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1.
Cancer Med ; 13(10): e7300, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38800978

RESUMO

BACKGROUND: Numerous observational studies have investigated the potential link between hypertensive disorders of pregnancy (HDPs) and the subsequent risks of gynecologic tumors, yet the findings have been inconsistent. In this study, we utilized Mendelian randomization (MR) approach to assess the influence of HDPs on the future risks of ovarian, cervical, endometrial, and breast cancer and uterine fibroids, controlling for confounding factors. METHODS: The genome-wide association studies (GWAS) summary data relevant to HDPs was obtained from the FinnGen databases (10,736 cases and 136,325 controls). Gynecologic tumor outcomes were extracted from the IEU Open GWAS project and UK Biobank (47,690 cases and 1, 092,073 controls). The inverse variance weighted (IVW) approach was selected as the principal method for MR analysis, supplemented by MR-Egger, weighted median, weighted model, simple model methods, MR pleiotropy residual sum and outlier (MR-PRESSO) test, and leave-one-out method. Multivariate MR (MVMR) analysis was conducted after adjusting systolic blood pressure (SBP), body mass index (BMI) and type 2 diabetes mellitus (T2DM). RESULTS: Our univariate MR analysis (UVMR) results revealed no significant relationship between HDPs and the risks of ovarian cancer (odds ratio [OR] = 0.924, p = 0.360), cervical cancer (OR = 1.230, p = 0.738), endometrial cancer (OR = 1.006, p = 0.949), uterine fibroids (OR = 1.155, p = 0.158), and breast cancer (OR = 0.792, p = 0.241) by IVW test. Similar results were observed in gestational hypertension and preeclampsia/eclampsia. Additionally, our study detected neither heterogeneity nor pleiotropy. MVMR analysis also provided no evidence of a causal association between HDPs and common gynecologic tumors after adjusting SBP, BMI, and T2DM. CONCLUSION: We discovered no causal relationship between HDPs and ovarian, cervical, endometrial, breast cancer, and uterine fibroids in European populations. However, present analysis did not explore the effect of HDPs on the subtypes of gynecologic tumors across varied ethnic populations, which may require additional research.


Assuntos
Neoplasias dos Genitais Femininos , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Humanos , Feminino , Gravidez , Neoplasias dos Genitais Femininos/genética , Neoplasias dos Genitais Femininos/epidemiologia , Neoplasias dos Genitais Femininos/etiologia , Hipertensão Induzida pela Gravidez/genética , Hipertensão Induzida pela Gravidez/epidemiologia , Hipertensão Induzida pela Gravidez/etiologia , Fatores de Risco , Polimorfismo de Nucleotídeo Único
2.
Stem Cell Rev Rep ; 20(3): 601-616, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38170319

RESUMO

Acute liver failure (ALF) results from severe liver damage or end-stage liver disease. It is extremely fatal and causes serious health and economic burdens worldwide. Once ALF occurs, liver transplantation (LT) is the only definitive and recommended treatment; however, LT is limited by the scarcity of liver grafts. Consequently, the clinical use of bioartificial liver (BAL) has been proposed as a treatment strategy for ALF. Human primary hepatocytes are an ideal cell source for these methods. However, their high demand and superior viability prevent their widespread use. Hence, finding alternatives that meet the seed cell quality and quantity requirements is imperative. Stem cells with self-renewing, immunogenic, and differentiative capacities are potential cell sources. MSCs and its secretomes encompass a spectrum of beneficial properties, such as anti-inflammatory, immunomodulatory, anti-ROS (reactive oxygen species), anti-apoptotic, pro-metabolomic, anti-fibrogenesis, and pro-regenerative attributes. This review focused on the recent status and future directions of stem cell-based strategies in BAL for ALF. Additionally, we discussed the opportunities and challenges associated with promoting such strategies for clinical applications.


