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1.
Exp Dermatol ; 33(7): e15128, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38973249

RESUMO

Dry skin is common to many pruritic diseases and is difficult to improve with oral traditional antihistamines. Recently, increasing evidence indicated that histamine H4 receptor (H4R) plays an important role in the occurrence and development of pruritus. Extracellular signal-regulated kinase (ERK) phosphorylation activation in the spinal cord mediates histamine-induced acute and choric itch. However, whether the histamine H4 receptor regulates ERK activation in the dry skin itch remains unclear. In the study, we explore the role of the histamine H4 receptor and p-ERK in the spinal cord in a dry skin mouse model induced by acetone-ether-water (AEW). q-PCR, Western blot, pharmacology and immunofluorescence  were applied in the study. We established a dry skin itch model by repeated application of AEW on the nape of neck in mice. The AEW mice showed typically dry skin histological change and persistent spontaneous scratching behaviour. Histamine H4 receptor, instead of histamine H1 receptor, mediated spontaneous scratching behaviour in AEW mice. Moreover, c-Fos and p-ERK expression in the spinal cord neurons were increased and co-labelled with GRPR-positive neurons in AEW mice. Furthermore, H4R agonist 4-methyhistamine dihydrochloride (4-MH)induced itch. Both 4-MH-induced itch and the spontaneous itch in AEW mice were blocked by p-ERK inhibitor U0126. Finally, intrathecal H4R receptor antagonist JNJ7777120 inhibited spinal p-ERK expression in AEW mice. Our results indicated that spinal H4R mediates itch via ERK activation in the AEW-induced dry skin mice.


Assuntos
Acetona , MAP Quinases Reguladas por Sinal Extracelular , Prurido , Receptores Histamínicos H4 , Medula Espinal , Animais , Prurido/induzido quimicamente , Prurido/metabolismo , Receptores Histamínicos H4/metabolismo , Camundongos , Medula Espinal/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Masculino , Acetona/farmacologia , Água , Éter , Modelos Animais de Doenças , Fosforilação , Indóis/farmacologia , Butadienos/farmacologia , Piperazinas/farmacologia , Nitrilas/farmacologia , Pele/metabolismo , Doença Crônica , Metilistaminas , Proteínas Proto-Oncogênicas c-fos/metabolismo , Camundongos Endogâmicos C57BL
2.
Cancer Biomark ; 39(3): 187-195, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38043005

RESUMO

BACKGROUND: Circular RNAs (circRNAs) are critical regulators of lung adenocarcinoma (LA) progression. Although a molecular marker targeting hsa_circ_0000018 has been developed and used for diagnosing colon cancer, the role of this circRNA in LA progression has not been explored till now. OBJECTIVES: This study aimed to elucidate the role and regulatory mechanisms of hsa_circ_0000018 in LA progression. METHODS: LA tissues and corresponding adjacent non-tumor tissues were collected from 36 patients to confirm the levels of circRNAs, microRNAs (miRNAs), and messenger RNAs (mRNAs) using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). We also cultured two LA cell lines (A549, PC-9), and the human normal lung epithelial cell line BEAS-2B. Cell function experiments were conducted to assess malignancy in LA cells, including proliferation, migration, and invasion, following forced hsa_circ_0000018 expression. The correlation between hsa_circ_0000018, let-7f-5p, and family with sequence similarity 96 member A (FAM96A) was confirmed by using starBase (miRNA-circRNA interaction database), luciferase assay, and western blotting. RESULTS: Expression of hsa_circ_0000018 and FAM96A was reduced, whereas that of let-7f-5p was upregulated in LA. Cell function assays revealed that upregulation of hsa_circ_0000018 had a suppressive effect on the proliferation, migration, and invasion of LA cells. Additionally, hsa_circ_0000018 sponge binds let-7f-5p, resulting in upregulation of FAM96A expression. CONCLUSION: Our data reveal hsa_circ_0000018 as a tumor suppressor in LA that targets the let-7f-5p/FAM96A axis. Our findings enrich the known regulatory network of circRNAs in LA.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , MicroRNAs , RNA Circular , Humanos , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , RNA Mensageiro
3.
Int J Biol Macromol ; 254(Pt 3): 127892, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37952799

