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1.
Sci Total Environ ; 776: 146035, 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33652320

RESUMO

Electrochemical technology has unique superiorities in chlorine-mediated pollutant oxidation, but has limited application in saline wastewater treatment due to inadequate efficiency and high energy consumption. To promote electrochemical oxidation capacity, a novel but low-cost electrode containing TiO2/Co-WO3/SiC was prepared and optimized, achieving highly efficient chlorine-mediated ammonium nitrogen oxidation (98.3 ± 2.2% in 120 min, with initial NH4+-N of 10.2 ± 0.5 mg L-1) in a simple electrochemical system with supplied current density only at 1.00 mA cm-2. Comparing with unmodified carbon fiber cloth, the catalytic anode achieved 96.0% nitrogen selectivity, enhanced the system current efficiency by 20.6% and reduced the energy consumption by 54.4%, making the treatment of simulated mariculture wastewater both energy-saving (36.5 ± 2.8 kWh kg-1 NH4+-N) and cost-effective (1.45 US$ m-3), comparing with previously reported electrochemical processes (54-622 kWh kg-1 NH4+-N). The nitrogen content (<1 mg L-1) in the treated wastewater, containing only 0.18 mg L-1 NH4+-N, meets the discharge standard of mariculture wastewater. The promoted electrochemical oxidation should be attributed to the chloride derived species (HOCl and ClO-) and related active species (Cl, ClO, OH, etc.). This easily prepared and reusable catalytic electrode is a promising alternative to conventional anode materials in sustainable electrochemical treatment of saline wastewater.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33656630

RESUMO

The aim of this study is to explore the feasibility of using a non-sedation protocol for the evaluation of neonatal congenital heart disease by using 16-cm wide-detector CT with a low radiation dose. Thirty-four neonates (group 1) were enrolled to undergo cardiac CT without sedation between August 2018 and March 2019. The control group (group 2) comprising 20 inpatient neonates was sedated. Cardiac CT was performed using 16-cm area detector 320-row CT with free breathing and prospective ECG-triggering scan mode. The examination completion time, radiation dose, and image quality were compared between the groups. The results of cardiac CT for patients in group 1 who underwent surgery were compared with surgical findings. Intergroup differences in body weight, age, examination completion time, radiation dose, and image quality evaluation were not significant. There was no significant difference in oxygen saturation before and after the examination in group 1. In all, 98 separate cardiovascular abnormalities in 27 group 1 patients were confirmed using surgical reports. The overall sensitivity, specificity, positive predictive value, and negative predictive value of cardiac CT were 94.90%, 100.0%, 100.0%, and 98.53%. The non-sedation protocol can be applied in neonates with congenital heart disease by using 16-cm wide-detector CT with a low radiation dose. Based on the image quality obtained, non-sedative examination did not extend the examination completion time and helped avoid the possible side effects of sedative drugs.

3.
J Affect Disord ; 282: 662-668, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33445089

RESUMO

Identifying cognitive dysfunction in the early stages of Bipolar Disorder (BD) can allow for early intervention. Previous studies have shown a strong correlation between cognitive dysfunction and number of manic episodes. The objective of this study was to apply machine learning (ML) techniques on a battery of cognitive tests to identify first-episode BD patients (FE-BD). Two cohorts of participants were used for this study. Cohort #1 included 74 chronic BD patients (CHR-BD) and 53 healthy controls (HC), while the Cohort #2 included 37 FE-BD and 18 age- and sex-matched HC. Cognitive functioning was assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB). The tests examined domains of visual processing, spatial memory, attention and executive function. We trained an ML model to distinguish between chronic BD patients (CHR-BD) and HC at the individual level. We used linear Support Vector Machines (SVM) and were able to identify individual CHR-BD patients at 77% accuracy. We then applied the model to Cohort #2 (FE-BD patients) and achieved an accuracy of 76% (AUC = 0.77). These results reveal that cognitive impairments may appear in early stages of BD and persist into later stages. This suggests that the same deficits may exist for both CHR-BD and FE-BD. These cognitive deficits may serve as markers for early BD. Our study provides a tool that these early markers can be used for detection of BD.

