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OBJECTIVE: Our study aimed to assess the ability of high-sensitivity modified Glasgow prognostic Score (HS-mGPS) predicting survival in patients undergoing radical surgery for hepatocellular carcinoma (HCC) and to compare the impact with other Inflammation-Based prognostic scoring systems including Glasgow prognostic Score (GPS) and modified GPS (mGPS). METHODS: Our study evaluated 293 patients with HCC who had undergone hepatectomy at the Third Affiliated Hospital of Soochow University between 2010 and 2018. The HS-mGPS, mGPS, and GPS were calculated based on particular cut-off values of preoperative C-reactive protein and albumin, and the correlations between HS-mGPS and clinicopathological parameters were evaluated. Univariate and multivariate survival analyses were conducted by Kaplan-Meier method and Cox proportional hazards model. To evaluate the discrimination ability of each prognostic score, the receiver operating characteristic (ROC) curve were generated and the areas under the curve (AUC) were measured and compared. RESULT: The study results indicated a correlation between elevated HS-mGPS scores and adverse clinical factors, including higher BCLC stage, C-P grade, multiple tumors, and larger tumor diameter. Kaplan-Meier and univariate survival analyses revealed that higher scores of HS-mGPS, GPS, and mGPS were all associated with significantly reduced overall survival (OS) (all p < 0.001). In multivariate survival analysis, HS-mGPS emerged as an independent risk factor for poor OS in patients undergoing hepatectomy for HCC (p = 0.010), along with factors including maximal tumor diameter (p < 0.001), microvascular invasion (MVI) (p = 0.008), and BCLC stage (p = 0.001). The analysis of ROC curves and the AUC values indicated that HS-mGPS outperforms GPS and mGPS in predicting the long-term prognosis of patients with resectable HCC. CONCLUSION: Preoperative HS-mGPS proves superior in predicting adverse long-term outcomes in HCC patients undergoing radical surgery.
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Carcinoma Hepatocelular , Hepatectomia , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/sangue , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Idoso , Estudos Retrospectivos , Adulto , Estimativa de Kaplan-Meier , Taxa de Sobrevida , Proteína C-Reativa/análiseRESUMO
PURPOSE: Long noncoding RNAs (lncRNAs) exert a significant influence on various cancer-related processes through their intricate interactions with RNAs. Among these, lncRNA ZFAS1 has been implicated in oncogenic roles in multiple cancer types. Nevertheless, the intricate biological significance and underlying mechanism of ZFAS1 in the initiation and progression of hepatocellular carcinoma (HCC) remain largely unexplored. METHODS: Analysis of The Cancer Genome Atlas Program (TCGA) database revealed a notable upregulation of lncRNA ZFAS1 in HCC tissues. To explore its function, we investigated colony formation and performed CCK-8 assays to gauge cellular proliferation and wound healing, Transwell assays to assess cellular migration, and an in vivo study employing a nude mouse model to scrutinize tumor growth and metastasis. Luciferase reporter assay was used to confirm the implicated interactions. Rescue experiments were conducted to unravel the plausible mechanism underlying the activation of the PI3K/AKT pathway by lncRNAs ZFAS1 and ATIC. RESULTS: ZFAS1 and ATIC were significantly upregulated in the HCC tissues and cells. ZFAS1 knockdown inhibited cell proliferation and migration. We observed a direct interaction between the lncRNA ZFAS1 and ATIC. ATIC knockdown also suppressed cell proliferation and migration. SC79, an activator of AKT, partially restores the effects of lncRNA ZFAS1/ATIC knockdown on cell proliferation and migration. Knockdown of lncRNA ZFAS1/ATIC inhibited tumor growth and lung metastasis in vivo. CONCLUSION: Overall, lncRNA ZFAS1 regulates ATIC transcription and contributes to the growth and migration of HCC cells through the PI3K/AKT signaling pathway.