RESUMO

Underwater superoleophobic (UWSO) materials have garnered significant attention in separating oil/water mixtures. But, the majority of these materials are made from non-degradable and non-renewable raw materials, polluting the environment and wasting scarce resources while using them. Against this backdrop, this study aimed to fabricate an environmental-friendly UWSO textile using biobased materials. To achieve this, hydrogel consisting of chitosan (CS) and poly(tannic acid) (PTA) were formed and coated on cotton fabric (CTF) via dip-coating followed by oxidative polymerization. CS&PTA hydrogel endowed the CTF with a rough surface and high surface energy, leading to an UWSO CTF with an underwater oil contact angle as high as 166.84°. The CS&PTA/CTF had excellent separation capability toward various oil/water mixtures, showing separation efficiency above 99.84 % and water flux higher than 23, 999 L m-2 h-1. Moreover, CS&PTA/CTF possessed excellent mechanical and environmental stability with underwater superoleophobicity unchanged after sandpaper friction, ultrasonication, organic solvents, NaCl (m/v, 30 %) solution, and acid/base solution immersion, due to the strong interaction between the hydrogel and cotton fabric generated by the mussel-inspired adhesion owing to the presence of PTA. The fully biobased UWSO CTF exhibits great promising to be an alternative to traditional superwetting materials for separation of oil/water mixtures.


Assuntos
Quitosana , Hidrogéis , Humanos , Caquexia , Têxteis
4.
Front Endocrinol (Lausanne) ; 13: 962154, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36465612

RESUMO

Polycystic ovary syndrome (PCOS) is a universal endocrine and metabolic disorder prevalent in reproductive aged women. PCOS is often accompanied with insulin resistance (IR) which is an essential pathological factor. Although there is no known cure for PCOS, cangfudaotan (CFDT) decoction is widely used for the treatment of PCOS; nevertheless, the underlying mechanism is not clear. In this study, 40 Sprague-Dawley (SD) rats (female) were randomized to 4 groups, namely the control group, PCOS group, PCOS+CFDT group, and PCOS+metformin group. The rats in the control group were fed a normal-fat diet, intraperitoneally injected with 0.5% carboxymethyl cellulose (CMC, 1 mL/kg/d) for 21 days and orally given saline (1 mL/kg/d) for the next 4 weeks. The rats in the PCOS group, PCOS+CFDT group, and PCOS+Metformin group were fed a high-fat diet (HFD) and intraperitoneally injected with letrozole (1.0 mg/kg) for 21 days. During this period, we recorded the body weight, estrous cycles, and rate of pregnancy in all rats. We also observed the ovarian ultrastructure. Blood glucose indices, serum hormones, and inflammatory factors were also recorded. Then, we detected apoptotic and mitochondrial function, and observed mitochondria in ovarian granular cells by transmission electron microscopy. We also detected genes of ASK1/JNK pathway at mRNA and protein levels. The results showed that CFDT alleviated pathohistological damnification and apoptosis in PCOS rat model. In addition, CFDT improved ovarian function, reduced inflammatory response, inhibited apoptosis of granular cells, and inhibited the operation of ASK1/JNK pathway. These findings demonstrate the occurrence of ovary mitochondrial dysfunction and granular cell apoptosis in PCOS. CFDT can relieve mitochondria-dependent apoptosis by inhibiting the ASK1/JNK pathway in PCOS rats.


Assuntos
Metformina , Síndrome do Ovário Policístico , Feminino , Gravidez , Humanos , Ratos , Animais , Síndrome do Ovário Policístico/tratamento farmacológico , Ratos Sprague-Dawley , Células da Granulosa , Mitocôndrias , Apoptose , Metformina/farmacologia
5.
J Oncol ; 2022: 3819564, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35498543

