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1.
Talanta ; 236: 122899, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34635272

RESUMO

A real-time quartz crystal microbalance (QCM) cytosensor was first developed for dynamical and noninvasive monitoring of cell viscoelasticity for evaluation of apoptosis degree. In this work, human breast cancer cells MCF-7 and MDA-MB-231 were employed as cell model and respectively captured on the surface of QCM electrode modified with mercaptosuccinic acid and poly-l-lysine. Cell viscoelasticity was measured dynamically by real-time monitoring energy dissipation with QCM, and the dynamic diagram of the energy dissipation of MDA-MB-231 cells treated with curcumin was first obtained. The results displayed that the changes of energy dissipation in MDA-MB-231 cells and MCF-7 cells were 8.81 × 10-6 and 5.29 × 10-6, particularly due to the difference in cell viscoelasticity. Furthermore, curcumin was used to induce cell apoptosis and suppress energy dissipation of MDA-MB-231 cells. Combining apoptosis assay with QCM measurement, the results revealed good linear relationship between cell viscoelasticity inhibition and apoptosis rate with correlation coefficient R = 0.9908. The QCM cytosensor could rapidly, accurately, dynamically, and noninvasively monitor the changes of cell viscoelasticity for evaluation of apoptosis degree in MDA-MB-231 cells. The study established a new model for cell apoptosis assessment, facilitating understanding of the mechanisms of cell apoptosis on the aspect of mechanical properties.


Assuntos
Técnicas Biossensoriais , Neoplasias da Mama , Curcumina , Apoptose , Neoplasias da Mama/tratamento farmacológico , Curcumina/farmacologia , Feminino , Humanos , Viscosidade
2.
Food Chem ; 371: 131156, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34583183

RESUMO

The spoiled dry-cured ham commonly shows unpleasant taste and odour. To deepen the understanding in the formation mechanism of unpleasant taste in spoiled ham, sensory attributes, texture parameters, protein degradation, metabolites were investigated between normal and spoiled hams; the relationship between the sensory quality and metabolites of dry-cured ham was further evaluated by partial least square discriminant analysis (PLS-DA). The scores of richness and overall acceptance were significantly lower in spoiled ham, and more than 12.5-fold values in adhesiveness were found in spoiled ham than normal ham. Myofibrillar proteins including actin, troponin-T and myosin light chain showed excessive degradation in spoiled ham. Forty-two kinds of metabolites mainly derived from protein degradation were identified by LC-MS/MS, and amino acid derivatives and oligopeptides were the key components to distinguish spoiled and normal hams demonstrated by PLS-DA. Purine metabolism, pyrimidine metabolism and protein degradation were the main metabolism pathways in spoiled ham.


Assuntos
Produtos da Carne , Carne de Porco , Cromatografia Líquida , Produtos da Carne/análise , Metabolômica , Espectrometria de Massas em Tandem
3.
Crit Rev Food Sci Nutr ; : 1-17, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34748438

RESUMO

ß-glucan from cereals such as wheat, barley, oats and rye are a water-soluble dietary fiber, which are composed of repeating (1→4)-ß-bond ß-D-glucopyranosyl units and a single (1→3)-ß-D-bond separated unit. ß-glucan has a series of physicochemical properties (such as viscosity, gelling properties, solubility, etc.), which can be used as a food gel and fat substitute. Its structure endows the healthy functions, including anti-oxidative stress, lowering blood glucose and serum cholesterol, regulating metabolic syndrome and exerting gut immunity via gut microbiota. Due to their unique structural properties and efficacy, cereal ß-glucan are not only applied in food substrates in the food industry, but also in food coatings and packaging. This article reviewed the applications of cereal ß-glucan in hydrogels, aerogels, intelligent packaging systems and targeted delivery carriers in recent years. Cereal ß-glucan in edible film and gel packaging applications are becoming more diversified and intelligent in recent years. Those advances provide a potential solution based on cereal ß-glucan as biodegradable substances for immune regulation delivery system and intelligent gelling material in the biomedicine field.

