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1.
J Reconstr Microsurg ; 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38499044

RESUMO

BACKGROUND: Oral cavity cancers requiring excision of the oral commissure and free flap reconstruction often requires commissuroplasty to manage oral incontinence. We aimed to evaluate the implications of primary versus delayed commissuroplasty on drooling, and interincisal distance outcomes in this cohort. METHODS: A retrospective query of head and neck cancer patients operated by a single surgeon from 2017 to 2020 was performed. Patients were included if they underwent free flap reconstruction of the oral commissure, had an immediate or delayed commissuroplasty, and had 2 years of follow-up data including Thomas-Stonell and Greenberg drooling rating scales and interincisal distance measurements. RESULTS: Thirty-five patients were included in the review. Twelve patients received immediate commissuroplasty and 23 patients had delayed commissuroplasty. Interincisal distance was similar at baseline, although significantly varied between immediate and delayed commissuroplasty groups at 1 month and 2 years postoperative. Drooling scores were significantly elevated in the group treated with delayed commissuroplasty, but eventually normalized after staged surgery and follow-up. Patients treated with adjunct radiation therapy had lower interincisal distance than patients who did not have radiation. CONCLUSION: Delayed commissuroplasty increased interincisal distance and normalize drooling in patients who required full-thickness excision of the buccal mucosa and oral commissure and free tissue reconstruction. The presented data can help to educate patients on expected postoperative outcomes and likely advocates for a second-stage procedure after completion of adjunct radiotherapy to achieve optimal commissural placement and oral competence.

2.
J Nanobiotechnology ; 20(1): 220, 2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36310171

RESUMO

BACKGROUND: Glucocorticoids (GCs) overuse is associated with decreased bone mass and osseous vasculature destruction, leading to severe osteoporosis. Platelet lysates (PL) as a pool of growth factors (GFs) were widely used in local bone repair by its potent pro-regeneration and pro-angiogenesis. However, it is still seldom applied for treating systemic osteopathia due to the lack of a suitable delivery strategy. The non-targeted distribution of GFs might cause tumorigenesis in other organs. RESULTS: In this study, PL-derived exosomes (PL-exo) were isolated to enrich the platelet-derived GFs, followed by conjugating with alendronate (ALN) grafted PEGylated phospholipid (DSPE-PEG-ALN) to establish a bone-targeting PL-exo (PL-exo-ALN). The in vitro hydroxyapatite binding affinity and in vivo bone targeting aggregation of PL-exo were significantly enhanced after ALN modification. Besides directly modulating the osteogenic and angiogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and endothelial progenitor cells (EPCs), respectively, PL-exo-ALN also facilitate their coupling under GCs' stimulation. Additionally, intravenous injection of PL-exo-ALN could successfully rescue GCs induced osteoporosis (GIOP) in vivo. CONCLUSIONS: PL-exo-ALN may be utilized as a novel nanoplatform for precise infusion of GFs to bone sites and exerts promising therapeutic potential for GIOP.


Assuntos
Exossomos , Células-Tronco Mesenquimais , Osteoporose , Humanos , Exossomos/metabolismo , Glucocorticoides/metabolismo , Células-Tronco Mesenquimais/metabolismo , Osteogênese , Osteoporose/induzido quimicamente , Osteoporose/tratamento farmacológico , Alendronato/farmacologia
4.
J Cardiovasc Transl Res ; 15(4): 816-827, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35040081