Assuntos
Falência Hepática Aguda , Transplante de Fígado , Fígado Artificial , Humanos , Hepatócitos , Falência Hepática Aguda/terapia , Células-Tronco
3.
J Matern Fetal Neonatal Med ; 37(1): 2299110, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38185625

RESUMO

BACKGROUND: Low-hemoglobin concentration and anemia are important risk factors for the health and development of women and children. The aim of this study was to investigate the correlation between blood indicators in early pregnancy among non-anemia women and anemia in the third trimester among pregnant women in China with uncomplicated pregnancies >36 weeks. METHODS: This was a multicenter, prospective cohort study. Pregnant women registered at the survey hospitals from May 2019 to December 2020 were included and followed up until delivery and discharge. The predictive value of serum ferritin (SF) and routine blood indexes (platelet count, red blood cell count, hemoglobin level, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration) were analyzed using a receiver operating characteristic (ROC) curve for the occurrence of anemia in the third trimester. RESULTS: The area under the ROC curve of the first trimester hemoglobin for predicting anemia during late pregnancy (cutoff value 128 g/L, sensitivity 82.3%, specificity 49.6%) and iron deficiency anemia (cutoff value 124 g/L, sensitivity 66.3%, specificity 66.4%) in the third trimester was larger than those of other blood variables. CONCLUSIONS: Hemoglobin levels in the first trimester were significantly better predictors of anemia during the third trimester than the other indices. Our study contributes to the clinical practice of early intervention for anemia, thus taking effective measures to improve maternal and infant outcomes.


Assuntos
Anemia , Criança , Lactente , Gravidez , Feminino , Humanos , Estudos Prospectivos , Anemia/epidemiologia , Terceiro Trimestre da Gravidez , China/epidemiologia , Hemoglobinas
4.
J Vis Exp ; (202)2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-38108411

RESUMO

Laparoscopic anterior right hepatectomy (LARH) has been used in some hospitals. However, data on the feasibility and safety of this procedure are still limited, due to the demanding technical requirements. The primary objective of this study was to compare the clinical outcomes of LARH with those of laparoscopic conventional right hepatectomy (LCRH) in patients with large right hepatocellular carcinoma, as well as to confirm the safety and feasibility of LARH. Furthermore, the article presents a step-by-step description of the surgical procedures for LARH to help perform this surgery in the clinic. The principle of LARH is to first prioritize the hepatic inlet duct separation while separating the right hepatic perihepatic ligament after transecting the liver. From December 2015 to June 2022, 82 patients with large right hepatocellular carcinoma (maximum tumor diameter ≥ 5 cm), were recruited for the study. In this cohort, 54 and 28 patients underwent LARH and LCRH, respectively. The perioperative clinical data and survival outcomes of the two groups were compared. Compared with LCRH, LARH exhibited the advantages of less contact and extrusion, thereby leading to the achievement of superior results. Thus, we propose that LARH is the optimal choice for patients with large right hepatocellular carcinoma.


Assuntos
Carcinoma Hepatocelular , Laparoscopia , Neoplasias Hepáticas , Humanos , Hepatectomia , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia
5.
Bioeng Transl Med ; 8(5): e10552, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37693041

RESUMO

Acute liver failure (ALF) is a life-threatening condition. Cell-based and cell-free-based therapies have proven to be effective in treating ALF; however, their clinical application is limited by cell tumorigenicity and extracellular vesicle (EV) isolation in large doses. Here, we explored the effectiveness and mechanism of umbilical cord mesenchymal stem cells (hUCMSCs)-based bioartificial liver (hUCMSC-BAL), which is a simple and efficient strategy for ALF. D-galactosamine-based pig and mouse ALF models were used to explore the effectiveness of hUCMSC-BAL and hUCMSC-sEV therapies. Furthermore, high-throughput sequencing, miRNA transcriptome analysis, and western blot were performed to clarify whether the miR-139-5p/PDE4D axis plays a critical role in the ALF model in vivo and in vitro. hUCMSC-BAL significantly reduced inflammatory responses and cell apoptosis. hUCMSC-sEV significantly improved liver function in ALF mice and enhanced the regeneration of liver cells. Furthermore, hUCMSC-sEV miRNA transcriptome analysis showed that miR-139-5p had the highest expression and that PDE4D was one of its main target genes. The sEV miR-139-5p/PDE4D axis played a role in the treatment of ALF by inhibiting cell apoptosis. Our data indicate that hUCMSC-BAL can inhibit cytokine storms and cell apoptosis through the sEV miR-139-5p/PDE4D axis. Therefore, we propose hUCMSC-BAL as a therapeutic strategy for patients with early ALF.

