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1.
Aging (Albany NY) ; 122021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-33428593

RESUMO

In this study, we found that ALKBH5, a key component of the N6-methyladenosine (m6A) methyltransferase complex, was significantly elevated in uveal melanoma (UM) cell lines and that ALKBH5 downregulation inhibited tumor growth in vivo. High ALKBH5 expression predicted worse outcome in patients with UM. EP300-induced H3K27 acetylation activation increased ALKBH5 expression. Downregulation of ALKBH5 inhibited UM cell proliferation, migration, and invasion and increased apoptosis in vitro. Besides, ALKBH5 may promote UM metastasis by inducing epithelial-to-mesenchymal transition (EMT) via demethylation of FOXM1 mRNA, which increases its expression and stability. In sum, our study indicates that AKLBH5-induced m6A demethylation of FOXM1 mRNA promotes UM progression. Therefore, AKLBH5 is a potential prognostic biomarker and therapeutic target in UM.

2.
Chem Commun (Camb) ; 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33393549

RESUMO

In recent years, graphdiyne and its derivatives with fascinating electro-optic properties have attracted tremendous scientific attention. Here we design and synthesize a graphdiyne-derived discotic liquid crystal material by decorating six wedge-shaped 3,4,5-tris(dodecyloxy)benzoate groups on the fundamental structural unit of graphdiyne, the dehydrotribenzo[18]annulene core. This graphdiyne-derived liquid crystal material exhibits a cubic phase and a hexagonal columnar phase at varied temperatures. Most interestingly, this molecule displays a tunable phase-dependent photoluminescence behavior. Under the irradiation of 365 nm wavelength ultraviolet light, the luminescent material emits pale blue, green and azure light in the cubic, hexagonal columnar and isotropic phases respectively. This graphdiyne-derived discotic liquid crystal with excellent optical characteristics might have application potentials in organic optoelectronic functional materials and devices.

3.
J Med Virol ; 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33393678

RESUMO

OBJECTIVES: To explore the relation between inflammation-associated factors and in-hospital mortality and investigate which factor is an independent predictor of in-hospital death in patients with coronavirus disease-2019. METHODS: This study included patients with coronavirus disease-2019 who were hospitalized between February 9, 2020, and March 30, 2020. Univariate Cox regression analysis and least absolute shrinkage and selection operator regression (LASSO) were used to select variables. Multivariate Cox regression analysis was applied to identify independent risk factors in coronavirus disease-2019. RESULTS: 1135 patients were analysed during the study period. A total of 35 variables were considered to be risk factors after the univariate regression analysis of the clinical characteristics and laboratory parameters (p < 0.05), and LASSO regression analysis screened out seven risk factors for further study. The six independent risk factors revealed by multivariate Cox regression were myoglobin (HR 5.353, 95% CI 2.633-10.882; p < 0.001), C-reactive protein (HR 2.063, 95% CI 1.036-4.109; p = 0.039), neutrophil count (HR 2.015, 95% CI 1.154-3.518; p = 0.014), interleukin 6 (HR 9.753, 95% CI 2.952-32.218; p < 0.001), age (HR 2.016, 95% CI 1.077-3.773; p = 0.028), and international normalized ratio (HR 2.595, 95% CI 1.412-4.769; p = 0.002). CONCLUSION: Our results suggested that inflammation-associated factors were significantly associated with in-hospital mortality in coronavirus disease-2019 patients. C-reactive protein, neutrophil count and interleukin 6 were independent factors for predicting in-hospital mortality and had a better independent predictive ability. We believe these findings may allow early identification of the patients at high risk for death, and can also assist better management of these patients. This article is protected by copyright. All rights reserved.

