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1.
J Hepatol ; 80(6): 928-940, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38336346

RESUMO

BACKGROUND & AIMS: Men are more prone to develop and die from liver fibrosis than women. In this study, we aim to investigate how sex-determining region Y gene (SRY) in hepatocytes promotes liver fibrosis. METHODS: Hepatocyte-specific Sry knock-in (KI), Sry knockout (KO), and Sry KI with platelet-derived growth factor receptor α (Pdgfrα) KO mice were generated. Liver fibrosis was induced in mice by bile duct ligation for 2 weeks or carbon tetrachloride treatment for 6 weeks. In addition, primary hepatocytes, hepatic stellate cells (HSCs), and immortalized cell lines were used for in vitro studies and mechanistic investigation. RESULTS: Compared to females, the severity of toxin- or cholestasis-induced liver fibrosis is similarly increased in castrated and uncastrated male mice. Among all Y chromosome-encoded genes, SRY was the most significantly upregulated and consistently increased gene in fibrotic/cirrhotic livers in male patients and in mouse models. Sry KI mice developed exacerbated liver fibrosis, whereas Sry KO mice had alleviated liver fibrosis, compared to age- and sex-matched control mice after bile duct ligation or administration of carbon tetrachloride. Mechanistically, both our in vivo and in vitro studies illustrated that SRY in hepatocytes can transcriptionally regulate Pdgfrα expression, and promote HMGB1 (high mobility group box 1) release and subsequent HSC activation. Pdgfrα KO or treatment with the SRY inhibitor DAX1 in Sry KI mice abolished SRY-induced HMGB1 secretion and liver fibrosis. CONCLUSIONS: SRY is a strong pro-fibrotic factor and accounts for the sex disparity observed in liver fibrosis, suggesting its critical role as a potentially sex-specific therapeutic target for prevention and treatment of the disease. IMPACT AND IMPLICATION: We identified that a male-specific gene, sex-determining region Y gene (SRY), is a strong pro-fibrotic gene that accounts for the sex disparity observed in liver fibrosis. As such, SRY might be an appropriate target for surveillance and treatment of liver fibrosis in a sex-specific manner. Additionally, SRY might be a key player in the sexual dimorphism observed in hepatic pathophysiology more generally.


Assuntos
Células Estreladas do Fígado , Hepatócitos , Cirrose Hepática , Proteína da Região Y Determinante do Sexo , Animais , Feminino , Masculino , Camundongos , Tetracloreto de Carbono/toxicidade , Tetracloreto de Carbono/efeitos adversos , Colestase/genética , Colestase/metabolismo , Colestase/fisiopatologia , Modelos Animais de Doenças , Células Estreladas do Fígado/metabolismo , Hepatócitos/metabolismo , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/genética , Cirrose Hepática/metabolismo , Camundongos Knockout , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismo , Caracteres Sexuais , Proteína da Região Y Determinante do Sexo/genética , Proteína da Região Y Determinante do Sexo/metabolismo
2.
BMC Infect Dis ; 24(1): 479, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38730338

RESUMO

BACKGROUND & AIMS: Pyogenic liver abscess (PLA) is a common hepatobiliary infection that has been shown to have an increasing incidence, with biliary surgery being identified as a trigger. Our aim was to investigate the clinical characteristics and treatments of PLA patients with and without a history of biliary surgery (BS). METHODS: The study included a total of 353 patients with PLA who received treatment at our hospital between January 2014 and February 2023. These patients were categorized into two groups: the BS group (n = 91) and the non-BS group (n = 262). In the BS group, according to the anastomosis method, they were further divided into bilioenteric anastomoses group (BEA, n = 22) and non-bilioenteric anastomoses group (non-BEA, n = 69). Clinical characteristics were recorded and analyzed. RESULTS: The percentage of PLA patients with BS history was 25.78%. The BS group exhibited elevated levels of TBIL and activated APTT abnormalities (P = 0.009 and P = 0.041, respectively). Within the BS group, the BEA subgroup had a higher prevalence of diabetes mellitus (P < 0.001) and solitary abscesses (P = 0.008) compared to the non-BEA subgroup. Escherichia coli was more frequently detected in the BS group, as evidenced by positive pus cultures (P = 0.021). The BS group exhibited reduced treatment efficacy compared to those non-BS history (P = 0.020). Intriguingly, the BS group received a higher proportion of conservative treatment (45.05% vs. 21.76%), along with reduced utilization of surgical drainage (6.59% vs. 16.41%). CONCLUSIONS: Patients with BS history, especially those who have undergone BEA, have an increased susceptibility to PLA formation without affecting prognosis.


