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1.
Front Public Health ; 12: 1279293, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38496394

RESUMO

Background: During the coronavirus disease-2019 (COVID-19) pandemic, there have been many studies on knowledge, attitudes, and practices (KAP) toward prevention of COVID-19 infection in China. Except for symptomatic treatment and vaccination, KAP toward COVID-19 plays an important role in the prevention of COVID-19. There is no systematic evaluation and meta-analysis of KAP toward COVID-19 in China. This study is the earliest meta-analysis of KAP toward COVID-19 in China's general population. Hence, this systematic review aimed to summarize the knowledge, attitudes, and practices (KAP) of Chinese residents toward COVID-19 during the pandemic. Methodology: Following the PRISMA guidelines, articles relevant to COVID-19 KAP that were conducted among the Chinese population were found in databases such as Scopus, ProQuest, PubMed, EMbase, Web of Science, Cochrane Library, China Biology Medicine, China National Knowledge Infrastructure, CQVIP, Wanfang and Google Scholar. A random-effect meta-analysis is used to summarize studies on knowledge, attitudes, and practice levels toward COVID-19 infection in China's general population. Results: Fifty-seven articles published between August 2020 and November 2022 were included in this review. Overall, 75% (95% CI: 72-79%) of Chinese residents had good knowledge about COVID-19, 80% (95% CI: 73-87%) of Chinese residents had a positive attitude toward COVID-19 pandemic control and prevention (they believe that Chinese people will win the battle against the epidemic), and the aggregated proportion of residents with a correct practice toward COVID-19 was 84% (95% CI: 82-87%, I2 = 99.7%).In the gender subgroup analysis, there is no significant difference between Chinese men and Chinese women in terms of their understanding of COVID-19. However, Chinese women tend to have slightly higher levels of knowledge and a more positive attitude toward the virus compared to Chinese men. When considering the urban and rural subgroup analysis, it was found that Chinese urban residents have a better understanding of COVID-19 compared to Chinese rural residents. Interestingly, the rural population displayed higher rates of correct behavior and positive attitudes toward COVID-19 compared to the urban population. Furthermore, in the subgroup analysis based on different regions in China, the eastern, central, and southwestern regions exhibited higher levels of knowledge awareness compared to other regions. It is worth noting that all regions in China demonstrated good rates of correct behavior and positive attitudes toward COVID-19. Conclusion: This study reviews the level of KAP toward COVID-19 during the pandemic period in China. The results show that the KAP toward COVID-19 in Chinese residents was above a favorable level, but the lack of translation of knowledge into practice should be further reflected on and improved. A subgroup analysis suggests that certain groups need more attention, such as males and people living in rural areas. Policy makers should pay attention to the results of this study and use them as a reference for the development of prevention and control strategies for major public health events that may occur in the future. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=348246, CRD42022348246.


Assuntos
COVID-19 , População do Leste Asiático , Feminino , Humanos , Masculino , China/epidemiologia , COVID-19/epidemiologia , Conhecimentos, Atitudes e Prática em Saúde , Pandemias/prevenção & controle , Inquéritos e Questionários
3.
Vet Microbiol ; 288: 109943, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38113574

RESUMO

O-acetyl-homoserine sulfhydrylase (OAHS) is a pyridoxal 5'-phosphate-dependent enzyme involved in microbial methionine biosynthesis, which catalyzes the conversion of o-acetyl-homoserine (OAH) to homocysteine. In our previous study, we found that OAHS of Streptococcus suis serotype 2 (SS2) can interact with the porcine blood-brain barrier (BBB) model, but whether OAHS regulates the penetration of BBB during SS2 infection is still unclear. To explore the role of OAHS in SS2 infection, OAHS-deficient SS2 mutant strain (SC19-ΔOAHS) and gene complemental strain (SC19-cΔOAHS) were constructed. Compared to the parent strain, with the loss of oahs, the chain length of SC19-ΔOAHS was shortened, the virulence was significantly reduced, the survival rate of mice infected with SC19-ΔOAHS was obviously increased accompanied by the relieved clinical symptoms. And the survival ability of SC19-ΔOAHS in whole blood was also remarkably decreased. Interestingly, the adhesion of SC19-ΔOAHS to endothelial cells was markedly increased, but the deficiency of OAHS significantly inhibited the strain penetrating BBB both in vivo and in vitro. Most of these phenomena can be reversed by the complemental strain (SC19-cΔOAHS). Further study showed that the deficiency of OAHS severely reduced SC19-induced endothelial cell apoptosis, tight junctions (TJs) protein impairment and the expression of SS2 virulence factor Enolase (Eno), involved in the destruction of BBB. Additionally, SC19-ΔOAHS immunized mice were able to resist SC19 or JZLQ022 infection. In conclusion, we confirmed that OAHS promoted the pathogenicity by enhancing host's BBB permeability and immune escape, and SC19- ΔOAHS is a potential live vaccine.


