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1.
Cell Mol Neurobiol ; 36(7): 1087-95, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27015680

RESUMO

Although Butylphthalide (BP) has protective effects that reduce ischemia-induced brain damage and neuronal cell death, little is known about the precise mechanisms occurring during cerebral ischemia/reperfusion (I/R). Therefore, the aim of this study was to investigate the neuroprotective mechanisms of BP against ischemic brain injury induced by cerebral I/R through inhibition of the c-Jun N-terminal kinase (JNK)-Caspase3 signaling pathway. BP in distilled non-genetically modified Soybean oil was administered intragastrically three times a day at a dosage of 15 mg/(kg day) beginning at 20 min after I/R in Sprague-Dawley rats. Immunohistochemical staining and Western blotting were performed to examine the expression of related proteins, and TUNEL-staining was used to detect the percentage of neuronal apoptosis in the hippocampal CA1 region. The results showed that BP could significantly protect neurons against cerebral I/R-induced damage. Furthermore, the expression of p-JNK, p-Bcl2, p-c-Jun, FasL, and cleaved-caspase3 was also decreased in the rats treated with BP. In summary, our results imply that BP could remarkably improve the survival of CA1 pyramidal neurons in I/R-induced brain injury and inhibit the JNK-Caspase3 signaling pathway.


Assuntos
Apoptose/efeitos dos fármacos , Benzofuranos/farmacologia , Isquemia Encefálica/tratamento farmacológico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Animais , Benzofuranos/química , Isquemia Encefálica/metabolismo , Caspase 3/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Masculino , Neurônios/metabolismo , Ratos Sprague-Dawley , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Transdução de Sinais/efeitos dos fármacos
2.
Biotechnol Appl Biochem ; 63(1): 5-14, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-25522670

RESUMO

Osteosarcoma (OS) remains the most frequent primary malignant bone tumor in adolescents. However, the molecular cause of the disease is poorly elucidated. In the present study, we primarily found that translationally controlled tumor protein (TCTP) was overexpressed in human OS tissues and cell lines. To investigate the function of TCTP in OS cell growth, an RNA interference lentivirus system was employed to deplete TCTP expression in Saos-2 and U2OS cell lines. Specific knockdown of TCTP significantly impaired cell proliferation and colony-formation capacity in both OS cell lines. Moreover, depletion of TCTP caused a significant accumulation of OS cells in the S phase and eventually induced cell apoptosis. Expression levels of the G2/M phase regulators cyclin B1 and Cdc25A were decreased, and apoptotic markers Bad and caspase-3 were increased in both OS cell lines after depletion of TCTP. Furthermore, depletion of TCTP potently inhibited the growth of xenografts in nude mice. Our results indicate that inhibition of TCTP expression exerts potential antitumor activity and may be a novel therapeutic approach in human OS.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Ósseas/genética , Neoplasias Ósseas/terapia , Osteossarcoma/genética , Osteossarcoma/terapia , RNA Interferente Pequeno/uso terapêutico , Terapêutica com RNAi , Animais , Apoptose , Neoplasias Ósseas/patologia , Osso e Ossos/metabolismo , Osso e Ossos/patologia , Ciclo Celular , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos Nus , Osteossarcoma/patologia , RNA Interferente Pequeno/genética , Proteína Tumoral 1 Controlada por Tradução
3.
Aging Clin Exp Res ; 28(2): 303-11, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26138818

RESUMO

BACKGROUND: Recent studies indicate that consumption of the different calorie diet may be an important way to accelerate or slow the neurodegenerative disorder related to age. Long-term consumption of a high-calorie diet affects the brain and increase the risk of neurodegenerative disorders. And consumption of a low-calorie diet (caloric restriction, CR) could delay aging, and protect the central nervous system from neurodegenerative disorders. The underlying mechanisms have not yet been clearly defined. METHOD: Thirty 6-week-old C57/BL6 mice were randomly assigned to a NC group (fed standard diet, n = 10), a CR group (fed a low-calorie diet, n = 10) or a HC group (fed a high-calorie diet, n = 10) for 10 months. Body weight was measured monthly. Learning and memory capacity were determined by Morris water maze. Pathological changes of the hippocampus cells were detected with HE and Nissl staining. The expression of GFAP was determined by immunofluorescence and western blot. The expression of mTOR, S6K and LC3B in the hippocampus was determined by immunofluorescence. RESULTS: After feeding for 10 months, compared with mice in the NC group, mean body weight was significantly higher in the HC group and significantly lower in the CR group. The result of Morris water maze showed that compared with mice in the NC group, the learning and memory capacity was significantly increased in the CR group, and significantly decreased in the HC group. HE and Nissl staining of the hippocampus showed cells damaged obviously in the HC group. In the hippocampus, the expression of GFAP, mTOR and S6K was increased in the HC group, and decreased in the CR group. The expression of LC3B was decreased in the HC group, and increased in the CR group. CONCLUSIONS: Long-term consumption of a high-calorie diet could inhibit autophagy function, and facilitate neuronal loss in the hippocampus, which in turn aggravate age-related cognition impairment. And consumption of a low-calorie diet (caloric restriction, CR) could enhance the degree of autophagy, protect neurons effectively against aging and damage, and keep learning and memory capacity better.


