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1.
Front Plant Sci ; 14: 1064732, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36968359

RESUMO

The coexistence of heavy metal-polluted soils and global warming poses serious threats to plants. Many studies indicate that arbuscular mycorrhizal fungi (AMF) can enhance the resistance of plants to adverse environments such as heavy metals and high temperature. However, few studies are carried out to explore the regulation of AMF on the adaptability of plants to the coexistence of heavy metals and elevated temperature (ET). Here, we investigated the regulation of Glomus mosseae on the adaptability of alfalfa (Medicago sativa L.) to the coexistence of cadmium (Cd)-polluted soils and ET. G. mosseae significantly enhanced total chlorophyll and carbon (C) content in the shoots by 15.6% and 3.0%, respectively, and Cd, nitrogen (N), and phosphorus (P) uptake by the roots by 63.3%, 28.9%, and 85.2%, respectively, under Cd + ET. G. mosseae significantly increased ascorbate peroxidase activity, peroxidase (POD) gene expression, and soluble proteins content in the shoots by 13.4%, 130.3%, and 33.8%, respectively, and significantly decreased ascorbic acid (AsA), phytochelatins (PCs), and malondialdehyde (MDA) contents by 7.4%, 23.2%, and 6.5%, respectively, under ET + Cd. Additionally, G. mosseae colonization led to significant increases in POD (13.0%) and catalase (46.5%) activities, Cu/Zn-superoxide dismutase gene expression (33.5%), and MDA (6.6%), glutathione (22.2%), AsA (10.3%), cysteine (101.0%), PCs (13.8%), soluble sugars (17.5%), and proteins (43.4%) contents in the roots and carotenoids (23.2%) under ET + Cd. Cadmium, C, N, G. mosseae colonization rate, and chlorophyll significantly influenced shoots defenses and Cd, C, N, P, G. mosseae colonization rate, and sulfur significantly affected root defenses. In conclusion, G. mosseae obviously improved the defense capacity of alfalfa under ET + Cd. The results could improve our understanding of the regulation of AMF on the adaptability of plants to the coexistence of heavy metals and global warming and phytoremediation of heavy metal-polluted sites under global warming scenarios.

2.
Ying Yong Sheng Tai Xue Bao ; 33(10): 2760-2768, 2022 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-36384612

RESUMO

As the core region of the "Grain to Green" Program, the Loess Plateau of Northern Shaanxi became an example with the most dramatic changes in earth surface pattern and vegetation cover. Evaluating the effectiveness of vegetation restoration is important for promoting regional ecological environment. In this study, the fractional vegetation coverage (FVC) was used as the index to analyze the changes in vegetation coverage in this area. Soil conservation service, carbon sequestration service, habitat quality, and water yield were used to characterize the regional ecosystem services (ESs). The effects of FVC on ESs were analyzed based on the bivariate spatial autocorrelation model. The trade-off synergies and spatio-temporal variations of different scales of those indices were discussed. The results showed that the FVC of the study area presented a fluctuating upward trend from 2000 to 2020, with the annual average value increasing from 31.7% to 47.1%. Carbon sequestration service and soil conservation service were increased, habitat quality was stable. Water yield increased firstly and then decreased, with an overall upward trend. The ESs changes were scale-dependent. There was an obvious synergistic relationship among ESs. There was a significant spatial dependence between FVC and ESs, with some differences in the degree of correlation. FVC had the strongest impact on soil conservation, followed by carbon sequestration service. However, the increase of vegetation coverage and water consumption of forest and grass led to the negative effect of water yield reduction. In gene-ral, FVC in the Loess Plateau of Northern Shaanxi had achieved remarkable success, and the ecological environment had been significantly improved.