Assuntos
Procedimentos Cirúrgicos do Sistema Biliar , Abscesso Hepático Piogênico , Humanos , Abscesso Hepático Piogênico/microbiologia , Abscesso Hepático Piogênico/cirurgia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Adulto , Antibacterianos/uso terapêutico , Escherichia coli/isolamento & purificação , Drenagem
3.
Future Oncol ; 20(29): 2213-2224, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39073412

RESUMO

Lung cancer is one of the most common malignancies worldwide, with non-small cell lung cancer (NSCLC) being the most common type. As understanding of precise treatment options for NSCLC deepens, circulating tumor DNA (ctDNA) has emerged as a potential biomarker that has become a research hotspot and may represent a new approach for the individualized diagnosis and treatment of NSCLC. This article reviews the applications of ctDNA for the early screening of patients with NSCLC, guiding targeted therapy and immunotherapy, evaluating chemotherapy and postoperative efficacy, assessing prognosis and monitoring recurrence. With the in-depth study of the pathogenesis of NSCLC, plasma ctDNA may become an indispensable part of the precise treatment of NSCLC, which has great clinical application prospects.


[Box: see text].


Assuntos
Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas , DNA Tumoral Circulante , Detecção Precoce de Câncer , Neoplasias Pulmonares , Humanos , DNA Tumoral Circulante/sangue , DNA Tumoral Circulante/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/sangue , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/sangue , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Prognóstico , Detecção Precoce de Câncer/métodos , Imunoterapia/métodos , Terapia de Alvo Molecular/métodos
4.
Ann Surg ; 276(2): 345-356, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-33086308

RESUMO

OBJECTIVES: To identify the role and mechanism of a male specific gene, SRY, in I/R-induced hepatic injury. BACKGROUND: Males are more vulnerable to I/R injury than females. However, the mechanism of these sex-based differences remains poorly defined. METHODS: Clinicopathologic data of patients who underwent hepatic resection were identified from an international multi-institutional database. Liver specific SRY TG mice were generated, and subjected to I/R insult with their littermate WT controls in vivo. In vitro experiments were performed by treating primary hepatocytes from TG and WT mice with hypoxia/reoxygen-ation stimulation. RESULTS: Clinical data showed that postoperative aminotransferase level, incidence of overall morbidity and liver failure were markedly higher among 1267 male versus 508 female patients who underwent hepatic resection. SRY was dramatically upregulated during hepatic I/R injury. Overexpression of SRY in male TG mice and ectopic expression of SRY in female TG mice exacerbated liver I/R injury compared with WTs as manifested by increased inflammatory reaction, oxidative stress and cell death in vivo and in vitro. Mechanistically, SRY interacts with Glycogen synthase kinase-3ß (GSK-3ß) and ß-catenin, and promotes phosphorylation and degradation of ß-catenin, leading to suppression of the downstream FOXOs, and activation of NF-κBand TLR4 signaling. Furthermore, activation of ß-catenin almost completely reversed the SRYoverexpression-mediated exacerbation of hepatic I/R damage. CONCLUSIONS: SRY is a novel hepatic I/R mediator that promotes hepatic inflammatory reaction, oxidative stress and cell necrosis via inhibiting Wnt/ß-catenin signaling, which accounts for the sex-based disparity in hepatic I/R injuries.


Assuntos
Hepatopatias , Traumatismo por Reperfusão , Proteína da Região Y Determinante do Sexo/metabolismo , Animais , Apoptose , Feminino , Glicogênio Sintase Quinase 3 beta/metabolismo , Isquemia , Fígado/patologia , Hepatopatias/metabolismo , Masculino , Camundongos , Caracteres Sexuais , beta Catenina
5.
BMC Gastroenterol ; 22(1): 27, 2022 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-35057742