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Carcinoma Hepatocelular , Movimento Celular , Proliferação de Células , Neoplasias Hepáticas , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , RNA Longo não Codificante , Transdução de Sinais , Animais , Feminino , Humanos , Masculino , Camundongos , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Nus , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , RNA Longo não Codificante/genética , Transdução de Sinais/genéticaRESUMO
Acute cholestatic liver injury (ACLI) is a disease associated with bile duct obstruction that causes liver inflammation and apoptosis. Although G protein-coupled bile acid receptor1 (Gpbar-1) has diverse metabolic roles, its involvement in ACLI-associated immune activation remains unclear. Liver tissues and blood samples from 20 patients with ACLI and 20 healthy individuals were analyzed using biochemical tests, H&E staining, western blotting, and immunohistochemistry to verify liver damage and expression of Gpbar-1. The expression of Gpbar-1, cAMP/PKA signaling, and the NLRP3 inflammasome was tested in wild-type (WT) and Gpbar-1 knockdown (si-Gpbar-1) mice with ACLI induced by bile duct ligation (BDL) and in primary Kupffer cells (KCs) with or without Gpbar-1-siRNA. The results showed that total bile acids and Gpbar-1 expressions were elevated in patients with ACLI. Gpbar-1 knockdown significantly worsened BDL-induced acute hepatic damage, inflammation, and liver apoptosis in vivo. Knockdown of Gpbar-1 heightened KC sensitivity to lipopolysaccharide (LPS) stimulation. Gpbar-1 activation inhibited LPS-induced pro-inflammatory responses in normal KCs but not in Gpbar-1-knockdown KCs. Notably, NLRP3-ASC inflammasome expression was effectively enhanced by Gpbar-1 deficiency. Additionally, Gpbar-1 directly increased intracellular cAMP levels and PKA phosphorylation, thus disrupting the NLRP3-ASC inflammasome. The pro-inflammatory characteristic of Gpbar-1 deficiency was almost neutralized by the NLRP3 inhibitor CY-09. In vitro, M1 polarization was accelerated in LPS-stimulated Gpbar-1-knockdown KCs. Therapeutically, Gpbar-1 deficiency exacerbated BDL-induced ACLI, which could be rescued by inhibition of the NLRP3-ASC inflammasome. Our study reveal that Gpbar-1 may act as a novel immune-mediated regulator of ACLI by inhibiting the NLRP3-ASC inflammasome.
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Colestase , Proteínas Quinases Dependentes de AMP Cíclico , AMP Cíclico , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Receptores Acoplados a Proteínas G , Transdução de Sinais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Animais , Humanos , Inflamassomos/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , AMP Cíclico/metabolismo , Camundongos , Masculino , Colestase/metabolismo , Colestase/patologia , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Células de Kupffer/metabolismo , Camundongos Endogâmicos C57BL , Feminino , Macrófagos/metabolismo , Macrófagos/imunologia , Fígado/metabolismo , Fígado/patologia , Fígado/lesões , Lipopolissacarídeos/toxicidade , Adulto , Pessoa de Meia-IdadeRESUMO
The liver is a major metastatic site (organ) for gastrointestinal cancers (such as colorectal, gastric, and pancreatic cancers) as well as non-gastrointestinal cancers (such as lung, breast, and melanoma cancers). Due to the innate anatomical position of the liver, the apoptosis of T cells in the liver, the unique metabolic regulation of hepatocytes and other potential mechanisms, the liver tends to form an immunosuppressive microenvironment and subsequently form a pre-metastatic niche (PMN), which can promote metastasis and colonization by various tumor cells(TCs). As a result, the critical role of immunoresponse in liver based metastasis has become increasingly appreciated. T cells, a centrally important member of adaptive immune response, play a significant role in liver based metastases and clarifying the different roles of the various T cells subsets is important to guide future clinical treatment. In this review, we first introduce the predisposing factors and related mechanisms of liver metastasis (LM) before introducing the PMN and its transition to LM. Finally, we detail the role of different subsets of T cells in LM and advances in the management of LM in order to identify potential therapeutic targets for patients with LM.