Assuntos
Ecossistema , Solo , Sequestro de Carbono , China , Água
3.
Ying Yong Sheng Tai Xue Bao ; 33(7): 2001-2008, 2022 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-36052805

RESUMO

With the acceleration of regional economic integration, human activities have played an increasingly crucial role in regional sustainable development. In this study, MODIS remote sensing data and ecological footprint of net primary productivity (EF-NPP) were leveraged to calculate the equivalence factor and yield factor of the six major biologically productive land areas in the Pearl River Delta Urban Agglomeration. We analyzed the changes in per capita ecological footprint, per capita ecological carrying capacity, natural resource utilization efficiency and ecological moderate population from 2000 to 2020. Results showed that the per capita ecological footprint in the Pearl River Delta Urban Agglomeration continued to rise from 2000 to 2020. The ecological occupation of energy land was the highest. The ecological footprint was high in west, low in middle, and higher in northwest of the study area. The per capita ecological carrying capacity was relatively high in Zhaoqing and Jiangmen and low in Shenzhen, Dongguan, Foshan and Zhongshan. The gap between the ecological moderate population and the regional actual population widened over time, reaching 30.62 million in 2020. The regional actual population was much larger than the ecological moderate population, indicating huge population pressure. The natural resource utilization efficiency of the three main industries was high. The economic benefits created by the per capita ecological footprint increased by 36800 yuan·hm-2 during the research period, with an average annual growth rate of 1800 yuan·hm-2. The growth rate of the tertiary industry was the highest. Therefore, the results could provide reference for the study on natural resource utilization efficiency in medium and small-scale regions.


Assuntos
Ecologia , Rios , China , Cidades , Conservação dos Recursos Naturais , Ecologia/métodos , Humanos , Indústrias , Desenvolvimento Sustentável
4.
World J Clin Cases ; 10(8): 2491-2496, 2022 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-35434062

RESUMO

BACKGROUND: Trastuzumab is a generally safe agent prescribed in the systemic treatment of breast cancer. Tinnitus is not a currently known adverse event related to trastuzumab. Here, we describe a rare case of severe tinnitus and a migraine headache induced by trastuzumab used for adjuvant therapy. CASE SUMMARY: A 37-year-old woman was diagnosed with hormone receptor-positive and human epidermal growth factor receptor 2-positive breast cancer. After surgery, she was treated with four cycles of epirubicin and cyclophosphamide; she then received docetaxel and a loading dose of trastuzumab plus pertuzumab. Less than half an hour after trastuzumab infusion, the patient complained of severe tinnitus and left-sided migraine headache. Trastuzumab monotherapy was discontinued immediately, and symptoms disappeared after 10 min. Trastuzumab was readministered, and severe tinnitus and migraine headache recurred. Trastuzumab was stopped, and severe tinnitus diminished after 10 min. Pertuzumab and docetaxel therapy was then administered, and no adverse events were observed. Subsequent infusions of trastuzumab every three weeks did not show the same symptoms. CONCLUSION: Although trastuzumab is well-tolerated in most patients, we should pay attention to the risk of severe tinnitus and migraine.

5.
Phytomedicine ; 67: 153158, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31999981

RESUMO

Background Shengui Sansheng Pulvis (SSP) has about 300 years history used for stroke treatment, and evidences suggest it has beneficial effects on neuro-angiogenesis and cerebral energy metabolic amelioration post-stroke. However, its protective action and mechanisms on blood-brain barrier (BBB) is still unknown. Purpose Based on multiple neuroprotective properties of vasoactive intestinal peptide (VIP) in neurological disorders, we investigate if SSP maintaining BBB integrity is associated with VIP pathway in rat permanent middle cerebral artery occlusion (MCAo) model. Methods Three doses of SSP extraction were administered orally. Evaluations of motor and balance abilities and detection of brain edema were performed, and BBB permeability were assessed by Evans blue (EB) staining. Primary brain microvascular endothelial cells (BMECs) were subjected to oxygen-glucose deprivation, and incubated with high dose SSP drug-containing serum and VIP-antagonist respectively. Transendothelial electrical resistance (TEER) assay and Tetramethylrhodamine isothiocyanate (TRITC)-dextran (4.4 kDa) and fluorescein isothiocyanate (FITC)-dextran (70 kDa) were used to evaluate the features of paracellular junction. Western blot detected the expressions of Claudin-5, ZO-1, Occludin and VE-cadherin, matrix metalloproteinase (MMP) 2/9 and VIP receptors 1/2, and immunofluorescence staining tested VIP and Claudin-5 expressions. Results Our results show that SSP significantly reduces EB infiltration in dose-dependent manner in vivo and attenuates TRITC- dextran and FITC-dextran diffusion in vitro, and strengthens endothelial junctional complexes as represented by decreasing Claudin-5, ZO-1, Occludin and VE-cadherin degradations and MMP 2/9 expression, as well as promoting TEER in BMECs after ischemia. Moreover, it suggests that SSP notably enhances VIP and its receptors 1/2 expressions. VIP-antagonist exacerbates paracellular barrier of BMECs, while the result is reversed after incubation with high dose SSP drug-containing serum. Additionally, SSP also improve brain edema and motor and balance abilities after ischemic stroke. Conclusions we firstly demonstrate that the ameliorated efficacy of SSP on BBB permeability is related to the enhancements of VIP and its receptors, suggesting SSP might be an effective therapeutic agent on maintaining BBB integrity post-stroke.