RESUMO

BACKGROUND: Although marginal donor livers expand the donor pool, an ideal method for quantitatively evaluating the quality of donor livers has not been developed. This study aimed to explore the feasibility of indocyanine green (ICG) fluorescence imaging for estimating liver function in an ischemia-reperfusion model. METHODS: Forty-eight rats were randomly and evenly divided into 8 groups: the control group and the experimental groups (I-VII). The portal vein blocking period was 0 min, 10 min, 20 min, 30 min, 40 min, 50 min and 60 min. After blood flow was reestablished and the hemodynamics stabilized, ICG was injected through the dorsal penile vein as a bolus, and the fluorescence signal was recorded for 30 min in real time. The fluorescence intensity (FI) curve of the liver was fitted with an asymptotic regression model. Fresh liver tissues and serum were obtained from the middle lobe of the liver on postoperative day (POD) 1 and POD 7 for histopathological evaluation and liver function tests. RESULTS: The growth rate of the FI curve, parameter b3, decreased from groups I to VII. According to the two sudden changes in b3 (20 min, 50 min), the experimental groups could be classified into 3 groups (A, B and C). Hepatocytes in groups I-II showed slight edema, group III began to show obvious hepatocyte edema and vacuolar degeneration, and in groups VI-VII, severe hepatocyte degeneration, necrosis and large inflammatory cell infiltration were observed. Suzuki's scores in the 3 groups were also significantly different (P < 0.01). At the same time, the serum liver function in the experimental groups showed a significant increase on POD 1 and a decrease on POD 7. The alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TB) levels of groups A, B, and C were significantly different on POD 1 (P < 0.05), and the ALT and direct bilirubin (DB) levels were significantly different on POD 7 (P < 0.05); the lactic dehydrogenase (LDH) level of the group C was significantly higher than that of the groups A and B on POD 1 and POD 7. Meanwhile, the 7-day survival rate of the rats in group C was poor compared to that of the rats in groups A and B (58.3% vs. 100% vs. 100%). CONCLUSION: ICG fluorescence imaging is effective for estimating the degree of liver damage and grading in an ischemia-reperfusion model. It probably has the potential for use in assessing the quality of the donor liver in liver transplantation.


Assuntos
Verde de Indocianina , Transplante de Fígado , Animais , Humanos , Isquemia , Doadores Vivos , Imagem Óptica , Ratos , Reperfusão
6.
Hepatobiliary Pancreat Dis Int ; 21(4): 340-346, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35022144

RESUMO

BACKGROUND: Although laparoscopic technology has achieved rapid development in the surgical field, it has not been applied to liver transplantation, primarily because of difficulties associated with laparoscopic vascular anastomosis. In this study, we introduced a new magnetic-assisted vascular anastomosis technique and explored its application in laparoscopic liver transplantation in pigs. METHODS: Two sets of magnetic vascular anastomosis rings (MVARs) with different diameters were developed. One set was used for anastomosis of the suprahepatic vena cava (SHVC) and the other set was used for anastomosis of the infrahepatic vena cava (IHVC) and portal vein (PV). Six laparoscopic orthotopic liver transplantations were performed in pigs. Donor liver was obtained via open surgery. Hepatectomy was performed in the recipients through laparoscopic surgery. Anastomosis of the SHVC was performed using hand-assisted magnetic anastomosis, and the anastomosis of the IHVC and PV was performed by magnetic anastomosis with or without hand assistance. RESULTS: Liver transplants were successfully performed in five of the six cases. Postoperative ultrasonographic examination showed that the portal inflow was smooth. However, PV bending and blood flow obstruction occurred in one case because the MVARs were attached to each other. The durations of loading of MVAR in the laparoscope group and manual assistance group for IHVC and PV were 13 ± 5 vs. 5 ± 1 min (P < 0.01) and 10 ± 2 vs. 4 ± 1 min (P < 0.05), respectively. The durations of MVAR anastomosis in the laparoscope group and manual assistance group for IHVC and PV were 5 ± 1 vs. 1 ± 1 min (P < 0.01), and 5 ± 1 vs. 1 ± 1 min (P < 0.01), respectively. The anhepatic phase was 43 ± 4 min in the laparoscope group and 23 ± 2 min in the manual assistance group (P < 0.01). CONCLUSIONS: Our study showed that magnetic-assisted laparoscopic liver transplantation can be successfully carried out in pigs.


Assuntos
Laparoscopia , Transplante de Fígado , Anastomose Cirúrgica/métodos , Animais , Humanos , Transplante de Fígado/métodos , Doadores Vivos , Fenômenos Magnéticos , Veia Porta/diagnóstico por imagem , Veia Porta/cirurgia , Suínos , Veia Cava Inferior/cirurgia
7.
Zhongguo Yi Liao Qi Xie Za Zhi ; 46(6): 643-647, 2022 Nov 30.
Artigo em Zh | MEDLINE | ID: mdl-36597392

RESUMO

The diagnosis and differential diagnosis of bile duct stenosis are the foundation for personalized treatment. However, accurate diagnosis of bile duct stenosis remains a significant challenge in the era of precise medicine. In recent years, several novel diagnostic techniques of bile duct stenosis have been developed. And various biomarker detection, non-invasive imaging diagnostic techniques and invasive endoscopic diagnostic techniques have gradually become the conventional techniques for diagnosing bile duct stenosis. Here, we systematically reviewed the current status and future directions of diagnostic techniques related to bile duct stenosis.