Assuntos
Infecções Estreptocócicas , Streptococcus suis , Doenças dos Suínos , Animais , Camundongos , Células Endoteliais , Homosserina/genética , Sorogrupo , Infecções Estreptocócicas/veterinária , Suínos , Doenças dos Suínos/metabolismo , Virulência
4.
Cancer ; 129(17): 2685-2693, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37129197

RESUMO

BACKGROUND: In lung cancer, overexpression of nuclear export proteins can result in inactivation of critical tumor suppressor proteins and cell-cycle regulators. Selective suppression of nuclear export proteins has immunomodulatory activities. Here, clinical safety and early efficacy data are presented on the combination of pembrolizumab and an oral selective nuclear export inhibitor, selinexor, for the treatment of metastatic non-small cell lung cancer (mNSCLC). METHODS: The primary objective of this prospective investigator-initiated study was to determine the safety and tolerability of selinexor in combination with pembrolizumab in patients with mNSCLC. Secondary objectives included determination of objective tumor response rate, disease control rate, and progression-free survival duration. RESULTS: A total of 17 patients were included in the final analysis. Fifteen (88%) received more than two lines of prior systemic therapy and 10 (59%) had prior exposure to anti-PD-1/programmed death-ligand 1 (PD-L1) therapy. The median age was 67.5 years. Ten patients had grade ≥3 adverse events related to selinexor treatment. Responses to treatment occurred in patients who did and did not undergo previous anti-PD-1/PD-L1 therapy and in patients with activating driver mutations. The median overall survival and progression-free survival were 11.4 months (95% CI, 3.4-19.8 months) and 3.0 months (95% CI, 1.7-5.7 months), respectively. The overall response rate was 18% and the 6-month disease control rate was 24%. CONCLUSIONS: Selinexor in combination with pembrolizumab demonstrated promising antitumor activity in patients with mNSCLC, including those who had previously received anti-PD-1/PD-L1 therapy. The therapy-related toxic effects were consistent with the prior safety data for both drugs, and no overlapping toxic effects were observed. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02419495. PLAIN LANGUAGE SUMMARY: New strategies to prevent or reverse resistance to immune checkpoint inhibitors are under investigation. Selective inhibitors of nuclear export proteins, such as selinexor, can induce restoration of tumor-suppressing pathways and induce potent immunomodulatory activities. This article contains the clinical safety and early efficacy data on the combination of pembrolizumab and selinexor in treatment of metastatic non-small cell lung cancer.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Idoso , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/patologia , Antígeno B7-H1 , Estudos Prospectivos
5.
Foods ; 11(2)2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35053916

RESUMO

Processed unhusked rice is prone to mildew during storage. In this study, the storage conditions were simulated at temperatures of 20, 30, and 35 °C and a relative humidity of 40%, 60% and 80%, respectively. The water, fatty acid, and total starch content and the peak viscosity, mold colony number, protein secondary structure, and spatial structure of rice were monitored in order to propose the critical point of mildew during storage. In the process of rice from lively to moldy, the water content, fatty acid contents and the peak viscosity were increased. The total starch content decreased and then showed a slow increasing trend, while the microstructure of the powder particles changed from smooth and complete to loosen and hollow. With the increase in storage time, the vibration of the amide Ⅰ band of the rice samples decreased slightly, indicating that the total contents of ß-fold, ß-turn, α-helix, and random curl of the rice protein also changed. PCA (Principal Component Analysis) analysis showed that rice mildew index was closely related to temperature and humidity during storage. In our investigation, the best and most suitable temperature and relative humidity for rice storge is 20 °C and 40%, respectively. These results suggested that temperature and environmental humidity are vital factors affecting the physicochemical properties and nutrient changes, which provides a theoretical basis for the early warning of rice mildew during storage.