6.
Cell Oncol (Dordr) ; 46(5): 1333-1350, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37099250

RESUMO

BACKGROUND: Circular RNAs (circRNAs) are noncoding RNAs. Accumulating evidence suggests that circRNAs play a critical role in human biological processes, especially tumorigenesis, and development. However, the exact mechanisms of action of circRNAs in hepatocellular carcinoma (HCC) remain unclear. METHODS: Bioinformatic tools and RT-qPCR were used to identify the role of circDHPR, a circRNA derived from the dihydropteridine reductase (DHPR) locus, in HCC and para-carcinoma tissues. Kaplan-Meier analysis and the Cox proportional hazard model were used to analyze the correlation between circDHPR expression and patient prognosis. Lentiviral vectors were used to establish stable circDHPR-overexpressing cells. In vitro and in vivo studies have shown that tumor proliferation and metastasis are affected by circDHPR. Mechanistic assays, including Western blotting, immunohistochemistry, dual-luciferase reporter assays, fluorescence in situ hybridization, and RNA immunoprecipitation, have demonstrated the molecular mechanism underlying circDHPR. RESULTS: CircDHPR was downregulated in HCC, and low circDHPR expression was associated with poor overall survival and disease-free survival rates. CircDHPR overexpression inhibits tumor growth and metastasis in vitro and in vivo. Further systematic studies revealed that circDHPR binds to miR-3194-5p, an upstream regulator of RASGEF1B. This endogenous competition suppresses the silencing effect of miR-3194-5p. We confirmed that circDHPR overexpression inhibited HCC growth and metastasis by sponging miR-3194-5p to upregulate the expression of RASGEF1B, which is regarded as a suppressor of the Ras/MAPK signaling pathway. CONCLUSIONS: Aberrant circDHPR expression leads to uncontrolled cell proliferation, tumorigenesis, and metastasis. CircDHPR may serve as a biomarker and therapeutic target for HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Humanos , Carcinoma Hepatocelular/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Neoplasias Hepáticas/metabolismo , Di-Hidropteridina Redutase/genética , Di-Hidropteridina Redutase/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Hibridização in Situ Fluorescente , Linhagem Celular Tumoral , Proliferação de Células/genética , Carcinogênese/patologia , Regulação Neoplásica da Expressão Gênica
7.
Front Oncol ; 13: 1119744, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36959801

RESUMO

Background: Minimal residual disease (MRD) is considered an essential factor leading to relapse within 2 years (early relapse) after radical surgery, which is challenging to be detected by conventional imaging. Circulating tumor DNA (ctDNA) provides a novel approach for detecting MRD and predicting clinical outcomes. Here, we tried to construct a fixed panel for plasma-only ctDNA NGS to enable tumor-uninformed MRD detection in hepatocellular carcinoma (HCC). Methods: Here, we performed the followings: (i) profiling genomic alteration spectrum of ctDNA from the Chinese HCC cohort consisting of 493 individuals by NGS; (ii) screening of MRD monitoring genes; and (iii) performance evaluation of MRD monitoring genes in predicting early relapse in the ZJZS2020 cohort comprising 20 HCC patients who underwent curative resection. Results: A total of 493 plasma samples from the Chinese HCC cohort were detected using a 381/733-gene NGS panel to characterize the mutational spectrum of ctDNA. Most patients (94.1%, 464/493) had at least one mutation in ctDNA. The variants fell most frequently in TP53 (45.1%), LRP1B (20.2%), TERT (20.2%), FAT1 (16.2%), and CTNNB1 (13.4%). By customized filtering strategy, 13 MRD monitoring genes were identified, and any plasma sample with one or more MRD monitoring gene mutations was considered MRD-positive. In the ZJZS2020 cohort, MRD positivity presented a sensitivity of 75% (6/8) and a specificity of 100% (6/6) in identifying early postoperative relapse. The Kaplan-Meier analysis revealed a significantly short relapse-free survival (RFS; median RFS, 4.2 months vs. NR, P=0.002) in the MRD-positive patients versus those with MRD negativity. Cox regression analyses revealed MRD positivity as an independent predictor of poor RFS (HR 13.00, 95% CI 2.60-69.00, P=0.002). Conclusions: We successfully developed a 13-gene panel for plasma-only MRD detection, which was effective and convenient for predicting the risk of early postoperative relapse in HCC.