Assuntos
Colestase , Humanos , Constrição Patológica/diagnóstico , Colestase/diagnóstico , Diagnóstico por Imagem , Ductos Biliares/diagnóstico por imagem
8.
J Cell Mol Med ; 25(24): 11310-11321, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34786826

RESUMO

Extracellular cold-inducible RNA-binding protein (CIRP) is a proinflammatory mediator that aggravates ischaemia-reperfusion injury (IRI). Normothermic machine perfusion (NMP) could effectively alleviate the IRI of the liver, but the underlying mechanism remains to be explored. We show that human DCD livers secreted a large amount of CIRP during static cold storage (CS), which is released into the circulation after reperfusion. The expression of CIRP was related to postoperative IL-6 levels and liver function. In a rat model, the CIRP expression was upregulated during warm ischaemia and cold storage. Then, rat DCD livers were preserved using CS, hypothermic oxygenated machine perfusion (HOPE) and NMP. C23, a CIRP inhibitor, was administrated in the HOPE group. Compared with CS, NMP significantly inhibited CIRP expression and decreased oxidative stress by downregulating NADPH oxidase and upregulating UCP2. NMP markedly inhibited the mitochondrial fission-related proteins Drp-1 and Fis-1. Further, NMP increased the mitochondrial biogenesis-related protein, TFAM. NMP significantly reduced inflammatory reactions and apoptosis after reperfusion, and NMP-preserved liver tissue had higher bile secretion and ICG metabolism compared to the CS group. Moreover, C23 administration attenuated IRI in the HOPE group. Additionally, HL-7702 cells were stimulated with rhCIRP and C23. High rhCIRP levels increased oxidative stress and apoptosis. In summary, NMP attenuates the IRI of DCD liver by inhibiting CIRP-mediated oxidative stress and mitochondrial fission.


Assuntos
Fígado/irrigação sanguínea , Fígado/metabolismo , Dinâmica Mitocondrial , Estresse Oxidativo , Perfusão , Proteínas de Ligação a RNA/metabolismo , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/metabolismo , Animais , Biomarcadores , Células Cultivadas , Modelos Animais de Doenças , Humanos , Células de Kupffer/metabolismo , Fígado/patologia , Fígado/ultraestrutura , Testes de Função Hepática , Masculino , Preservação de Órgãos/métodos , Perfusão/instrumentação , Perfusão/métodos , Proteínas de Ligação a RNA/genética , Ratos , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/terapia , Temperatura
9.
J Cell Physiol ; 236(2): 931-945, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32583428

RESUMO

Ischemia reperfusion (I/R)-induced acute kidney injury (AKI) is a common and serious condition. Irisin, an exercise-induced hormone, improves mitochondrial function and reduces reactive oxygen species (ROS) production. Glutathione peroxidase 4 (GPX4) is a key regulator of ferroptosis and its inactivation aggravates renal I/R injury by inducing ROS production. However, the effect of irisin on GPX4 and I/R-induced AKI is still unknown. To study this, male adult mice were subjected to renal I/R by occluding bilateral renal hilum for 30 min, which was followed by 24 hr reperfusion. Our results showed serum irisin levels were decreased in renal I/R mice. Irisin (250 µg/kg) treatment alleviated renal injury, downregulated inflammatory response, improved mitochondrial function, and reduced ER stress and oxidative stress after renal I/R, which were associated with upregulation of GPX4. Treated with RSL3 (a GPX4 inhibitor) abolished irisin's protective effect. Thus, irisin attenuates I/R-induced AKI through upregulating GPX4.


Assuntos
Injúria Renal Aguda/metabolismo , Fibronectinas/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Traumatismo por Reperfusão/metabolismo , Animais , Modelos Animais de Doenças , Regulação para Baixo/fisiologia , Ferroptose/fisiologia , Inflamação/metabolismo , Rim/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Estresse Oxidativo/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Reperfusão/métodos , Regulação para Cima/fisiologia
10.
Nanotechnology ; 32(1): 015202, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33043902

RESUMO

The investigation of two-dimensional (2D) nonlinear optical materials offers a promising way to construct the high-performance optical devices in fundamental and industrial applications because of their rich distinct optoelectronic properties. Herein, by utilizing the liquid exfoliation method, vanadium disulfide (VS2) nanosheets are prepared and the thickness is measured to be 3.16 nm. In addition, we have fabricated the VS2-based optical device and the nonlinear optical property is characterized with modulation depth of 23.97%. By using VS2 as saturable absorber, a high stable passively mode-locking Er-doped fiber laser is obtained with pulse duration of 169 fs and the largest average output power of 70.5 mW. The slope efficiency is up to 7.9%. In comparison to recent results of mode-locking fiber lasers with 2D materials, the VS2-based fiber laser demonstrates better performance. To the best of our knowledge, this is the first example of using VS2 for generating femtosecond mode-locked laser pulse. Our experimental results not only reveal VS2 ultrafast photonics application, but also advance the high-performance applications for information science and nonlinear optics.