4.
Radiat Oncol ; 16(1): 15, 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33446231

RESUMO

BACKGROUND: Stereotactic body radiotherapy (SBRT) is an emerging modality for hepatocellular carcinoma (HCC). However, there is scant information about its safety and effectiveness in the neoadjuvant setting prior to liver transplantation (LT). We present the clinical outcome and pathologic assessment of SBRT followed by LT for patients with advanced HCC. METHODS: This retrospective study included HCC patients treated with neoadjuvant SBRT prior to LT between 2009 and 2018. Radiographic response and adverse effects, including radiation-induced liver disease (RILD), were evaluated. Pathologic response was assessed by the percentage of tumor necrosis relative to the total tumor volume. Overall survival (OS) and recurrence-free survival (RFS) were calculated using the Kaplan-Meier method. RESULTS: Fourteen patients underwent SBRT for a total of 25 HCC lesions, followed by LT. The median tumor size was 4.45 cm in diameter, and the median prescribed dose was 45 Gy in 5 fractions. SBRT provided significant AFP reduction, 100% infield control, and a 62.5% response rate. The maximum detected toxicity included grade 3 thrombocytopenia and two grade 3-4 hyperbilirubinemia. One patient developed non-classic RILD. Patients were bridged to LT with a median time of 8.4 months after SBRT, and 23.1% of them achieved a complete pathologic response. The median OS and RFS were 37.8 and 18.3 months from the time of LT, respectively. CONCLUSIONS: SBRT provides favorable tumor control and acceptable adverse effects for patients awaiting LT. Further prospective studies to test SBRT as a bridging therapy for LT are feasible.

5.
Cell Death Dis ; 12(1): 18, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33414447

RESUMO

MIEF2 (mitochondrial elongation factor 2) is one of the key regulators of mitochondrial fission. Bioinformatics analysis indicated that high expression of MIEF2 predicted a poor prognosis in ovarian cancer patients. However, the relationship between MIEF2 and aberrant lipid metabolism in OC remains elusive. In this study, we demonstrated that MIEF2 significantly promoted lipid synthesis, while has no significant effect on fatty acid uptake and oxidation in OC cells. MIEF2 enhanced de novo fatty acid synthesis through up-regulating the expression of sterol regulatory element binding protein 1 (SREBP1) and its transcriptional target lipogenic genes ACC1, FASN and SCD1. Meanwhile, MIEF2-promoted cholesterol biosynthesis through up-regulating the expression of sterol regulatory element binding protein 2 (SREBP2) and its transcriptional target cholesterol biosynthesis genes HMGCS1 and HMGCR. Mechanistically, increased mitochondrial reactive oxygen species (ROS) production and subsequently activation of AKT/mTOR signaling pathway was found to be involved in the up-regulation of SREBP1 and SREBP2 in OC cells. Moreover, cell growth and metastasis assays indicated that MIEF2-regulated fatty acid synthesis and cholesterol biosynthesis played a critical role in the progression of OC. Taken together, our findings indicate that MIEF2 is a critical regulator of lipid synthesis in OC, which provides a strong line of evidence for this molecule to serve as a drug target in the treatment of this malignancy.

6.
J Mycol Med ; 31(2): 101111, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33454614

RESUMO

INTRODUCTION: Malassezia species can induce the expression of interleukin-17 (IL-17), which plays an important role in the inflammatory and immune response in psoriasis (PS). The purpose of this study was to investigate the Malassezia species composition in patients with PS and healthy individuals and explore the role of Malassezia species in the pathogenesis of PS. MATERIALS AND METHODS: A total of 28 patients with PS and 10 age- and sex-matched healthy individuals participated in this study. Specimens collected from the lesional and non-lesional skin of patients with PS and the skin of healthy individuals were analyzed by using nested PCR. RESULTS: The relative abundance of Malassezia species was 84.96% in healthy subjects, more than twice that in patients with PS (P<0.01). M. restricta (43.09%) and M. globosa (41.38%) were the main Malassezia species in patients with PS followed by M. furfur (4.84%) and M. sympodialis (2.49%). M. sympodialis accounted for 18. 81% of the Malassezia species in healthy subjects, which was nearly eight times higher than in patients with PS (P<0.01). Further, M. furfur was detected both on lesional and non-lesional psoriatic skin, but it was not found on the skin of healthy individuals. CONCLUSIONS: The Malassezia species composition in patients with PS differed from that of healthy individuals. M. restricta and M. globosa were the main Malassezia species in patients with PS.

