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1.
PLoS One ; 19(5): e0299838, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38771815

RESUMO

BACKGROUND: Fertility intentions, as a direct driver of fertility behavior, play an important role in the implementation of national fertility policy and population development. This study explored the influencing factors of college teachers' second child fertility intentions in Jinan, China on the basis of TPB. METHODOLOGY/PRINCIPAL FINDINGS: Based on the theory of planned behavior, this paper employs basic characteristics analysis, difference analysis, and factor analysis related to the fertility intentions of the participants. Analysis found participants between 31 and 40 years old had the highest second child fertility intentions, and participants with a college-age first child had the lowest second child fertility intentions. Attitude and subjective norms had a positive impact on second child fertility intentions, and policy awareness had a positive impact on attitude, which indirectly affected second child fertility intentions. Subjective norms had the greatest influence on second child fertility intentions, followed by attitude, and policy awareness had the least influence on second child fertility intentions. SIGNIFICANCE/FUTURE RESEARCH: The findings of this paper can enrich the theoretical research on fertility intentions, and also provide more optimal practical references for the formulation and propagation of China's fertility policy as well as the improvement of the division of family roles in China. Future research can further explore the impact of fertility policy on the fertility intentions of other groups.


Assuntos
Fertilidade , Intenção , Humanos , China , Adulto , Feminino , Masculino , Universidades , Atitude , Adulto Jovem
2.
Mol Cancer ; 23(1): 46, 2024 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-38459592

RESUMO

Nucleic acid vaccines have shown promising potency and efficacy for cancer treatment with robust and specific T-cell responses. Improving the immunogenicity of delivered antigens helps to extend therapeutic efficacy and reduce dose-dependent toxicity. Here, we systematically evaluated chemokine-fused HPV16 E6/E7 antigen to improve the cellular and humoral immune responses induced by nucleotide vaccines in vivo. We found that fusion with different chemokines shifted the nature of the immune response against the antigens. Although a number of chemokines were able to amplify specific CD8 + T-cell or humoral response alone or simultaneously. CCL11 was identified as the most potent chemokine in improving immunogenicity, promoting specific CD8 + T-cell stemness and generating tumor rejection. Fusing CCL11 with E6/E7 antigen as a therapeutic DNA vaccine significantly improved treatment effectiveness and caused eradication of established large tumors in 92% tumor-bearing mice (n = 25). Fusion antigens with CCL11 expanded the TCR diversity of specific T cells and induced the infiltration of activated specific T cells, neutrophils, macrophages and dendritic cells (DCs) into the tumor, which created a comprehensive immune microenvironment lethal to tumor. Combination of the DNA vaccine with anti-CTLA4 treatment further enhanced the therapeutic effect. In addition, CCL11 could also be used for mRNA vaccine design. To summarize, CCL11 might be a potent T cell enhancer against cancer.


Assuntos
Vacinas Anticâncer , Neoplasias , Proteínas Oncogênicas Virais , Vacinas contra Papillomavirus , Vacinas de DNA , Animais , Camundongos , Vacinas Baseadas em Ácido Nucleico , Vacinas de DNA/genética , Vacinas contra Papillomavirus/genética , Neoplasias/genética , Neoplasias/terapia , Linfócitos T CD8-Positivos , Proteínas E7 de Papillomavirus/genética , Proteínas Oncogênicas Virais/genética , Camundongos Endogâmicos C57BL , Microambiente Tumoral
3.
ChemSusChem ; 16(17): e202300377, 2023 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-37140478

RESUMO

The development of sustainable and efficient C1 substitution methods is of central interest for organic synthesis and pharmaceuticals production, the methylation motifs bound to a carbon, nitrogen, or oxygen atom widely exist in natural products and top-selling drugs. In the past decades, a number of methods involving green and inexpensive methanol have already been disclosed to replace industrial hazardous and waste-generating C1 source. Among the various efforts, photochemical strategy is considered as a "renewable" alternative that shows great potential to selectively activate methanol to achieve a series of C1 substitutions at mild conditions, typically C/N-methylation, methoxylation, hydroxymethylation, and formylation. Herein the recent advances in selective transformation of methanol to various C1 functional groups via well-designed photochemical systems involving different types of catalysts or not is systematically reviewed. Both the mechanism and corresponding photocatalytic system were discussed and classified on specific methanol activation models. Finally, the major challenges and perspectives are proposed.

