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1.
J Psychiatr Res ; 138: 492-499, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33971483

RESUMO

BACKGROUND: Cognitive impairment is one of the core symptoms of schizophrenia patients. There are often various differences in the efficacy of different antipsychotics in the treatment of cognitive impairment by sex. The purpose of this study was to explore whether there are gender differences in the association between serum BDNF levels and cognitive performance in patients with schizophrenia taking different antipsychotics. METHODS: We used Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) to assess the cognitive function of three groups of schizophrenia patients (420 on clozapine, 183 on risperidone, 215 on typical antipsychotic drugs) and 467 healthy controls. Positive and Negative Syndrome Scale (PANSS) was used to assess schizophrenia symptoms of patients. Enzyme-Linked ImmunoSorbent Assay was used to measure serum brain-derived neurotrophic factor (BDNF) levels. RESULTS: Among the patients taking clozapine and typical antipsychotic drugs, the RBANS total score, immediate memory, attention, and delayed memory subscores in females were higher than those in males (all p < 0.05). The RBANS total score and the delayed memory subscores in female patients taking risperidone were higher than those in male patients (all p < 0.05). Significant correlation between BDNF and cognition only existed in male patients taking clozapine, male patients taking risperidone, and male and female patients taking typical antipsychotic drugs (all p < 0.05). CONCLUSION: Regardless of antipsychotic effect, the cognitive function of female patients is better compared to that of male patients. For male patients, the association between BDNF and cognitive performance exists in each medication group. For female patients, this significant association was only shown in the typical antipsychotic group, but not in the clozapine and risperidone groups.

2.
Genome Biol ; 22(1): 145, 2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-33971932

RESUMO

Recent development of spatial transcriptomic technologies has made it possible to characterize cellular heterogeneity with spatial information. However, the technology often does not have sufficient resolution to distinguish neighboring cell types. Here, we present spatialDWLS, to quantitatively estimate the cell-type composition at each spatial location. We benchmark the performance of spatialDWLS by comparing it with a number of existing deconvolution methods and find that spatialDWLS outperforms the other methods in terms of accuracy and speed. By applying spatialDWLS to a human developmental heart dataset, we observe striking spatial temporal changes of cell-type composition during development.

3.
Cell Mol Neurobiol ; 2021 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-33893939

RESUMO

Ferroptosis is a type of regulated cell death that plays an essential role in various brain diseases, including cranial trauma, neuronal diseases, and brain tumors. It has been reported that cancer cells rely on their robust antioxidant capacity to escape ferroptosis. Therefore, ferroptosis exploitation could be an effective strategy to prevent tumor proliferation and invasion. Glioma is a common malignant craniocerebral tumor exhibiting complicated drug resistance and survival mechanisms, resulting in a high mortality rate and short survival time. Recent studies have determined that metabolic alterations in glioma offer exploitable therapeutic targets. These metabolic alterations allow targeted therapy to achieve some initial efficacy but have failed to inhibit glioma growth, invasion, and drug resistance effectively. It has been proposed that the reason for the high malignancy and drug resistance observed with glioma is that these tumors can effectively evade ferroptosis. Ferroptosis-inducing drugs were found to exert a positive effect by targeting this particular characteristic of glioma cells. Moreover, gliomas develop enhanced drug resistance through anti-ferroptosis mechanisms. In this study, we provided an overview of the mechanisms by which glioma aggressiveness and drug resistance are mediated by the evasion of ferroptosis. This information might provide new targets for glioma therapy as well as new insights and ideas for future research.

