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1.
Hum Gene Ther ; 31(1-2): 103-109, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31802713

RESUMO

Liver fibrosis is a chronic liver disease that could further develop to cirrhosis and liver carcinoma. Hepatic stellate cells (HSCs) are primary effector cells to initiate liver fibrosis. We aimed to explore the function and underlying mechanisms of mitochondrial fusion protein Mitofusin-2 (MFN2) in liver fibrosis. First, we utilized an alpha-smooth muscle actin promoter to overexpress MFN2 specifically in HSCs using adeno-associated virus (AAV) vector (AAV-MFN2). Overexpression of MFN2 was specifically achieved in HSC-T6 cells, but not in murine bone marrow-derived macrophages or hepatocyte AML-12 cells. We found that high expression of MFN2 induced apoptosis of HSC-T6 cells. Mechanistically, we demonstrated that high level of MFN2 inhibited TGF-ß1/Smad signaling pathway, triggered downregulation of type I, type III, and type IV collagen, and antagonized the formation of factors associated with liver fibrosis. Furthermore, we found that overexpression of MFN2 using AAV-MFN2 ameliorated CCl4-induced liver fibrosis in vivo with significantly decreased immune cell infiltration. Taken together, our findings indicate that MFN2 is critical in regulating apoptosis and liver fibrosis in HSCs, which might be a useful therapeutic target to treat liver fibrosis.

2.
Clin Lab ; 65(12)2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31854959

RESUMO

BACKGROUND: The current study aims to detect the expression of miR-142-5p and T-cell lymphoma invasion and metastasis 1 (Tiam1) in colon cancer tissues and adjacent normal tissues, thereby exploring their association with clinical stage and lymph node metastasis of colon cancer. METHODS: Thirty specimens of colon cancer tissues and adjacent tissues were collected. The expressions of miR-142-5p and Tiam1 were detected by RT-PCR. The correlation between them and clinical pathology was analyzed using person correlation assay. RESULTS: The expression of miR-142-5p in colon cancer tissues (0.46 ± 0.25) was lower than that in adjacent tissues (1.00 ± 0.23), and the difference was statistically significant. The expression of Tiam1 gene in colon cancer tissues (5.46 ± 2.34) was higher than that in adjacent tissues (1.00 ± 0.43). There was a significant negative correlation between miR-142-5p and Tiam1 (r = -0.873, p < 0.01). The expression level of miR-142-5p (0.22 ± 0.07) in stage III and IV colon cancer tissues was significantly lower than that in stage I and II colon cancer tissues (0.71 ± 0.21, p < 0.05), while the expression level of Tiam1 mRNA (6.37 ± 1.98) in stage III and IV colon cancer tissues was significantly higher than that in stage I and II colon cancer tissues (2.86 ± 1.32, p < 0.05). Furthermore, the expression of miR-142-5p in colon cancer with lymph node metastasis was significantly lower than that in colon cancer without lymph node metastasis, while the expression of Tiam1 was contrary to that in colon cancer without lymph node metastasis. CONCLUSIONS: In summary, miR-142-5p and Tiam-1 may be potential diagnostic markers for colon cancer.


Assuntos
Colo/metabolismo , Neoplasias do Colo/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Proteínas de Ligação a RNA/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Colo/patologia , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/metabolismo , Feminino , Células HT29 , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Proteínas de Ligação a RNA/metabolismo
3.
Pharmazie ; 73(1): 42-48, 2018 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-29441950

RESUMO

AIMS: Long non-coding RNAs (lncRNAs) play key roles in cancers, yet their potential molecular mechanisms are not well understood. The objective of this study is to examine the expression, biological functions and mechanism of lncRNA CCAL in gastric cancer (GC). METHODS: MTT and Colony formation assay were used to detect cell proliferation and the colony formation ability of gastric cancer cells. Wound healing, Migration, and invasion assay were respectively used to explore the migration, and invasion in gastric cancer cell lines. Real-time polymerase chain reaction (RT-PCR) was performed to determine the expression level of CCAL. Western Blot was used to determine the expression of related proteins. RESULTS: In the present study, we found that CCAL was upregulated in gastric cancer cell lines. Patients whose tumors had high CCAL expression had a shorter overall survival than patients whose tumors had low CCAL expression. Overexpression CCAL promoted the proliferation, migration and invasion of GC by regulating the expression of myc. CONCLUSION: The present study reveals that CCAL is an oncogenic lncRNA that promotes the tumorigenesis and progression of GC.