Assuntos
Envelhecimento/fisiologia , Ingestão de Energia , Hipocampo , Doenças Neurodegenerativas , Animais , Autofagia/fisiologia , Restrição Calórica/métodos , Dieta , Hipocampo/metabolismo , Hipocampo/patologia , Aprendizagem/fisiologia , Masculino , Memória , Camundongos , Camundongos Endogâmicos C57BL , Modelos Animais , Doenças Neurodegenerativas/fisiopatologia , Doenças Neurodegenerativas/prevenção & controle , Serina-Treonina Quinases TOR/metabolismo
4.
World J Clin Cases ; 12(12): 2109-2115, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38680257

RESUMO

BACKGROUND: Lateral window approach for sinus floor lift is commonly used for vertical bone augmentation in cases when the residual bone height is less than 5 mm. However, managing cases becomes more challenging when a maxillary sinus pseudocyst is present or when there is insufficient bone width. In this case, we utilized the bone window prepared during the lateral window sinus lift as a shell for horizontal bone augmentation. This allowed for simultaneous horizontal and vertical bone augmentation immediately after the removal of the maxillary sinus pseudocyst. CASE SUMMARY: A 28-year-old female presented to our clinic with the chief complaint of missing upper left posterior teeth. Intraoral examination showed a horizontal deficiency of the alveolar ridge contour. The height of the alveolar bone was approximately 3.6 mm on cone beam computed tomography (CBCT). And a typical well-defined 'dome-shaped' lesion in maxillary sinus was observed on CBCT imaging. The lateral bony window was prepared using a piezo-ultrasonic device, then the bony window was fixed to the buccal side of the 26 alveolar ridge using a titanium screw with a length of 10 mm and a diameter of 1.5 mm. The space between the bony window and the alveolar ridge was filled with Bio-Oss, covered with a Bio-Gide collagen membrane, and subsequently sutured. Nine months later, the patient's bone width increased from 4.8 to 10.5 mm, and the bone height increased from 3.6 to 15.6 mm. Subsequently, a Straumann® 4.1 mm × 10 mm implant was placed. The final all-ceramic crown restoration was completed four months later, and both clinical and radiographic examinations showed that the implant was successful, and the patient was satisfied with the results. CONCLUSION: The bone block harvested from the lateral window sinus lift can be used for simultaneous horizontal bone augmentation acting as a shell for good two-dimensional bone augmentation.

5.
Arch Med Sci ; 20(1): 267-279, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38414469

RESUMO

Introduction: The ITGB6 gene encoding a protein that can regulate the integrin αvß6 heterodimer protein expression in different status was shown to play an important role in multiple human cancers, such as brain cancer, colon cancer and oral cancer, and is related to clinical progression. This study aims to explore the function and the mechanism of the ITGB6 gene or protein in pancreatic cancer. Material and methods: We examined the expression of ITGB6 in pancreatic cancer using immunohistochemistry and analyzed the relationship between the expression of ITGB6 and the clinicopathologic features in pancreatic cancer patients. In addition, a bioinformatic method was used to analyze the ITGB6 mRNA level in pancreatic tumor tissues compared with normal pancreatic tissues and to analyze the correlation between high KIF23 expression and prognosis in pancreatic cancer patients. Moreover, colony formation assay, MTT assay, cell scratch, cell invasion and western blot assays in vitro and a xenograft mouse model in vivo were performed to analyze the effect of KIF23 on proliferation and invasion of pancreatic cancer cells. Results: Increased expression of ITGB6 was significantly correlated with poor clinical outcome in both our clinical data and TCGA data of pancreatic cancer. Furthermore, functional assays revealed that ITGB6 knockdown in vivo and in vitro might inhibit cancer cell proliferation and the ability of invasion or migration. Conclusions: Our data suggest that ITGB6 is associated with pancreatic cancer malignant progression. Hence, ITGB6 may serve as a potential target of pancreatic cancer for future research, and further study is needed.