7.
EMBO Mol Med ; : e13249, 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33459505

RESUMO

Idiopathic normal pressure hydrocephalus (iNPH) is a neurological disorder that occurs in about 1% of individuals over age 60 and is characterized by enlarged cerebral ventricles, gait difficulty, incontinence, and cognitive decline. The cause and pathophysiology of iNPH are largely unknown. We performed whole exome sequencing of DNA obtained from 53 unrelated iNPH patients. Two recurrent heterozygous loss of function deletions in CWH43 were observed in 15% of iNPH patients and were significantly enriched 6.6-fold and 2.7-fold, respectively, when compared to the general population. Cwh43 modifies the lipid anchor of glycosylphosphatidylinositol-anchored proteins. Mice heterozygous for CWH43 deletion appeared grossly normal but displayed hydrocephalus, gait and balance abnormalities, decreased numbers of ependymal cilia, and decreased localization of glycosylphosphatidylinositol-anchored proteins to the apical surfaces of choroid plexus and ependymal cells. Our findings provide novel mechanistic insights into the origins of iNPH and demonstrate that it represents a distinct disease entity.

8.
JAMA Oncol ; 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33443541

RESUMO

Importance: There is no current consensus on the role of chemotherapy in addition to radiation for postoperative adjuvant treatment of patients with early-stage cervical cancer with adverse pathological factors. Objective: To evaluate the clinical benefits of sequential chemoradiation (SCRT) and concurrent chemoradiation (CCRT) compared with radiation alone (RT) as a postoperative adjuvant treatment in early-stage cervical cancer. Design, Setting, and Participants: After radical hysterectomy at 1 of 8 participating hospitals in China, patients with FIGO (International Federation of Gynecology and Obstetrics) stage IB to IIA cervical cancer with adverse pathological factors were randomized 1:1:1 to receive adjuvant RT, CCRT, or SCRT. Data were collected from February 2008 to December 2018. Interventions: Patients received adjuvant RT (total dose, 45-50 Gy), CCRT (weekly cisplatin, 30-40 mg/m2), or SCRT (cisplatin, 60-75 mg/m2, plus paclitaxel, 135-175 mg/m2) in a 21-day cycle, given 2 cycles before and 2 cycles after radiotherapy, respectively. Main Outcomes and Measures: The primary end point was the rate of disease-free survival (DFS) at 3 years. Results: A total of 1048 women (median [range] age, 48 [23-65] years) were included in the analysis (350 in the RT group, 345 in the CCRT group, and 353 in the SCRT group). Baseline demographic and disease characteristics were balanced among the treatment groups except that the rate of lymph node involvement was lowest in the RT group (18.3%). In the intention-to-treat population, SCRT was associated with a higher rate of DFS than RT (3-year rate, 90.0% vs 82.0%; hazard ratio [HR], 0.52; 95% CI, 0.35-0.76) and CCRT (90.0% vs 85.0%; HR, 0.65; 95% CI, 0.44-0.96). Treatment with SCRT also decreased cancer death risk compared with RT (5-year rate, 92.0% vs 88.0%; HR, 0.58; 95% CI, 0.35-0.95) after adjustment for lymph node involvement. However, neither DFS nor cancer death risk was different among patients treated with CCRT or RT. Conclusions and Relevance: In this randomized clinical trial, conducted in a postoperative adjuvant treatment setting, SCRT, rather than CCRT, resulted in a higher DFS and lower risk of cancer death than RT among women with early-stage cervical cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT00806117.