RESUMO

Background: Whether more tumor numbers detected in surgery compared to preoperative image affecting survival of colorectal liver metastases (CRLM) patients after hepatectomy combined with microwave ablation (MWA) remains unclear. Methods: From 2013 to 2018, 85 CRLM patients who underwent hepatectomy combined with MWA were retrospectively assessed. Compared to the tumor numbers in preoperative image, patients with equal intraoperative tumor numbers were defined as the equal number group (n = 45); patients detected more tumor numbers in surgery were defined as the more number group (n = 40). Clinicopathological factors and prognosis were compared between two groups. Results: Compared to the equal number group, the more number group was characterized by more lymphatic metastasis, synchronous metastasis of liver lesion, and tumor numbers over 5 (all P < 0.05). Median survival time was 46.7 months and 26.8 months in the equal and more number group. Significantly worse overall survival (OS) was found in more number group to the equal number group (P = 0.027). In Cox analysis, more tumor number than image and high level of carbohydrate antigen 19-9 (CA19-9) were poor prognostic factors for OS. Conclusion: In patients receiving hepatectomy combined with MWA, detecting more liver metastases in surgery than preoperative image indicates poor long-term survival. These patients were characterized by more lymphatic metastasis, synchronous metastasis of liver lesion, and tumor numbers over 5. Intensive follow-up to detect early recurrence and potent postoperative therapy to improve survival may be justified in patients detected more tumor numbers in surgery with a high CA19-9 level.

6.
Int J Biol Macromol ; 209(Pt A): 279-289, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35398058

RESUMO

Superhydrophilic and underwater superoleophobic materials exhibit excellent oil/water separation performance but are usually fabricated from nonrenewable and nondegradable feedstocks and thus would cause secondary pollution after use. Herein, we report a fully biobased and mussel-inspired underwater superoleophobic hydrogel coated cotton fabric (CF) prepared by surface coating and subsequent oxidation polymerization of chitosan & dopamine mixtures. The obtained chitosan & polydopamine hydrogel coated CF (CS&PDA/CF) showed superhydrophilicity and underwater superoleophobicity, due to the formed rough surface structure with hydrophilic complex hydrogel. The CS&PDA/CF exhibited excellent oil/water separation performance with separation efficiency higher than 99.5% for various oil/water mixtures. Moreover, the CS&PDA/CF showed excellent resistance against various harsh conditions such as boiling water, ultrasonication, and concentrated salt solution, due to the mussel-inspired strong adhesion stabilized structure and morphology. We believe that the fully biobased and mussel-inspired underwater superoleophobic cotton fabric shows great potential as an eco-friendly and high-efficient oil/water separation material.


Assuntos
Quitosana , Purificação da Água , Hidrogéis , Interações Hidrofóbicas e Hidrofílicas , Óleos/química
7.
J Hepatocell Carcinoma ; 8: 657-670, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34235104

RESUMO

BACKGROUND: The importance of alpha-fetoprotein (AFP) and des-gamma-carboxyprothrombin (DCP) in hepatocellular carcinoma (HCC) has been studied extensively in Japan, where hepatitis C virus is the predominant aetiology of HCC. The clinical profiles of HCC regarding the state of AFP and DCP in a hepatitis B virus epidemic area have not been comprehensively investigated, and the value of these tumour markers in evaluating the response to treatment and the detection of recurrence has yet to be determined. PATIENTS AND METHODS: A total of 4792 patients treated in our centre were continuously analysed regarding accessible AFP and DCP data pre- and posttreatment. Baseline characteristics were summarized, and comparisons of progression-free survival (PFS) and overall survival (OS) rates were made independently. The prognostic significance of each factor was tested with the Cox proportional hazards model. Patients who had AFP and DCP data pretreatment, pre- and posttreatment, and those who were continuously monitored more than twice were analysed separately. RESULTS: A total of 2600 patients (53.4%) were positive for AFP and DCP; 362 (7.6%) and 1211 (25.3%) patients were AFP- or DCP-positive, respectively, and 619 patients (12.9%) were negative for both AFP and DCP. Patients in the AFP single-positive or double-negative groups had the best OS (P<0.001). Patients with less than 50% responses in AFP and DCP after treatments suffered from worse prognostic survival (P<0.001). In the multivariate analysis, elevated AFP and DCP were identified as independent prognostic factors of PFS and OS. In addition, different tumour markers were related to different clinical and pathological traits. CONCLUSION: The present study comprehensively explored the clinical value of classical tumour markers for HCC using the "point-to-line" method. Positivity of pretreatment AFP and DCP or less than 50% treatment response rates exhibited more aggressive HCC, resulting in poor PFS and OS in HCC patients.