4.
Toxicol Res (Camb) ; 11(4): 662-672, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36051660

RESUMO

Background: Radioprotectors safeguard biological system exposed to ionizing radiation (IR) by protecting normal cells from radiation damage during radiotherapy. Due to the toxicity and limited clinical utility of the present radioprotectors, it prompts us to identify novel radioprotectors that could alleviate IR-induced cytotoxicity of normal tissues. Aims and Methods: To identify new radioprotectors, we screened a chemical molecular library comprising 253 compounds in normal human fibroblasts (HFs) or 16HBE cells upon IR by CCK-8 assays and clonogenic survival assays. Fasudil was identified as a potential effective radioprotector. Results: The results indicated that Fasudil exerts radioprotective effects on HFs against IR-induced DNA double-strand breaks (DSBs) through the regulation of DSB repair. Fasudil increased homologous recombination (HR) repair by 45.24% and decreased non-homologous end-joining (NHEJ) by 63.88% compared with untreated cells, without affecting changes to cell cycle profile. We further found that fasudil significantly facilitated the expression and foci formation of HR core proteins such as Rad51 and BRCA1 upon IR, and decreased the expression of NHEJ-associated proteins such as DNA-PKcs at 24 h post-IR. Conclusion: Our study identified fasudil as a novel radioprotector that exert radioprotective effects on normal cells through regulation of DSB repair by promoting HR repair.

5.
PLoS One ; 17(9): e0274620, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36108080

RESUMO

Although electroacupuncture (EA) has been shown to be effective in the treatment of stroke, its mechanisms of action remain undefined. This study explored the therapeutic effects of EA in rats with cerebral ischemia-reperfusion injury (CIRI) and evaluated its possible mechanisms in promoting angiogenesis. To evaluate the effect of EA, we used 2, 3, 5-Triphenyl-2H-Tetrazolium Chloride (TTC) staining and behavior score to calculate the cerebral infarct volume and neurological deficit score after CIRI. Western blot (WB) analysis was employed to evaluate the expression of cluster of differentiation 34 (CD34), erythropoietin (EPO), vascular endothelial growth factor (VEGF) and phospho-Src (p-Src) in the brain of the rats with CIRI. On the other hand, we established an oxygen-glucose deprivation/reoxygenation (OGD/R) injury model using brain microvascular endothelial cells (BMECs), and analyzed cell viability and expression of VEGF or p-Src using cell counting kit-8 (CCK-8) and WB, respectively. Our data showed that EA at the GV26 acupoint could significantly promote the expression of CD34, EPO, VEGF and p-Src in CIRI rats. Our CCK-8 results demonstrated that intervention with recombinant EPO and VEGF proteins remarkably improved the viability of BMECs after OGD/R, while a Src inhibitor, PP1, reversed this phenotype. The WB results showed that the recombinant EPO protein increased the expression of VEGF and p-Src, which was significantly inhibited by PP1. Taken together, our findings showed that EA at the GV26 acupoint can significantly attenuate ischemic injury after stroke and promote angiogenesis via activation of EPO-mediated Src and VEGF signaling pathways. Besides, the upregulation of VEGF may also be associated with the activation of Src by EPO.


Assuntos
Eletroacupuntura , Eritropoetina , Traumatismo por Reperfusão , Acidente Vascular Cerebral , Animais , Cloretos/metabolismo , Células Endoteliais/metabolismo , Eritropoetina/metabolismo , Glucose/metabolismo , Isquemia/metabolismo , Oxigênio/metabolismo , Ratos , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/terapia , Transdução de Sinais , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/metabolismo , Acidente Vascular Cerebral/terapia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fatores de Crescimento do Endotélio Vascular/metabolismo
6.
J Agric Food Chem ; 70(27): 8254-8263, 2022 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-35758304