6.
Biofactors ; 47(3): 444-460, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34003544

RESUMO

Activation of hypoxia-inducible factors (HIFs) as a result of intratumoral hypoxia modulates a cascade of molecular pathways thus leading to angiogenesis and metastasis in many solid tumors, including breast cancer (BC). In our paper, we report a regulatory axis of HIF-1, SNHG1, miR-199a-3p, and mitochondrial transcription factor A (TFAM) involved in tumor angiogenesis and metastasis under hypoxic conditions in BC. The expression of SNHG1 was determined in human BC cells cultured in hypoxia (1% O2 , 24 h) and normoxia (20% O2 , 24 h). Cultured MDA-MB-231 cells were assayed for the proliferation, migration, invasion, angiogenesis in vitro by using EdU staining, transwell chamber assays, Matrigel-based angiogenesis assays, tumorigenesis, and lung metastasis in vivo by using an orthotopic-transplant model of human BC. Dual-luciferase reporter assay, chromatin immunoprecipitation quantitative polymerase chain reaction assay, fluorescence in situ hybridization assay, RNA-binding protein immunoprecipitation assay, and RNA pull-down were performed to test interaction between HIF-1 and SNHG1, SNHG1 and miR-199a-3p, miR-199a-3p and TFAM. SNHG1 was increased under hypoxic conditions at a HIF-1-dependent manner. SNHG1 knockdown tempered MDA-MB-231 cell proliferation, migration, invasion, angiogenesis, in vitro, tumorigenesis, and lung metastasis in vitro. SNHG1 was co-expressed with miR-199a-3p and regulated the TFAM, a target gene of miR-199a-3p. SNHG1 increased the TFAM by binding with miR-199a-3p, thus promoting BC development and metastasis. These results support a regulatory axis consisting of HIF-1, SNHG1, miR-199a-3p, and TFAM during BC development and metastasis under hypoxic conditions, providing an opportunity to develop targeted therapeutics for BC.


Assuntos
Neoplasias da Mama/metabolismo , Fator 1 Induzível por Hipóxia/metabolismo , Hipóxia/metabolismo , MicroRNAs/metabolismo , Metástase Neoplásica/genética , Neovascularização Patológica/metabolismo , RNA Nucleolar Pequeno/metabolismo , Animais , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Proteínas de Ligação a DNA , Modelos Animais de Doenças , Feminino , Proteínas de Grupo de Alta Mobilidade , Hipóxia/genética , Fator 1 Induzível por Hipóxia/genética , Camundongos , Camundongos Endogâmicos NOD , MicroRNAs/genética , Neovascularização Patológica/genética , RNA Nucleolar Pequeno/genética
7.
Cancer Biother Radiopharm ; 36(1): 18-22, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31702382

RESUMO

Background: LncRNA LINC00974 participates in oral fibrogenesis, indicating possible involvement in other oral diseases. Results: The authors found that LINC00974 was upregulated in oral squamous cell carcinoma (OSCC) and predicted poor survival. In OSCC tissues, LINC00974 was inversely correlated with miR-122 and positively correlated with RhoA. In OSCC cells, LINC00974 overexpression resulted in upregulated, whereas overexpression of miR-122 led to downregulated RhoA. Moreover, downregulated miR-122 was observed after LINC00974 overexpression, whereas LINC00974 expression was not significantly affected by miR-122 overexpression. In invasion and migration assay, miR-122 overexpression resulted in reduced, whereas LINC00974 and RhoA overexpression resulted in increased rate of cancer cell migration and invasion. In addition, miR-122 overexpression reduced the effects of LINC00974 overexpression. Conclusion: Therefore, LINC00974 can downregulate miR-122 to upregulate RhoA in OSCC, thereby promoting cell invasion and migration.