8.
Front Oncol ; 10: 1639, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33194569

RESUMO

Background: Both stereotactic body radiotherapy (SBRT) and radiofrequency ablation (RFA) are effective local treatments for hepatocellular carcinoma (HCC), but whether RFA is superior to SBRT is still controversial. Therefore, we performed a meta-analysis to compare the treatment outcomes of SBRT with RFA as curable or bridge intention. Methods: We searched online databases for studies that compared treatment outcomes for SBRT and RFA. Eligibility criteria included evaluation of local control, overall survival (OS), transplant rate, and post-transplant pathological necrosis. Results: As no randomized clinical trials met the criteria, 10 retrospective studies with a total of 2,732 patients were included. Two studies were in favor of SBRT in local control, two studies preferred RFA in OS, and others reported comparable outcomes for both. SBRT demonstrated significantly higher 1- and 3-year local control than RFA [odds ratio (OR) 0.42, 95% CI 0.24-0.74, P = 0.003; and OR 0.54, 95% CI 0.37-0.80, P = 0.002, respectively]. However, SBRT reported significantly shorter 1- and 2-year OS (OR 1.52, 95% CI 1.21-1.90, P = 0.0003; and OR 1.66, 95% CI 1.38-2.01, P < 0.00001, respectively). As bridge treatment, no significant difference was shown in transplant rate and post-transplant pathological necrosis rate (OR 0.57, 95% CI 0.32-1.03, P = 0.060; and OR 0.49, 95% CI 0.13-1.82, P = 0.290, respectively). Conclusions: This study demonstrates SBRT is able to complete a better local control for HCC than RFA, though the OS is inferior to RFA because of tumor burden or liver profiles of the enrolled studies. Well-designed, randomized, multicenter trials will be required to further investigate the conclusion.

9.
Genes (Basel) ; 11(8)2020 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-32784402

RESUMO

Currently, an increasing number of studies suggest that long non-coding RNAs (lncRNAs) and methylation-regulated lncRNAs play a critical role in the pathogenesis of various cancers including hepatocellular carcinoma (HCC). Therefore, methylated differentially expressed lncRNAs (MDELs) may be critical biomarkers of HCC. In this study, 63 MDELs were identified by screening The Cancer Genome Atlas (TCGA) HCC lncRNAs expression data set and lncRNAs methylation data set. Based on univariate and multivariate survival analysis, four MDELs (AC025016.1, LINC01164, LINC01183 and LINC01269) were selected to construct the survival prognosis prediction model. Through the PI formula, the study indicates that our new prediction model performed well and is superior to the traditional staging method. At the same time, compared with the previous prediction models reported in the literature, the results of time-dependent receiver operating characteristic (ROC) curve analysis show that our 4-MDELs model predicted overall survival (OS) stability and provided better prognosis. In addition, we also applied the prognostic model to Cancer Cell Line Encyclopedia (CCLE) cell lines and classified different hepatoma cell lines through the model to evaluate the sensitivity of different hepatoma cell lines to different drugs. In conclusion, we have established a new risk scoring system to predict the prognosis, which may have a very important guiding significance for the individualized treatment of HCC patients.


Assuntos
Biomarcadores Tumorais , Carcinoma Hepatocelular/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/genética , Processamento Pós-Transcricional do RNA , RNA Longo não Codificante/genética , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/mortalidade , Biologia Computacional/métodos , Bases de Dados Genéticas , Perfilação da Expressão Gênica , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidade , Metilação , Prognóstico , Modelos de Riscos Proporcionais , RNA Longo não Codificante/metabolismo , Curva ROC , Reprodutibilidade dos Testes , Transcriptoma
10.
Biosci Rep ; 40(2)2020 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-32068236