4.
J Evid Based Integr Med ; 26: 2515690X211010733, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33926244

RESUMO

The combination of Aidi injection (ADI) and epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) in treating non-small cell lung cancer (NSCLC) has been reported, but the effects of this therapy have not been systematically assessed. Randomized controlled trials (RCTs) published before June 2020 were searched from 6 databases. Two reviewers independently assessed the methodological quality of 8 RCTs involving 667 patients diagnosed with stage III-IV NSCLC. We found that ADI combined with EGFR-TKI increased the objective response rate (ORR) significantly (relative risk [RR]: 1.60; 95% confidence interval [CI]: 1.28-1.99, P < 0.0001). There was also improvement in the disease control rate (DCR) (RR: 1.25; 95% CI: 1.11-1.40, P = 0.0002) as compared with EGFR-TKI alone. This therapy also increased the percentage of CD3+ cells (weighted mean difference [WMD]: 9.86; 95% CI: 4.62-15.10), CD4+ cells (WMD: 6.10; 95% CI: 1.67-10.53), and the CD4+/CD8+ (WMD: 0.35; 95% CI: 0.28-0.43). With regard to drug toxicity, the occurrence of rash was significantly reduced by ADI combined with EGFR-TKI (RR: 0.78, 95% CI: 0.63-0.97, P = 0.03); however, we did not find a significant reduction in the occurrence of dry skin, nausea and vomiting, as well as diarrhea between the 2 therapies. ADI combined with first-generation EGFR-TKIs may be more effective in improving tumor response, reducing the occurrence of rash, and enhancing immune function in NSCLC than EGFR-TKI alone.

5.
Curr Med Sci ; 41(2): 336-341, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33877551

RESUMO

Placenta accreta spectrum disorder (PASD) and placenta previa (PP) are two of the most hideous obstetric complications which are usually associated with a history of cesarean section (CS). Moreover, women with PASD, PP and/or a cesarean scarred uterus are more likely to have adverse pregnancy outcomes, including blood transfusion, hysterectomy, pelvic organs damage, postpartum hemorrhage, disseminated intravascular coagulation, multi-organ dysfunction syndrome and even maternal or fetal death. This study aimed to investigate the efficacy of precesarean internal iliac artery balloon catheterization (BC) for managing severe hemorrhage caused by PASD and PP with a history of CS. This participant-assigned interventional study was conducted in Tongji Hospital. We recruited 128 women with suspected PASD, PP and a history of CS. Women in the BC group accepted precesarean BC of bilateral internal iliac arteries before the scheduled cesarean delivery. Women in the control group underwent a conventional cesarean delivery. Intraoperative hemorrhage, transfusion volume, radiation dose, exposure time, complications and neonatal outcomes were discussed. There were significant differences in calculated blood loss (CBL) between BC group and control group (1015.0±144.9 vs. 1467.0±171.0 mL, P=0.04). Precesarean BC could reduce intraoperative red blood cell (RBC) transfusion as compared with control group (799.5±136.1 vs. 1286.0±161.6 mL, P=0.02) and lessen the rate of using blood products (57.1% vs. 76.4%, P=0.02). The incidence of hysterectomy was also lower in BC group than in control group. Postpartum outcomes showed no significant differences between the two groups, except that postoperation hospitalization was longer in BC group than in control group (6.7±0.4 vs. 5.8±0.2 days, P=0.03). Precesarean BC of internal iliac artery is an effective method for managing severe hemorrhage caused by PASD and PP with a cesarean scarred uterus, as it could reduce intraoperative blood loss, lessen intraoperative RBC transfusions and potentially decrease hysterectomies.

6.
Chin J Nat Med ; 19(4): 255-266, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33875166

RESUMO

Polyphyllin I (PPI) purified from Polyphyllarhizomes displays puissant cytotoxicity in many kinds of cancers. Several researches investigated its anti-cancer activity. But novel mechanisms are still worth investigation. This study aimed to explore PPI-induced endoplasmic reticulum (ER) stress as well as the underlying mechanism in non-small cell lung cancer (NSCLC). Cell viability or colony-forming was detected by MTT or crystal violet respectively. Cell cycle, apoptosis, reactive oxygen species (ROS) and mitochondrial membrane potential were assessed by flow cytometry. Gene and protein levels were evaluated by qRT-PCR and immunoblotting respectively. Protein interaction was determined by immunoprecipitation or immunofluorescence assay. Gene overexpression or silencing was carried out by transient transfection with plasmids or small interfering RNAs. The Cancer Genome Atlas (TCGA) database was used for Gene Set Enrichment Analysis (GSEA), survival analysis, gene expression statistics or pathway enrichment assay. PPI inhibited the propagation of NSCLC cells, increased non-viable apoptotic cells, arrested cell cycle at G2/M phase, induced ROS levels but failed to decrease mitochondrial membrane potential. High levels of GRP78 indicates poor prognosis in NSCLC patients. PPI selectively suppressed unfolded protein response (UPR)-induced GRP78 expression, subsequently protected CHOP from GRP78-mediated ubiquitination and degradation. We demonstrated that the natural product PPI, obtained from traditional herbal medicine, deserves for further study as a valuable candidate for lead compound in the chemotherapy of NSCLC.

