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1.
Eur Rev Med Pharmacol Sci ; 28(2): 721-733, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38305614

RESUMO

OBJECTIVE: This study aimed to explore the role of alanine aminotransferase (ALT) in the effects of urinary caffeine and its primary metabolites on cognitive function in elderly people. MATERIALS AND METHODS: In this investigation, we meticulously curated a cohort from the 2011-2014 National Health and Nutrition Examination Survey (NHANES) database. Animal fluency emerged as the pivotal metric for assessing cognitive function within our study population. In order to navigate the intricacies of mixture analysis and circumvent potential complexities, we harnessed the power of Bayesian kernel machine regression (BKMR) models. This method allowed us to dissect the nuanced impacts of caffeine and its primary urinary metabolites on cognitive function. While accounting for caffeine and its metabolites, we analyzed the relationship between ALT and cognitive function through non-linear dynamics. Lastly, employing structural equation modeling, we probed the intriguing question of whether ALT mediates the influence of 3,7-dimethylxanthine on cognitive function. This comprehensive approach has unveiled a deeper understanding of the multifaceted interplay among these variables, offering invaluable insights into the determinants of cognitive function within our cohort. RESULTS: After meticulous adjustment for various covariates, our linear regression analysis unveiled a noteworthy finding: 3,7-dimethylxanthine demonstrated a significant positive correlation with cognitive function (p < 0.05). Importantly, within the BKMR model employed, 3,7-dimethylxanthine emerged as the most influential factor within the compound, with posterior inclusion probabilities of 0.995 and 0.939. Furthermore, our single-exposure effect model confirmed its presence at the 25th, 50th, and 75th percentile concentrations of other components within the compound. Interestingly, bivariate concentration curves indicated no interaction within the compound, underscoring the prominent impact of 3,7-dimethylxanthine on cognitive function. Subsequently, through a test of Restricted Cubic Splines (RCS), we revealed a non-linear relationship between ALT and cognitive function at the 10th, 50th, and 90th percentiles (p < 0.05), indicating a heightened risk of diminished cognitive function in the low ALT group. Employing structural equation modeling, we meticulously examined the mediating role of ALT in relation to 3,7-dimethylxanthine and cognitive function. However, our study results did not yield significant evidence of a mediating effect. This comprehensive analysis elucidates the intricate interplay between these variables, unveiling the subtle mechanisms governing cognitive function. CONCLUSIONS: In this study, a noteworthy positive correlation was observed between 3,7-dimethylxanthine and cognitive function. Additionally, a non-linear relationship was identified between ALT and cognitive function, with lower levels of ALT associated with a decline in cognitive function. The RCS trend suggested that higher levels of ALT may similarly lead to diminished cognitive performance. However, in our pursuit to ascertain potential mediation, we regrettably found no significant evidence supporting mediation among these factors involving ALT. This underscores the need for more comprehensive investigations and expanded clinical explorations into the intricate associations among these three pivotal elements.


Assuntos
Alanina Transaminase , Cafeína , Cognição , Idoso , Humanos , Alanina Transaminase/metabolismo , Teorema de Bayes , Cafeína/urina , Análise de Mediação , Inquéritos Nutricionais
2.
Eur Rev Med Pharmacol Sci ; 27(20): 10016-10030, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37916372