RESUMO

Platelet chemokines play well-established roles in the atherosclerotic inflammation. Cyanidin-3-O-ß-glucoside (Cy-3-g) is one of the main bioactive compounds in anthocyanins, but its effects on chemokines during atherosclerosis have not been determined yet. In the present study, ApoE-/- mice were fed on the chow diet, high-fat diet (HFD), and HFD-supplemented Cy-3-g at 200, 400, and 800 mg/kg diet. After 16 weeks, Cy-3-g significantly alleviated the atherosclerotic lesion and inhibited platelet aggregation and activation. Moreover, Cy-3-g significantly reduced inflammatory chemokines CXCL4, CXCL7, CCL5, CXCL5, CXCL12, and CCL2 in plasma and downregulated CXCR4, CXCR7, and CCR5 on platelets and peripheral blood mononuclear cells. Besides, Cy-3-g decreased the mRNA of TNFα, IFNγ, ICAM-1, VCAM-1, CD68, MMP7, CCL5, CXCR4, and CCR5 in the aorta of mice. Therefore, it suggests that Cy-3-g plays important preventive roles in the process of atherosclerosis via attenuating chemokines and receptors in ApoE-/- mice.


Assuntos
Antocianinas , Aterosclerose , Animais , Antocianinas/farmacologia , Apolipoproteínas E/genética , Aterosclerose/tratamento farmacológico , Aterosclerose/genética , Quimiocinas/genética , Glucosídeos/farmacologia , Inflamação , Leucócitos Mononucleares , Camundongos , Camundongos Endogâmicos C57BL
7.
Zhongguo Dang Dai Er Ke Za Zhi ; 24(3): 309-313, 2022 Mar 15.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-35351263

RESUMO

OBJECTIVES: To investigate the mutation rate of the RAS gene and its clinical significance in children with acute lymphoblastic leukemia. METHODS: A retrospective analysis was performed on the medical data of 120 children with newly diagnosed acute lymphoblastic leukemia, who were admitted to the Third Affiliated Hospital of Zhengzhou University from January 2015 to January 2020 and underwent next-generation sequencing. The clinical and molecular features were analyzed. The impact of RAS gene mutation on the overall survival rate was evaluated in these children. RESULTS: Among the 120 children, 35 (29.2%) had RAS gene mutation, 30 (25.0%) had KRAS gene mutation, and 5 (4.2%) had both NRAS and KRAS gene mutations. All NRAS mutations and 71% (25/35) of KRAS mutations were located at the 12th and 13th codons. RAS gene mutation was detected in 35 (33.3%) out of 105 children with B-lineage acute lymphoblastic leukemia, but it was not detected in those with acute T lymphocyte leukemia. Of all the children, 11 (9.2%) were lost to follow-up, and among the 109 children followed up, 16 (14.7%) died. The children with RAS gene mutation had a significantly lower 2-year overall survival rate than those without RAS gene mutation (P<0.05). The prognosis of children with RAS gene mutation combined with WT1 overexpression and WBC>50×109/L at diagnosis was worse (P<0.05). CONCLUSIONS: RAS gene mutation is commonly observed in children with B-lineage acute lymphoblastic leukemia and may have an adverse effect on prognosis.


Assuntos
Genes ras , Leucemia-Linfoma Linfoblástico de Células Precursoras , Criança , Humanos , Mutação , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Prognóstico , Estudos Retrospectivos
8.
Vaccines (Basel) ; 10(3)2022 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-35335039

RESUMO

SARS-CoV-2 spike (S) variants that may evade antibody-mediated immunity are emerging. Evidence shows that vaccines with a stronger immune response are still effective against mutant strains. Here, we report a targeted type 1 conventional dendritic (cDC1) cell strategy for improved COVID-19 vaccine design. cDC1 cells specifically express X-C motif chemokine receptor 1 (Xcr1), the only receptor for chemokine Xcl1. We fused the S gene sequence with the Xcl1 gene to deliver the expressed S protein to cDC1 cells. Immunization with a plasmid encoding the S protein fused to Xcl1 showed stronger induction of antibody and antigen-specific T cell immune responses than immunization with the S plasmid alone in mice. The fusion gene-induced antibody also displayed more powerful SARS-CoV-2 wild-type virus and pseudovirus neutralizing activity. Xcl1 also increased long-lived antibody-secreting plasma cells in bone marrow. These preliminary results indicate that Xcl1 serves as a molecular adjuvant for the SARS-CoV-2 vaccine and that our Xcl1-S fusion DNA vaccine is a potential COVID-19 vaccine candidate for use in further translational studies.

