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1.
Planta ; 259(6): 131, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38652171

RESUMO

MAIN CONCLUSION: The anatomical structures of Carex moorcroftii roots showing stronger plasticity during drought had a lower coefficient of variation in cell size in the same habitats, while those showing weaker plasticity had a higher coefficient of variation. The complementary relationship between these factors comprises the adaptation mechanism of the C. moorcroftii root to drought. To explore the effects of habitat drought on root anatomy of hygrophytic plants, this study focused on roots of C. moorcroftii. Five sample plots were set up along a soil moisture gradient in the Western Sichuan Plateau to collect experimental materials. Paraffin sectioning was used to obtain root anatomy, and one-way ANOVA, correlation analysis, linear regression analysis, and RDA ranking were applied to analyze the relationship between root anatomy and soil water content. The results showed that the root transverse section area, thickness of epidermal cells, exodermis and Casparian strips, and area of aerenchyma were significantly and positively correlated with soil moisture content (P < 0.01). The diameter of the vascular cylinder and the number and total area of vessels were significantly and negatively correlated with the soil moisture content (P < 0.01). The plasticity of the anatomical structures was strong for the diameter and area of the vascular cylinder and thickness of the Casparian strip and epidermis, while it was weak for vessel diameter and area. In addition, there was an asymmetrical relationship between the functional adaptation of root anatomical structure in different soil moisture and the variation degree of root anatomical structure in the same soil moisture. Therefore, the roots of C. moorcroftii can shorten the water transport distance from the epidermis to the vascular cylinder, increase the area of the vascular cylinder and the number of vessels, and establish a complementary relationship between the functional adaptation of root anatomical structure in different habitats and the variation degree of root anatomical structure in the same habitat to adapt to habitat drought. This study provides a scientific basis for understanding the response of plateau wetland plants to habitat changes and their ecological adaptation strategies. More scientific experimental methods should be adopted to further study the mutual coordination mechanisms of different anatomical structures during root adaptation to habitat drought for hygrophytic plants.


Assuntos
Carex (Planta) , Secas , Ecossistema , Raízes de Plantas , Solo , Água , Raízes de Plantas/anatomia & histologia , Raízes de Plantas/fisiologia , China , Carex (Planta)/fisiologia , Carex (Planta)/anatomia & histologia , Água/fisiologia , Água/metabolismo , Adaptação Fisiológica
2.
Zhongguo Zhong Yao Za Zhi ; 47(24): 6541-6550, 2022 Dec.
Artigo em Zh | MEDLINE | ID: mdl-36604902

RESUMO

Cannabidiol is the main non-psychoactive component of Cannabis sativa, which has multiple medicinal activities, such as antiepileptic, immunomodulation, analgesic, antioxidant, anticonvulsant, anti-anxiety and other functions. In recent years, it has been found that cannabidiol can inhibit the proliferation of various tumor cells, induce apoptosis and autophagy of tumor cells, arrest cell cycle, interrupt invasion and metastasis of tumor cells, regulate tumor microenvironment, exert synergistic therapy with other chemotherapeutic drugs, and reduce the toxicity of chemotherapeutic drugs. However, its anti-tumor effect remains controversial and its application is limited. The study of microspheres, nano liposomes and other new drug delivery systems can improve the anti-tumor effect of cannabidiol. In this study, the anti-tumor mechanism and application of cannabidiol were summarized and discussed in order to provide inspirations for its further investigation and application.


Assuntos
Canabidiol , Cannabis , Neoplasias , Humanos , Canabidiol/farmacologia , Canabidiol/uso terapêutico , Neoplasias/tratamento farmacológico , Apoptose , Transtornos de Ansiedade/tratamento farmacológico , Microambiente Tumoral
3.
Inflamm Res ; 70(10-12): 1151-1164, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34661679