9.
Front Med (Lausanne) ; 10: 1283279, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38179282

RESUMO

Objective: The assessment of the relative impacts of uterine artery embolization (UAE) treatment for female patients is a critical field that informs clinical decisions, yet there is a noticeable scarcity of high-quality, long-term comparative studies. This meta-analysis aimed to focus on the pregnancy rate and outcomes in female patients following UAE and to conduct subgroup analyses based on different patient populations or various control treatments. Methods: A systematic literature search was conducted on 2 August 2023 through the Web of Science, PubMed, Embase, and the Cochrane Library of Clinical Trials for all potential studies. Relative risks (RRs) with 95% confidence intervals (CIs) were applied to compare pregnancy rates and outcomes between the UAE group and the control group. Heterogeneity was evaluated statistically by using the chi-square-based Cochran's Q test and Higgins I2 statistics, and 95% prediction interval (PI). Software R 4.3.1 and Stata 12.0 were used for meta-analysis. The trial sequential analysis (TSA) was performed with TSA v0.9.5.10 Beta software. Results: A total of 15 eligible studies (11 cohort studies, 3 randomized controlled trials, and 1 non-randomized clinical trial) were included in this meta-analysis. The overall results revealed that UAE significantly decreased postoperative pregnancy rate [RR (95% CI): 0.721 (0.531-0.979), 95% PI: 0.248-2.097] and was associated with an increased risk of postoperative PPH [RR (95% CI): 3.182 (1.319-7.675), 95% PI: 0.474-22.089]. Analysis grouped by population indicated that UAE decreased the risk of preterm delivery [RR (95% CI): 0.326 (0.128-0.831), p = 0.019] and cesarean section [RR (95% CI): 0.693 (0.481-0.999), p = 0.050] and increased the risk of placenta previa [RR (95% CI): 8.739 (1.580-48.341), p = 0.013] in patients with UFs, CSP, and PPH, respectively. When compared with myomectomy, HIFU, and non-use of UAE, UAE treatment was associated with the reduced risks of preterm delivery [RR (95% CI): 0.296 (0.106-0.826)] and cesarean section [(95% CI): 0.693 (0.481-0.999), p = 0.050] and increased placenta previa risk [RR (95% CI): 10.682 (6.859-16.636)], respectively. Conclusion: UAE treatment was associated with a lower postoperative pregnancy rate and increased risk of PPH. Subgroup analysis suggested that UAE was shown to decrease the risk of preterm delivery and cesarean section and increase placenta previa risk.Systematic review registration:https://www.crd.york.ac.uk/prospero/, Identifier CRD42023448257.

10.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 53(6): 1003-1006, 2022 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-36443042

RESUMO

Preeclampsia-eclampsia is a common obstetric critical disease and obstetricians have studied it assiduously for hundreds of years. We have attempted to explore the etiology, pathology, prevention, intervention, and treatment of preeclampsia-eclampsia, but we still have not arrived at a thorough understanding of its causes, and it is difficult to find effective prevention and treatment methods. Although the research process has been fraught with difficulties and frustrations, we are nonetheless gradually gaining a better understanding of the disease. Perhaps, in the near future, we will be able to acquire a full understanding of the disease and find better ways to ensure the health and safety of mothers and fetuses.


Assuntos
Eclampsia , Pré-Eclâmpsia , Feminino , Gravidez , Humanos , Pré-Eclâmpsia/prevenção & controle , Feto
11.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 53(6): 1016-1020, 2022 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-36443045

RESUMO

Preeclampsia gravely threatens the health of mothers and infants. At present, treatment based on the relevant mechanisms of pathogenesis is still not available, and there is no independent reliable clinical index for early prediction of preeclampsia. According to recent studies, analysis of the cell-free RNA in the peripheral blood of pregnant women has shown that testing certain cell-free RNA levels can help predict in advance the occurrence of preeclampsia before clinical symptoms appear. In this paper, we described the status of research and progress in using maternal cell-free RNA analysis in predicting preeclampsia. In addition, we stated that cell-free RNA in peripheral blood may become a promising, real-time and non-invasive monitoring method that can be used to explore the mechanisms of pathogenesis and pathophysiology of preeclampsia and to identify different subtypes of preeclampsia.


