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1.
Cell Rep Med ; 5(2): 101416, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38350451

RESUMO

Peripheral T cell lymphoma (PTCL) is a heterogeneous group of non-Hodgkin's lymphomas varying in clinical, phenotypic, and genetic features. The molecular pathogenesis and the role of the tumor microenvironment in PTCL are poorly understood, with limited biomarkers available for genetic subtyping and targeted therapies. Through an integrated genomic and transcriptomic study of 221 PTCL patients, we delineate the genetic landscape of PTCL, enabling molecular and microenvironment classification. According to the mutational status of RHOA, TET2, histone-modifying, and immune-related genes, PTCL is divided into 4 molecular subtypes with discrete patterns of gene expression, biological aberrations, and vulnerabilities to targeted agents. We also perform an unsupervised clustering on the microenvironment transcriptional signatures and categorize PTCL into 4 lymphoma microenvironment subtypes based on characteristic activation of oncogenic pathways and composition of immune communities. Our findings highlight the potential clinical rationale of future precision medicine strategies that target both molecular and microenvironment alterations in PTCL.


Assuntos
Linfoma de Células T Periférico , Humanos , Linfoma de Células T Periférico/genética , Linfoma de Células T Periférico/metabolismo , Perfilação da Expressão Gênica , Genômica , Mutação , Microambiente Tumoral/genética
2.
Biosci Rep ; 43(8)2023 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-37530723

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Salidroside (SAL), a phenolic natural product present in Rhodiola rosea, are commonly used in the treatment of various ischemic-hypoxic diseases, including intestinal ischemia-reperfusion (IR) injury. However, their efficacy and potential mechanisms in the treatment of intestinal IR injury have not been investigated. OBJECTIVE: The objective of the present study is to investigate the pharmacological mechanism of action of SAL on intestinal IR injury using a network pharmacology approach combined with experimental validation. METHODS: In the present study, we used the Traditional Chinese Medicine Systematic Pharmacology (TCMSP) database and analysis platform and Comparative Toxicogenomics Database (CTD) to predict possible target genes of SAL, collected relevant target genes of intestinal IR injury from GeneCards and DisGenet websites, and collected summary data to screen common target genes. Then, the protein-protein interaction (PPI) target network was constructed and analyzed by STRING database and Cytoscape 3.8.2 with the above intersecting genes. Then, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed and the component-target-pathway network was constructed, followed by the use of molecular docking and molecular dynamic simulation to verify the possible binding conformation between SAL and candidate targets to further explore the potential targets of SAL in the treatment of intestinal IR injury. Finally, an in vivo model of mouse superior mesenteric artery ligation was established to assess the anti-intestinal IR injury effect of SAL by assessing histopathological changes in mouse small intestine by HE staining, detecting inflammatory factor expression by ELISA kit, and detecting the expression of key protein targets by Western blotting. RESULTS: A total of 166 SAL target genes and 1740 disease-related targets were retrieved, and 88 overlapping proteins were obtained as potential therapeutic targets. The pathway enrichment analysis revealed that the pharmacological effects of SAL on intestinal IR injury were anti-hypoxic, anti-inflammatory and metabolic pathway related, and the molecular docking and molecular dynamic simulation results showed that the core bioactive components had good binding affinity for TXNIP and AMPK, and the immunoblotting results indicated that the expression levels of TXNIP and AMPK in the small intestinal tissues of mice in the drug-treated group compared with the model group were significantly changed. CONCLUSION: SAL may target AMPK and TXNIP domains to act as a therapeutic agent for intestinal IR. These findings comprehensively reveal the potential therapeutic targets for SAL against intestinal IR and provide theoretical basis for the clinical application of SAL in the treatment of intestinal IR.


