP), Aß1-40 and Aß1-42 levels in hippocampus were detected by enzyme-linked immunosorbent assay, γ-secretase was detected by dual luciferase assaying, the levels of APH-1a, hypoxia-inducible factor 1α (HIF-1α), cAMP response element-binding protein (CREB) and PEN-2 and their mRNA expression was measured by Western blot and real-time polymerase chain reaction. RESULTS: HYF can ameliorate learning and memory deficits in APP/PS1 transgenic mice by decreasing the escape latency, improving the number of platform crossing and swimming speed (P<0.01, P<0.05). HYF can decrease the levels of APP, Aß1-40, Aß1-42 and the activity of γ-secretase in hippocampus of Alzheimer's disease model mice. HYF can down-regulate the levels of CREB and PEN-2 and the expression of their mRNA. CONCLUSION: HYF can improve the learning and memory ability by inhibiting the activity of γ-secretase through the CREB/PEN-2 signaling pathway, and this may be one of the therapeutic mechanisms of HYF in Alzheimer's disease.
Assuntos
Secretases da Proteína Precursora do Amiloide/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Endopeptidases/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Hipocampo/metabolismo , Presenilina-1/metabolismo , Presenilina-2/genética , Animais , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Medicamentos de Ervas Chinesas/uso terapêutico , Endopeptidases/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Imuno-Histoquímica , Aprendizagem/efeitos dos fármacos , Masculino , Proteínas de Membrana , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/genética , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Presenilina-2/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
OBJECTIVE: Huannao Yicong Decoction (, HYD), an effective herbal formula against Alzheimer's disease (AD), has been proven to have neuroprotective action in amyloid ß-protein1-42 (Aß1-42)-induced rat model. This study was designed to characterize mechanisms by which HYD leads to suppression of inflflammation and apoptosis in the brains of Aß1-42-induced rat. METHODS: A total of 72 rats were divided into 6 groups, which were referred to as: sham operation group, model group, donepezil-treated group, HYD low-dose group (HYDL), HYD middle-dose group (HYDM) and HYD high-dose group (HYDH). Rats in HYDL, HYDM and HYDH were injected with Aß1-42 at the CA1 region of hippocampus to form AD model and were fed the HYD extract at different dose of 3.78, 7.56 and 18.90 g crude drug/kg. The behavioral changes of rats were evaluated by Morris water maze (MWM) before sacrififice. Pathological changes of the brain tissue were evaluated using hematoxylin eosin (HE) staining. The levels of interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α) were measured by radioimmunoassay. The levels of Aß and proteins that are associated with apoptosis such as B-cell lymphoma-2 protein (Bcl-2), Bcl-2-associated X protein (Bax), cysteine-aspartic protease (caspase)-3, -8, -9 and -12 in serum were measured by immunohistochemistry. RESULTS: Compared with the sham operation group, the spatial learning and memory abilities of AD rats were signifificantly decreased (P<0.05 or P<0.01; Expressions of IL-1, TNF-α, Aß and apoptosis-signaling proteins caspase-3, -8, -9, -12 were signifificantly up-regulated (P<0.05 or P<0.01). The ratio of Bcl-2 to Bax were signifificantly decreased in the model group (P<0.01). When treated with HYD extract, the spatial learning and memory abilities of AD-model rats were significantly increased (P<0.05 or P<0.01), IL-1, TNF-α, Aß, caspase-3, -8, -9 and -12 were down-regulated (P<0.05 or P<0.01), and the ratio of Bcl-2 to Bax were reduced (P<0.05 or P<0.01). CONCLUSIONS: HYD extract can improve the learning and memory ability defificits, alleviate the inflflammatory response and pathological manifestations induced by Aß1-42 injection in the rat model of AD. HYD down-regulates the levels of IL-1, TNF-α and Aß, and decreases the rate of apoptosis by modulating apoptosis-signaling-related proteins such as caspase-3, -8, -9, and -12.