Assuntos
MicroRNAs/metabolismo , Neoplasias Bucais/genética , RNA Longo não Codificante/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Proteína rhoA de Ligação ao GTP/genética , Adulto , Idoso , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Invasividade Neoplásica/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Regulação para Cima
8.
Life Sci ; 266: 118829, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33259864

RESUMO

AIMS: Circular RNA (circRNA) is abnormally expressed in cancers and has been linked to cancer progression, including breast cancer (BC). However, the role and mechanism of circ-UBR1 in BC progression remains to be further studied. MATERIALS AND METHODS: Quantitative real-time PCR (qRT-PCR) was conducted to analyze the expression of circ-UBR1, miR-1299 and Cyclin D1 (CCND1). Cell counting kit 8 (CCK8) assay was used to measure cell viability. Cell apoptosis and cell cycle distribution were analyzed by flow cytometry. Then, the migration and invasion of cells were determined by transwell assay. Moreover, BC tumor xenograft model was built to evaluate the function of circ-UBR1 silencing on BC tumor volume and weight. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were applied to illuminate the interaction between miR-1299 and circ-UBR1 or CCND1. In addition, relative CCND1 protein expression was assessed using western blot (WB) analysis. KEY FINDINGS: Our results revealed that circ-UBR1 was upregulated in BC, and its silencing could inhibit BC cell proliferation, metastasis, and promote apoptosis in vitro, as well as restrain BC tumor growth in vivo. Meanwhile, we found that circ-UBR1 could sponge miR-1299, and miR-1299 inhibitor could reverse the effect of circ-UBR1 knockdown on BC cell progression. Furthermore, CCND1 was a target of miR-1299, and CCND1 overexpression could reverse the effect of miR-1299 mimic on BC cell progression. Also, the downregulation of circ-UBR1 could inhibit CCND1 expression, while this effect could be inverted by miR-1299 inhibitor. SIGNIFICANCE: Our data indicated that circ-UBR1 might play a pro-cancer role in BC progression by regulating the miR-1299/CCND1 axis.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/patologia , Ciclina D1/metabolismo , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , RNA Circular/genética , Ubiquitina-Proteína Ligases/genética , Animais , Apoptose , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Movimento Celular , Proliferação de Células , Ciclina D1/genética , Progressão da Doença , Feminino , Humanos , Metástase Linfática , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Prognóstico , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
9.
Mol Cell ; 80(6): 1013-1024.e6, 2020 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-33338401

RESUMO

Impaired DNA crosslink repair leads to Fanconi anemia (FA), characterized by a unique manifestation of bone marrow failure and pancytopenia among diseases caused by DNA damage response defects. As a germline disorder, why the hematopoietic hierarchy is specifically affected is not fully understood. We find that reprogramming transcription during hematopoietic differentiation results in an overload of genotoxic stress, which causes aborted differentiation and depletion of FA mutant progenitor cells. DNA damage onset most likely arises from formaldehyde, an obligate by-product of oxidative protein demethylation during transcription regulation. Our results demonstrate that rapid and extensive transcription reprogramming associated with hematopoietic differentiation poses a major threat to genome stability and cell viability in the absence of the FA pathway. The connection between differentiation and DNA damage accumulation reveals a novel mechanism of genome scarring and is critical to exploring therapies to counteract the aplastic anemia for the treatment of FA patients.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Reprogramação Celular/genética , Anemia de Fanconi/genética , Formaldeído/toxicidade , Dano ao DNA/efeitos dos fármacos , Reparo do DNA/genética , Anemia de Fanconi/sangue , Anemia de Fanconi/patologia , Formaldeído/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Regulação da Expressão Gênica no Desenvolvimento/genética , Instabilidade Genômica/genética , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/efeitos dos fármacos , Humanos , Células K562 , Transcrição Gênica
10.
Sheng Li Xue Bao ; 72(6): 683-689, 2020 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-33349824

RESUMO

Here we perform a review on applications and funded projects at Division of Physiology and Integrative Biology in Department of Life Sciences sponsored by National Natural Science Foundation of China in the past ten years. Based on the research fields of applications and funded projects and the funding cost, we analyzed the sub-disciplines of the funded applications, key support areas, research frontiers and trends in the subjects of physiology and integrative biology, which gives us an insight into the future applications to optimize the layout of research areas in Division of Physiology and Integrative Biology.