RESUMO

OBJECTIVE: Gallbladder cancer (GBC) is a highly aggressive malignancy that is associated with a high mortality rate globally. Unfortunately, distant metastases are often detected at the time of diagnosis. Therefore, we investigated the survival outcomes of gallbladder cancer patients with different metastases targeting organs, analyzed their prognosis, and explored their hidden clinical value. PATIENTS AND METHODS: Through data screening, a total of 398 patients with GBC with different target organ metastases were analyzed retrospectively, including patients with solitary bone metastasis, solitary liver metastasis, solitary lung metastasis, and multiple organ metastases. The survival results of different variables were plotted as Kaplan-Meier survival curves. Univariate and multivariate Cox regression models were used to screen study variables and identify independent prognostic factors. Finally, a nomogram was established to systematically evaluate the prognosis of patients with multiple organ metastasis. RESULTS: In the patient cohort, thirteen (3.3%) had solitary bone metastasis, 290 (72.9%) had solitary liver metastasis, 22 (5.5%) had solitary lung metastasis, and 73 (18.3%) had multiple organ metastases (including liver, lung, bone and brain metastases). Multivariate Cox analysis showed that the overall survival (OS) of patients with solitary lung metastasis was significantly better than that of patients with other organ metastasis (p = 0.038), while the difference in tumor cancer-specific survival (CSS) of this factor was not statistically significant (p > 0.05). Surgery and chemotherapy were independent prognostic protective factors for OS and CSS. The OS-related models exhibited a C-index of 0.74 (95% CI: 0.71-0.77), while the CSS-related models showed a slightly lower C-index of 0.73 (0.70-0.76). Both the OS- and CSS-related clinical prediction models had good accuracy. CONCLUSIONS: This study shows that different target organ metastases may affect the OS of patients with distant metastatic GBC. Patients receiving palliative surgery, primary site resection, radical surgery, and chemotherapy have significant survival benefits in terms of OS and CSS.


Assuntos
Neoplasias da Vesícula Biliar , Neoplasias Hepáticas , Neoplasias Pulmonares , Humanos , Nomogramas , Estudos Retrospectivos
3.
Zhonghua Wei Chang Wai Ke Za Zhi ; 26(7): 619-624, 2023 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-37583018

RESUMO

The successful report of total mesorectal excision (TME)/complete mesocolic excision (CME) has encouraged people to apply this concept beyond colorectal surgery. However, the negative results of the JCOG1001 trial denied the effect of complete resection of the "mesogastrium" including the greater omentum on the oncological survival of gastric cancer patients. People even believe that the mesentery is unique in the intestine, because they have a vague understanding of the structure of the mesentery. The discovery of proximal segment of the dorsal mesogastrium (PSDM) proved that the greater omentum is not the mesogastrium, and further revised the structure (definition) of the mesentery and revealed its container characteristics, i.e. the mesentery is an envelope-like structure, which is formed by the primary fascia (and serosa) that enclose the tissue/organ/system and its feeding structures, leading to and suspended on the posterior wall of the body. Breakdown of this structure leads to the simultaneous reduction of surgical and oncological effects of surgery. People quickly realized the universality of this structure and causality which cannot be matched by the existing theories of organ anatomy and vascular anatomy, so a new theory and surgical map- membrane anatomy began to form, which led to radical surgery upgraded from histological en bloc resection to anatomic en bloc resection.


Assuntos
Laparoscopia , Mesocolo , Humanos , Fáscia/anatomia & histologia , Excisão de Linfonodo/métodos , Mesentério/cirurgia , Mesocolo/cirurgia , Omento , Membrana Serosa , Ensaios Clínicos como Assunto
4.
Zhonghua Wei Chang Wai Ke Za Zhi ; 26(7): 707-712, 2023 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-37583030

RESUMO

In the past decade, the concept of membrane anatomy has been gradually applied in gastric cancer surgery. Based on this theory, D2 lymphadenectomy plus complete mesogastric excision (D2+CME) has been proposed, which has been demonstrated to significantly reduce intraoperative bleeding and intraperitoneal free cancer cells during surgery, decrease surgical complications, and improve survival. These results indicate that membrane anatomy is feasible and efficacious in gastric cancer surgery. In this review, we will describe the important contents of membrane anatomy, including "Metastasis V"(2013, 2015), proximal segmentation of dorsal mesogastrium (2015), D2+CME procedure (2016), "cancer leak"(2018), and surgical outcomes of D2+CME (2022).


