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BACKGROUND: Whether radiofrequency ablation (RFA) and liver resection (LR) are comparable treatments for early-stage hepatocellular carcinoma (HCC) is controversial. We conducted this study to provide ample clinical evidence for the argument. METHODS: The PubMed, Embase, Web of Science, and Cochrane Library databases were systematically searched to identify randomized controlled trials (RCTs) and propensity score-matched (PSM) studies that compared long-term outcomes of both RFA and LR for patients with early-stage HCC. The hazard ratios (HRs) with 95% confidence intervals (95% CI) of overall survival (OS) and disease-free survival (DFS) were calculated. RESULTS: Thirty-six studies consisting of six RCTs and 30 PSM studies were included in this study, and a total of 7384 patients were involved, with 3694 patients being treated with LR and 3690 patients with RFA. Meta-analysis showed that LR provided better OS and DFS than RFA (HR: 1.22, 95% CI: 1.13-1.31; HR: 1.56, 95% CI: 1.39-1.74, respectively). A sensitivity analysis indicated that the results were stable. For the subgroup of patients with BCLC 0 stage, RFA and LR resulted in similar OS and DFS. For the subgroup of patients with single tumor sizes less than 3 cm, RFA reached similar OS (HR: 1.19, 95% CI: 0.90-1.58) but worse DFS compared with LR (HR: 1.45, 95% CI: 1.11-1.90). For the subgroup of ablation margin larger than 0.5 cm, LR still resulted in better OS than RFA (HR: 1.29, 95% CI: 1.09-1.53); while the ablation margin was larger than 1 cm, both RFA and LR resulted in similar OS. The modality of RFA was also a factor that affected results. Subgroup analysis showed that patients receiving ultrasound-guided RFA had worse OS and DFS than LR (HR: 1.24, 95% CI: 1.14-1.36; HR: 1.44, 95% CI: 1.25-1.66, respectively). CONCLUSIONS: Meta-analysis showed that LR provided better OS and DFS for patients with early-stage HCC. However, RFA and LR had similar effects on long-term survival in patients with BCLC 0 stage HCC. RFA and LR probably had similar effects on OS in patients with solitary HCC less than 3 cm or when the ablation margin was larger than 1 cm which need more studies to confirm. The effects of different modalities of RFA on long-term survival are needed for further assessment.
Assuntos
Carcinoma Hepatocelular , Hepatectomia , Neoplasias Hepáticas , Pontuação de Propensão , Ablação por Radiofrequência , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Hepatectomia/mortalidade , Hepatectomia/métodos , Ablação por Radiofrequência/mortalidade , Ablação por Radiofrequência/métodos , Taxa de Sobrevida , Estadiamento de Neoplasias , Prognóstico , Ablação por Cateter/mortalidade , Ablação por Cateter/métodosRESUMO
BACKGROUND: Intermittent Pringle maneuver (IPM) is commonly used to control bleeding during liver resection. IPM can cause ischemia-reperfusion injury, which may affect the prognosis of patients with hepatocellular carcinoma (HCC). The present meta-analysis was conducted to evaluate the effect of IPM use on perioperative outcomes and long-term survival in patients with HCC. METHODS: A systemic literature search was performed in the PubMed, Embase, Web of Science, and Cochrane Library databases to identify randomized controlled trials and retrospective studies that compared the effect of IPM with no Pringle maneuver during liver resection in patients with HCC. Hazard ratio (HR), risk ratio, standardized mean difference, and their 95% confidence interval (CI) values were calculated based on the type of variables. RESULTS: This meta-analysis included nine studies comprising one RCT and eight retrospective studies and involved a total of 3268 patients. Perioperative outcomes, including operation time, complications, and length of hospital stay, except for blood loss, were comparable between the two groups. After removing the studies that led to heterogeneity, the results showed that IPM was effective in reducing blood loss. Five studies reported overall survival (OS) and disease-free survival (DFS) data and eight studies reported perioperative outcomes. No significant difference in OS and DFS was observed between the two groups (OS: HR, 1.01; 95% CI, 0.85-1.20; p = 0.95; DFS: HR, 1.01; 95% CI, 0.88-1.17; p = 0.86). CONCLUSION: IPM is a useful technique to control blood loss during liver resection and does not affect the long-term survival of patients with HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Estudos Retrospectivos , Perda Sanguínea Cirúrgica/prevenção & controle , Hepatectomia/métodos , Resultado do TratamentoRESUMO
Hepatocyte-derived inducible nitric oxide synthase (iNOS) was proved to impart protection against liver ischemia reperfusion (I/R) injury in our prior analysis. However, the mechanism for this hepatoprotection remains incompletely understood. Bone marrow chimeric mice were generated using expression of iNOS in a hepatocyte-selective manner against an iNOS-knockout background. The function of heme oxygenase 1 (HO-1) in iNOS-stimulated hepatoprotection and the molecular mechanisms were explored in vitro and in vivo, respectively. Hepatocyte-derived iNOS conferred protection from I/R injury and anoxia/reoxygenation stimulation. Mechanistically, iNOS activated nuclear factor erythroid 2-related factor 2 (Nrf-2) and subsequently, stimulated the transcription of HO-1. Results from our study led to the conclusion that HO-1 is another potent mediator of iNOS-mediated protection after liver I/R.