Assuntos
Barreira Hematoencefálica/efeitos dos fármacos , Isquemia Encefálica/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Acidente Vascular Cerebral/tratamento farmacológico , Peptídeo Intestinal Vasoativo/metabolismo , Animais , Isquemia Encefálica/metabolismo , Isquemia Encefálica/fisiopatologia , Claudina-5/metabolismo , Medicamentos de Ervas Chinesas/química , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Endotélio Vascular/citologia , Endotélio Vascular/efeitos dos fármacos , Infarto da Artéria Cerebral Média/fisiopatologia , Masculino , Permeabilidade , Ratos Endogâmicos , Receptores Tipo II de Peptídeo Intestinal Vasoativo/metabolismo , Receptores Tipo I de Polipeptídeo Intestinal Vasoativo/metabolismo , Acidente Vascular Cerebral/fisiopatologia
6.
Chin J Integr Med ; 25(10): 723-727, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31782008

RESUMO

Ischemic stroke accounts for the majority of all strokes and has been primary causes of long-term disability and mortality in worldwide. Mesenchymal stem cell (MSC) therapy suggests significantly improved effects on neurological functional outcome, neurogenesis, angiogenesis, blood-brain barrier permeability, inflammatory injury, neuroprotection and so on, following stroke. However, the occurrence of adverse effects results in restriction of the therapy. Chinese medicine accumulates abundant clinical experiences on stroke for over two thousand years, and some formulae and active ingredients of Chinese medicines have presented obvious efficacies in clinical treatment. Therefore, based on Chinese medicine theory, we provide some ideas of screening agents for combination treatment of Chinese medicines and MSC for ischemic stroke, and summarize the potentials of Chinese medicines in MSC treatment and analyze the feasibilities of Chinese medicines against side effects of MSC therapy. Consequently, we propose Chinese medicines combing with MSC should be a promising approach to clinical stroke treatment in future.


Assuntos
Isquemia Encefálica/terapia , Medicina Tradicional Chinesa , Transplante de Células-Tronco Mesenquimais , Terapia Combinada , Humanos
7.
Chin Med ; 14: 32, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31548850

RESUMO

BACKGROUND: Acupoint catgut embedding therapy characterized by acupoint, needle and catgut are superior to traditional acupuncture, due to exerting more comprehensive therapeutic efficacy. However, it is still deficient in clinical evidence for polyglycolic acid sutures, a novel biodegradable material instead of catgut, embedded for the treatment of simple obesity. In our study, we investigate the efficacy and related mechanism of polyglycolic acid sutures embedded in abdominal acupoints on simple obese persons by a randomized control trial. METHODS: A total of 51 eligible participators were randomly allocated to a polyglycolic acid sutures embedding therapy (PASET) group (n = 28) or control group (n = 23). Participators in PASET group received polyglycolic acid sutures alternatively embedded in abdominal I group and II group acupoints in odd and even number therapeutic courses, and participators in control group were required to perform lifestyle modification. The duration of the study was 10 weeks. RESULTS: It suggested that PASET significantly reduced weight, body mass index, hip circumference, waist circumference, waist/hip ratio, waist-to-height ratio and thickness of abdominal subcutaneous fat tissue compared with those before treatment (p < 0.01), but lifestyle modification only illustrated downward trend of weight (p < 0.05). Moreover, PASET group also improved the evaluated scores in aspects of physical function, self-esteem, public distress and sexual life, as well as decreased blood pressure, glycemia, low density lipoprotein, uric acid and the levels of tumor necrosis factor-alpha, interleukin-1ß, and increased high density lipoprotein in comparison with those before treatment (p < 0.05), whose efficacies are superior to control group. Additionally, our results also indicate PASET is relative safe and its pain and discomfort can be tolerable. CONCLUSIONS: PASET distinctly ameliorates anthropometric data and quality of life in obese population, which associates with improvements of metabolic profile and inflammatory response. Based on the advantageous actions, we think PASET is an effective therapeutic approach to simple obesity treatment.Trial registration ChiCTR, ChiCTR1800015591. Registered 10 April 2018, http://www.chictr.org.cn/showproj.aspx?proj=23258.