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/patologia , Apoptose , Medicamentos de Ervas Chinesas/uso terapêutico , Inflamação/tratamento farmacológico , Inflamação/patologia , Extratos Vegetais/uso terapêutico , Doença de Alzheimer/sangue , Doença de Alzheimer/complicações , Peptídeos beta-Amiloides , Animais , Apoptose/efeitos dos fármacos , Caspases/metabolismo , Cromatografia Líquida de Alta Pressão , Modelos Animais de Doenças , Feminino , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Inflamação/sangue , Inflamação/complicações , Interleucina-1/sangue , Interleucina-1/metabolismo , Masculino , Fragmentos de Peptídeos , Ratos Sprague-Dawley , Aprendizagem Espacial/efeitos dos fármacos , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/metabolismo , Proteína X Associada a bcl-2/metabolismoRESUMO
OBJECTIVE: To investigate the epidemic features of persistent genital chlamydial infection (GCI) in Tianjin area. METHODS: We statistically analyzed the clinical data about the persistent GCI patients received at the Venereal Disease Clinic of Tianjin Medical University General Hospital from 2009 to 2011. RESULTS: A total of 158 patients with persistent GCI were received from Tianjin area. The patients ranged in age from 19 to 67 years, 39.24% from 20 to 29 and 34.81% from 30 to 39 years, 36.71% with commercial occupation, and 55.06% with college education or above. The sex partners of the patients included their spouses (32.91%) and waitresses (41.77%). The incidence probability of persistent GCI was higher in the females (59.49%) than in the males. Many of the patients were complicated with infections of mycoplasma, syphilis, candida albicans, or condyloma acuminatum. CONCLUSIONS: The epidemic trend of persistent GCI is rather grim in Tianjin area. New measures have to be developed targeting the epidemiological features of persistent GCI for better prevention and control of the disease.
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Infecções por Chlamydia/epidemiologia , Adulto , Idoso , China/epidemiologia , Infecções por Chlamydia/transmissão , Estudos Epidemiológicos , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Distribuição por Sexo , Parceiros Sexuais , Adulto JovemRESUMO
Alzheimer's disease (AD), the most common neurodegenerative disorder associated with dementia, not only severely decreases the quality of life for its victims, but also brings a heavy economic burden to the family and society. Unfortunately, few chemical drugs designed for clinical applications have reached the expected preventive or therapeutic effect so far, and combined with their significant side-effects, there is therefore an urgent need for new strategies to be developed for AD treatment. Traditional Chinese Medicine has accumulated many experiences in the treatment of dementia during thousands of years of practice; modern pharmacological studies have confirmed the therapeutic effects of many active components derived from Chinese herbal medicines (CHM). Ginsenoside Rg1, extracted from Radix Ginseng, exerts a [Formula: see text]-secretase inhibitor effect so as to decrease A[Formula: see text] aggregation. It can also inhibit the apoptosis of neuron cells. Tanshinone IIA, extracted from Radix Salviae miltiorrhizae, and baicalin, extracted from Radix Scutellariae[Formula: see text] can inhibit the oxidative stress injury in neuronal cells. Icariin, extracted from Epimedium brevicornum, can decrease A[Formula: see text] levels and the hyperphosphorylation of tau protein, and can also inhibit oxidative stress and apoptosis. Huperzine A, extracted from Huperzia serrata, exerts a cholinesterase inhibitor effect. Evodiamine, extracted from Fructus Evodiae, and curcumin, extracted from Rhizoma Curcumae Longae, exert anti-inflammatory actions. Curcumin can act on A[Formula: see text] and tau too. Due to the advantages of multi-target effects and fewer side effects, Chinese medicine is more appropriate for long-term use. In this present review, the pharmacological effects of commonly used active components derived from Chinese herbal medicines in the treatment of AD are discussed.