4.
Calcif Tissue Int ; 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33247326

RESUMO

We identified the strength cutpoints concerning mobility impairment, then identified the muscle mass cutpoints concerning weakness, and compared the results with other diagnostic criteria to develop the clinical diagnostic criteria associated with functional impairment. In 7583 elderly people, classification and regression tree (CART) and receiver operating characteristic curve (ROC) analyses were used for determining cutpoints for handgrip strength (HGS) and appendicular lean mass (ALM) indices associated with slowness or weakness. Logistic regressions were then used to quantify the strength of the association between muscle mass (or strength) categories and weakness (or slowness). The CART second cutpoints of muscle mass and strength indices were lower than those specified by the ROC method and were between those cutpoints determined by the 20th and Mean-2SD methods. After adjusting for covariates, the associations remained significant in handgrip strength categories defined by the CART and ROC cutpoints and HGS/BMI categories defined by the CART, ROC, and 20th cutpoints in men and women (P < 0.05), ALM, ALM/Ht2 categories defined by all four cutpoints (P < 0.05) and ALM/BMI categories defined by CART and ROC cutpoints in men (P < 0.05), and ALM and ALM/Ht2 categories defined by the CART cutpoints in women (P < 0.05). Our approaches resulted in a definition of weak strength as handgrip strength or HGS/BMI less than 26.55 kg or 1.114 in men and less than 16.45 kg or 0.697 in women and then defined ALM, ALM/Ht2, or ALM/BMI less than 18.92 kg, 7.08 kg/m2, or 0.795 in men and less than 15.04 kg, 5.99 kg/m2, or 0.517 in women as low lean mass.

5.
J Med Chem ; 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33201699

RESUMO

Fatal infectious diseases caused by HIV-1, influenza A virus, Ebola virus, and currently pandemic coronavirus highlight the great need for the discovery of antiviral agents in mechanisms different from current viral replication-targeted approaches. Given the critical role of virus-host interactions in the viral life cycle, the development of entry or shedding inhibitors may expand the current repertoire of antiviral agents; the combination of antireplication inhibitors and entry or shedding inhibitors would create a multifaceted drug cocktail with a tandem antiviral mechanism. Therefore, we provide critical information about triterpenoids as potential antiviral agents targeting entry and release, focusing specifically on the emerging aspect of triterpenoid-mediated inhibition of a variety of virus-host membrane fusion mechanisms via a trimer-of-hairpin motif. These properties of triterpenoids supply their host an evolutionary advantage for chemical defense and may protect against an increasingly diverse array of viruses infecting mammals, providing a direction for antiviral drug discovery.

6.
Nat Commun ; 11(1): 5510, 2020 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-33139737

RESUMO

In living cells, dynamics of the endoplasmic reticulum (ER) are driven by the cytoskeleton motor machinery as well as the action of ER-shaping proteins such as atlastin GTPases including RHD3 in Arabidopsis. It is not known if the two systems interplay, and, if so, how they do. Here we report the identification of ARK1 (Armadillo-Repeat Kinesin1) via a genetic screen for enhancers of the rhd3 mutant phenotype. In addition to defects in microtubule dynamics, ER organization is also defective in mutants lacking a functional ARK1. In growing root hair cells, ARK1 comets predominantly localize on the growing-end of microtubules and partially overlap with RHD3 in the cortex of the subapical region. ARK1 co-moves with RHD3 during tip growth of root hair cells. We show that there is a functional interdependence between ARK1 and RHD3. ARK1 physically interacts with RHD3 via its armadillo domain (ARM). In leaf epidermal cells where a polygonal ER network can be resolved, ARK1, but not ARK1ΔARM, moves together with RHD3 to pull an ER tubule toward another and stays with the newly formed 3-way junction of the ER for a while. We conclude that ARK1 acts together with RHD3 to move the ER on microtubules to generate a fine ER network.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Retículo Endoplasmático/metabolismo , Proteínas de Ligação ao GTP/metabolismo , Cinesina/metabolismo , Microtúbulos/metabolismo , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Proteínas de Arabidopsis/genética , Proteínas do Domínio Armadillo , Proteínas de Ligação ao GTP/genética , Mutação , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Plantas Geneticamente Modificadas
7.
Cell Regen ; 9(1): 17, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33000315