8.
Acta Pharmacol Sin ; 40(9): 1193-1204, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30833709

RESUMO

Gluconeogenesis is a major source of hyperglycemia in patients with type 2 diabetes mellitus (T2DM), thus targeting gluconeogenesis to suppress glucose production is a promising strategy for anti-T2DM drug discovery. In our preliminary in vitro studies, we found that a small-molecule (E)-3-(2-(quinoline-4-yl)vinyl)-1H-indol-6-ol (QVO) inhibited the hepatic glucose production (HGP) in primary hepatocytes. We further revealed that QVO suppressed hepatic gluconeogenesis involving calmodulin-dependent protein kinase kinase ß- and liver kinase B1-adenosine monophosphate-activated protein kinase (AMPK) pathways as well as AMPK-independent mitochondrial function-related signaling pathway. To evaluate QVO's anti-T2DM activity in vivo, which was impeded by the complicated synthesis route of QVO with a low yield, we designed and synthesized 4-[2-(1H-indol-3-yl)vinyl]quinoline (IVQ) as a prodrug with easier synthesis route and higher yield. IVQ did not inhibit the HGP in primary hepatocytes in vitro. Pharmacokinetic studies demonstrated that IVQ was quickly converted to QVO in mice and rats following administration. In both db/db and ob/ob mice, oral administration of IVQ hydrochloride (IVQ-HCl) (23 and 46 mg/kg every day, for 5 weeks) ameliorated hyperglycemia, and suppressed hepatic gluconeogenesis and activated AMPK signaling pathway in the liver tissues. Furthermore, IVQ caused neither cardiovascular system dysfunction nor genotoxicity. The good druggability of IVQ has highlighted its potential in the treatment of T2DM and the prodrug design for anti-T2DM drug development.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Gluconeogênese/efeitos dos fármacos , Hipoglicemiantes/uso terapêutico , Indóis/uso terapêutico , Pró-Fármacos/uso terapêutico , Quinolinas/uso terapêutico , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Diabetes Mellitus Experimental/tratamento farmacológico , Complexo I de Transporte de Elétrons/antagonistas & inibidores , Complexo III da Cadeia de Transporte de Elétrons/antagonistas & inibidores , Ativadores de Enzimas/uso terapêutico , Ativadores de Enzimas/toxicidade , Inibidores Enzimáticos/uso terapêutico , Inibidores Enzimáticos/toxicidade , Glucose-6-Fosfatase/antagonistas & inibidores , Hepatócitos/efeitos dos fármacos , Hipoglicemiantes/toxicidade , Indóis/toxicidade , Fígado/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Mitocôndrias/efeitos dos fármacos , Fosfoenolpiruvato Carboxiquinase (GTP)/antagonistas & inibidores , Pró-Fármacos/toxicidade , Quinolinas/toxicidade , Transdução de Sinais/efeitos dos fármacos
9.
J Cell Mol Med ; 23(1): 126-142, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30421523

