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1.
Stem Cell Res Ther ; 12(1): 244, 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33863383

RESUMO

BACKGROUND: ABO-incompatible liver transplantation (ABO-i LT) has become a rescue therapeutic option for patients with severe hepatic failure. Although the use of rituximab greatly reduces the morbidity of antibody-mediated rejection (AMR), severe adverse effects, such as infection and biliary complications, still seriously threaten the survival of transplant recipients. The aim of this study was to evaluate the safety and feasibility of using mesenchymal stem cells (MSCs) to replace rituximab in ABO-i LT. METHODS: Twenty-two patients with severe hepatic failure undergoing ABO-i LT were enrolled and randomly divided into two groups: the MSC group and the rituximab group. The safety of the application of MSCs and the incidence of allograft rejection, including antibody-mediated rejection (AMR) and acute cellular rejection (ACR), were evaluated in both groups at the 2-year follow-up period as primary endpoints. Recipients and graft survival and other postoperative complications were compared as secondary endpoints. RESULTS: No severe MSC-related adverse events were observed during the trial. MSC treatment yielded comparable, if not better, results than rituximab at decreasing the incidence of acute rejection (9.1% vs 27.3%). Inspiringly, compared to those in the rituximab group, the rates of biliary complications (0% vs 45.5%) and infection (9.1% vs 81.8%) were significantly decreased in the MSC group. In addition, there were no significant differences in 2-year graft and recipient survival between the two groups (81.8% vs 72.7%). CONCLUSIONS: Our data show that MSC transfusion is comparable to rituximab treatment for AMR prophylaxis following ABO-i LT. Additionally, the results indicate that MSCs are more beneficial to the prevention of infection and biliary complications and may be introduced as a novel immunosuppressive approach for ABO-i LT. TRIAL REGISTRATION: Trial registration: chictr.org.cn , ChiCTR2000037732. Registered 31 August 2020- Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=57074 .

2.
Aging (Albany NY) ; 13(2): 2251-2263, 2020 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-33323551

RESUMO

Hepatic ischemia-reperfusion injury (IRI) remains a common complication during liver transplantation (LT), partial hepatectomy and hemorrhagic shock in patients. As a member of the G protein-coupled receptors adaptors, ARRB2 has been reported to be involved in a variety of physiological and pathological processes. However, whether ß-arrestin-2 affects the pathogenesis of hepatic IRI remains unknown. The goal of the present study was to determine whether ARRB2 protects against hepatic IR injury and elucidate the underlying mechanisms. To this end, 70% hepatic IR models were established in ARRB2 knockdown mice and wild-type littermates, with blood and liver samples collected at 1, 6 and 12 h after reperfusion to evaluate liver injury. The effect of ARBB2 on PI3K/Akt signaling during IR injury was evaluated in vivo, and PI3K/Akt pathway regulation by ARRB2 was further assessed in vitro. Our results showed that ARRB2 knockdown aggravates hepatic IR injury by promoting the apoptosis of hepatocytes and inhibiting their proliferation. In addition, ARRB2 deficiency inhibited PI3K/Akt pathway activation, while the administration of the PI3K/Akt inhibitor PX866 resulted in severe IR injury in mice. Furthermore, the liver-protecting effect of ARRB2 was shown to depend on PI3K/Akt pathway activation. In summary, our results suggest that ß-Arrestin-2 protects against hepatic IRI by activating PI3K/Akt signaling, which may provide a novel therapeutic strategy for treating liver ischemia-reperfusion injury.