4.
Front Pediatr ; 9: 685956, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34604134

RESUMO

Background: The anatomic variation of hepatic vein in the left lateral segment (LLS) increases the risk of outflow complication in pediatric living liver transplantation (LDLT). Here, we share a modified method for dual hepatic vein reconstruction in pediatric LDLT using LLS with two wide orifices. Methods: From Sep 2018 to Dec 2019, 434 pediatric LDLTs using LLS were performed in our center. Hepatic veins of grafts were classified into three types with emphasis on the number, size, and location of orifices at the cut surface: a single opening (type I, n = 341, 78.57%); two adjacent orifices (type II, n = 66, 15.21%); two wide orifices with orifices distances <20 mm (type IIIa, n = 15, 3.46%); and two wide orifices with orifices distances >20 mm (type IIIb, n = 12, 2.76%). Rv was defined as the ratio of diameter of V2 and V3 (refer to hepatic vein drained segments II and III). We developed a modified dual hepatic vein anastomosis to reconstruct outflow for type IIIb grafts with Rv ≤1. Briefly, the hepatic vein of segment II was anastomosed to the common stump of middle hepatic vein (MHV) and left hepatic vein (LHV), followed by unification of V3 and the longitudinal incision orifice in inferior venous cave (IVC). Results: During median follow-up of 15.6 months (7.5-22.9 months), no hepatic vein complications occurred. Conclusion: This novel modified dual hepatic vein anastomosis could serve as a feasible surgical option for type IIIb LLS grafts with Rv ≤1 in pediatric LDLT.

5.
Liver Int ; 2021 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-34719108

RESUMO

BACKGROUND AND AIMS: Liver regeneration is a complex process regulated by a variety of cells, cytokines and biological pathways. Aurora kinase A (AURKA) is a serine/threonine kinase that plays a role in centrosome maturation and spindle formation during the cell division cycle. The purpose of this study was to further explore the mechanism of AURKA on liver regeneration and to identify new possible targets for liver regeneration. METHODS: The effect and mechanism of AURKA on liver regeneration were studied using a 70% hepatectomy model. Human liver organoids were used as an in vitro model to investigate the effect of AURKA on hepatocyte proliferation. RESULTS: AURKA inhibition significantly reduced the level of ß-catenin protein by reducing the phosphorylation level of glycogen synthase kinase-3ß (GSK-3ß), leading to the inhibition of liver regeneration. Further studies showed that AURKA co-localized and interacted with GSK-3ß in the cytoplasm of hepatocytes. When phosphorylation of GSK-3ß was enhanced, the total GSK-3ß level remained unchanged, while AURKA was not affected, and ß-catenin protein levels were increased. In addition, AURKA inhibition affected the formation and proliferation of human liver organoids. Furthermore, AURKA inhibition led to the polarization of M1 macrophages and the release of interleukin-6 and Tumour necrosis factor α, which also led to reduced liver regeneration and increased liver injury. CONCLUSIONS: These results provide more details on the mechanism of liver regeneration and suggest that AURKA is an important regulator of this mechanism.

7.
Chem Phys Lipids ; 242: 105150, 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34673008

RESUMO

Phloretin is a powerful antioxidant with many effects, such as anti-cancer, anti-inflammatory, promoting cell renewal, delaying aging and so on. However, the application of phloretin was limited by its low water solubility, low absorption in vivo and unstable properties. A phloretin-loaded nanostructured lipid carrier was designed with a high-pressure homogenization technique. The mean particle size of phloretin NLC was 137.40 ± 3.27 nm, and the Polydispersity index (PdI) value was 0.237 ± 0.005. The encapsulation efficiency was 96.68% ± 0.06%. Transmission electron microscopy images showed that the phloretin-loaded nanostructured lipid carriers were spherical. Phloretin in NLC showed a sustained release pattern in vitro. The results showed that phloretin NLC is more suitable for absorption than phloretin ethanol solution, and NLC can be a promising carrier for phloretin in the food industry.

8.
Int J Med Sci ; 18(15): 3361-3366, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34522161

RESUMO

Ferroptosis is an iron-dependent form of regulated cell death, which is characterized by a large amount of lipid peroxide accumulation and the imbalance of redox state in cells. Ferroptosis is usually accompanied with the dysfunction of lipid repair enzyme (glutathione peroxidase 4, GPX4), large masses of iron accumulation and lipid peroxidation of polyunsaturated fatty acids (PUFAs). Ferroptosis is related to several signaling pathways, including amino acid and iron metabolism, ferritinophagy, cell adhesion and p53 and Keap1/Nrf2 signaling pathways. A number of studies have indicated that ferroptosis is closely associated with acute renal failure, tumor, ischemia and reperfusion injury, neurodegenerative diseases and liver fibrosis. Liver fibrosis, which has long been a global health problem, still lacks effective treatment till now, and the discovery of ferroptosis provides a new insight into addressing this issue.