RESUMO

Retinoic acid (RA) and 2-phospho-L-ascorbic acid trisodium salt (AscPNa) promote the reprogramming of mouse embryonic fibroblasts to induced pluripotent stem cells. In the current studies, the lower abilities of RA and AscPNa to promote reprogramming in the presence of each other suggested that they may share downstream pathways at least partially. The hypothesis was further supported by the RNA-seq analysis which demonstrated a high-level overlap between RA-activated and AscPNa activated genes during reprogramming. In addition, RA upregulated Glut1/3, facilitated the membrane transportation of dehydroascorbic acid, the oxidized form of L-ascorbic acid, and subsequently maintained intracellular L-ascorbic acid at higher level and for longer time. On the other hand, AscPNa facilitated the mesenchymal-epithelial transition during reprogramming, downregulated key mesenchymal transcriptional factors like Zeb1 and Twist1, subsequently suppressed the expression of Cyp26a1/b1 which mediates the metabolism of RA, and sustained the intracellular level of RA. Furthermore, the different abilities of RA and AscPNa to induce mesenchymal-epithelial transition, pluripotency, and neuronal differentiation explain their complex contribution to reprogramming when used individually or in combination. Therefore, the current studies identified a positive feedback between RA and AscPNa, or possibility between vitamin A and C, and further explored their contributions to reprogramming.

8.
Ann Rheum Dis ; 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32998865

RESUMO

OBJECTIVES: Autoreactive B cells play a crucial role in the pathogenesis of rheumatoid arthritis (RA), and B cell-depleting therapies using an antibodies, such as rituximab, have been suggested to be effective in RA treatment. However, transient B cell depletion with rituximab is associated with significant safety challenges related to global suppression of the immune system and thus increases the risks of infection and cancer development. To address selective and persistent issues associated with RA therapy, we developed a customised therapeutic strategy employing universal antifluorescein isothiocyanate (FITC) chimeric antigen receptor T cells (CAR-T cells) combined with FITC-labelled antigenic peptide epitopes to eliminate autoreactive B cell subsets recognising these antigens in RA. METHODS: For a proof-of-concept study, four citrullinated peptide epitopes derived from citrullinated autoantigens, namely, citrullinated vimentin, citrullinated type II collagen, citrullinated fibrinogen and tenascin-C, and a cyclocitrulline peptide-1 were selected as ligands for targeting autoreactive B cells; Engineered T cells expressing a fixed anti-FITC CAR were constructed and applied as a universal CAR-T cell system to specifically eliminate these protein-specific autoreactive B cells via recognition of the aforementioned FITC-labelled autoantigenic peptide epitopes. RESULTS: We demonstrated that anti-FITC CAR-T cells could be specifically redirected and kill hybridoma cells generated by immunisation with antigenic peptides, and autoreactive B cell subsets from RA patients via recognition of corresponding FITC-labelled citrullinated peptide epitopes. Additionally, the cytotoxicity of the CAR-T cells was dependent on the presence of the peptides and occurred in a dose-dependent manner. CONCLUSIONS: The approach described here provides a direction for precise, customised approaches to treat RA and can likely be applied to other systemic autoimmune diseases.

9.
Nat Commun ; 11(1): 5196, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-33060592

RESUMO

Pericytes play essential roles in blood-brain barrier (BBB) integrity and dysfunction or degeneration of pericytes is implicated in a set of neurological disorders although the underlying mechanism remains largely unknown. However, the scarcity of material sources hinders the application of BBB models in vitro for pathophysiological studies. Additionally, whether pericytes can be used to treat neurological disorders remains to be elucidated. Here, we generate pericyte-like cells (PCs) from human pluripotent stem cells (hPSCs) through the intermediate stage of the cranial neural crest (CNC) and reveal that the cranial neural crest-derived pericyte-like cells (hPSC-CNC PCs) express typical pericyte markers including PDGFRß, CD146, NG2, CD13, Caldesmon, and Vimentin, and display distinct contractile properties, vasculogenic potential and endothelial barrier function. More importantly, when transplanted into a murine model of transient middle cerebral artery occlusion (tMCAO) with BBB disruption, hPSC-CNC PCs efficiently promote neurological functional recovery in tMCAO mice by reconstructing the BBB integrity and preventing of neuronal apoptosis. Our results indicate that hPSC-CNC PCs may represent an ideal cell source for the treatment of BBB dysfunction-related disorders and help to model the human BBB in vitro for the study of the pathogenesis of such neurological diseases.


