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1.
Nat Commun ; 13(1): 2638, 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35551189

RESUMO

The rapid recognition of DNA double-strand breaks (DSBs) by the MRE11/RAD50/NBS1 (MRN) complex is critical for the initiation of DNA damage response and DSB end resection. Here, we show that MRN complex interacting protein (MRNIP) forms liquid-like condensates to promote homologous recombination-mediated DSB repair. The intrinsically disordered region is essential for MRNIP condensate formation. Mechanically, the MRN complex is compartmentalized and concentrated into MRNIP condensates in the nucleus. After DSB formation, MRNIP condensates move to the damaged DNA rapidly to accelerate the binding of DSB by the concentrated MRN complex, therefore inducing the autophosphorylation of ATM and subsequent activation of DNA damage response signaling. Meanwhile, MRNIP condensates-enhanced MRN complex loading further promotes DSB end resection. In addition, data from xenograft models and clinical samples confirm a correlation between MRNIP and radioresistance. Together, these results reveal an important role of MRNIP phase separation in DSB response and the MRN complex-mediated DSB end resection.

2.
Circ Heart Fail ; : 101161CIRCHEARTFAILURE121008547, 2022 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-35418250

RESUMO

BACKGROUND: High doses of doxorubicin put cancer patients at risk for developing dilated cardiomyopathy. Previously, we showed that doxorubicin treatment decreases SIRT3 (sirtuin 3), the main mitochondrial deacetylase and increases protein acetylation in rat cardiomyocytes. Here, we hypothesize that SIRT3 expression can attenuate doxorubicin induced dilated cardiomyopathy in vivo by preventing the acetylation of mitochondrial proteins. METHODS: Nontransgenic, M3-SIRT3 (truncated SIRT3; short isoform), and M1-SIRT3 (full-length SIRT3; mitochondrial localized) transgenic mice were treated with doxorubicin for 4 weeks (8 mg/kg body weight per week). Echocardiography was performed to assess cardiac structure and function and validated by immunohistochemistry and immunofluorescence (n=4-10). Mass spectrometry was performed on cardiac mitochondrial peptides in saline (n=6) and doxorubicin (n=5) treated hearts. Validation was performed in doxorubicin treated primary rat and human induced stem cell derived cardiomyocytes transduced with adenoviruses for M3-SIRT3 and M1-SIRT3 and deacetylase deficient mutants (n=4-10). RESULTS: Echocardiography revealed that M3-SIRT3 transgenic mice were partially resistant to doxorubicin induced changes to cardiac structure and function whereas M1-SIRT3 expression prevented cardiac remodeling and dysfunction. In doxorubicin hearts, 37 unique acetylation sites on mitochondrial proteins were altered. Pathway analysis revealed these proteins are involved in energy production, fatty acid metabolism, and oxidative stress resistance. Increased M1-SIRT3 expression in primary rat and human cardiomyocytes attenuated doxorubicin-induced superoxide formation, whereas deacetylase deficient mutants were unable to prevent oxidative stress. CONCLUSIONS: Doxorubicin reduced SIRT3 expression and markedly affected the cardiac mitochondrial acetylome. Increased M1-SIRT3 expression in vivo prevented doxorubicin-induced cardiac dysfunction, suggesting that SIRT3 could be a potential therapeutic target for mitigating doxorubicin-induced dilated cardiomyopathy.

3.
J Clin Sleep Med ; 2022 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-35338617

RESUMO

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is a heterogeneous disease with varying phenotype. A cluster analysis based on multidimensional disease characteristics, including symptom, anthropometry, polysomnography (PSG), and craniofacial morphology, in combination with auto-continuous positive airway pressure (CPAP) titration response and comorbidity profiles was performed within a well-characterized cohort of patients with OSA, with the aim to refine current phenotypic expressions of OSA with clinical implications. METHODS: Two hundred and ninety-one subjects with a new diagnosis of moderate to severe OSA, referred for auto-CPAP titration to the sleep center were included for analysis. In-laboratory PSG and craniofacial computed tomography (CT) scanning was performed, followed by an auto-CPAP titration. The symptom of excessive daytime sleepiness (EDS) was assessed by Epworth sleepiness scale (ESS). RESULTS: Three patient phenotypes, corresponding to the "normal weight, non-sleepy and moderate OSA", the "obese, non-sleepy and severe OSA" and "obese, sleepy, very severe OSA with craniofacial limitation" were identified. Among the PSG parameters, only N3% and mean pulse oxygen saturation (SPO2) were found to be associated with ESS, and they only explain small fraction of the variation (R2=0.136). Neck circumference and craniofacial limitation were associated the more severe phenotype, which had higher prevalence of hypertension, metabolic syndrome, greater diurnal blood gas abnormalities and worse PAP titration response. CONCLUSIONS: Three OSA phenotypes were identified according to multiple aspect of clinical features in patients with moderate to severe OSA, which differed in prevalence of hypertension, metabolic syndrome, diurnal blood gas parameters and CPAP titration response. Self-reported EDS was not related with the severity of sleep breathing disturbance, and craniofacial limitation was associated the more severe phenotype. These findings highlight the necessity of integrate multiple disease characters into phenotyping to achieve better understanding of the clinical pictures of OSA.