9.
Arch Microbiol ; 2021 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-33386867

RESUMO

A Gram stain-negative bacterial strain, designated SY4-7T, was isolated from rhizosphere mudflat of a halophyte (Zoysia sinica) collected around Seonyu Island, Republic of Korea. Cells of the organism were strictly aerobic, non-sporulating, non-motile rods and grew at 20-42 °C, pH 6-8 and 1-6% (w/v) NaCl. The 16S rRNA gene-based phylogenetic analyses revealed that strain SY4-7T formed an independent cluster separated from the recognized genera of the family Stappiaceae, which was also supported by phylogenomic analysis-based 92-core gene sequences. The type stains of the phylogenetically closest relatives were Stappia indica (95.6% sequence similarity), Stappia stellulata (95.1%) and Roseibium hamelinense (95.1%). The isoprenoid quinone was Q-10. The polar lipids consisted of phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, three unidentified aminophospholipids, an unidentified phosphoglycolipid, an unidentified aminolipid, two unidentified phospholipids and an unidentified lipid. The major cellular fatty acids are C18:1ω7c and C19:1 cyclo ω8c. The G + C content of the genomic DNA is 60.7%. Discrimination of the organism from all the recognized genera of the family Stappiaceae was apparent by the chemotaxonomic and phylogenetic features. Based on the results presented here, strain SY4-7T (= KCTC 72226T = NBRC 113902T) represents a novel species of a new genus in the family Stappiaceae, for which the name Hongsoonwoonella zoysiae sp. nov. is proposed.

11.
Artigo em Inglês | MEDLINE | ID: mdl-33415526

RESUMO

PURPOSE: The application of laparoscopic-assisted total gastrectomy (LATG) for resectable gastric cancer (GC) remains controversial compared with open total gastrectomy (OTG), especially for advanced gastric cancer (AGC) patients according to the inconsistent results demonstrated in the previous studies. The aim of this study was to evaluate the short-term and long-term outcomes between LATG and OTG in a population with more than 80% AGC patients by applying propensity score matching (PSM) method. METHODS: The data of 365 clinical stage I-III GC cases who underwent total gastrectomy with D2 lymphadenectomy were retrospectively collected from January 2011 to April 2018 in the Department of Gastrointestinal Surgery IV of Peking University Cancer Hospital. Propensity scores were generated through taking all covariates into consideration and 131 pairs of patients receiving either LATG or OTG were matched. Intraoperative, postoperative, and survival parameters were compared in the matched groups accordingly. Risk factors for postoperative complications and overall survival were further analyzed. RESULTS: Patient characteristics in the LATG and OTG groups were well balanced after PSM. LATG showed advantages with respect to shorter time to ambulation, first flatus, and first whole liquid diet intake. No significant differences were found between the two groups with regard to postoperative complications as well as overall survival in terms of different pathological stage. Older age was found as an independent risk factor for postoperative complications, and pathological stage for overall survival as well. CONCLUSION: LATG appears to have comparable surgical and oncological safety with OTG by experienced surgeons.

12.
Tissue Eng Regen Med ; 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33415672

RESUMO

BACKGROUND: Corneal scarring or disease may lead to severe corneal opacification and consequently, severe loss of vision due to the complete loss of corneal epithelial cells. We studied the use of epithelial cell sheets differentiated from fetal cartilage-derived stem cells (FCSC) to resurface damaged cornea. METHODS: The FCSC were isolated from the femoral head of immature cartilage tissue. The ability of the FCSCs to differentiate into corneal epithelial cells was evaluated using differentiation media at 2 days and 7 days post-seeding. A sheet fabricated of FCSCs was also used for the differentiation assay. The results of the in vitro studies were evaluated by immunocytochemistry and Western blots for corneal epithelial cell markers (CK3/12 and Pax6) and limbal epithelial stem cell markers (ABCG2 and p63). To test the material in vivo, an FCSC-sheet was applied as a treatment in a chemically burned rabbit model. The healing ability was observed histologically one week after treatment. RESULTS: The in vitro experiments showed morphological changes in the FCSCs at two and seven days of culture. The differentiated cells from the FCSCs or the FCSC-sheet expressed corneal epithelial cells markers. FCSC were create cell sheet that successfully differentiated into corneal epithelial cells and had sufficient adhesion so that it could be fused to host tissue after suture to the ocular surface with silk suture. The implanted cell sheet maintained its transparency and the cells were alive a week after implantation. CONCLUSION: These results suggest that carrier-free sheets fabricated of FCSCs have the potential to repair damaged corneal surfaces.