3.
J Hepatol ; 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33217494

RESUMO

BACKGROUND & AIMS: Liver fibrosis is a wound-healing response that arises from various aetiologies. The intermediate filament protein, Nestin, has been reported to participate in maintaining tissue homeostasis during wound healing responses. However, little is known about the role Nestin plays in liver fibrosis. This study investigated the function and precise regulatory network of Nestin during liver fibrosis. METHODS: Nestin expression was assessed via immunostaining and quantitative real-time polymerase chain reaction (qPCR) in fibrotic/cirrhotic samples. The induction of Nestin expression by transforming growth factor beta (TGFß)-Smad2/3 signalling was investigated through luciferase reporter assays. The functional role of Nestin in hepatic stellate cells (HSCs) was investigated by examining the pathway activity of pro-fibrogenic TGFß-Smad2/3 signalling and degradation of TGFß receptor I (TßRI) after interfering with Nestin. The in vivo effects of knocking down Nestin were examined with an adeno-associated virus vector (serotype 6, AAV6) carrying short hairpin RNA (shRNA) targeting Nestin in fibrotic mouse models. RESULTS: Nestin was mainly expressed in activated HSCs and increased with the progression of liver fibrosis. The pro-fibrogenic pathway TGFß-Smad2/3 induced Nestin expression directly. Knocking down Nestin promoted Caveolin1 (Cav-1)-mediated TßRI degradation, resulting in TGFß-Smad2/3 pathway impairment and reduced fibrosis marker expression in HSCs. In AAV6-treated murine fibrotic models, knocking down Nestin resulted in decreased levels of inflammatory infiltration, hepatocellular damage, and a reduced degree of fibrosis. CONCLUSION: The expression of Nestin in HSCs was induced by TGFß and positively correlated with the degree of liver fibrosis. Knockdown of Nestin decreased activation of TGFß pathway and alleviated liver fibrosis both in vitro and in vivo. Our data demonstrate a novel role of Nestin in controlling HSC activation in liver fibrosis.

4.
Adv Sci (Weinh) ; 7(18): 1903746, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32999825

RESUMO

As a cause of postoperative complications and early hepatic failure after liver transplantation, liver ischemia/reperfusion injury (IRI) still has no effective treatment during clinical administration. Although the therapeutic potential of mesenchymal stem cells (MSCs) for liver IRI has been previously shown, the underlying mechanisms are not completely clear. It is accepted that MSC-derived extracellular vesicles (MSC-EVs) are newly uncovered messengers for intercellular communication. Herein, it is reported that umbilical cord-derived MSCs (UC-MSCs) improve liver IRI in mice through their secreted EVs. It is also visualized that UC-MSC-EVs mainly concentrate in liver after 6 h of reperfusion. Furthermore, UC-MSC-EVs are found to significantly modulate the membranous expression of CD154 of intrahepatic CD4+ T cells, which is an initiation of inflammatory response in liver and can aggravate liver IRI. Mechanistically, protein mass spectrum analysis is performed and it is revealed that Chaperonin containing TCP1 subunit 2 (CCT2) enriches in UC-MSC-EVs, which regulates the calcium channels to affect Ca2+ influx and suppress CD154 synthesis in CD4+ T cells. In conclusion, these results highlight the therapeutic potential of UC-MSC-EVs in attenuating liver IRI. This finding suggests that CCT2 from UC-MSC-EVs can modulate CD154 expression of intrahepatic CD4+ T cells during liver IRI through the Ca2+-calcineurin-NFAT1 signaling pathway.

5.
Cell Oncol (Dordr) ; 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33034848

RESUMO

PURPOSE: Multiple circular RNAs (circRNAs) have been reported to be dysregulated in hepatocellular carcinoma (HCC). However, their functions and modes of action are still largely unclear. Identifying key circRNAs and revealing their potential functions and molecular mechanisms is considered important for improving the diagnosis and treatment of HCC. METHODS: Dysregulated circRNAs in HCC were identified through integration of three human HCC circRNAs microarray datasets (GSE94508, GSE97332 and GSE 78520), followed by qRT-PCR validation in primary HCC tissues and cell lines. circRNA characteristics were verified through Sanger sequencing, RNase R treatment, northern blotting and intracellular localization analyses. In addition, circRNA functions in HCC development were assessed using CCK8, colony formation, EDU incorporation, flow cytometry, transwell and scratch wound healing assays in vitro and tumor xenograft assays in vivo. Next, underlying molecular mechanisms in HCC were assessed using dual-luciferase reporter, RNA pull-down, RNA immunoprecipitation and western blotting assays. RESULTS: We found that a novel circular RNA, circ-102,166, was down-regulated in HCC and that its expression level was significantly associated with multiple clinicopathologic characteristics, as well as the clinical prognosis of HCC patients. In vitro and in vivo experiments revealed that circ-102,166 overexpression significantly inhibited the proliferation, invasion, migration and tumorigenicity of HCC cells. Furthermore, we found that circ-102,166 can bind to miR-182 and miR-184 to regulate the expression of several of their downstream targets (FOXO3a, MTSS1, SOX7, p-RB and c-MYC). CONCLUSION: Our data revealed a tumor-suppressing role of circ-102,166 in HCC. Down-regulation of circ-102,166 enhanced the proliferation and invasion of HCC cells by releasing the oncomiRs miR-182 and miR-184.