4.
Sci Rep ; 12(1): 5387, 2022 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-35354883

RESUMO

Freezing-thawing actions can affect the mechanical features of soil greatly, which is vital for the stability of soil slope in cold regions. Firstly, triaxial compression tests on sand samples under undrained conditions were performed to investigate the influences of freezing-thawing cycles, which shows that the freezing-thawing actions can weaken their strength and stiffness, and with the increasing freezing-thawing cycles, both the deviatoric stress and pore water pressure decrease gradually. Then, the double hardening constitutive model was revised to model the influences of freezing-thawing cycles in consideration of the influences of freezing-thawing actions, and the model was also validated by the test results. Finally, the proposed constitutive model was incorporated into a finite element code to numerically simulate the distribution of displacement and pore water pressure of sand slope subjected to freezing-thawing cycles, which shows that the freezing-thawing actions accelerate the dissipation of the pore water pressure and enlarge the displacement of the slope. The study here can provide a help in designing and construction of civil engineering in cold regions.

5.
ACS Appl Mater Interfaces ; 14(11): 13136-13146, 2022 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-35285610

RESUMO

Liver failure is a serious disease that is characterized by global hepatocyte necrosis. Hepatocyte proliferation and liver regeneration are critically important for the success of treatments for liver disease. Tetrahedral framework nucleic acids (TFNAs), which are widely used antioxidants and anti-inflammatory nanomaterials, activate multiple proliferation and prosurvival pathways. Therefore, the effects of a TFNA on hepatocyte proliferation and liver regeneration in mouse livers injured by 70% partial hepatectomy (PHx), acetaminophen overdose, and carbon tetrachloride were explored in this study. The TFNA, which was successfully self-assembled from four specifically designed ssDNAs, entered the body quickly and was taken up effectively by hepatocytes in the liver and could eventually be cleared by the kidneys. The TFNA promoted hepatocyte proliferation in vitro by activating the Notch and Wnt signaling pathways. In the three in vivo mouse models of liver injury, the TFNA attenuated the injuries and enhanced liver regeneration by regulating the cell cycle and the P53 signaling pathway. Therefore, by promoting hepatocyte proliferation and enhancing liver regeneration, the TFNA shows potential as an effective therapeutic agent for treating acute liver injury induced by 70% PHx and other factors, thereby preventing the progression to acute liver failure and reducing the associated mortality rate.


Assuntos
Falência Hepática Aguda , Ácidos Nucleicos , Animais , Proliferação de Células , Hepatócitos , Fígado/metabolismo , Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/tratamento farmacológico , Falência Hepática Aguda/metabolismo , Regeneração Hepática/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Ácidos Nucleicos/farmacologia , Via de Sinalização Wnt
6.
Entropy (Basel) ; 24(3)2022 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-35327818

RESUMO

A cascaded lattice Boltzmann (CLB) model is constructed for simulating heat transfer in metal-foam-based solid-liquid phase change materials (PCMs). The present model captures the phase interface implicitly via the enthalpy methodology, and to avoid iterations in simulations, the CLB equation of the PCM employs the enthalpy as the basic evolution variable through modifying the cascaded collision process. Numerical results demonstrate the effectiveness and practicability of the CLB model for investigating heat transfer in solid-liquid PCMs with metal foams. The effects of the inertial coefficient, permeability and porosity on the melting process are investigated. The results indicate that the empirical correlations of inertial coefficient and permeability based on packed beds overestimate the melting rate at high porosities. Moreover, the porosity has significant impact on phase-change processes. The melting rate increases as the porosity of the metal foam decreases since heat conduction through high thermal conductive metal foam dominates the total heat transfer.