9.
World Neurosurg ; 161: e355-e362, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35134576

RESUMO

BACKGROUND: Gliomas are the most common primary malignant tumor of the central nervous system. At the present time, radiotherapy (RT) is the cornerstone of therapeutic approaches, but the worldwide research trends in RT for gliomas in the world are unclear. This bibliometric analysis aimed to investigate trends in glioma RT research since 2011. METHODS: The Web of Science database was searched, and SigmaPlot 14.0 and VOSviewer software were used to analyze and visualize the trends. RESULTS: Bibliometric analysis of 5106 articles was conducted. While the number of publications per year was relatively steady, the number of citations grew exponentially from 356 in 2011 to 21,051 in 2020. Articles originated from 89 countries, with the majority from the United States. Journal of Neuro-Oncology and Texas A&M University were the journal and institution, respectively, with the highest number of publications. The articles mainly involved oncology, neurology, radiology, and surgery. CONCLUSIONS: This bibliometric analysis found an increased focus on glioblastoma, survival, and chemotherapy in glioma RT research.


Assuntos
Glioblastoma , Glioma , Radioterapia (Especialidade) , Radiologia , Bibliometria , Glioma/radioterapia , Humanos
10.
Aquat Toxicol ; 244: 106106, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35131552

RESUMO

Diuron is one of the most widely used herbicides worldwide. It has been widely detected in various aquatic environments, especially in marine ecosystems. Although direct effects of diuron exposure on various organisms have been reported, little is known about its effects on marine fishes including multigenerational effects. Herein, the filial generation (F1) of diuron-exposed marine medaka (Oryzias melastigma) (F0) was raised in clean seawater from fertilized eggs to adulthood and used as a marine fish model to study the potential multigenerational effects of diuron. We found that the successful hatching of F1 larvae was significantly reduced and that ovarian development in F1 females was retarded. A significant increase in the percentage of previtellogenic oocytes, along with a visual decrease in the percentage of vitellogenic and mature oocytes in the F1 ovary, were observed. The hormone levels of the hypothalamus-pituitary-gonad-liver axis and vitellogenin-related transcription were downregulated. In addition, the mRNA levels of DNA methyltransferase in the brain, ovary and liver of F1 adult fish exhibited significant upregulation, suggesting that the probable underlying multigenerational mechanism might be associated with epigenetic modifications. Taken together, these results demonstrated that chronic environmental diuron exposure in F0 marine medaka can inhibit F1 ovary development and suggested that diuron may affect marine fish thriving in the ocean.


Assuntos
Oryzias , Poluentes Químicos da Água , Animais , Diurona , Ecossistema , Feminino , Ovário/química , Poluentes Químicos da Água/toxicidade
11.
Trials ; 23(1): 152, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-35168637

RESUMO

BACKGROUND: Insomnia is a common sleep-related condition that includes dissatisfaction with sleep quality, difficulty in initiating or maintaining sleep, and early morning waking. Insomnia can affect daytime functioning by causing fatigue, depression, and anxiety. Medications are the most common method for the management of insomnia but can cause adverse effects, including psychological and physical dependence, residual daytime sedation, and cognitive impairment. Acupuncture is a common traditional Chinese therapy. It has been used in the treatment of insomnia, depression, and anxiety in China. However, there are no high-quality studies focusing on acupuncture for insomnia, especially for depression and anxiety due to insomnia. Therefore, we have designed a randomized controlled trial (RCT) involving a placebo control to ensure blinding of participants to investigate the effects of acupuncture on insomnia in improving sleep quality and psychosocial symptoms. METHODS: We have designed a single-center, parallel-group, single-blinded RCT. A total of 252 participants who meet the eligibility criteria will be randomly allocated into a manual acupuncture group or sham acupuncture group in a 1:1 ratio. All participants will receive 24 sessions of acupuncture (30 min per session, three sessions per week for 8 weeks). Participants will be assessed using the Pittsburgh Sleep Quality Index score, self-assessment anxiety scale, self-assessment depression scale, and Medical Outcomes Study 36-Item Short-Form Health Survey at baseline and 8 weeks. All analyses will be based on an intention-to-treat principle. The results will be published in an international peer-reviewed journal. DISCUSSION: The results of this study are expected to clarify the effects of acupuncture on sleep quality and psychosocial symptoms in patients with insomnia. This will contribute to the clinical practice of acupuncture in the management of insomnia. TRIAL REGISTRATION: Chinese Clinical Trail Registry ChiCTR2100049172 . Registered on 24 July 2021.


