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1.
Immunity ; 45(3): 555-569, 2016 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-27637147

RESUMO

During viral infection, sensing of cytosolic DNA by the cyclic GMP-AMP synthase (cGAS) activates the adaptor protein STING and triggers an antiviral response. Little is known about the mechanisms that determine the kinetics of activation and deactivation of the cGAS-STING pathway, ensuring effective but controlled innate antiviral responses. Here we found that the ubiquitin ligase Trim38 targets cGas for sumoylation in uninfected cells and during the early phase of viral infection. Sumoylation of cGas prevented its polyubiquitination and degradation. Trim38 also sumoylated Sting during the early phase of viral infection, promoting both Sting activation and protein stability. In the late phase of infection, cGas and Sting were desumoylated by Senp2 and subsequently degraded via proteasomal and chaperone-mediated autophagy pathways, respectively. Our findings reveal an essential role for Trim38 in the innate immune response to DNA virus and provide insight into the mechanisms that ensure optimal activation and deactivation of the cGAS-STING pathway.


Assuntos
Vírus de DNA/imunologia , DNA/metabolismo , Nucleotídeos Cíclicos/metabolismo , Nucleotidiltransferases/metabolismo , Sumoilação/fisiologia , Viroses/metabolismo , Animais , Proteínas de Transporte/metabolismo , Cisteína Endopeptidases/metabolismo , Imunidade Inata/imunologia , Cinética , Proteínas de Membrana/metabolismo , Camundongos , Complexo de Endopeptidases do Proteassoma/metabolismo , Transdução de Sinais/imunologia , Transdução de Sinais/fisiologia , Sumoilação/imunologia , Proteínas com Motivo Tripartido , Ubiquitina-Proteína Ligases , Ubiquitinação/imunologia , Ubiquitinação/fisiologia
2.
Small ; 20(14): e2307809, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37988684

RESUMO

Multi-shelled hollow metal-organic frameworks (MH-MOFs) are highly promising as electrode materials due to their impressive surface area and efficient mass transfer capabilities. However, the fabrication of MH-MOFs has remained a formidable challenge. In this study, two types of double-shelled open hollow Prussian blue analogues, one with divalent iron (DHPBA-Fe(II)) and the other with trivalent iron (DHPBA-Fe(III)), through an innovative inner-outer growth strategy are successfully developed. The growth mechanism is found to involve lattice matching growth and ligand exchange processes. Subsequently, DHPBA-Fe(II) and DHPBA-Fe(III) are employed as cathodes in aqueous Zn-ion batteries. Significantly, DHPBA-Fe(II) demonstrated exceptional performance, exhibiting a capacity of 92.5 mAh g-1 at 1 A g-1, and maintaining remarkable stability over an astounding 10 000 cycles. This research is poised to catalyze further exploration into the fabrication techniques of MH-MOFs and offer fresh insights into the intricate interplay between electronic structure and battery performance.

3.
Arch Microbiol ; 206(8): 341, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38967784

RESUMO

Soil salinization poses a great threat to global agricultural ecosystems, and finding ways to improve the soils affected by salt and maintain soil health and sustainable productivity has become a major challenge. Various physical, chemical and biological approaches are being evaluated to address this escalating environmental issue. Among them, fully utilizing salt-tolerant plant growth-promoting bacteria (PGPB) has been labeled as a potential strategy to alleviate salt stress, since they can not only adapt well to saline soil environments but also enhance soil fertility and plant development under saline conditions. In the last few years, an increasing number of salt-tolerant PGPB have been excavated from specific ecological niches, and various mechanisms mediated by such bacterial strains, including but not limited to siderophore production, nitrogen fixation, enhanced nutrient availability, and phytohormone modulation, have been intensively studied to develop microbial inoculants in agriculture. This review outlines the positive impacts and growth-promoting mechanisms of a variety of salt-tolerant PGPB and opens up new avenues to commercialize cultivable microbes and reduce the detrimental impacts of salt stress on plant growth. Furthermore, considering the practical limitations of salt-tolerant PGPB in the implementation and potential integration of advanced biological techniques in salt-tolerant PGPB to enhance their effectiveness in promoting sustainable agriculture under salt stress are also accentuated.