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Doença de Alzheimer/tratamento farmacológico , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/uso terapêutico , Fitoterapia , Abietanos/isolamento & purificação , Abietanos/farmacologia , Abietanos/uso terapêutico , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Alcaloides/uso terapêutico , Curcuma/química , Curcumina/isolamento & purificação , Curcumina/farmacologia , Curcumina/uso terapêutico , Epimedium/química , Evodia/química , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Ginsenosídeos/isolamento & purificação , Ginsenosídeos/farmacologia , Ginsenosídeos/uso terapêutico , Humanos , Huperzia/química , Panax/química , Extratos Vegetais/química , Quinazolinas/isolamento & purificação , Quinazolinas/farmacologia , Quinazolinas/uso terapêutico , Salvia miltiorrhiza/química , Scutellaria baicalensis/química , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/farmacologia , Sesquiterpenos/uso terapêuticoRESUMO
Traditional Chinese medicine Curcuma Zedoary ( E'Zhu) contains essential oil, curcuminoid and other effective constituents, with such pharmacological actions as anti-platelet aggregation, lowing blood lipid, anti-oxidation and anti-inflammation. In recent years, studies have showed that certain extracts and chemical components of E'Zhu could mitigate myocardial cell mitochondria injury and protect vascular endothelium by enhancing heme oxygenase-1 activity, inhibit nuclear factor NF-kappaB, target genes interleukin-associated kinase-1 (IRAK-1), tumor necrosis factor receptor-6 (TRAF-6) and vascular cell adhesion molecule-1 (VCAM-1), reduce inflammatory infiltration, and inhibit growth factor-induced smooth muscle cells (SMCs) proliferation and migration by impacting oxidation of cellular phosphatases. Due to its different functions in vascular endothelial cells and smooth muscle cells, E'Zhu has been applied in drug-eluting stents, with a potential effect in preventing in-stent restenosis and thrombogenesis. In this paper, studies on pharmacological effects and mechanisms of extracts and main chemical constituents from E'Zhu in preventing vascular restenosis were summarized.
Assuntos
Constrição Patológica/prevenção & controle , Curcuma/química , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Animais , Constrição Patológica/tratamento farmacológico , Constrição Patológica/cirurgia , Endotélio Vascular/efeitos dos fármacos , Humanos , StentsRESUMO
OBJECTIVE: To observe the reconstruction features of adventitia in senescent rats, and to explore the intervention mechanism of Chinese herbs (CH, extracts from Radix Ginseng, Radix Notoginseng, and Rhizoma Chuanxiong). METHODS: Totally 85 20-month senescent rats were randomly divided into 5 groups according to body weight, i.e., the aging model group, the high dose CH group, the middle dose CH group, the low dose CH group, the Losartan group, 17 in each group. Another 14 2-month old Wistar rats were selected as a young group. Extracts of CH at the daily dose of 1493. 4, 746. 7, and 373. 4 mg/kg were administered to rats in the 3 CH groups respectively by gastrogavage. Losartan suspension at the daily dose of 10 mg/kg was administered to rats in the Losartan group by gastrogavage. Equal volume of distilled water was administered to rats in the aging model group and the young group. All medication was performed once daily. After 15-week intervention, morphological changes of thoracic aorta were observed by HE staining. The types, distribution, and contents of vessel wall collagens were determined using picric acid picrosirius red staining. The plasma renin activity (PRA) , the concentration of rennin angiotensin II (Ang II), and the content of Ang II in adventitia were detected by radioimmunoassay. The content of hydroxyproline ( Hyp) was detected by biochemical analysis. mRNA contents and protein expressions of angiotensin II receptor 1 (AT1R) and angiotensin II receptor 2 (AT2R) were detected by real-time PCR (RT-PCR) and Western blot. RESULTS: Compared with the young group, thickened adventitia, increased adventitia thickness/caliber, accumulated collagen fiber, increased area of type I collagen, decreased area of type III collagen, decreased type III/I collagen area ratio (P <0. 