RESUMO

The remodelling of structural and functional neurovascular unit (NVU) becomes a central therapeutic strategy after cerebral ischaemic stroke. In the present study, we investigated the effect of combined therapy of sodium ferulate (SF), n-butylidenephthalide (BP) and adipose-derived stromal cells (ADSCs) to ameliorate the injured NVU in the photochemically induced thrombotic stroke in rats. After solely or combined treatment, the neovascularization, activation of astrocytes, neurogenesis, expressions of vascular endothelial growth factor (VEGF) and claudin-5 were assessed by immunohistochemical or immunofluorescence staining. In order to uncover the underlying mechanism of therapeutic effect, signalling of protein kinase B/mammalian target of rapamycin (AKT/mTOR), extracellular signal-regulated kinase 1/2 (ERK1/2), and Notch1 in infarct zone were analysed by western blot. 18 F-2-deoxy-glucose/positron emission tomography, magnetic resonance imaging, Evans blue staining were employed to evaluate the glucose metabolism, cerebral blood flow (CBF), and brain-blood barrier (BBB) permeability, respectively. The results showed that combined treatment increased the neovascularization, neurogenesis, and VEGF secretion, modulated the astrocyte activation, enhanced the regional CBF, and glucose metabolism, as well as reduced BBB permeability and promoted claudin-5 expression, indicating the restoration of structure and function of NVU. The activation of ERK1/2 and Notch1 pathways and inhibition of AKT/mTOR pathway might be involved in the therapeutic mechanism. In summary, we have demonstrated that combined ADSCs with SF and BP, targeting the NVU remodelling, is a potential treatment for ischaemic stroke. These results may provide valuable information for developing future combined cellular and pharmacological therapeutic strategy for ischaemic stroke.


Assuntos
Ácidos Cumáricos/farmacologia , Neurogênese/efeitos dos fármacos , Anidridos Ftálicos/farmacologia , Acidente Vascular Cerebral/prevenção & controle , Células Estromais/metabolismo , Tecido Adiposo/citologia , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Astrócitos/citologia , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Edema Encefálico/complicações , Células Cultivadas , Circulação Cerebrovascular/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacologia , Ratos Sprague-Dawley , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/fisiopatologia , Células Estromais/citologia , Fator A de Crescimento do Endotélio Vascular/metabolismo
10.
Cell Transplant ; 26(2): 229-242, 2017 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-27772541

RESUMO

Being a potential candidate for stroke treatment, bone marrow-derived mesenchymal stem/stromal cells (BM-MSCs) have been demonstrated to be able to enhance angiogenesis and proliferation of reactive astrocytes, which subsequently leads to the amelioration of neurological injury. Increasing evidence further indicates that combining BM-MSCs with certain agents, such as simvastatin, may improve therapeutic effects. Sodium ferulate (SF) and n-butylidenephthalide (BP), two main components of Radix Angelica Sinensis, are proven to be important regulators of stem cells in cell migration, differentiation, and pluripotency maintenance. This study aimed to investigate whether combining BM-MSCs with SF and BP had better therapeutic effect in the treatment of stroke, and the underlying molecular basis for the therapeutic effects was also investigated. The results showed that combination treatment notably reduced neurological injury after stroke and increased the expression of astrocyte-derived vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), and von Willebrand factor-positive vascular density in the ischemic boundary zone as evaluated by immunofluorescence staining. After treatment with BM-MSCs plus SF and BP, astrocytes showed increased expression of VEGF and BDNF by upregulating protein kinase B/mammalian target of rapamycin (AKT/mTOR) expression in an oxygen- and glucose-deprived (OGD) environment. Human umbilical vein endothelial cells (HUVECs) incubated with the conditioned medium (CM) derived from OGD astrocytes treated with BM-MSCs plus SF and BP showed significantly increased migration and tube formation compared with those incubated with the CM derived from OGD astrocytes treated with BM-MSCs alone. These results demonstrate that combination treatment enhances the expression of astrocyte-derived VEGF and BDNF, which contribute to angiogenesis after cerebral ischemia, and the underlying mechanism is associated with activation of the astrocytic AKT/mTOR signaling pathway. Our study provides a potential therapeutic approach for ischemic stroke.


Assuntos
Células da Medula Óssea/citologia , Isquemia Encefálica/terapia , Ácidos Cumáricos/farmacologia , Células-Tronco Mesenquimais/fisiologia , Anidridos Ftálicos/farmacologia , Acidente Vascular Cerebral/terapia , Animais , Astrócitos/citologia , Astrócitos/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Células Cultivadas , Imunofluorescência , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Células-Tronco Mesenquimais/citologia , Neovascularização Fisiológica/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Serina-Treonina Quinases TOR/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Cicatrização/efeitos dos fármacos , Fator de von Willebrand/metabolismo
11.
Mol Imaging Biol ; 17(6): 802-10, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25962973