6.
Cell Death Dis ; 11(9): 746, 2020 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-32920597

RESUMO

This work was supported by National 13th Five-Year Science and Technology Plan Major Projects of China (2017ZX10203205-006-001); National Key R&D Plan (2017YFA0104304); National Natural Science Foundation of China (81770648 81972286); Guangdong Natural Science Foundation (2015A030312013, 2018A0303130305); Science and Technology Program of Guangdong Province (2017B020209004, 20169013, 2017B030314027). This has now been corrected in both the PDF and HTML versions of the Article.

7.
Int J Biol Sci ; 16(14): 2542-2558, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32792856

RESUMO

Cancer-associated fibroblasts (CAFs) play crucial roles in enhancing cell survival, proliferation, invasion, and metastasis. We previously showed that hepatocellular carcinoma-derived CAFs (H-CAFs) promoted proliferation of hepatocellular carcinoma (HCC) cells. This study aimed to further explore the role of CAFs in HCC epithelial-mesenchymal transition (EMT) and the underlying mechanism. High CAF density was significantly associated with liver cirrhosis, inferior clinicopathologic characteristics, elevated EMT-associated markers, and poorer survival in human HCC. Within HCC cells, EMT was induced after co-culture with H-CAFs. Secretomic analysis showed that IL-6 and HGF were the key EMT-stimulating cytokines secreted by H-CAFs. Proteomic analysis revealed that TG2 was significantly upregulated in HCC cells with EMT phenotypes. Overexpression of TG2 promoted EMT of HCC cells, and knockdown of TG2 remarkably attenuated the H-CAF-induced EMT. Furthermore, during EMT, TG2 expression was enhanced after HCC cells were stimulated by IL-6, but not HGF. Inhibition of the IL-6/STAT3 signaling decreased TG2 expression. The principal TG2 transcription control element and a potential STAT3 binding site were identified using promoter analysis. Hence, H-CAFs facilitates HCC cells EMT mediated by IL-6, which in turn activates IL-6/IL6R/STAT3 axis to promote TG2 expression.

8.
Cell Death Dis ; 11(8): 657, 2020 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-32814765

RESUMO

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the severe lung damage and respiratory failure without effective therapy. However, there was a lack of understanding of the mechanism by which exosomes regulate autophagy during ALI/ARDS. Here, we found lipopolysaccharide (LPS) significantly increased inflammatory factors, administration of exosomes released by human umbilical cord mesenchymal stem cells (hucMSCs) successfully improved lung morphometry. Further studies showed that miR-377-3p in the exosomes played a pivotal role in regulating autophagy, leading to protect LPS induced ALI. Compared to exosomes released by human fetal lung fibroblast cells (HFL-1), hucMSCs-exosomes overexpressing miR-377-3p more effectively suppressed the bronchoalveolar lavage (BALF) and inflammatory factors and induced autophagy, causing recoveration of ALI. Administration of miR-377-3p expressing hucMSCs-exosomes or its target regulatory-associated protein of mTOR (RPTOR) knockdown significantly reduced ALI. In summary, miR-377-3p released by hucMSCs-exosomes ameliorated Lipopolysaccharide-induced acute lung injury by targeting RPTOR to induce autophagy in vivo and in vitro.