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Heme Oxigenase-1/metabolismo , Hepatócitos/enzimologia , Fígado/patologia , Óxido Nítrico Sintase Tipo II/metabolismo , Traumatismo por Reperfusão/enzimologia , Traumatismo por Reperfusão/patologia , Animais , Núcleo Celular/metabolismo , Células Cultivadas , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fator 2 Relacionado a NF-E2/metabolismo , Transporte Proteico , Regulação para Cima/genéticaRESUMO
Multiple molecular events are involved in non-alcoholic steatohepatitis (NASH). There is no consensus on the role of inducible nitric oxide synthase (iNOS) in the progression of NASH. The present study therefore investigated the role of iNOS in NASH pathogenesis using bone marrow-transplanted iNOS chimeric mice under high-fat diet (HFD) conditions. The chimeric mice were fed a HFD for 16â¯wk, and primary hepatocytes were stimulated with oleic acid (OA). The molecular mechanisms underlying the role of iNOS in NASH were investigated. Marked hepatic steatosis and injury observed in the HFD mice and OA-stimulated hepatocytes were reduced by hepatocyte-derived iNOS. Mechanistically, iNOS upregulated heme oxygenase 1 (HO-1) by augmenting nuclear factor erythroid 2-related factor 2 (Nrf-2) binding to the HO-1 gene promoter. In conclusion, hepatocyte-derived iNOS may play a protective role against the progression of NASH by upregulating HO-1 through Nrf-2. Upregulation of hepatocellular iNOS may represent a potentially new therapeutic paradigm to combat NASH.
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Heme Oxigenase-1/metabolismo , Hepatócitos/metabolismo , Fígado/metabolismo , Proteínas de Membrana/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Animais , Ativação Enzimática , Feminino , Fígado/enzimologia , Fígado/patologia , Masculino , Camundongos , Hepatopatia Gordurosa não Alcoólica/enzimologia , Hepatopatia Gordurosa não Alcoólica/metabolismoRESUMO
Although the role of inducible nitric oxide synthase (iNOS) in hepatic ischemia/reperfusion (I/R) injury remains controversial and confusing, with both harmful and beneficial effects in animal studies, the mechanism of these incongruous actions remains unclear. In the current study, we generated bone marrow chimeric mice with hepatocyte-restricted expression of iNOS. Chimeric mice and primary hepatocytes were subjected to I/R or anoxia/reoxygenation stimulation, respectively. The role of iNOS in liver I/R injury and the underlying molecular mechanisms were investigated. Hepatocyte-derived iNOS resulted in hepatoprotection from I/R injury, as well as in vitro experiments. Mechanistically, iNOS upregulates Heat shock protein (HSP) 70 by augmenting heat shock factor 1 (HSF1) binding to the HSP70 gene promoter. Importantly, inhibition of HSP70 partly reversed the iNOS overexpression-mediated hepatoprotection. The present findings demonstrate that hepatocellular iNOS protects from hepatic I/R injury through the HSF1-dependent activation of the HSP70. The upregulation of hepatocellular iNOS may offer a promising strategy for protecting against I/R injury.