Assuntos
Fundações , Disciplinas das Ciências Naturais , Biologia , China , Humanos
11.
Proc Natl Acad Sci U S A ; 117(52): 33436-33445, 2020 12 29.
Artigo em Inglês | MEDLINE | ID: mdl-33376220

RESUMO

Fanconi anemia (FA) is caused by defects in cellular responses to DNA crosslinking damage and replication stress. Given the constant occurrence of endogenous DNA damage and replication fork stress, it is unclear why complete deletion of FA genes does not have a major impact on cell proliferation and germ-line FA patients are able to progress through development well into their adulthood. To identify potential cellular mechanisms that compensate for the FA deficiency, we performed dropout screens in FA mutant cells with a whole genome guide RNA library. This uncovered a comprehensive genome-wide profile of FA pathway synthetic lethality, including POLI and CDK4 As little is known of the cellular function of DNA polymerase iota (Pol ι), we focused on its role in the loss-of-function FA knockout mutants. Loss of both FA pathway function and Pol ι leads to synthetic defects in cell proliferation and cell survival, and an increase in DNA damage accumulation. Furthermore, FA-deficient cells depend on the function of Pol ι to resume replication upon replication fork stalling. Our results reveal a critical role for Pol ι in DNA repair and replication fork restart and suggest Pol ι as a target for therapeutic intervention in malignancies carrying an FA gene mutation.


Assuntos
Replicação do DNA , DNA Polimerase Dirigida por DNA/metabolismo , Anemia de Fanconi/enzimologia , Estresse Fisiológico , Sistemas CRISPR-Cas/genética , Quinase 4 Dependente de Ciclina , Dano ao DNA , Genoma Humano , Células HCT116 , Humanos , Mutação/genética , Mutações Sintéticas Letais/genética , DNA Polimerase iota
12.
Nat Genet ; 52(11): 1178-1188, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33020667

RESUMO

Somatic mutations in driver genes may ultimately lead to the development of cancer. Understanding how somatic mutations accumulate in cancer genomes and the underlying factors that generate somatic mutations is therefore crucial for developing novel therapeutic strategies. To understand the interplay between spatial genome organization and specific mutational processes, we studied 3,000 tumor-normal-pair whole-genome datasets from 42 different human cancer types. Our analyses reveal that the change in somatic mutational load in cancer genomes is co-localized with topologically-associating-domain boundaries. Domain boundaries constitute a better proxy to track mutational load change than replication timing measurements. We show that different mutational processes lead to distinct somatic mutation distributions where certain processes generate mutations in active domains, and others generate mutations in inactive domains. Overall, the interplay between three-dimensional genome organization and active mutational processes has a substantial influence on the large-scale mutation-rate variations observed in human cancers.


Assuntos
Cromatina/química , Genoma Humano , Mutação , Neoplasias/genética , Linhagem Celular Tumoral , Cromossomos Humanos X/genética , Reparo de Erro de Pareamento de DNA , Análise Mutacional de DNA , DNA de Neoplasias , Conjuntos de Dados como Assunto , Feminino , Humanos , Masculino , Conformação Proteica , Domínios Proteicos , Dobramento de Proteína , Inativação do Cromossomo X
13.
Mikrochim Acta ; 187(11): 632, 2020 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-33128139

RESUMO

A sensitive molecularly imprinted fluorescent nanosensor based on zeolitic imidazolate frameworks-8 (ZIF-8) and upconversion nanoparticles (UCNPs) was developed for the determination of trace alpha-cypermethrin (α-CPM) for the first time. The sensor was synthesized by a layer-by-layer self-assembly strategy. UCNPs with a maximum emission wavelength of 544.5 nm under 980 nm excitation were firstly prepared as the luminous core. Then, ZIF-8 with the large specific surface and porosity was introduced, which not only improved the mass transfer and adsorption capacity of the sensor but also increased the fluorescence intensity of UCNPs as a protective layer. Finally, molecularly imprinted polymers (UCNPs@ZIF-8@MIPs) were fabricated in mixed solutions containing UCNPs@ZIF-8 (support material), α-CPM (template), acrylamide (functional monomer), and divinylbenzene (cross-linker). Under the optimal condition, the fluorescence intensity of UCNPs@ZIF-8@MIP was linearly quenched with increasing concentration of α-CPM in the range 0.10-12 mg L-1 with a detection limit of 0.03 mg L-1 (S/N = 3). The developed UCNPs@ZIF-8@MIP probe was used to detect α-CPM in real samples; the satisfactory results obtained were consistent with those obtained by GC-MS.Graphical abstract.