11.
BMC Gastroenterol ; 21(1): 1, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407176

RESUMO

BACKGROUND: The role of platelets on the prognosis of patients with liver transplantation remains unclear. Thus, we aimed to evaluate the influence of preoperative platelet count on postoperative morbidity after liver transplantation. METHODS: Clinical data of the patients who received liver transplantation from January 2015 to September 2018 were evaluated. RESULTS: Of the 329 patients included, the average age was 46.71 ± 0.55 years, and 243 were men (75.2%). The incidence of posttransplant portal vein complication was significantly higher in the high platelet count group (> 49.5 × 109/L; n = 167) than in the low platelet count group (≤ 49.5 × 109/L, n = 162, 12.6% vs. 1.9%). After multivariable regression analysis, high platelet count was independently associated with postoperative portal vein complication (odds ratio [OR]: 8.821, 95% confidence interval [CI]: 2.260 to 34.437). After the inverse probability of treatment weighting analysis, patients in the high platelet count group had significantly higher risk of portal vein complication (OR: 9.210, 95%CI: 1.907 to 44.498, p = 0.006) and early allograft dysfunction (OR: 2.087, 95%CI: 1.131 to 3.853, p = 0.019). CONCLUSIONS: Preoperative platelet count > 49.5 × 109/L was an independent risk factor for posttransplant portal vein complication and early allograft dysfunction. High preoperative platelet count could be an adverse prognostic predictor for liver transplantation recipients.


Assuntos
Transplante de Fígado , Feminino , Humanos , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Veia Porta , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Pontuação de Propensão , Estudos Retrospectivos , Fatores de Risco
12.
Surg Endosc ; 35(10): 5665-5674, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33420599

RESUMO

BACKGROUND: The aim of this study was to evaluate the feasibility, safety, and efficacy of magnetic anchoring and guidance-assisted endoscopic irreversible electroporation (MAG-IRE) for gastric mucosal ablation. METHODS: A catheter-based, donut-like, and MAG-assisted electrode was developed. MAG-IRE for gastric mucosal ablation was performed in eight beagle canines. The parameters of one set of IRE was 500 V voltage, 100 µs pulse duration, and 99 pulses. The MAG time, operation time, success rate, and adverse events were measured. Endoscopic examination was performed from 30 min to 28 days post-IRE. Full-thickness gastric tissue was harvested by wedge biopsy for histopathological analysis. RESULTS: 30 (93.75%) of the 32 lesions were successfully ablated by MAG-IRE. The median MAG time was 300 s (IQR 120-422.5 s), and the median operation time was 491.5 s (IQR 358.3-632.5 s). No adverse events occurred. Ulceration was observed, starting from 3 days post-IRE. The mucosa healed 14 to 28 days post-IRE. Hematoxylin-Eosin (H&E) staining showed inflammatory infiltration, edema, and congestion in the ablated mucosa. Masson's Trichrome staining showed that the gastric wall and blood vessels in the ablation area were intact. TUNEL assay showed diffuse positive cells in ablated mucosa as early as 30 min post-IRE. CONCLUSIONS: MAG-IRE for gastric mucosal ablation is feasible, safe, and effective. It can be a potential therapeutic option for minimally invasive treatment of gastric neoplasm.


Assuntos
Técnicas de Ablação , Eletroporação , Animais , Cães , Endoscopia , Mucosa Gástrica/cirurgia , Fenômenos Magnéticos
13.
Zhongguo Yi Liao Qi Xie Za Zhi ; 45(6): 655-661, 2021 Nov 30.
Artigo em Zh | MEDLINE | ID: mdl-34862780

RESUMO

This study firstly introduced the mechanism, benefits and applications of irreversible electroporation(IRE) for tumor ablation. In addition, this study also introduced the most advanced IRE systems cleared by FDA or CFDA and IRE research equipment. The clinically licensed IRE systems include the Nanoknife 3.0 of Angiodynamics, the DophiTM N3000's steep pulse therapy system of Sanoway, and compound steep pulse therapy equipment of Reeves Technology IRE research equipment include the BTX and Bio-Rad electroporation devices.