6.
Clin Rheumatol ; 42(2): 407-413, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36414863

RESUMO

The objective of this study is to characterize the association between platelet to albumin ratio (PAR) and disease activity in patients with ankylosing spondylitis (AS) and axial psoriatic arthritis (axPsA). Baseline platelet count, albumin, PAR, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), Bath ankylosing spondylitis disease index (BASDAI), Bath ankylosing spondylitis functional index (BASFI), and ankylosing spondylitis disease activity score (ASDAS) were collected from patients with a definitive diagnosis of AS or axPsA. Spearman's correlation analysis, quantile regression, and receiver operating characteristic (ROC) curves were performed. Four hundred forty-six patients with AS and 68 patients with axPsA were included. AS patients had higher CRP, ASDAS-CRP, and ASDAS-ESR than axPsA patients (median: CRP, 6.8 vs. 3.5 mg/L, p = 0.02; ASDAS-CRP, 2.32 vs.1.93, p = 0.001; ASDAS-ESR, 2.57 vs.1.97, p = 0.007; respectively). Platelet count, albumin, PAR, ESR, BASDAI, and BASFI did not significantly differ between the two populations (all p > 0.05). In AS patients, PAR was positively correlated with BASDAI (r = 0.204, p < 0.01), BASFI (r = 0.24, p < 0.01), ASDAS-CRP (r = 0.475, p < 0.01), and ASDAS-ESR (r = 0.483, p < 0.01), while these coefficients were not significant in axPsA patients. The quantile regression further confirmed that, in AS patients, PAR was independently associated with BASDAI, BASFI, ASDAS-CRP, and ASDAS-ESR at their individual quantiles (all p < 0.01). However, in axPsA patients, PAR was not significantly associated with these disease activities. The optimal cut-off value of PAR for AS disease activity was 5.87, with an AUC of 0.745, a sensitivity of 72.4%, and a specificity of 71%. PAR could serve as an alternative indicator for AS disease activity. Key Points • Platelet to albumin ratio is independently associated with ankylosing spondylitis disease activity. • Platelet to albumin ratio could serve as an alternative indicator for ankylosing spondylitis disease activity.


Assuntos
Artrite Psoriásica , Espondilite Anquilosante , Humanos , Índice de Gravidade de Doença , Proteína C-Reativa/análise , Sedimentação Sanguínea
7.
Expert Opin Drug Discov ; 18(4): 371-383, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36995192

RESUMO

INTRODUCTION: Flaviviruses are emerging or reemerging pathogens that have caused several outbreaks throughout the world and pose serious threats on human health and economic development. RNA-based therapeutics are developing rapidly, and hold promise in the fight against flaviviruses. However, to develop efficient and safe therapeutics for flaviviruses, many challenges remain unsolved. AREAS COVERED: In this review, the authors briefly introduced the biology of flaviviruses and the current advances in RNA-based therapeutics for them. Furthermore, the authors list the challenges and possible solutions in this area. Finally, the authors give their opinion on the development and future of RNA-based therapeutics for flaviviruses. EXPERT OPINION: With the rapid development of structural biology, the crystal structures of flavivirus proteins may lay the foundation for future rational drug design. Studies regarding the interactions between the flavivirus and the host will also be invaluable to inhibitor design. Researchers should maintain the current momentum to bring about safe and effective anti-flavivirus drugs to licensure through joint efforts of academia, government, and industry.


Assuntos
Infecções por Flavivirus , Flavivirus , Humanos , Flavivirus/genética , Flavivirus/metabolismo , RNA/metabolismo , RNA/farmacologia , Infecções por Flavivirus/tratamento farmacológico
8.
Kaohsiung J Med Sci ; 39(9): 916-926, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37338034

RESUMO

The blood-retinal barrier (BRB), homeostasis, neuronal integrity, and metabolic processes are all directly influenced by Müller cells, the most important retinal glial cells. We isolated primary Müller cells from Sprague-Dawley (SD) neonatal rats and treated them with glucose at varying doses. CCK-8 was used to quantify cellular viability, and a TUNEL assay was performed to detect cell apoptosis. ELISA, immunofluorescence, and western blotting were used to assess cAMP/PKA/CREB signaling, Kir4.1, AQP4, GFAP, and VEGF levels, respectively. H&E staining was used to examine histopathological alterations in diabetic retinopathy (DR)-affected retinal tissue in rats. As glucose concentration increases, gliosis of Müller cells became apparent, as evidenced by a decline in cell activity, an increase in apoptosis, downregulation of Kir4.1 level, and overexpression of GFAP, AQP4, and VEGF. Treatments with low, intermediate, and high glucose levels led to aberrant activation of cAMP/PKA/CREB signaling. Interestingly, blocking cAMP and PKA reduced high glucose-induced Müller cell damage and gliosis by a significant amount. Further in vivo results suggested that cAMP or PKA inhibition significantly improved edema, bleeding, and retinal disorders. Our findings showed that high glucose exacerbated Müller cell damage and gliosis via a mechanism involving cAMP/PKA/CREB signaling.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Ratos , Animais , Retinopatia Diabética/genética , Ratos Sprague-Dawley , Fator A de Crescimento do Endotélio Vascular/genética , Gliose , Glucose/farmacologia
9.
Acta Biomater ; 168: 551-564, 2023 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-37414113