13.
Inorg Chem ; 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33417439

RESUMO

It is of great research interest to understand the nanostructures contributing to the activity observed in the reduction of oxygen by non-platinum group metal (PGM) electrocatalysts in acidic media. Iron- and nitrogen-containing carbon networks are often the most studied structures, among which single-atom iron-coordinated nitrogen (FeNx) moieties have often been proposed to be the structures leading to the high activity in these non-PGM electrocatalysts. Iron nanoparticles embedded within a carbon support are also formed under certain conditions as a result of the synthetic processes in making non-PGM electrocatalysts. In this study, we present a study to understand the oxygen reduction reaction (ORR) activity of prepared iron- and nitrogen-containing non-PGM electrocatalysts obtained through the pyrolysis of metal-organic framework (MOF) precursors. We studied the structure-property relationship among nanostructures made from the MOF precursor ZIF-8 under different pyrolysis conditions. Density functional theory calculations were used to explain the effect of structural moieties on the ORR activity. Our results suggest that iron-coordinated C-N structures and iron nanoparticles act synergistically to catalyze the ORR.

14.
J Ethnopharmacol ; : 113765, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33418031

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Aconite is a processed product of seminal root of perennial herbaceous plant Aconitum Carmichaclii Debx. of Ranunculaceae. It has the effects of warming and tonifying heart yang and restoring yang to save from collapse. Aconitine is the main effective constituent of aconite and used to prevent and treat heart disease. However, how aconitine exerts myocardial protection is still poorly understood. AIM OF THE STUDY: The present study aimed to investigate the effects of aconitine on mitochondrial dysfunction and explore its mechanism of action. MATERIALS AND METHODS: The model of myocardial injury was induced by Angiotensin II (Ang II) (1×10-6 mol·L-1), and H9c2 cells were incubated with different concentrations of aconitine. The effect of aconitine on mitochondrial was determined by flow cytometry, transmission electron microscopy, luciferase, Seahorse technique and western blot. The effects of aconitine on sirtuin-3 (Sirt3) activity and Cyclophilin D (CypD) acetylation were detected by immunofluorescence, RT-PCR and co-immunoprecipitation. RESULTS: We demonstrate that aconitine alleviates the energy metabolic dysfunction of H9c2 cells by activating Sirt3 to deacetylate CypD and inhibiting mitochondrial permeability transition pore (mPTP) opening. In cardiomyocytes, aconitine significantly reduced mitochondrial fragmentation, inhibited acetylation of CypD, suppressed the mPTP opening, mitigated mitochondrial OXPHOS disorders, and improved the synthesis ability of ATP. In contrast, Sirt3 deficiency abolished the effects of aconitine on mPTP and OXPHOS, indicating that aconitine improves mitochondrial function by activating Sirt3. CONCLUSIONS: These results showed that aconitine attenuated the energy metabolism disorder by promoting Sirt3 expression and reducing CypD-mediated mPTP excess openness, rescuing mitochondrial function. Improve mitochondrial function may be a therapeutic approach for treating heart disease, which will generate fresh insight into the cardioprotective of aconitine.