RESUMO

Microglia/macrophage activation plays an essential role in Ischemic stroke (IS). Nuclear receptor corepressor 1 (NCoR1) has been identified as a vital regulator in macrophages. The present study aims to explore the functions of macrophage NCoR1 in IS. Macrophage NCoR1 knockout (MNKO) mice and littermate control mice were subjected to middle cerebral artery occlusion (MCAO). Our data showed that macrophage NCoR1 deficiency significantly reduced the infarct size and infarct volume as well as brain edema after MCAO. Additionally, MNKO induced less microglia/macrophage infiltration and activation, neuroinflammation, apoptosis of neuronal cells, and BBB disruption in brains after IS. Mechanistic studies revealed that NCoR1 interacted with LXRß in microglia and MNKO impaired the activation of the Nuclear factor-κB signaling pathway in brains after IS. Our data demonstrated that macrophage NCoR1 deficiency inhibited microglia/macrophage activation and protected against IS. Targeting NCoR1 in microglia/macrophage may be a potential approach for IS treatment.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Camundongos , Animais , Camundongos Endogâmicos C57BL , Macrófagos/metabolismo , Infarto da Artéria Cerebral Média/genética , Camundongos Knockout , Acidente Vascular Cerebral/genética , Acidente Vascular Cerebral/prevenção & controle , Correpressor 1 de Receptor Nuclear/genética
5.
Zhonghua Nan Ke Xue ; 28(1): 26-31, 2022 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-37459074

RESUMO

Objective: To investigate the sexual behavior and sexual function of the male partners of breast cancer patients and their potential relationship with socio-demographic and clinical variables. METHODS: In this cross-sectional study, we conducted an investigation among 196 male partners (aged 23-59 years) of breast cancer patients between May 2020 and October 2020. We completed the Male Sexual Function Questionnaire (BSFI) by online and telephone interview with the subjects and collected relevant socio-demographic and clinical variables. RESULTS: The average age of the interviewees was (46.13 ± 7.75) years old, and the mean duration of the patients' breast cancer was (1.58 ± 0.48) years at the time of the investigation. The incidence rate of sexual dysfunction in the male partners of the patients was dramatically higher after the onset of breast cancer than before it (49.76% vs 9.68%, P < 0.01). Low libido was found to be the main type of sexual dysfunction (38.3%) among the male subjects, with an even high incidence rate among those whose wives received mastectomy (OR = 5.533, P = 0.017, 95% CI: 1.366-22.412) and radiotherapy (OR = 3.439, P < 0.044, 95% CI: 1.058-11.171) and significantly correlated with age (OR = 1.134, P = 0.001, 95% CI: 1.053-1.222). CONCLUSIONS: Breast cancer and its treatment methods may affect the sexual function of the male partners of the patients. It is necessary for doctors to pay attention to the factors affecting the sexual function of the patients and their partners so as to take appropriate intervention measures.

6.
Anal Chem ; 93(48): 15931-15940, 2021 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-34780171

RESUMO

Alterations of protein glycosylation are closely related with pathophysiological regulation. Due to the structural macro- and microheterogeneity, low stoichiometry, and low ionization efficiency of glycopeptides, high-performance tools to enrich glycopeptides, especially the negatively charged and labile sialoglycopeptides, are essential to enhance the identification of the underexplored glycoproteome. Here, we present the first implementation of zwitterionic hydrophilic interaction chromatography with the exposed choline group (ZIC-cHILIC) in StageTip for simultaneous enrichment and fractionation of intact glycopeptides. In a model study using lung cancer cells, early elution by a high percentage of acetonitrile prominently prefilters nonglycopeptides, facilitating high enrichment specificity for glycopeptides (92-96%) and sialoglycopeptides (77-89%) in the subsequent hydrophilic fractions. The stepwise elution shows a high glycopeptide fractionation efficiency by a <10% overlap of glycopeptides between adjacent fractions. Most importantly, the ZIC-cHILIC stepwise strategy demonstrated good reproducibility (>80% in triplicate analysis) as well as superior coverage of 4.6- to 12.0-fold and 2.1- to 35.6-fold more glycopeptides and sialoglycopeptides compared to conventional TiO2 and ZIC-HILIC, respectively. To the best of our knowledge, the result with 2742 sialoglycopeptides among 7367 unique glycopeptides and 166 glycans from 2434 N-glycosites of 1118 glycoproteins (Byonic score > 100) provides one of the deepest glycoproteomic profiles in single-cell type. Without the immunoprecipitation step, the large-scale glycoproteomic atlas also reveals site-specific glycosylation of many druggable receptor proteins, such as EGFR, MET, ERBB2, ERBB3, AXL, and IGF1R. The demonstrated high enrichment specificity and identification depth show that stepwise ZIC-cHILIC is an efficient method to explore the under-represented sialoglycoproteome.