Assuntos
Corantes Fluorescentes/química , Estruturas Metalorgânicas/química , Impressão Molecular , Nanoestruturas/química , Piretrinas/química , Análise de Alimentos , Contaminação de Alimentos , Frutas/química , Inseticidas/química , Limite de Detecção , Verduras/química , Difração de Raios X
14.
Med Sci Monit ; 26: e922139, 2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32419697

RESUMO

BACKGROUND Glutamate (GLU) is the most excitatory amino acid in the central nervous system and plays an important role in maintaining the normal function of the nervous system. During cerebral ischemia, massive release of GLU leads to neuronal necrosis and apoptosis. It has been reported that dexmedetomidine (DEX) possesses anti-oxidant and anti-apoptotic properties. The objective of this study was to investigate the effects of DEX on GLU-induced neurotoxicity in PC12 cells. MATERIAL AND METHODS PC12 cells were treated with 20 mM GLU to establish an ischemia-induced injury model. Cell viability was accessed by MTT assay. MDA content and SOD activity were analyzed by assay kits. Apoptosis rate, ROS production, intracellular Ca²âº concentration, and MMP were evaluated by flow cytometry. Western blot analysis was performed to analyze expressions of caspase-3, caspase-9, cyt-c, bax, and bcl-2. RESULTS PC12 cells treated with GLU exhibited reduced cell viability and increased apoptosis rates, which were ameliorated by pretreatment with DEX. DEX significantly increased SOD activity, reduced content of MDA, and decreased production of ROS in PC12 cells. In addition, DEX clearly reduced the level of intracellular Ca²âº and attenuated the decline of MMP. Moreover, DEX notably reduced expressions of caspase-3, caspase-9, cyt-c, and bax and increased expression of bcl-2. CONCLUSIONS Our findings suggest that DEX can protect PC12 cells against GLU-induced cytotoxicity, which may be attributed to its anti-oxidative property and reduction of intracellular calcium overload, as well as its ability to inhibit the mitochondria-mediated apoptotic pathway.


Assuntos
Apoptose/efeitos dos fármacos , Dexmedetomidina/farmacologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Animais , Apoptose/fisiologia , Sobrevivência Celular/efeitos dos fármacos , Citocromos c/metabolismo , Dexmedetomidina/metabolismo , Glucose/metabolismo , Ácido Glutâmico/efeitos adversos , Ácido Glutâmico/metabolismo , Ácido Glutâmico/farmacologia , Mitocôndrias/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Células PC12 , Substâncias Protetoras/farmacologia , Ratos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos
15.
Innate Immun ; 26(6): 505-513, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32456598

RESUMO

Allergic rhinitis (AR) is a nasal mucosal inflammatory disease mediated by environmental allergens. At present, the relationship between the IL-33/ST2 axis, ERK1/2 pathway and AR progression needs further exploration. In our study, an AR model was constructed in vitro by treating HNEpC cells with Der p1. qRT-PCR was applied to assess the mRNA levels of IL-33, ST2, TNF-α, IL-6, and IL-8. Western blotting was used to measure the protein levels of IL-33, ST2, and the downstream proteins p-ERK1/2, ERK1/2, p-RSK, and RSK. IL-6, IL-8, IL-33, and TNF-α protein levels in cell supernatants were evaluated by ELISA. Flow cytometry was performed to check cell apoptosis of HNEpC in the presence or absence of Der p1. Our results indicate that the relative levels of IL-33, ST2, TNF-α, IL-6, and IL-8 were increased significantly in the AR model group. The above effects were notably reversed after transfection with shIL-33 or shST2. IL-33 stimulation further resulted in the increase in both ST2 and inflammation-associated cytokines, and these effects were restored after shST2 treatment. Also, the levels of inflammatory factors induced by IL-33 stimulation or ST2 overexpression were reversed after applying an ERK1/2 pathway blocker. In conclusion, IL-33/ST2 mediated inflammation of nasal mucosal epithelial cells by inducing the ERK1/2 pathway.