Assuntos
Terapia por Acupuntura , Distúrbios do Início e da Manutenção do Sono , Terapia por Acupuntura/efeitos adversos , Ansiedade/diagnóstico , Ansiedade/terapia , Humanos , Avaliação de Resultados em Cuidados de Saúde , Ensaios Clínicos Controlados Aleatórios como Assunto , Sono , Distúrbios do Início e da Manutenção do Sono/diagnóstico , Distúrbios do Início e da Manutenção do Sono/terapia , Resultado do Tratamento
12.
Drug Chem Toxicol ; 45(1): 61-69, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31476926

RESUMO

The mechanisms by which cigarette smoke (CS) exposure has a detrimental effect on the male reproductive system is still not fully understood. We aimed to elucidate the role of cigarette smoke-induced injury by the Fas/FasL pathway by using a Sprague-Dawley rat model of cigarette smoking exposure. Here, 200 rats were randomaly divided into five groups with different smoking exposure durations. Forty animals per group were further divided into four groups: a control group, and groups exposed to cigarette smoke at doses of 10, 20 or 30 cigarettes/day. The testes were harvested and the effects of CS exposure on the testis were characterized on the basis of morphological changes, oxidative stress, and a significant elevation in the expression of FAS/FASL pathway related genes, such as FAS, FASL, FADD, caspase 8 and caspase 3. Oxidative stress was reflected by significant time-dependent changes in SOD and GSH-Px activity, and MDA content. Taken together, our data suggest that CS exposure induces testis injury, which is related to the increased oxidative stress and activation of the FAS/FASL apoptotic pathway in the testes.


Assuntos
Poluição por Fumaça de Tabaco , Animais , Apoptose , Masculino , Estresse Oxidativo , Ratos , Ratos Sprague-Dawley , Fumaça , Testículo/metabolismo
13.
Nanoscale ; 13(16): 7792-7800, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33876171

RESUMO

Zeolitic octahedral metal oxides (ZOMOs) are fully inorganic crystalline materials, mostly containing transition metals, and possess a defined framework as well as regular hollow channels. Therefore, they have significant application potential in many fields, particularly catalysis. Herein, we report the synthesis and characterization of zeolitic octahedral niobium oxides (ZOMO-NbOx) and the framework was made of {NbOx} polyhedra ({NbO6} octahedron and {Nb6O27} pentagon units). Microchannels consisting of 7-membered rings with ∼0.4 nm diameter were realized, and rarely reported plural {Nb6O27} units including dimers, trimers, and tetramers were discovered. Owing to the continuous hollow microporous structure that provides a large surface area as well as a shortened transfer path for charge carriers from bulk to the surface, considerably enhanced activities beyond pristine Nb2O5 were achieved towards photocatalytic H2 evolution from (saline) water. The results show a practical case of solo-Nb-based zeolitic materials, which expand the ZOMO family and provide further insights into the design and synthesis of efficient zeolitic semiconductors for artificial photocatalysis.

14.
Nanoscale ; 13(8): 4444-4450, 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33586716

RESUMO

The development of cost-effective and high-performance catalysts for the production of hydrogen via electrocatalytic water splitting is crucial for meeting the increasing energy demand and expanding the hydrogen economy. In this study, a series of metal-free carbon nanotube (CNT) catalysts were designed and in situ functionalized by imidazolium ionic liquids (ILs) for enhanced electrocatalytic hydrogen evolution reaction (HER). The theoretical calculations and experimental results reveal that the functionalization of CNTs with imidazolium ILs facilitated the electron transfer process and exhibited superior hydrogen adsorption, thereby enhancing the performance of the HER. In particular, CNT-IM-Cl displays excellent electrocatalytic activity and shows a low onset overpotential and Tafel slope of 80 mV and 38 mV dec-1, respectively. This study highlights the significant potential of IL in situ functionalized metal-free CNTs for the electrocatalytic HER and provides insight into the structure design of highly efficient electrocatalysts.