Assuntos
Medicamentos de Ervas Chinesas , Traumatismo por Reperfusão , Animais , Camundongos , Farmacologia em Rede , Proteínas Quinases Ativadas por AMP , Simulação de Acoplamento Molecular , Reperfusão , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/genética , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico
3.
Clin. transl. oncol. (Print) ; 24(12): 2272-2284, dec. 2022.
Artigo em Inglês | IBECS | ID: ibc-216075

RESUMO

Lung cancer is one of the most common malignant tumors with growing morbidity and mortality worldwide. Several treatments are used to manage lung cancer, including surgery, radiotherapy and chemotherapy, as well as molecular-targeted therapy. However, the current measures are still far from satisfactory. Therefore, the current research should focus on exploring the molecular mechanism and then finding an effective treatment. Interestingly, we and others have embarked on a line of investigations focused on the mechanism of lung cancer. Specifically, lncRNA small nucleolar RNA host gene has been shown to be associated with biological characteristics and therapeutic resistance of lung cancer. In addition, small nucleolar RNA host genes may be used as diagnostic biomarker in the future. Herein, we will provide a brief review demonstrating the importance of small nucleolar RNA host genes in lung cancer, especially non-small cell lung cancer. Although lncRNA has shown a crucial role in tumor-related research, a large number of studies are needed to validate its clinical application in the future (AU)


Assuntos
Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , RNA Longo não Codificante/genética , RNA Citoplasmático Pequeno/genética , Biomarcadores Tumorais
4.
Clin Transl Oncol ; 24(12): 2272-2284, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36008615

RESUMO

Lung cancer is one of the most common malignant tumors with growing morbidity and mortality worldwide. Several treatments are used to manage lung cancer, including surgery, radiotherapy and chemotherapy, as well as molecular-targeted therapy. However, the current measures are still far from satisfactory. Therefore, the current research should focus on exploring the molecular mechanism and then finding an effective treatment. Interestingly, we and others have embarked on a line of investigations focused on the mechanism of lung cancer. Specifically, lncRNA small nucleolar RNA host gene has been shown to be associated with biological characteristics and therapeutic resistance of lung cancer. In addition, small nucleolar RNA host genes may be used as diagnostic biomarker in the future. Herein, we will provide a brief review demonstrating the importance of small nucleolar RNA host genes in lung cancer, especially non-small cell lung cancer. Although lncRNA has shown a crucial role in tumor-related research, a large number of studies are needed to validate its clinical application in the future.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , RNA Longo não Codificante , Biomarcadores , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , RNA Longo não Codificante/genética , RNA Nucleolar Pequeno
5.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(6): 1923-1928, 2021 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-34893135

RESUMO

OBJECTIVE: To investigate the characteristics of platelet antibody in patients with hematological diseases, so as to research the effect of immunized platelet transfusion refractoriness (PTR) on the prognosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT) recepients with malignant hematological diseases patients. METHODS: The clinical data of platelet antibody positive patients tested by Capture-P in the First Affiliated Hospital of Soochow University from July 1, 2014 to July 1, 2019 were retrospectively analyzed, including sex, age, disease, platelet transfusion assessments, CD34+ cells, transplant prognosis, and so on. RESULTS: In 5 years, 913 (7.28%) hematologic patients with platelet antibody positive were identified, the detection rate of females (513 cases) were higher than males (400 cases). Among the 913 patients, the antibody positive rates of 520 patients with malignant hematological diseases (acute myeloid leukemia, acute lymphoblastic leukemia and myelodysplastic syndrome) showed significantly statistical different (10.27%, 8.01%, and 7.20%) (P<0.01), and the positive rate of the acute myeloid leukemia of those patients was higher than myelodysplastic syndrome patients(α<0.0125). There were 35 cases diagnosed as immunized PTR before allo-HSCT, the platelet increments, 14 h correct count increment, progression-free survival rate and overall survival rate of those patients were significantly lower than those in negative transfusion effective patients (P<0.01), while the percentage of ABO matching was significantly higher (α<0.0125). CONCLUSION: The positive rate of platelet antibody identification is high in females and acute myeloid leukemia patients, and immunized PTR caused by antibody is a risk factor for poor prognosis of allo-HSCT in malignant hematological disease patients.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Feminino , Humanos , Masculino , Transfusão de Plaquetas , Estudos Retrospectivos
6.
Zhongguo Zhen Jiu ; 41(12): 1313-6, 2021 Dec 12.
Artigo em Chinês | MEDLINE | ID: mdl-34936266