Assuntos
Bactérias , Produtos Agrícolas , Estresse Salino , Microbiologia do Solo , Produtos Agrícolas/microbiologia , Produtos Agrícolas/crescimento & desenvolvimento , Bactérias/metabolismo , Bactérias/genética , Bactérias/crescimento & desenvolvimento , Desenvolvimento Vegetal , Tolerância ao Sal , Reguladores de Crescimento de Plantas/metabolismo , Solo/química , Plantas Tolerantes a Sal/microbiologia , Plantas Tolerantes a Sal/crescimento & desenvolvimento , Salinidade
4.
Exp Cell Res ; 427(2): 113605, 2023 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-37080417

RESUMO

As a member of Ubiquitin-specific protease subfamily, ubiquitin specific protease 7 (USP7) has been reported to participate in a variety of cellular processes, including cell cycle, apoptosis, DNA damage response, and epigenetic modification. However, its function in preimplantation embryos is still obscure. To investigate the functions of USP7 during preimplantation embryo development, we used siRNA to degrade endogenous USP7 messenger RNA. We found that USP7 knockdown significantly decreased the development rate of mouse early embryos. Moreover, depletion of USP7 induced the accumulation of the DNA lesions and apoptotic blastomeres in early embryos. In addition, USP7 knockdown caused an abnormal H3K27me3 modification in 2-cell embryos. Overall, our results indicate that USP7 maintains genome stability perhaps via regulating H3K27me3 and DNA damage, consequently controlling the embryo quality.


Assuntos
Histonas , Ubiquitina Tiolesterase , Animais , Camundongos , Peptidase 7 Específica de Ubiquitina/genética , Peptidase 7 Específica de Ubiquitina/metabolismo , Histonas/genética , Ubiquitina Tiolesterase/genética , Ubiquitina Tiolesterase/metabolismo , Dano ao DNA/genética , Proteases Específicas de Ubiquitina/genética
5.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(7): 723-729, 2024 Jul 15.
Artigo em Chinês | MEDLINE | ID: mdl-39014949

RESUMO

OBJECTIVES: To explore the diagnostic efficacy of serum 14-3-3ß protein combined with fractional exhaled nitric oxide (FeNO) and conventional ventilatory lung function parameters in diagnosing bronchial asthma (referred to as "asthma") in children. METHODS: A prospective study included 136 children initially diagnosed with asthma during an acute episode as the asthma group, and 85 healthy children undergoing routine health checks as the control group. The study compared the differences in serum 14-3-3ß protein concentrations between the two groups, analyzed the correlation of serum 14-3-3ß protein with clinical indices, and evaluated the diagnostic efficacy of combining 14-3-3ß protein, FeNO, and conventional ventilatory lung function parameters for asthma in children. RESULTS: The concentration of serum 14-3-3ß protein was higher in the asthma group than in the control group (P<0.001). Serum 14-3-3ß protein showed a positive correlation with the percentage of neutrophils and total serum immunoglobulin E, and a negative correlation with conventional ventilatory lung function parameters (P<0.05). Cross-validation of combined indices showed that the combination of 14-3-3ß protein, FeNO, and the percentage of predicted value of forced expiratory flow at 75% of lung volume had an area under the curve of 0.948 for predicting asthma, with a sensitivity and specificity of 88.9% and 93.7%, respectively, demonstrating good diagnostic efficacy (P<0.001). The model had the best extrapolation. CONCLUSIONS: The combination of serum 14-3-3ß protein, FeNO, and the percentage of predicted value of forced expiratory flow at 75% of lung volume can significantly improve the diagnostic efficacy for asthma in children. Citation:Chinese Journal of Contemporary Pediatrics, 2024, 26(7): 723-729.