7.
Front Pediatr ; 10: 837247, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35174110

RESUMO

BACKGROUND: The failed clearance of jaundice (CJ) in patients with biliary atresia (BA) after the Kasai procedure (KP) often leads to a shorter native liver survival (NLS) time and earlier liver transplantation. We aimed to investigate risk factors of failed CJ and establish a novel nomogram model to predict the status of CJ. METHODS: We retrospectively reviewed institutional medical records from January 2015 to April 2020 and enrolled BA patients post-KP, randomly divided into training and testing cohorts at a ratio of 7:3, and further subdivided into cleared and uncleared jaundice groups. Univariate and multiple logistic regression analyses were used to select risk factors to establish the nomogram in the training cohort. The performance of the nomogram was evaluated by calculating the areas under the receiver operating curve (AUC) in both cohorts. RESULTS: This study included 175 BA patients post-KP. After univariate and multiple logistic regression analyses, Cytomegalovirus IgM +ve associated BA (OR = 3.38; 95% CI 1.01-11.32; P = 0.04), ln γ-glutamyl transpeptidase (GGT) (OR = 0.41; 95% CI 0.22-0.80; P = 0.009), thickness of the fibrous portal plate (OR = 0.45; 95% CI 0.27-0.76; P = 0.003), liver stiffness measurement (LSM) (OR = 1.19; 95% CI 1.06-1.34; P = 0.002), and multiple episodes of cholangitis (OR = 1.65; 95% CI 1.13-2.41; P = 0.01) were identified as independent risk factors of unsuccessful CJ to construct the nomogram. The receiver operating characteristic curve (ROC) analysis suggested good nomogram performance in both the training (AUC = 0.96) and testing cohorts (AUC = 0.91). CONCLUSION: Our nomogram model including several risk factors effectively predicts CJ in patients post-KP, which could aid in clinical decision-making.

8.
Mater Horiz ; 9(4): 1232-1242, 2022 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-35175266

RESUMO

Developing advanced solar-driven interfacial evaporators with both ultrahigh energy efficiency and long-term tolerability is highly desired but still a great challenge. Herein, inspired by the natural lotus, we develop a high-performance solar interfacial evaporator with a novel 3D biomimetic architecture. The lotus-inspired biomimetic evaporator (LBE) combines three key components, including a large "leaf" having strong solar energy absorption ability, hydrophilic "stems" working as water transport channels, and lotus root-like porous "roots" with minimized heat loss for improved respiration. The photothermal part in the LBE, analogous to a lotus leaf, possesses Janus wettability with a hydrophobic side above and a hydrophilic side below, which is achieved by a scalable method of in situ inducing ZIF-67 nanocubes into an electrospun fiber film followed by pyrolysis. In particular, the top side has a unique hierarchical network structure consisting of long porous carbon nanofibers with internally dispersed metal oxide nanocrystals, leading to highly efficient solar absorption of 91.37%. The 3D-LBE exhibits an extremely high evaporation rate of 3.23 kg m-2 h-1 and energy efficiency reaching 153.20% under 1-sun, which exceeds the theoretical limit and is the highest recorded, to the best of our knowledge. Notably, the 3D-LBE also shows impressive pollutant removal capabilities assuring long-term interfacial evaporation stability. The high-performance LBE promises many applications, such as wastewater treatment, sea salt production, and metal recovery.


Assuntos
Energia Solar , Purificação da Água , Biomimética , Vapor , Luz Solar
9.
Nat Commun ; 13(1): 866, 2022 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-35165282

RESUMO

Epstein-Barr virus (EBV) is reportedly the first identified human tumor virus, and is closely related to the occurrence and development of nasopharyngeal carcinoma (NPC), gastric carcinoma (GC), and several lymphomas. PD-L1 expression is elevated in EBV-positive NPC and GC tissues; however, the specific mechanisms underlying the EBV-dependent promotion of PD-L1 expression to induce immune escape warrant clarification. EBV encodes 44 mature miRNAs. In this study, we find that EBV-miR-BART11 and EBV-miR-BART17-3p upregulate the expression of PD-L1 in EBV-associated NPC and GC. Furthermore, EBV-miR-BART11 targets FOXP1, EBV-miR-BART17-3p targets PBRM1, and FOXP1 and PBRM1 bind to the enhancer region of PD-L1 to inhibit its expression. Therefore, EBV-miR-BART11 and EBV-miR-BART17-3p inhibit FOXP1 and PBRM1, respectively, and enhance the transcription of PD-L1 (CD274, http://www.ncbi.nlm.nih.gov/gene/29126 ), resulting in the promotion of tumor immune escape, which provides insights into potential targets for EBV-related tumor immunotherapy.