15.
Sci Rep ; 10(1): 9868, 2020 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-32555320

RESUMO

The function of Latexin (LXN) in inflammation has attracted attention. However, no data are available regarding its role in colitis. We report that LXN is a suppressor of colitis. LXN deficiency leads to the severity of colitis in DSS-induced mice, and LXN is required for the therapeutic effect of retinoic acid on colitis. Using a proteomics approach, we demonstrate that LXN interacts and forms a functional complex with HECTD1 (an E3 ubiquitin ligase) and ribosomal protein subunit3 (Rps3). IκBα is one of the substrates of HECTD1. Ectopic expression of LXN leads to IκBα accumulation in intestinal epithelial cells, however, LXN knockdown enhances the interaction of HECTD1 and Rps3, contributing to the ubiquitination degradation of IκBα, and subsequently enhances inflammatory response. Thus, our findings provided a novel mechanism underlying LXN modulates colitis via HECTD1/Rps3/NF-κB pathway and significant implications for the development of novel strategies for the treatment of colitis by targeting LXN.


Assuntos
Colite/genética , Colite/patologia , Técnicas de Inativação de Genes , Proteínas do Tecido Nervoso/deficiência , Proteínas do Tecido Nervoso/genética , Transdução de Sinais/genética , Regulação para Cima , Sequência de Aminoácidos , Animais , Linhagem Celular , Humanos , Inflamação/genética , Inflamação/patologia , Camundongos , Inibidor de NF-kappaB alfa/metabolismo , NF-kappa B/metabolismo , Proteínas Ribossômicas/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Ubiquitina-Proteína Ligases/química , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação
16.
J Toxicol Pathol ; 32(4): 223-232, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31719749

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is a disorder of the liver found worldwide. The molecular mechanisms underlying NAFLD initiation and progression, however, remain poorly understood. In this study, fluorescence difference gel electrophoresis (DIGE) combined with mass spectrometry was performed to profile the intracellular processes in the rat liver at the proteome level when rats were fed a high-fat diet for 8 weeks. Dynamic changes of 27 protein spots were observed. Among them, upregulation of 14 spots and downregulation of 13 spots were observed during the eight weeks of the high fat diet-induction period. These spots were analyzed by matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry (MALDI-TOF/TOF), and ultimately 24 proteins were identified with more than 95% confidence. Gene ontology (GO) annotation indicated that these proteins were implicated in the metabolism of carbohydrates, lipids, and amino acids. Four proteins were validated by western blot. Further functional studies on these dynamically changing proteins may lead to a better understanding of the mechanisms of high fat diet-induced fatty liver disease.

17.
Int Immunopharmacol ; 69: 1-10, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30660871

RESUMO

Cyanidin-3-O-ß-glucoside (Cy-3-g), a typical and abundant monomer of anthocyanins, exhibits a variety of biological activities, such as anti-atherosclerosis, anti-obesity, and anticancer effects. However, to date little is known about its effects on asthma. This study aimed to investigate the efficacy of dietary Cy-3-g on allergic asthma in an animal model. BALB/c mice were sensitized and challenged with ovalbumin (OVA) to induce allergic asthma. The pathological changes of the lung tissues, type 2 helper (Th2)-associated cytokine production in bronchoalveolar lavage fluid (BALF), and the interleukin 4 receptor alpha (IL-4Rα)-signal transducer and activator of transcription 6 (STAT6) signaling pathway activities were assessed. We found that Cy-3-g significantly inhibited OVA-induced inflammatory cell infiltration and mucus hyper-production in lung tissues, reduced the production of interleukin 4 (IL-4), interleukin 5 (IL-5) and interleukin 13 (IL-13) in BALF. Furthermore, Cy-3-g effectively suppressed OVA-induced up-regulation of the IL-4Rα-STAT6 signaling pathway activity of the lung tissues. These results demonstrated that dietary Cy-3-g could attenuate allergic airway inflammation in a murine asthma model, and Cy-3-g might be used as an agent for asthma prevention and/or treatment in the future.