7.
Neurochem Res ; 46(5): 1058-1067, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33761044

RESUMO

Albicanol is a natural terpenoid derived from Dryopteris fragrans. Herein, we assessed the ability of Albicanol to protect against oxidative stress-induced senescence. Using a murine model of D-galactose (D-gal)-induced aging, we determined that Albicanol treatment can reverse D-gal-mediated learning impairments and behavioral changes, while also remediating brain tissue damage in treated mice. We found that serum SOD, CAT, GSH-Px, and T-AOC levels were significantly decreased in aging mice, and that Albicanol treatment significantly increased the serum levels of these antioxidant enzymes. We additionally evaluated the impact of Albicanol treatment on the Keap1/Nrf2/ARE signaling pathway, and found that it was able to decrease Keap1 expression while increasing the expression of Nrf2, thereby activating this signaling pathway, suppressing oxidative damage, and enhancing the expression of downstream target genes including SOD, GSH, GST, HO-1, and NQO1 in this murine aging model system. Albicanol treatment also inhibited the secretion of inflammatory TNF-a and IL-1b. Together, these data indicated that Albicanol can activate Nrf2 pathway-related genes, thereby inhibition of delayed aging by alleviating oxidative stress-induced damage.

8.
Genome Biol ; 22(1): 78, 2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33685491

RESUMO

Spatial transcriptomic and proteomic technologies have provided new opportunities to investigate cells in their native microenvironment. Here we present Giotto, a comprehensive and open-source toolbox for spatial data analysis and visualization. The analysis module provides end-to-end analysis by implementing a wide range of algorithms for characterizing tissue composition, spatial expression patterns, and cellular interactions. Furthermore, single-cell RNAseq data can be integrated for spatial cell-type enrichment analysis. The visualization module allows users to interactively visualize analysis outputs and imaging features. To demonstrate its general applicability, we apply Giotto to a wide range of datasets encompassing diverse technologies and platforms.

9.
J Cell Mol Med ; 25(7): 3524-3536, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33683826

RESUMO

It has been becoming increasingly evident that long non-coding RNAs (lncRNAs) play important roles in various human cancers. However, the biological processes and clinical significance of most lncRNAs in hepatoblastoma (HB) remain unclear. In our previous study, genome-wide analysis with a lncRNA microarray found that lncRNA HOXA-AS2 was up-regulated in HB. Stable transfected cell lines with HOXA-AS2 knockdown or overexpression were constructed in HepG2 and Huh6 cells, respectively. Our data revealed knockdown of HOXA-AS2 increased cell apoptosis and inhibited cell proliferation, migration and invasion in HB. Up-regulation of HOXA-AS2 promoted HB malignant biological behaviours. Mechanistic investigations indicated that HOXA-AS2 was modulated by chromatin remodelling factor ARID1B and transcription co-activator SUB1, thereby protecting HOXA3 from degradation. Therefore, HOXA-AS2 positively regulates HOXA3, which might partly demonstrate the involvement of HOXA3 in HOXA-AS2-mediated HB carcinogenesis. In conclusion, HOXA-AS2 is significantly overexpressed in HB and the ARID1B/HOXA-AS2/HOXA3 axis plays a critical role in HB tumorigenesis and development. These results might provide a potential new target for HB diagnosis and therapy.