Assuntos
Proliferação de Células/genética , Proteínas Proto-Oncogênicas c-myc/genética , RNA Longo não Codificante/genética , Neoplasias Gástricas/patologia , Linhagem Celular Tumoral , Movimento Celular , Progressão da Doença , Humanos , Invasividade Neoplásica/genética , Reação em Cadeia da Polimerase em Tempo Real , Neoplasias Gástricas/genética , Regulação para Cima , Cicatrização/genética
4.
Oncol Res ; 25(9): 1589-1599, 2017 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-28337962

RESUMO

Gastric cancer (GC) is one of the most common malignant tumors of the digestive system. The etiology of GC is complex, and much more attention should be paid to genetic factors. In this study, we explored the role and function of LINC00052 in GC. We applied qRT-PCR and Northern blot to detect the expression of LINC00052 and found it was highly expressed during GC. We also investigated the effects of LINC00052 on tumor prognosis and progression and found that LINC00052 indicated poor prognosis and tumor progression. By performing MTT, colony formation, and Transwell assays, we found that LINC00052 promoted MGC-803 cell proliferation and metastasis. Pull-down and RIP assays showed that LINC00052 could interact with ß-catenin and methyltransferase SMYD2, and immunoprecipitation detection showed that LINC00052 promoted ß-catenin methylation to maintain its stability, so as to activate the Wnt/ß-catenin pathway. Furthermore, XAV939 (inhibitor of ß-catenin) was used to treat MGC-803 cells, and we found that LINC00052 promoted proliferation and metastasis, possibly by activation of the Wnt/ß-catenin pathway. In conclusion, our research demonstrated a carcinogenic role for LINC000052 in GC, which may represent a new approach for the prevention and therapy of this cancer.


Assuntos
RNA Longo não Codificante/biossíntese , Neoplasias Gástricas/metabolismo , Via de Sinalização Wnt , Adulto , Linhagem Celular Tumoral , Proliferação de Células , Progressão da Doença , Feminino , Compostos Heterocíclicos com 3 Anéis/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , RNA Longo não Codificante/genética , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Transfecção , beta Catenina/antagonistas & inibidores
5.
Nutr Clin Pract ; 32(2): 258-265, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27589260

RESUMO

BACKGROUND: Previous studies have noticed the high incidence of suboptimal vitamin D (VtD) status and bone loss in short bowel syndrome (SBS) with parenteral nutrition (PN) dependence. However, limited data have focused on adult SBS without PN dependence. Therefore, our objective was to investigate the incidence and risk factors of suboptimal VtD status and bone loss in adult SBS even after weaning off PN. MATERIALS AND METHODS: We performed a prospective study of 60 adult patients with SBS. Serum 25-hydroxyvitamin D (25-OHD) was measured by radioimmunoassay. Bone mineral density (BMD) was measured using dual-energy x-ray absorptiometry (DEXA). Medical records and various laboratory parameters were collected in all participants. RESULTS: Suboptimal VtD status was identified in all individuals, including 3 (5.0%) with VtD insufficiency and 57 (95.0%) with VtD deficiency. Residual small bowel length (B, 0.072, P = .001) and duration of SBS (B, -0.066, P = .020) were both significantly correlated with suboptimal VtD levels. Overall, only 2 patients presented a normal BMD; osteopenia and osteoporosis were noted in 41 (68.3%) and 17 (28.3%) individuals, respectively. Low 25-OHD concentration was associated with a decreased BMD (B, 0.065, P = .029). There were no other demographic characteristics or clinical examinations associated with suboptimal VtD levels and bone loss. CONCLUSION: Suboptimal VtD status and bone loss were common in adult SBS even after weaning off PN. Despite routine oral VtD supplementation, most patients did not achieve satisfactory status. This emphasizes the critical importance of routine surveillance of 25-OHD and BMD, as well as consideration of alternative methods of supplementation after weaning off PN.


Assuntos
Doenças Ósseas/sangue , Doenças Ósseas/epidemiologia , Síndrome do Intestino Curto/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/epidemiologia , Vitamina D/sangue , Absorciometria de Fóton , Adulto , Densidade Óssea , Doenças Ósseas/etiologia , Suplementos Nutricionais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Nutrição Parenteral/efeitos adversos , Prevalência , Estudos Prospectivos , Fatores de Risco , Síndrome do Intestino Curto/terapia , Vitamina D/administração & dosagem , Deficiência de Vitamina D/etiologia , Adulto Jovem
6.
Mol Clin Oncol ; 5(1): 79-82, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27330771

RESUMO

Since its introduction as an alternative treatment technique, radiotherapy has been increasingly used as the medical treatment of choice for patients with malignant tumors. However, radiotherapy is associated with a number of common, well-described side effects, which may compromise the quality of life of the patients. Scrotal edema is an infrequent complication in patients who undergo pelvic irradiation, which is suspected to be due to lymphatic obstruction. An extensive literature search found no previous case report describing this complication in patients receiving pelvic radiotherapy. Herein, we present a case of recurrent scrotal edema in a 59-year-old man with prostate cancer and radiation enteritis. Conservative therapy was applied and was successful in relieving the symptoms. To the best of our knowledge, this is the first case report of scrotal edema in a patient with radiation enteritis.