RESUMO

OBJECTIVE: Gisenoside Rg1 is a potent neuroprotectant in ginseng. The aim of this study was to investigate the elimination effect of Rg1 on cadmium (Cd)-induced neurotoxicity. MATERIALS AND METHODS: A cumulative Cd exposure mouse model was established. Also, the toxicity of Cd and the protective effect of Rg1 were examined in vitro using cultured neurons and microglia. RESULTS: We found that Cd-intoxicated mice exhibited significant injury in the liver, kidney, small intestine, and testis, along with cognitive impairment. Antioxidant enzymes such as SOD, GSH-Px and CAT were reduced in the blood and brain, and correspondingly, the lipid peroxidation product MDA was elevated. In the brain, astrocytes and microglia were activated, characterized by an increase in inflammatory factors such as TNF-α, IL-1ß and IL-6, as well as their protein markers GFAP and IBA1. However, Rg1 eliminated Cd-induced toxicity and restored oxidative stress and inflammatory responses, correspondingly restoring the behavioral performance of the animals. Meanwhile, the BDNF-TrkB/Akt and Notch/HES-1 signaling axes were involved in the Rg1-mediated elimination of Cd-induced toxicity. CONCLUSION: Rg1 is a promising agent for the elimination of Cd-induced toxicity.


Assuntos
Anti-Inflamatórios/uso terapêutico , Cádmio , Ginsenosídeos/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Síndromes Neurotóxicas/tratamento farmacológico , Animais , Anti-Inflamatórios/farmacologia , Apoptose/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/imunologia , Encéfalo/patologia , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Citocinas/genética , Citocinas/imunologia , Ginsenosídeos/farmacologia , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/patologia , Rim/efeitos dos fármacos , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Microglia/patologia , Neurônios/efeitos dos fármacos , Neurônios/patologia , Fármacos Neuroprotetores/farmacologia , Síndromes Neurotóxicas/imunologia , Síndromes Neurotóxicas/patologia , Estresse Oxidativo/efeitos dos fármacos , Oxirredutases/imunologia , Testículo/efeitos dos fármacos , Testículo/patologia
4.
Cell Biol Int ; 45(6): 1316-1326, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33620117

RESUMO

Hyperglycemia can drive advanced glycation end product (AGE) accumulation and associated nucleus pulposus cell (NPC) dysfunction, but the basis for this activity has not been elucidated. Hypoxia-inducible factor-1α (HIF-1α) is subject to cell-type-specific AGE-mediated regulation. In the current study, we assessed the mechanistic relationship between AGE accumulation and HIF-1α degradation in NPCs. Immunohistochemical staining of degenerated nucleus pulposus (NP) samples was used to assess AGE levels. AGE impact on NPC survival and glycolysis-related gene expression was assessed via 3-(4,5)-dimethylthiazol(-z-y1)-3,5-di-phenyltetrazolium bromide assay and quantitative reverse-transcription polymerase chain reaction (qRT-PCR), while HIF-1α expression in NPCs following AGE treatment was monitored via Western blot analysis and qRT-PCR. Additionally, a luciferase reporter assay was used to monitor HIF-1α transcriptional activity. The importance of the receptor for activated C-kinase 1 (RACK1) as a mediator of HIF-1α degradation was evaluated through gain- and loss-of-function experiments. Competitive binding of RACK1 and HSP90 to HIF-1α was evaluated via immunoprecipitation. Increased AGE accumulation was evident in NP samples from diabetic patients, and AGE treatment resulted in reduced HIF-1α protein levels in NPCs that coincided with reduced HIF-1α transcriptional activity. AGE treatment impaired the stability of HIF-1α, leading to its RACK1-mediated proteasomal degradation in a manner independent of the canonical PHD-mediated degradation pathway. Additionally, RACK1 competed with HSP90 for HIF-1α binding following AGE treatment. AGE treatment of NPCs leads to HIF-1α protein degradation. RACK1 competes with HSP90 for HIF-1α binding following AGE treatment, resulting in posttranslational HIF-1α degradation. These results suggest that AGE is an intervertebral disc degeneration risk factor, and highlight potential avenues for the treatment or prevention of this disease.