10.
Ann Palliat Med ; 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33752425

RESUMO

BACKGROUND: To investigate the association between operation time and serious postoperative symptom severity (PoSS) in patients following the surgical removal of mandibular third molar (M3M), independent of the degree of impaction. METHODS: A retrospective hospital-based observational study was carried out at the Stomatology Hospital of Tianjin Medical University. The operation time was recorded and divided by quartiles (Q1-Q4). The primary outcome was PoSS. Clinical, demographic and radiologic variables were also recorded. A descriptive bivariate analysis was performed. Associations were analyzed using the adjusted multivariate logistic regression. The association between time and impaction status was also tested. Potential nonlinear associations were evaluated with the restricted cubic spline. P values of <0.05 were considered as statistically significant. RESULTS: A total of 321 patients met our inclusion criteria (114 men and 207 women). The mean operation time was 16.0 minutes (range, 1.1 to 40.5 minutes). The odds ratio (OR) and 95% confidence interval (CI) were determined after multivariate adjustments for the risk of serious PoSS per 5-min incremental increase in operation time (OR 1.201, 95% CI, 1.005-1.434). The multivariable-adjusted ORs (95% CI) of PoSS across the categories of operation time were as follows: 1.00 (reference), 1.765 (0.770-4.045), 2.567 (1.047- 6.293), and 3.085 (1.180-8.064) (P for trend =0.027). The test of interaction effect was not significant (all P for interaction >0.05). No evidence of a nonlinear association was observed (P for nonlinearity=0.117). CONCLUSIONS: Operation time was significantly and positively associated with a high risk of serious PoSS independent of impaction status in patients who underwent the surgical removal of M3M.

11.
Huan Jing Ke Xue ; 42(3): 1403-1415, 2021 Mar 08.
Artigo em Chinês | MEDLINE | ID: mdl-33742937

RESUMO

Suzhou is a water-deficient city with water quality issues. Despite water conservation measures, emission reductions, source control, and pollution interception, water quality remains poor. To understand the total mass and distribution characteristics of carbon, nitrogen, and phosphorus bearing pollutants and inform decisions regarding river dredging, sediment and water samples were collected from 20 representative sections in the town's rivers during the spring of 2019. The depths of the sediments were measured along with the concentrations of carbon, nitrogen, and phosphorus bearing pollutants in the sediments and water, and the pollution degree was evaluated. Variations in various parameters were predicted for change water, diversion water, rainfall, and dredging. The results show that the sediment depths ranged between 22 and 1025 mm (average=266 mm), and the total mass of sediment was approximately 5.2×105 t in the ancient town rivers of Suzhou. The average proportions and concentrations of TOC, TN, NH4+-N, TP, and AP in the sediments were 3.4%, 2074 mg·kg-1, 140.2 mg·kg-1, 1765 mg·kg-1, and 57.2 mg·kg-1, respectively, indicating a moderate level of pollution. The concentration of TP in the sediments at 90% of the sampling points exceeds the national standard. Huancheng River was found to have the highest concentration of TP, suggesting that dredging shuld be targeted here first. In the water samples, the average concentrations of TOC, BOD5, COD, TN, NH4+-N, Kjeldahl nitrogen, TP, and PO43--P were 7.8, 0.6, 13.1, 2.5, 0.643, 1.3, 0.18, and 0.09 mg·L-1, respectively, indicating a severe level of pollution. Overall, water quality in these rivers falls below Class V surface water, and the concentration of TN seriously exceeds the national standard. Based on the patterns of total carbon mass and nitrogen and phosphorus bearing pollutants, the recommended order of dredging in Suzhou is the Huancheng River, the northern rivers of the ancient town, Ganjiang River, and the southern rivers of the ancient town. Under the rainfall scenario, the initial concentrations of pollutants in runoff were high, which leads to a decline in water quality. The total mass of TN in the water was reduced by 0.2 t under the change water and diversion water scenarios, and was further reduced by 4.58 t and 2.19 t, respectively, after dredging. Phosphorus bearing pollutants in the sediment were mainly imported from other sources, meaning that the total mass of TP in the water may increase following dredging activities.