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Neoplasias Hepáticas , Linfócitos T , Humanos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/patologia , Linfócitos T/imunologia , Animais , Microambiente Tumoral/imunologiaRESUMO
AIMS: Non-alcoholic steatohepatitis (NASH) is characterized by aberrant lipid metabolism in hepatocytes. We investigated the involvement of a histone H3K9 methyltransferase Suv39h2 in the pathogenesis of NASH. METHODS AND MATERIALS: NASH is induced by feeding the mice with a high-fat high-carbohydrate (HFHC) diet or a high-fat choline-deficient amino acid defined (HFD-CDAA) diet. The Suv39h2f/f mice were crossbred with the Alb-Cre mice to specifically delete Suv39h2 in hepatocytes. KEY FINDINGS: Ablation of Suv39h2 in hepatocytes improved insulin sensitivity of the mice fed either the HFHC diet or the CDAA-HFD diet. Importantly, Suv39h2 deletion significantly ameliorated NAFLD as evidenced by reduced lipid accumulation, inflammation, and fibrosis in the liver. RNA-seq uncovered Vanin-1 (Vnn1) as a novel transcriptional target for Suv39h2. Mechanistically, Suv39h2 repressed Vnn1 transcription in hepatocytes exposed to free fatty acids. Consistently, Vanin-1 knockdown normalized lipid accumulation in Suv39h2-null hepatocytes. Importantly, a significant correlation between Suv39h2, Vanin-1, and hepatic triglyceride levels was identified in NASH patients. SIGNIFICANCE: Our study uncovers a novel mechanism whereby Suv39h2 may contribute to NASH pathogenesis and suggests that targeting the Suv39h2-Vanin-1 axis may yield novel therapeutic solutions against NASH.
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Hepatócitos , Histona-Lisina N-Metiltransferase , Hepatopatia Gordurosa não Alcoólica , Animais , Humanos , Camundongos , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Hepatócitos/enzimologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Hepatopatia Gordurosa não Alcoólica/genética , Histona-Lisina N-Metiltransferase/genética , Metabolismo dos LipídeosRESUMO
Adhesive hydrogels (AHs) are considered ideal materials for flexible sensors. However, the lack of effective energy dissipation networks and sparse surface polar groups in AHs lead to poor mechanical properties and interfacial adhesion, which limit their practical application. Herein, a tough, long-lasting adhesive and highly conductive nanocomposite hydrogel (PACPH) was fabricated via the synergy of interfacial entanglement and adhesion group densification. PACPH was obtained by the in situ polymerization of highly carboxylated cellulose nanocrystals (SCNCPA, surface pre-grafted polyacrylic acid chains, C-COOH = 11.5 mmol g-1) with the acrylic acid precursor. The unique tacticity of SCNCPA provides strong interface entanglement and multiple hydrogen bonds with the PACPH network, which further increases the energy dissipated during SCNCPA displacements, and enhances the mechanical properties of PACPH (tensile strength = 1.45 MPa, modulus = 332 kPa, and fracture toughness = 13.2 MJ m-3). Meanwhile, SCNCPA increases the density of surface polar groups in PAPCH and also acts as an anchor point to improve the adhesion strength (>2-3 times) of PACPH on various substrates. The combination of excellent mechanical, adhesive, and conductive properties of the PAPCH-integrated patches enables long-term monitoring of human daily activities and electrocardiogram (ECG) signals, verifying that PAPCH is a promising material platform for the further development of flexible sensors and other health management devices.