Assuntos
Proteínas 14-3-3 , Asma , Óxido Nítrico , Humanos , Asma/diagnóstico , Asma/sangue , Asma/fisiopatologia , Masculino , Feminino , Criança , Proteínas 14-3-3/sangue , Óxido Nítrico/análise , Óxido Nítrico/sangue , Pré-Escolar , Estudos Prospectivos , Testes de Função Respiratória , Teste da Fração de Óxido Nítrico Exalado , Adolescente , Testes Respiratórios
6.
Artigo em Inglês | MEDLINE | ID: mdl-37606970

RESUMO

OBJECTIVE: The aim of this study is to identify whether low lupus disease activity status (LLDAS) and clinical remission (CR) of belimumab plus standard of care (SoC) therapy are achievable goals in childhood-onset SLE (cSLE). METHODS: This multicentre, one arm pre-post intervention study was conducted at 15 centers in China. The primary end point was to describe the proportion of patients who achieved LLDAS and CR after 3, 6, and 12 months after treatment with belimumab plus SoC therapy. A multiple regression model was used to impute missing data. A Poisson regression model was used to calculate the effect of belimumab treatment on the reduced risk of serious diseases and the incidence of new damage. RESULT: 193 (92.2% female) with active cSLE from 15 centers were included. At 3, 6 and 12 months, the proportion of LLDAS (CR) was 12.4% (1.0%), 25.6% (4.5%) and 70.3% (29.7%), respectively. The mean SELENA-SLEDAI score decreased from 11.0 at baseline to 3.7, 2.9 and 1.7 at 3, 6, and 12 months. At baseline, all patients received steroids at a mean (SD) prednisone equivalent dose of 31.0 (18.2) mg/day, which decreased to 19.4 (10.8) mg/day at month 3, 12.6 (7.2) mg/day at month 6 and 6.7 (5.3) mg/day at month 12. The symptoms and immunological indicators were also significantly improved. CONCLUSION: This is the first and largest sample size prospective clinical intervention study of cSLE patients treated with belimumab in China. LLDAS and CR were attainable treat-to-target of belimumab plus SoC therapy in cSLE.

7.
Support Care Cancer ; 32(1): 65, 2023 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-38150049

RESUMO

OBJECTIVE: The objective of this study was to conduct a systematic review of the measurement properties and methodological quality of stigma assessment tools designed for breast cancer patients. The aim was to provide clinical medical staff with a foundation for selecting high-quality assessment tools. METHODS: A comprehensive computer search was carried out across various databases, including SinoMed, China National Knowledge Infrastructure (CNKI), Wanfang Database, China Science and Technology Journal Database(VIP), Embase, PubMed, Web of Science, The Cochrane Library, and Scopus, which were searched from the inception of the databases until March 20, 2023. Literature screening and data extraction were performed independently by two researchers, adhering to predefined inclusion and exclusion criteria. The assessment tools were evaluated using the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) systematic evaluation guidelines. RESULTS: In the final analysis, a total of 9 assessment tools were included. However, none of these tools addressed measurement error, cross-cultural validity, criterion validity, and responsiveness. Following the COSMIN guidelines, BCSS and CSPDS were assigned to Class A recommendations, while the remaining tools received Class B recommendations. CONCLUSION: The BCSS and CSPDS scales demonstrated comprehensive assessment in terms of their measurement characteristics, exhibiting good methodological quality, measurement attribute quality, and supporting evidence. Therefore, it is recommended to utilize these scales for evaluating breast cancer stigma. However, further validation is required for the remaining assessment tools.


Assuntos
Neoplasias da Mama , Humanos , Feminino , China , Consenso , Bases de Dados Factuais , Conhecimento
8.
BMC Med Educ ; 23(1): 294, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-37127607

RESUMO

BACKGROUND: The mastery and application of the "Plan-Do-Check-Act" (PDCA) cycle by hospital clinical department managers are essential for hospitals to carry out total quality management and continuously improve medical quality. This study investigated the degree of cognition of the PDCA cycle by clinical department managers and the factors affecting their cognition. METHODS: A self-designed questionnaire was used to evaluate the cognition of clinical department managers regarding the PDCA cycle in 11 municipal public Class III Grade A hospitals in Western China. RESULTS: More than 25% of clinical department managers in the surveyed hospitals are unaware or partially aware of the PDCA cycle. Logistic regression analysis showed that sex (P = 0.049), education (P < 0.001), duty (P < 0.001), and tenure (P = 0.002) had a significant influence on managers' cognition of PDCA. Participants who were female (P < 0.001), undergraduate (P < 0.001), head nurses, or deputy head nurses (P < 0.001), with a tenure of 5-10 years (P = 0.024) had a better cognition of the PDCA cycle. In the daily management of the department, the vast majority of managers do not implement the Check and Action steps. Among the trained managers, only 65.44% applied the complete PDCA cycle in daily management. Nearly a third of managers thought PDCA was a response to hospital demands; 82.83% of the managers need to receive PDCA cycle training, and half of them indicated a preference for online training. CONCLUSIONS: The cognition level of hospital clinical department managers regarding the PDCA cycle is relatively low, especially among the clinical department heads, and most of them are willing to accept PDCA cycle training.