RESUMO

OBJECTIVE: To verify the superiority of Fu's acupuncture for cervical spondylosis of vertebral artery type (CSA) based on Cheng's Tongtuo method. METHODS: A total of 150 patients with CSA were randomly divided into a Tongtuo Fu's acupuncture group, a Tongtuo acupuncture group and a conventional Fu's acupuncture group, 50 cases in each group. Under the guidance of the theory of Tongtuo method, the Tongtuo Fu's acupuncture group was treated with Fu's acupuncture, the distal Tong method was performed at the distal myofascial trigger point (MTrP) of the dorsal forearm, and then the Tuo method was performed at the proximal MTrP of the cervical muscle group. In the Tongtuo acupuncture group, acupuncture was given at distal acupoints (Neiguan [PC 6], Quchi [LI 11], Taichong [LR 3], Xingjian [LR 2], etc.), and then at proximal acupoints (Fengchi [GB 20] and Baihui [GV 20]). In the conventional Fu's acupuncture group, Fu's acupuncture was only performed at the MTrP of cervical muscle group. Each group was treated once a day, 3 days were taken as one course, and 2 courses were given. The score of cervical vertigo symptoms and function evaluation scale, peak systolic velocity (PSV) and resistance index (RI) of vertebral artery were observed before and after treatment in the 3 groups. RESULTS: After treatment, the scores of cervical vertigo symptoms and function evaluation scale and PSV in each group were higher than those before treatment (P<0.01), and the RI was lower than that before treatment (P<0.01). The score of cervical vertigo symptoms and function evaluation scale and PSV in Tongtuo Fu's acupuncture group were higher than those in the other two groups (P<0.01), and the RI was lower than that in the other two groups (P<0.01). CONCLUSION: Fu's acupuncture based on Tongtuo method could improve the symptoms of cervical vertigo and the blood flow state of vertebral artery in patients with CSA, and the curative effect is better than Tongtuo acupuncture and conventional Fu's acupuncture.


Assuntos
Terapia por Acupuntura , Espondilose , Pontos de Acupuntura , Humanos , Pescoço , Espondilose/terapia , Resultado do Tratamento , Artéria Vertebral
7.
Mol Cancer ; 20(1): 8, 2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-33402171

RESUMO

Acute myeloid leukemia (AML) is still incurable due to its heterogeneity and complexity of tumor microenvironment. It is imperative therefore to understand the molecular pathogenesis of AML and identify leukemia-associated biomarkers to formulate effective treatment strategies. Here, we systematically analyzed the clinical characters and natural killer (NK) cells portion in seventy newly-diagnosis (ND) AML patients. We found that the proportion of NK cells in the bone marrow of ND-AML patients could predict the prognosis of patients by analyzing the types and expression abundance of NK related ligands in tumor cells. Furthermore, MCL1 inhibitor but not BCL2 inhibitor combined with NK cell-based immunotherapy could effectively improve the therapeutic efficiency via inhibiting proliferation and inducing apoptosis of AML primary cells as well as cell lines in vitro. There results provide valuable insights that could help for exploring new therapeutic strategies for leukemia treatment.


Assuntos
Medula Óssea/patologia , Células Matadoras Naturais/imunologia , Leucemia Mieloide Aguda/imunologia , Proteína de Sequência 1 de Leucemia de Células Mieloides/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Receptores KIR/metabolismo , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Prognóstico , Análise de Sobrevida , Adulto Jovem
8.
Zhen Ci Yan Jiu ; 45(8): 652-6, 2020 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-32869576

RESUMO

OBJECTIVE: To observe the short-term and long-term clinical effect on posterior circulation ischemic vertigo treated with "xiao xingnao kaiqiao" acupuncture (minor regaining consciousness and opening orifice) and explore its effect mechanism. METHODS: Ninety patients with posterior circulation ischemic vertigo were randomly divided into a treatment group and a control group, 45 cases in each group. The patients of the two groups were all treated on the base of neurological medicine. In the control group, Flunarizine Hydrochloride was prescribed for oral administration (5 mg, once daily, for 21 days totally). In the treatment group, acupuncture of "xiao xingnao kaiqiao" was provided at Yintang (EX-HN3), bilateral Neiguan (PC6), bilateral Sanyinjiao (SP6), Baihui (GV20), bilateral Fengchi (GB20), bilateral Wangu (GB12) and bilateral Tianzhu (BL10). The needles were retained for 30 min, once daily for 21 days totally. The changes in vertigo score of traditional Chinese medicine (TCM) were observed, and the changes in the mean blood velocity (Vm) of the left vertebral artery (LVA), the right vertebral artery (RVA) and the basilar artery (BA) as well as the vascular pulsatility index (PI) were monitored and determined by transcranial Doppler (TCD). Additionally, the recurrence rate was followed up after 3 months to evaluate the long-term clinical effects. RESULTS: After treatment, the total effective rate of the treatment group was 91.11% (41/45) and 75.56% (34/45) in the control group. The total effective rate in the treatment group was higher than that in the control group (P<0.05). Compared with their own pre-treatment, the vertigo scores of TCM were reduced in either the treatment group or the control group after treatment (P<0.05) and the score in the treatment group was lower than that in the control group (P<0.05). Compared with their own pre-treatment, Vm and PI were all improved after treatment in either group (P < 0.05). After treatment, the improvements in Vm and PI of LVA、RVA and BA in the treatment group were better than those in the control group (P<0.05). In the follow-up after 3 months, the recurrence rate was 19.51% (8/41) in the treatment group and was 50.00% (17/34) in the control group. The recurrence rate in the treatment group was lower than that in the control group (P<0.05). CONCLUSION: "Xiao xingnao kaiqiao" acupuncture obviously relieves the clinical symptoms of posterior circulation ischemic vertigo. The mechanism of acupuncture is potentially related with its effects in improving Vm and PI of LVA,RVA and BA, as well as improving blood supply of brain tissue.