RESUMO

In recent years, aggregation-induced emission (AIE)-active materials have been emerging as a promising means for bioimaging and phototherapy. However, the majority of AIE luminogens (AIEgens) need to be encapsulated into versatile nanocomposites to improve their biocompatibility and tumor targeting. Herein, we prepared a tumor- and mitochondria-targeted protein nanocage by the fusion of human H-chain ferritin (HFtn) with a tumor homing and penetrating peptide LinTT1 using genetic engineering technology. The LinTT1-HFtn could serve as a nanocarrier to encapsulate AIEgens via a simple pH-driven disassembly/reassembly process, thereby fabricating the dual-targeting AIEgen-protein nanoparticles (NPs). The as designed NPs exhibited an improved hepatoblastoma-homing property and tumor penetrating ability, which is favorable for tumor-targeted fluorescence imaging. The NPs also presented a mitochondria-targeting ability, and efficiently generated reactive oxygen species (ROS) upon visible light irradiation, making them valuable for inducing efficient mitochondrial dysfunction and intrinsic apoptosis in cancer cells. In vivo experiments demonstrated that the NPs could provide the accurate tumor imaging and dramatic tumor growth inhibition with minimal side effects. Taken together, this study presents a facile and green approach for fabrication of tumor- and mitochondria-targeted AIEgen-protein NPs, which can serve as a promising strategy for imaging-guided photodynamic cancer therapy. STATEMENT OF SIGNIFICANCE: AIE luminogens (AIEgens) show strong fluorescence and enhanced ROS generation in the aggregate state, which would facilitate the image-guided photodynamic therapy [12-14]. However, the major obstacles that hinder biological applications are their lack of hydrophilicity and selective targeting [15]. To address this issue, this study presents a facile and green approach for the fabrication of tumor­ and mitochondria­targeted AIEgen-protein nanoparticles via a simple disassembly/reassembly of the LinTT1 peptide-functionalized ferritin nanocage without any harmful chemicals or chemical modification. The targeting peptide-functionalized nanocage not only restricts the intramolecular motion of AIEgens leading to enhanced fluorescence and ROS production, but also confers good targeting to AIEgens.


Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Espécies Reativas de Oxigênio/metabolismo , Fotoquimioterapia/métodos , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Mitocôndrias/metabolismo , Nanopartículas/uso terapêutico , Nanopartículas/química , Imagem Óptica/métodos , Ferritinas/farmacologia
10.
Front Oncol ; 13: 1298684, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38304038

RESUMO

Juxtaglomerular cell tumor (JCT) is an endocrine tumor marked by elevated renin levels and high blood pressure. This case report presents the clinical findings of a 47-year-old woman with a history of recurrent hypokalemia, headaches, hypertension, and increased plasma renin activity (PRA). Dynamic enhanced magnetic resonance imaging (MRI) revealed a small nodule on the upper part of the right kidney. Selective renal venous sampling indicated a higher PRA only in the right upper pole renal vein. The patient underwent surgical removal of the right kidney mass, and the pathology results confirmed the diagnosis of JCT. This case underscores the importance of conducting selective renal venous sampling for accurate JCT diagnosis.

11.
Zhonghua Bing Li Xue Za Zhi ; 41(5): 309-13, 2012 May.
Artigo em Zh | MEDLINE | ID: mdl-22883669

RESUMO

OBJECTIVE: To explore prognostic factors and the expression of glypican-3, hepatocyte antigen (HEP), alpha-fetoprotein (AFP), CD34 and CD10 in hepatocellular carcinoma (HCC) and their prognostic value. METHODS: Clinicopathologic data were analyzed in 375 cases of HCC, in which 80 cases with follow-up were examined by immunohistochemical staining to detect the expression of glypican-3, HEP, AFP, CD34 and CD10 proteins. The relationship between the proteins expression and clinicopathologic features was also evaluated. RESULTS: Tumor number (P = 0.000), tumor size (P = 0.025), tumor differentiation (P = 0.001) and vessel invasion (P = 0.000) were closely related to prognosis of HCC patients; the expression of glypican-3 (66/80,82.5%; P = 0.002), HEP (64/80,80.0%; P = 0.021), AFP (38/80,47.5%; P = 0.014) and CD10 (28/80,35.0%; P = 0.002) was significantly related to tumor differentiation; that of glypican-3 was significantly correlated with tumor number and presence of satellite nodules (P = 0.028) and that of AFP and CD10 was significantly correlated with portal vein thrombi (P = 0.000, P = 0.010). On Kaplan-Meier regression analysis, both low expression of HEP and high expression of AFP were closely related to poor prognosis. CONCLUSIONS: Tumor number, size, differentiation and vessel invasion were important factors affecting the prognosis of patients with HCC. HEP and AFP have prognostic significance in HCC.