Assuntos
Laparoscopia , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Gastrectomia/métodos , Laparoscopia/métodos , Excisão de Linfonodo/métodos , Mesentério/cirurgia
5.
Zhonghua Yi Xue Za Zhi ; 101(31): 2471-2477, 2021 Aug 17.
Artigo em Chinês | MEDLINE | ID: mdl-34399562

RESUMO

Objective: To establish a nomogram model for hematoma expansion (HE) prediction after intracerebral hemorrhage (ICH) and evaluate its performance in a multidimensionally way. Methods: A total of 348 ICH patients who were firstly diagnosed and hospitalized in the Second Affiliated Hospital of Soochow University from January 2017 to December 2019 were collected retrospectively. There were 236 males and 112 females, and their age ranged from 18 to 94 (62.0±14.6) years. All patients were divided into HE group (n=121) or non-HE group (n=227) according to the presence or absence of HE. The clinical and imaging features were compared between the two groups. Multivariate logistic regression analysis was performed for determining the independent predicting factors for HE prediction and a Nomogram model was established by using these factors. Receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to evaluate the prediction effectiveness, accuracy and clinical practicability of the model, respectively. Bootstrap method was used for internal validation. Results: There were significant differences in onset time, swirl sign, history of anticoagulants administrations, systolic blood pressure when admission, Glasgow coma scale (GCS) scores and RBC distribution width between the two groups[(1.77(1.0, 2.5) h vs 2(1, 3) h, 72 cases (59.5%) vs 94 cases (41.4%), 17 cases (14.0%) vs 15 cases (6.6%), (170.69±29.19) mmHg(1 mmHg=0.133 kPa) vs (163.84±26.07) mmHg, 11(8, 14) scores vs 14(10, 15) scores, 44.3% (41.2%, 46.8%) vs 42.4% (40.1%, 45.3%);respectively, all P<0.05]. Multivariate logistic regression analysis demonstrated that onset time (OR=0.809, 95%CI: 0.682-1.961, P=0.015), swirl sign (OR=0.562, 95%CI:0.349-0.905, P=0.018), history of anticoagulants administrations (OR=0.394, 95%CI: 0.180-1.861, P=0.020), and GCS (OR=0.881, 95%CI: 0.815-1.952, P=0.001) were the predicting factors for HE. The area under the curve (AUC) of the Nomogram model was 0.735(95%CI: 0.687-0.805), which demonstrated that the model has an ideal prediction effectiveness. The calibration curve showed that the prediction probability of HE of the model fits well with the actual probability, and with high calibration. DCA showed relatively wide range of optional threshold probability of the model (ranging from 14% to 72%), the clinical practicability of this model was high. The internal validation results showed a C-index of 0.703, indicated a good discrimination power. Conclusion: The established Nomogram model can predict the HE of ICH with good prediction effectiveness, discrimination power and with good clinical practicability, which can be capable of providing an intuitive and visual guidance tool for timely identifying ICH patients who may have HE.


Assuntos
Hemorragia Cerebral , Nomogramas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Hematoma , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Estudos Retrospectivos , Adulto Jovem
6.
Zhonghua Wei Chang Wai Ke Za Zhi ; 24(7): 557-559, 2021 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-34289536

RESUMO

Anatomical plane and fascia have been described in medical behaviors for hundreds of years since the appearance of anatomy and operation. Generally, these descriptions can be sorted into three theories, i.e. plane surgery, fascia theory and mesentery anatomy. However, these theories are difficult to satisfy the scientific paradigm that includes consistency in description, independence in validation, potential to solve practical problems, and the interaction of the above-mentioned theries. Recently, membrane anatomy was proposed as the anatomy of mesentery and its beds in broad sense. Behind it lies fascia membrane/serous membrane structure, as well as inherent life events and general order. Mesentery in broad sense is described as the fascia membrane/serous membrane in serous cavity, which envelops and suspends the organ/tissue and its feeding structures to the posterior wall of the body. Anatomy is the setting/structure, in which life events/functions occur. In the research and discussion of membrane anatomy, abiding by the scientific paradigm and upholding the scientific spirit are the only way to obtain reliable knowledge and the criterion for in-depth scientific research.