Assuntos
Terapia por Acupuntura , Vertigem/terapia , Artéria Basilar , Humanos , Isquemia/complicações , Resultado do Tratamento , Vertigem/etiologia
9.
Oncol Lett ; 17(6): 4907-4913, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31186699

RESUMO

Clear cell renal cell carcinoma (ccRCC) is one of the most common types of kidney cancer and is accompanied by a poor prognosis due to a high potential for metastasis and recurrence. The mechanism of ccRCC metastasis is not well known. N-lysine methyltransferase KMT5A serves a crucial role in the progression of human cancer; however, the function of KMT5A in the development of ccRCCs has not yet been investigated, which has triggered an interest in investigating the potential association between KMT5A and ccRCC. The present study demonstrates for the first time that KMT5A is a driving factor in ccRCC metastasis. The KMT5A expression level was revealed to be significantly higher in ccRCC tissues compared with adjacent normal tissues. Patients with ccRCC whose tumors expressed high levels of KMT5A were demonstrated to have significantly shorter postoperative survival times. In vitro knockdown of KMT5A expression in 786-O cells inhibited cell migration and invasion. KMT5A reduced cadherin-1 (CDH1) protein levels by directly inhibiting its transcription. The CDH1 mRNA levels were inversely correlated with KMT5A expression in ccRCC samples. Patients with high tumor KMT5A or low CDH1 levels had the poorest prognosis with the shortest overall survival (OS) time, and this combination was demonstrated to be an independent prognostic indicator for patient OS time in ccRCC, more accurate than monitoring KMT5A or CDH1 alone. Together, these results indicate that KMT5A serves a vital role in ccRCC development and progression, and it may be a novel target for ccRCC treatment and prevention.

10.
Am J Cancer Res ; 9(5): 1061-1073, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31218112

RESUMO

Slingshot phosphatase 3 (SSH3) is a member of the SSH phosphatase family that regulates actin filament dynamics. However, its role in cancer metastasis is relatively unclear compared to that of SSH1. Here, we showed that SSH3 was upregulated in colorectal cancer (CRC). Of note, SSH3 was upregulated in the tumor thrombus and lymph node metastasis compared with that in paired primary CRC tissues. High SSH3 expression was associated with the aggressive phenotype of CRC and may be an independent prognostic factor for the poor survival of patients with CRC. SSH3 significantly enhanced the invasion and metastasis of CRC cells in vitro and in vivo. Moreover, SSH3 regulated the remodeling of actin, which is involved in the cytoskeleton signaling pathway, through its interaction with LIMK1/Rac1 and subsequently promoted CRC cell invasion and metastasis. Our data elucidate an important role for SSH3 in the progression of CRC, and SSH3 may be considered a potential therapeutic target for CRC.

11.
Med Gas Res ; 9(4): 221-228, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31898607

RESUMO

Medical gas is a large class of bioactive gases used in clinical medicine and basic scientific research. At present, the role of medical gas in neuroprotection has received growing attention. Stroke is a leading cause of death and disability in adults worldwide, but current treatment is still very limited. The common pathological changes of these two types of stroke may include excitotoxicity, free radical release, inflammation, cell death, mitochondrial disorder, and blood-brain barrier disruption. In this review, we will discuss the pathological mechanisms of stroke and the role of two medical gases (hydrogen and hydrogen sulfide) in stroke, which may potentially provide a new insight into the treatment of stroke.


