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1.
J Clin Transl Hepatol ; 11(2): 405-415, 2023 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-36643038

RESUMO

Background and Aims: Hepatic ischemia/reperfusion (I/R) injury has become an inevitable issue during liver transplantation, with no effective treatments available. However, peptide drugs provide promising regimens for the treatment of this injury and peptidomics has gradually attracted increasing attention. This study was designed to analyze the spectrum of peptides in injured livers and explore the potential beneficial peptides involved in I/R injury. Methods: C57BL/6 mice were used to establish a liver I/R injury animal model. Changes in peptide profiles in I/R-injured livers were analyzed by mass spectrometry, and the functions of the identified peptides were predicted by bioinformatics. AML12 cells were used to simulate hepatic I/R injury in vitro. After treatment with candidate liver-derived peptides (LDPs) 1-10, the cells were collected at various reperfusion times for further study. Results: Our preliminary study demonstrated that 6 h of reperfusion caused the most liver I/R injury. Peptidomic results suggested that 10 down-regulated peptides were most likely to alleviate I/R injury by supporting mitochondrial function. Most importantly, a novel peptide, LDP2, was identified that alleviated I/R injury of AML12 cells. It increased cell viability and reduced the expression of inflammation- and apoptosis-related proteins. In addition, LDP2 inhibited the expression of proteins related to autophagy. Conclusions: Investigation of changes in the profiles of peptides in I/R-injured livers led to identification of a novel peptide, LDP2 with potential function in liver protection by inhibiting inflammation, apoptosis, and autophagy.

2.
Contemp Oncol (Pozn) ; 25(1): 64-67, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33911984

RESUMO

Chyle leakage can be caused by abdominal surgery and managed successfully without surgical treatment; however, no preventive measures are available. Therefore, we introduce a new method to prevent post-operative chyle leakage. To investigate the role of indocyanine green (ICG) lymphangiography in the reduction of chyle fistula formation after radical resection of right colon cancer. Five patients with a diagnosis of right colon cancer undergoing laparoscopic radical colectomy with D3 lymph node dissection were examined in this study. At the end of the operation, two points of 2.5 mg ICG were injected subserosally at the proximal end of the anastomosis (1 ml per point). Then the surgical field was screened by using ICG fluorescence to accurately locate the chyle leakage. Chyle leakage was noted and repaired with a Hem-O-Lock. The volume of output of each drain after surgery was measured daily until the patients were discharged. We were able to observe ICG fluorescence in the lymphatic vessels within 3 minutes of ICG injection. This visualization allowed us to accurately locate and quickly repair chyle leakage within 5 minutes. Clinical observation after surgery and at a 1-month follow-up showed no chyle leakage in all 5 patients. Indocyanine green lymphangiography can feasibly guide the location and repair of chyle leakage after right colon cancer resection.

3.
Scand J Gastroenterol ; 54(9): 1124-1131, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31491354

RESUMO

Background: The Enhanced Recovery After Surgery (ERAS) pathway is widely applied in the perioperative period of stomach and colorectal surgery, and can decrease the length of hospital stay of the patients without compromising the safety of the patients. However, some patients are removed from this pathway for various reasons. Here we found some factors that taking the patients out from the procedures. Methods: A retrospective analysis of collected data of 550 patients over a 3-year period was conducted, with 292 in the ERAS group and 258 in the conventional care group. Then various basic elements were analyzed to explore the reasons for the failure to complete the ERAS program. Results: Total length of hospital stay after surgery was significantly shorter in the ERAS group, and a similar incidence of complication rates were observed in the two groups. In this study, the significant factors that associated with complications were advanced age (OR 2.18; p = .031), history of abdominal surgery (OR 2.03; p = .04), incomplete gastrointestinal obstruction (OR 3.42; p < .001), laparoscopic surgery (OR 0.39; p = .004) and intraoperative neostomy (OR 2.37; p = .006). Conclusions: We found that advanced age (>80 years old), history of abdominal surgery, gastrointestinal obstruction and stoma formation were the risk factors. We anticipated to design a risk assessment system upon the high-risk patients from the present ERAS pathway, and make a modified ERAS pathway for those patients.