Assuntos
Fáscia , Mesentério , Humanos , Membrana Serosa
7.
Zhonghua Wei Chang Wai Ke Za Zhi ; 24(7): 567-571, 2021 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-34289538

RESUMO

In radical gastrectomy, D2 systemic lymphadenectomy, which includes complete resection of the bursa sac and omentum, and D2 extended lymphadenectomy outside the bursa sac, is a standard procedure accepted by gastrointestinal surgeons generally. However, a series of clinical trials showed that both D2 extended lymphadenectomy and bursectomy could not improve oncologic benefit, but increase surgical risk. These findings showed a lot of conflicts in gastric cancer surgery, gastrointestinal surgery, even in oncological surgery. It was demonstrated that bursa sac and greater omentum were neither mesogastrium nor the proximal segment of dorsal mesogastrium (PSDM), which has been identified recently. Local physiological structures (such as blood vessels and lymphatic nodes) and pathological events (such as lymph nodes metastasis and metastasis V) only occur in mesentery in broad sense (i.e. PSDM). Broken PSDM during radical gastrectomy can result in cancer cell leakage into the operational field. Therefore, complete PSDM excision in the D2 field (D2+CME) is suggested as a better procedure for local advanced gastric cancer, which can get benefits not only in surgical hazard, but also in oncologic result. The results of PSDM research could lead to three changes: (1) resolving some long standing problems in gastric cancer surgery, gastrointestinal surgery, and even oncologic surgery; (2) opening an new era for finding and utilizing extra-intestinal mesentery in broad sense; (3) formulating the theory of membrane anatomy which may update, iterate and upgrade related information of classical anatomy, pathology, surgery and oncology.


Assuntos
Gastrectomia , Neoplasias Gástricas , Humanos , Excisão de Linfonodo , Metástase Linfática , Mesentério , Neoplasias Gástricas/cirurgia
9.
Eur Rev Med Pharmacol Sci ; 25(5): 2409-2414, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33755980

RESUMO

The COVID-19 (Corona Virus Disease 2019) outbreak, which seriously affected people's lives across the world, has not been effectively controlled. Previous studies have demonstrated that SARS-COV-2 (Severe acute respiratory syndrome coronavirus 2) infecting host cells mainly rely on binding to receptor proteins, namely ACE2 and TMPRSS2. COVID-19 transmission is faster than the severe acute respiratory syndrome (SARS) pneumonia outbreak in 2002. This is mainly attributed to the different pathways of virus-infected host cells, coupled with patients' atypical clinical characteristics. SARS-CoV-2 is mainly transmitted through respiratory droplets and contact, infecting lung tissues before damaging other body organs, such as the liver, brain, kidney and heart. The present study identified potential target genes for SARS-COV-2 receptors, ACE2 and TMPRSS2, in normal human lung tissue. The findings provide novel insights that will guide future drug development approaches for treatment of COVID-19.


Assuntos
Enzima de Conversão de Angiotensina 2/genética , COVID-19/genética , Receptores Virais/genética , Serina Endopeptidases/genética , Enzima de Conversão de Angiotensina 2/biossíntese , Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/metabolismo , COVID-19/virologia , Correlação de Dados , Expressão Gênica , Humanos , Receptores Virais/biossíntese , Receptores Virais/metabolismo , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/metabolismo , Serina Endopeptidases/biossíntese , Serina Endopeptidases/metabolismo
10.
Eur Rev Med Pharmacol Sci ; 25(3): 1724-1731, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33629341

RESUMO

The outbreak of COVID-19 seriously affected people's life and safety, and it has not been effectively controlled all over the world at present. The binding of S protein of SARS-COV-2 virus to ACE2 receptor requires the assistance of Transmembrane Serine Protease 2 (TMPRSS2), which can activate the S protein on the surface of virus and promote its binding to the ACE2 receptor. With the continuous accumulation of experience in the treatment of COVID-19 patients and the experimental studies of a large number of scientific researchers, it was found that COVID-19 patients had a higher mortality rate in patients with underlying diseases. Therefore, for COVID-19 patients with tumors, the mortality rate may be significantly higher than other people. Clinical studies had found that some patients were complicated with cytokine storm in clinical treatment, which was also the direct cause of death for some patients. The infiltration of immune cells and the release of a variety of cytokines were important factors causing cytokine storm. Therefore, for COVID-19 patients with tumors, it was of great clinical significance to explore the relationship between COVID-19 virus receptor ACE2, TMPRSS2 and immune cell infiltration, which can help clinicians to make some more appropriate treatment plans.