Assuntos
Gases/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Barreira Hematoencefálica/metabolismo , Gases/química , Humanos , Hidrogênio/uso terapêutico , Sulfeto de Hidrogênio/uso terapêutico , Mitocôndrias/metabolismo , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Acidente Vascular Cerebral/patologia
12.
BMC Infect Dis ; 17(1): 599, 2017 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-28854892

RESUMO

BACKGROUND: Rabies is a global fatal infectious viral disease that is characterized by a high mortality after onset of clinical symptoms. Recently, there has been an increase in the incidence of rabies in China. The aim of this study was to investigate the incidence of human rabies and characterize the rabies virus nucleoprotein gene in dogs sampled from Fujian Province, Southeast China from 2002 to 2012. METHODS: Data pertaining to human rabies cases in Fujian Province during the period from 2002 through 2012 were collected, and the epidemiological profiles were described. The saliva and brain specimens were collected from dogs in Quanzhou, Longyan and Sanming cities of the province, and the rabies virus antigen was determined in the canine saliva specimens using an ELISA assay. Rabies virus RNA was extracted from canine brain specimens, and rabies virus nucleoprotein gene was amplified using a nested RT-PCR assay, followed by sequencing and genotyping. RESULTS: A total of 226 human rabies cases were reported in Fujian Province from 2002 to 2012, in which 197 cases were detected in three cities of Quanzhou, Longyan and Sanming. ELISA assay revealed positive rabies virus antigen in six of eight rabid dogs and 165 of 3492 seemingly healthy dogs. The full-length gene fragment of the rabies virus nucleoprotein gene was amplified from the brain specimens of seven rabid dogs and 12 seemingly healthy dogs. Sequence alignment and phylogenetic analysis revealed that these 19 rabies virus nucleoprotein genes all belonged to genotype I, and were classified into three genetic groups. Sequencing analysis showed a 99.7% to 100% intra-group and an 86.4% to 89.3% inter-group homology. CONCLUSIONS: This study is the first description pertaining to the epidemiological characteristics of human rabies cases and characterization of the rabies virus nucleoprotein gene in dogs in Fujian Province, Southeast China. Our findings may provide valuable knowledge for the development of strategies targeting the prevention and control of rabies.


Assuntos
Nucleoproteínas/genética , Vírus da Raiva/genética , Raiva/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Antígenos Virais/análise , Encéfalo/virologia , Criança , Pré-Escolar , China/epidemiologia , Doenças do Cão/virologia , Cães , Ensaio de Imunoadsorção Enzimática , Feminino , Genótipo , Humanos , Incidência , Lactente , Masculino , Pessoa de Meia-Idade , Filogenia , Raiva/veterinária , Raiva/virologia , Vírus da Raiva/patogenicidade , Saliva/virologia , Adulto Jovem
13.
Oncotarget ; 8(28): 46191-46203, 2017 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-28521288

RESUMO

The progression of CRC is a multistep process involving several genetic changes or epigenetic modifications. NDN is a member of the MAGE family, encoding a protein that generally suppresses cell proliferation and acting as a transcriptional repressor. Immunohistochemical staining revealed that the expression of NDN was significantly down-regulated in CRC tissues compared with normal tissues and the down-regulation of NDN in CRC could reflect the hypermethylation of the NDN promoter. Treatment of the CRC cell line SW480 with the demethylating agent 5-Aza-CdR restored the NDN expression level. The down-regulation of NDN was closely related to poor differentiation, advanced TNM stage and poor prognosis of CRC. The inhibition of NDN promoted CRC cell proliferation by enriching cells in the S phase. Furthermore, we observed that NDN binds to the GN box in the promoter of LRP6 to attenuate LRP6 transcription and inhibit the Wnt signaling pathway in CRC. In conclusion, our study revealed that the hypermethylation of NDN promotes cell proliferation by activating the Wnt signaling pathway through directly increasing the transcription of LRP6 in CRC. These findings might provide a new theoretical basis for the pathogenesis of CRC and facilitate the development of new therapeutic strategies against CRC.