Assuntos
Antígenos de Dermatophagoides/imunologia , Proteínas de Artrópodes/imunologia , Cisteína Endopeptidases/imunologia , Células Epiteliais/imunologia , Inflamação/imunologia , Proteína 1 Semelhante a Receptor de Interleucina-1/metabolismo , Interleucina-33/metabolismo , Mucosa Nasal/imunologia , Rinite Alérgica/imunologia , Apoptose , Células Cultivadas , Citocinas/metabolismo , Progressão da Doença , Humanos , Mediadores da Inflamação/metabolismo , Proteína 1 Semelhante a Receptor de Interleucina-1/genética , Interleucina-33/genética , Sistema de Sinalização das MAP Quinases , RNA Interferente Pequeno/genética
16.
Cell Rep ; 30(4): 1235-1245.e4, 2020 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-31995761

RESUMO

DNA-protein crosslinks (DPCs) are a frequent form of DNA lesion and are strongly inhibitive in diverse DNA transactions. Despite recent developments, the biochemical detection of DPCs remains a limiting factor for the in-depth mechanistic understanding of DPC repair. Here, we develop a sensitive and versatile assay, designated ARK, for the quantitative analysis of DPCs in cells. ARK uses sequential chaotropic and detergent-based isolation of DPCs and substantially enhances sample purity, resulting in a 5-fold increase in detection sensitivity and a 10-fold reduction in background reading. We validate the ARK assay with genetic mutants with established deficiencies in DPC repair and demonstrate its robustness by using common DPC-inducing reagents, including formaldehyde, camptothecin, and etoposide. In addition, we show that the Fanconi anemia pathway contributes to the repair of DPCs. Thus, ARK is expected to facilitate various studies aimed at understanding both fundamental biology and translational applications of DNA-protein crosslink repair.


Assuntos
Reagentes de Ligações Cruzadas/farmacologia , Proteínas de Ligação a DNA/metabolismo , DNA/metabolismo , Camptotecina/farmacologia , Reparo do DNA/genética , Etoposídeo/farmacologia , Anemia de Fanconi/genética , Anemia de Fanconi/metabolismo , Técnicas de Inativação de Genes , Técnicas Genéticas , Células HeLa , Humanos , Inibidores da Topoisomerase I/farmacologia
17.
RSC Adv ; 10(9): 5443-5453, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-35498275

RESUMO

The discharge of industrial printing and dyeing wastewater is one of the main reasons for the increasing water shortage and deterioration. The treatment of dyestuff wastewater is an issue and needs to be urgently solved. In this work, anionic ionic liquid functional covalent organic materials (COMs) were firstly synthesized and used for the selective adsorption of cationic dyes. First, a series of sulfonic acid group (SO3H)-functionalized anionic TpPa-SO3, TpBd-(SO3)2, and TpCR-(SO3)2 were prepared, respectively, and then imidazole was grafted onto TpBd-(SO3)2 to obtain ImI@TpBd-(SO3)2. The full characterization using X-ray diffraction, FT-IR spectroscopy, 13C cross-polarization magic-angle spinning NMR spectroscopy, zeta-potentials, BET surface and pore analysis indicated that these COMs and ImI@TpBd-(SO3)2 exhibited different morphologies, porosities, and potentials. The effects of the type of dye, adsorption time, initial dye concentration, and pH on the adsorption of dyes on ImI@TpBd-(SO3)2 were systematically investigated, respectively. The results revealed that ImI@TpBd-(SO3)2 possessed good adsorption performance for nine different cationic dyes with adsorption capacities in the range from 2865.3 mg g-1 for methylene blue (MB) to 597.9 mg g-1 for basic orange 2 (BO), but little adsorption for anionic and neutral dyes, revealing charge selectivity. The adsorption ratio of ImI@TpBd-(SO3)2 for MB was as high as 74.0% at 10 min by using 1.0 mg material, owing to the post modification of TpBd-(SO3)2 with imidazole. The adsorption of MB on ImI@TpBd-(SO3)2 was pH dependent. The adsorption isotherm and kinetics fitted well with the Freundlich and pseudo second-order kinetic model, respectively. Finally, the very outstanding advantages of superior selective adsorption, desorption, convenient preparation, and low density of ImI@TpBd-(SO3)2 predicted its research and application potential in dye wastewater recovery.