Assuntos
Enzima de Conversão de Angiotensina 2/genética , COVID-19/imunologia , Neoplasias/imunologia , SARS-CoV-2 , Serina Endopeptidases/genética , COVID-19/complicações , COVID-19/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias/complicações , Neoplasias/genética , Ligação Proteica , Glicoproteína da Espícula de Coronavírus/genética
11.
Zhonghua Wai Ke Za Zhi ; 58(11): 822-825, 2020 Nov 01.
Artigo em Chinês | MEDLINE | ID: mdl-33120442

RESUMO

The bursa sac and greater omentum were considered as the dorsal mesogastrium more than 100 years. Bursectomy and omentectomy has been used as an essential part of radical gastrectomy with extended lymphadenectomy. However, structure of the bursa sac and omentum were difficult to be consistent with the definition and deduction of the mesentery. Also, it was hard to be proved that bursectomy and omentectomy could get oncological benefit from clinical randomized control trials recent years. We proposed a model of the proximal segment of dorsal mesogastrium (PSDM) here to compared with bursa model. It was demonstrated that the PSDM was consisted by the right gastric mesentery, right gastroepiploic mesentery, left gastric mesentery, left gastroepiploic mesentery, posterior gastric mesentery, and short gastric mesentery. The complete PSDM excision have been proved efficient in decreasing bleeding during operation and preventing cancer leak from PSDM during lymphadenectomy, as well as limiting the surgical hazard and developing oncological benefit. So that, PSDM model was presented as an alternative model for surgeons to practice and prove, even more evidences are still on the way.


Assuntos
Laparoscopia , Mesentério , Neoplasias Gástricas , Gastrectomia , Humanos , Excisão de Linfonodo , Mesentério/cirurgia , Omento/cirurgia , Neoplasias Gástricas/cirurgia
12.
Zhonghua Wei Chang Wai Ke Za Zhi ; 23(7): 629-633, 2020 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-32683821

RESUMO

Membrane anatomy is the anatomy of mesentery in broad sense and its beds, which was merged from clinical results of surgical practice, optic observation and traditional theories contradiction or omission. Membrane anatomy is not only a plane, but also a body or bloc which is surrounded by fascia and serous membrane. It is not only fascia, but also a channel or pathway, in which the life event occurred. It is not only mesentery anatomy, but included mesentery beds, on which the mesentery was lied, even buried in. Following the new version of this anatomy map, surgical hazard during operation and postoperative oncological recurrence will be decreased simultaneously. And, following the definition of the mesentery in broad sense, new mesenteries will be discovered under macro surgery, which will optimize surgical operation and get better surgical and oncological results.


Assuntos
Fáscia/anatomia & histologia , Mesentério/anatomia & histologia , Fáscia/patologia , Humanos , Mesentério/patologia , Mesentério/cirurgia , Peritônio/anatomia & histologia , Peritônio/patologia , Peritônio/cirurgia
13.
Zhonghua Gan Zang Bing Za Zhi ; 27(10): 737-740, 2019 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-31734985

RESUMO

Over 70% of hepatocellular carcinoma patients have not received traditional surgery because of their own disease characteristics and the limitations of traditional surgical methods. With the advancement of medical technology and the development of minimally invasive concepts, minimally invasive surgery, transcatheter arterial chemoembolization, and local ablation have received increasing attention. The combination of various treatment methods can help to strengthen the characteristics of each treatment, but the guiding standard of comprehensive treatment still needs further exploration and research.


Assuntos
Carcinoma Hepatocelular/cirurgia , Ablação por Cateter , Quimioembolização Terapêutica , Neoplasias Hepáticas/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos , Terapia Combinada , Humanos , Resultado do Tratamento
14.
Zhonghua Gan Zang Bing Za Zhi ; 27(10): 760-765, 2019 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-31734989

