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1.
Animal Model Exp Med ; 5(1): 72-80, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35229996

RESUMO

BACKGROUND: Porcine pancreatic elastase (PPE) is successfully used to induce abdominal aortic aneurysm (AAA) in mice. However, differences between mouse strains in susceptibility to PPE induction have been reported. Kunming mouse is one of the most frequently used strains in China but whether it is suitable for induction of AAA by PPE application remains unclear. METHODS: PPE infusion (1.5 units/ml) in temporary controlled aorta was performed to induce AAAs in both C57BL/6J and Kunming mice. Phosphate-buffered saline (PBS) application was used as vehicle control. The aorta diameters of all mice were measured at days 0 and 14 after surgery to evaluate the AAA formation. RESULTS: After 14 days of PPE or PBS infusion, all mice were sacrificed and aorta tissues were collected for histological staining analysis. At the 14th day after infusion, PPE successfully induced aortic dilation in Kunming mice and typical AAA in C57BL/6J mice. The aorta diameter increased by 0.23 mm in Kunming mice after PPE infusion, while it was 0.72 mm in the C57BL/6J strain. PPE induced mild elastin degradation, smooth muscle cell (SMC) depletion and mural leucocyte infiltration in Kunming mice, but in PPE-sensitive C57BL/6J mice, it induced total loss of SMCs, elastin disappearance and diffused infiltrated leucocytes in aortic aneurysmal segments. The effects of PPE in inducing angiogenesis and upregulating matrix metalloproteinase 2 and 9 expression in Kunming mice were also weaker than that in C57BL/6J mice. CONCLUSION: At the reported dose of PPE, Kunming mouse is not as susceptible to AAA formation as C57BL/6J mice. The failure of PPE to induce AAA formation in Kunming mice may be associated to its inability to boost a strong inflammatory response.


Assuntos
Aneurisma da Aorta Abdominal , Elastase Pancreática , Animais , Aorta Abdominal , Aneurisma da Aorta Abdominal/induzido quimicamente , Modelos Animais de Doenças , Metaloproteinase 2 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Elastase Pancreática/efeitos adversos , Suínos
2.
Future Oncol ; 18(15): 1861-1872, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35156841

RESUMO

Aim: This study was designed to evaluate the contribution of GBAP1 variants to gastric cancer (GC) risk in a Chinese Han population. Methods: The genotypes of GBAP1 polymorphisms were detected using the Agena MassARRAY platform. Logistic regression analysis was used to calculate odds ratios (ORs) and 95% CIs. Results: GBAP1 rs140081212 (OR = 0.51, p = 4.50 × 10-07), rs1057941 (OR = 0.48, p = 1.19 × 10-08) and rs2990220 (OR = 0.46, p = 7.34 × 10-09) contribute to reduced GC risk, especially gastric adenocarcinoma. Interestingly, the contribution of GBAP1 variants to GC susceptibility was associated with age, sex, BMI, smoking and drinking. Conclusion: This research suggested that GBAP1 polymorphisms might provide a protective effect against GC occurrence in a Chinese Han population.


Assuntos
Neoplasias Gástricas , Estudos de Casos e Controles , China/epidemiologia , Predisposição Genética para Doença , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia
3.
Oxid Med Cell Longev ; 2022: 8502059, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35126822

RESUMO

BACKGROUND: Dapagliflozin, a sodium glucose transporter protein-2 (SGLT-2) inhibitor, reduces the risk for cardiovascular diseases. However, the influence of dapagliflozin on nondissecting abdominal aortic aneurysms (AAAs) remains unclear. METHODS: AAAs were created in male C57BL/6 mice via intra-aortic porcine pancreatic elastase (PPE) infusion. Mice were daily treated with dapagliflozin (1 or 5 mg/kg body weight) or an equal volume of vehicle through oral gavage beginning one day prior to PPE infusion for 14 days. To investigate its translational value, dapagliflozin or vehicle was also administered to mice with existing AAAs in another cohort. Aortic diameters were measured prior to (day 0 for baseline) and 14 days after PPE infusion. After sacrifice, mice aortae were collected, and following histological analyses were performed. RESULTS: Dapagliflozin treatment significantly reduced aneurysmal aortic expansion following PPE infusion as compared to vehicle treatment especially at 5 mg/kg body weight (approximately 21% and 33% decreases in 1 and 5 mg/kg treatment groups, respectively). The dose-dependent attenuation of AAAs by dapagliflozin was also confirmed on histological analyses. Dapagliflozin remarkably reduced aortic accumulation of macrophages, CD4+ T cells, and B cells particularly following dapagliflozin treatment at 5 mg/kg. Dapagliflozin treatment also markedly attenuated medial SMC loss. Though the difference was not significant, dapagliflozin treatment tended to attenuate CD8+ T cells and elastin degradation. Dapagliflozin treatment at 5 mg/kg caused a 53% reduction in neovessel density. Furthermore, dapagliflozin treatment mitigated further progress of existing AAAs. CONCLUSION: Dapagliflozin treatment ameliorated PPE-induced AAAs by inhibiting aortic leukocytes infiltration and angiogenesis.