Assuntos
Antígenos/metabolismo , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , alfa-Fetoproteínas/metabolismo , Antígenos CD34/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/cirurgia , Diferenciação Celular , Feminino , Seguimentos , Glipicanas/metabolismo , Hepatócitos/imunologia , Humanos , Neoplasias Hepáticas/cirurgia , Masculino , Neprilisina/metabolismo , Veia Porta/patologia , Prognóstico , Taxa de Sobrevida , Carga Tumoral , Trombose Venosa/etiologia , Trombose Venosa/patologia
12.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 41(4): 425-9, 2012 07.
Artigo em Zh | MEDLINE | ID: mdl-22927078

RESUMO

OBJECTIVE: To investigate the effect of Colquhounia root tablet on IL-2 and IFN-γ mRNA expression in experimental allergic encephalomyelitis (EAE) of rats. METHODS: The allergic encephalomyelitis model was established in Wistar rats by immunization with myelin basic protein of spinal cord of guinea pig and complete Freund's adjuvant. The rats in treatment group received Colquhounia root tablet (300 mg*kg(-1), BID). The symptom of EAE was observed; pathological feature and myelin of brain and spinal cord were detected with HE stain and Loyez's stain, respectively. The expressions of IL-2 and IFN-γ mRNA were assayed by RT-PCR. RESULTS: No EAE symptoms were developed in treatment group, the expressions of IL-2 and IFN-γ mRNA were 0.345 ± 0.032 and 0.353 ± 0.023, which were significantly lower than those of model group (P<0.01). The histopathologic examinations revealed that less inflammation cells around vessels and demyelination in white matter of brain and spinal cords were observed in treatment group than in model group. CONCLUSION: Colquhounia root tablets are effective in treatment of EAE of rats, which may be associated with inhibition of the expression of IL-2 and IFN-γ mRNA.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Encefalomielite Autoimune Experimental/metabolismo , Interferon gama/metabolismo , Interleucina-2/metabolismo , Tripterygium , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/uso terapêutico , Encefalomielite Autoimune Experimental/tratamento farmacológico , Feminino , Cobaias , Masculino , Ratos , Ratos Wistar
13.
Front Psychol ; 13: 817960, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35910991

RESUMO

The domestic situation of the past few years shows the practices of employees' unpaid leave and layoffs and the constant drain on capital, talent, and technologies in hospitality. Owners expect to reduce the losses to as low as possible by saving on human costs. Nevertheless, in face of such a changing environment, hospitality has to accumulate high-quality human capital through systematic investment, sensitive development, and continuous learning and growth to discover competitive advantages through the cultivation of human capital. The pre-service education of new employees could accelerate their familiarity with the operations of the company and their understanding of their job role and duties. More importantly, with good planning, it could make employees feel emphasized with and respected with the result of largely changing their thoughts and working habits. Aiming at supervisors and employees in hospitality in Zhejiang as the research objects, a total of 420 copies of our questionnaire are distributed, and 357 valid copies were retrieved, with a retrieval rate of 85%. According to the results to propose discussions, it is expected to generate systematic and proper education methods for the pre-service education in hospitality, promote the education effectiveness, and promote employees' capability and organizational performance.

14.
Transbound Emerg Dis ; 69(6): 3181-3197, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36218169

RESUMO

The novel coronavirus disease (COVID-19) outbreak that emerged at the end of 2019 has now swept the world for more than 2 years, causing immeasurable damage to the lives and economies of the world. It has drawn so much attention to discovering how the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originated and entered the human body. The current argument revolves around two contradictory theories: a scenario of laboratory spillover events and human contact with zoonotic diseases. Here, we reviewed the transmission, pathogenesis, possible hosts, as well as the genome and protein structure of SARS-CoV-2, which play key roles in the COVID-19 pandemic. We believe the coronavirus was originally transmitted to human by animals rather than by a laboratory leak. However, there still needs more investigations to determine the source of the pandemic. Understanding how COVID-19 emerged is vital to developing global strategies for mitigating future outbreaks.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Animais , COVID-19/epidemiologia , COVID-19/veterinária , Pandemias , Zoonoses , Surtos de Doenças
15.
World J Oncol ; 13(5): 299-310, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36406193

RESUMO

Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancers, with more than a million cases per year by 2025. Cuproptosis is a novel form of programmed cell death, and is caused by mitochondrial lipoylation and destabilization of iron-sulfur proteins triggered by copper, which was considered as a key player in various biological processes. However, the roles of cuproptosis-related genes (CRGs) in HCC remain largely unknown. Methods: In the present study, we constructed and validated a four CRGs signature for predicting the overall survival (OS) of HCC patients in both The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. Results: Patients with high CRGs risk score showed shorter OS than those with low CRGs risk score. Functional analysis suggested that the CRGs-based prognostic signature was associated with metabolism remodeling which facilitated liver cancer progression. In addition, reduced infiltration of CD8+ T cells and increased macrophages were found in HCCs from patients with high CRGs risk score. As one of the four CRGs, higher expression of dihydrolipoamide S-acetyltransferase (DLAT) was accompanied by higher expression of program death ligand 1 (PD-L1) in HCC. Further, we confirmed that DLAT was up-regulated and correlated with poor prognosis in a clinical HCC cohort. Conclusion: In conclusion, our study constructed a four CRGs signature prognostic model and identified DLAT as an independent prognostic factor for HCC, thus providing new clues for understanding the association between cuproptosis and HCC.