Assuntos
Glicopeptídeos , Proteoma , Glicoproteínas , Glicosilação , Interações Hidrofóbicas e Hidrofílicas , Reprodutibilidade dos Testes
7.
J Cell Physiol ; 236(3): 1939-1949, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32730652

RESUMO

Osteoarthritis (OA) is a degenerative joint disease characterized by destruction of articular cartilage. The inflammatory response is the most important factor affecting the disease process. As interleukin-1ß (IL-1ß) stimulates several key mediators in the inflammatory response, it plays a major role in the pathogenesis of OA. Maslinic acid (MA) is a natural compound distributed in olive fruit. Previous studies have found that maslinic acid has an inhibitory effect on inflammation, but its specific role in the progression of OA disease has not been studied so far. In this study, we aim to assess the protective effect of MA on OA progression by in vitro and in vivo experiments. Our results indicate that, in IL-1ß-induced inflammatory response, MA is effective in attenuating some major inflammatory mediators such as nitric oxide (NO) and prostaglandin E2, and inhibits the expression of IL-6, inducible nitric oxide synthase, cyclooxygenase-2, and tumor necrosis factor-α (TNF-α) in a concentration-dependent manner. Also, MA downregulated the expression levels of thrombospondin motif 5 (ADAMTS5) and matrix metalloproteinase 13 in chondrocytes, resulting in reduced degradation of its extracellular matrix. Mechanistically, MA exhibits an anti-inflammatory effect by inactivating the PI3K/AKT/NF-κB pathway. In vivo, the protective effect of MA on OA development can be detected in a surgically induced mouse OA model. In summary, these findings suggest that MA can be used as a safe and effective potential OA therapeutic strategy.


Assuntos
Inflamação/prevenção & controle , NF-kappa B/metabolismo , Osteoartrite/tratamento farmacológico , Osteoartrite/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Triterpenos/uso terapêutico , Idoso , Animais , Sobrevivência Celular/efeitos dos fármacos , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Condrócitos/patologia , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Modelos Animais de Doenças , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/metabolismo , Feminino , Humanos , Inflamação/complicações , Interleucina-1beta/efeitos adversos , Interleucina-6/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Modelos Biológicos , Inibidor de NF-kappaB alfa/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Transporte Proteico/efeitos dos fármacos , Proteólise/efeitos dos fármacos , Fator de Transcrição RelA/metabolismo , Triterpenos/química , Triterpenos/farmacologia , Fator de Necrose Tumoral alfa/metabolismo
8.
J Exp Clin Cancer Res ; 39(1): 115, 2020 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-32552756

RESUMO

An amendment to this paper has been published and can be accessed via the original article.

9.
J Exp Clin Cancer Res ; 39(1): 79, 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32381034

RESUMO

BACKGROUND: The poor prognosis of patients with ovarian cancer is mainly due to cancer progression. γ-Synuclein (SNCG) has reported as a critical player in cancer metastasis. However, its biological roles and mechanism are yet incompletely understood in ovarian cancer, especially in high-grade serous ovarian cancer (HGSOC). METHODS: This is a retrospective study of 312 patients with ovarian cancer at a single center between 2006 and 2016. Ovarian cancer tissues were stained by immunohistochemistry to analyze the relationship between SNCG expression and clinicopathologic factors. The clinical outcomes versus SNCG expression level were evaluated by Kaplan-Meier method and multiple Cox regression analysis. Next, systematical functional experiments were given to examine the proliferation and metastatic abilities of SNCG both in vitro and in vivo using loss- and gain- of function approaches. Furthermore, the mechanisms of SNCG overexpression were examined by human phospho-kinase array kit and western blot analysis. RESULTS: Clinically, the expression of SNCG was significantly upregulated in ovarian cancer compared with the borderline and benign tumor, normal ovary, and fallopian tube. Notably, the high level of SNCG correlated with high-risk clinicopathologic features and showed poor survival for patients with HGSOC, indicating an independent prognostic factor for these patients. Functionally, we observed that overexpression of SNCG promoted cell proliferation, tumor formation, migration, and invasion both in vitro and in vivo. Mechanistically, we identified that SNCG promoted cancer cell metastasis through activating the PI3K/AKT signaling pathway. CONCLUSIONS: Our results reveal SNCG up-regulation contributes to the poor clinical outcome of patients with HGSOC and highlight the metastasis-promoting function of SNCG via activating the PI3K/Akt signaling pathway in HGSOC.