Assuntos
Ácidos Nucleicos Livres , Pré-Eclâmpsia , Gravidez , Lactente , Feminino , Humanos , Gestantes , Pré-Eclâmpsia/diagnóstico , Família
12.
J Vis Exp ; (189)2022 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-36408986

RESUMO

Among the lymphatic system in the human body, the spleen is the most extensive one and has hematopoietic, hemofiltration, blood storage, and immune functions. As a new method of preserving the spleen, laparoscopic partial splenectomy (LPS) has been increasingly applied in clinical practice with people's deeper insights into minimally invasive treatment and the development of technical equipment. Compared with conventional open splenectomy, LPS can preserve normal spleen tissue as much as possible, decrease the occurrence of complications after total splenectomy, and reduce postoperative hospital stay. The bipolar radiofrequency excision hemostatic device used for LPS can solidify the splenic tissue and close the small blood vessels, which reduces the hemorrhage of the spleen cross-section and clears the operative field, thus achieving the ideal effect of "bloodless partial splenectomy". Therefore, under the premise of strictly mastering the indications and fully understanding the vascular anatomy of the spleen, the application of the bipolar radiofrequency excision hemostatic device in LPS is worthy of clinical promotion.


Assuntos
Hemostáticos , Laparoscopia , Humanos , Esplenectomia/métodos , Lipopolissacarídeos , Laparoscopia/métodos , Baço/cirurgia
13.
J Tissue Eng ; 13: 20417314221132093, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36313857

RESUMO

Mesenchymal stem cells (MSCs) have potential role in organ regeneration therapy. Previous work indicating that MSCs confer protection against liver disease. Here, we aimed to determine the potential application in liver regeneration of human placenta-derived MSCs extracellular vesicles (hPMSCs-EVs) via experimental hepatectomy. hPMSCs-EVs were administered intravenously 24 h before 70% partial hepatectomy, the specific composition of hPMSCs-EVs was identified by sequencing and validated by the quantitative polymerase chain reaction, including circ-RBM23. The role of circ-RBM23 in L02 cell was evaluated and it was found that circ-RBM23 knockdown inhibited L02 cell proliferation both in vitro and in vivo. The competing endogenous RNA function of circ-RBM23 was evaluated by the RNA immunoprecipitation assay and found that circ-RBM23 shares miRNA response elements with RRM2. Overexpressed circ-RBM23 bound competitively to miR-139-5p, preventing the miRNA-mediated degradation of RRM2, activating the expression of eIF4G and AKT/mTOR, and facilitating liver regeneration. These results indicate that hPMSCs-EVs prevent hepatic dysfunction and improve liver regeneration in vivo and hepatocytes proliferation in vitro, potentially via circ-RBM23 delivery.

14.
World J Clin Cases ; 10(26): 9361-9367, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36159400

RESUMO

BACKGROUND: Multicystic biliary hamartoma (MCBH) is a rare hamartomatous nodule of the liver, which has recently been described as a new category of hepatic nodular cystic lesion. Most of them are benign. The imaging findings are similar to those of many other hepatic cystic lesions, but MCBH also has some notable features, such as large cysts, smooth cyst walls, and lack of communication with the hepatic duct. Due to the non-specific radiology, preoperative diagnosis is difficult, and is usually diagnosed by postoperative pathology. Complete resection is the best treatment option, and the postoperative prognosis is good. CASE SUMMARY: When the patients have MCBH, the symptoms may not very typical, and they require a combination of imaging and pathology for diagnosis. Under normal circumstances, the prognosis of MCBH is good. However, in patients with MCBH, more cases need to be observed for verification. CONCLUSION: When the patients have MCBH, the symptoms may not very typical, and they require a combination of imaging and pathology for diagnosis. Under normal circumstances, the prognosis of MCBH is good. However, in patients with MCBH, more cases need to be observed for verification.

15.
Front Immunol ; 13: 999763, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36119069

RESUMO

Portal vein tumor thrombus (PVTT) is a frequent complication in hepatocellular carcinoma (HCC). HCC patients with PVTT have the characteristics of less treatment tolerance and poor prognosis. Immunotherapy, especially combined immunotherapy, has been successfully used in advanced HCC. However, there are no recognized universally indicators that can predict response or resistance to immunotherapy for HCC. Herein, we reported a 58-year-old HCC patient with PVTT, cirrhosis and chronic viral hepatitis, who achieved complete response (CR) after combined immunotherapy (camrelizumab combined with sorafenib or regorafenib), according to his high enrichment of tumor-infiltrating immune cells and tertiary lymphoid structure (TLS). In this case, we revealed the characteristics of the baseline tumor immune microenvironment (TIME) in a HCC patient who responded well to combined immunotherapy, suggesting that TIME can be used to assist in clinical decision making of immunotherapy for HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Trombose , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Humanos , Imunoterapia , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Pessoa de Meia-Idade , Veia Porta/patologia , Sorafenibe/uso terapêutico , Trombose/patologia , Microambiente Tumoral
16.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 53(3): 543-548, 2022 May.
Artigo em Chinês | MEDLINE | ID: mdl-35642169