10.
Ann Transl Med ; 9(13): 1071, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34422983

RESUMO

Background: Fungal encephalitis is uncommon and sometimes fatal in liver transplant (LT) recipients. Early diagnosis of central nervous system (CNS) fungal infections, especially aspergillosis, is difficult based on routine tests of cerebrospinal fluid (CSF) alone. Next-generation sequencing (NGS) as a new tool may help in this respect. Methods: Shotgun metagenomics was used to detect pathogens in CSF of patients, who were clinically suspected of CNS infection. Sequencing was performed at BGIseq-50 platform (BGI, Shenzhen). Results: NGS technique identified Aspergillus in CSF of 5 patients, who were suspected of CNS infection, although clinical symptoms of these patients varied dramatically. The resulting sequence reads corresponding to Aspergillus species ranged from 2 to 25, with genomic coverage ranging from 0.0003% to 0.0036%. Rapid identification of Aspergillus enabled early appropriate antifungal therapy, although 4 patients eventually died of severe infection. Conclusions: This is the first study to highlight the utility of NGS in early diagnosis of CNS aspergillosis in LT recipients. This new tool may be helpful in improving the diagnosis of CNS aspergillosis.

11.
Hepatobiliary Surg Nutr ; 10(4): 464-475, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34430525

RESUMO

Background: Intrahepatic cholangiocarcinoma has heterogeneous outcomes after resection. There remains a need for broadly applicable recurrence-specific tool offering precise evaluation on curativeness of resection. Methods: A four hospital-based clinical cohort involving 1,655 patients with intrahepatic cholangiocarcinoma who received surgical resection were studied. Cox and logistic models were networked into one system containing risk categories with distinctive probabilities of recurrence. Prediction of time-to-recurrence was performed by formulizing time-dependent risk probabilities. The model was validated in three clinical cohorts (n=332). Results: From the training cohort, 10 and 11 covariates, including diabetes, cholelithiasis, albumin, platelet count, alpha fetoprotein, carbohydrate antigen 19-9, carcinoembryonic antigen, hepatitis B virus infection, tumor size and number, resection type, and lymph node metastasis, from Cox and logistic models were identified significant for recurrence-free survival (RFS). The combined Cox & logistic ranking system (CCLRS)-adjusted time-dependent probabilities were categorized into seven ranks (5-yr RFS for lowest and highest ranks were 75% vs. 0%; hazard ratio 18.5, 95% CI: 14.7-24.9, P<0.0001). The CCLRS was validated with a minimum area under curve value of 0.8086. Prediction of time-to-recurrence was validated to be excellent (Pearson r, 0.8204; P<0.0001). Conclusions: The CCLRS allows precise estimation on risk of recurrence for intrahepatic cholangiocarcinoma after resection. It could be applicative when estimating time-dependent disease status and stratifying individuals who sole resection of the tumor would not be curative.

12.
Front Immunol ; 12: 653437, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34349755

RESUMO

Programmed cell death 1 (PD-1) blockade is considered contraindicated in liver transplant (LT) recipients due to potentially lethal consequences of graft rejection and loss. Though post-transplant PD-1 blockade had already been reported, pre-transplant use of PD-1 blockade has not been thoroughly investigated. This study explores the safety and efficacy of neoadjuvant PD-1 blockade in patients with hepatocellular carcinoma (HCC) after registration on the waiting list. Seven transplant recipients who underwent neoadjuvant PD-1 blockade combined with lenvatinib and subsequent LT were evaluated. The objective response rate (ORR) and disease control rate (DCR) was 71% and 85% according to the mRECIST criteria. Additionally, a literature review contained 29 patients were conducted to summarize the PD-1 blockade in LT for HCC. Twenty-two LT recipients used PD-1 inhibitors for recurrent HCC. 9.1% (2/22) and 4.5% (1/22) recipients achieved complete remission (CR) and partial remission (PR), respectively; 40.9% (9/22) recipients had progressive disease (PD). Allograft rejection occurred in 45% of patients. In total, seven patients from our center and three from the literature used pretransplant anti-PD-1 antibodies, eight patients (80%) had a PR, and the disease control rate was 100%. Biopsy-proven acute rejection (BPAR) incidence was 30% (3 in 10 patients), two patients died because of BPAR. This indicated that neoadjuvant PD-1-targeted immunotherapy plus tyrosine kinase inhibitors (TKI) exhibited promising efficacy with tolerable mortality in transplant recipients under close clinical monitoring.