Assuntos
Cirurgia Colorretal/reabilitação , Recuperação Pós-Cirúrgica Melhorada , Gastrostomia/reabilitação , Laparoscopia/reabilitação , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , China , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Estudos Retrospectivos , Fatores de Risco , Falha de Tratamento
5.
J Hepatol ; 69(5): 1110-1122, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29958938

RESUMO

BACKGROUND & AIMS: The hepatic injury caused by ischemia/reperfusion (I/R) insult is predominantly determined by the complex interplay of sterile inflammation and liver cell death. Caspase recruitment domain family member 6 (CARD6) was initially shown to play important roles in NF-κB activation. In our preliminary studies, CARD6 downregulation was closely related to hepatic I/R injury in liver transplantation patients and mouse models. Thus, we hypothesized that CARD6 protects against hepatic I/R injury and investigated the underlying molecular mechanisms. METHODS: A partial hepatic I/R operation was performed in hepatocyte-specific Card6 knockout mice (HKO), Card6 transgenic mice with CARD6 overexpression specifically in hepatocytes (HTG), and the corresponding control mice. Hepatic histology, serum aminotransferases, inflammatory cytokines/chemokines, cell death, and inflammatory signaling were examined to assess liver damage. The molecular mechanisms of CARD6 function were explored in vivo and in vitro. RESULTS: Liver injury was alleviated in Card6-HTG mice compared with control mice as shown by decreased cell death, lower serum aminotransferase levels, and reduced inflammation and infiltration, whereas Card6-HKO mice had the opposite phenotype. Mechanistically, phosphorylation of ASK1 and its downstream effectors JNK and p38 were increased in the livers of Card6-HKO mice but repressed in those of Card6-HTG mice. Furthermore, ASK1 knockdown normalized the effect of CARD6 deficiency on the activation of NF-κB, JNK and p38, while ASK1 overexpression abrogated the suppressive effect of CARD6. CARD6 was also shown to interact with ASK1. Mutant CARD6 that lacked the ability to interact with ASK1 could not inhibit ASK1 and failed to protect against hepatic I/R injury. CONCLUSIONS: CARD6 is a novel protective factor against hepatic I/R injury that suppresses inflammation and liver cell death by inhibiting the ASK1 signaling pathway. LAY SUMMARY: The protein CARD6 plays an important role during the process of liver blood flow restriction (ischemia) and restoration (reperfusion). By suppressing the activity of ASK1, CARD6 can protect against hepatocyte injury. Targeting CARD6 is a potential strategy for prevention and treatment of ischemia/reperfusion injury.


Assuntos
Proteínas Adaptadoras de Sinalização CARD/fisiologia , Fígado/irrigação sanguínea , MAP Quinase Quinase Quinase 5/fisiologia , Traumatismo por Reperfusão/prevenção & controle , Animais , Humanos , Inflamação/prevenção & controle , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases JNK Ativadas por Mitógeno/fisiologia , MAP Quinase Quinase Quinase 5/antagonistas & inibidores , Sistema de Sinalização das MAP Quinases , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/fisiologia
6.
Hepatology ; 68(6): 2359-2375, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29742804

RESUMO

Sterile inflammation is an essential factor causing hepatic ischemia/reperfusion (I/R) injury. As a critical regulator of inflammation, the role of monocyte chemoattractant protein-induced protein 1 (MCPIP1) in hepatic I/R injury remains undetermined. In this study, we discovered that MCPIP1 downregulation was associated with hepatic I/R injury in liver transplant patients and a mouse model. Hepatocyte-specific Mcpip1 gene knockout and transgenic mice demonstrated that MCPIP1 functions to ameliorate liver damage, reduce inflammation, prevent cell death, and promote regeneration. A mechanistic study revealed that MCPIP1 interacted with and maintained hypoxia-inducible factor 1α (HIF-1α) expression by deubiquitinating HIF-1α. Notably, the HIF-1α inhibitor reversed the protective effect of MCPIP1, whereas the HIF-1α activator compensated for the detrimental effect of MCPIP1 deficiency. Thus, we identified the MCPIP1-HIF-1α axis as a critical pathway that may be a good target for intervention in hepatic I/R injury. (Hepatology 2018; 00:000-000).


Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Hepatopatias/metabolismo , Traumatismo por Reperfusão/metabolismo , Ribonucleases/metabolismo , Fatores de Transcrição/metabolismo , Animais , Apoptose , Estudos de Casos e Controles , Hepatócitos/fisiologia , Humanos , Fígado/patologia , Hepatopatias/patologia , Regeneração Hepática , Masculino , Camundongos , Cultura Primária de Células
7.
Hepatology ; 68(6): 2212-2229, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29729191