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Proteínas de Choque Térmico HSP70/metabolismo , Fatores de Transcrição de Choque Térmico/metabolismo , Fígado/irrigação sanguínea , Óxido Nítrico Sintase Tipo II/metabolismo , Traumatismo por Reperfusão/metabolismo , Animais , Proteínas de Choque Térmico HSP70/genética , Hepatócitos/metabolismo , Hepatócitos/patologia , Fígado/fisiopatologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Óxido Nítrico Sintase Tipo II/genética , Regiões Promotoras Genéticas , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/patologia , Regulação para CimaRESUMO
Ureaplasma spp. are known to be associated with human genitourinary tract diseases and perinatal diseases and Ureaplasma spp. Lipid-associated membrane proteins (LAMPs) play important roles in their related diseases. However, the exact mechanism underlying pathogenesis of Ureaplasma spp. LAMPs is largely unknown. In this study, we explored the pathogenic mechanisms of Ureaplasma spp. LAMPs by elucidating their role in modulating the cell cycle and related signaling pathways in human monocytic cell U937, which is highly related to the inflammatory and protective effect in infectious diseases. We utilized the two ATCC reference strains (Ureaplasma parvum serovar 3 str. ATCC 27,815 (UPA3) and Ureaplasma urealyticum serovar 8 str. ATCC 27,618 (UUR8)) and nine clinical isolates which including both UPA and UUR to study the effects of Ureaplasma spp. LAMPs on U937 in vitro. We found that LAMPs derived from UUR8 and both UPA and UUR of clinical strains markedly inhibited the cell proliferation, while UPA3 LAMPs suppressed slightly. Besides, the result of flow cytometry analysis indicated all the Ureaplasma spp. LAMPs could arrest U937 cells in G1 phase. Next, we found that the cell cycle arrest was associated with increased levels of p53 and p21, and a concomitant decrease in the levels of CDK2, CDK4, CDK6 and cyclin E1 at both transcriptional and translational levels after treatment with LAMPs derived from UUR8 or clinical strains, while only cyclin E1 was down-regulated after treatment with UPA3 LAMPs. Further study showed that p53 down-regulation had almost no effect on the distribution of cell cycle and the expression of p21. In conclusion, this study demonstrated that LAMPs derived from UUR8 and clinical strains could inhibit the proliferation of U937 cells by inducing G1 cell cycle arrest through increasing the p21 expression in a p53-independent manner, while UPA3 LAMPs could induce the cell cycle arrest slightly. Our study could contribute to the understanding of Ureaplasma spp. pathogenesis, which has potential value for the treatment of Ureaplasma spp. infections.
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Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Pontos de Checagem da Fase G1 do Ciclo Celular/fisiologia , Lipoproteínas/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Infecções por Ureaplasma/patologia , Ureaplasma/patogenicidade , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Ciclina E/biossíntese , Quinase 2 Dependente de Ciclina/biossíntese , Quinase 4 Dependente de Ciclina/biossíntese , Quinase 6 Dependente de Ciclina/biossíntese , Humanos , Proteínas Oncogênicas/biossíntese , Células U937 , Ureaplasma/isolamento & purificação , Doenças Urológicas/microbiologiaRESUMO
BACKGROUND: Butyrate is normally fermented from undigested fiber by intestinal microflora. The goal of the present study was to determine the effects of butyrate and its underlying mechanisms on intestinal injury in a rat model of ischemia and reperfusion (I/R). METHODS: Male Sprague-Dawley rats were subjected to warm ischemia for 45 min by clamping the superior mesenteric artery after treatment with butyrate, followed by 6 and 72 h of reperfusion. Pathologic histology analysis, enzyme-linked immunosorbent assay, immunofluorescence, and Western blot were performed. RESULTS: Butyrate preconditioning markedly improved intestinal injury. The inflammatory factor levels and leukocyte infiltration were attenuated by butyrate. Butyrate also maintained the intestinal barrier structures, increased the expression of tight junction proteins, and decreased endotoxin translocation. CONCLUSIONS: We conclude that butyrate administration attenuates intestinal I/R injury, which is associated with preservation of intestinal tight junction barrier function and suppression of inflammatory cell infiltration in the intestinal mucosa. This suggests butyrate as a potential strategy to prevent intestinal I/R injury.