10.
Am J Case Rep ; 18: 589-592, 2017 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-28550278

RESUMO

BACKGROUND Torsion of an intra-abdominal lipoma is rarely the cause of acute abdominal pain. Most of the previously reported cases of intra-abdominal lipoma torsion originated in the mesentery or omentum. However, an antimesenteric lipoma of the ileum with torsion has not been reported before. CASE REPORT A 67-year-old man presented to the emergency department with acute abdominal pain. Contrast-enhanced computed tomography (CECT) of the abdomen and pelvis only showed a giant fat-containing, soft-tissue, intra-abdominal tumor, suspected to be a lipoma. Laparotomy was performed, and the presence of torsion of the antimesenteric lipoma of the ileum was confirmed. Beside tumor resection, en bloc segmental resection of the ileum with end-to-end anastomosis was performed to avoid bowel stricture and obtain tumor-free margins. CONCLUSIONS CECT is the modality of choice to detect an intra-abdominal lipoma. Urgent surgical intervention should be considered if the symptoms persist and torsion cannot be excluded. If simple excision is not adequate because of poor accessibility of the tumor stalk, en bloc segmental resection with end-to-end anastomosis should be considered.


Assuntos
Dor Abdominal/etiologia , Dor Aguda/etiologia , Neoplasias do Íleo/patologia , Lipoma/patologia , Anormalidade Torcional/patologia , Idoso , Humanos , Neoplasias do Íleo/cirurgia , Lipoma/cirurgia , Masculino , Anormalidade Torcional/cirurgia
11.
Cancer Lett ; 383(1): 73-84, 2016 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-27693633

RESUMO

The epithelial-mesenchymal transition (EMT) plays a crucial role in pancreatic ductal adenocarcinoma (PDAC) development and progression. TWIST activated by intra-tumoral hypoxia functions to promote the EMT. We hypothesized that TWIST and the downstream gene pathway could mediate PDAC progression under hypoxia. Therefore, 90 PDAC tissue specimens were immunostained for TWIST and other proteins. Pancreatic cancer cell lines were used for in vitro experiments and nude mice were used to confirm the in vivo data. Expression of TWIST and HIF-1α proteins was significantly upregulated, whereas expression of E-cadherin and p16 was down-regulated in PDAC tissues compared to that of non-tumor tissues and in tumor tissues obtained from patients with tumor involving splenic artery than those without splenic artery involvement. Up-regulated TWIST in tumor tissues were associated with worse prognosis in PDAC patients. The in vitro data showed that HIF-1α-induced TWIST overexpression promoted tumor cell growth and EMT under a hypoxic condition via TWIST interaction with Ring1B and EZH2. In vivo data showed that TWIST overexpression or a hypoxic condition induce xenograft growth, abdominal metastasis and low mouse survival, whereas knockdown of either Ring1B or EZH2 expression suppressed tumor xenograft growth and metastasis and prolonged survival of nude mice. TWIST was the key player in promotion of pancreatic cancer development and metastasis under a hypoxic condition through interaction with Ring1B and EZH2 to regulate expression of E-cadherin and p16 proteins in pancreatic cancer cells.