Assuntos
Carcinoma Hepatocelular/terapia , Rejeição de Enxerto/epidemiologia , Neoplasias Hepáticas/terapia , Transplante de Fígado/efeitos adversos , Terapia Neoadjuvante/métodos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/mortalidade , Quimioterapia Adjuvante/efeitos adversos , Quimioterapia Adjuvante/métodos , Feminino , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Humanos , Incidência , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Compostos de Fenilureia/administração & dosagem , Compostos de Fenilureia/efeitos adversos , Receptor de Morte Celular Programada 1/metabolismo , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Quinolinas/administração & dosagem , Quinolinas/efeitos adversos , Critérios de Avaliação de Resposta em Tumores Sólidos , Estudos Retrospectivos , Taxa de Sobrevida
13.
Artigo em Inglês | MEDLINE | ID: mdl-34432321

RESUMO

BACKGROUND AND AIMS: Epidemiological studies have shown direct associations between type 2 diabetes and the risk of cancers. Accumulating evidence indicates that metformin is profoundly implicated in preventing tumor development. However, the exact mechanism underlying the antitumor effects of metformin in hepatocellular carcinoma (HCC) is still not clear. METHODS: In this study, we investigated the effects of metformin on a mouse HCC model and interleukin-22 (IL-22)-associated carcinogenesis in vitro. RESULTS: We found that metformin significantly suppressed the incidence and tumor burden of HCC in the diethyl-nitrosamine-induced HCC mouse model. As expected, the expression of IL-22, an important factor involved in HCC progression, was markedly reduced by metformin. Treatment of HCC cells with metformin inhibited IL-22 induced cell proliferation, migration, and invasion, and promoted cell apoptosis. Furthermore, ectopic expression of IL-22 makes HCC more aggressive, whereas metformin largely compromised it in vitro and in vivo. Mechanistically, the whole transcriptome analysis and functional analysis revealed that Hippo signaling pathway was involved in the antitumor ability of metformin. Consistent with this, metformin directly inhibited LATS1/2 and activated Mst1/2, phosphorylated YAP1 in vitro. After blocking the Hippo pathway by XMU-MP-1, the inhibitor of MST1/2, the inhibitory effects by metformin were dramatically attenuated as shown by in vitro study. CONCLUSIONS: Collectively, our findings illuminate a new regulatory mechanism, metformin activates Hippo signaling pathway to regulate IL-22 mediated HCC progression and provide new insights into its tumor-suppressive roles.

14.
Gut ; 2021 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-34344785

RESUMO

OBJECTIVE: Altered metabolites are important for the tumourigenicity of hepatocellular carcinoma (HCC). We performed integrative metabolomics analysis of the metabolites changes in portal venous blood and in comparison with the metabolites changes in liver tissues and stool samples of HCC patients and healthy liver donors. DESIGN: Serum (portal and central vein), liver tissue (HCC tumour and adjacent non-tumour, normal liver) and stool samples were collected from 102 subjects (52 HCC patients and 50 healthy controls) in the discovery cohort; and 100 subjects (50 HCC patients and 50 healthy controls) in an independent validation cohort. Untargeted metabolomic profiling was performed using high-performance liquid chromatography-mass spectrometry. The function of candidate metabolites was validated in hepatocyte cell lines. RESULTS: Detailed metabolomic evaluation showed distinct clusters of metabolites in serum, liver tissue and stool samples from patients with HCC and control individuals (p<0.001). HCC patients had significantly higher levels of portal vein serum and HCC tissue metabolites of DL-3-phenyllactic acid, L-tryptophan, glycocholic acid and 1-methylnicotinamide than healthy controls, which were associated with impaired liver function and poor survival. On the other hand, HCC patients had lower levels of linoleic acid and phenol in portal vein and stool samples than healthy controls. Linoleic acid and phenol significantly inhibited HCC proliferation, inferring their anti-HCC function as protective metabolites. CONCLUSIONS: The integrative metabolome analysis of serum, tissue and stool metabolites revealed unreported metabolic alterations in HCC patients. In portal vein, we identified elevated and depleted metabolites signifying that they might play a role in HCC development.