Assuntos
Cognição , Hospitais , Humanos , Feminino , Masculino , Inquéritos e Questionários , China
9.
Small ; 18(32): e2203240, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35843877

RESUMO

Nanozymes are widely applied for treating various major diseases, including neurological diseases and tumors. However, the biodegradability of nanozymes remains a great challenge, which hinders their further clinical translation. Based on the microenvironment of osteoarthritis (OA), a representative pH-responsive biodegradable hollow-structured manganese Prussian blue nanozyme (HMPBzyme) is designed and applied for treatment of OA. HMPBzyme with good pH-responsive biodegradability, biocompatibility, and multi-enzyme activities is constructed by bovine serum albumin bubbles as a template-mediated biomineralization strategy. HMPBzyme suppresses hypoxia-inducible factor-1α (HIF-1α) expression and decreases reactive oxygen species (ROS) level in the in vitro experiment. Furthermore, HMPBzyme markedly suppresses the expression of ROS and alleviates the degeneration of cartilage in OA rat models. The results indicate that the biodegradable HMPBzyme inhibits oxidative damage and relieves hypoxia synergistically to suppress inflammation and promote the anabolism of cartilage extracellular matrix by protecting mitochondrial function and down-regulating the expression of HIF-1α, which modulates the phenotypic conversion of macrophages from pro-inflammatory M1 subtype to anti-inflammatory M2 subtype for OA treatment. This research lays a solid foundation for the design, construction, and biomedical application of biodegradable nanozymes and promotes the application of nanozymes in biomedicine.


Assuntos
Osteoartrite , Animais , Hipóxia/metabolismo , Hipóxia/patologia , Inflamação/patologia , Macrófagos/metabolismo , Osteoartrite/tratamento farmacológico , Ratos , Espécies Reativas de Oxigênio/metabolismo
10.
J Transl Med ; 20(1): 552, 2022 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-36463215

RESUMO

BACKGROUND: Associations of drugs with diseases provide important information for expediting drug development. Due to the number of known drug-disease associations is still insufficient, and considering that inferring associations between them through traditional in vitro experiments is time-consuming and costly. Therefore, more accurate and reliable computational methods urgent need to be developed to predict potential associations of drugs with diseases. METHODS: In this study, we present the model called weighted graph regularized collaborative non-negative matrix factorization for drug-disease association prediction (WNMFDDA). More specifically, we first calculated the drug similarity and disease similarity based on the chemical structures of drugs and medical description information of diseases, respectively. Then, to extend the model to work for new drugs and diseases, weighted [Formula: see text] nearest neighbor was used as a preprocessing step to reconstruct the interaction score profiles of drugs with diseases. Finally, a graph regularized non-negative matrix factorization model was used to identify potential associations between drug and disease. RESULTS: During the cross-validation process, WNMFDDA achieved the AUC values of 0.939 and 0.952 on Fdataset and Cdataset under ten-fold cross validation, respectively, which outperforms other competing prediction methods. Moreover, case studies for several drugs and diseases were carried out to further verify the predictive performance of WNMFDDA. As a result, 13(Doxorubicin), 13(Amiodarone), 12(Obesity) and 12(Asthma) of the top 15 corresponding candidate diseases or drugs were confirmed by existing databases. CONCLUSIONS: The experimental results adequately demonstrated that WNMFDDA is a very effective method for drug-disease association prediction. We believe that WNMFDDA is helpful for relevant biomedical researchers in follow-up studies.