15.
Chemosphere ; 262: 127830, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32763580

RESUMO

Atrazine residue in soil is one of the serious environmental problems and continues to risk ecosystem and human health. To address the environmental behaviors and dissipation of atrazine and better manage the application of atrazine in reality, we comprehensively investigated the adsorption and desorption, migration ability, and vanishing of atrazine in three distinct soils in China including Jiangxi (JX, pH 5.45, TOC 0.54%), Nanjing (NJ, pH 6.15, TOC 2.13%), and Yancheng (YC, pH 8.60, TOC 0.58%) soils. The atrazine adsorptive capacity to the soils was arranged in the order of NJ > YC > JX. The leaching assay with profiles of the soils showed strong migration, suggesting it had a high bioavailability to weeds and potential for underground water contamination. We further investigated the effects of environmental factors such as soil moisture, microbial activity and photolysis on atrazine degradation and showed that the degradation of atrazine in the soil mainly underwent the abiotic process, most likely through hydrolysis and photolysis-mediated mechanisms, and to less extend through soil microbial catabolism. Using HRLC-Q-TOF-MS/MS and by comparing the measured and theoretical m/z values and fragmentation data, ten metabolites comprising eight degraded products and two conjugates were characterized. Atrazine existing in the soils and sprayed coordinately blocked the growth of three common weeds, which prompted us to use the minimal atrazine in practice to control the waste of the pesticide and its impact on the environment. Overall, our work provided an insight into the mechanisms for the degradation of atrazine residues in the soils and contributed to the environmental risk assessment of the pesticide and management in its application control in the crop rotation and safe production.


Assuntos
Atrazina/química , Plantas Daninhas/metabolismo , Poluentes do Solo/metabolismo , Adsorção , Atrazina/metabolismo , Biodegradação Ambiental , Disponibilidade Biológica , China , Ecossistema , Herbicidas/química , Praguicidas/análise , Fotólise , Solo/química , Microbiologia do Solo , Poluentes do Solo/análise , Espectrometria de Massas em Tandem
16.
Chemosphere ; 262: 128422, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33182085

RESUMO

This study evaluated the toxicity of Cr(VI) to microalgae Chlorella vulgaris, and its removal by continuous microalgae cultivation in membrane photobioreactor (MPBR). Batch cultivation in photobioreactors showed that low concentration of Cr(VI) (0.5 and 1.0 mg L-1) stimulated the growth of C. vulgaris, while 2.0 and 5.0 mg L-1 Cr(VI) in the wastewater significantly inhibited the growth of C. vulgaris. Superoxide dismutase and catalase activities that represented cellular antioxidant capacity significantly increased at 0.5 and 1.0 mg L-1 Cr(VI), and then gradually decreased with the continuous increase of Cr(VI) concentration. The content of malondialdehyde, which represents the degree of cellular oxidative damage, increased with the increase of Cr(VI) concentration and reached the peak value at 2.0 mg L-1 Cr(VI). C. vulgaris was then cultured in MPBR equipped with hollow-fiber ultrafiltration membrane module to achieve continuous removal of Cr from wastewater. With the in-situ solid-liquid separation function of the membrane module, solid retention time (SRT) and hydraulic retention time (HRT) of the reactor could be controlled separately. Experimental results showed that both SRT and HRT had significant effects on the algal biomass production and pollutants removal. During the continuous operation, MPBR achieved a maximum total Cr reduction of 50.0% at HRT of 3-day and SRT of 40-day, and a maximum volumetric removal rate of total Cr of 0.21 mg L-1 d-1 at HRT of 2-day and SRT of 40-day.