RESUMO

Plasma D-dimer, a special cross-linked fibrin derivative, is produced when fibrin is degraded by plasminase. During pregnancy, D-dimer increases along with the increase of gestational age, and the reference value of plasma D-dimer (≤0.5 mg/L) traditionally used for the screening of venous thrombosis in the normal population is not applicable to the pregnant population. Due to the lack of uniform D-dimer detection methods or measurement units, there is currently no unified D-dimer reference values for pregnancy or puerperium. Each region or laboratory should establish its own pregnancy D-dimer reference value for different gestational weeks through blood coagulation function testing of large numbers of samples of different gestational periods. More and more studies have been conducted to investigate the association between D-dimer and venous thromboembolism (VTE) during pregnancy, gestational hypertensive disorders (GHD) and pregnancy outcome. We reviewed, herein, the generation and measurement of D-dimer, the reference values of D-dimer during normal pregnancy, and the association between D-dimer and some pathological pregnancies, intending to help clinicians develop a more thorough understanding of D-dimer during pregnancy.


Assuntos
Produtos de Degradação da Fibrina e do Fibrinogênio , Gravidez , Tromboembolia Venosa , Feminino , Fibrina , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Humanos , Gravidez/sangue , Valores de Referência , Tromboembolia Venosa/diagnóstico
17.
Int J Artif Organs ; 45(5): 523-532, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35416082

RESUMO

BACKGROUND: Acute liver failure (ALF), which can potentially be treated with an artificial liver, is a fatal condition. The purpose of this study was to evaluate the safety and effectiveness of a novel hybrid bioartificial liver system (NHBLS) using simulated liver failure serum in vitro. METHODS: The bioreactor in experimental group was cultivated with primary porcine hepatocytes, whereas in control group was not. Next, the simulated liver failure serum was treated using the NHBLS for 10 h. Changes in albumin (ALB), total bilirubin (TBIL), ammonia (Amm), total bile acid (TBA), creatinine (Cr), and blood urea nitrogen (BUN) were measured before treatment (0 h) and every 2 h during treatment. In addition, changes in NHBLS pressures, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lidocaine metabolism were also recorded. RESULTS: The NHBLS worked steadily without unexpected occurrences during the treatment. Blood culture showed no bacterial growth after 7 days, and the endotoxin level was less than 0.5 EU. The TBIL, TBA, Cr, and BUN levels in both groups were markedly lower than those at 0 h (p < 0.05). The Amm level in experimental group was significantly lower than that in control group (p < 0.05). NHBLS pressures were also stable, and the hepatocytes in the bioreactor functioned well. CONCLUSIONS: The preparation method for the simulated liver failure serum was optimized successfully, and the safety and effectiveness of the NHBLS in vitro were verified. Furthermore, the NHBLS significantly reduced the levels of Amm which can lead to hepatic encephalopathy.


Assuntos
Falência Hepática Aguda , Fígado Artificial , Alanina Transaminase/metabolismo , Animais , Bilirrubina , Hepatócitos/metabolismo , Fígado/metabolismo , Falência Hepática Aguda/terapia , Suínos
18.
Front Immunol ; 13: 1079294, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36685560

RESUMO

Studies have shown that fetal immune cell activation may result from potential exposure to microbes, although the presence of microbes in fetus has been a controversial topic. Here, we combined metagenomic and virome techniques to investigate the presence of bacteria and viruses in fetal tissues (small intestine, cecum, and rectum). We found that the fetal gut is not a sterile environment and has a low abundance but metabolically rich microbiome. Specifically, Proteobacteria and Actinobacteria were the dominant bacteria phyla of fetal gut. In total, 700 species viruses were detected, and Human betaherpesvirus 5 was the most abundant eukaryotic viruses. Especially, we first identified Methanobrevibacter smithii in fetal gut. Through the comparison with adults' gut microbiota we found that Firmicutes and Bacteroidetes gradually became the main force of gut microbiota during the process of growth and development. Interestingly, 6 antibiotic resistance genes were shared by the fetus and adults. Our results indicate the presence of microbes in the fetal gut and demonstrate the diversity of bacteria, archaea and viruses, which provide support for the studies related to early fetal immunity. This study further explores the specific composition of viruses in the fetal gut and the similarities between fetal and adults' gut microbiota, which is valuable for understanding human fetal immunity development during gestation.