12.
Biomed Res Int ; 2021: 5592472, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33763475

RESUMO

Myasthenia gravis (MG) is a chronic autoimmune disease of the nervous system, which is still incurable. In recent years, with the progress of immunosuppressive and supportive treatment, the therapeutic effect of MG in the acute stage is satisfactory, and the mortality rate has been greatly reduced. However, there is still no consensus on how to conduct long-term management of stable MG, such as guiding patients to identify relapses, practice exercise, return to work and school, etc. In the international consensus guidance for management of myasthenia gravis published by the Myasthenia Gravis Foundation of America (MGFA) in 2020, for the first time, "the role of physical training/exercise in MG" was identified as the topic of discussion. Finally, due to a lack of high-quality evidence on physical training/exercise in patients with MG, the topic was excluded after the literature review. Therefore, this paper reviewed the current status of MG rehabilitation research and the difficulties faced by stable MG patients in self-management. It is suggested that we should take advantage of artificial intelligence (AI) and leverage it to develop the data-driven decision support platforms for MG management which can be used for adverse event monitoring, disease education, chronic management, and a wide variety of data collection and analysis.

13.
Pharmacol Res ; 167: 105583, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33775864

RESUMO

With the development of precision medicine, molecular targeted therapy has been widely used in the field of cancer, especially in non-small-cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) is a well-recognized and effective target for NSCLC therapies, targeted EGFR therapy with EGFR-tyrosine kinase inhibitors (EGFR-TKIs) has achieved ideal clinical efficacy in recent years. Unfortunately, resistance to EGFR-TKIs inevitably occurs due to various mechanisms after a period of therapy. EGFR mutations, such as T790M and C797S, are the most common mechanism of EGFR-TKI resistance. Here, we discuss the mechanisms of EGFR-TKIs resistance induced by secondary EGFR mutations, highlight the development of targeted drugs to overcome EGFR mutation-mediated resistance, and predict the promising directions for development of novel candidates.

14.
Cancer Biomark ; 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33780361

RESUMO

BACKGROUND: Hepatoblastoma (HB) is an embryonic solid tumor and the most common primary malignant liver tumor in children. HB usually occurs in infants and children. Although treatment diversity is increasing, some patients still have very poor prognosis. Many studies have investigated USP7 inhibitors for tumors. Using database information, we found that USP7 is highly expressed in HB. METHODS: Lentivirus-mediated USP7 knockdown and overexpression was performed in HB cell lines HepG2 and Huh6. CCK8 and transwell assays were used to determine cell viability and metastasis. Flow cytometry was used to study cell cycle and apoptosis. Levels of proteins were detected using western blots. RESULTS: Downregulation of USP7 resulted in significant decrease in cell proliferation, clonal formation, and cell migration and invasion. With overexpression of USP7, cellular malignant behavior increased. Cell cycle assays showed that USP7 knockdown inhibited G1 to S phase transition in the cell cycle. Upregulation of USP7 promoted the transition. Animal experiments showed USP7 facilitated tumor growth in vivo. Western blots indicated that USP7 may affect HB tumorigenesis through the PI3K/AKT signaling pathway. Furthermore, USP7 inhibitor P5091 inhibited HB development and PI3K/AKT pathway. CONCLUSION: USP7 upregulation contributed to HB genesis and development through the PI3K/AKT signaling pathway. USP7 could be a potential target for future HB treatment.