Assuntos
Algoritmos , Asma , Humanos , Análise por Conglomerados , Bases de Dados Factuais , Projetos de Pesquisa
11.
Inorg Chem ; 61(43): 16981-16985, 2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36251482

RESUMO

Metal-organic framework (MOF) glass is a new type of glass material, but it usually lacks sufficient porosity. Thus, regulating the pore structure of MOF glass to improve its adsorption performance is very important. Herein, we found that the porosity of MOF glasses agZIF-62 and agZIF-76 can be regulated via an ammonia-immersion approach. After ammonia immersion, the resulting agZIF-62-NH3 and agZIF-76-NH3 could be maintained in their glass states or converted to their amorphous states, respectively. Their porosity changed according to the gas adsorption experiments. Notably, compared with agZIF-62 and agZIF-76, the iodine uptake capacities for agZIF-62-NH3 and agZIF-76NH3 increased by 12 and 21 times, respectively. This work shows that the subsequent treatment of MOF glass can regulate their adsorption performance.

12.
Acta Pharmacol Sin ; 43(6): 1495-1507, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34671110

RESUMO

Ulcerative colitis (UC) is a chronic inflammatory disease of the gastrointestinal tract, which is closely related to gut barrier dysfunction. Emerging evidence shows that interleukin-22 (IL-22) derived from group 3 innate lymphoid cells (ILC3s) confers benefits on intestinal barrier, and IL-22 expression is controlled by aryl hydrocarbon receptor (AhR). Previous studies show that baicalein protects the colon from inflammatory damage. In this study we elucidated the molecular mechanisms underlying the protective effect of baicalein on intestinal barrier function in colitis mice. Mice were administered baicalein (10, 20, 40 mg·kg-1·d-1, i.g.) for 10 days; the mice freely drank 3% dextran sulfate sodium (DSS) on D1-D7 to induce colitis. We showed that baicalein administration simultaneously ameliorated gut inflammation, decreased intestinal permeability, restored tight junctions of colons possibly via promoting AhR/IL-22 pathway. Co-administration of AhR antagonist CH223191 (10 mg/kg, i.p.) partially blocked the therapeutic effects of baicalein in colitis mice, whereas AhR agonist FICZ (1 µg, i.p.) ameliorated symptoms and gut barrier function in colitis mice. In a murine lymphocyte line MNK-3, baicalein (5-20 µM) dose-dependently increased the expression of AhR downstream target protein CYP1A1, and enhanced IL-22 production through facilitating AhR nuclear translocation, these effects were greatly diminished in shAhR-MNK3 cells, suggesting that baicalein induced IL-22 production in AhR-dependent manner. To further clarify that, we constructed an in vitro system consisting of MNK-3 and Caco-2 cells, in which MNK-3 cell supernatant treated with baicalein could decrease FITC-dextran permeability and promoted the expression of tight junction proteins ZO-1 and occluding in Caco-2 cells. In conclusion, this study demonstrates that baicalein ameliorates colitis by improving intestinal epithelial barrier via AhR/IL-22 pathway in ILC3s, thus providing a potential therapy for UC.


Assuntos
Colite Ulcerativa , Colite , Animais , Células CACO-2 , Colite/metabolismo , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Colo/metabolismo , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Flavanonas , Humanos , Imunidade Inata , Interleucinas , Mucosa Intestinal/metabolismo , Linfócitos , Camundongos , Camundongos Endogâmicos C57BL , Receptores de Hidrocarboneto Arílico/metabolismo , Receptores de Hidrocarboneto Arílico/uso terapêutico , Interleucina 22
13.
Hepatobiliary Pancreat Dis Int ; 21(6): 551-558, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35000845