Assuntos
Isquemia Encefálica/metabolismo , Pericitos/metabolismo , Recuperação de Função Fisiológica/fisiologia , Acidente Vascular Cerebral/metabolismo , Animais , Barreira Hematoencefálica/metabolismo , Isquemia Encefálica/patologia , Diferenciação Celular/genética , Infarto da Artéria Cerebral Média , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Crista Neural/metabolismo , Células-Tronco Pluripotentes/metabolismo , Receptor beta de Fator de Crescimento Derivado de Plaquetas/metabolismo , Recuperação de Função Fisiológica/genética , Acidente Vascular Cerebral/patologia , Transcriptoma
10.
Cell Chem Biol ; 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33113407

RESUMO

Chimeric antigen receptor (CAR)-T-based therapeutics are a breakthrough in cancer treatment; however, they are hampered by constitutive activation, which leads to worrisome side effects. Engineering CAR-T cells to be as tightly controllable as possible remains a topic of ongoing investigation. Here, we report a photoswitchable approach that uses a mediator for the at-will regulation of CAR-T cells. This mediator carries dual folate and fluorescein isothiocyanate moieties tethered by an ortho-nitrobenzyl ester photocleavable linker. CAR-T cells were shown to be highly cytotoxic to targeted cells only in the presence of the mediator and acted in a dose-dependent manner. The toxicity of CAR-T cells can be rapidly terminated by cleavage of the mediator, and the effects of CAR-T cells can be activated again by resupplementation with the mediator without compromising tumor therapy. The approach described here provides a direction for enhancing the controllability of CAR-T cells and can likely be applied in other immunotherapies.

11.
Artigo em Inglês | MEDLINE | ID: mdl-33093010

RESUMO

BACKGROUND: Currently, breast cancer patients undergoing mastectomy (MA) have three surgical options: MA only and reconstruction at the time of MA ("immediate," IBR) or at a later time ("delayed," DBR). To assess the oncological safety and complication risks associated with different surgical choices, a systematic review with Bayesian network analysis was conducted. METHODS: Cochrane library, PubMed/MEDLINE, EMBASE, and the China National Knowledge Infrastructure were systematically searched in November 2019. The odds ratios [OR] were estimated for oncological safety (including disease-free survival, overall survival, local recurrence, and distant metastases) and complication risks (including overall complications, surgical site infection, and lymphedema) among MA, IBR, and DBR groups. RESULTS: In the included 51 studies (265,522 patients), reconstruction after MA for IBR or DBR was associated with increased overall survival compared to simple MA (DBR vs. MA: OR 4.12, 95% credible interval [CrI] 1.80-10.01; IBR vs. MA: OR 1.75, 95% CrI 1.32-2.32). Additionally, IBR was associated with a decreased distant metastasis rate compared to MA (IBR vs. MA: OR 0.67, 95% CrI 0.51-0.90). However, the risk of overall complications and surgical site infection was higher in the IBR group than in the other two groups (complications, IBR vs. DBR: OR 1.40, 95% CrI 1.01-1.93; surgical site infection, IBR vs. MA: OR 1.77, 95% CrI 1.03-3.13). CONCLUSIONS: Evidence suggested that breast reconstruction, whether IBR or DBR, does not adversely affect oncological safety in the setting of breast cancer. IBR is associated with an increased risk of overall complications and surgical site infection, but technical advances in this surgical procedure have cumulated over time.

12.
Bipolar Disord ; 2020 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-32981096

RESUMO

BACKGROUND: Bipolar I disorder (BD-I) is associated with a high risk of suicide attempt; however, the neural circuit dysfunction that confers suicidal vulnerability in individuals with this disorder remains largely unknown. Resting-state functional magnetic resonance imaging (rs-fMRI) allows non-invasive mapping of brain functional connectivity. The current study used an unbiased voxel-based graph theory analysis of rs-fMRI to investigate the intrinsic brain networks of BD-I patients with and without suicide attempt. METHODS: A total of 30 BD-I patients with suicide attempt (attempter group), 82 patients without suicide attempt (non-attempter group), and 67 healthy controls underwent rs-fMRI scan, and then global brain connectivity (GBC) was computed as the sum of connections of each voxel with all other gray matter voxels in the brain. RESULTS: Compared with the non-attempter group, we found regional differences in GBC values in emotion-encoding circuits, including the left superior temporal gyrus, bilateral insula/rolandic operculum, and right precuneus (PCu)/cuneus in the bipolar disorder (BD) attempter group, and these disrupted hub-like regions displayed fair to good power in distinguishing attempters from non-attempters among BD-I patients. GBC values of the right PCu/cuneus were positively correlated with illness duration and education in the attempter group. CONCLUSIONS: Our results indicate that abnormal connectivity patterns in emotion-encoding circuits are associated with the increasing risk of vulnerability to suicide attempt in BD patients, and global dysconnectivity across these emotion-encoding circuits might serve as potential biomarkers for classification of suicide attempt in BD patients.