05), decreased plasma PRA and Ang II (P < 0.01, P < 0.05), increased contents of Ang II and Hyp in adventitia, down-regulated mRNA and protein expressions of AT1R, and up-regulated mRNA and protein expression of AT2R could be seen in the aging model group (P < 0.05). Compared with the aging model group, morphological changes could be improved in the 3 CH groups. Adventitia thickness/caliber was reduced in middle and high dose CH groups, as well as the Losartan group. The area of type I collagen was reduced and the area of type III collagen was enlarged, type III/I collagen area ratio obviously increased, contents of adventitia Hyp was obviously lowered in the high dose CH groups and the Losartan group (P < 0.05, P < 0.01). Ang II levels in adventitia decreased in middle and high dose CH groups and the Losartan group (P < 0.05, P < 0.01). There was no statistical difference in PAR among all groups (P > 0.05). Compared with the aging model group, mRNA expression of AT1R all increased in each treatment group (P < 0.01); mRNA expression of AT2R also increased in middle and high dose CH groups (P < 0.05). Protein expression of AT1R increased in the high dose CH group and the Losartan group (P < 0.01, P < 0.05); protein expression of AT2R also increased in middle and high dose CH groups (P < 0.05). CONCLUSIONS: Adventitia remodeling occurred in aged rats, manifested as thickened adventitia and accumulated collagens, disordered ratios of collagen I and III. Its mechanism might be possibly associated with aactivation of renin-angiotensin system (RAS). Extracts from Radix Ginseng, Radix Notoginseng, and Rhizoma Chuanxiong could improve adventitial remodeling possibly by interfering multi-targets, such as Ang II and AT1R, thereby delaying vascular aging.
Assuntos
Túnica Adventícia/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Envelhecimento , Angiotensina II , Animais , Aorta Torácica , Losartan , Panax , Raízes de Plantas , RNA Mensageiro , Ratos , Ratos Wistar , Sistema Renina-Angiotensina , RizomaRESUMO
Our aim for this study was to quantitatively develop an early epidural hematoma (EDH) natural evolutionary curve and assess association of the most common radiological signs of initially nonsurgical supratentorial EDHs on early computed tomography (CT), in addition to their CT time for EDH enlargement. We retrospectively reviewed pertinent data of supratentorial EDH cases with CT ≤ 6 h postinjury (1997-2013) in three medical institutions in Shanghai. Cases involved were divided into six groups according to their initial CT time postinjury (≤ 1, 1-2, 2-3, 3-4, 4-5, and 5-6 h for groups 1 through 6, respectively). Time of initial CT, EDH-associated fractures, EDH volume, and EDH locations were the focus in the present study. A total of 797 eligible cases were included. The EDH growth curve showed that EDH reached 98.1% of its final stabilized size by volume in 5 â¼ 6 h postinjury. EDH volume and locations on initial CT was greatly associated with subsequent EDH increase ≥ 30 mL with EDH increase requiring surgery when CT time was added. Multi-variate analysis succeeded in determining two risk factors for EDH enlargement ≥ 30 mL and EDH enlargement requiring an operation for EDH cases with an early CT/EDH volume >10 mL on CT performed ≤ 2 h and EDH located at the temporal or temporoparietal region on CT ≤ 1 h post brain injury. Using recursive partitioning analysis, "high-risk" identification criteria were derived to predict EDH enlargement ≥ 30 mL with sensitivity of 90.5% (95% confidence interval [CI], 77.9-96.2), specificity of 60.1% (95% CI, 54.3-65.7), and EDH enlargement requiring surgery with sensitivity of 100.0% (95% CI, 89.9-100.0), and specificity of 59.9% (95% CI, 54.1-65.4). A redo-CT 5 â¼ 6 h post impact for cases at high risk is recommended.