10.
Artigo em Inglês | MEDLINE | ID: mdl-32852634

RESUMO

PURPOSE: Microvascular invasion (MVI) is a valuable predictor of survival in hepatocellular carcinoma (HCC) patients. This study developed predictive models using eXtreme Gradient Boosting (XGBoost) and deep learning based on CT images to predict MVI preoperatively. METHODS: In total, 405 patients were included. A total of 7302 radiomic features and 17 radiological features were extracted by a radiomics feature extraction package and radiologists, respectively. We developed a XGBoost model based on radiomics features, radiological features and clinical variables and a three-dimensional convolutional neural network (3D-CNN) to predict MVI status. Next, we compared the efficacy of the two models. RESULTS: Of the 405 patients, 220 (54.3%) were MVI positive, and 185 (45.7%) were MVI negative. The areas under the receiver operating characteristic curves (AUROCs) of the Radiomics-Radiological-Clinical (RRC) Model and 3D-CNN Model in the training set were 0.952 (95% confidence interval (CI) 0.923-0.973) and 0.980 (95% CI 0.959-0.993), respectively (p = 0.14). The AUROCs of the RRC Model and 3D-CNN Model in the validation set were 0.887 (95% CI 0.797-0.947) and 0.906 (95% CI 0.821-0.960), respectively (p = 0.83). Based on the MVI status predicted by the RRC and 3D-CNN Models, the mean recurrence-free survival (RFS) was significantly better in the predicted MVI-negative group than that in the predicted MVI-positive group (RRC Model: 69.95 vs. 24.80 months, p < 0.001; 3D-CNN Model: 64.06 vs. 31.05 months, p = 0.027). CONCLUSION: The RRC Model and 3D-CNN models showed considerable efficacy in identifying MVI preoperatively. These machine learning models may facilitate decision-making in HCC treatment but requires further validation.

11.
Bioresour Technol ; 315: 123772, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32653750

RESUMO

The objective was to evaluate effects of Lactobacillus plantarum and/or cellulase on fermentation, aerobic stability and bacterial community of mixed high-moisture amaranth (AF) and rice straw (RS) silage. The mixtures were treated with no addition (C), L. plantarum (L), cellulase (F) and their combination (LF). Additives increased the abundances of Lactobacillus and reduced the abundances of Weissella, Pediococcus, Lactococcus, decreased pH, acetic acid, ammonia nitrogen and increased lactic acid concentration as compared to C silage over the ensiling period. The LF silage had the highest lactic acid concentration among all silages over the 7 d of ensiling and also the lowest abundance of Enterobacteriaceae over 30 d of ensiling. Aerobic spoilage occurred in C and LF silages after 2 d of aerobic exposure, whereas the L and F silages remained stable > 4 d. In conclusion, silage treated with LF showed best silage quality.


Assuntos
Celulase , Lactobacillus plantarum , Oryza , Aerobiose , Fermentação , Silagem/análise , Zea mays
12.
Am J Transl Res ; 12(6): 2984-2997, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32655824

RESUMO

The gamma-glutamyl transpeptidase to platelet ratio (GPR) has been reported as a non-invasive parameter for evaluating hepatic fibrosis and cirrhosis. However, only a few of studies investigated the relationship between GPR and liver cancer. Here, we sought to clarify the prognostic value of GPR as well as its combination with fibrinogen in patients with HBV-related hepatocellular carcinoma (HCC). We performed a retrospective study using data collected from 302 HCC patients, and evaluated the association between GPR, fibrinogen and clinicopathological characteristics using the chi-square test. Additionally, we assessed disease-free survival (DFS) and overall survival (OS) using the Kaplan-Meier method and log-rank test, then performed univariate and multivariate COX analyses to identify the prognostic factors. The prognostic performance of combined GPR and fibrinogen was evaluated by the receiver operating characteristic curve analysis. Results showed that GPR was associated with gender, history of smoking and drinking, cirrhosis, antiviral treatments, tumor number, and Child-Pugh grade. Univariate analysis revealed a significant correlation between tumor diameter, vascular invasion, BCLC stage, alpha-fetal protein, GPR, fibrinogen, and NLR with both DFS and OS in HCC patients. Only GPR and fibrinogen were found to be independently associated with both DFS and OS according to multivariate analysis. Furthermore, predictive capacity was enhanced by combining GPR with fibrinogen owing to a larger area under the curve than other indexes or models. Overall, preoperative GPR could be an effective non-invasive predictor for prognosis of HBV-related HCC patients, and a combination of GPR and fibrinogen improved the prognostic performance.