Assuntos
Produtos Finais de Glicação Avançada/metabolismo , Proteínas de Choque Térmico HSP90/metabolismo , Hiperglicemia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Proteínas de Neoplasias/fisiologia , Núcleo Pulposo , Receptores de Quinase C Ativada/fisiologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Núcleo Pulposo/metabolismo , Núcleo Pulposo/patologia , Ligação Proteica
5.
J Pharmacol Exp Ther ; 367(2): 292-301, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30171039

RESUMO

The N-methyl-d-aspartate receptor coagonist d-serine is a substrate for the neutral amino acid transporters ASCT1 and ASCT2, which may regulate its extracellular levels in the central nervous system (CNS). We tested inhibitors of ASCT1 and ASCT2 for their effects in rodent models of schizophrenia and visual dysfunction, which had previously been shown to be responsive to d-serine. L-4-fluorophenylglycine (L-4FPG), L-4-hydroxyPG (L-4OHPG), and L-4-chloroPG (L-4ClPG) all showed high plasma bioavailability when administered systemically to rats and mice. L-4FPG showed good brain penetration with brain/plasma ratios of 0.7-1.4; however, values for L-4OHPG and L-4ClPG were lower. Systemically administered L-4FPG potently reduced amphetamine-induced hyperlocomotion in mice, whereas L-4OHPG was 100-fold less effective and L-4ClPG inactive at the doses tested. L-4FPG and L-4OHPG did not impair visual acuity in naive rats, and acute systemic administration of L-4FPG significantly improved the deficit in contrast sensitivity in blue light-treated rats caused by retinal degeneration. The ability of L-4FPG to penetrate the brain makes this compound a useful tool to further evaluate the function of ASCT1 and ASCT2 transporters in the CNS.


Assuntos
Sistema ASC de Transporte de Aminoácidos/antagonistas & inibidores , Esquizofrenia/metabolismo , Transtornos da Visão/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Glicina/farmacologia , Locomoção/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Antígenos de Histocompatibilidade Menor , Ratos , Ratos Long-Evans , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Esquizofrenia/tratamento farmacológico , Serina/farmacologia , Transtornos da Visão/tratamento farmacológico
6.
Zhongguo Zhong Yao Za Zhi ; 43(3): 544-550, 2018 Feb.
Artigo em Zh | MEDLINE | ID: mdl-29600620

RESUMO

The dynamic changes of active components in stems and leaves of Mentha Haplocalycis Herba(mint) at different harvest periods were investigated, and the optimum harvest time of mint was explored. In this study, hesperidin, diosmin, didymin and buddleoside were selected as flavonoids index components of mint, and the QAMS method was established to measure the contents of these flavonoids in mint. The contents of 4 flavonoid glycosides in the mint stems and leaves from three habitats harvested in different time were studied and evaluated comprehensively using statistical analysis and principal component analysis (PCA). The results showed that the contents of 4 components in the leaves are higher than that in the stems despite of habitats and harvest time, and they all exhibited dynamic changes along with the harvest periods within the same habitat. Three harvest periods in mid April, mid September and late October scored higher in comprehensive evaluation in Jiangsu region, the genuine producing area of Mentha Haplocalycis Herba. Combined with the yield and contents of active compounds, the optimum harvest time of mint in Jiangsu region was mid September and late October, which is basically consistent with the traditional harvesting periods.


Assuntos
Flavonoides/análise , Mentha/química , Estações do Ano , Compostos Fitoquímicos/análise , Extratos Vegetais , Folhas de Planta/química , Caules de Planta/química
7.
Expert Rev Vaccines ; 23(1): 523-534, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38682812

RESUMO

BACKGROUND: Traditional vaccine development, often a lengthy and costly process of three separated phases. However, the swift development of COVID-19 vaccines highlighted the critical importance of accelerating the approval of vaccines. This article showcases a seamless phase 2/3 trial design to expedite the development process, particularly for multi-valent vaccines. RESEARCH DESIGN AND METHODS: This study utilizes simulation to compare the performance of seamless phase 2/3 design with that of conventional trial design, specifically by re-envisioning a 9-valent HPV vaccine trial. Across three cases, several key performance metrics are evaluated: overall power, type I error rate, average sample size, trial duration, the percentage of early stop, and the accuracy of dose selection. RESULTS: On average, when the experimental vaccine was assumed to be effective, the seamless design that performed interim analyses based solely on efficacy saved 555.73 subjects, shortened trials by 10.29 months, and increased power by 3.70%. When the experimental vaccine was less effective than control, it saved an average of 887.73 subjects while maintaining the type I error rate below 0.025. CONCLUSION: The seamless design proves to be a compelling strategy for vaccine development, given its versatility in early stopping, re-estimating sample sizes, and shortening trial durations.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Projetos de Pesquisa , Desenvolvimento de Vacinas , Humanos , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , Desenvolvimento de Vacinas/métodos , Tamanho da Amostra , Vacinas contra Papillomavirus/administração & dosagem , Vacinas contra Papillomavirus/imunologia , Simulação por Computador
8.
Nat Prod Bioprospect ; 14(1): 26, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38691189