Assuntos
Herpesvirus Humano 4/genética , MicroRNAs/genética , Carcinoma Nasofaríngeo/imunologia , Neoplasias Nasofaríngeas/imunologia , Neoplasias Gástricas/imunologia , Evasão Tumoral/imunologia , Antígeno B7-H1/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Proteínas de Ligação a DNA/antagonistas & inibidores , Proteínas de Ligação a DNA/metabolismo , Infecções por Vírus Epstein-Barr/virologia , Fatores de Transcrição Forkhead/antagonistas & inibidores , Fatores de Transcrição Forkhead/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , Herpesvirus Humano 4/imunologia , Humanos , Linfoma/imunologia , Linfoma/virologia , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/virologia , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/virologia , Proteínas Repressoras/antagonistas & inibidores , Proteínas Repressoras/metabolismo , Neoplasias Gástricas/virologia , Fatores de Transcrição/antagonistas & inibidores , Fatores de Transcrição/metabolismo , Evasão Tumoral/genética , Microambiente Tumoral/imunologia
10.
Diabetologia ; 65(4): 733-747, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35091821

RESUMO

AIMS/HYPOTHESIS: Obesity and hepatic steatosis are risk factors for gestational diabetes mellitus (GDM), a common complication of pregnancy. Adiponectin is a fat-derived hormone that improves hepatic steatosis and insulin sensitivity. Low levels of circulating adiponectin are associated with GDM development. We hypothesised that adiponectin deficiency causes fatty liver during pregnancy, contributing to the development of GDM. METHODS: To determine the role of adiponectin in fatty liver development during pregnancy, we compared pregnant (third week of pregnancy) adiponectin knockout (KO) mice (strain B6;129-Adipoqtm1Chan/J) with wild-type mice and assessed several variables of hepatic lipid metabolism and glucose homeostasis. The impact of adiponectin supplementation was measured by administering adenovirus-mediated full-length adiponectin at the end of the second week of pregnancy and comparing with green fluorescent protein control. RESULTS: In the third week of pregnancy, fasted pregnant adiponectin KO mice were hyperglycaemic on a low-fat diet (9.2 mmol/l vs 7.7 mmol/l in controls, p<0.05) and were glucose and pyruvate intolerant relative to wild-type mice. Pregnant adiponectin KO mice developed hepatic steatosis and a threefold elevation in hepatic triacylglycerols (p<0.05) relative to wild-type mice. Gestational weight gain and food consumption were similar in KO and wild-type mice. Adenoviral-mediated adiponectin supplementation to pregnant adiponectin KO mice improved glucose tolerance, prevented fasting hyperglycaemia and attenuated fatty liver development. CONCLUSIONS/INTERPRETATION: Adiponectin deficiency increased hepatic lipid accumulation during the period of pregnancy associated with increased fat utilisation. Consequently, adiponectin deficiency contributed to glucose intolerance, dysregulated gluconeogenesis and hyperglycaemia, all of which are characteristic of GDM. Increasing adiponectin in the last week of pregnancy alleviated hepatic steatosis and restored normal glucose homeostasis during pregnancy.


Assuntos
Diabetes Gestacional , Fígado Gorduroso , Hiperglicemia , Resistência à Insulina , Adiponectina/deficiência , Adiponectina/metabolismo , Animais , Diabetes Gestacional/genética , Diabetes Gestacional/metabolismo , Fígado Gorduroso/metabolismo , Feminino , Glucose/metabolismo , Humanos , Hiperglicemia/metabolismo , Fígado/metabolismo , Erros Inatos do Metabolismo , Camundongos , Camundongos Knockout , Gravidez
11.
Blood ; 139(11): 1619-1630, 2022 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-35030255