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Butiratos/uso terapêutico , Fármacos Gastrointestinais/uso terapêutico , Intestinos/irrigação sanguínea , Traumatismo por Reperfusão/prevenção & controle , Animais , Biomarcadores/metabolismo , Western Blotting , Ensaio de Imunoadsorção Enzimática , Mucosa Intestinal/metabolismo , Estimativa de Kaplan-Meier , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Junções Íntimas/metabolismo , Isquemia QuenteRESUMO
BACKGROUND: The inflammatory response after hepatic ischemia reperfusion (I/R) contributes to liver dysfunction and failure after transplantation. Butyrate is a four-carbon fatty acid, normally produced by bacterial fermentation of fiber in mammalian intestines, with anti-inflammatory activities. The purpose of the present study was to investigate the protective effect of butyrate preconditioning, if any, against hepatic I/R injury in rats and the underlying mechanisms involved. METHODS: Male Sprague-Dawley rats were subjected to a partial (70%) hepatic ischemia for 60 min after pretreatment with either vehicle or butyrate, followed by 3, 6, and 24 h of reperfusion. Hepatic injury was evaluated by biochemical and histopathologic examinations. Neutrophil infiltration was measured by myeloperoxidase (MPO) activity. The expression of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) was measured by enzyme-linked immunosorbent assay (Elisa) and Real-time reverse-transcriptase polymerase chain reaction (RT-PCR). The expression of nuclear factor kappa B (NF-κB) p65 was determined by immunohistochemistry and Western blot analysis. RESULTS: Butyrate treatment markedly improved hepatic function and histology, as indicated by reduced transaminase levels and ameliorated tissue pathologic changes. The expression of tumor necrosis factor-alpha, interleukin-6, and myeloperoxidase activity was attenuated by butyrate. Butyrate also reduced I/R-induced nuclear translocation of NF-κB p65 in Kupffer cells. CONCLUSION: Our results suggest that butyrate alleviates I/R-induced liver injury, possibly by suppressing inflammatory factors production and preventing NF-κB activation in Kupffer cells.
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Butiratos/farmacologia , Hepatite/tratamento farmacológico , Células de Kupffer/efeitos dos fármacos , Traumatismo por Reperfusão/tratamento farmacológico , Fator de Transcrição RelA/antagonistas & inibidores , Condicionamento Pré-Transplante/métodos , Animais , Núcleo Celular/metabolismo , Hepatite/imunologia , Hepatite/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Células de Kupffer/metabolismo , Fígado/efeitos dos fármacos , Fígado/imunologia , Fígado/metabolismo , Transplante de Fígado , Masculino , Neutrófilos/imunologia , Peroxidase/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/imunologia , Traumatismo por Reperfusão/metabolismo , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
We showed previously that pretreatment of butyrate, which is an endogenous histone deacetylase (HDAC) inhibitor normally fermented from undigested fiber by intestinal microflora, seriously alleviated ischemia reperfusion (I/R)-induced liver injury by inhibiting the nuclear factor κB (NF-κB) pathway. The goal of this study was to investigate the effect of butyrate administrated at the onset of ischemia for HDAC inhibition in hepatic I/R injury. Sprague Dawley rats were subjected to warm ischemia for 60 min followed by 6 and 24 h of reperfusion. Butyrate was administrated at the onset of ischemia. Liver injury was evaluated by serum levels of aminotransferase, inflammatory factors, and histopathology. The levels of acetylated histone H3 and expression of heat shock protein (Hsp) 70 were measured by Western blot. After reperfusion, the levels of acetylated histone H3 significantly decreased. Butyrate treatment markedly prevented the reduction of acetylated histone H3 and upregulated the expression of Hsp70, thereby reducing liver injury. Our study demonstrated that I/R resulted in marked reduction of histone acetylation; butyrate exerted a great hepatoprotective effect through HDAC inhibition and Hsp70 induction.