RESUMO

BACKGROUND: The optimal width of resection margin (RM) for hepatocellular carcinoma (HCC) remains controversial. This study aimed to investigate the value of imaging tumor capsule (ITC) and imaging tumor size (ITS) in guiding RM width for patients with HCC. METHODS: Patients who underwent hepatectomy for HCC in our center were retrospectively reviewed. ITC (complete/incomplete) and ITS (≤ 3 cm/> 3 cm) were assessed by preoperative magnetic resonance imaging (MRI). Using subgroup analyses based on ITC and ITS, the impact of RM width [narrow RM (< 5 mm)/wide RM (≥ 5 mm)] on recurrence-free survival (RFS), overall survival (OS), and RM recurrence was analyzed. RESULTS: A total of 247 patients with solitary HCC were included. ITC and ITS were independent predictors for RFS and OS in the entire cohort. In patients with ITS ≤ 3 cm, neither ITC nor RM width showed a significant impact on prognosis, and the incidence of RM recurrence was comparable between the narrow RM and wide RM groups (15.6% vs. 4.3%, P = 0.337). In patients with ITS > 3 cm and complete ITC, the narrow RM group exhibited comparable RFS, OS, and incidence of RM recurrence with the wide RM group (P = 0.606, 0.916, and 0.649, respectively). However, in patients with ITS > 3 cm and incomplete ITC, the wide RM group showed better RFS and OS and a lower incidence of RM recurrence compared with the narrow RM group (P = 0.037, 0.018, and 0.046, respectively). CONCLUSIONS: As MRI-based preoperative markers, conjoint analysis of ITC with ITS aids in determining RM width for solitary HCC patients. Narrow RM is applicable in patients with ITS ≤ 3 cm regardless of ITC status and in those with ITS > 3 cm and complete ITC. Wide RM is preferred in those with ITS > 3 cm and incomplete ITC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Margens de Excisão , Estudos Retrospectivos , Recidiva Local de Neoplasia/patologia , Hepatectomia/efeitos adversos , Hepatectomia/métodos , Prognóstico
14.
J Cell Mol Med ; 25(23): 10837-10845, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34750955

RESUMO

Melanoma is one of the most aggressive and life-threatening skin cancers, and in this research, we aimed to explore the functional role of circular RNA VANGL1 (circVANGL1) in melanoma progression. The expression levels of circVANGL1 were observed to be significantly increased in clinical melanoma tissues and cell lines. Moreover, circVANGL1 knockdown suppressed, while circVANGL1 overexpression promoted the proliferation, migration and invasion abilities of melanoma cells. Further investigations confirmed the direct binding relation between circVANGL1 and miR-150-5p in melanoma, and restoration of miR-150-5p blocked the effects of circVANGL1 overexpression in melanoma cells. We further found that circVANGL1 was up-regulated by TGF-ß treatment, and the enhanced EMT of TGF-ß-treated melanoma cells was blocked by circVANGL1 knockdown. In conclusion, these results indicated that circVANGL1 might serve as a promising therapeutic target for melanoma.


Assuntos
Proteínas de Transporte/genética , Transição Epitelial-Mesenquimal/genética , Melanoma/genética , Proteínas de Membrana/genética , MicroRNAs/genética , RNA Circular/genética , Fator de Crescimento Transformador beta/genética , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , RNA Longo não Codificante/genética , Neoplasias Cutâneas/genética , Regulação para Cima/genética
15.
J Nanobiotechnology ; 19(1): 126, 2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-33947395

RESUMO

BACKGROUND: Photothermal therapy (PTT), involving application of localized hyperthermia to kill cancer cells, has attracted wide attention in cancer therapy. The production of reactive oxygen species (ROS) during PTT may cause irreversible damage to healthy tissues around the tumor. Simultaneously, hyperthermia can stimulate inflammatory response, thus promoting tumor recurrence and metastasis. Therefore, it is of paramount importance to reduce the undesired side effects for further development of PTT. RESULTS: Using a hydrothermal method, spherical Prussian blue nanoparticles (PBs) with uniform size were prepared. The PBs exhibited good dispersion and stability in saline with an average hydrodynamic size of 110 nm. The prepared PBs had a high photothermal conversion efficiency and photothermal stability. The PBs showed intrinsic ROS scavenging properties in vitro. Antioxidant and anti-inflammatory effects of PBs were also observed in vivo. Assessment of toxicity and endoplasmic reticulum stress-inducing ability showed that PBs did not induce an inflammatory response. Tissues of major organs of mice stained with hematoxylin-eosin showed no significant damage, indicating good biocompatibility and safety of PBs. CONCLUSION: The designed single-component PBs with intrinsic ROS scavenging and anti-inflammatory properties could avoid inflammatory response and heat stress-induced ROS during PTT. Thus, further research on PBs is worthwhile to achieve their clinical translation and promote the development of PTT.