RESUMO

The Kasabach-Merritt phenomenon (KMP) in kaposiform hemangioendothelioma (KHE) is characterized by life-threatening thrombocytopenia and consumptive coagulopathy. This study compared the efficacy and safety of sirolimus plus prednisolone vs sirolimus monotherapy as treatment strategies for KHE with KMP in the largest cohort to date. Participants were randomized to receive either sirolimus in combination with a short course of prednisolone or sirolimus monotherapy for at least 12 months. The primary outcome was defined as achievement of a durable platelet response (platelet count >100 × 109/L) at week 4. Participants completed efficacy assessments 2 years after the initial treatment. At week 4, a durable platelet response was achieved by 35 of 37 patients given sirolimus and prednisolone compared with 24 of 36 patients given sirolimus monotherapy (difference 27.9%; 95% confidence interval, 10.0-44.7). Compared with the sirolimus monotherapy group, the combination treatment group showed improvements in terms of measures of durable platelet responses at all points during the initial 3-week treatment period, median platelet counts during weeks 1 to 4, increased numbers of patients achieving fibrinogen stabilization at week 4, and objective lesion responses at month 12. Patients receiving combination therapy had fewer blood transfusions and a lower total incidence of disease sequelae than patients receiving sirolimus alone. The frequencies of total adverse events and grade 3-4 adverse events during treatment were similar in both groups. The responses seen in patients with KHE with KMP were profound and encouraging, suggesting that sirolimus plus prednisolone should be considered a valid treatment of KHE with KMP. This trial was registered at www.clinicaltrials.gov as #NCT03188068.


Assuntos
Hemangioendotelioma , Síndrome de Kasabach-Merritt , Sarcoma de Kaposi , Hemangioendotelioma/complicações , Hemangioendotelioma/tratamento farmacológico , Hemangioendotelioma/patologia , Humanos , Lactente , Síndrome de Kasabach-Merritt/complicações , Síndrome de Kasabach-Merritt/tratamento farmacológico , Síndrome de Kasabach-Merritt/patologia , Prednisolona/uso terapêutico , Sarcoma de Kaposi/complicações , Sirolimo/uso terapêutico
12.
Surg Today ; 2022 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-35059844

RESUMO

The ideal surgical management for reconstruction after excision of congenital biliary dilatation remains controversial. This updated meta-analysis compared the clinical outcomes of hepaticoduodenostomy (HD) and hepaticojejunostomy (HJ) after resection of congenital biliary dilatation. PubMed, Web of Science, Embase, Ovid, and the Cochrane Library were searched for studies published from November 1981 through July 2020. The primary outcomes were the operative time, enteral feeding time, hospital stay, and postoperative complications. The quality and risk of bias were assessed with the Newcastle-Ottawa Quality Assessment Scale. Odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs) were pooled using random-effects models. Thirteen total studies included 518 (55.76%) HD cases and 411 (44.24%) HJ cases. Five studies were published post-2013; one was a randomized clinical trial. Patients undergoing HD had a shorter hospital stay (MD, 0.40; p = 0.02) and operative time (MD, 59.54; p < 0.00001) and a lower incidence of adhesive intestinal obstruction (OR, 0.20; p = 0.02) than HJ. HD was comparable to conventional HJ with regard to most postoperative outcomes; however, it was associated with a higher incidence of postoperative bilious gastritis (OR, 6.24; p = 0.002). HD is as safe and feasible as HJ with better outcomes in the short run, although reports with long-term follow-up are relatively few. Long-term follow-up will be necessary to monitor possible associated malignancies in the future.

13.
BMC Pediatr ; 22(1): 18, 2022 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-34980070

RESUMO

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare condition that has a variety of clinical manifestations. But LCH in children localized only in the hepatobiliary system is unusual. CASE PRESENTATION: Here we reported a rare case of a 2-year-old boy who was serendipitously found to have elevated liver enzymes while undergoing treatment of a perianal abscess. After a period of earlier conservative treatment in another hospital, the perianal abscess had resolved but the levels of liver enzymes were still rising slowly. The child was then referred to our institution for a definitive diagnosis. After laboratory tests, imaging and pathological examinations, a diagnosis of liver cirrhosis and sclerosing cholangitis was established, although the cause was unclear. Subsequently, living-donor liver transplantation was performed due to deterioration in liver function. Following successful liver transplantation, a diagnosis of LCH localized only within the hepatobiliary system was finally confirmed, based on additional pathological and imaging investigation. Additionally, the BRAF V600E mutation in this patient was also confirmed. The child has now recovered without evidence of LCH recurrence. CONCLUSIONS: LCH localized only within the hepatobiliary system is unusual. The presence of unexplainable sclerosing cholangitis and liver cirrhosis in any child should raise the suspicion of LCH.