RESUMO

Seven undescribed compounds, including three flavones (1-3), one phenylpropanoid (19), three monoaromatic hydrocarbons (27-29), were isolated from the twigs of Mosla chinensis Maxim together with twenty-eight known compounds. The structures were characterized by HRESIMS, 1D and 2D NMR, and ECD spectroscopic techniques. Compound 20 displayed the most significant activity against A/WSN/33/2009 (H1N1) virus (IC50 = 20.47 µM) compared to the positive control oseltamivir (IC50 = 6.85 µM). Further research on the anti-influenza mechanism showed that compound 20 could bind to H1N1 virus surface antigen HA1 and inhibit the early attachment stage of the virus. Furthermore, compounds 9, 22, 23, and 25 displayed moderate inhibitory effects on the NO expression in LPS inducing Raw 264.7 cells with IC50 values of 22.78, 20.47, 27.66, and 30.14 µM, respectively.

9.
J Mol Cell Cardiol ; 59: 167-75, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23500391

RESUMO

Insulin can translocate Akt to mitochondria in cardiac muscle. The goals of this study were to define sub-mitochondrial localization of the translocated Akt, to dissect the effects of insulin on Akt isoform translocation, and to determine the direct effect of mitochondrial Akt activation on Complex V activity in normal and diabetic myocardium. The translocated Akt sequentially localized to the mitochondrial intermembrane space, inner membrane, and matrix. To confirm Akt translocation, in vitro import assay showed rapid entry of Akt into mitochondria. Akt isoforms were differentially regulated by insulin stimulation, only Akt1 translocated into mitochondria. In the insulin-resistant Type 2 diabetes model, Akt1 translocation was blunted. Mitochondrial activation of Akt1 increased Complex V activity by 24% in normal myocardium in vivo and restored Complex V activity in diabetic myocardium. Basal mitochondrial Complex V activity was lower by 22% in the Akt1(-/-) myocardium. Insulin-stimulated Complex V activity was not impaired in the Akt1(-/-) myocardium, due to compensatory translocation of Akt2 to mitochondria. Akt1 is the primary isoform that relayed insulin signaling to mitochondria and modulated mitochondrial Complex V activity. Activation of mitochondrial Akt1 enhanced ATP production and increased phosphocreatine in cardiac muscle cells. Dysregulation of this signal pathway might impair mitochondrial bioenergetics in diabetic myocardium.


Assuntos
Adenosina Trifosfatases/metabolismo , Proteínas de Transporte/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Proteínas de Membrana/metabolismo , Mitocôndrias/metabolismo , Miocárdio/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Cálcio/metabolismo , Técnicas In Vitro , Insulina/farmacologia , Espectrometria de Massas , Camundongos , ATPases Mitocondriais Próton-Translocadoras , Fosforilação Oxidativa , Fosfocreatina/metabolismo , Ratos
10.
Fitoterapia ; 170: 105670, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37690598

RESUMO

Verbena officinalis is used as a Chinese folk medicine for the treatment of rheumatism and bronchitis. Herein, four undescribed triterpenes, officinalisoids A-D (1-4), together with thirty-three known compounds (5-37) were isolated from the aerial parts of V. officinalis. The chemical structures of the new compounds were determined by spectrometric data interpretation using NMR, HRESIMS, IR and UV spectroscopy. Biological evaluation results revealed that compound 30 exhibited potential anti-inflammatory activity with IC50 value of 6.07 µM (CC50 > 50 µM) and compound 12 showed moderate anti-dengue virus activity with the IC50 value of 24.55 µM (CC50 > 50 µM).