Assuntos
Proliferação de Células , Transição Epitelial-Mesenquimal , Proteínas Nucleares/metabolismo , Neoplasias Pancreáticas/metabolismo , Hipóxia Tumoral , Proteína 1 Relacionada a Twist/metabolismo , Neoplasias Abdominais/genética , Neoplasias Abdominais/metabolismo , Neoplasias Abdominais/secundário , Idoso , Animais , Antígenos CD , Sítios de Ligação , Caderinas/genética , Caderinas/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Inibidor p16 de Quinase Dependente de Ciclina/genética , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Células HEK293 , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica , Proteínas Nucleares/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Complexo Repressor Polycomb 1/genética , Complexo Repressor Polycomb 1/metabolismo , Regiões Promotoras Genéticas , Interferência de RNA , Transdução de Sinais , Fatores de Tempo , Transfecção , Carga Tumoral , Proteína 1 Relacionada a Twist/genética , Regulação para Cima
12.
Artigo em Chinês | MEDLINE | ID: mdl-23755793

RESUMO

OBJECTIVE: To investigate the incidence and severity of pulmonary function impairment in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). METHODS: In this prospective study, fifty-six patients with bilateral CRSwNP who were scheduled for functional endoscopic sinus surgery during a period from March to June 2010 in the Department of Otolaryngology of Qilu Hospital, were recruited in this study. Routine medical and rhinological examinations such as nasal endoscopy, sinus CT scan, and skin prick tests (SPT) for common inhalant and food allergens, and cytological examination of the paraffin-embedded NP tissues were performed together with a full assessment of the pulmonary functions. RESULTS: Based on the pulmonary function tests, the rate of patients showing bronchial hyperresponsiveness (BHR), asthma, and abnormal pulmonery functions were 37.5%, 44.6%, and 53.6%. In patients who did not have a history of lower airway symptoms, the rate of abnormal pulmonary functions was 50.0%, the rate of BHR was 43.2%. There was an increased rate of BHR, asthma and abnormal pulmonary functions in patients with a higher polyp grading score or Lund Mackay CT scan score (polyp grading score: χ(2) were 8.077, 3.989 and 7.445, P < 0.01 or < 0.05. CT scan score: χ(2) were 3.863, 5.380 and 4.309; 4.293, 4.293 and 4.572; 10.572, 13.504 and 13.295, P < 0.01 or < 0.05). The rate of BHR and asthma in patients with positive SPT were higher (P < 0.05). In patients with eosinophils hyperplasia in nasal polyps, the rate of BHR, asthma and abnormal pulmonary functions were higher (χ(2) were 4.065, 5.217 and 3.376, P < 0.05 or P < 0.01). CONCLUSIONS: There is a high risk of developing lower airway diseases in patients with CRSwNP.


Assuntos
Pulmão/fisiopatologia , Pólipos Nasais/fisiopatologia , Sinusite/fisiopatologia , Adolescente , Adulto , Asma/epidemiologia , Doença Crônica , Eosinófilos/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pólipos Nasais/complicações , Estudos Prospectivos , Testes de Função Respiratória , Sinusite/complicações , Adulto Jovem
13.
Artigo em Chinês | MEDLINE | ID: mdl-23141393

RESUMO

OBJECTIVE: To investigate the effects of sIL-5Rα and sIL-13Rα2 on VCAM-1 and IFN-γ in allergic rhinitis rats. METHODS: A total of 50 Wistar rats were randomly divided into 5 groups: the normal group (group A), the allergic rhinitis model group (group B), the sIL-5Rα treatment group (group C), the sIL-13Rα2 treatment group (group D), the combination of sIL-5Rα and sIL-13Rα2 treatment group (group E or the combined treatment group). Rats in the latter 4 groups were sensitized with ovalbumin (OVA) and Al(OH)(3), and challenged with OVA to establish allergic rhinitis models, while rats in the normal group were treated with saline. Rats in the sIL-5Rα treatment group, the sIL-13Rα2 treatment group and the combined treatment group were absorbed on day 31 to day 38 once daily once nasal cavity with sIL-5Rα(100 µg), sIL-13Rα2 (100 µg) and the combination of sIL-5Rα (100 µg) and sIL-13Rα2 (100 µg) 30 min before challenged, while rats in the allergic rhinitis model group received PBS(50 µl). Then the levels of VCAM-1 and IFN-γ in serum and nasal lavage fluid (NLF) were measured by ELISA. RESULTS: Compared with the normal group, the levels of VCAM-1 in the allergic rhinitis model group were higher, while IFN-γ were lower (all P < 0.01). Compared with the allergic rhinitis model group, the sIL-5Rα treatment group, the sIL-13Rα2 treatment group and the combined treatment group could effectively reduced serum and NLF VCAM-1 level [group E: (283.5 ± 5.7) µg/L, (101.8 ± 4.8) µg/L; group C: (311.5 ± 12.6) µg/L, (133.9 ± 5.8) µg/L; group D: (304.7 ± 6.6) µg/L, (128.5 ± 7.7) µg/L], and increased IFN-γ level [group E: (874.7 ± 9.6) pg/ml, (349.2 ± 12.1) pg/ml; group C: (600.2 ± 16.1) pg/ml, (195.5 ± 16.1) pg/ml; group D: (577.9 ± 9.6) pg/ml, (196.7 ± 9.9) pg/ml ]; compared with single treatment, the combined treatment group also had significant differences(P < 0.01). CONCLUSIONS: Combined treatment with sIL-5Rα and sIL-13Rα2 to treat the allergic rhinitis rats can significantly reduce VCAM-1 levels in serum and NLF, and increase IFN-γ levels, thus, to achieve the purpose of mitigation and treatment of allergic rhinitis.