Assuntos
Lesões Encefálicas/diagnóstico por imagem , Hematoma Epidural Craniano/diagnóstico por imagem , Adolescente , Adulto , Idoso , Lesões Encefálicas/complicações , Criança , Pré-Escolar , China , Progressão da Doença , Hematoma Epidural Craniano/etiologia , Humanos , Pessoa de Meia-Idade , Prognóstico , Radiografia , Estudos Retrospectivos , Adulto JovemAssuntos
Doença de Alzheimer/enzimologia , Medicamentos de Ervas Chinesas/farmacologia , Terapia de Alvo Molecular , Fitoterapia/métodos , Doença de Alzheimer/tratamento farmacológico , Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Animais , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Medicina Tradicional Chinesa/métodos , Glicoproteínas de Membrana/antagonistas & inibidores , Presenilinas/antagonistas & inibidoresRESUMO
A very efficient and environmentally benign method has been developed for the synthesis of 25-hydroxycholesterol. The reaction was performed in THF-water (4:1, v/v) using NBS as the brominating agent, followed by the easy reduction of C-Br with lithium aluminum hydride in THF, to yield the final product corresponding to a Markovnikov's rule. Excellent yields and regioselectivity have been obtained.
Assuntos
Colecalciferol/síntese química , Desmosterol/síntese química , Hidroxicolesteróis/síntese química , Catálise , Colecalciferol/química , Desmosterol/química , Hidroxicolesteróis/química , Estrutura MolecularRESUMO
OBJECTIVE: To examine the effect of the zedoary essential component-eluting stent (ZES) on a porcine coronary neointimal formation. METHODS: ZES, sirolimus-eluting stents (SES), and bare metal stents (BMS) were randomly implanted in three different major epicardial vessels in 36 balloon-injured pigs. Coronary angiography, optical coherence tomography, and histomorphological analysis were used to determine antihyperplasia effects. RESULTS: ZES and SES had a significantly larger lumen diameter and area, and reduced diameter and area of stenosis in arteries at 30 and 90 days compared with arteries implanted with BMS (P<0.01). Histomorphometric analysis showed moderate inflammatory responses, such as infiltration of mononuclear cells, lymphocytes, and multinucleated giant cells in some arteries with SES compared with ZES (P<0.05). Injury scores were not different among the three groups at 30 and 90 days. The endothelialization score in the SES group was 2.69 ± 0.42 at 30 days and 2.83 ± 0.39 at 90 days compared with the ZES and BMS groups (both were 3.00 ± 0.00 at either 30 or 90 days, P<0.05). Well developed endothelium was observed in the ZES group, while incomplete endothelium and inflammatory cells were observed with stent struts partly naked at the vessel lumen in the SES group. CONCLUSION: The ZES inhibits neointimal hyperplasia with good endothelia coverage in the porcine balloon injury coronary model.