13.
Int J Biol Macromol ; 164: 2861-2872, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32810537

RESUMO

Microwave-assisted extraction of polysaccharides from Trichosanthes kirilowii Maxim seeds (TKMSP) was optimized using Response surface methodology (RSM) base on Central composite design (CCD). The optimum extraction conditions are detailed as follows: liquid-solid ratio 42 mL/g, extraction temperature 80 °C, microwave power 570 W, extraction time 26 min. Under this conditions, the mean value of TKMSP yield 2.43 ± 0.45% (n = 3), which was consistent closely with the predicted value (2.44%). The five polysaccharides (TKMSP-1, TKMSP-2, TKMSP-3, TKMSP-4 and TKMSP-5) were isolated from TKMSP by DEAE-52. TKMSP-1, TKMSP-2 and TKMSP-4 were common in containing Man, Rib, Rha, GluA, GalA, Glu, Gal, Xyl, Arab and Fuc. However, there was no Fuc in TKMSP-3, while TKMSP-5 lacked GluA, GalA and Fuc. UV-vis and FT-IR analysis combined with molecular weight determination further indicated that the five fractions were polydisperse polysaccharides. A significant difference was achieved in the structural characterization of these five fractions. TKMSP exhibited immunosuppressive activity on RAW264.7 cells. It can be applied as a potential immunosuppressant agent in medicine.

14.
PLoS One ; 15(8): e0237023, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32785244

RESUMO

OBJECTIVE: Melanocytes play a central role in skin homeostasis. In this study, we focus on the function of melanocyte releasing exosomes as well as exosomal microRNAs (miRNAs) and investigate whether ultraviolet B (UVB) irradiation exerts an impact on it. MATERIALS AND METHODS: Exosomes derived from human primary melanocytes were isolated through differential centrifugation and were identified in three ways, including transmission electron microscopy observation, nanoparticle tracking analysis, and Western blot analysis. Melanocytes were irradiated with UVB for the indicated time, and then melanin production and exosome secretion were measured. The exosomal miRNA expression profile of melanocytes were obtained by miRNA sequencing and confirmed by real-time PCR. RESULTS: Exosomes derived from human primary melanocytes were verified. UVB irradiation induced melanin production and increased the exosome release by the melanocytes. In total, 15 miRNAs showed higher levels in UVB-irradiated melanocyte-derived exosomes compared with non-irradiated ones, and the top three upregulated exosomal miRNAs were miR-4488, miR-320d, and miR-7704 (fold change > 4.0). CONCLUSION: It is verified for the first time that UVB irradiation enhanced the secretion of exosomes by melanocytes and changed their exosomal miRNA profile. This findings open a new direction for investigating the communication between melanocytes and other skin cells, and the connection between UVB and skin malignant initiation.


Assuntos
Exossomos/genética , Melanócitos/metabolismo , Melanócitos/efeitos da radiação , Secreções Corporais/metabolismo , Exossomos/metabolismo , Humanos , Melaninas/análise , MicroRNAs/genética , Cultura Primária de Células , Transcriptoma/genética , Raios Ultravioleta/efeitos adversos
15.
Plant Cell ; 32(9): 2964-2978, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32616662