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Lightweight porous hydrogels provide a worldwide scope for functional soft mateirals. However, most porous hydrogels have weak mechanical strength, high density (>1 g cm-3 ), and high heat absorption due to weak interfacial interactions and high solvent fill rates, which severely limit their application in wearable soft-electronic devices. Herein, an effective hybrid hydrogel-aerogel strategy to assemble ultralight, heat-insulated, and tough polyvinyl alcohol (PVA)/SiO2 @cellulose nanoclaws (CNCWs) hydrogels (PSCG) via strong interfacial interactions with hydrogen bonding and hydrophobic interaction is demonstrated. The resultant PSCG has an interesting hierarchical porous structure from bubble template (≈100 µm), PVA hydrogels networks introduced by ice crystals (≈10 µm), and hybrid SiO2 aerogels (<50 nm), respectively. PSCG shows unprecedented low density (0.27 g cm-3 ), high tensile strength (1.6 MPa) & compressive strength (1.5 MPa), excellent heat-insulated ability, and strain-sensitive conductivity. This lightweight porous and tough hydrogel with an ingenious design provides a new way for wearable soft-electronic devices.
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Introduction: In emergency surgery for acute obstruction of the common bile duct (CBD), primary duct closure (PC) of the CBD after laparoscopic common bile duct exploration (LCBDE) remains challenging. Aim: To explore the safety and effectiveness of this surgical method after LCBDE in patients with acute choledocholithiasis and discuss the feasibility of PC in the CBD. Material and methods: This retrospective study on surgical efficacy and safety involved 232 patients treated at The Third Affiliated Hospital of Soochow University between January 2015 and December 2019. These patients underwent LC + LCBDE for acute choledocholithiasis and were categorized into PC and T-tube drainage (TD) groups based on the method of closure of the CBD. The basic preoperative information, intraoperative situation, postoperative situation, and complications were analysed and compared between groups. Results: The baseline characteristics and preoperative information of patients between the 2 groups were balanced. Patients in the PC group had a shorter operation time (p < 0.001) and CBD suturing time (p < 0.001) than those in the TD group. In addition, compared with the TD group in postoperative situations, gastrointestinal recovery (p = 0.002), drainage removal (p < 0.001), and the length of postoperative hospital stay (p = 0.004) were markedly decreased in the PC group. In terms of intraoperative blood loss (p = 0.961), use of pipe washing (49.0 vs. 54.6%, p = 0.397), use of stone basket (50.0 vs. 42.3%, p = 0.243), use of electrohydraulic lithotripsy (1.0 vs. 3.1%, p = 0.525), postoperative liver function, and complications there was no significant difference between the PC and TD groups. No intraoperative transfusion and postoperative mortality occurred in either group. During 6 months of follow-up, only 1 patient showed biliary stricture in the PC group, and 2 and 4 patients in the PC and TD groups, respectively, showed residual stones. Conclusions: PC after LCBDE in acute choledocholithiasis patients displays better therapeutic outcomes than TD in some intraoperative and postoperative situations. PC of the CBD after LCBDE is a safe and effective therapeutic option in acute choledocholithiasis patients.
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The ability of the human liver to both synthesize extracellular matrix(ECM), as well as regulate fibrogenesis, are integral functions to maintaining homoeostasis. Chronic liver injury stimulates fibrogenesis in response to the imbalance between ECM accumulation and fibrosis resolution. Liver disease that induces fibrogenesis is associated with multiple risk factors like hepatitis infection, schistosomiasis, alcohol, certain drugs, toxicants and emerging aetiology like diabetes and obesity. The activation of hepatic stellate cells (HSCs), whose function is to generate and accumulate ECM, is a pivotal event in liver fibrosis. Simultaneously, HSCs selectively promote regulatory T-cells (Tregs) in an interleukin-2-dependent pattern that displays a dual relationship. On the one hand, Tregs can protect HSCs from NK cell attack, while on the other hand, they demonstrate an inhibitory effect on HSCs. This paper reviews the dual role of Tregs in liver fibrogenesis which includes its promotion of immunosuppression, as well as its activation of fibrosis. In particular, the balance between Tregs and the Th17 cell population, which produce interleukin (IL)-17 and IL-22, is explored to demonstrate their key role in maintaining homoeostasis and immunoregulation. The contradictory roles of Tregs in liver fibrosis in different immune microenvironments and molecular pathways need to be better understood if they are to be deployed to manage this disease.