11.
Am J Physiol Heart Circ Physiol ; 302(3): H716-23, 2012 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-22081709

RESUMO

We recently reported translocation and activation of Akt in cardiac mitochondria. This study was to determine whether activation of Akt in mitochondria could inhibit apoptosis of cardiac muscle cells. Insulin stimulation induced translocation of phosphorylated Akt to the mitochondria in primary cardiomyocytes. A mitochondria-targeted constitutively active Akt was overexpressed via adenoviral vector and inhibited efflux of cytochrome c and apoptosis-inducing factor from mitochondria to cytosol and partially prevented loss of mitochondria cross-membrane electrochemical gradient. Activation of caspase 3 was suppressed in the cardiomyocytes transduced with mitochondria-targeted active Akt, whereas a mitochondria-targeted dominant negative Akt enhanced activation of caspase 3. Terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling assay showed that mitochondrial activation of Akt significantly reduced the number of apoptotic cells. When the endogenous Akt was abolished by LY294002, the antiapoptotic actions of mitochondrial Akt remained effective. These experiments suggested that mitochondrial Akt suppressed apoptosis signaling independent of cytosolic Akt in cardiac muscle cells.


Assuntos
Apoptose/fisiologia , Mitocôndrias/metabolismo , Miócitos Cardíacos/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/fisiologia , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Núcleo Celular/metabolismo , Cromonas/farmacologia , Citosol/metabolismo , Inibidores Enzimáticos/farmacologia , Potencial da Membrana Mitocondrial/fisiologia , Morfolinas/farmacologia , Mutagênese/fisiologia , Miócitos Cardíacos/citologia , Cultura Primária de Células , Proteínas Proto-Oncogênicas c-akt/genética , Ratos , Ratos Sprague-Dawley
12.
J Surg Res ; 178(2): 982-7, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22835951

RESUMO

BACKGROUND: There is limited information concerning older donors in living donor liver transplantation (LDLT). In the present study, we attempted to clarify whether it is safe to use older donors in LDLT. METHODS: A total of 129 cases were reviewed in the present study. Donors and recipients were divided into group A (donors aged ≥ 50 y, n=21) and group B (donors aged <50 y, n=108). The pre-, intra-, and postoperative variables of the two groups were statistically compared. RESULTS: Donors' complication rates were 38.10% and 28.70% for groups A and B, respectively (P=0.719). The overall 1-, 3-, and 5-y survival rates were 90%, 80%, and 66% for group A and 86%, 83%, and 75% for group B, respectively (P=0.573). Similar Clavien III or more complication rates for recipients were observed. CONCLUSIONS: The present study suggested that LDLT using older donors had no negative influence on the outcomes of both donors and recipients.


Assuntos
Transplante de Fígado , Doadores Vivos , Adulto , Fatores Etários , Idoso , Feminino , Humanos , Transplante de Fígado/efeitos adversos , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida
13.
Ann Hepatol ; 11(4): 471-7, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22700628

RESUMO

BACKGROUND: Living donor liver transplantation (LDLT) for patients with high model for end-stage liver disease (MELD) scores is controversial due to its poor outcome. However, there is little information regarding which factor would negatively impact the outcome of patients with high MELD scores. The aim of this study was to identify factors associated with the in-hospital mortality of patients with high MELD scores after LDLT. MATERIAL AND METHODS: All patients with an MELD scores ≥ 20 who received LDLT from 2005 to 2011 were recruited for the present study. Pre- and intra-operative variables were retrospectively and statistically analyzed. RESULTS: A total of 61 patients were included in the current study. The overall 3-month survival rate was 82% for patients with high MELD scores. Preoperative renal dysfunction, hyponatremia, starting albumin level < 2.8 g/dL, preoperative renal replacement for severe renal failure, anhepatic period > 100 minutes and intraoperative red blood cell (RBC) transfusion ≥ 10 units were identified as potential risk factors by univariate analysis. However, only hyponatremia, preoperative dialysis and massive RBC transfusion were independent risk factors in a multivariate analysis. The 3-month survival rates of patients with two or more independent risk factors and patients with none or one risk factor were 91 and 25%, respectively. A significant difference was observed (P < 0.001). CONCLUSION: Hyponatremia, preoperative dialysis and massive RBC transfusion were related to poor outcome for sicker patients. Patients with two or more of the above-mentioned risk factors and high MELD scores may exhibit extremely poor short-term survival.