RESUMO

The rapidly increasing prevalence of metabolic disorders associated with nonalcoholic fatty liver disease (NAFLD) warrants further study of the underlying mechanisms to identify key regulators as targets for the development of therapeutic interventions. Caspase recruitment domain protein 6 (Card6), as a member of the CARD family that regulates cell death and immunity, may potentially control this process. Indeed, Card6 down-regulation was found to be closely associated with the fatty livers observed in NAFLD patients, obese mice, and a palmitate-treated hepatocyte model. Gain-of-function and loss-of-function Card6 mouse models demonstrated that Card6 protected mice from insulin resistance, hepatic steatosis, and inflammatory responses upon high-fat diet administration. Mechanistically, Card6 interacted with and inhibited apoptosis signal-regulating kinase 1 (Ask1) and its subsequent downstream c-Jun N-terminal kinase/p38 signaling. Furthermore, Ask1 was sufficient to mediate Card6 function, and the interaction between Ask1 and Card6 was absolutely required for Card6 function in vivo. Adenovirus-mediated Card6 overexpression in the liver effectively ameliorated insulin resistance and hepatic steatosis in ob/ob mice. Therefore, we identified Card6 as an important negative regulator in NAFLD. Conclusion: Targeting Ask1 by Card6 may be a good strategy to develop a therapeutic method against NAFLD.


Assuntos
Proteínas Adaptadoras de Sinalização CARD/metabolismo , MAP Quinase Quinase Quinase 5/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Obesidade/complicações , Animais , Células HEK293 , Humanos , Resistência à Insulina , MAP Quinase Quinase Quinase 5/genética , Sistema de Sinalização das MAP Quinases , Masculino , Camundongos , Camundongos Transgênicos , Hepatopatia Gordurosa não Alcoólica/genética , Obesidade/genética
8.
Cancer Biomark ; 19(1): 113-117, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28282801

RESUMO

Here one concurrent case of a patient with both thyroid and breast cancers was discussed with a comprehensive literature review. On March 21, 2016, a 42-year-old female patient was admitted into our hospital because of right neck mass and left breast mass for 1 week during a routine health examination. On March 22, the combined procedures of complete resection of right thyroid gland plus isthmus with dissection of lymph nodes in right VI region plus left breast regional lumpectomy were performed under endotracheal anesthesia. Final diagnosis: Mammary cancer (right thyroid gland), PT1aN1aM0 (stage I); ductal breast cancer (left breast), PT1NxM0 (re-operation within two weeks). For either disease, a practicing clinician should stay on a high alert for individual and familial endocrine diseases. And breast molybdenum target imaging and type B ultrasound should be performed regularly for screening. It is always prudent to catch and treat diseases as early as possible. The conclusion is as follows.


Assuntos
Adenocarcinoma/patologia , Neoplasias da Mama/patologia , Neoplasias da Glândula Tireoide/patologia , Adenocarcinoma/complicações , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/cirurgia , Adulto , Neoplasias da Mama/complicações , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Feminino , Humanos , Metástase Linfática , Estadiamento de Neoplasias , Glândula Tireoide/patologia , Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/complicações , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/cirurgia
9.
Asian Pac J Cancer Prev ; 15(9): 3895-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24935570

RESUMO

C4.4A, a metastasis-associated gene, encodes a glycolipid-anchored membrane protein which is overexpressed in several human malignancies. However, there are few data available on C4.4A expression and its relationship with progression in gastric cancer. Our study was designed to explore the expression of C4.4A in gastric cancer and to correlate it with clinical outcome. C4.4A expression was studied by quantitative real-time RT-PCR and immunohistochemistry for assessment of correlations with clinicopathological factors. C4.4A mRNA expression was significantly up-regulated in gastric cancer as compared with noncancerous tissue (p<0.05)., being observed in 107 (88.4%) of the 121 gastric cancer cases by immunohistochemistry. We found that the expression of C4.4A mRNA was correlated with size of the tumor, depth of invasion, lymph node metastasis, distant metastasis and TNM stage. Moreover, patients with overexpression of C4.4A has a significantly worse survival (p<0.05). Further multivariable analysis indicated that the expression of C4.4A was an independent prognostic indicator for gastric cancer (p<0.05). In conclusion, overexpression of C4.4A correlates with metastatic potential of gastric cancer and C4.4A could be a novel independent prognostic marker for predicting outcome.


Assuntos
Moléculas de Adesão Celular/biossíntese , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/biossíntese , Moléculas de Adesão Celular/genética , Progressão da Doença , Intervalo Livre de Doença , Feminino , Proteínas Ligadas por GPI/biossíntese , Proteínas Ligadas por GPI/genética , Humanos , Metástase Linfática/genética , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , RNA Mensageiro/biossíntese , Resultado do Tratamento
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