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This study aimed to investigate the therapeutic efficacy of programmed spatial anatomy of myopectineal orifice technique in laparoscopic total extraperitoneal hernioplasty (TEP) surgery. A total of 121 adult male patients with unilateral inguinal hernias who underwent TEP in the Department of General Surgery, Wujin Hospital, affiliated with Jiangsu University, from January 2019 to December 2020 were selected. Patients were divided into the procedural (63 cases) and traditional groups (58 cases) according to the surgical methods adopted. The procedural group underwent programmed spatial anatomy of the myopectineal orifice combined with TEP, and the traditional group underwent traditional TEP. The perioperative evaluation indicators and postoperative complications were observed and compared between the two groups. Compared with the traditional group, the time of handling hernia, the intraoperative operation time, intraoperative blood loss, postoperative ambulation time, and postoperative hospital stay in the procedural group were significantly reduced (P < 0.05). The incidence of postoperative complications such as sensory nerve abnormalities and chronic pain was significantly decreased (P < 0.05), and the total incidence of complications in the procedural group was significantly lower than that in the traditional group (P < 0.05). While there was no significant difference in postoperative incision infection (P > 0.05). The programmed spatial anatomy of the myopectineal orifice can significantly improve the treatment outcome of TEP, significantly improve the patients' intraoperative and postoperative indicators, and reduce the incidence of postoperative complications. It is worthy of being promoted among young physicians and basic hospitals.
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Hérnia Inguinal , Laparoscopia , Adulto , Humanos , Masculino , Herniorrafia/métodos , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Estudos Retrospectivos , Hérnia Inguinal/cirurgia , Resultado do Tratamento , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgiaRESUMO
BACKGROUND AND AIMS: Myofibroblasts are considered the major effector cell type of liver fibrosis and primarily derived from hepatic stellate cells (HSCs). In the present study, we investigated the contribution of C-C motif chemokine (CCL11) to HSC-myofibroblast trans -differentiation and its implication in liver fibrosis. APPROACH AND RESULTS: We report that CCL11 levels were elevated in HSCs, but not in hepatocytes or Kupffer cells, isolated from mice with liver fibrosis compared with the control mice. CCL11 levels were also up-regulated by 2 pro-fibrogenic growth factors TGF-ß and platelet derived growth factor in cultured HSCs. Mechanistically, zinc finger factor 281 bound to the CCL11 promoter and mediated CCL11 trans -activation in HSCs. Depletion of CCL11 attenuated whereas treatment with recombinant CCL11 promoted HSC activation. Further, global CCL11 deletion ( CCL11-/- ) or HSC/myofibroblast-specific CCL11 knockdown mitigated fibrogenesis in mice. RNA-sequencing revealed that CCL11 might regulate HSC activation by stimulating the transcription of Jagged 1. Reconstitution of Jagged 1 restored the fibrogenic response in CCL11-/- mice. Finally, several targeting strategies that aimed at blockading CCL11 signaling, either by administration of an antagonist to its receptor C-C motif chemokine receptor 3 or neutralizing antibodies against CCL11/C-C motif chemokine receptor 3, ameliorated liver fibrosis in mice. CONCLUSIONS: Our data unveil a previously unrecognized role for CCL11 in liver fibrosis and provide proof-of-concept evidence that targeting CCL11 can be considered as an effective therapeutic approach.