RESUMO

PURPOSE: Promoters developed for radiogene therapy always show non-negligible transcriptional activities, even when cells are not irradiated. This study developed a tightly radiation-controlled molecular switch based on radiation responsive element (CArG) repeats for in vivo molecular imaging using the Cre/loxP system. PROCEDURES: Different numbers of CArG repeats were cloned as a basal promoter directly, and its pre- and postirradiation transcriptional activities were analyzed by luciferase assay. Nine CArG repeats (E9) were chosen for use as a radiation-controlled molecular switch for the Cre/loxP system, and the feasibility of the switch in vitro and in vivo was demonstrated by luciferase assay and bioluminescence imaging, respectively. RESULTS: The E9 promoter, which exhibits extremely low transcriptional activity, showed a 1.8-fold enhancement after irradiation with a clinical dose of 2 Gy. Both in vitro and in vivo results indicated that E9 is relatively inert but sufficient to trigger the Cre/loxP system. The luciferase activity of stable H1299/pSTOP-FLuc cells transfected with pE9-NLSCre and exposed to 2-Gy radiation can reach 44 % of that of the same cells transfected with pCMV-NLSCre and not subjected to irradiation. By contrast, no appreciable difference was observed in reporter gene expression in both H1299/pSTOPFluc cells and tumors transfected with pE4Pcmv-NLSCre before and after irradiation, because the strong basal transcriptional activity of the CMV promoter, which acts as a copartner of E4, masked the response of E4 to radiation. CONCLUSIONS: Our results provide detailed insight into CArG elements as a radiation-controlled molecular switch that can facilitate the development of radiogene therapy.


Assuntos
Imagem Molecular , Regiões Promotoras Genéticas/efeitos da radiação , Sequências Repetitivas de Ácido Nucleico , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Integrases/genética , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Plasmídeos , Transcrição Gênica
12.
Am J Chin Med ; 42(1): 61-77, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24467535

RESUMO

Ischemic stroke is a clinical acute disease which causes neurological dysfunction and threatens a patient's life. Because the mechanism of pathology is complicated and most patients miss the best therapeutic window time, the effect of the treatment is not satisfied at present. Numerous studies indicated new vessels not only recuperated blood flow in the ischemic boundary zone, but also facilitated endogenous neurogenesis and improved neurological function after ischemic stroke. Therefore, angiogenesis has been an important research field in neurovascular regeneration. Recently, some Chinese medicines, bone marrow stromal cells (BMSCs) and their combination treatment were demonstrated to have beneficial effects in promoting angiogenesis both in vitro and in vivo. In this review, we summarized the effective mechanisms of Chinese medicines and BMSCs, as well as BMSCs in combination with Chinese medicines on angiogenesis post-stroke.


Assuntos
Transplante de Medula Óssea , Encéfalo/fisiologia , Medicamentos de Ervas Chinesas/uso terapêutico , Neovascularização Fisiológica , Fitoterapia , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/terapia , Aloenxertos , Animais , Terapia Combinada , Ácidos Cumáricos , Medicamentos de Ervas Chinesas/química , Ginsenosídeos , Humanos , Fator 1 Induzível por Hipóxia/fisiologia , Glucosídeos Iridoides , Regeneração Nervosa , Neurogênese , Óxido Nítrico Sintase Tipo III , Acidente Vascular Cerebral/genética , Fator A de Crescimento do Endotélio Vascular
13.
Am J Chin Med ; 41(2): 353-67, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23548125