RESUMO

ROOT HAIR DEFECTIVE3 (RHD3) is an atlastin GTPase involved in homotypic fusion of endoplasmic reticulum (ER) tubules in the formation of the interconnected ER network. Because excessive fusion of ER tubules will lead to the formation of sheet-like ER, the action of atlastin GTPases must be tightly regulated. We show here that RHD3 physically interacts with two Arabidopsis (Arabidopsis thaliana) LUNAPARK proteins, LNP1 and LNP2, at three-way junctions of the ER, the sites where different ER tubules fuse. Recruited by RHD3 to newly formed three-way junctions, LNPs act negatively with RHD3 to stabilize the nascent three-way junctions of the ER. Without this LNP-mediated stabilization, in Arabidopsis lnp1-1 lnp2-1 mutant cells, the ER becomes a dense tubular network. Interestingly, in lnp1-1 lnp2-1 mutant cells, the expression level of RHD3 is higher than that in wild-type plants. RHD3 is degraded more slowly in the absence of LNPs as well as in the presence of MG132 and concanamycin A. However, in the presence of LNPs, the degradation of RHD3 is promoted. We have provided in vitro evidence that Arabidopsis LNPs have E3 ubiquitin ligase activity and that LNP1 can directly ubiquitinate RHD3. Our data show that after ER fusion is completed, RHD3 is degraded by LNPs so that nascent three-way junctions can be stabilized and a tubular ER network can be maintained.

16.
Life Sci ; 255: 117859, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32474020

RESUMO

Excessive fibrosis and extracellular matrix deposition resulting from upregulation of target genes expression mediated by transforming growth factor-beta (TGF-ß)/SMAD and hypoxia inducible factor-1 (HIF-1) signaling pathways are the main mechanisms that drive keloid formation. Sumoylation is a protein posttranslational modification that regulates the function of proteins in many biological processes. In the present study, we aimed to investigate the mechanism underlying the effects of sumoylation on the TGF-ß/SMAD and HIF-1 signaling pathways in keloids. We used 2-D08 to block sumoylation and silenced the expression of sentrin sumo-specific protease 1 (SENP1) to enhance sumoylation in human foreskin fibroblasts (HFFs) and human keloid fibroblasts (HKFs). We also reduced and increased intracellular SUMO1 levels by silencing SUMO1 and transfecting cells with a SUMO1 overexpression lentivirus, respectively. Sumoylation has the ability to amplify TGF-ß/SMAD and HIF-1 signals in keloids, while SUMO1, especially the SUMO1-RanGAP1 complex, is the key molecule affecting the TGF-ß/SMAD and HIF-1 signaling pathways. In addition, we also found that hypoxia promotes sumoylation in keloids and that HIF-1α is covalently modified by SUMO1 at Lys 391 and Lys 477 in HKFs. In summary, we elucidated the role and molecular mechanism of sumoylation in the formation of keloids, providing a new perspective for a potential therapeutic target of keloids.


Assuntos
Queloide/patologia , Proteína SUMO-1/genética , Proteínas Smad/metabolismo , Sumoilação/fisiologia , Fator de Crescimento Transformador beta/metabolismo , Matriz Extracelular/metabolismo , Fibroblastos/metabolismo , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Transdução de Sinais/fisiologia , Regulação para Cima
17.
Life Sci ; 254: 117746, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32376266

RESUMO

AIMS: Transmembrane 4 L six family member 1 (TM4SF1) is a small plasma membrane glycoprotein that is highly expressed in cancers. However, the role of TM4SF1 that plays in keloids remains unknown. We investigated the expression, function and the microRNA (miRNA) regulatory network of TM4SF1 in keloids. MAIN METHODS: Small interfering RNAs and lentivirus were used to alter the expression of TM4SF1 in fibroblasts. Dual-luciferase reporter assays were applied to determine the miRNA targets. Immunohistochemistry, western blotting, qRT-PCR, wound healing assays, Transwell assays, cell count kit-8 assays and flow cytometry were also employed in this study. KEY FINDINGS: TM4SF1 was frequently upregulated in human keloid fibroblasts (HKFs) compared with human normal skin fibroblasts (HSFs). The downregulation of TM4SF1 significantly inhibited proliferation and migration, and induced apoptosis in HKFs. Furthermore, si-TM4SF1 inhibited the AKT/ERK signaling. Meanwhile, the upregulation of TM4SF1 promoted proliferation, migration and the activation of AKT/ERK signaling in human foreskin fibroblasts (HFF-1). Moreover, TM4SF1 can be regulated by miRNAs, which have been validated to play important roles in keloids by posttranscriptional regulation of gene expression. After screening, we found miR-1-3p and miR-214-5p targeted TM4SF1, inhibited TM4SF1 expression, cell proliferation, migration, and induced apoptosis in HKFs. And the level of miR-1-3p and miR-214-5p were found lower in HKFs than in HSFs. SIGNIFICANCE: Our study demonstrates a novel regulatory mechanism by which miR-1-3p, miR-214-5p, and TM4SF1 are involved in proliferation, cell motility, and apoptosis, suggesting that they may be potential targets in therapies for keloids.