Assuntos
Acetilação/efeitos dos fármacos , Butiratos/uso terapêutico , Inibidores de Histona Desacetilases/uso terapêutico , Hepatopatias/prevenção & controle , Fígado/efeitos dos fármacos , Traumatismo por Reperfusão/prevenção & controle , Animais , Proteínas de Choque Térmico HSP70/metabolismo , Histona Desacetilases/metabolismo , Histonas/metabolismo , Fígado/metabolismo , Fígado/patologia , Hepatopatias/metabolismo , Hepatopatias/patologia , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
Background: Tenofovir (TDF) and entecavir (ETV) are highly effective and well-tolerated nucleos(t)ide analogs commonly prescribed for hepatitis B virus (HBV) treatment. Yet, it is unclear whether survival outcomes differ for HBV-related hepatocellular carcinoma (HCC) patients treated with ETV and TDF. Thus, this meta-analysis aimed to compare the prognostic effectiveness of ETV and TDF in HBV-related HCC patients. Methods: We comprehensively searched four databases, PubMed, Web of Science, Embase, and the Cochrane Library, to identify pertinent studies utilizing keywords "entecavir," "tenofovir," "hepatocellular carcinoma," and "liver resection." Our primary outcomes of interest encompassed overall survival (OS), recurrence-free survival (RFS), early recurrence, and late recurrence. The statistical effect size for these measures was expressed in terms of hazard ratios (HRs). Results: Our search yielded 10 studies encompassing 11 datasets involving 7,400 patients. Our meta-analysis revealed that patients treated with TDF achieved better OS (HR = 0.53; 95% confidence interval [CI] = 0.40-0.70, p < 0.0001), RFS (HR = 0.68; 95% CI = 0.57-0.80; p < 0.0001), early recurrence (HR = 0.80; 95% CI = 0.67-0.94; p < 0.0077), and late recurrence (HR = 0.64; 95% CI = 0.43-0.97; p = 0.0368). We detected publication bias potentially affecting OS but not RFS. Conclusion: Our findings demonstrated that TDF outperformed ETV regarding RFS for HBV-related HCC patients. However, to bolster the evidence and establish more conclusive conclusions, further validation via extensive and high-quality randomized controlled trials is essential. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/#recordDetails, identifier CRD 42024542579.
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Background: Administering adjuvant therapy following liver resection is crucial for patients with hepatocellular carcinoma (HCC) exhibiting high-risk recurrence factors. Immune checkpoint inhibitors (ICIs) are effective against unresectable HCC; however, their effectiveness and safety for this specific patient group remain uncertain. Methods: We conducted an extensive literature search across four scholarly databases to identify relevant studies. Our primary endpoints were overall survival (OS), recurrence-free survival (RFS), and adverse events (AEs). OS and RFS were quantified using hazard ratios (HRs), whereas the 1-, 2-, and 3-year OS and RFS rates were expressed as risk ratios (RRs). Additionally, the incidence of AEs was calculated. Results: Our meta-analysis included 11 studies (N = 3,219 patients), comprising two randomized controlled trials (RCTs) and nine retrospective studies. Among these, eight studies reported HRs for OS, showing a statistically significant improvement in OS among patients receiving adjuvant ICIs (HR, 0.60; 95% confidence interval [CI], 0.45-0.80; p < 0.0001). All included studies reported HRs for RFS, indicating a favorable impact of adjuvant ICIs (HR, 0.62; 95% CI, 0.52-0.73; p < 0.0001). Moreover, aggregated data demonstrated improved 1- and 2-year OS and RFS rates with adjuvant ICIs. The incidence rate of AEs of any grade was 0.70 (95% CI, 0.49-0.91), with grade 3 or above AEs occurring at a rate of 0.12 (95% CI, 0.05-0.20). Conclusion: Adjuvant ICI therapy can enhance both OS and RFS rates in patients with HCC exhibiting high-risk recurrence factors, with manageable AEs. Systematic review registration: https://www.crd.york.ac.uk/prospero/#recordDetails PROSPERO, identifier CRD42023488250.
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Background: Allogeneic blood transfusion is required in a part of liver resection. The effect of allogeneic blood transfusion on the prognosis of patients with hepatocellular carcinoma (HCC) remains controversial. To investigate whether perioperative allogeneic blood transfusion (PBT) affects the long-term prognosis of patients with HCC, we conducted a meta-analysis that included only propensity score-matched (PSM) studies. Methods: The Cochrane Library, Embase, PubMed, and Web of Science databases were systematically searched to identify PSM studies that compared the long-term outcomes of allogeneic blood transfusion in resected HCC patients. Overall survival (OS) and recurrence-free survival (RFS) rates were calculated. Results: This meta-analysis included 9 PSM studies with 12 datasets involving 2476 patients. Lower OS and RFS in HCC patients receiving allogeneic blood transfusion were observed than those in patients not receiving blood transfusion (OS: hazard ratio [HR], 1.34; 95% confidence interval [CI], 1.10-1.64; p < 0.01; RFS: HR, 1.29; 95% CI, 1.07-1.56; p < 0.01). Subgroup analysis revealed that among patients with BCLC A HCC, those receiving allogeneic blood transfusion had lower OS and RFS (OS: HR, 2.27; 95% CI, 1.61-3.21; RFS: HR, 2.11; 95% CI, 1.30-3.41). OS and RFS were similar in both groups of patients with BCLC B and C HCC. Conclusion: The receipt of perioperative allogeneic blood transfusion is associated with a decrease in OS and RFS. These results seem to be reliable for patients in BCLC stage A. But more high-quality research is needed to confirm this conclusion.