Assuntos
Interferon gama/sangue , Receptores de Interleucina-13/uso terapêutico , Receptores de Interleucina-5/uso terapêutico , Rinite Alérgica Perene/metabolismo , Rinite Alérgica Perene/terapia , Molécula 1 de Adesão de Célula Vascular/sangue , Animais , Masculino , Ratos , Ratos Wistar , Rinite Alérgica
14.
Artigo em Chinês | MEDLINE | ID: mdl-21575417

RESUMO

OBJECTIVE: To explore the feasibility of laryngeal function preservation in surgical treatment of hypopharyngeal carcinoma with restrained vocal cord motility. METHODS: Twenty-six cases of hypopharyngeal carcinoma treated with conservative hypopharyngectomy were retrospectively analyzed. Partial resection of pyriform sinus and partial laryngectomy were performed. Suturing the remaining hypopharyngeal mucosa was used to cove the wound of hypopharynx in 5 cases, epiglottis complex flap in 21 cases. All patients received postoperative radiotherapy. RESULTS: The overall 3- and 5-year survival rates were 61.4% and 50.8% respectively. 76.9% (20/26) patients have laryngeal functions (voice, respiration and deglutition) completely restored and 23.1% (6/26) partially restored (voice and deglutition). CONCLUSIONS: To improve the quality of life of the cases, the preservative surgery is feasible for the selected hypopharyngeal carcinoma cases with restrained vocal cord motility.


Assuntos
Neoplasias Hipofaríngeas/cirurgia , Prega Vocal/fisiopatologia , Idoso , Feminino , Humanos , Neoplasias Hipofaríngeas/complicações , Laringectomia , Masculino , Pessoa de Meia-Idade , Transtornos dos Movimentos/complicações , Faringectomia , Estudos Retrospectivos
15.
Artigo em Chinês | MEDLINE | ID: mdl-21429339