RESUMO

Objective: To study the expression level of monoacylglycerol lipase (MAGL) in liver tissues of patients with hepatocellular carcinoma (HCC), and its clinical correlation. Methods: Immunohistochemistry was employed to detect MAGL protein in 353 cases with hepatocellular carcinoma (HCC) and tissue microarray (TMA) for paracancerous liver tissues. The expression levels of MAGL in TMA were quantitatively analyzed using Image-Pro plus 6.0. The difference in MAGL expression between liver cancer tissues and paracancerous liver tissues was compared. Combined with the clinical follow-up data of TMA patients, the correlation between the expression of MAGL in TMA and the degree of HCC tumors differentiation and the survival rate of 1-year and 3-year were analyzed using Logistic regression analysis. The survival curves of patients with different levels of MAGL protein was plotted and analyzed using Kaplan-Meier method. The expression of MAGL protein was analyzed by multiple linear regression analysis. COX regression was used to analyze the correlation between MAGL protein expression level and the risk of HCC death in the included patients. Results: The expression of MAGL in HCC tissues was significantly higher than paracancerous liver tissues. The expression level of MAGL was correlated to the degrees of HCC tumors differentiation (P < 0.001) and 1-year survival rate (P = 0.01), but not with 3-year survival rate (P = 0.91). Survival curve showed that the expression level of MAGL was negatively correlated with prognosis and survival of HCC patients (P = 0.001). Multiple linear regressions showed a negative correlation between MAGL expression level and overall survival time of HCC patients (P=0.010, R2=0.166, Durbin-Watson value: 1.989). COX regression showed that the expression of MAGL was a risk factor for death of patients with HCC [P = 0.004, Exp (B) = 1.000]. Conclusion: The expression level of MAGL has positive correlation with the malignant degree in HCC patients, and negative correlation with its prognosis. Therefore, MAGL may serve as a new prognostic indicator for HCC patients.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Monoacilglicerol Lipases/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/enzimologia , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/enzimologia , Prognóstico
15.
Eur Rev Med Pharmacol Sci ; 23(18): 8158-8167, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31599445

RESUMO

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) has been proven to be the most common liver disease in the world, which is a sterile liver disease and is characterized by chronic hepatic steatosis and inflammation. The first step of the spectrum of the disease is the non-alcoholic fatty liver (NAFL). Based on hepatocellular necrosis and inflammation, NAFL will progress to non-alcoholic steatohepatitis (NASH), which may have the potential to progress cirrhosis, and even hepatocellular carcinoma (HCC) in a few years. Kupffer cells (KCs) are liver-resident macrophages and have been proven to play a crucial role in NAFLD development. Cardiolipin is reported to be effective to trigger the activation of NLRP3 inflammasome through a ROS-independent signaling pathway. However, the exact mechanism of NLRP3 inflammasome activated by cardiolipin in KCs is still unclear. MATERIALS AND METHODS: To make clear of the specific mechanism mentioned above, we firstly used a MCD-induced NASH mice model to demonstrate that CLS1 suppression reduced hepatic steatosis and inflammation. Secondly, the results of IHC staining indicated that the expressions of CLS1 and NLRP3 in liver tissues were significantly upregulated in the NASH group compared to the ND group. On the contrary, CLS1 inhibition significantly downregulated NLRP3 expression in liver tissues, which indicated that CLS1 probably regulated the level of NLRP3 expression. Furthermore, we demonstrated that CLS1 suppression significantly ameliorated the liver function and decreased the TG level, and interleukin-1ß (IL-1ß) and IL-18 were markedly reduced upon CLS1 inhibition. RESULTS: In this work, we reported that cardiolipin is involved in the development of NASH, and the suppression of the cardiolipin synthesis by shRNA-CLS1 could ameliorate the hepatic pathogenic manifestations, as well as the serum inflammatory biomarkers. We further showed that the protein expressions of CLS1, NLRP3, ASC, and Caspase-1 were all upregulated in the NASH liver tissues and palmitic stimulated KCs. CONCLUSIONS: Our study showed that the upregulation of NLRP3 inflammasome activated by cardiolipin is crucial in NASH pathogenesis, which might provide a novel potential role of cardiolipin blockade in the treatment of NASH.