Assuntos
Antígenos de Superfície/fisiologia , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Queloide/patologia , MicroRNAs/metabolismo , Proteínas de Neoplasias/fisiologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Humanos , Queloide/metabolismo
18.
Front Oncol ; 10: 485, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32373519

RESUMO

Currently, non-small cell lung carcinoma (NSCLC) is a major worldwide health problem. Meanwhile accumulating evidence indicates that histone deacetylase (HDAC) activation could induce PD-L1 expression in various types of cancer, especially in myeloma and B-cell lymphomas. Therefore, we hypothesized that high-level expression of HDAC10 is associated with PD-L1 induction and poor prognosis in patients with NSCLC. In total 180 NSCLC patients receiving complete pulmonary resection and systematic lymph node dissection were enrolled from April 2004 to August 2009. The patients with integrated clinicopathological records were followed up. The expression level of HDAC10 and PD-L1 in tissue samples was determined by immunohistochemistry. We observed that HDAC10 expression in lung cancer tissue is significantly higher than that in corresponding para-cancer tissue. Moreover, HDAC10 expression positively correlated with the expression level of PD-L1 (r = 0.213, P < 0.05) in NSCLC patients. Subgroup, multivariate analysis showed that the expression level of HDAC10 can be an independent prognostic factor and high-level expression of HDAC10 indicated poor overall survival for pulmonary carcinoma (r = 0.540, P < 0.001). Our findings suggest that the expression level of HDAC10 is positively associated with PD-L1 expression and may predict the outcome of patients with NSCLC.

19.
Cell Metab ; 31(4): 726-740.e8, 2020 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-32268115

RESUMO

Nonalcoholic steatohepatitis (NASH) is an unmet clinical challenge due to the rapid increase in its occurrence but the lack of approved drugs to treat it. Further unraveling of the molecular mechanisms underlying NASH may identify potential successful drug targets for this condition. Here, we identified TNFAIP3 interacting protein 3 (TNIP3) as a novel inhibitor of NASH. Hepatocyte-specific TNIP3 transgenic overexpression attenuates NASH in two dietary models in mice. Mechanistically, this inhibitory effect of TNIP3 is independent of its conventional role as an inhibitor of TNFAIP3. Rather, TNIP3 directly interacts with TAK1 and inhibits its ubiquitination and activation by the E3 ligase TRIM8 in hepatocytes in response to metabolic stress. Notably, adenovirus-mediated TNIP3 expression in the liver substantially blocks NASH progression in mice. These results suggest that TNIP3 may be a promising therapeutic target for NASH management.

20.
J Hazard Mater ; 394: 122534, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32203714

RESUMO

Heavy metal ions and organic acids are common pollutants in electroplating wastewater. Effective and economic treatment of such wastewater needs novel technologies. In this study, WO3/PPy-1/ACF electrode was prepared using a hydrothermal modification method and it has large specific area (788.27 m2 g-1), high areal capacitance (2.58 F cm-2 under 5 mA cm-2 charge and discharge) and excellent conductivity. The modified electrode was used in an electrochemical system with activated carbon fiber felt (ACF) as counter electrode. The system simultaneously and successfully removed 97.8 % Cu2+ and 80.1 % citric acid (CA) from a simulated electroplating wastewater (typically 100 mg L-1 Cu2+ and 800 mg L-1 CA) in five- hour optimized operation. The influence of operating parameters (circulating inflow rate, applied voltage and influent pH) on the treatment performance was compared. There is interplay between Cu2+ reductive deposition and CA oxidation. The synergetic electrochemical treatment mechanism involves formation of hydrogen peroxide, free radicals, and catalytic effect of Cu species was proposed. This electrochemical system which is low-cost, easy to operate and highly efficient, may be applicable in treating acid-wash or electroplating wastewater, containing heavy-metal ions and organic acids.

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