Assuntos
Neoplasias do Colo/genética , Neoplasias Colorretais/genética , Proteínas Supressoras de Tumor/metabolismo , Animais , Azacitidina/farmacologia , Carcinogênese , Movimento Celular , Proliferação de Células , Neoplasias do Colo/patologia , Neoplasias Colorretais/patologia , Metilação de DNA , Epigênese Genética , Feminino , Regulação Neoplásica da Expressão Gênica , Células HCT116 , Células HT29 , Humanos , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Estadiamento de Neoplasias , RNA Interferente Pequeno/genética , Proteínas Supressoras de Tumor/genética , Via de Sinalização Wnt , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Cell Signal ; 36: 67-78, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28455144

RESUMO

Signal transducer and activator of transcription 3 (STAT3) is known to activate targets associated with invasion, proliferation, and angiogenesis in a wide variety of cancers. The adaptor protein NCK1 is involved in cytoskeletal movement and was identified as a STAT3-associated target in human tumors. However, the underlying molecular mechanism associated with colorectal cancer (CRC) metastasis is not yet completely understood. In this study, we report a novel STAT3 to NCK1 signaling pathway in colorectal cancer (CRC). We investigated the expression of NCK1 and its potential clinical and biological significance in CRC. NCK1 was noticeably up-regulated in human CRC tissues. NCK1 was also significantly associated with serosal invasion, lymph metastasis, and tumor-node-metastasis classification but was inversely correlated with differentiation. Gain-of-function and loss-of-function studies have shown that ectopic expression of NCK1 enhanced metastasis and angiogenesis in CRC cells. By gene expression analyses, we revealed a high co-overexpression of STAT3 and NCK1 in CRC tissues. Ectopic overexpression of STAT3 in CRC cells induced the expression of NCK1, whereas STAT3 knockdown decreased the expression of NCK1. Promoter activation and binding analyses demonstrated that STAT3 promoted the expression of NCK1 via direct action on the NCK1 promoter. The knock down of NCK1 partially reduced the CRC cell metastasis and angiogenesis promoted by STAT3. Additionally, by co-immunoprecipitation assays, we verified that NCK1 interacted with PAK1, which resulted in the activation of the PAK1/ERK pathway. STAT3 induced the transcription of NCK1 and triggered a PAK1/ERK cascade in CRC. These findings suggest a novel STAT3 to NCK1 to PAK1/ERK signaling mechanism that is potentially critical for CRC metastasis and angiogenesis.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Neoplasias Colorretais/irrigação sanguínea , Neoplasias Colorretais/patologia , Metástase Linfática/patologia , Neovascularização Patológica/metabolismo , Proteínas Oncogênicas/metabolismo , Fator de Transcrição STAT3/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Movimento Celular , Galinhas , Neoplasias Colorretais/genética , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Quinase 2 de Adesão Focal/metabolismo , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Camundongos Nus , Pessoa de Meia-Idade , Proteínas Oncogênicas/genética , Transcrição Gênica
15.
Guang Pu Xue Yu Guang Pu Fen Xi ; 35(9): 2516-20, 2015 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-26669158

RESUMO

Soil available phosphorus (P) and available potassium (K) don't possess direct spectral response in the near infrared (NIR) region. They are predictable because of their correlation with spectrally active constituents (organic matter, carbonates, clays, water, etc.). Such correlation may of course differ between the soil sample sets. Therefore, the NIR calibration models with fixed structure are difficult to achieve good prediction performances for soil P and K. In this work, the method of recursive partial least squares (RPLS), which is able to update the model coefficients recursively during the prediction process, has been applied to improve the predictive abilities of calibration models. This work compared the performance of partial least squares regression (PLS), locally weighted PLS (LW-PLS), moving window LW-PLS (LW-PLS2) and RPLS for the measurement of soil P and K. The entire data set of 194 soil samples was split into calibration set and prediction set based on soil types. The calibration set was composed of 120 Anthrosols samples, while the prediction set included 29 Ferralsols samples, 23 Anthrosols samples and 22 Primarosols samples. The best prediction results were obtained by the RPLS model. The coefficient of determination (R2) and residual prediction deviation (RPD) were respectively 0.61, 0.76 and 1.60, 2.05 for soil P and K. The results indicate that RPLS is able to learn the information from the latest modeling sample by recursively updating the model coefficients. The proposed method RPLS has the advantages of wider applicability and better performance for NIR prediction of soil P and K compared with other methods in this work.