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Ischemia reperfusion injury remains a major barrier to liver transplantation, especially using grafts from donation after circulatory death, and it is also a pressing issue to be solved in clinical practice. Kupffer cell polarization toward a proinflammatory M1 phenotype is an early trigger of liver ischemia-reperfusion injury. However, the molecular mechanism regulating Kupffer cell polarization has not yet been fully elucidated. We induced liver ischemia reperfusion injury in mice and obtained samples from patients undergoing liver transplantation, serum and hepatocytes-derived extracellular vesicles were isolated by differential ultracentrifugation. Kupffer cell polarization was examined by flow cytometry and immunofluorescence histochemistry. RNA-seq was conducted to detect the differentially expressed miRNAs in extracellular vesicles. The role and mechanism of exosomal miR-122-5p in liver ischemia-reperfusion injury were determined both in vitro and in vivo. We identified ischemia reperfusion induced extracellular vesicles as a major cause of hepatic inflammation and tissue damage using adoptive transfer and release inhibition. The study also demonstrated that hepatocyte-derived exosomal miR-122-5p mediates liver ischemia reperfusion injury by polarizing Kupffer cell via PPARδ down-regulation and NF-κB pathway activation using profiling and functional analysis. Moreover, inhibiting miR-122-5p with antagomir suppressed Kupffer cell M1 polarization and attenuated liver ischemia reperfusion injury. Overall, our study demonstrated that hepatocyte-derived exosomal miR-122-5p played a critical role in promoting hepatic ischemia reperfusion injury through modulating PPARδ signaling and NF-κB pathway to introduce M1 polarization of Kupffer cell. Inhibition of miR-122-5p exhibited a protective effect against liver ischemia reperfusion injury, suggesting a potential therapeutic target for liver transplantation.
Assuntos
MicroRNAs , PPAR delta , Traumatismo por Reperfusão , Animais , Camundongos , Hepatócitos/metabolismo , Células de Kupffer/metabolismo , Fígado/metabolismo , MicroRNAs/metabolismo , NF-kappa B/metabolismo , PPAR delta/metabolismo , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/metabolismo , HumanosRESUMO
BACKGROUND: The mean platelet volume-to-lymphocyte ratio (MPVLR), as a novel marker of thrombosis and inflammation, has been demonstrated to be closely linked to poor cardiovascular disease prognosis. However, the correlation between MPVLR and acute ischemic stroke (AIS) remains unclear. This study, therefore, aimed to clarify the relationship between MPVLR and the short-term prognosis of AIS. METHODS: A total of 315 patients with first-time AIS diagnoses were recruited and divided into 3 groups based on the tri-sectional quantiles for MPVLR on admission: group 1 (Nâ =â 105) with a MPVLRâ ≤â 4.93, group 2 (Nâ =â 105) with a MPVLR of 4.94 to 7.21, and group 3 (Nâ =â 105) with a MPVLRâ ≥â 7.22. All patients were followed-up for 3 months, and death within 3 months was defined as the endpoint. Baseline characteristics, stroke severity, and functional outcomes were evaluated. RESULTS: The Spearman's correlation coefficient test showed that MPVLR was significantly positively correlated with the National Institutes of Health Stroke Scale score (Râ =â 0.517, Pâ <â .001). Multivariate analysis revealed that MPVLR was an independent predictor of both short-term mortality (adjusted odds ratio [OR] 1.435, Pâ <â .001) and poor outcome (adjusted OR 1.589, Pâ <â .001). The receiver operating characteristic (ROC) curve analysis showed that the best cutoff value of MPVLR for short-term mortality and poor outcome were 6.69 (sensitivity: 86.4%, specificity: 68.6%) and 6.38 (sensitivity: 78.8%, specificity: 72.3%), respectively. CONCLUSIONS: MPVLR on admission was positively associated with stroke severity. An elevated MPVLR is an independent predictor of short-term mortality and poor outcome after AIS.