Assuntos
Proteínas Adaptadoras de Sinalização CARD/metabolismo , Cardiolipinas/metabolismo , Caspase 1/metabolismo , Inflamassomos/metabolismo , Células de Kupffer/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Alanina Transaminase/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Modelos Animais de Doenças , Ácidos Graxos não Esterificados/metabolismo , Inflamação , Interleucina-18/metabolismo , Interleucina-1beta/metabolismo , Fígado/metabolismo , Fígado/patologia , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Hepatopatia Gordurosa não Alcoólica/patologia , RNA Interferente Pequeno , Transferases (Outros Grupos de Fosfato Substituídos)/antagonistas & inibidores , Transferases (Outros Grupos de Fosfato Substituídos)/genética , Transferases (Outros Grupos de Fosfato Substituídos)/metabolismo , Triglicerídeos/metabolismo
16.
Oncogene ; 38(35): 6319-6321, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366984

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

17.
Zhonghua Wei Chang Wai Ke Za Zhi ; 22(5): 401-405, 2019 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-31104421

RESUMO

Membrane anatomy is in broad sense the anatomy of the mesentery and its bed, both of which are consisted of fascia membrane or/and serous membrane. Although the traditional mesentery has the definition of mesentery, people unconsciously identify them according to their "fan-shaped" and "free" characteristics. The "generalized mesentery" we propose refers to the fascia and/or serosa, envelope-like organs and their blood vessels, suspending to the posterior wall of the body, regardless of its shape, free or not. So the main points of the anatomy are as follows.(1) Organs or tissues with their feeding structures are enveloped by the fascia membrane or/and serous membrane, suspending to posterior wall of the body, to form different shapes of the mesentery in broad sense, and most of them are buried in the mesentery bed. (2) Cancer metastasis type V of in the gut moves in the envelop of the mesentery in broad sense.(3) Intraoperative breach of the envelop membrane not only results in intraoperative bleeding, but also cancer cell leakage from the mesentery. (4) The cancer of gut can be divided into cancer in the mesentery, cancer out of the mesentery and cancer at edge of the mesentery based on this anatomy. Radical tumor resection is effective for cancer in the mesentery, which should not be artificially breached into those of cancer out of the mesentery. The essence of neoadjuvant chemoradiation is to push cancer at edge of the mesentery back inside the mesentery.(5) Based on such anatomy, radical gut tumor operations are divided into D2/D3 procedure, without emphasizing the integrity of the mesentery during lymphatic dissection; CME procedure, which emphasizes the integrity of the mesentery but does not strictly define the extent of lymphatic dissection; D2/D3 + CME procedure, which strictly defines the integrity of the mesentery and the extent of lymphatic dissection.(6)For gastrointestinal tumors of the same T stage, shorter mesentery indicates worse prognosis.(7) For gastrointestinal tumors with the same T stage and the same length of mesentery, the more mesentery buried in the mesentery bed, the worse prognosis. (8) The above seven principles are universal in the organs of the body cavity (and even all internal organs).Membrane anatomy, unlike traditional "plane surgery" , is completely different from the "anatomy of the membrane..." described by Japanese scholars, but mainly bases on generalized mesentery and mesentery bed, meanwhile inherent life events can be accurately defined and confirmed.


Assuntos
Antineoplásicos/farmacologia , Neoplasias do Sistema Digestório/patologia , Neoplasias do Sistema Digestório/cirurgia , Mesentério/patologia , Antineoplásicos/uso terapêutico , Dissecação , Fáscia/patologia , Humanos , Mesentério/anatomia & histologia , Mesentério/efeitos dos fármacos , Mesentério/cirurgia , Estadiamento de Neoplasias , Prognóstico , Membrana Serosa/patologia
18.
Oncogene ; 38(11): 1951-1965, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30390075

RESUMO

Cancer stem cells (CSCs) are inherently resistant to chemotherapy, and CSCs in chemotherapy-failed recurrent tumors are enriched; however, the cellular origin of chemotherapy-induced CSC enrichment remains unclear. Communication with stromal fibroblasts may induce cancer cell dedifferentiation into CSCs through secreted factors. We recently demonstrated that fibroblast-derived exosomes promote chemoresistance in colorectal cancer (CRC). Here, we report that fibroblasts confer CRC chemoresistance via exosome-induced reprogramming (dedifferentiation) of bulk CRC cells to phenotypic and functional CSCs. At the molecular level, we provided evidence that the major reprogramming regulators in fibroblast-exosomes are Wnts. Exosomal Wnts were found to increase Wnt activity and drug resistance in differentiated CRC cells, and inhibiting Wnt release diminished this effect in vitro and in vivo. Together, our results indicate that exosomal Wnts derived from fibroblasts could induce the dedifferentiation of cancer cells to promote chemoresistance in CRC, and suggest that interfering with exosomal Wnt signaling may help to improve chemosensitivity and the therapeutic window.