RESUMO

There is increasing evidence that starvation induces autophagy, which may be protective during starvation, in an AMPK-dependent manner. Polysaccharides from Fuzi (FPS) reportedly have protective effects on nutrition-limited livers. The present study was designed to determine whether FPS protected H9c2 cells against starvation-induced cytotoxicity using an AMPK/mTOR-dependent mechanism. H9c2 cells were incubated in serum and glucose starvation media for 12 hours to establish a cell injury model. 3-Methyladenine (3MA, an autophagy inhibitor) was used to identify the exact role of autophagy in starvation. Cells were incubated with different FPS concentrations, and the cell injury levels, autophagy activity and AMPK/mTOR phosphorylation were measured. Adenine 9-ß-D-arabinofuranoside (Ara-A, an AMPK inhibitor) and 5-amino-4-imidazole-carboxamide riboside (AICAR, an AMPK activator) were used to identify whether the AMPK/mTOR pathway was involved in FPS-mediated cardioprotection. We demonstrated that starvation decreased cell viability in a time-dependent manner, and 3MA-induced autophagy inhibition aggravated the reduced cell viability. FPS treatment attenuated the cell viability decrement and the starvation-induced decline in the mitochondrial membrane potential (MMP), and autophagy; also, the AMPK/mTOR pathways were activated during treatment. Ara-A treatment abolished the protective effect of FPS, while AICAR treatment had a similar effect to FPS. We conclude that autophagy attenuates starvation-induced cardiomyocyte death, and FPS increases autophagy activity to protect against starvation-induced cytotoxicity in H9c2 cells, likely through AMPK/mTOR pathway activation.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Aconitum/química , Autofagia/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Miócitos Cardíacos/citologia , Polissacarídeos/farmacologia , Substâncias Protetoras/farmacologia , Inanição/complicações , Serina-Treonina Quinases TOR/metabolismo , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Ratos , Transdução de Sinais/efeitos dos fármacos
14.
Int J Infect Dis ; 17(7): e539-45, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23510538

RESUMO

BACKGROUND: Steatosis and insulin resistance induced by hepatitis C virus (HCV) infection are, at least in part, critical factors for the progression of chronic hepatitis C (CHC) and can influence the outcome of antiviral treatment. Silent information regulator 1 (SIRT1) and adenosine monophosphate-activated protein kinase (AMPK) play a key role in the regulation of hepatic glucose and lipid metabolism. The aim of this study was to investigate the possible effect of HCV core protein on energy, glucose, and lipid metabolism of hepatocytes and expression of SIRT1 and AMPK. METHODS: HCV core protein expression plasmid was transfected into HepG2 cells. The level of reactive oxygen species (ROS) and values of NAD(+)/NADH and ATP/ADP were detected. Intracellular levels of triacylglycerol (TG), cholesterol, glucose uptake by hepatocytes, and glucose production were measured. The expression levels of mRNA and protein of SIRT1 and AMPK were detected. The mRNA levels of SIRT1 and AMPK downstream glucose and lipid metabolism genes were measured. RESULTS: In HepG2 cells expressing HCV core protein, the level of ROS increased, the value of NAD(+)/NADH decreased, the activity and expression levels of mRNA and protein of SIRT1 and AMPK decreased, glucose uptake and its regulator gene GLUT2 mRNA levels decreased, glucose production and its regulator genes PEPCK and G6Pase mRNA levels increased, intracellular TG and cholesterol contents and their regulator gene (SREBP-1c, FAS, ACC, HMGR, and HMGS) mRNA levels increased, the glycolytic gene GK and fatty acid oxidation genes PPARα and CPT1A mRNA levels decreased. CONCLUSIONS: HCV core protein induces alterations in cellular redox state (decrease in the NAD(+)/NADH ratio), which could influence the activity of SIRT1 and secondarily AMPK, then change the expression profile of glucose and lipid metabolism-related genes, thereby causing metabolism disorders of hepatocytes.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Hepacivirus/metabolismo , Hepatopatias/metabolismo , Sirtuína 1/metabolismo , Proteínas do Core Viral/metabolismo , Western Blotting , Células Cultivadas , Colesterol/metabolismo , Regulação para Baixo , Glucose/metabolismo , Células Hep G2 , Humanos , Plasmídeos , RNA Mensageiro/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais , Sirtuína 1/genética , Transfecção , Triglicerídeos/metabolismo
15.
J Tradit Chin Med ; 32(2): 289-92, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22876459

RESUMO

Combined treatment of ischemic stroke with Chinese medicine and exogenous bone marrow mesenchymal stem cell (BMSC) transplantation may improve the removal of blood stasis and stimulation of neogenesis. Chinese medicines that remove blood stasis not only promote blood circulation but also calm the endopathic wind, remove heat, resolve phlegm, remove toxic substances and strengthen body resistance. The medicinal targeting effect of Chinese medicine can promote the homing of BMSCs, and the synergistic therapeutic effects of drugs can contribute to BMSC differentiation. As such, exogenous BMSC transplantation has potential advantages for neogenesis. Chinese medicines and exogenous BMSCs provide complementary functions for the removal of blood stasis and tion of Chinese medicine and transplantation of exogenous BMSCs may be particularly suited to ischemic stroke treatment.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Transplante de Medula Óssea , Isquemia Encefálica/terapia , Medicina Tradicional Chinesa , Transplante de Células-Tronco Mesenquimais , Acidente Vascular Cerebral/terapia , Isquemia Encefálica/sangue , Isquemia Encefálica/fisiopatologia , Diferenciação Celular , Terapia Combinada , Humanos , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/fisiopatologia
16.
Hepatobiliary Pancreat Dis Int ; 11(2): 185-92, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22484588