Assuntos
Colangite Esclerosante , Histiocitose de Células de Langerhans , Transplante de Fígado , Criança , Pré-Escolar , Colangite Esclerosante/complicações , Colangite Esclerosante/cirurgia , Histiocitose de Células de Langerhans/complicações , Histiocitose de Células de Langerhans/diagnóstico , Histiocitose de Células de Langerhans/cirurgia , Humanos , Cirrose Hepática/complicações , Transplante de Fígado/efeitos adversos , Doadores Vivos , Masculino
15.
Br J Cancer ; 126(8): 1113-1124, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34750493

RESUMO

Alternative splicing (AS) is a key process in which precursor RNAs produce different mature RNAs, and the disorder of AS is a key factor in promoting cancer development. Compared with coding RNA, studies on the functions of long non-coding RNAs (lncRNAs) are far from enough. In fact, lncRNA is an important participant and regulator in the process of AS. On the one hand, lncRNAs regulate cancer progression as AS products of precursor messenger RNA (mRNA), but on the other hand, precursor lncRNA generates cancer-related abnormal splicing variants through AS. In addition, lncRNAs directly or indirectly regulate the AS events of downstream target genes, thus affecting the occurrence and development of cancer. Here, we reviewed how lncRNAs regulate AS and influence oncogenesis in different ways.


Assuntos
Neoplasias , RNA Longo não Codificante , Processamento Alternativo/genética , Transformação Celular Neoplásica , Humanos , Neoplasias/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro
16.
Oncogene ; 41(2): 233-245, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34725462

RESUMO

Nasopharyngeal carcinoma (NPC) demonstrates significant regional differences and a high incidence in Southeast Asia and Southern China. Bactericidal/permeability-increasing-fold- containing family B member 1 (BPIFB1) is a relatively specific and highly expressed protein in the nasopharyngeal epithelium. BPIFB1 expression is substantially downregulated in NPC and is significantly associated with poor prognosis in patients with NPC. However, the specific molecular mechanism by which BPIFB1 regulates NPC is not well understood. In this study, we found that BPIFB1 inhibits vasculogenic mimicry by regulating the metabolic reprogramming of NPC. BPIFB1 decreases GLUT1 transcription by downregulating the JNK/AP1 signaling pathway. Altered glycolysis reduces the acetylation level of histone and decreases the expression of vasculogenic mimicry-related genes, VEGFA, VE-cadherin, and MMP2, ultimately leading to the inhibition of vasculogenic mimicry. To our knowledge, this is the first report on the role and specific mechanism of BPIFB1 as a tumor suppressor gene involved in regulating glycolysis and vasculogenic mimicry in NPC. Overall, these results provide a new therapeutic target for NPC diagnosis and treatment.


Assuntos
Autoantígenos/metabolismo , Proteínas de Ligação a Ácido Graxo/metabolismo , Transportador de Glucose Tipo 1/metabolismo , Neoplasias Nasofaríngeas/genética , Acetilação , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Camundongos , Camundongos Nus , Neoplasias Nasofaríngeas/patologia , Transfecção
17.
Autophagy ; 18(2): 240-253, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-33904341