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Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Biomarcadores , Humanos , Linfócitos , Volume Plaquetário Médio , Prognóstico , Curva ROC , Acidente Vascular Cerebral/diagnósticoRESUMO
OBJECTIVE: To investigate the effects of ambroxol on rat models with nitrofen-induced congenital diaphragmatic hernia (CDH) and its potential mechanism. METHODS: Nine pregnant female SD rats were randomly divided into 3 groups at Day 9.5: 2 ml olive oil intragastrically in control group (2 rats) and 200 mg nitrofen in nitrofen (2 rats) and ambroxol groups (5 rats). Antenatal ambroxol was given intraperitoneally to ambroxol group at Days 18.5, 19.5 and 20.5 of gestation while control and nitrofen groups only received intraperitoneal normal saline. At Day 21.5 the fetuses were delivered by cesarean section. Incidence of hernia, lung weight/body weight (LW/BW), mean terminal branch density (MTBD), percentage of lung alveolar area (PLAA), percentage of wall thickness (MT%) and the expression of TGF-ß1 were observed. RESULTS: There were 19 CDH fetuses in nitrofen group (68.4%). The incidence of hernia in ambroxol group was 65.1% (28/43). There was no significant difference (P>0.05) between two groups. LW/BW and PLAA decreased while MTBD and MT% increased significantly in the nitrofen group versus the control group [(45±6) mg/g vs (60±7) mg/g, (50.1±4.0)% vs (58.4±3.0)%, (14.0±1.8) vs (8.5±1.1), (45±6)% vs (29±6)%, all P=0.001]. After ambroxol intervention, the ambroxol group showed a higher PLAA but a lower MTBD and MT% [(54.0±2.0)%, (12.2±2.1), (39±4)%] than those in the nitrofen group (P=0.001, 0.006, 0.002). The expression of TGF-ß1 in pulmonary tissues of the nitrofen group was significantly higher than that in the control group (13,594±3113 vs 9447±1355, P=0.001). It decreased after ambroxol intervention (10 015±818, P=0.01). CONCLUSION: Though with no effect upon the occurrence of CDH in rats, the administration of ambroxol may improve the pulmonary maturity. The down-regulated expression of TGF-ß1 and the oxidative stability are possible mechanisms.
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Ambroxol/farmacologia , Pulmão/efeitos dos fármacos , Pulmão/embriologia , Animais , Modelos Animais de Doenças , Feminino , Hérnia Diafragmática/induzido quimicamente , Hérnia Diafragmática/embriologia , Hérnias Diafragmáticas Congênitas , Pulmão/crescimento & desenvolvimento , Exposição Materna , Éteres Fenílicos/efeitos adversos , Gravidez , Ratos , Ratos Sprague-Dawley , Fator de Crescimento Transformador beta1/metabolismoRESUMO
Congenital dysfibrinogenemia (CD) is a rare hereditary fibrinogen disorder characterized by normal fibrinogen antigen levels associated with lower functional activities. The aim of this study is to analyze the phenotype and genotype of a family of CD. Routine coagulation screening tests were performed on the proband, her parents, and her grandparents. Then, the purified genomic DNA extracted from peripheral blood was amplified by PCR, and Sanger sequencing was performed to further confirm the mutation. The prothrombin time and activated partial thromboplastin time of the proband were normal, thrombin time prolonged, and the activity of fibrinogen (Fg:Ac) decreased significantly, but fibrinogen antigen (Fg:Ag) level was normal. The coagulation function indices of the proband's father and grandfather were similar to her, and the indices of her mother and grandmother were normal. Sequencing results showed that the proband had a heterozygous missense mutation in FGA gene c.92G > A, which caused the mutation of amino acid 31 from glycine to glutamic acid (p.Gly31Glu). Her father had the same heterozygous mutation. In conclusion, the proband suffered from CD. The change of Gly31Glu in A chain due to the c.92G > A heterozygous missense mutation in the FGA gene is the cause of CD in the family. To the best of our knowledge, the mutation site is new and first reported so far.
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Multiple myeloma (MM) is an immunoglobulin-producing tumor of plasma cells, which occurs commonly in the elderly. The incidence of myocardial amyloidosis with MM is extremely low and early clinical manifestations are nonspecific. The diversity of clinical manifestations and first episode symptoms often cause misdiagnosis in young patients with myocardial amyloidosis following MM. In this study, we analyzed the clinical data of a young woman with MM and impaired cardiac function combined with echocardiography, electrocardiography (ECG), laboratory data, cell Congo Red staining, and other manifestations to diagnose amyloidosis. Considering the rapid progression, short survival, and poor prognosis in most patients, a clear, definitive, and timely diagnosis is essential for the treatment of patients with MM complicated with myocardial amyloidosis.