Assuntos
Doença Hepática Terminal/mortalidade , Doença Hepática Terminal/cirurgia , Transplante de Fígado/mortalidade , Doadores Vivos , Adulto , Distribuição de Qui-Quadrado , China/epidemiologia , Doença Hepática Terminal/diagnóstico , Transfusão de Eritrócitos/mortalidade , Feminino , Mortalidade Hospitalar , Humanos , Hiponatremia/mortalidade , Estimativa de Kaplan-Meier , Nefropatias/mortalidade , Nefropatias/terapia , Transplante de Fígado/efeitos adversos , Masculino , Análise Multivariada , Modelos de Riscos Proporcionais , Diálise Renal/mortalidade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
14.
Hepatogastroenterology ; 59(113): 224-7, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22260833

RESUMO

BACKGROUND/AIMS: Graft size is recognized as one of the most important factors that affect prognosis of the liver recipients. This study determines whether the graft to recipient weight ratio (GRWR) alone can be used to select the liver donor and as an outcome predictor before living donor liver transplantation (LDLT). METHODOLOGY: LDLT patients (202) were divided into three groups according to the GRWR: Group S (n=46, GRWR <0.8); Group M (n=83, GRWR 0.8-1.0); Group L (n=73, GRWR >1.0). Recovery of graft function, incidence of small-for-size syndrome and rate of complications were compared among the three groups. RESULTS: There were no significant differences in the baseline characteristics in both the donors and recipients, nor in the intensive care unit stay hours, re-operation rate, hospital stay after operation, Clavien System score and recovery of graft function after transplantation, among the three groups. The small-for-size syndrome rates were 13%, 7.23% and 11% in Groups S, M and B, and no significant difference was noted among the three groups. CONCLUSIONS: GRWR may not be the only factor affecting recipient prognosis after LDLT. Local graft dysfunction such as impaired venous outflow, severity of disease and portal hyperperfusion in the recipient, and fatty liver in donor may influence the graft and thus the prognosis of transplantation.


Assuntos
Seleção do Doador , Transplante de Fígado , Fígado/cirurgia , Doadores Vivos , Adulto , China , Feminino , Humanos , Fígado/anatomia & histologia , Transplante de Fígado/efeitos adversos , Masculino , Tamanho do Órgão , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Reoperação , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
15.
Hepatobiliary Pancreat Dis Int ; 11(1): 28-33, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22251467

RESUMO

BACKGROUND: Liver transplantation can lead to the development of posttraumatic stress disorder (PTSD), but the risk factors associated with this progression are not well understood. To study this syndrome in adult liver transplant recipients, a cross-sectional investigation of 296 recipients at our hospital was carried out between January and June 2010. METHODS: Study participants completed two questionnaires [a PTSD self-rating scale (PTSD-SS) and a validated Chinese version of the Medical Outcomes Study Short Form-36 (SF-36)]. Clinical and demographic data were collected from the records of the Chinese Liver Transplant Registry and via questionnaires. RESULTS: The prevalence of full PTSD and partial PTSD (that met the criteria for 2 of the 3 symptom clusters) was 3.7% and 5.4%, respectively, for all transplant recipients. Significant differences between the recipients with no PTSD, partial PTSD, and full PTSD were found in all SF-36 domains except for physical functioning (P=0.466). In general, domain scores were the highest in the recipients who did not meet the criteria for PTSD and the lowest in the recipients who met the criteria for full PTSD. Greater severity of posttraumatic stress symptoms was correlated with poorer quality of life, especially in the bodily pain (P=0.004), social functioning (P=0.001), role-emotional (P=0.048), and mental health (P<0.001) domains. The model for end-stage liver disease (MELD) scores, complications, and educational status were identified by multiple regression analysis as risk factors for developing PTSD. CONCLUSIONS: PTSD occurred after liver transplantation and was significantly associated with decreased quality of life. Higher MELD scores and complications after transplantation were risk factors that contributed to PTSD, and higher education was a protective factor.