Assuntos
Eletroporação , Neoplasias , Eletricidade , Frequência Cardíaca , Humanos , Neoplasias/terapia
14.
J Cell Mol Med ; 24(1): 996-1009, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31701659

RESUMO

Disruption of the gut barrier results in severe clinical outcomes with no specific treatment. Metabolic disorders and destruction of enterocytes play key roles in gut barrier dysfunction. Irisin is a newly identified exercise hormone that regulates energy metabolism. However, the effect of irisin on gut barrier function remains unknown. The therapeutic effect of irisin on gut barrier dysfunction was evaluated in gut ischemia reperfusion (IR). The direct effect of irisin on gut barrier function was studied in Caco-2 cells. Here, we discovered that serum and gut irisin levels were decreased during gut IR and that treatment with exogenous irisin restored gut barrier function after gut IR in mice. Meanwhile, irisin decreased oxidative stress, calcium influx and endoplasmic reticulum (ER) stress after gut IR. Moreover, irisin protected mitochondrial function and reduced enterocyte apoptosis. The neutralizing antibody against irisin significantly aggravated gut injury, oxidative stress and enterocyte apoptosis after gut IR. Further studies revealed that irisin activated the AMPK-UCP 2 pathway via binding to the integrin αVß5 receptor. Inhibition of integrin αVß5, AMPK or UCP 2 abolished the protective role of irisin in gut barrier function. In conclusion, exogenous irisin restores gut barrier function after gut IR via the integrin αVß5-AMPK-UCP 2 pathway.


Assuntos
Epitélio/metabolismo , Fibronectinas/administração & dosagem , Enteropatias/prevenção & controle , Mucosa Intestinal/metabolismo , Receptores de Vitronectina/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Animais , Apoptose , Estresse do Retículo Endoplasmático , Epitélio/patologia , Fibronectinas/metabolismo , Enteropatias/etiologia , Enteropatias/patologia , Mucosa Intestinal/lesões , Mucosa Intestinal/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Estresse Oxidativo , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/patologia , Transdução de Sinais
15.
J Cell Mol Med ; 24(22): 13081-13092, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32954626

RESUMO

Liver steatosis is associated with increased ischaemia reperfusion (I/R) injury. Our previous studies have shown that irisin, an exercise-induced hormone, mitigates I/R injury via binding to αVß5 integrin. However, the effect of irisin on I/R injury in steatotic liver remains unknown. Kindlin-2 directly interacts with ß integrin. We therefore suggest that irisin protects against I/R injury in steatotic liver via a kindlin-2 dependent mechanism. To study this, hepatic steatosis was induced in male adult mice by feeding them with a 60% high-fat diet (HFD). At 12 weeks after HFD feeding, the mice were subjected to liver ischaemia by occluding partial (70%) hepatic arterial/portal venous blood for 60 minutes, which was followed by 24 hours reperfusion. Our results showed HFD exaggerated I/R-induced liver injury. Irisin (250 µg/kg) administration at the beginning of reperfusion attenuated liver injury, improved mitochondrial function, and reduced oxidative and endoplasmic reticulum stress in HFD-fed mice. However, kindlin-2 inhibition by RNAi eliminated irisin's direct effects on cultured hepatocytes. In conclusion, irisin attenuates I/R injury in steatotic liver via a kindlin-2 dependent mechanism.


Assuntos
Proteínas do Citoesqueleto/metabolismo , Fibronectinas/metabolismo , Hepatopatias/metabolismo , Proteínas Musculares/metabolismo , Traumatismo por Reperfusão/metabolismo , Animais , Dieta Hiperlipídica , Modelos Animais de Doenças , Estresse do Retículo Endoplasmático , Fígado Gorduroso/metabolismo , Hepatócitos/metabolismo , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo
16.
J Surg Res ; 245: 249-256, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31421370