RESUMO

BACKGROUND: In China, hepatitis C virus (HCV) infection is characterized by an increasing prevalence during aging. This study was undertaken to evaluate the efficacy of treatment with peginterferon alpha-2a and ribavirin in elderly chronic hepatitis C (CHC) patients and study the factors related to the sustained virologic response (SVR). METHODS: The medical records of 417 patients treated with peginterferon and ribavirin were retrospectively analyzed. These patients were divided into two groups according to age: patients aged ≥ 65 years (n=140) and patients aged <65 years (n=277). The rate of ribavirin reduction or discontinuation and virologic response rates of the two groups were compared. The factors influencing SVR were studied by multivariate analysis. RESULTS: Ribavirin reduction or discontinuation was more frequent in patients aged ≥ 65 years than patients aged <65 years (37.1%, 52/140 vs 20.2%, 56/277; X2=13.883, P<0.001). For genotype 1, patients aged ≥ 65 years had a higher relapse rate (50.0%, 42/84 vs 29.2%, 52/178; X2=10.718, P=0.001) and a lower SVR rate (40.0%, 42/105 vs 60.0%, 126/210; X2=11.250, P=0.001) than patients aged <65 years. There were no significant differences in virologic response rates between the two groups for patients with genotype 2. For genotype 1, in patients aged ≥ 65 years, the SVR rate of females was lower than that of males (28.6%, 12/42 vs 47.6%, 30/63; X2=8.150, P=0.004); in the high viral load group, patients aged ≥ 65 years had a lower SVR rate than patients aged <65 years (30.0%, 18/60 vs 54.8%, 69/126; X2=10.010, P=0.002). In multivariate logistic regression analysis, the independent factors associated with SVR in patients aged ≥ 65 years were sex (P=0.020), genotype (P=0.005), ribavirin reduction or discontinuation (P=0.009) and presence of rapid virologic response (RVR) (P=0.001). CONCLUSIONS: The rate of ribavirin reduction or discontinuation and relapse rate of patients aged ≥ 65 years with genotype 1 are high, and the SVR rate is low. Age has no impact on virologic responses rates for genotype 2. Among patients ≥ 65 years old, genotype 2 patients and genotype 1 patients with a low baseline viral load or achieving RVR or male may benefit from combination therapy.


Assuntos
Antivirais/uso terapêutico , Genótipo , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/genética , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Fatores Etários , Idoso , Antivirais/farmacologia , Biópsia , Relação Dose-Resposta a Droga , Tratamento Farmacológico , Feminino , Hepacivirus/genética , Humanos , Interferon-alfa/farmacologia , Fígado/patologia , Masculino , Análise Multivariada , Polietilenoglicóis/farmacologia , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêutico , Estudos Retrospectivos , Ribavirina/farmacologia , Resultado do Tratamento , Carga Viral/efeitos dos fármacos
17.
Chin J Integr Med ; 17(9): 715-20, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21910075

RESUMO

Many laboratories have been attempting to integrate Chinese medicine (CM) with the research of stem cells in order to explore this promising frontier. Studies on the combination of CM and bone marrow-derived mesenchymal stem cells (BMSCs) have found that some effective components from CM could activate endogenous stem cells and induce stem cells to differentiate into neural-like cells in vitro and promote angiogenesis. This review summarized the latest research findings of BMSCs and their application combined with CM in the treatment of cerebral ischemia.


Assuntos
Células da Medula Óssea/citologia , Isquemia Encefálica/terapia , Medicamentos de Ervas Chinesas/uso terapêutico , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Isquemia Encefálica/tratamento farmacológico , Terapia Combinada , Humanos
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