16.
Zhonghua Bing Li Xue Za Zhi ; 40(1): 11-6, 2011 Jan.
Artigo em Zh | MEDLINE | ID: mdl-21429352

RESUMO

OBJECTIVE: To study the expression and significance of GPC3, CD10 and CD34 in hepatocellular carcinoma (HCC), dysplastic nodules (DN), cirrhotic regenerative nodules (CRN), focal nodular hyperplasia (FNH) and hepatocellular adenoma (HA). METHODS: Immunohistochemical study for GPC3, CD10, CD34 and AFP was performed on 80 cases of HCC (30 cases of well-differentiated HCC and 50 cases of advanced HCC), 30 cases of DN (18 cases of high-grade DN and 12 cases of low-grade DN), 36 cases of CRN, 20 cases of FNH and 20 cases of HA. RESULTS: (1) The positive expression rate of GPC3 was 92% (46/50) in advanced HCC, 66.7% (20/30) in well-differentiated HCC, 2/18 in high-grade DN, and 0 in low-grade DN, CRN, FNH and HA. The expression rate of GPC3 in well-differentiated HCC was lower than that in advanced HCC and higher than that in high-grade DN (P < 0.05). (2) The negative expression rate of CD10 was 78% (39/50) in advanced HCC, 43.3% (13/30) in well-differentiated HCC, 20% (4/20 and 4/20) in both FNH and HA, 2.8% (1/36) in CRN and 0 in both high-grade DN and low-grade DN. The occurrence of CD10-strongly positive cells was 2% (1/50) in advanced HCC, 16.7% (5/30) in well-differentiated HCC, 15/18 in high-grade DN, 11/12 in low-grade DN, 80.6% (29/36) in CRN and 60% (12/20 and 12/20) in both FNH and HA. The positive expression rate of CD10 in well-differentiated HCC was higher than that in advanced HCC and lower than that in high-grade DN, low-grade DN, CRN, FNH and HA (P < 0.05). (3) The positive expression rates of CD34 in advanced HCC and well-differentiated HCC ranged from 25% to 100% [and strongly positive in 76% (38/50) and 70% (21/30), respectively]. The rates in high-grade DN and low-grade DN ranged from 5% to 25% (and weakly positive in 16/18 and 10/12, respectively). In CRN, the rate ranged from 0 to 5% [and weakly positive in 27.8% (10/36)]. In FNH and HA, the positive rates ranged from 25% to 50%. The positive expression rate of CD34 in well-differentiated HCC was significantly higher than that in high-grade DN, low-grade DN, CRN, FNH and HA (P < 0.05). (4) The positive expression rate of AFP was 44% (22/50) in advanced HCC, 20% (6/30) in well-differentiated HCC, no expression in DN, LCN, LCN, FNH and HA. The positive expression rate of AFP in well-differentiated HCC was lower than that in advanced HCC and higher than that in LCN, FNH and HA. The different expression had statistical significance (P < 0.05). CONCLUSIONS: GPC3 is a relatively sensitive and specific marker in pathologic diagnosis of HCC. When coupled with immunohistochemical results of CD34, CD10 and AFP, GPC3 is useful in differentiating HCC from DN, LCN, FNH and HA.


Assuntos
Carcinoma Hepatocelular/metabolismo , Glipicanas/metabolismo , Neoplasias Hepáticas/metabolismo , Adenoma de Células Hepáticas/metabolismo , Adenoma de Células Hepáticas/patologia , Antígenos CD34/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/patologia , Diagnóstico Diferencial , Hiperplasia Nodular Focal do Fígado/metabolismo , Hiperplasia Nodular Focal do Fígado/patologia , Humanos , Imuno-Histoquímica , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Neoplasias Hepáticas/patologia , Neprilisina/metabolismo , alfa-Fetoproteínas/metabolismo
17.
Zhonghua Zhong Liu Za Zhi ; 32(8): 609-13, 2010 Aug.
Artigo em Zh | MEDLINE | ID: mdl-21122415