Assuntos
Materiais Revestidos Biocompatíveis/farmacologia , Vasos Coronários/efeitos dos fármacos , Vasos Coronários/patologia , Curcuma/química , Neointima/patologia , Stents , Animais , Estenose Coronária/patologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/patologia , Inflamação/patologia , Microscopia Eletrônica de Varredura , Implantação de Prótese , Sus scrofa , Fatores de TempoRESUMO
OBJECTIVE: To study the effects of Huannao Yicong Recipe (HNYCR)extract on the learning and memory ability, and the expressions of amyloid precursor protein (APP), beta-site APP-cleaving enzyme 1 (BACE1), presenilin-1 (PS-1), and beta amyloid protein (Abeta)in hippocampus CA1 area of APP transgenic mice, and to explore its mechanisms for treating Alzheimer's disease (AD). METHODS: Totally 3-month-old APP695V7171 transgenic mice were used to establish the AD model in this research. They were randomly divided into the model group, the Donepezil group, the large dose HNYCR extract group, the small dose HNYCR extract group, and the normal control group (C57BL/6J mice), 15 in each group. These animals were gavaged for 4 continuous months. Relevant indicators were detected: Morris water maze test was used to measure the spatial learning and memory ability. The immunohistochemical assay was used to detect the expressions of APP, BACE1, PS-1, and Abeta. RESULTS: The times of crossing the original platform and the swimming time and distance in the fourth quadrant of the 7-month-old APP transgenic mice were significantly reduced in Morris water maze test, when compared with the normal control group (P < 0.01). The times of crossing original platform and the swimming time and distance in the fourth quadrant of all treatment groups significantly increased in Morris water maze test, when compared with the model group (P < 0.05). The expressions of APP, BACE1, PS-1, and Abeta in hippocampus CA1 area of 7-month-old model mice increased significantly (P < 0.01), when compared with the normal control group. The expressions of APP, BACE1, PS-1, and Abeta in each 7-month-old intervention groups were significantly reduced, when compared with the model group (P < 0.01). CONCLUSION: Early application of HNYCR extract can obviously improve the learning and memory ability of APP transgenic mice that has declined, reduce the expressions of APP, BACE1, PS-1, and Abeta in the hippocampal CA1 area, reduce the production of Abeta, and slow down the pathological process of brains in APP transgenic mice.
Assuntos
Doença de Alzheimer/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Encéfalo/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Aprendizagem em Labirinto/efeitos dos fármacos , Secretases da Proteína Precursora do Amiloide/genética , Secretases da Proteína Precursora do Amiloide/metabolismo , Peptídeos beta-Amiloides/genética , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Animais , Ácido Aspártico Endopeptidases/genética , Ácido Aspártico Endopeptidases/metabolismo , Encéfalo/efeitos dos fármacos , Região CA1 Hipocampal/efeitos dos fármacos , Região CA1 Hipocampal/metabolismo , Modelos Animais de Doenças , Feminino , Masculino , Memória/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Presenilina-1/genética , Presenilina-1/metabolismoRESUMO
OBJECTIVE: To observe blood flow features in elderly hypertension patients of different Chinese medical syndrome types and to test their correlation with rheological properties of red blood cells (RBCs) by applying micro-channel array flow analyzer (MC-FAN). METHODS: Recruited were 109 elderly hypertension patients were assigned to phlegm-stasis blocking collateral group (35 cases), yin deficiency yang hyperactivity group (42 cases), Shen deficiency group (32 cases) according to Chinese medical syndrome typing. Besides, another 21 elderly healthy subjects were recruited as the control group. The hemorheology visualization testing of elderly hypertension patients was detected using MC-FAN. The erythrocyte deformation index (DI), erythrocyte aggregation index (EAI), and erythrocyte related plasma ATPase activity were observed. The correlation between the transiting time (TT) of blood hemorheology visualization and rheological indicators of RBCs were analyzed. RESULTS: The hemorheology visualization TT was significantly prolonged more in the phlegm-stasis blocking collateral group than in the yin deficiency yang hyperactivity group, the Shen deficiency group, and the control group (P < 0.05). Compared with the control group, the DI was significantly lower in the phlegm-stasis blocking collateral group than in the yin deficiency yang hyperactivity group, the Shen deficiency group, and the control group (P < 0.05) when the shear rate was 100 s(-1). Compared with the control group, the plasma Na+ -K(+) -ATPase activity and the plasma Ca2+ -Mg2+ -ATPase activity were significantly lower in elderly hypertension patients (P < 0.01). Among the three groups, plasma Ca2+ -Mg2+ -ATPase activity was significantly lower in the phlegm stasis blocking collateral group than in the Shen deficiency group (P < 0. 05). The hemorheology visualization TT (10, 30, 60, and 100 microL) was negatively correlated with DI. The hemorheology visualization TT at 100 microL was positively correlated with EAI. CONCLUSION: Changes of hemorheology visualization TT of elderly hypertension patients were significant and correlated with traditional EAI.