13.
Ann Transl Med ; 8(6): 334, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32355778

RESUMO

Background: Acute lung injury (ALI) is a devastating syndrome with no effective pharmacological therapies in the clinic. Mesenchymal stromal cells (MSCs) have been demonstrated to promote inflammation resolution and tissue repair in ALI. However, the specific mechanisms of this have not been clearly elucidated. Stanniocalcin-2 (STC2) is a stress-responsive protein that has anti-oxidative properties. Our previous study found that STC2 is a highly expressed stanniocalcin in MSCs, which may be involved in immunomodulatory activities. However, the role of STC2 in MSCs to resolve ALI has never been elucidated. Methods: Specific shRNA was used to downregulate STC2 in MSCs. We detected ROS, cell apoptosis, and paracrine factors changes in MSCs. STC2-associated antioxidant genes were also investigated by Co-immunoprecipitation (Co-IP) and immunofluorescence. Macrophage (THP1 cells) phenotype transitions were measured by flow cytometry after coculturing with MSCs in vitro. Then, we used MSCs to treat LPS-induced ALI in mice, and assessed injury scores inflammation, and antioxidant activities in the lungs of the mice. Alveolar macrophage (AM) phenotypes and CFSE-labeled MSC apoptosis in collected bronchoalveolar fluids (BALF) were also analyzed by flow cytometry. Results: After the STC2 knockdown, MSCs increased ROS generation and cell apoptosis after PX12 pretreatment. The antioxidant protein Nrf2 was colocalized with STC2 in the nucleus. A lack of STC2 expression in MSCs produced less interleukin 10 (IL10) and blunted macrophage polarization in THP1 cells. Furthermore, in the murine LPS-induced ALI model, the STC2 knockdown counteracted the inflammatory resolution and antioxidative effect of MSCs in the lungs. MSCshSTC2-treated mice had a higher lung injury score than the controls, which may be attributed to diminished AM polarization and increased apoptosis of MSCs in vivo. Conclusions: Collectively, these results suggested that STC2 is essential to the anti-oxidative and anti-inflammation properties of MSCs and could prove to be crucial for stem cell therapies for ALI.

14.
Mol Med Rep ; 22(2): 1342-1350, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32468001

RESUMO

The aim of the present study was to examine the role of sirtuin 3 (Sirt3)­autophagy in regulating myocardial energy metabolism and inhibiting myocardial hypertrophy in angiotensin (Ang) II­induced myocardial cell hypertrophy. The primary cultured myocardial cells of neonatal Sprague Dawley rats were used to construct a myocardial hypertrophy model induced with Ang II. Following the activation of Sirt3 by resveratrol (Res), Sirt3 was silenced using small interfering (si)RNA­Sirt3, and the morphology of the myocardial cells was observed under an optical microscope. Reverse transcription­polymerase chain reaction was used to detect the mRNA expression of the following myocardial hypertrophy markers; atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), Sirt3, medium­chain acyl­CoA dehydrogenase (MCAD) and pyruvate kinase (PK). Western blot analysis was used to detect the protein expression of Sirt3, light chain 3 (LC3) and Beclin1. Ang II may inhibit the protein expression of Sirt3, LC3 and Beclin1. Res, an agonist of Sirt3, may promote the protein expression of Sirt3, LC3 and Beclin1. Res inhibited the mRNA expression of ANP and BNP, and reversed the Ang II­induced myocardial cell hypertrophy. The addition of siRNA­Sirt3 decreased the protein expression of Sirt3, LC3 and Beclin1, increased the mRNA expression of ANP and BNP, and weakened the inhibitory effect of Res on myocardial cell hypertrophy. Res promoted the mRNA expression of MCAD, inhibited the mRNA expression of PK, and reversed the influence of Ang II on myocardial energy metabolism. siRNA­Sirt3 intervention significantly decreased the effect of Res in eliminating abnormal myocardial energy metabolism. In conclusion, Sirt3 may inhibit Ang II­induced myocardial hypertrophy and reverse the Ang II­caused abnormal myocardial energy metabolism through activation of autophagy.