16.
Mol Med Rep ; 11(2): 1009-16, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25371092

RESUMO

There is currently no effective vaccine to prevent dengue infection, despite the existence of multiple studies on potential methods of immunization. The aim of the present study was to explore the effect of DNA and/or recombinant protein on levels of neutralizing antibodies. For this purpose, envelope domain IIIs of dengue serotypes 1 and 2 (DEN-1/2)were spliced by a linker (Gly­Gly­Ser­Gly­Ser)3 and cloned into the prokaryotic expression plasmid pET30a (+) and eukaryotic vector pcDNA3.1 (+). The chimeric bivalent protein was expressed in Escherichia coli, and one­step purification by high­performance liquid chromatography was conducted. Protein expression levels of the DNA plasmid were tested in BHK­21 cells by indirect immunofluorescent assay. In order to explore a more effective immunization strategy and to develop neutralizing antibodies against the two serotypes, mice were inoculated with recombinant bivalent protein, the DNA vaccine, or the two given simultaneously. Presence of the specific antibodies was tested by ELISA and the presence of the neutralizing antibodies was determined by plaque reduction neutralization test. Results of the analysis indicated that the use of a combination of DNA and protein induced significantly higher titers of neutralizing antibodies against either DEN­1 or DEN­2 (1:64.0 and 1:76.1, respectively) compared with the DNA (1:24.7 and 1:26.9, DEN­1 and DEN­2, respectively) or the recombinant protein (1:34.9 and 1:45.3 in DEN­1 and DEN­2, respectively). The present study demonstrated that the combination of recombinant protein and DNA as an immunization strategy may be an effective method for the development of a vaccine to prevent dengue virus infection.


Assuntos
Anticorpos Neutralizantes/farmacologia , Dengue/imunologia , Proteínas Recombinantes/imunologia , Vacinas de DNA/imunologia , Vacinas Virais/imunologia , Animais , Anticorpos Antivirais/imunologia , Vírus da Dengue , Ensaio de Imunoadsorção Enzimática , Escherichia coli/metabolismo , Imunização , Camundongos , Camundongos Endogâmicos BALB C , Testes de Neutralização , Plasmídeos
17.
Guang Pu Xue Yu Guang Pu Fen Xi ; 34(8): 2070-5, 2014 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-25474936

RESUMO

In the present work, recursive variable selection methods (updating both the model coefficients and effective variables during the prediction process) were applied to maintain the predictive abilities of calibration models. This work compared the performances of partial least squares (PLS), recursive PLS (RPLS) and three recursive variable selection methods, namely vari- able importance in the projection combined with RPLS (VIP-RPLS), VIP-PLS, and uninformative variable elimination combined with PLS (UVE-PLS) for the measurement of soil total nitrogen (TN) and organic matter (OM) using Vis-NIR spectroscopy. The dataset consisted of 195 soil samples collected from eight towns in Wencheng County, Zhejiang Province, China. The entire data set was split randomly into calibration set and prediction set. The calibration set was composed of 120 samples, while the prediction set included 75 samples. The best prediction results were obtained by the VIP-RPLS model. The coefficient of determination (R2) and residual prediction deviation (RPD) were respectively 0.85, 0.86 and 2.6%, 2.7% for soil TN and OM. The results indicate that VIP-RPLS is able to capture the effective information from the latest modeling sample by recursively updating the effective variables. The proposed method VIP-RPLS has the advantages of better performance for Vis-NIR prediction of soil N and OM compared with other methods in this work.


Assuntos
Nitrogênio/análise , Compostos Orgânicos/análise , Solo/química , Espectroscopia de Luz Próxima ao Infravermelho , China , Análise dos Mínimos Quadrados , Modelos Teóricos
18.
BMC Infect Dis ; 14: 531, 2014 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-25287717