RESUMO

The processes that lead to lung adenocarcinoma (LUAD) metastasis are poorly characterized. Spindle and kinetochore associated complex subunit 3 (SKA3) plays a key role in cervical cancer development, but its contribution to LUAD is unknown. Here, we found that SKA3 is overexpressed in LUAD and its expression correlates with lymph node metastasis and poor prognosis. SKA3 silencing experiments identified SKA3 as an oncogene that promotes the metastasis of LUAD cell lines and tissues. SKA3 was found to induce the expression of matrix metalloproteinase (MMP)-2, -7, and -9, which activate PI3K-AKT. SKA3 was also found to bind and activate EGFR to activate PI3K-AKT. In summary, we identify a role for SKA3 in LUAD metastasis through its ability to bind EFGR and activate PI3K-AKT signaling.


Assuntos
Adenocarcinoma de Pulmão/enzimologia , Proteínas de Ciclo Celular/metabolismo , Movimento Celular , Neoplasias Pulmonares/enzimologia , Proteínas Associadas aos Microtúbulos/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/secundário , Animais , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Receptores ErbB/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Metástase Linfática , Masculino , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 7 da Matriz/genética , Metaloproteinase 7 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Camundongos Nus , Proteínas Associadas aos Microtúbulos/genética , Transdução de Sinais
11.
Cancers (Basel) ; 11(8)2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31387248

RESUMO

(1) Background: To investigate the clinical outcomes between radiofrequency ablation (RFA) and stereotactic body radiotherapy (SBRT) for residual hepatocellular carcinoma (RHCC). (2) Methods: 139 patients were diagnosed with the RHCC after post-operative checkup, among whom 39 and 33 patients underwent RFA or SBRT as salvage treatments, respectively. We applied the propensity score matching (PSM) to adjust for imbalances in treatment assignment. Local disease progression, progression-free survival (PFS), overall survival (OS), and treatment-related side effects were the study endpoints. (3) Results: Before PSM, the SBRT group demonstrated significantly lower local disease progression rate (6/33 vs. 23/39; p = 0.002), better PFS (the 1- and 3-year PFS were 63.3% and 49.3% vs. 41.5% and 22.3%, respectively, p = 0.036), and comparable OS (the 1- and 3-year OS were 85.4% and 71.1% vs. 97.3% and 57.6%, respectively, p = 0.680). After PSM of 23 matched cases, the SBRT group demonstrated significantly lower local disease progression rate, better PFS and comparable OS. Centrally located tumor predicted the worse OS. No acute grade 3+ toxicity was observed in both groups. (4) Conclusion: SBRT might be the preferred treatment for RHCC, especially for patients with larger tumors or tumors abutting major vessels, rather than repeated RFA.

12.
Med Sci Monit ; 25: 2368-2376, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30933965

RESUMO

BACKGROUND At present, there is no effective targeted therapy for esophageal squamous cell carcinoma (ESCC), and it is urgent to find new targets for the treatment of ESCC. TRAF4 has been regarded as a cause of carcinogenesis due to overexpression in many cancer types and participation in multiple signaling pathways. However, there are few studies on TRAF4 in ESCC worldwide. Its expression in ESCC and whether it affects the prognosis of patients still remain unclear. MATERIAL AND METHODS We detected the expressions of TRAF4, ki-67, and p53 in 100 cases of ESCC and 80 cases of adjacent normal esophageal squamous epithelium tissues by immunohistochemical technique. We further explored the relationship between TRAF4 and ESCC and its prognosis through statistical analysis. RESULTS TRAF4 was highly expressed in ESCC tissues and was mainly expressed in the cytoplasm. Overexpression of TRAF4 in ESCC was also associated with high expression of ki-67 and p53 (P<0.05). We also found that patients with high expression of TRAF4 had significantly lower OS than in patients with low TRAF4 expression (P<0.05). Overexpression of TRAF4 was an independent risk factor affecting the prognosis of patients (P<0.05). CONCLUSIONS We found that TRAF4 was highly expressed in ESCC tissues and was mainly expressed in the cytoplasm of cancer cells. Overexpression of TRAF4 was an independent risk factor affecting the overall prognosis of patients. The results indicated that TRAF4 may become a new target for the treatment of ESCC in the future.