RESUMO

OBJECTIVE: To analyze the clinicopathologic features and prognostic factors of hepatocellular carcinoma. METHODS: Clinicopathological data of 185 cases of hepatocellular carcinoma treated in our hospital between 2000 and 2005 were collected and their follow up information was obtained. The clinicopathological features and prognostic factors were analyzed by Kaplan-Meier and multivariate Cox regression analysis. RESULTS: The 185 patients had a median age of 51.0 ± 11.0 (range, 19 - 72) years. The apparent peak incidence age was 40 to 60 years old, and the ratio of male to female was 10.6:1; the 3- and 5-year postoperational survival rates were 52.0% and 38.0%; respectively. The tumour numbers (P = 0.000), tumor size (P = 0.025), histological pattern (P = 0.000), nuclear features (P = 0.000), differentiation (P = 0.001) and vascular invasion (P = 0.000) were significantly correlated with prognosis. The postoperational survival times of patients with thin trabeculae pattern, compact pattern and pseudoglandular pattern were significantly longer than that of thick trabeculae, scirrhous pattern, and solid pattern (P ≤ 0.009). The postoperational survival time of patients with nuclear features grade 1 and 2 was significantly longer than that of grade 3 and 4 (P = 0.000). Multivariate Cox regression analysis showed that the tumor number (P = 0.001), tumor size (P = 0.042), nuclear features (P = 0.023) and vascular invasion (P = 0.000) were independent prognostic factors. CONCLUSION: The postoperational survival rate of HCC patients is low. The tumor size, tumor number, differentiation and vascular invasion are major prognostic factors of hepatocellular carcinoma, The higher is the tumor number, tumor size, degree of differentiation and presence of vascular invasion, the higher risk of mortality is.


Assuntos
Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Adulto , Idoso , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/cirurgia , Diferenciação Celular , Núcleo Celular/patologia , Feminino , Seguimentos , Antígenos de Superfície da Hepatite B/sangue , Humanos , Cirrose Hepática/complicações , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Células Neoplásicas Circulantes , Modelos de Riscos Proporcionais , Taxa de Sobrevida , Carga Tumoral , Adulto Jovem
18.
J Cardiothorac Surg ; 15(1): 296, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33008451

RESUMO

BACKGROUND: The Surgical Pleth Index (SPI) is a monitoring method that reflects painful stimuli during general anesthesia, and dexmedetomidine is an analgesic adjuvant with an opioid-sparing effect. But up to now, it is still unclear whether dexmedetomidine has any influence on SPI. To investigate whether dexmedetomidine has an effect on SPI during video-assisted thoracoscopic surgery. METHODS: We enrolled 94 patients who underwent video-assisted thoracoscopic lung lobectomy. Patients were randomly assigned to a dexmedetomidine group (dexmedetomidine: 0.8 µg/kg administered for 10 min before anesthesia) or normal saline group (equal volume of normal saline). SPI and vital signs were recorded. The number rating scale (NRS) pain score was also evaluated. RESULTS: SPI values were significantly lower in the dexmedetomidine group than in the normal saline group at intubation and at discharge from the postanesthesia care unit. Compared with the normal saline group, mean arterial pressure and heart rate were both significantly lower in the dexmedetomidine group at intubation. Heart rate was lower at skin incision in the dexmedetomidine group. The NRS score in the normal saline group was noticeably higher vs. the dexmedetomidine group at discharge from the postanesthesia care unit. CONCLUSIONS: Dexmedetomidine decreased intraoperative SPI and NRS scores. Our results showed that dexmedetomidine attenuated noxious stimuli. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR): ChiCTR-OOC-16009450 , Registered 16 October, 2016.


Assuntos
Analgésicos não Narcóticos/uso terapêutico , Dexmedetomidina/uso terapêutico , Pneumopatias/cirurgia , Adolescente , Adulto , Idoso , Anestesia Geral , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Cuidados Intraoperatórios , Masculino , Pessoa de Meia-Idade , Dor Pós-Operatória , Pneumonectomia , Estudos Prospectivos , Cirurgia Torácica Vídeoassistida , Adulto Jovem
19.
Medicine (Baltimore) ; 99(14): e19647, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32243396

RESUMO

Currently, the association of the initiation time of hepatitis B virus (HBV) screening and antiviral prophylaxis with adverse liver outcomes in cancer patients undergoing chemotherapy remains conflicting.This retrospective study was designed to determine the association of HBV screening and antiviral prophylaxis with adverse liver outcomes, and then proposed optimal management strategies on HBV screening and antiviral prophylaxis.We analyzed the medical data of Chinese cancer patients undergoing chemotherapy between 2000 and 2015. Descriptive statistics and Chi square tests were performed to analyze the basic characteristics of patients. Time-to-event analysis was used to determine incidence, and competing risk analysis was used to determine the hazard ratios (HRs) for outcomes.A total of 12,158 patients (81.1% with solid tumors) were analyzed. Among solid tumors patients, late screening and late antiviral therapy of chronic HBV were associated with higher incidence of hepatitis flare (HR 3.29, 95% confidence interval [CI] 2.26-4.79; HR 6.79, 95% CI 4.42-10.41), hepatic impairment (HR 2.96, 95% CI 2.03-4.32; HR 8.03, 95% CI 4.78-13.48), liver failure (HR 2.19, 95% CI 1.41-3.40; HR 14.81, 95% CI 6.57-33.42), and HBV-related death (HR 3.29, 95% CI 2.26-4.79; HR 8.30, 95% CI 4.95-13.91) in comparison with early screening and early therapy.Early HBV screening and antiviral therapy could reduce the risk of adverse liver outcomes among chronic HBV patients receiving chemotherapy. Hepatitis B surface antibody-positivity was associated with a decreased risk of liver failure and chronic HBV, late screening or late antiviral therapy were predictors of liver failure for patients with anti-tumor therapy. However, it should be applied cautiously into each types of solid tumors and hematologic malignancies because subgroup analysis according to type of cancer was not designed.