15.
Braz J Microbiol ; 52(4): 2287-2298, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34449069

RESUMO

Soy isoflavone glycoside cannot be effectively absorbed by the human intestinal tract, but probiotics with related hydrolases can transform it into aglycone to promote its absorption. In this study, a novel flavonoid-enriched yogurt was developed using an isolated ß-glucosidase-producing strain (Lactiplantibacillus plantarum GY). The flavonoid aglycone-enhanced yogurt was fed to ICR mice for 21 days, and its effects were observed. The yogurt can affect the gut microbial diversity of mice, especially increasing the abundance of Parasutterella, the Bacteroidales S24-7 group, and Phascolarctobacterium in the intestinal tract of mice. Meanwhile, the ratio of Bacteroidetes/Firmicutes in the intestinal tract of mice fed with the flavonoid aglycone-enriched yogurt increased. The difference in the content of butyric acid between the L-GY + IS and the control groups was significant (P < 0.05). Therefore, milk fermentation with ß-glucosidase-producing strains is a promising approach for developing flavonoid glycoside-enriched yogurt products.

16.
Ann Transl Med ; 9(9): 778, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34268391

RESUMO

Background: Precise prediction of survival after treatment is of great importance for patients with diseases with high mortality. RNA sequencing data and deep learning (DL) methods are expected to become promising approaches in the development of prediction models in the future. We aimed to evaluate the optimal covariates and methodology for patients with hepatocellular carcinoma (HCC) undergoing surgical resection. Methods: The Cox proportional hazards regression model and the DL approach were used to develop prediction models incorporating clinical, genetic, and combined clinical and genetic variables for survival prediction in patients with HCC after resection. A total of 1,114 patients and 184 patients were enrolled in the present study from 2,163 and 601 patients from Eastern Hepatobiliary Surgery Hospital and Renji Hospital, respectively. The models were internally validated through random sampling and externally validated in clinical cohorts. Between-model comparisons were carried out in terms of the integrated discrimination improvement and net reclassification index. Results: The Cox and DL clinical models were developed by adopting 7 independent prognostic factors (total bilirubin, prothrombin time, tumor size, tumor number, lymph node metastasis, and vascular invasion) and 22 clinical factors, respectively. Both the Cox clinical model and the DL clinical model showed excellent performances in the derivation [area under the curve (AUC): 0.75 vs. 0.77] and validation (AUC: 0.83 vs. 0.80) sets. The derived Cox genetic model with 6 significant prognostic genes was not as effective as the DL approach involving 686 genes. A combined clinical and genetic approach modified the performances of both the Cox and DL models. The integrated discrimination improvement and net reclassification index of the DL clinical model were generally better than those of the Cox clinical model. Conclusions: Our Cox clinical model sufficiently provided precise survival prediction in patients with HCC after resection. It may serve as an accurate and cost-effective tool for predicting survival in such patients.

17.
Genes Dis ; 8(5): 623-628, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34291133

RESUMO

Cirrhosis is characterized as the progress of regenerative nodules surrounded by fibrous bands in response to chronic hepatic injury and causes portal hypertension and end-stage hepatic disease. Following liver injury, liver progenitor cells (LPCs) can be activated and differentiate into hepatocytes in order to awaken liver regeneration and reach homeostasis. Recent research has uncovered some new sources of LPCs. Here, we update the mechanisms of LPCs-mediated liver regeneration in cirrhosis by introducing the origin of LPCs and LPCs' niche with a discussion of the influence of LPC-related cells. This article analyzes the mechanism of regeneration and activation of LPCs in cirrhosis in recent years aiming to provide help for clinical application.