Assuntos
Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas do Esôfago/metabolismo , Fator 4 Associado a Receptor de TNF/biossíntese , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Humanos , Antígeno Ki-67/biossíntese , Antígeno Ki-67/genética , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Prognóstico , Transdução de Sinais , Fator 4 Associado a Receptor de TNF/genética , Transcriptoma , Proteína Supressora de Tumor p53/biossíntese , Proteína Supressora de Tumor p53/genética
13.
Food Chem Toxicol ; 120: 253-260, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30009888

RESUMO

Cholestasis is characterized by the obstruction of bile duct, including primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). The complicated etiology and injury mechanism greatly limits the development of new drugs for its treatment. To better understand the mechanism of cholestatic liver damage, ultra-performance liquid chromatography-linked electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOFMS) and multivariate data analysis were used to determine the metabolic changes in three recognized mouse cholestasis models. The cholestatic liver damage was generated by alphanaphthyl isothiocyanate (ANIT), 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) and lithocholic acid (LCA). The results indicated that the levels of bile acids were commonly increased in plasma of three mouse cholestasis models, while arginine was decreased. The level of plasma glutathione was decreased in ANIT- and LCA-induced intrahepatic PBC and PSC, respectively. But, the liver glutathione was decreased in DDC induced extrahepatic PSC. The level of plasma phospholipids was elevated in ANIT and DDC models, whereas that was depleted in LCA model. And protoporphyrin IX was significantly increased in the liver of DDC model. These metabolomics data could potentially distinguish the metabolic differences of three types of cholestasis, contributing to the understanding of the potential mechanism of cholestatic liver damage.


Assuntos
Colangite Esclerosante/metabolismo , Colestase/metabolismo , Colestase/patologia , Cirrose Hepática Biliar/metabolismo , Metabolômica , Animais , Arginina/sangue , Ácidos e Sais Biliares/sangue , Biomarcadores/metabolismo , Colangite Esclerosante/sangue , Colangite Esclerosante/patologia , Cromatografia Líquida , Modelos Animais de Doenças , Glutationa/sangue , Cirrose Hepática Biliar/sangue , Cirrose Hepática Biliar/patologia , Masculino , Espectrometria de Massas , Camundongos Endogâmicos C57BL , Fosfolipídeos/sangue
14.
Med Sci Monit ; 24: 698-705, 2018 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-29397026

RESUMO

BACKGROUND The coiled-coil domain-containing proteins have been shown to have a series of functions in biological synthesis. Recent studies have found that CCDC34 is highly expressed in bladder cancer, but the underlying molecular mechanisms still remain unclear. Therefore, we performed the present study to assess the expression of the coiled-coil domain-containing protein 34 (CCDC34) in esophageal squamous cell carcinoma (ESCC) patients. We also explored the relationships between CCDC34 expression and clinicopathologic characteristics, tumor angiogenesis, and prognosis. MATERIAL AND METHODS We detected the expressions of CCDC34, VEGF, and MVD by immunohistochemical technique in 100 cases of ESCC and 80 cases of corresponding paracarcinomatous normal tissues. The relationship between CCDC34 expression and clinicopathologic characteristics, tumor angiogenesis, and prognosis were also explored. RESULTS The expression of CCDC34 protein was obviously increased in ESCC tissues, which was significantly correlated with sex (p=0.038), TNM stage (p=0.003), and lymphatic metastasis (p=0.024). In addition, we found that the expression of CCDC34 was an independent prognostic factor for ESCC patients. The overexpression of CCDC34 protein in ESCC was associated with tumor progression, angiogenesis, and poor survival. CONCLUSIONS Our results demonstrate that CCDC34 is overexpressed in ESCC and can be used as an independent parameter for indicating the poor prognosis of ESCC patients, suggesting that CCDC34 might be a new potential therapeutic target for ESCC patients in the future.