RESUMO

Circular RNAs (circRNAs) are non-coding RNAs that have attracted considerable attention in recent years. Owing to their distinct circular structure, circRNAs are stable in cells. Autophagy is a catabolic process that helps in the degradation and recycling of harmful or inessential biological macromolecules in cells and enables cells to adapt to stress and changes in the internal and external environments. Evidence has shown that circRNAs influence the course of a disease by regulating autophagy, which indicates that autophagy is involved in the onset and development of various diseases and can affect drug resistance (for example, it affects cisplatin resistance in tumors). In this review, we summarized the role of circRNAs in autophagy and their influence on disease onset and progression as well as drug resistance. The review will expand our understanding of tumors as well as cardiovascular and neurological diseases and also suggest novel therapeutic strategies.Abbreviations: ACR: autophagy-related circRNA; ADSCs: adipogenic mesenchymal stem cells; AMPK: AMP-activated protein kinase; ATG: autophagy related; BCL2: BCL2 apoptosis regulator; BECN1: beclin 1; ceRNA: competing endogenous RNA; circRNA: circular RNA; CMA: chaperone-mediated autophagy; EPCs: endothelial progenitor cells; LE/MVBs: late endosomes/multivesicular bodies; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MTOR: mechanistic target of rapamycin kinase; NSCLC: non-small cell lung cancer; PDLSCs: periodontal ligament stem cells; PE: phosphatidylethanolamine; PtdIns: phosphatidylinositol; PtdIns3K: phosphatidylinositol 3-kinase; PtdIns3P: phosphatidylinositol-3-phosphate 1,2-dipalmitoyl; PTEN: phosphatase and tensin homolog; RBPs: RNA-binding proteins; SiO2: silicon dioxide; TFEB: transcription factor EB; ULK: unc-51 like autophagy activating kinase 1.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Autofagia/genética , Progressão da Doença , Humanos , Fosfatidilinositóis , Proteínas Proto-Oncogênicas c-bcl-2 , RNA Circular/genética , Dióxido de Silício
19.
J Nanobiotechnology ; 19(1): 403, 2021 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-34863202

RESUMO

The cyclic signal amplification technology has been widely applied for the ultrasensitive detection of many important biomolecules, such as nucleic acids, proteins, enzymes, adenosine triphosphate (ATP), metal ions, exosome, etc. Due to their low content in the complex biological samples, traditional detection methods are insufficient to satisfy the requirements for monitoring those biomolecules. Therefore, effective and sensitive biosensors based on cyclic signal amplification technology are of great significance for the quick and simple diagnosis and treatment of diseases. Fluorescent biosensor based on cyclic signal amplification technology has become a research hotspot due to its simple operation, low cost, short time, high sensitivity and high specificity. This paper introduces several cyclic amplification methods, such as rolling circle amplification (RCA), strand displacement reactions (SDR) and enzyme-assisted amplification (EAA), and summarizes the research progress of using this technology in the detection of different biomolecules in recent years, in order to provide help for the research of more efficient and sensitive detection methods.


Assuntos
Técnicas Biossensoriais/métodos , Corantes Fluorescentes , Sondas Moleculares , Técnicas de Amplificação de Ácido Nucleico/métodos , Ácidos Nucleicos , Animais , Corantes Fluorescentes/análise , Corantes Fluorescentes/química , Humanos , Camundongos , Sondas Moleculares/análise , Sondas Moleculares/química , Ácidos Nucleicos/análise , Ácidos Nucleicos/química , Ácidos Nucleicos/metabolismo , Proteínas/análise , Proteínas/química
20.
Front Genet ; 12: 760182, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34899846

RESUMO

The prognosis of children with biliary atresia (BA) after Kasai operation remains difficult to predict, and liver fibrosis is closely related to the prognosis of children with BA. We aimed to find biomarkers for native liver survival (NLS) prediction by weighted gene co-expression network analysis (WGCNA). The biological processes and signal pathways that biomarkers involved in were further analyzed by bioinformatics. Quantitative Real-time PCR, Western blot and immunohistochemistry was performed to detect biomarkers expression. The relationship of biomarkers with clinicopathological characteristics of BA was also investigated. LECT2 was overexpressed or knockdown in LX-2 cells, and the expression of fibrogenic genes such as a-SMA and COL1A1 was quantified. We found that LECT2 mRNA expression was higher in BA liver tissues compared with normal liver tissues. Bioinformatics showed that LECT2 mainly played a fibrosis-promoting role in the development in BA by regulating bile acid metabolism and promoting inflammatory response. LECT2 immunohistochemistry scores of BA children were higher than control group (p = 0.001). Survival analysis revealed that LECT2 high expression is an unfavorable prognostic factor for native liver survival in BA patients. Additionally, the high LECT2 expression was an independent prognostic factor affecting native liver survival (HR 3.702, 95%CI:2.085-6.575, p = 0.001). LECT2 modulates TGF-ß mediated a-SMA and COL1A1 expression in LX-2 cells. siRNA-LECT2 inhibits the expression of a-SMA and COL1A1 in LX-2 cells. Overexpression of LECT2 resulted in an increase in a-SMA and COL1A1 expression. Knockdown of LECT2 inhibits the proliferation and increase apoptosis in activated LX-2 cells. LECT2 may act as a new prognostic biomarker for native liver survival in BA patients.

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