RESUMO

OBJECTIVE: To investigate the effects of intranasal interferon gamma (IFN-γ) on nasal mucosa remodeling and expression of transforming growth factor-ß1 (TGF-ß1), Smad2, Smad3, Smad7 in allergic rhinitis (AR) rat model. METHODS: Ovalbumin (OVA) and aluminum hydroxide were used to construct the AR model. Thirty AR rats were randomly divided into positive control group (group B, n = 10), IFN-γ treatment group (group C, n = 10) and negative control group (normal rats, n = 10). After the AR models were built, 50 µl PBS, 1 µg IFN-γ was dropped into the nasal cavity of each rat in group B and group C, from the fouth week to tenth week, twice a week. The nasal mucosa was collected on day 71 in order to observe the pathologic changes, and the expression of TGF-ß1, TGF-ß1 mRNA, Smad2 mRNA, Smad3 mRNA and Smad7 mRNA by immunohistochemistry and reverse transcriptase-polymerase chain reaction. RESULTS: Decreases of TGF-ß1, Smad2 and Smad3 mRNA were seen in nasal tissue of group C (0.59 ± 0.04, 0.39 ± 0.08, 0.46 ± 0.15) as compared with group B (0.82 ± 0.12, 0.70 ± 0.18, 0.95 ± 0.26), the differences were significant (q value were 3.15, 4.47, 3.03, all P < 0.05). The levels of Smad7 mRNA expression increased significantly (q = 2.98, P < 0.05) in group C (0.31 ± 0.05) as compared with group B (0.25 ± 0.06). Immunohistochemistry showed significant decrease of TGF-ß1 expression in the nasal tissue of group C much lesser than that in group B. CONCLUSIONS: Intranasal IFN-γ could decrease the expression of TGF-ß1, TGF-ß1 mRNA, Smad2 mRNA, Smad3 mRNA, increase the expression of Smad7 mRNA in AR rats model and inhibit the nasal mucosa remodeling.


Assuntos
Interferon gama/farmacologia , Mucosa Nasal/efeitos dos fármacos , Rinite Alérgica Perene/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Animais , Modelos Animais de Doenças , Feminino , Interferon gama/administração & dosagem , Masculino , Cavidade Nasal , Mucosa Nasal/metabolismo , Mucosa Nasal/patologia , Ratos , Ratos Wistar , Rinite Alérgica Perene/patologia , Transdução de Sinais , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo , Proteína Smad7/metabolismo
16.
BMC Cancer ; 10: 552, 2010 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-20939933

RESUMO

BACKGROUND: Fibronectin (FN) is known to be a large multifunction glycoprotein with binding sites for many substances, including N-terminal and C-terminal heparin-binding domains. We investigated the effects of highly purified rhFNHN29 and rhFNHC36 polypeptides originally cloned from the two heparin-binding domains on the adhesion and invasion of highly metastatic human hepatocellular carcinoma cells (MHCC97H) and analyzed the underlying mechanism involved. METHODS: The MHCC97H cells that adhered to FN in the presence of various concentrations of rhFNHN29 and rhFNHC36 polypeptides were stained with crystal violet and measured, and the effects of rhFNHN29 and rhFNHC36 on the invasion of the MHCC97H cells were then detected using the Matrigel invasion assay as well as a lung-metastasis mouse model. The expression level of integrins and focal adhesion kinase (FAK) phosphotyrosyl protein was examined by Western blot, and the activity of matrix metalloproteinases (MMPs) and activator protein 1 (AP-1) was analyzed by gelatin zymography and the electrophoretic mobility band-shift assay (EMSA), respectively. RESULTS: Both of the polypeptides rhFNHN29 and rhFNHC36 inhibited adhesion and invasion of MHCC97H cells; however, rhFNHC36 exhibited inhibition at a lower dose than rhFNHN29. These inhibitory effects were mediated by integrin αvß3 and reversed by a protein tyrosine phosphatase inhibitor. Polypeptides rhFNHN29 and rhFNHC36 abrogated the tyrosine phosphorylation of focal adhesion kinase (p-FAK) and activation of activator protein 1 (AP-1), resulting in the decrease of integrin αv, ß3 and ß1 expression as well as the reduction of MMP-9 activity. CONCLUSIONS: Polypeptides rhFNHN29 and rhFNHC36 could potentially be applicable to human liver cancer as anti-adhesive and anti-invasive agents.


Assuntos
Fibronectinas/química , Heparina/química , Neoplasias Hepáticas/patologia , Peptídeos/química , Animais , Carcinoma Hepatocelular/metabolismo , Adesão Celular , Linhagem Celular Tumoral , Colágeno/química , Combinação de Medicamentos , Glicoproteínas/química , Humanos , Laminina/química , Neoplasias Hepáticas/metabolismo , Masculino , Camundongos , Camundongos Nus , Invasividade Neoplásica , Metástase Neoplásica , Estrutura Terciária de Proteína , Proteoglicanas/química
17.
Artigo em Chinês | MEDLINE | ID: mdl-20079073