RESUMO

BACKGROUND: China has the largest number of the elderly in the world. As the proportion of elderly is rapidly increasing among national reported HIV/AIDS cases, it is a concern about HIV epidemic among older MSM in China. However, studies on HIV prevalence and unprotected anal intercourse (UAI) among Chinese older MSM were relatively few or generally had small sample sizes. METHODS: English and Chinese articles published in peer-reviewed journals were identified by systematically searching 5 electronic databases including PubMed and through cross-referencing. Summary prevalence rates of HIV infection and UAI with male sexual partners were calculated, and analyses were performed using the software Comprehensive Meta-Analysis V2.0 and SPSS V17.0. Subgroup analyses were performed separately by sample size, study year, study location, recruitment settings and sampling method. RESULTS: Twenty eligible cross-sectional studies (3 in English and 17 in Chinese), published between 2005 and 2013, with a total of 2812 older MSM participants, were identified. Our meta-analyses showed that the prevalence of HIV, syphilis and UAI in the last 6 months were 11.6% (95% confidence interval [CI]: 8.0%-16.6%), 23.0% (95% CI: 15.8%-32.3%) and 79.5% (95% CI: 72.7%-84.9%), respectively. HIV prevalence increased over the study period (6.3% in 2003-2007; 8.6% in 2008-2009, and 11.5% in 2010-2011, trend test Chi-square = 7.02, p = 0.008). The pooled prevalence of HIV (11.6% vs. 5.2%, Chi-square value = 36.2, p < 0.001) and UAI (79.5% vs. 52.6%, Chi-square value = 440.04, p < 0.001) among older MSM were both significantly higher than among younger age group (age < 50 years). CONCLUSIONS: Older Chinese MSM have high prevalence of HIV and syphilis. Unprotected anal sex is common and further puts them at high risks of acquiring and transmitting HIV, which was one of reasons for the rapid increasing of national reported older male HIV/AIDS cases. Prevention intervention programs should be specially tailored for this high risk MSM subgroup.


Assuntos
Infecções por HIV/epidemiologia , Sexo sem Proteção/estatística & dados numéricos , Distribuição por Idade , China/epidemiologia , Estudos Transversais , Infecções por HIV/transmissão , Homossexualidade Masculina/estatística & dados numéricos , Humanos , Masculino , Prevalência , Comportamento Sexual/estatística & dados numéricos , Sífilis/epidemiologia , Sífilis/transmissão
19.
Zhongguo Zhen Jiu ; 34(5): 517-20, 2014 May.
Artigo em Chinês | MEDLINE | ID: mdl-25022136

RESUMO

Literatures of study on acupoint functional effect of encephalic region with functional magnetic resonance imaging (fMRI) are collected from the database of China National Knowledge Information (CNKI) and Wan fang database. Analysis and comments are made respectively from the status quo of studies on combination of single acupoint, two acupoints and multiple acupoints under both physiological and pathological conditions. The results show that the corresponding encephalic regions can be specifically activated by acupuncture. And different regions can be activated by different acupoints. However, studies on single acupoint, two acupoints and three acupoints are the major researches carried out at present. It is still lack of observation on effect of commonly-used combinations in clinic. Moreover, the reliability of the research results are also affected by disunity of operations protocol, reinforcing or reducing manipulations, intensity or depth of stimulation and duration of needling retention. Therefore, it is necessary to establish a unified and standard operation protocol to strictly control the bias factors which may affect the result of research in the future, and take patients as the study target as much as possible, so as to further explore the central effect mechanism.


Assuntos
Pontos de Acupuntura , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Imageamento por Ressonância Magnética , Terapia por Acupuntura , Humanos , Radiografia
20.
Artigo em Chinês | MEDLINE | ID: mdl-24330873

RESUMO

OBJECTIVE: To research the role of lymph tracers to protect parathyroid in surgery for papillary thyroid carcinoma. METHODS: Patients with papillary thyroid carcinoma who met selected criteria were enrolled in this study. Patients were divided into carbon nanoparticle group, methylene blue group, and conventional surgery group. RESULTS: No significant complication occurred in the patients of carbon nanoparticle and methylene blue groups. In carbon nanoparticle group, methylene blue group and conventional surgery group, the mean numbers of parathyroid glands detected during surgery were 3.1 ± 0.3, 2.9 ± 0.4 and 2.3 ± 0.3 (F = 3.78, P < 0.01) , the rates that parathyroid was cut mistakenly were 1.37% (2/146) , 2.62% (2/97) and 7.14% (6/84) respectively (χ(2) = 17.372, P < 0.05) ; and the incidence of postoperative hypocalcemia were 10.4% (5/48) , 9.1% (3/33) and 17.5% (7/40,χ(2) = 0.671, P = 0.037) . CONCLUSION: Thyroid lymphography technique is helpful to protect from the injury to the parathyroid glands in surgery.


Assuntos
Linfografia , Tireoidectomia , Humanos , Hipocalcemia , Glândulas Paratireoides
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