Assuntos
Antivirais/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/virologia , Hepatite B Crônica/tratamento farmacológico , Programas de Rastreamento/estatística & dados numéricos , Neoplasias/virologia , Adolescente , Adulto , Idoso , Anticorpos Antivirais/sangue , Antineoplásicos/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , China/epidemiologia , Feminino , Antígenos de Superfície da Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Hepatite B Crônica/complicações , Hepatite B Crônica/diagnóstico , Humanos , Incidência , Fígado/efeitos dos fármacos , Fígado/virologia , Falência Hepática/induzido quimicamente , Falência Hepática/epidemiologia , Falência Hepática/virologia , Masculino , Pessoa de Meia-Idade , Neoplasias/sangue , Neoplasias/tratamento farmacológico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Tempo , Ativação Viral , Adulto Jovem
20.
Behav Brain Res ; 384: 112520, 2020 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-32006563

RESUMO

Cerebral ischemia/reperfusion (I/R) injury is a leading cause of learning and memory dysfunction. Hydrogen sulfide (H2S) has been shown to confer neuroprotection in various neurodegenerative diseases, including cerebral I/R-induced hippocampal CA1 injury. However, the underlying mechanisms have not been completely understood. In the present study, rats were pretreated with SAM/NaHS (SAM, an H2S agonist, and NaHS, an H2S donor) only or SAM/NaHS combined with CaM (an activator of CaMKII) prior to cerebral ischemia. The Morris water maze test demonstrated that SAM/NaHS could alleviate learning and memory impairment induced by cerebral I/R injury. Cresyl violet staining was used to show the survival of hippocampal CA1 pyramidal neurons. SAM/NaHS significantly increased the number of surviving cells, whereas CaM weakened the protection induced by SAM/NaHS. The immunohistochemistry results indicated that the number of Iba1-positive microglia significantly increased after cerebral I/R. Compared with the I/R group, the number of Iba1-positive microglia in the SAM/NaHS groups significantly decreased. Co-Immunoprecipitation and immunoblotting were conducted to demonstrate that SAM/NaHS suppressed the assembly of CaMKII with the ASK1-MKK3-p38 signal module after cerebral I/R, which decreased the phosphorylation of p38. In contrast, CaM significantly inhibited the effects of SAM/NaHS. Taken together, the results suggested that SAM/NaHS could suppress cerebral I/R injury by downregulating p38 phosphorylation via decreasing the assembly of CaMKII with the ASK1-MKK3-p38 signal module.


Assuntos
Região CA1 Hipocampal/efeitos dos fármacos , Calmodulina/farmacologia , Sulfeto de Hidrogênio/metabolismo , AVC Isquêmico/metabolismo , Transtornos da Memória/metabolismo , Traumatismo por Reperfusão/metabolismo , S-Adenosilmetionina/farmacologia , Sulfetos/farmacologia , Animais , Região CA1 Hipocampal/metabolismo , Região CA1 Hipocampal/patologia , Proteínas de Ligação ao Cálcio/efeitos dos fármacos , Proteínas de Ligação ao Cálcio/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/efeitos dos fármacos , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Regulação para Baixo , AVC Isquêmico/fisiopatologia , Aprendizagem/efeitos dos fármacos , MAP Quinase Quinase 3/efeitos dos fármacos , MAP Quinase Quinase 3/metabolismo , MAP Quinase Quinase Quinase 5/efeitos dos fármacos , MAP Quinase Quinase Quinase 5/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Memória/efeitos dos fármacos , Transtornos da Memória/fisiopatologia , Proteínas dos Microfilamentos/efeitos dos fármacos , Proteínas dos Microfilamentos/metabolismo , Microglia/efeitos dos fármacos , Microglia/metabolismo , Microglia/patologia , Teste do Labirinto Aquático de Morris , Fosforilação , Células Piramidais/efeitos dos fármacos , Células Piramidais/metabolismo , Ratos , Traumatismo por Reperfusão/fisiopatologia , Proteínas Quinases p38 Ativadas por Mitógeno/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
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