Assuntos
Antígenos de Neoplasias/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Proteínas de Neoplasias/metabolismo , Neovascularização Patológica/metabolismo , Idoso , Antígenos CD34/metabolismo , Intervalo Livre de Doença , Carcinoma de Células Escamosas do Esôfago , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Microvasos/patologia , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Fator A de Crescimento do Endotélio Vascular/metabolismo
16.
Mol Med Rep ; 15(5): 2620-2624, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28447753

RESUMO

The present study demonstrated the effect of fucoidan, isolated from Fucus vesiculosus, on cell growth and apoptosis in anaplastic thyroid cancer cells. The cell viability was analyzed using a Cell Counting Kit­8 cell proliferation kit. Diamidino-2-phenylindole and terminal deoxynucleotidyl transferase-mediated dUTP nick­end labeling assays were used to examine the apoptotic effect of fucoidan, which revealed the presence of apoptotic bodies and DNA fragmentation. Fucoidan inhibited the growth of FTC133 and TPC1 ATC cells in a dose­dependent manner. It also induced the apoptosis of FTC133 cells by promoting the expression levels of cleaved poly ADP­ribose polymerase and caspase­3. Significant decreases in the levels expression of hypoxia-inducible factor 1α and vascular endothelial growth factor were observed in the FTC133 cells following treatment of the cells with fucoidan. In addition, inhibition in tube formation and the migration of FTC133 cells were observed in the cells treated with fucoidan, compared with the cells in the control group. Therefore, fucoidan inhibited cell growth, induced apoptosis and suppressed angiogenesis in the thyroid cancer cells.


Assuntos
Inibidores da Angiogênese/farmacologia , Apoptose/efeitos dos fármacos , Neovascularização Patológica , Polissacarídeos/farmacologia , Neoplasias da Glândula Tireoide , Linhagem Celular Tumoral , Células Endoteliais da Veia Umbilical Humana , Humanos , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Neoplasias da Glândula Tireoide/irrigação sanguínea , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologia
17.
Artigo em Inglês | MEDLINE | ID: mdl-28223387

RESUMO

Candida albicans biofilms show resistance to many clinical antifungal agents and play a considerable contributing role in the process of C. albicans infections. New antifungal agents against C. albicans biofilms are sorely needed. The aim of this study was to evaluate sanguinarine (SAN) for its activity against Candida albicans biofilms and explore the underlying mechanism. The MIC50 of SAN was 3.2 µg/ml, while ≥0.8 µg/ml of SAN could suppress C. albicans biofilms. Further study revealed that ≥0.8 µg/ml of SAN could decrease cellular surface hydrophobicity (CSH) and inhibited hypha formation. Real-time reverse transcription-PCR (RT-PCR) results indicated that the exposure of C. albicans to SAN suppressed the expression of some adhesion- and hypha-specific/essential genes related to the cyclic AMP (cAMP) pathway, including ALS3, HWP1, ECE1, HGC1, and CYR1 Consistently, the endogenous cAMP level of C. albicans was downregulated after SAN treatment, and the addition of cAMP rescued the SAN-induced filamentation defect. In addition, SAN showed relatively low toxicity to human umbilical vein endothelial cells, the 50% inhibitory concentration (IC50) being 7.8 µg/ml. Collectively, the results show that SAN exhibits strong activity against C. albicans biofilms, and the activity was associated with its inhibitory effect on adhesion and hypha formation due to cAMP pathway suppression.


Assuntos
Antifúngicos/farmacologia , Benzofenantridinas/farmacologia , Biofilmes/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Hifas/efeitos dos fármacos , Isoquinolinas/farmacologia , Células Cultivadas , AMP Cíclico/genética , AMP Cíclico/metabolismo , Regulação para Baixo/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana , Humanos , Interações Hidrofóbicas e Hidrofílicas/efeitos dos fármacos , Hifas/genética , Testes de Sensibilidade Microbiana
18.
Neurotox Res ; 31(2): 204-217, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27848175