7.
BMC Gastroenterol ; 16: 12, 2016 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-26822147

RESUMO

BACKGROUND: Fundamental researches suggest that ileum presents greater adaptive potential than the jejunum. However, few studies estimate the association between ileum and adaptive potential in human. To discover the association, we conducted this matched case-control study. METHODS: A 1:2 pair-matched, case-control study was conducted from January 1, 2001 to January 1, 2015 in Intestinal Rehabilition and Transplant Center. The case group was ileum predominated (IP) group and the control group was jejunum predominated (JP) group. Demographic data, medical history and progression of each patient were collected. RESULTS: There were 24 IP cases and 48 JP controls in this study. The cumulative probabilities of parenteral nutrition (PN) weaning in IP group were higher than that in JP group. The Bristol stool scale scores of IP group were lower than that of JP group at third month. The Cox proportional hazards regression model confirmed that IP had a higher odds of PN weaning (OR = 2.69; 95 % CI: 1.27, 5.70, p = 0.01) as compared with JP group. The conditional logistic regression with 1:2 matching also confirmed IP group had a higher odds (OR = 4.84; 95 % CI: 2.02, 11.56, p <0.01). CONCLUSIONS: Our results indicated that ileum presents greater adaptive potential than the jejunum in nutrition and fluid absorption. And a potential anatomic subtype of short bowel syndrome was proposed. Further research need to be conducted to more fully understand the adaptive potential of ileum besides nutrition and fluid absorption.


Assuntos
Adaptação Fisiológica/fisiologia , Íleo/fisiopatologia , Jejuno/fisiopatologia , Nutrição Parenteral/estatística & dados numéricos , Síndrome do Intestino Curto/fisiopatologia , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Síndrome do Intestino Curto/classificação , Síndrome do Intestino Curto/terapia , Desmame
8.
Eur J Trauma Emerg Surg ; 41(1): 99-105, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26038172

RESUMO

PURPOSE: Early enteral feeding within 24-48 h of intensive care unit admission is recommended for critically ill patients. This study aimed to determine if early enteral feeding could be safely implemented with purported benefits in patients with abdominal trauma. METHODS: A retrospective cohort study was performed that included 88 adult patients with abdominal trauma. Patients receiving enteral feeding within 72 h of surgical intensive care unit (SICU) admission (early-initiation group, n = 28) were compared to those receiving enteral feeding later (delayed-initiation group, n = 60). RESULTS: The two groups were comparable in demographic characteristics and injury severity. There were no differences in feeding intolerance (53.6 vs. 43.3%, p = 0.37) and mortality at 28 days (0 vs. 5%, p = 0.55) between the early-initiation group and the delayed-initiation group. However, patients in the early-initiation group had fewer infectious complications (17.9 vs. 40 %, p = 0.04) and shorter length of stay in SICU and hospital (p < 0.01) than patients in the delayed-initiation group. CONCLUSIONS: Early enteral feeding administered within 72 h of SICU admission was associated with improved clinical outcomes without risk of increasing feeding intolerance in patients with abdominal trauma. Our results support the implementation of early enteral feeding in abdominal trauma management.


Assuntos
Traumatismos Abdominais/terapia , Cuidados Críticos/métodos , Estado Terminal/terapia , Nutrição Enteral , Adulto , Ingestão de Energia , Nutrição Enteral/métodos , Medicina Baseada em Evidências , Feminino , Humanos , Masculino , Guias de Prática Clínica como Assunto , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
9.
Clin Lab ; 61(3-4): 371-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25975005