RESUMO

BACKGROUND: Technical improvement of gastrojejunostomy is critical in bariatric and metabolic surgery. In this study, a novel magnetic compression approach for gastrojejunostomy was evaluated. MATERIALS AND METHODS: Both cylindrical and rectangular magnets were used in rabbits, and the magnets were named according to their location. All the magnets were perorally introduced into the stomach. The position of the jejunal magnet was controlled by a connecting line. When the jejunal magnet spontaneously entered the jejunum, the gastric magnet was introduced into the stomach. An extracorporeal magnet was used to guide these two magnets together, and the magnet pair was left to create a side-to-side anastomosis. The state of the animals and extrusion time of the magnets were observed. The anastomoses were evaluated by burst pressure and histology. RESULTS: Gastrojejunostomy was successfully established in all animals. Cylindrical and rectangular magnets spontaneously entered the jejunum through the pylorus within 2.4 ± 0.5 and 6.0 ± 0.8 d, respectively (P < 0.01). The cylindrical and rectangular magnet pairs fell off within 15.3 ± 0.8 and 11.9 ± 1.1 d, respectively (P < 0.01). The burst pressures were statistically similar between the two types of magnets (P > 0.05). Histological examination showed sealed anastomoses with mild inflammation of the mucosa and fibrosis within the submucosa. CONCLUSIONS: The feasibility and efficacy of establishing gastrojejunostomy by guidewire introduction of magnets, which were guided together with an extracorporeal magnet, were confirmed in rabbits. In humans, with the clinical use of this procedure, surgery would be greatly simplified.


Assuntos
Derivação Gástrica/instrumentação , Gastrostomia/instrumentação , Jejunostomia/instrumentação , Imãs , Animais , Desenho de Equipamento , Estudos de Viabilidade , Feminino , Derivação Gástrica/efeitos adversos , Derivação Gástrica/métodos , Gastrostomia/efeitos adversos , Gastrostomia/métodos , Jejunostomia/efeitos adversos , Jejunostomia/métodos , Masculino , Modelos Animais , Pressão , Coelhos
17.
BMC Infect Dis ; 20(1): 145, 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32066406

RESUMO

BACKGROUND: Pyogenic liver abscess (PLA) is an inflammatory disease with increasing incidence. When it occurs with diabetes mellitus (DM), the risk of recurrence and mortality may increase. However, the effect of DM on the short-term prognosis of PLA patients after hospitalization remained unknown. METHODS: Two hundred twenty-seven PLA patients who received treatment at the First Affiliated Hospital of Xi'an Jiaotong University from January 2011 to January 2018 were retrospectively enrolled. They were divided into two groups as the DM group (n = 61) and the Non-DM group (n = 166). In the DM group, HbA1C level < 7% was considered to be good-control of glycaemia (n = 23). The clinical characteristics and overall short-term survival were analyzed. RESULTS: The proportion of PLA patients with DM was 26.87%. In the DM group, there was a higher incidence of hypertension and Candida spp. infection. Conservative administration and percutaneous drainage were mainly used in patients with good- (60.87%) and poor-control (60.53%) of glycaemia, respectively. During follow-up, 24 (10.57%) died due to uncontrolled systemic infections and other serious complications. Compared with PLA patients without DM, patients in the DM group had significantly increased 6-month mortality rate after discharge (Log-Rank test, P = 0.021). Poor-control of glycaemia did not reduce the six-month survival, while the recurrence rate of PLA within 3 months showed an almost 3-fold increase (13.16% vs. 4.35%). Further multivariate analyses found that DM was the only independent risk factor for the PLA six-month survival (odds ratio [OR]: 3.019, 95% confidence interval [CI]: 1.138-8.010, P = 0.026). However, the blood glucose level had no significant effect on the short-term survival of PLA patients with DM (Log-Rank test, P = 0.218). CONCLUSIONS: In PLA patients, DM aggravated short-term mortality and blood glucose levels should be well controlled.


Assuntos
Complicações do Diabetes/complicações , Complicações do Diabetes/epidemiologia , Abscesso Hepático Piogênico/complicações , Abscesso Hepático Piogênico/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Glicemia , Criança , Complicações do Diabetes/mortalidade , Feminino , Hospitalização , Humanos , Abscesso Hepático Piogênico/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Adulto Jovem
18.
Surg Endosc ; 34(2): 580-589, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31011863

RESUMO

BACKGROUND: Irreversible electroporation (IRE) is an emerging tissue ablation technique, which is safe for sites where thermal-basis techniques are not suitable. The aim of this study is to evaluate the safety and efficacy of magnetic anchoring electrode (MAE)-assisted IRE for normal gastric tissue ablation in a rabbit model. METHODS: IRE (500 V, 100 µs, 99 pulses, 1 Hz) of the gastric wall was performed in 24 adult New Zealand rabbits with a novel catheter-mounted MAE with fluoroscopy and a surgical approach. Procedure time, procedure-related bleeding, perforation, and other complications were recorded. Animals were sacrificed at 30 min, 1 day, 3 days, 7 days, 14 days, and 28 days post-IRE. The stomach was removed en bloc, and the diameter of each lesion was measured. Histopathological analyses by Hematoxylin-Eosin (H&E), masson trichrome, alpha-smooth muscle action (α-SMA), and terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) were performed. RESULTS: Gastric tissue ablation with MAE-assisted IRE was successfully performed without any interruption. No perforation or bleeding was observed during IRE or throughout the follow-up period. A demarcated hemorrhage was found in the ablated area upon gross examination. H&E staining showed complete cell death with inflammatory infiltration, edema, and hemorrhaging. TUNEL presented diffuse positive cells in the ablated area. The tissue scaffold was well preserved without damage as indicated by Masson trichrome staining. Ulceration was observed starting from 3 days post-IRE. The mucosal layer was gradually recovered and regenerated within 14-28 days. No other complication was observed post-IRE. CONCLUSIONS: MAE-assisted IRE is safe and effective for normal gastric tissue ablation and the gastric wall recovered in 14-28 days post-IRE.