Assuntos
Chlorella vulgaris/fisiologia , Cromo/toxicidade , Fotobiorreatores , Eliminação de Resíduos Líquidos , Biomassa , Chlorella vulgaris/crescimento & desenvolvimento , Cromo/análise , Estudos Longitudinais , Membranas Artificiais , Microalgas/crescimento & desenvolvimento , Oxirredução , Águas Residuárias
17.
Life Sci ; 264: 118626, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33148417

RESUMO

AIMS: Circular RNAs (circRNAs) have been shown to play crucial roles in various biological processes and human diseases. However, their exact functions in ischemic stroke remain largely unknown. In this study, we explored the functional role of circRNA HECTD1 (circ-HECTD1) and its underlying mechanism in cerebral ischemia/reperfusion injury. METHODS: Mouse middle cerebral artery occlusion (MCAO) model and oxygen-glucose deprivation (OGD) model in HT22 cells were used to mimic the cerebral ischemia/reperfusion injury. Brain infarct volume, flow cytometry, caspase 3 activity, NF-κB activity, and TUNEL staining were performed to evaluate the function of circ-HECTD1. Luciferase report assay was used to explore the regulatory mechanism. FINDINGS: The results showed that the expression of circ-HECTD1 and tumor necrosis factor receptor-associated factor 3 (TRAF3) was remarkably up-regulated, while miR-133b was down-regulated in oxygen-glucose deprivation (OGD)-induced HT22 cells and mouse middle cerebral artery occlusion (MCAO) model. circ-HECTD1 knockdown relieved OGD-caused neuronal cell death in vitro. Simultaneously, circ-HECTD1 knockdown improved cerebral infarction volume and neuronal apoptosis in MCAO mice. circ-HECTD1 was able to negatively regulate the expression of miR-133b, and TRAF3 is one of the targets of miR-133b. Upregulation of miR-133b inhibited the expression of TRAF3 in OGD-stimulated cells, whereas circ-HECTD1 upregulation reversed this effect. Furthermore, upregulation of miR-133 was able to inhibit OGD-caused cell apoptosis and NF-κB activation, whereas upregulation of circ-HECTD1 attenuated these effects of miR-133b mimics. SIGNIFICANCE: Taken together, circ-HECTD1 knockdown inhibited the expression of TRAF3 by targeting miR-133b, thereby attenuating neuronal injury caused by cerebral ischemia.


Assuntos
/genética , MicroRNAs/genética , Neurônios/patologia , RNA Circular/genética , Fator 3 Associado a Receptor de TNF/genética , Ubiquitina-Proteína Ligases/genética , Animais , Apoptose , Glicemia/metabolismo , Encéfalo/patologia , Isquemia Encefálica/patologia , Caspase 3/metabolismo , Regulação para Baixo , Técnicas de Silenciamento de Genes , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Artéria Cerebral Média/patologia , Neuroproteção , Oxigênio/metabolismo , Traumatismo por Reperfusão/patologia
18.
J Steroid Biochem Mol Biol ; 205: 105772, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33091596

RESUMO

Porcine pancreatic stem cells (pPSCs) can be induced to differentiate into insulin-producing cells in vitro and thus serve as a major cells source for ß-cell regeneration. However, this application is limited by the weak cell proliferation ability and low insulin induction efficiency. In this study, we explored the role of folic acid in the proliferation of pPSCs and the formation of insulin-secreting cells. We found that FA-treated pPSCs cells had a high EDU positive rate, and the proliferation marker molecules PCNA, CyclinD1 and c-Myc were up-regulated, while the expression of folate receptor α (FOLRα) was up-regulated. In further research, interference FOLRα or adding canonical Wnt signaling pathway or ERK signaling pathway inhibitors could significantly inhibit the effect of FA on pPSCs proliferation. Meanwhile, during the differentiation of pPSCs into insulin-secreting cells, we found that the maturation marker genes Insulin, NKX6.1, MafA, and NeuroD1 was upregulated in insulin-secreting cell masses differentiationed from pPSCs after FA treatment, and the functional molecules Insulin and C-peptide were increased, the ability to secrete insulin in response to high glucose was also increased. With the addition of Wnt and ERK signaling pathway inhibitors, the pro-differentiation effect of FA was weakened. In conclusion, FA promotes the proliferation of pPSCs by binding to folate receptor α (FOLRα) and increase the efficiency of directed differentiation of pPSCs into insulin-producing cells by regulating canonical Wnt and ERK signaling pathway. This study lays theoretical foundation for solving the bottleneck in the treatment of diabetes with stem cell transplantation in future.