RESUMO

BACKGROUND: Chemotherapy-induced mucosal barrier dysfunction is of clinical interest. However, the assessment of mucosal barrier dysfunction still poses challenges. In this study, we compared several biomarkers with the dual sugar gut permeability test for assessing mucosal barrier dysfunction during chemotherapy. METHODS: Forty-two patients with gastric or colorectal cancer underwent chemotherapy, including FAM or FOLFOX4 regimens. Patients were asked to grade and record their symptoms of gastrointestinal toxicity daily. The urinary lactulose-mannitol ratio was measured to assess the intestinal permeability. Plasma levels of citrulline, diamine oxidase (DAO), D-lactic acid, and endotoxin were also measured. Intestinal permeability was observed in the subgroup of patients with diarrhea or constipation. RESULTS: The urinary lactulose-mannitol ratio and plasma citrulline levels increased on the third and sixth post-chemotherapy days, respectively. There were no significant differences in the plasma levels of D-lactic acid, endotoxin or DAO activity compared to their levels before chemotherapy. The urinary lactulose-mannitol ratio in diarrhea patients was significantly higher than in constipation patients. CONCLUSIONS: These results indicate that the urinary lactulose-mannitol ratio and plasma citrulline level are appropriate biomarkers for assessing mucosal barrier dysfunction in patients receiving chemotherapy. Mucosal barrier dysfunction in diarrhea patients was greater than in constipation patients.


Assuntos
Antineoplásicos/efeitos adversos , Biomarcadores/sangue , Neoplasias Colorretais/sangue , Neoplasias Colorretais/complicações , Mucosa Intestinal/patologia , Neoplasias Gástricas/sangue , Neoplasias Gástricas/complicações , Adulto , Idoso , Amina Oxidase (contendo Cobre)/sangue , Citrulina/sangue , Neoplasias Colorretais/tratamento farmacológico , Endotoxinas/metabolismo , Feminino , Humanos , Absorção Intestinal , Mucosa Intestinal/metabolismo , Ácido Láctico/sangue , Masculino , Pessoa de Meia-Idade , Permeabilidade , Neoplasias Gástricas/tratamento farmacológico , Fatores de Tempo
10.
Indian J Surg ; 77(Suppl 3): 1154-8, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27011528

RESUMO

Prosthetic mesh used for ventral incisional hernia makes hernia repair surgery simple, effective, and safe. The mesh infection is a formidable complication and bimodal distribution. The differences between early- and late-onset are unknown. This is a cohort study of patients undergoing ventral incisional hernia (VIH) repair from January 2003 to September 2013. Data of specific risk variables were collected from electronic medical record systems in Jinling Hospital. And, the quality of lives was evaluated by WHO Quality of Life-BREF. A total of 102 VIH repair patients were analyzed and followed including the noninfection group and early- and late-onset group. There were significant differences between the early- and late-onset group in clinical manifestation, descriptive analysis of the study population, and postoperative quality of lives. These differences might imply the different pathophysiologic process of early- and late-onset mesh infection. Permanent prosthetic mesh should be used with caution, and the study of intraperitoneal onlay mesh is still needed in long-term follow-up.

11.
Nutr Clin Pract ; 29(5): 656-61, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24920224

RESUMO

BACKGROUND: Published experience in feeding patients with enteroatmospheric fistulae is scarce. This study aimed to determine if enteral nutrition (EN) could be safely delivered in the presence of enteroatmospheric fistula. MATERIALS AND METHODS: This is a retrospective descriptive study from a major fistula treatment center in China. Medical records of patients who developed enteroatmospheric fistulae in the open abdomen after abdominal trauma were reviewed. The timing of initiation and achievement of full strength (25 kcal/kg/d) EN after enteroatmospheric fistula were noted, as well as the incidence of feeding-associated complications and weaning of parenteral nutrition (PN). The outcomes of open abdomen and enteroatmospheric fistula were also noted. RESULTS: Nine patients were included in this study. EN was successfully implemented in all patients. The median timing of initiation and achievement of full strength of EN after enteroatmospheric fistula was 9 (interquartile range [IQR], 3­22) and 27 (IQR, 22­43) days, respectively. Feeding-associated complications developed in 1 (11.1%) patient. All patients were liberated from PN at hospital discharge. Split-thickness skin grafting was performed in all patients, of whom 5 underwent successful delayed abdominal closure, and 4 were awaiting definitive closure. Repair or resection of enteroatmospheric fistula occurred in 8 (88.9%) patients. CONCLUSION: This study showed that EN could be safely implemented in patients with enteroatmospheric fistulae without complicating the treatment of open abdomen and enteroatmospheric fistula.


Assuntos
Abdome/patologia , Nutrição Enteral , Fístula Intestinal/terapia , Pele/patologia , Cicatrização , Abdome/cirurgia , Adulto , China , Nutrição Enteral/efeitos adversos , Feminino , Fístula , Humanos , Fístula Intestinal/cirurgia , Masculino , Pessoa de Meia-Idade , Nutrição Parenteral Total , Estudos Retrospectivos , Transplante de Pele , Adulto Jovem
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