Assuntos
Ferrocianetos/química , Ferrocianetos/farmacologia , Hipertermia Induzida/métodos , Hipertermia/tratamento farmacológico , Nanopartículas/química , Nanopartículas/uso terapêutico , Terapia Fototérmica/métodos , Animais , Neoplasias da Mama , Feminino , Hipertermia/patologia , Inflamação , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Fármacos Fotossensibilizantes/farmacologia , Células RAW 264.7 , Espécies Reativas de Oxigênio
16.
Pharmacology ; 106(1-2): 29-36, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32694250

RESUMO

INTRODUCTION: Homeostasis of cholesterol is crucial for cellular function, and dysregulated cholesterol biosynthesis is a metabolic event that can lead to hepatic and cardiovascular abnormalities. OBJECTIVE: The aim of this study was to investigate the effects and mechanisms of domain-associated protein (Daxx) and androgen receptor (AR) on intracellular cholesterol synthesis. METHODS: HepG2 cells were transfected with pCDNA3.1(+)/Daxx plasmid or treated with testosterone propionate to observe the effects of Daxx and AR on intracellular cholesterol levels. Co-immunoprecipitation experiments were performed to identify the interaction between Daxx and AR and to explore the regulatory effects of this interaction on cholesterol synthesis. RESULTS: Our experiments showed that AR promoted cholesterol synthesis and accumulation by activating sterol-regulatory element-binding protein isoform 2. AR-induced cholesterol synthesis was inhibited by Daxx; however, the expression of AR was not affected. Further studies demonstrated the existence of direct binding between Daxx and AR and this interaction was required to suppress AR activity. CONCLUSIONS: The Daxx-mediated antagonism of AR depicts a more complete picture as to how Daxx regulates intracellular cholesterol level and provides a new target for treatment of atherosclerosis.


Assuntos
Colesterol/biossíntese , Proteínas Correpressoras/metabolismo , Chaperonas Moleculares/metabolismo , Receptores Androgênicos/metabolismo , Compostos Azo , Colesterol/análise , Cromatografia Líquida de Alta Pressão , Colorimetria , Células Hep G2 , Humanos , Hidroximetilglutaril-CoA Redutases/metabolismo , Imunoprecipitação , Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismo
17.
Proc Natl Acad Sci U S A ; 115(45): 11567-11572, 2018 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-30348779

RESUMO

Whole-exome sequencing has been successful in identifying genetic factors contributing to familial or sporadic Parkinson's disease (PD). However, this approach has not been applied to explore the impact of de novo mutations on PD pathogenesis. Here, we sequenced the exomes of 39 early onset patients, their parents, and 20 unaffected siblings to investigate the effects of de novo mutations on PD. We identified 12 genes with de novo mutations (MAD1L1, NUP98, PPP2CB, PKMYT1, TRIM24, CEP131, CTTNBP2, NUS1, SMPD3, MGRN1, IFI35, and RUSC2), which could be functionally relevant to PD pathogenesis. Further analyses of two independent case-control cohorts (1,852 patients and 1,565 controls in one cohort and 3,237 patients and 2,858 controls in the other) revealed that NUS1 harbors significantly more rare nonsynonymous variants (P = 1.01E-5, odds ratio = 11.3) in PD patients than in controls. Functional studies in Drosophila demonstrated that the loss of NUS1 could reduce the climbing ability, dopamine level, and number of dopaminergic neurons in 30-day-old flies and could induce apoptosis in fly brain. Together, our data suggest that de novo mutations could contribute to early onset PD pathogenesis and identify NUS1 as a candidate gene for PD.