Assuntos
Desdiferenciação Celular , Neoplasias Colorretais/patologia , Resistencia a Medicamentos Antineoplásicos , Exossomos/metabolismo , Células-Tronco Neoplásicas/fisiologia , Via de Sinalização Wnt/fisiologia , Animais , Antineoplásicos/farmacologia , Desdiferenciação Celular/efeitos dos fármacos , Desdiferenciação Celular/genética , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Exossomos/efeitos dos fármacos , Exossomos/patologia , Feminino , Fibroblastos/patologia , Fibroblastos/fisiologia , Fluoruracila/farmacologia , Células HT29 , Humanos , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/patologia , Oxaliplatina/farmacologia , Comunicação Parácrina/efeitos dos fármacos , Pirazinas/farmacologia , Piridinas/farmacologia , Via de Sinalização Wnt/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Zhonghua Gan Zang Bing Za Zhi ; 26(9): 718-720, 2018 Sep 20.
Artigo em Chinês | MEDLINE | ID: mdl-30481877

RESUMO

Hepatocellular carcinoma (HCC) is a common and high incidence disease in China. It is presently thought that diabetes is one of the independent risk factor for HCC. Diabetes and liver cancer are closely related, but the relationship and mechanism of diabetes and liver cancer are quite complex and controversial. Insulin resistance, glucose metabolism and lipid metabolism disorders, and abnormal release of inflammatory mediators are the common bases of these two diseases. The molecular mechanisms of glycogen synthase kinase-3, toll like receptor 4, CCL5, CXCL14 and NCOA5, TCF7L2 genes affecting the correlation between liver cancer and diabetes mellitus are discussed and explained to provide the basis for the study and treatment of disease.


Assuntos
Carcinoma Hepatocelular , Diabetes Mellitus Tipo 2 , Neoplasias Hepáticas , Adulto , China , Humanos , Resistência à Insulina
20.
J Viral Hepat ; 25(7): 842-852, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29406564

RESUMO

The relation between hepatitis B virus (HBV) infection and fatty liver has been addressed by several observational studies, but their results remain controversial. To date, no study has precisely investigated the association of current and past HBV infection with the risk of nonalcoholic fatty liver disease (NAFLD) in the Chinese population. Therefore, we conducted a hospital-based case-control study in southwestern China to clarify this issue. A total of 631 newly ultrasound-diagnosed NAFLD cases and 2357 controls were selected from 123 243 consecutive patients admitted to a tertiary-care hospital between January 2015 and December 2016. Multivariate logistic regression was employed to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). A propensity score was developed for adjustment and matching. Subgroup analysis was conducted to identify potential effect modifiers. Current and past HBV infection had an overall prevalence of 9.7% and 55.2%, respectively. In the fully adjusted model, current HBV infection was associated with a decreased risk of NAFLD (OR 0.64; 95% CI 0.42-0.95). A similar inverse association was observed in both propensity-score-adjusted (OR 0.58; 95% CI 0.40-0.86) and propensity-score-matched analyses (OR 0.61; 95% CI 0.40-0.92).The inverse association was stronger in patients with hypertension than in those without (Pinteraction  = .018).No significant association between past HBV infection and NAFLD risk was found. In conclusion, current but not past HBV infection is associated with a decreased risk of NAFLD in the Chinese population. The corresponding biological mechanisms remain to be elucidated.


Assuntos
Hepatite B/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Idoso , Estudos de Casos e Controles , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Prevalência , Pontuação de Propensão , Medição de Risco , Ultrassonografia
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