18.
Onco Targets Ther ; 12: 10569-10578, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31819536

RESUMO

BACKGROUND: Recent studies revealed that long non-coding RNAs (lncRNA) play crucial roles in cancer initiation and progression. However, the function and underlying mechanism of lncRNAs in triple-negative breast cancer (TNBC) are little investigated. METHODS: qRT-PCR was used to investigate LINC00096 expression in TNBC tissues and cells. Function assays were used to test the effects of LINC00096 on TNBC cells progression. In addition, luciferase reporter and qRT-PCR assays were used to determine the underlying mechanism of LINC00096 on TNBC progression. RESULTS: In our present study, we identify LINC00096 as one of the most upregulated lncRNA in TNBC progression by using microarray screening. High LINC00096 expression was obviously related to advanced tumor stage, metastasis, poor prognosis of patients. Loss-of-function assays showed that LINC00096 suppression reduced TNBC cells proliferation and invasive abilities in vitro. Mechanistically, we demonstrated that LINC00096 directly interacted with miR-383-5p, subsequently acted as a miRNA sponge to increase RBM3 expression. CONCLUSION: In the present study, we indicated that LINC00096 might promote the proliferation and invasion through regulating the miR-383-5p/RBM3 pathway in TNBC, which providing a novel therapeutic target for cancer treatment.

19.
J Nanosci Nanotechnol ; 18(2): 951-958, 2018 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-29448519

RESUMO

We found that the peroxidase-like activity of gold nanoparticles (GNPs) followed the Michaelis-Menten kinetic model and was dependent on environmental pH and temperature, which was very similar to natural Horseradish Peroxidase (HRP). However, unlike HRP, which needs a lower H2O2 concentration with a very narrow range to reach a maximum reaction rate and avoid enzyme poisoning, GNPs have very high activity, even at an H2O2 concentration two orders of magnitude higher than HRP. It was demonstrated that H2O2 treatment could enhance the peroxidase-like activity of GNPs, resulting thus in the activity increase in a circular catalytic reaction by the reduplicative use of GNPs. It was also found that the peroxidase-like activity of GNPs responded sensitively to nanoparticle size and surface modifications. When used in an immunoassay, GNPs were generally conjugated with antibody and blocked with hydrophilic macromolecules to construct a nanoprobe. This strongly reduced the peroxidase-like activity and detection sensitivity of GNPs, therefore, restricting their use as peroxidase mimetics. We presented a novel strategy that combined the nanoprobes with gold staining to expose fresh catalytic gold surfaces and obtained a great increase in detection sensitivity.

20.
Sci Rep ; 7(1): 18023, 2017 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-29269783

RESUMO

The uplift of the Tibetan Plateau (TP) significantly affected both regional and global climates. Although there is evidence that the Tibetan Plateau experienced uplift during the Quaternary, the timing and amplitude are poorly constrained. However, the increased availability of long sedimentary records of vegetation change provides an opportunity to reconstruct the timing of the uplift. Here, we present a well-dated, high-resolution pollen record for the last 2.6 Ma from the Yinchuan Basin, which was incised by the Yellow River with its source in the northeastern Tibetan Plateau. Variations in the Artemisia/Chenopodiaceae (A/C) ratio of the reveal changes in moisture conditions in the Yinchuan Basin during glacial-interglacial cycles, as well as a gradual long-term aridification trend which is consistent with progressive global cooling. However, fluctuations in the percentages of Picea and Abies differ from those of the A/C ratio and we propose that they reflect changes in the vegetation and environment of high elevation areas. The Picea and Abies records reveal two phases of increased representation, at 2.1 and 1.2 Ma, which may indicate phases in the uplift of the northeastern Tibetan Plateau. Thus, they provide independent evidence for the timing of the uplift of the Tibetan Plateau during the Quaternary.


Assuntos
Clima , Fenômenos Geológicos , Pólen , China , Tibet
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