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Hepatócitos , Cirrose Hepática , Animais , Camundongos , Células Cultivadas , Células Estreladas do Fígado/metabolismo , Hepatócitos/metabolismo , Proteína Jagged-1/metabolismo , Fígado/patologia , Cirrose Hepática/patologia , Receptores de Quimiocinas/metabolismoRESUMO
High-performance thermally insulating nanocellulose-based aerogels with robust mechanical properties is highly desirable for energy-saving and thermal protection applications. However, the large-scale applications of traditional nanocellulose aerogels are still limited by their brittleness nature and rigorous processes. Herein, an effective biomimetic hybrid strategy for high strength and thermal insulated nanocellulose-based aerogel with hierarchical-ordered microstructure is designed and fabricated. The novel cellulose nanoclaws-based aerogels extracted from corncob are hybridized by nanosized silica aerogel layer in situ and have an intensified H-bonding crosslinked network after ambient-drying and hotpress treatment, endowing excellent mechanical properties (16-58 MPa) as well as scalable potential for structure materials. Benefitting from the synergistic effect of the tailored hierarchical-ordered microstructure, the resulting hybrid aerogels also possess high specific surface area (30-630 m2 g-1), low thermal conductivity (0.021 W m-1 K-1), and outstanding flame retardant. This hybrid strategy provides an avenue to produce thermal-insulated and mechanically robust materials.
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Celulose , Retardadores de Chama , Biomimética , Celulose/química , Géis/química , Dióxido de Silício/químicaRESUMO
[This corrects the article DOI: 10.3389/fcell.2021.733308.].
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The liver is a central immunomodulator that ensures a homeostatic balance between protection and immunotolerance. A hallmark of hepatocellular carcinoma (HCC) is the deregulation of this tightly controlled immunological network. Immune response in the liver involves a complex interplay between resident innate, innate, and adaptive immune cells. The immune response in the liver is modulated by its continuous exposure to toxic molecules and microorganisms that requires a degree of immune tolerance to protect normal tissue from damage. In HCC pathogenesis, immune cells must balance a dual role that includes the elimination of malignant cells, as well as the repair of damaged liver tissue to maintain homeostasis. Immune response in the innate and adaptive immune systems extends to the cross-talk and interaction involving immune-regulating non-hematopoietic cells, myeloid immune cells, and lymphoid immune cells. In this review, we discuss the different immune responses of resident immune cells in the tumor microenvironment. Current FDA-approved targeted therapies, including immunotherapy options, have produced modest results to date for the treatment of advanced HCC. Although immunotherapy therapy to date has demonstrated its potential efficacy, immune cell pathways need to be better understood. In this review article, we summarize the roles of specific resident immune cell subsets and their cross-talk subversion in HCC pathogenesis, with a view to identifying potential new biomarkers and therapy options.
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Background: Programmed cell death-1 (PD-1) immune checkpoint inhibitors are not effective in treating all patients with hepatocellular carcinoma (HCC), and regulatory T cells (Tregs) may determine the resistance to anti-PD-1 therapy. Methods: Patients were divided into two groups based on the clinical efficacy of anti-PD-1 therapy. Flow cytometry was used to determine the phenotype of CD4+, CD8+, and Tregs in peripheral blood mononuclear cells (PBMCs). CD4+CD45RA+T cells were sorted to analyze Treg differentiation and function. Results: No significant differences were found between resistant and sensitive patients in the percentage of CD4+ T cells and Tregs in PBMCs or the differentiation and function of induced Tregs (iTregs). However, iTregs from resistant patients presented higher monocarboxylate transporter (MCT) expression. Lactate induced more iTregs and improved OXPHOS levels in the resistant group. MCT1 and MCT2 were highly expressed in tumor-infiltrating Tregs, and patients with higher MCT1 expression had worse clinical outcomes. Combinatorial therapy with MCT antibody and anti-PD-1 therapy effectively inhibited tumor growth. Conclusion: MCT and its downstream lactate signal in Tregs can confer anti-PD-1 resistance and may be a marker of poor prognosis in HCC.