18.
Ann Transl Med ; 9(12): 975, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34277775

RESUMO

Background: To identify potential key genes predicting unfavorable prognosis in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC). Methods: Gene expression profiles of GSE121248, GSE62232, and GSE55092 from the GEO database were obtained and analyzed. Differentially expressed genes (DEGs) between HBV-associated HCC tissues and adjacent normal tissues were screened by the limma package and Venn diagram software. Functional assessment of DEGs was performed by Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Hub genes were selected by the protein-protein interaction (PPI) network and further validated by GSE14520 clinical data. Results: A total of 26 up-regulated genes and 76 down-regulated genes were identified by analyzing three databases. GO and KEGG analysis demonstrated that these genes were involved in cell division, metabolism-related biological processes, the p53 pathway, and the cell cycle, among others. PPI network suggested that 14 hub DEGs (TOP2A, HMMR, DTL, CCNB1, NEK2, PBK, RACGAP1, PRC1, CDK1, RRM2, ECT2, BUB1B, ANLN, and ASPM) were most dysregulated and had potential to distinguish between HBV-associated HCC and noncancerous tissues. Further survival analysis of hub genes demonstrated that high expression of TOP2A was significantly associated with poor clinical outcomes of HBV-associated HCC. Conclusions: TOP2A might serve as a key gene for prognosis and as a therapeutic target for HBV-associated HCC.

19.
Aging (Albany NY) ; 13(14): 18879-18893, 2021 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-34289451

RESUMO

BACKGROUND: DJ-1 (also known as PARK7), a noted protein implicated in modulating ROS production and immune response, has been observed to play critical roles in the pathogenesis of many forms of liver disease through multiple mechanisms. However, its role and specific mechanism in acetaminophen (APAP) -induced liver injury have not been explored. RESULTS: In this present study, by employing an acute liver injury induced by APAP overdose mouse model, we demonstrated that DJ-1 knockout (DJ-1-/-) mice showed reduced liver injury and lower mortality. In accordance with these changes, there were also alleviating inflammatory responses in both the serum and the liver of the DJ-1-/- mice compared to those of the wild-type (WT) mice. Functional experiments showed that APAP metabolism did not affected by DJ-1 deficiency. In addition, to investigate DJ-1 modulates which kind of cell types during APAP-overdose-induced acute liver injury, hepatocyte-specific DJ-1-knockout (Alb-DJ-1-/-) and myeloid-specific DJ-1-knockout (Lysm-DJ-1-/-) mice were generated. Interestingly, hepatic deletion of DJ-1 did not protect APAP-overdose induced hepatotoxicity and inflammation, whereas Lysm-DJ-1-/- mice showed similar protective effects as DJ-1-/- mice which suggest that the protective effects of deletion of DJ-1 was through modulating myeloid cell function. Consistently, there were alleviated pro-inflammatory cells infiltration and reduced reactive oxygen species (ROS) production in the liver of Lysm-DJ-1-/- mice relative to control mice. CONCLUSION: our findings clearly defined that deletion of DJ-1 protects APAP-induced acute liver injury through decreasing inflammatory response, and suggest DJ-1 as a potential therapeutic and/or prophylactic target of APAP-induced acute liver injury.

20.
Chem Rev ; 121(17): 10469-10558, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34254782

RESUMO

Nucleic acids, including deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), are natural biopolymers composed of nucleotides that store, transmit, and express genetic information. Overexpressed or underexpressed as well as mutated nucleic acids have been implicated in many diseases. Therefore, nucleic acid tests (NATs) are extremely important. Inspired by intracellular DNA replication and RNA transcription, in vitro NATs have been extensively developed to improve the detection specificity, sensitivity, and simplicity. The principles of NATs can be in general classified into three categories: nucleic acid hybridization, thermal-cycle or isothermal amplification, and signal amplification. Driven by pressing needs in clinical diagnosis and prevention of infectious diseases, NATs have evolved to be a rapidly advancing field. During the past ten years, an explosive increase of research interest in both basic research and clinical translation has been witnessed. In this review, we aim to provide comprehensive coverage of the progress to analyze nucleic acids, use nucleic acids as recognition probes, construct detection devices based on nucleic acids, and utilize nucleic acids in clinical diagnosis and other important fields. We also discuss the new frontiers in the field and the challenges to be addressed.

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