RESUMO

Severe hand-foot-and-mouth disease (HFMD) caused by Enterovirus 71 (EV71) always accompanies with inflammation and neuronal damage in the central nervous system (CNS). During neuronal injuries, cell surface-exposed calreticulin (Ecto-CRT) is an important mediator for primary phagocytosis of viable neurons by microglia. Our data confirmed that brainstem neurons underwent neuronophagia by glia in EV71-induced death cases of HFMD. EV71 capsid proteins VP1, VP2, VP3, or VP4 did not induce apoptosis of brainstem neurons. Interestingly, we found VP1-activated endoplasmic reticulum (ER) stress and autophagy could promote Ecto-CRT upregulation, but ER stress or autophagy alone was not sufficient to induce CRT exposure. Furthermore, we demonstrated that VP1-induced autophagy activation was mediated by ER stress. Meaningfully, we found dexamethasone treatment could attenuate Ecto-CRT upregulation by alleviating VP1-induced ER stress. Altogether, these findings identify VP1-promoted Ecto-CRT upregulation as a novel mechanism of EV71-induced neuronal cell damage and highlight the potential of the use of glucocorticoids to treat severe HFMD patients with CNS complications.


Assuntos
Calreticulina/metabolismo , Proteínas do Capsídeo/toxicidade , Dexametasona/farmacologia , Estresse do Retículo Endoplasmático/fisiologia , Neurônios/fisiologia , Fagocitose/fisiologia , Proteínas Estruturais Virais/toxicidade , Animais , Autofagia/efeitos dos fármacos , Autofagia/fisiologia , Tronco Encefálico/efeitos dos fármacos , Tronco Encefálico/fisiopatologia , Células Cultivadas , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Feminino , Humanos , Masculino , Fagocitose/efeitos dos fármacos , Ratos , Regulação para Cima
19.
Virulence ; 6(4): 347-61, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25714264

RESUMO

Candida albicans is both a commensal microorganism in healthy individuals and a major fungal pathogen causing high mortality in immunocompromised patients. Yeast-hypha morphological transition is a well known virulence trait of C. albicans. Host innate immunity to C. albicans critically requires pattern recognition receptors (PRRs). In this review, we summarize the PRRs involved in the recognition of C. albicans in epithelial cells, endothelial cells, and phagocytic cells separately. We figure out the differential recognition of yeasts and hyphae, the findings on PRR-deficient mice, and the discoveries on human PRR-related single nucleotide polymorphisms (SNPs).


Assuntos
Candida albicans/imunologia , Candida albicans/patogenicidade , Interações Hospedeiro-Patógeno , Receptores de Reconhecimento de Padrão/imunologia , Animais , Candida albicans/fisiologia , Células Dendríticas/imunologia , Células Dendríticas/microbiologia , Células Endoteliais/imunologia , Células Endoteliais/microbiologia , Células Epiteliais/imunologia , Células Epiteliais/microbiologia , Humanos , Hifas/imunologia , Hifas/patogenicidade , Hifas/fisiologia , Imunidade Inata , Camundongos , Fagócitos/imunologia , Fagócitos/microbiologia , Polimorfismo de Nucleotídeo Único , Receptores de Reconhecimento de Padrão/genética
20.
Artigo em Inglês | MEDLINE | ID: mdl-24974641

RESUMO

In order to identify early specific diagnostic antigens of Spirometra erinaceieuropaei (syn. S. erinacei or S. mansoni) sparganum, soluble proteins were analyzed by two-dimensional electrophoresis (2-DE) and western blotting probed with immune sera from infected mice at 14 days post-infection. From a total of approximately 462 proteins spots mainly distributed in pI range of 5-6.6 and with molecular mass of 25-48 kDa, 6 immuno-reactive protein spots with molecular mass of 31.8-38.3 kDa were characterized by MALDI-TOF/TOF-MS. Three proteins were identified as S. erinaceieuropaei cysteine protease, Toxoplasma gondii hypothetical protein and Pecten spp actin, while the remaining were unidentified. The cysteine protease from S. erinaceieuropaei soluble proteins recognized by early infection sera might be developed as diagnostic reagent for early detection of sparganosis.


Assuntos
Antígenos de Helmintos/imunologia , Proteínas de Helminto/imunologia , Proteômica/métodos , Esparganose/diagnóstico , Esparganose/imunologia , Plerocercoide/imunologia , Animais , Anticorpos Anti-Helmínticos/imunologia , Western Blotting , Eletroforese em Gel Bidimensional , Soros Imunes/imunologia , Imunoproteínas/imunologia , Camundongos , Peso Molecular , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
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