15.
Cell Death Dis ; 11(4): 256, 2020 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-32312955

RESUMO

Hepatocyte apoptosis is the main pathophysiological process underlying liver ischemia/reperfusion (I/R) injury. Mitochondrial abnormalities have a vital role in hepatocellular damage. The hepatoprotective effects of mesenchymal stem cells (MSCs) have been previously demonstrated. In this study, we aim to investigate the effect and potential mechanism of MSCs against liver I/R injury. Effects of MSCs were studied in mice liver I/R injury model and in a hypoxia/reoxygenation (H/R) model of L02 hepatocytes. The potential mechanisms of MSCs on these in vivo and in vitro I/R-induced hepatocellular apoptosis models were studies. Accompanied by the improvement of hepatic damage, MSCs exhibited capabilities of controlling mitochondrial quality, shown by reduced mitochondrial reactive oxygen species (mtROS) overproduction, decreased the accumulation of mitochondrial fragmentation, restored ATP generation and upregulated mitophagy. Furthermore, we descripted a potential mechanism of MSCs on upregulating mitophagy and found that the reduced Parkin and PINK1 expression and inactivated AMPKα pathway were observed in the liver tissue in I/R model. These effects were reversed by MSCs treatment. In vitro study showed that MSC-conditioned medium (MSC-CM) suppressed hepatocellular apoptosis and inhibited mtROS accumulation in the H/R environment. And these effects of MSC-CM were partially blocked after the cells were transfected with PINK1 siRNA or added with dorsomorphin. Collectively, our findings provide a novel pharmacological mechanism that MSCs exert hepatoprotective effect in liver I/R injury via upregulating PINK1-dependent mitophagy. In addition, this effect might be attributed to the modulation of AMPKα activation.

16.
Pest Manag Sci ; 76(5): 1881-1892, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31840379

RESUMO

BACKGROUND: Ecosystem services are key to human survival. In agriculture, they offer potential to intensify production while reducing reliance on hazardous inputs, including pesticides. Nectar plants can nourish natural enemies of pests and thereby promote the ecosystem service of biological control. To date, however, the selection of optimal plants has been reliant on laborious testing of multiple candidate species for use in each new agroecosystem. We report a hybrid meta-analysis of published literature, employing Bayesian network analysis. RESULTS: The hybrid meta-analysis identified the particular plant and parasitoid traits that were most predictive of promoted or suppressed parasitoid longevity. Integrating trait effects identified a combination of plant-parasitoid traits that had the highest impact on parasitoid longevity: compound umbel or raceme inflorescence form and shallow corolla, together with high potential fecundity of the parasitoid. CONCLUSION: Unlike earlier analyses focusing on taxonomic categories, we analyzed effect sizes in relation to the ecological traits of parasitoids and plants. This generated the first generalizable guidelines for selecting nectar plants as well as appropriate parasitoid targets for the enhancement of biological control. Within the guidelines, optimal outcomes resulted when plants with compound umbel or raceme inflorescences and shallow corollas were combined with fecund parasitoids. More widely, this type of ecological trait-based meta-analysis opens a new avenue for optimizing the delivery of other types of ecosystem services. © 2019 Society of Chemical Industry.


Assuntos
Vespas , Animais , Teorema de Bayes , Ecossistema , Interações Hospedeiro-Parasita , Fenótipo , Plantas
17.
Org Lett ; 22(1): 322-325, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31846341

RESUMO

In the presence of a catalytic amount of Pd(TFA)2 and a chiral Pyox ligand under oxygen atmosphere, oxidative Heck reaction between arylboronic acids and 4-substituted or 4,4-disubstituted cyclopent-1-enes afforded the chiral arylated products with concurrent creation of two stereocenters in good yields with excellent diastereo- and enantioselectivities.