Assuntos
Aneurisma da Aorta Abdominal/complicações , Aneurisma da Aorta Abdominal/tratamento farmacológico , Aortite/complicações , Aortite/tratamento farmacológico , Compostos Benzidrílicos/administração & dosagem , Progressão da Doença , Glucosídeos/administração & dosagem , Inibidores do Transportador 2 de Sódio-Glicose/administração & dosagem , Animais , Aorta Abdominal/patologia , Aneurisma da Aorta Abdominal/induzido quimicamente , Aneurisma da Aorta Abdominal/imunologia , Aortite/imunologia , Aortite/patologia , Linfócitos B/imunologia , Linfócitos T CD8-Positivos/imunologia , Estudos de Coortes , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neovascularização Patológica/tratamento farmacológico , Elastase Pancreática/efeitos adversos , Suínos , Resultado do Tratamento
4.
Sci Rep ; 12(1): 93, 2022 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-34997105

RESUMO

The stomach is the main digestive organ in humans. Patients with gastric cancer often develop digestive problems, which result in poor nutrition. Nutritional status is closely related to postoperative complications and quality of life (QoL) in patients with gastric cancer. The controlling nutritional status (CONUT) score is a novel tool to evaluate the nutritional status of patients. However, the relationship of the CONUT score with postoperative complications, QoL, and psychological status in patients with gastric cancer has not been investigated. The present follow-up study was conducted in 106 patients who underwent radical gastrectomy in our hospital between 2014 and 2019. The CONUT score, postoperative complications, psychological status, postoperative QoL scores, and overall survival (OS) of patients with gastric cancer were collected, and the relationship between them was analyzed. A significant correlation was observed between the CONUT score and postoperative complications of gastric cancer (P < 0.001), especially anastomotic leakage (P = 0.037). The multivariate regression analysis exhibited that the CONUT score (P = 0.002) is an independent risk factor for postoperative complications. The CONUT score was correlated with the state anxiety questionnaire (S-AI) for evaluating psychological status (P = 0.032). However, further regression analysis exhibited that the CONUT score was not an independent risk factor for psychological status. Additionally, the CONUT score was associated with postoperative QoL. The multivariate regression analysis exhibited that the CONUT score was an independent risk factor for the global QoL (P = 0.048). Moreover, the efficiency of CONUT score, prognostic nutrition index, and serum albumin in evaluating complications, psychological status, and QoL was compared, and CONUT score was found to outperform the other measures (Area Under Curve, AUC = 0.7368). Furthermore, patients with high CONUT scores exhibited shorter OS than patients with low CONUT scores (P = 0.005). Additionally, the postoperative complications (HR 0.43, 95% CI 0.21-0.92, P = 0.028), pathological stage (HR 2.26, 95% CI 1.26-4.06, P = 0.006), and global QoL (HR 15.24, 95% CI 3.22-72.06, P = 0.001) were associated with OS. The CONUT score can be used to assess the nutritional status of patients undergoing gastric cancer surgery and is associated with the incidence of postoperative complications and QoL.


Assuntos
Gastrectomia , Desnutrição/diagnóstico , Avaliação Nutricional , Estado Nutricional , Neoplasias Gástricas/cirurgia , Fístula Anastomótica/etiologia , Biomarcadores/sangue , Colesterol/sangue , Feminino , Gastrectomia/efeitos adversos , Gastrectomia/mortalidade , Humanos , Contagem de Linfócitos , Masculino , Desnutrição/etiologia , Desnutrição/mortalidade , Desnutrição/fisiopatologia , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Qualidade de Vida , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Albumina Sérica Humana/análise , Neoplasias Gástricas/complicações , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Fatores de Tempo , Resultado do Tratamento
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