19.
Mater Sci Eng C Mater Biol Appl ; 118: 111449, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33255037

RESUMO

The rapid developments of nanocarriers based on quantum dots (QDs) have been confirmed to show substantial promise for drug delivery and bioimaging. However, optimal QDs-based nanocarriers still need to have their controlled behavior in vitro and in vivo and decrease heavy metal-associated cytotoxicity. Herein, a pH-activated charge convertible QD-based nanocarrier was fabricated by capping multifunctional polypeptide ligands (mPEG-block-poly(ethylenediamine-dihydrolipoic acid-2,3-dimethylmaleic anhydride)-L-glutamate, PEG-P(ED-DLA-DMA)LG) onto the surface of core/multishell CdSe@ZnS/ZnS QD by means of a ligand exchange strategy, followed by uploading of cytochrome C (CC) (CC-loaded QD-PEG-P(ED-DLA-DMA)LG) via electrostatic interactions, in which QDs that were water-soluble and protein-loading were perfectly integrated. That is, the CC-loaded QD-PEG-P(ED-DLA-DMA)LG inherited excellent fluorescence properties from CdSe@ZnS/ZnS QD for real-time imaging, as well as tumor-microenvironment sensitivities from PEG-P(ED-DLA-DMA)LG for enhanced cellular uptake and CC release. Experimental results verified that the QD-PEG-P(ED-DLA-DMA)LG showed enhanced internalization, rapid endo/lysosomal escape, and supplied legible real-time imaging for lung carcinoma cells. Furthermore, pH-triggered charge-convertible ability enabled the QD-PEG-P(ED-DLA-DMA)LG-CC to effectively kill cancer cells better than did the control groups. Hence, constructing smart nanocomposites by facile ligand-exchange strategy is beneficial to QD-based nanocarrier for tumor-targeting cancer therapy.

20.
Sci Total Environ ; 758: 143618, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33248774

RESUMO

Mesotrione (MTR) is a highly effective pesticide widely used for weeding in farmland. Overload of MTR in agricultural soils may result in environmental problems. To evaluate the potential contamination of MTR in environments, a better understanding of the MTR degradation process and mechanisms in crops is required. This study investigated the impact of MTR on growth and toxicological responses in rice (Oryza sativa). The growth of rice tissues was significantly compromised with increasing MTR concentrations. RNA-sequencing combined with HRLC-Q-TOF-MS/MS analysis identified many transcriptional components responsible for MTR degradation. Four libraries composed of root and shoot tissues exposed to MTR were RNA-sequenced in biological triplicate. Compared to -MTR, treatment with environmentally realistic MTR concentration upregulated 1995 genes in roots and 326 genes in shoots. Gene enrichment revealed many MTR-degradative enzymes functioning in resistance to environmental stress and molecular metabolism of xenobiotics. Specifically, many differentially expressed genes are critical enzymes like cytochrome P450, glycosyltransferases, methyltransferase, glutathione S-transferases and acetyltransferase involved in the process. To evidence MTR degradative metabolisms, HRLC-Q-TOF-MS/MS was used to characterize eight metabolites and five conjugates in the pathways involving hydrolysis, reduction, glycosylation, methylation or acetylation. The precise association between the specific MTR-degraded products and enhanced activities of its corresponding enzymes was established. This study advanced our understanding of the detailed MTR degradative mechanisms and pathways, which may help engineer genotypes to facilitate MTR degradation in the paddy crop.


Assuntos
Atrazina , Oryza , Cicloexanonas , Oryza/genética , Raízes de Plantas , Espectrometria de Massas em Tandem
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