18.
Gastroenterol Rep (Oxf) ; 7(5): 354-360, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31687155

RESUMO

Background: Hepatocellular carcinoma (HCC) is frequently associated with metabolism dysfunction. Increasing evidence has demonstrated the crucial role of lipid metabolism in HCC progression. The function of apolipoprotein F (ApoF), a lipid transfer inhibitor protein, in HCC is incompletely understood. We aimed to evaluate the functional role of ApoF in HCC in this study. Methods: We used quantitative reverse-transcription polymerase chain reaction (qRT-PCR) to detect ApoF mRNA expression in HCC tissues and hepatoma cell lines (SMMC-7721, HepG2, and Huh7). Immunohistochemistry was performed to detect the expression of ApoF in HCC tissues. The associations between ApoF expression and clinicopathological features as well as HCC prognosis were analyzed. The effect of ApoF on cellular proliferation and growth of SMMC-7721 and Huh7 cells was examined in vitro and in vivo. Results: ApoF expression was significantly down-regulated at both mRNA and protein levels in HCC tissues as compared with adjacent tissues. In SMMC-7721 and Huh7 HCC cells, ApoF overexpression inhibited cell proliferation and migration. In a xenograft nude mouse model, ApoF overexpression effectively controlled HCC growth. Kaplan-Meier analysis results showed that the recurrence-free survival rate of HCC patients with low ApoF expression was significantly lower than that of other HCC patients. Low ApoF expression was associated with several clinicopathological features such as liver cirrhosis, Barcelona Clinic Liver Cancer stage and tumor-node-metastasis stage. Conclusions: ApoF expression was down-regulated in HCC, which was associated with low recurrence-free survival rate. ApoF may serve as a tumor suppressor in HCC and be a potential application for the treatment of this disease.

19.
World J Clin Cases ; 7(20): 3194-3201, 2019 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-31667169

RESUMO

BACKGROUND: Mesenchymal tumors such as perivascular epithelioid cell neoplasm (PEComa) and inflammatory pseudotumor-like follicular dendritic cell sarcoma (IPT-like FDC sarcoma) are relatively uncommon in the liver and are particularly rare in the caudate lobe. The clinical manifestations and available imaging tests lack specificity for hepatic mesenchymal tumors. To the best of our knowledge, no caudate PEComa or IPT-like FDC sarcoma has been completely resected by laparoscopy. The standard laparoscopic technique, surgical approaches, and tumor margins for potentially malignant or malignant caudate mesenchymal tumors are still being explored. AIM: To assess both the safety and feasibility of laparoscopic resection for rare caudate mesenchymal neoplasms. METHODS: Eleven patients who underwent isolated caudate lobe resection from 2003 to 2017 were identified from a prospective database. Three consecutive patients with rare caudate mesenchymal tumors underwent laparoscopic resection. Patient demographic data, intraoperative parameters, and postoperative outcomes were assessed and compared with the open surgery group. RESULTS: All procedures for the three resection patients with caudate mesenchymal tumors were completed using a total laparoscopic technique by two different approaches. The average operative time was 226 min, and the estimated blood loss was 133 mL. The average length of postoperative hospital stay was 6.3 ± 0.3 d for the laparoscopy group and 15.5 ± 2.3 d for the open surgery group (P < 0.05). There were no perioperative complications or patient deaths in this series. CONCLUSION: Laparoscopic isolated caudate lobe resection for rare mesenchymal neoplasms is a feasible and curative surgical option in selected patients.

20.
Aging (Albany NY) ; 11(20): 8879-8891, 2019 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-31663864

RESUMO

CD8+ T cells are thought to be the primary cytotoxic lymphocytes exerting antitumor effects. However, few studies have focused on the antitumor effects of CD8+ T cell-mediated humoral immunity or on interactions between CD8+ T cells and B cells in hepatocellular carcinoma (HCC). We found that the frequency of IL-21-producing CD8+CXCR5+ T cells was higher in HCC tumor tissue than in peritumoral tissue or peripheral blood from the same patients or in blood from healthy donors. Moreover, CD8+CXCR5+ T cells migrated in response to supernatants from primary HCC (HCC-SN) cells, and HCC-SN cells also powerfully induced CXCR5 expression in CD8+ T cells and IL-21 expression in CD8+CXCR5+ T cells. CD8+CXCR5+ T cells from HCC patients, but not those from healthy individuals, stimulated CD19+ B cells to differentiate into IgG-producing plasmablasts. These findings reveal that CD8+CXCR5+ T cells strongly infiltrate HCC tumors, and their infiltration is predictive of a better prognosis. Surprisingly, moreover, CD8+CXCR5+ T cells produced IL-21, which induced B cells to differentiate into IgG-producing plasmablasts and to play a key role in humoral immunity in HCC.


Assuntos
Linfócitos T CD8-Positivos/fisiologia , Carcinoma Hepatocelular/imunologia , Neoplasias Hepáticas/imunologia , Receptores CXCR5/metabolismo , Idoso , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Interleucinas/genética , Interleucinas/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Receptores CXCR5/genética
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