Assuntos
Encéfalo/metabolismo , Neurônios Dopaminérgicos/metabolismo , Mutação , Proteínas do Tecido Nervoso/genética , Doença de Parkinson/genética , Receptores de Superfície Celular/genética , Adulto , Idade de Início , Animais , Apoptose/genética , Translocador Nuclear Receptor Aril Hidrocarboneto/antagonistas & inibidores , Translocador Nuclear Receptor Aril Hidrocarboneto/genética , Translocador Nuclear Receptor Aril Hidrocarboneto/metabolismo , Sequência de Bases , Encéfalo/patologia , Estudos de Casos e Controles , Estudos de Coortes , Modelos Animais de Doenças , Dopamina/metabolismo , Neurônios Dopaminérgicos/patologia , Proteínas de Drosophila/antagonistas & inibidores , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Diagnóstico Precoce , Feminino , Expressão Gênica , Redes Reguladoras de Genes , Humanos , Masculino , Proteínas do Tecido Nervoso/metabolismo , Pais , Doença de Parkinson/diagnóstico , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Receptores de Superfície Celular/metabolismo , Irmãos
18.
Nano Lett ; 20(5): 3560-3567, 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32324411

RESUMO

Heterostructures built from 2D, atomically thin crystals are bound by the van der Waals force and exhibit unique optoelectronic properties. Here, we report the structure, composition and optoelectronic properties of 1D van der Waals heterostructures comprising carbon nanotubes wrapped by atomically thin nanotubes of boron nitride and molybdenum disulfide (MoS2). The high quality of the composite was directly made evident on the atomic scale by transmission electron microscopy, and on the macroscopic scale by a study of the heterostructure's equilibrium and ultrafast optoelectronics. Ultrafast pump-probe spectroscopy across the visible and terahertz frequency ranges identified that, in the MoS2 nanotubes, excitons coexisted with a prominent population of free charges. The electron mobility was comparable to that found in high-quality atomically thin crystals. The high mobility of the MoS2 nanotubes highlights the potential of 1D van der Waals heterostructures for nanoscale optoelectronic devices.

19.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(1): 39-44, 2021 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-33474887

RESUMO

Chronic stress activates the typical neuroendocrine system, hypothalamus pituitary adrenal axis and sympathetic nervous system, and leads to a sustained non-specific adaptive response. It has been proved that chronic stress can promote tumor initiation and induce tumor evolution, especially in immune function and remodeling of tumor microenvironment. However, due to the complex mechanism of chronic stress and the great difference in individual tolerance, the research evidence of chronic stress in tumor genesis and progression is still unclear. Therefore, in this paper, we review the research on the relationship between chronic stress and tumor initiation and evolution, focusing on the molecular mechanism of chronic stress promoting tumor occurrence and development, inhibiting immune response and remodeling tumor immune microenvironment, and exploring the stress management program of healthy people and cancer patients, so as to provide clues for exploring new strategies of cancer prevention and treatment. In our opinion, targeting the cAMP/PKA/CREB signaling pathway to reverse tumor treatment strategy, the relationship between the tumor and stress, inflammation, immunity, the suppressor activity of ß receptor antagonist and its mechanism as well as associated with different treatment options, still need to be further explored. A healthy lifestyle, positive life attitudes and professional stress management guidance are essential for the prevention and treatment of cancer.


Assuntos
Neoplasias , Sistema Hipófise-Suprarrenal , Humanos , Sistema Hipotálamo-Hipofisário , Inflamação , Sistema Nervoso Simpático , Microambiente Tumoral
20.
Cell Commun Signal ; 18(1): 119, 2020 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-32746850

RESUMO

Exosomes have been considered as novel and potent vehicles of intercellular communication, instead of "cell dust". Exosomes are consistent with anucleate cells, and organelles with lipid bilayer consisting of the proteins and abundant lipid, enhancing their "rigidity" and "flexibility". Neighboring cells or distant cells are capable of exchanging genetic or metabolic information via exosomes binding to recipient cell and releasing bioactive molecules, such as lipids, proteins, and nucleic acids. Of note, exosomes exert the remarkable effects on lipid metabolism, including the synthesis, transportation and degradation of the lipid. The disorder of lipid metabolism mediated by exosomes leads to the occurrence and progression of diseases, such as atherosclerosis, cancer, non-alcoholic fatty liver disease (NAFLD), obesity and Alzheimer's diseases and so on. More importantly, lipid metabolism can also affect the production and secretion of exosomes, as well as interactions with the recipient cells. Therefore, exosomes may be applied as effective targets for diagnosis and treatment of diseases. Video abstract.


Assuntos
Exossomos/metabolismo , Metabolismo dos Lipídeos , Animais , Humanos , Lipídeos/biossíntese , Modelos Biológicos
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