Assuntos
Transplante de Fígado/efeitos adversos , Transtornos de Estresse Pós-Traumáticos/etiologia , Adulto , Distribuição de Qui-Quadrado , China , Estudos Transversais , Escolaridade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Qualidade de Vida , Análise de Regressão , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Inquéritos e Questionários , Resultado do Tratamento
16.
Front Pharmacol ; 13: 902796, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35571137

RESUMO

The small molecule DAPT inhibits the Notch signaling pathway by blocking γ-secretase mediated Notch cleavage. Given the critical role of the Notch signaling axis in inflammation, we asked whether DAPT could block Notch-mediated inflammation and thus exert neuronal protection. We established a mouse model of chronic exposure to cadmium (Cd)-induced toxicity and treated it with DAPT. DAPT was effective in ameliorating Cd-induced multi-organ damage and cognitive impairment in mice, as DAPT restored abnormal performance in the Y-maze, forced swimming and Morris water maze (MWM) tests. DAPT also reversed Cd-induced neuronal loss and glial cell activation to normal as observed by immunofluorescence and immunohistochemistry of brain tissue sections. In addition, Cd-intoxicated mice showed significantly increased levels of the Notch/HES-1 signaling axis and NF-κB, as well as decreased levels of the inflammatory inhibitors C/EBPß and COP1. However, DAPT down regulated the elevated Notch/HES-1 signaling axis to normal, eliminating inflammation and thus protecting the nervous system. Thus, DAPT effectively eliminated the neurotoxicity of Cd, and blocking γ-secretase as well as Notch signaling axis may be a potential target for the development of neuronal protective drugs.

17.
Front Pharmacol ; 13: 860492, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35668945

RESUMO

Acute lung injury (ALI) or its aggravated stage acute respiratory distress syndrome (ARDS) is a common severe clinical syndrome in intensive care unit, may lead to a life-threatening form of respiratory failure, resulting in high mortality up to 30-40% in most studies. Nanotechnology-mediated anti-inflammatory therapy is an emerging novel strategy for the treatment of ALI, has been demonstrated with unique advantages in solving the dilemma of ALI drug therapy. Artesunate (ART), a derivative of artemisinin, has been reported to have anti-inflammatory effects. Therefore, in the present study, we designed and synthesized PEGylated ART prodrugs and assessed whether ART prodrugs could attenuate lipopolysaccharide (LPS) induced ALI in vitro and in vivo. All treatment groups were conditioned with ART prodrugs 1 h before challenge with LPS. Significant increased inflammatory cytokines production and decreased GSH levels were observed in the LPS stimulated mouse macrophage cell line RAW264.7. Lung histopathological changes, lung W/D ratio, MPO activity and total neutrophil counts were increased in the LPS-induced murine model of ALI via nasal administration. However, these results can be reversed to some extent by treatment of ART prodrugs. The effectiveness of mPEG2k-SS-ART in inhibition of ALI induced by LPS was confirmed. In conclusion, our results demonstrated that the ART prodrugs could attenuate LPS-induced ALI effectively, and mPEG2k-SS-ART may serve as a novel strategy for treatment of inflammation induced lung injury.

18.
Infect Dis Poverty ; 11(1): 74, 2022 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-35768826

RESUMO

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, seasonal influenza activity declined globally and remained below previous seasonal levels, but intensified in China since 2021. Preventive measures to COVID-19 accompanied by different epidemic characteristics of influenza in different regions of the world. To better respond to influenza outbreaks under the COVID-19 pandemic, we analyzed the epidemiology, antigenic and genetic characteristics, and antiviral susceptibility of influenza viruses in the mainland of China during 2020-2021. METHODS: Respiratory specimens from influenza like illness cases were collected by sentinel hospitals and sent to network laboratories in Chinese National Influenza Surveillance Network. Antigenic mutation analysis of influenza virus isolates was performed by hemagglutination inhibition assay. Next-generation sequencing was used for genetic analyses. We also conducted molecular characterization and phylogenetic analysis of circulating influenza viruses. Viruses were tested for resistance to antiviral medications using phenotypic and/or sequence-based methods. RESULTS: In the mainland of China, influenza activity recovered in 2021 compared with that in 2020 and intensified during the traditional influenza winter season, but it did not exceed the peak in previous years. Almost all viruses isolated during the study period were of the B/Victoria lineage and were characterized by genetic diversity, with the subgroup 1A.3a.2 viruses currently predominated. 37.8% viruses tested were antigenically similar to reference viruses representing the components of the vaccine for the 2020-2021 and 2021-2022 Northern Hemisphere influenza seasons. In addition, China has a unique subgroup of 1A.3a.1 viruses. All viruses tested were sensitive to neuraminidase inhibitors and endonuclease inhibitors, except two B/Victoria lineage viruses identified to have reduced sensitivity to neuraminidase inhibitors. CONCLUSIONS: Influenza activity increased in the mainland of China in 2021, and caused flu season in the winter of 2021-2022. Although the diversity of influenza (sub)type decreases, B/Victoria lineage viruses show increased genetic and antigenic diversity. The world needs to be fully prepared for the co-epidemic of influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus globally.