Assuntos
Microbiota , Vírus , Adulto , Humanos , Gravidez , Feminino , Viroma , Bactérias/genética , Metagenoma , Vírus/genética , Feto
19.
Neoplasia ; 23(12): 1227-1239, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34768109

RESUMO

Sorafenib is a first-line molecular-target drug for advanced hepatocellular carcinoma (HCC), and reducing sorafenib resistance is an important issue to be resolved for the clinical treatment of HCC. In the current study, we identified that ABCC5 is a critical regulator and a promising therapeutic target of acquired sorafenib resistance in human hepatocellular carcinoma cells. The expression of ABCC5 was dramatically induced in sorafenib-resistant HCC cells and was remarkably associated with poor clinical prognoses. The down-regulation of ABCC5 expression could significantly reduce the resistance of sorafenib to HCC cells. Importantly, activation of PI3K/AKT/NRF2 axis was essential for sorafenib to induce ABCC5 expression. ABCC5 increased intracellular glutathione (GSH) and attenuated lipid peroxidation accumulation by stabilizing SLC7A11 protein, which inhibited ferroptosis. Additionally, the inhibition of ABCC5 enhanced the anti-cancer activity of sorafenib in vitro and in vivo. These findings demonstrate a novel molecular mechanism of acquired sorafenib resistance and also suggest that ABCC5 is a new regulator of ferroptosis in HCC cells.


Assuntos
Sistema y+ de Transporte de Aminoácidos/metabolismo , Carcinoma Hepatocelular/metabolismo , Resistencia a Medicamentos Antineoplásicos/fisiologia , Neoplasias Hepáticas/metabolismo , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Ferroptose/fisiologia , Humanos , Neoplasias Hepáticas/patologia , Sorafenibe/farmacologia
20.
Biomed Res Int ; 2021: 6673125, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34595239

RESUMO

BACKGROUND: Pancreatic cancer (PC) is one of the most common cancers worldwide, with high mortality. The UGT1A gene family plays important roles in pharmacology and toxicology, contributing to interindividual differences in drug disposition. However, mRNA expression and prognostic value of the UGT1A gene family in PC have not been identified. METHODS: Oncomine, GEPIA2, DAVID 6.8, Metascape, Kaplan-Meier plotter, cBioPortal, GeneMANIA, TRRUST v2, TIMER, and R software were used in our study. RESULTS: The transcriptional levels of UGT1A1/3/6/8/9/10 in PC tissues were significantly higher than those in normal tissues. These results were further validated using five pairs of PC tumor tissues and adjacent nontumor tissues. A significant correlation was found between the expression of UGT1A1/6/10 and the pathological stage of PC. PC patients with lower transcriptional levels of UGT1A1/4/5/6/10 were associated with a better prognosis. The differentially expressed UGT1A gene family functions were primarily related to the glucuronidation pathway, cytokine-cytokine receptor interactions, and the ILK signaling pathway. Our data suggest that HNF1A, AHR, and CDX2 are key transcription factors for the UGT1A gene family. Furthermore, the expression levels of UGT1A1/3/8/9/10 were positively correlated with the activities of tumor-infiltrating immune cells, especially B cells. The expression levels of UGT1A6/9 were negatively correlated with macrophage infiltration levels. CONCLUSIONS: These results suggest that the UGT1A gene family could serve as a potential prognostic biomarker and target for PC. However, future studies are required to validate our findings and promote the clinical utility of the UGT1A gene family in PC.


Assuntos
Biomarcadores Tumorais/genética , Glucuronosiltransferase/genética , Família Multigênica , Neoplasias Pancreáticas/enzimologia , Neoplasias Pancreáticas/genética , Biomarcadores Tumorais/metabolismo , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Glucuronosiltransferase/metabolismo , Humanos , Estimativa de Kaplan-Meier , Linfócitos do Interstício Tumoral/imunologia , Neoplasias Pancreáticas/imunologia , Prognóstico , Ligação Proteica , Mapas de Interação de Proteínas/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reprodutibilidade dos Testes , Transcrição Gênica
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