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Recent evidence suggests the global incidence and mortality of hepatocellular carcinoma (HCC) are increasing. Although the highest incidence of HCC remains entrenched in WHO regions with high levels of HBV-HCV infection, the etiology of this disease is rapidly changing to include other lifestyle risk factors. Extrahepatic metastasis is a frequent feature of advanced HCC and most commonly locates in the lungs and bone. Bone metastasis in HCC (HCC-BM) signals a more aggressive stage of disease and a poorer prognosis, simultaneously HCC-BM compromises the function and integrity of bone tissue. HCC induced osteolysis is a prominent feature of metastasis that complicates treatment needed for pathologic fractures, bone pain and other skeletal events like hypercalcemia and nerve compression. Early detection of bone metastases facilitates the treatment strategy for avoiding and relieving complications. Although recent therapeutic advances in HCC like targeting agents and immunotherapy have improved survival, the prognosis for patients with HCC-BM remains problematic. The identification of critical HCC-BM pathways in the bone microenvironment could provide important insights to guide future detection and therapy. This review presents an overview of the clinical development of bone metastases in HCC, identifying key clinical features and identifying potential molecular targets that can be deployed as diagnostic tools or therapeutic agents.
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Infiltration of eosinophils is associated with and contributes to liver regeneration. Chemotaxis of eosinophils is orchestrated by the eotaxin family of chemoattractants. We report here that expression of eotaxin-1 (referred to as eotaxin hereafter), but not that of either eotaxin-2 or eotaxin-3, were elevated, as measured by quantitative PCR and ELISA, in the proliferating murine livers compared to the quiescent livers. Similarly, exposure of primary murine hepatocytes to hepatocyte growth factor (HGF) stimulated eotaxin expression. Liver specific deletion of Brahma-related gene 1 (Brg1), a chromatin remodeling protein, attenuated eosinophil infiltration and down-regulated eotaxin expression in mice. Brg1 deficiency also blocked HGF-induced eotaxin expression in cultured hepatocytes. Further analysis revealed that Brg1 could directly bind to the proximal eotaxin promoter to activate its transcription. Mechanistically, Brg1 interacted with nuclear factor kappa B (NF-κB)/RelA to activate eotaxin transcription. NF-κB knockdown or pharmaceutical inhibition disrupted Brg1 recruitment to the eotaxin promoter and blocked eotaxin induction in hepatocytes. Adenoviral mediated over-expression of eotaxin overcame Brg1 deficiency caused delay in liver regeneration in mice. On the contrary, eotaxin depletion with RNAi or neutralizing antibodies retarded liver regeneration in mice. More important, Brg1 expression was detected to be correlated with eotaxin expression and eosinophil infiltration in human liver specimens. In conclusion, our data unveil a novel role of Brg1 as a regulator of eosinophil trafficking by activating eotaxin transcription.
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Quimiocina CCL11 , DNA Helicases , Regeneração Hepática , Proteínas Nucleares , Fatores de Transcrição , Animais , Células Cultivadas , Quimiocina CCL11/genética , Quimiocina CCL11/metabolismo , DNA Helicases/genética , DNA Helicases/metabolismo , Camundongos , NF-kappa B/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Ativação TranscricionalRESUMO
BACKGROUND: This retrospective study aimed to present our surgical experience in patients with benign tumour or trauma in spleen who underwent laparoscopic partial splenectomy (LPS) and to compare the results with those of patients who underwent an open partial splenectomy (OPS). METHODS: We analysed the medical data of patients who underwent LPS or OPS between January 2010 and January 2020. RESULTS: In total, 41 patients were enrolled. Nine patients underwent open surgery, 32 patients underwent laparoscopic surgery. The proportion of patients with tumours in the upper pole in LPS group was more than patients in OPS group. No difference was observed in estimated blood loss, allogeneic transfusion, postoperative stay, pathology and complications between LPS and OPS groups. The operation time in the LPS group (137.5 ± 30.8 min) was longer than that in the OPS group (88.3 ± 30.1 min) for patients with splenic traumatic rupture (P = 0.019). CONCLUSIONS: LPS is an effective and safe spleen-preserving surgery as OPS. The advantages are small trauma, light pain and quick recovery. It is suitable for patients with benign tumours or trauma confined to one side of the spleen.