Assuntos
COVID-19 , Influenza Humana , Orthomyxoviridae , Antivirais/farmacologia , Antivirais/uso terapêutico , COVID-19/epidemiologia , China/epidemiologia , Humanos , Influenza Humana/epidemiologia , Neuraminidase/genética , Orthomyxoviridae/genética , Pandemias , Filogenia , SARS-CoV-2 , Estações do Ano
19.
Hepatobiliary Pancreat Dis Int ; 10(3): 248-53, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21669566

RESUMO

BACKGROUND: Living donor liver transplantation (LDLT) is considered to be the alterative choice in light of the great shortage of cadaveric donors. However, the characteristics of the patients who will benefit from LDLT have not been well identified. The aim of this study was to define the pre- and intra-operative factors that may influence patient outcome. METHODS: The data from 102 LDLT patients who had operations between 2002 and 2009 were collected and analyzed retrospectively. Data were analyzed using uni- and multi-variate analysis according to factors that are known to be associated with outcome in these patients. RESULTS: Overall, the accurate survival rate of recipients at 1, 3, and 5 years was 84%, 76%, and 70%, respectively. The independent risk factors, preoperative renal dysfunction, intraoperative red blood cell transfusions of greater than 5 units, and female to male match (donor to recipient matching), were identified by Cox regression analysis. The pre-transplant model for end-stage liver disease score and a graft to recipient weight ratio of less than 0.8% were not predictive of outcome. The overall 1-, 3-, and 5-year survival of patients with one or no risk factors and two or more risk factors were 91%, 86%, and 83% and 67%, 56%, and 47%, respectively (P<0.0001). CONCLUSIONS: In our retrospective study, preoperative renal dysfunction, intraoperative red blood cell transfusions of greater than 5 units, and female to male gender match were independent risk factors for LDLT recipient outcome. Two or more of these risk factors may contribute to poor outcome.


Assuntos
Transplante de Fígado/mortalidade , Doadores Vivos , Adolescente , Adulto , Idoso , Distribuição de Qui-Quadrado , China/epidemiologia , Transfusão de Eritrócitos/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Rim/fisiopatologia , Nefropatias/mortalidade , Nefropatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores Sexuais , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
20.
Hepatobiliary Pancreat Dis Int ; 10(2): 214-7, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21459731

RESUMO

BACKGROUND: Cholangiocarcinoma complicated by intra-abdominal desmoid-type fibromatosis (DTF) is uncommon. There are no reports on patients with this type of fibromatosis, in which the pre-operative treatment (including diagnosis), surgical approach, post-operative pathologic reports, and prognosis are discussed. METHOD: The clinicopathological features of a 49-year-old man were retrospectively analyzed. RESULTS: Cholangiocarcinoma located in the inferior segment of the bile duct was considered pre-operatively on the basis of clinical findings. At the time of pancreaticoduodenectomy, the mesojejunum was stiff without nodules or a mass at a distance of approximately 80 cm from the ligament of Treitz. Complete excision of the entire lesion of the intestinal mesenteric contracture and its subsidiary was performed. Post-operative pathologic findings confirmed an adenocarcinoma located at the extremity of the common bile duct and infiltrating the full thickness of the common bile duct as well as the deep muscular layer of the duodenum. The contracted jejunal mesentery was shown to have DTF. The patient was alive with no evidence of recurrence after a follow-up of 6 months. CONCLUSIONS: The patient had a rare hereditary disease with intra-abdominal DTF, which manifests the characteristics of an aggressive growth pattern and a high rate of local recurrence; conservative therapy is recommended. Complete excision of the fibromatous lesion during pancreaticoduodenectomy may maximally decrease the risk of local recurrence.


Assuntos
Neoplasias dos Ductos Biliares/complicações , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma/complicações , Colangiocarcinoma/cirurgia , Fibromatose Agressiva/complicações , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/cirurgia , Colangiocarcinoma/patologia , Fibromatose Agressiva/patologia , Fibromatose Agressiva/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Pancreaticoduodenectomia
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