Assuntos
Técnicas de Ablação/instrumentação , Eletrodos , Eletroporação/instrumentação , Mucosa Gástrica/cirurgia , Magnetismo , Animais , Modelos Animais de Doenças , Eletroporação/métodos , Fenômenos Magnéticos , Coelhos , Coloração e Rotulagem , Estômago/cirurgia
19.
Ann Vasc Surg ; 68: 487-496, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32428647

RESUMO

BACKGROUND: The resection and reconstruction of the vena cava is frequently needed in tumor resection. The goal of this study was to evaluate the performance of the magnetic compression anastomosis (MCA) device for fast nonsuture anastomosis of caval reconstruction with artificial blood vessel transplantation after resection in canines. METHODS: The MCA device consisted of paired neodymium-ferrum-boron (Nd-Fe-B) magnetic rings that were coated with titanium nitride and embedded in a polypropylene shell. Artificial blood vessel transplantation procedure was performed in sixteen canines and then they were divided into 2 groups: MCA group (n = 8), in which the novel magnetic pinned-ring device was used, and the traditional manual suture group (n = 8). In situ artificial blood vessel anastomoses were performed in the inferior vena cava (IVC). The anastomosis time and anastomotic patency and quality were investigated through ultrasonographic scans, angiographic, gross observation, histological staining, and scanning electron microscopy at 24 weeks postoperatively. RESULTS: The IVC anastomoses were reconstructed successfully in all canines and all animals survived. In the MCA group, the operation time for IVC anastomosis with artificial blood vessel was significantly shorter than that in the tradition manual suture group (P < 0.05). Vena cava angiography and ultrasound showed good blood patency. The scanning electron microscope showed the re-endothelialization was smooth and endothelial cells were arranged regularly at the anastomotic site. Histological examination confirmed that the MCA group was associated with infiltration of inflammatory cells compared with the manual suture group. CONCLUSIONS: The MCA device combined with artificial blood vessels is applicable in reconstruction of large vessels after resection. The magnetic pinned-ring device offers a simple, fast, reliable, and effective technique for nonsuture artificial blood vessel anastomosis of caval reconstruction in canines, and the anastomosis is functionally better than the traditional sutured anastomosis.


Assuntos
Implante de Prótese Vascular/instrumentação , Prótese Vascular , Imãs , Procedimentos Cirúrgicos sem Sutura/instrumentação , Veia Cava Inferior/cirurgia , Anastomose Cirúrgica , Animais , Cães , Células Endoteliais/ultraestrutura , Duração da Cirurgia , Desenho de Prótese , Reepitelização , Fatores de Tempo , Grau de Desobstrução Vascular , Veia Cava Inferior/diagnóstico por imagem , Veia Cava Inferior/ultraestrutura
20.
Zhongguo Yi Liao Qi Xie Za Zhi ; 44(2): 172-178, 2020 Feb 08.
Artigo em Zh | MEDLINE | ID: mdl-32400994

RESUMO

Irreversible electroporation (IRE) is an emerging tissue ablation technique. Compared with thermal ablation technique such as radiofrequency, IRE can achieve focal ablation in a shorter time without heat sink effect while sparing the tissue scaffold. IRE has been demonstrated to be a feasible therapeutic modality for the liver, pancreatic, and prostatic cancer. In recent years, several studies regarding of catheter-directed IRE for digestive tract, bronchus, urinary tract, and myocardium have been performed, which preliminarily demonstrated the safety and efficacy of IRE for tissue ablation under endoscopic or interventional technique. This study summarized the research progress of catheter-directed IRE for tissue ablation. The critical technique and future direction of catheter-based IRE are prosp.


Assuntos
Ablação por Cateter , Eletroporação , Catéteres , Endoscopia , Humanos
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