15.
J Colloid Interface Sci ; 591: 307-313, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33618290

RESUMO

The specific roles of Ni and Fe in nickel-iron (oxy)hydroxide catalyst (NiFeOx(OH)y) are extensively discussed during oxygen evolution reaction (OER). However, there still remains controversy about whether Ni or Fe species as the dominate active site. In this work, we reported the NiFeOx(OH)y catalysts with varied atomic ratio of nickel and iron for OER to explore the dominate active site during OER processes. From the electrochemical performances, the similar Tafel slopes of catalysts with Fe species can achieve at a level of 40 mV dec-1, outperforming the Tafel slopes of catalysts without Fe species. Thus, it can be concluded that the present Fe site can serve as the dominant active site in NiFeOx(OH)y for OER. Meanwhile, the Ni species is proved as the OH- adsorption site, which is beneficial to the Fe site to deliver a better OER performance. As a result, the catalyst with an optimal Ni/Fe interface (atomic ratio of 1 : 1.18) displays outstanding OER performances. It only requires a low overpotential of 250 mV to deliver current density of 10 mA cm-2 and exhibits a small Tafel slope of 39 mV dec-1. This catalyst also shows remarkable stability with negligible potential decay after 50 h at a current density of 50 mA cm-2. This work offers a new sight into the specific roles of Ni and Fe in NiFeOx(OH)y for OER.

16.
Stem Cell Res ; 52: 102212, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33550137

RESUMO

Mucopolysaccharidosis type IIIB (MPS IIIB) is an autosomal recessive metabolic disorder caused by mutations in NAGLU gene, and characterized by progressive cognitive decline and behavioral difficulties and motor function retardation. A human induced pluripotent stem cell line, SDQLCHi041-A was generated from peripheral blood mononuclear cells of a 4 years and 9 months old patient with MPS IIIB, who carried compound heterozygous mutation of c.1336G > A and c.608G > A in NAGLU gene. SDQLCHi041-A offers a useful cell model to investigate pathogenic mechanisms in MPS IIIB.

17.
Stem Cell Res ; 52: 102217, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33550138

RESUMO

Primary hypertrophic osteoarthropathy, autosomal recessive type 1 (PHOAR1, MIM259100) is caused by mutations in the 15-hydroxyprostaglandin dehydrogenase gene (HPGD, MIM601688) on chromosome 4q34. An induced pluripotent stem cells (iPSCs) line was generated in our lab from peripheral blood mononuclear cells (PBMCs) of a 2-year-7-month-old girl with PHOAR1 carrying a homozygous mutation of c.310_311del in HPGD. The expression of pluripotency markers, absence of episomal vectors, preservation of normal karyotype, the potential of trilineage differentiation in vitro, were confirmed in the obtained iPSCs line.

18.
Cancer Cell ; 39(2): 136-137, 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33385329
19.
Stem Cell Res ; 51: 102165, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33453577

RESUMO

X-linked agammaglobulinemia (XLA, OMIM #300755) is one of the most common pediatric primary immunodeficiencies characterized by failure to produce mature B lymphocytes and hypogammaglobulinemia, caused by mutation of the gene encoding Bruton's tyrosine kinase (BTK, OMIM *300300), a key regulator in B-cell development. Patientssuffering XLA are prone to recurrentbacterial infection. We established an induced pluripotent stem cells (iPSCs) line from a 3-year-5-month-old boy with XLA caused by a hemizygous in-frame 9-bp deletion in BTK (c.1530-1538delATACCTGGA, p.Y510_E513delEYLEinsE). The iPSCs was verified based on pluripotency markers, original gene mutation and demonstrated trilineage differentiation potential in vitro.

20.
Drug Deliv ; 28(1): 10-18, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33336604

RESUMO

Hepatic stellate cells (HSCs) play a crucial role in the progression of liver fibrosis, which can be considered as the specific therapeutic target of anti-fibrotic treatment. Targeted induction of HSCs to hepatocytes via delivery of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (dCas9) system holds promise for hepatic fibrosis treatment. Our study here revealed that CRISPR/dCas9-VP64 system encapsulated in AML12 cell-derived exosomes could efficiently and successfully be delivered into the HSCs. In turn, the CRISPR/dCas9-VP64 system loaded in the exosomes can be efficiently released into the HSCs. As a proof-of-concept study, gRNA against hepatocyte nuclear factor 4α (HNF4α) together with the delivery of CRISPR/dCas9-VP64 system induced the HSCs to hepatocyte-like phenotype. In conclusion, our study here revealed that CRISPR/dCas9-VP64 system encapsulated in AML12 cell-derived exosomes could be functional in HSCs, emerging as a gene therapy strategy for hepatic fibrosis.

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