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The present study investigated the clinical efficacy of S-1 plus oxaliplatin (SOX) regimen, with or without surgery in α-fetoprotein-producing gastric cancer (APGC) with liver metastasis. A total of 24 patients with APGC treated at the Liaocheng People's Hospital between January 2011 and December 2013 were retrospectively reviewed. Clinical efficacy and patient safety were compared between the two groups. The median progression-free survival (PFS) and overall survival (OS) in the SOX group were 6.5 [95% confidence interval (CI), 4.6-8.4] and 13.5 (95% CI, 8.1-18.9) months, respectively. The corresponding indicators in the SOX and surgery group were 7.0 (95% CI, 5.7-8.3) and 14 (95% CI, 11.0-17.1) months, respectively. There was no significant difference in PFS and OS between the two groups (P=0.703 and 0.710, respectively). The adverse effects of leucopenia, neutropenia, anemia and diarrhea occurred in ~10% of patients in the SOX group and in 14.3% (2/14), 7.14% (1/14), 14.3% (2/14) and 7.14% (1/14), respectively, in the surgery group. No significant difference was identified between groups in terms of overall incidence of adverse effects (P=0.17). However, severe adverse events, including gastroplegia, pancreatic fistula, pulmonary infection and refractory ascites, occurred only in the SOX plus surgery group [incidence rate for severe adverse events, 7.14% (1/14); P<0.001 between groups]. In conclusion, SOX chemotherapy is safe and effective in patients with APGC and liver metastasis. However, the addition of surgery to SOX chemotherapy may not improve the disease control rate and may increase the adverse effects.
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AIMS: To determine whether circulating multiple miRNAs can be used as novel biomarkers for the diagnosis in breast cancer, we performed a systematic review and meta-analysis. MATERIALS & METHODS: After searching the databases of PubMed, EMBASE and Web of Science, we used the bivariate meta-analysis model to summarize the diagnostic indices and plot the summary receiver operator characteristic curve. RESULTS: The summary estimates revealed that the pooled sensitivity was 88% (95% CI: 82-93%); specificity was 84% (95% CI: 74-91%); positive likelihood ratio was 4.69 (95% CI: 2.93-7.51); negative likelihood ratio was 0.15 (95% CI: 0.09-0.25); diagnostic odds ratio was 38.21 (95% CI: 13.41-108.85); and the area under the curve was 0.93 (95% CI: 0.90-0.95). CONCLUSION: These results suggested that circulating multiple miRNAs might serve as novel biomarkers for breast cancer, with a relatively high level of accuracy.
Assuntos
Neoplasias da Mama/diagnóstico , MicroRNAs/sangue , Área Sob a Curva , Neoplasias da Mama/genética , Bases de Dados Factuais , Feminino , Humanos , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real , Sensibilidade e EspecificidadeRESUMO
The aim of this study was to estimate the prevalence and antimicrobial resistance rate of Mycoplasma hominis among male and female populations. A total of 67921 individuals were examined. All samples were isolated from patients at an outpatient clinic from January 2005 to December 2014. Species identification and antibiotic susceptibility testing were performed using Mycoplasma IST2. In this study, 523 (0.8%) and 4625 (6.8%) cultures, respectively, were positive for single M. hominis identification and simultaneous identification of both M. hominis and Ureaplasma spp. The results showed that both single and simultaneous identification were more frequent in the female than the male population. Moreover, the highest positive rates of single M. hominis identification were observed in 56-60-year-old males and 61-65-year-old females, and the rates of simultaneous identification were high in males aged >65 years and females aged 15-20 years. Among the seven antibiotics assessed, tetracycline, josamycin, doxycycline and pristinamycin were the most effective, whilst clarithromycin, ciprofloxacin and ofloxacin displayed extremely high resistance rates. Different antimicrobial susceptibility rates were observed between the two sexes, and the resistance rates to ofloxacin showed a significant difference (P<0.05). In conclusion, this study demonstrates that the prevalence of M. hominis varied significantly between the two sexes in the past 10 years and that the optimal antimicrobial therapy strategy should be directed by local susceptibility testing.