RESUMO

OBJECTIVE: To study the voice function rehabilitation by mucosa tube performed in operation of late laryngocarcinoma and to improve the survival quality of patients with late laryngocarcinoma. METHODS: Forty-six patients were treated between Oct. 1991 and May 2006, including 41 males and 5 females. The average age of the patients was 54. Seventeen cases were glottic carcinomas (T3N0M0 12, T3N1M0 5), 27 cases were supraglottic carcinomas (T3N1M0 16, T4N1M0 5, T3N0M0 6), 2 cases were pyriform sinus cancer (T4N1M0 2). For those patients with late laryngocarcinoma, who had lost the chance of partial laryngectomy, mucosa tube shaping during the operation could realize voice functional rehabilitation. Only the survive arytenoids of healthy side was preserved, in order to rehabilitate voice, a mucosa tube was sutured using healthy survive arytenoids and a mucosa strip was connected to the trachea and the mucosa of hypopharynx. Survival analysis was performed by using Kaplan-Meier method. RESULTS: Forty-one out of 46 patients obtained almost normal voice and swallow function. The 5-years survival was 76%. CONCLUSIONS: The operation of voice function rehabilitation by mucosa tube performed can get good voice and swallow function to patients with late laryngo carcinoma.


Assuntos
Neoplasias Laríngeas , Laringectomia , Cartilagem Aritenoide/cirurgia , Humanos , Neoplasias Laríngeas/cirurgia , Mucosa , Análise de Sobrevida
18.
Artigo em Chinês | MEDLINE | ID: mdl-18510219

RESUMO

OBJECTIVE: To investigate the effects and mechanism of intranasal interferon gamma (IFN-gamma) in the treatment of allergic rhinitis. METHODS: Ovalbumin (OVA) absorbed to aluminum hydroxide was used to construct the allergic rhinitis model (group C), and the normal control group (group A), the allergic rhinitis model group (group B) and beclomethasone dipropionate group (group D) consisted of 8 rats for each. PBS 50 microl was absorbed to group B, IFN-gamma 1 microg was absorbed to group C and beclomethasone dipropionate 3.5 microg was absorbed to group D on day 31 to day 38 once daily once nasal cavity. The nasal lavage fluid was collected on day 39, and the cellular constituents, levels of interleukin-4 (IL-4), interleukin-5 (IL-5) and IgE were determined, together with the pathologic changes and expression of GATA-3 were observed. RESULTS: Decrease of eosinophils [(0.005 +/- 0.003) x 10(4)/ml, x +/- s] was seen in nasal lavage fluid of group C as comparing with group B [(0.225 +/- 0.060) x 10(4)/ml, (P < 0.01)], and the levels of IL-4 (7.8 +/- 3.5) pg/ml and IL-5 (12.5 +/- 4.3) pg/ml decreased significantly in comparing with group B (P < 0.01). The serum levels of total IgE (38.5 +/- 9.6) microg/ml and ovalbumin-specific IgE (19.8 +/- 5.4) IU/ml decreased significantly in comparing with those of group B (P < 0.01). In group B, mucosal congestion and edema thickening with inflammatory cells infiltration mainly of eosinophils; in group C, the above mentioned changes were much more ameliorated. Immunohistochemistry showed significant increase of GATA-3 expression in the nasal tissue of group B but much lesser than that in group C. CONCLUSIONS: IFN-gamma can inhibit the composition of IL-4 and IL-5, and inhibit the airway inflammation with eosinophilic infiltration and the serum levels of total IgE and ovalbumin specific IgE, probably through the mechanism of restraining the Th2 reaction by blockade of GATA-3 expression in the nasal tissue.


Assuntos
Interferon gama/uso terapêutico , Rinite Alérgica Perene/tratamento farmacológico , Animais , Eosinófilos/imunologia , Feminino , Imunoglobulina E/sangue , Interferon gama/administração & dosagem , Interleucina-4/imunologia , Interleucina-5/imunologia , Masculino , Cavidade Nasal/imunologia , Ratos , Ratos Wistar , Rinite Alérgica Perene/metabolismo
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