Assuntos
Antocianinas/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Asma/tratamento farmacológico , Glucosídeos/uso terapêutico , Pulmão/imunologia , Hipersensibilidade Respiratória/tratamento farmacológico , Alérgenos/imunologia , Animais , Citocinas/metabolismo , Suplementos Nutricionais , Modelos Animais de Doenças , Feminino , Humanos , Pulmão/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/imunologia , Receptores de Superfície Celular/metabolismo , Fator de Transcrição STAT6/metabolismo , Células Th2/imunologia
18.
Eur J Pharmacol ; 838: 23-31, 2018 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-30194942

RESUMO

Vine tea has been used as a medicinal herb in traditional Chinese medicine for hundreds of years. As the most abundant ingredient in vine tea, Dihydromyricetin (DHM) has been reported to exert anti-inflammatory, antioxidant, and anti-cardiovascular disease. However, the role of DHM in injury-induced neointimal formation remains poorly characterized. We determined the effects of DHM on ligation-induced carotid artery neointimal formation. We found that ligation-induced carotid artery neointimal formation could be significantly attenuated by DHM treatment. We provide evidence that DHM increases orphan nuclear receptor TR3 expression in smooth muscle cell (SMC) and carotid artery. Moreover, overexpression and loss-of-function strategies of TR3 were done to overexpression and knockdown of TR3, and demonstrate that DHM promotes SMC differentiation, however, inhibits SMC proliferation and migration, via regulating expression of TR3. Collectively, we reveal that DHM may be a therapeutic agent for the treatment of injury-induced vascular diseases.


Assuntos
Ampelopsis/química , Estenose das Carótidas/tratamento farmacológico , Flavonóis/farmacologia , Neointima/tratamento farmacológico , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares/metabolismo , Animais , Artérias Carótidas/efeitos dos fármacos , Artérias Carótidas/patologia , Estenose das Carótidas/etiologia , Estenose das Carótidas/patologia , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Flavonóis/uso terapêutico , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Músculo Liso Vascular/citologia , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Neointima/etiologia , Neointima/patologia , Ratos
19.
J Nutr ; 147(10): 1917-1925, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28855423

RESUMO

Background: Platelets play an important role in hemostasis, thrombosis, and atherosclerosis. Glycoprotein VI (GPVI) is a major platelet receptor that interacts with exposed collagen on injured vessel walls. Our previous studies have shown that anthocyanins (a type of natural plant pigment) attenuate platelet function; however, whether anthocyanins affect collagen-induced GPVI signaling remains unknown.Objective: The objective of this study was to explore the effects of cyanidin-3-glucoside (Cy-3-g, one of the major bioactive compounds in anthocyanins) on platelet activation and thrombosis and the GPVI signaling pathway.Methods: Platelets from healthy men and women were isolated and incubated with different concentrations (0, 0.5, 5, and 50 µM) of Cy-3-g. The expression of activated integrin αIIbß3, P-selectin, CD63, and CD40L, fibrinogen binding to platelets, and platelet aggregation were evaluated in vitro. Platelet adhesion and aggregation in whole blood under flow conditions were assessed in collagen-coated perfusion chambers. Thrombosis and hemostasis were assessed in 3-4-wk-old male C57BL/6J mice through FeCl3-induced intravital microscopy and tail bleeding time. The effect of Cy-3-g on collagen-induced human platelet GPVI signaling was explored with Western blot.Results: Cy-3-g attenuated platelet function in a dose-dependent manner. The 0.5-µM dose of Cy-3-g inhibited (P < 0.05) human platelet adhesion and aggregation to collagen at both venous (-54.02%) and arterial (-22.90%) shear stresses. The 5-µM dose inhibited (P < 0.05) collagen-induced human platelet activation (PAC-1: -48.21%, P-selectin: -50.63%), secretion (CD63: -73.89%, CD40L: -43.70%), fibrinogen binding (-56.79%), and aggregation (-17.81%). The 5-µM dose attenuated (P < 0.01) thrombus growth (-66.67%) without prolonging bleeding time in mice. The 50-µM dose downregulated (P < 0.05) collagen-induced GPVI signaling in human platelets and significantly decreased phosphorylation of Syk-linker for activation of T cells (LAT)-SLP76 (Syk: -39.08%, LAT: -32.25%, SLP76: -40.00%) and the expression of Lyn (-31.89%), Fyn (-36.27%), and phospholipase C-γ2 (-39.08%).Conclusions: Cy-3-g inhibits human platelet activation, aggregation, secretion, and thrombus formation, and downregulates the collagen-GPVI signaling pathway. Supplementation of Cy-3-g may have protective effects against atherothrombosis.


Assuntos
Plaquetas/metabolismo , Fitoterapia , Extratos Vegetais/farmacologia , Plantas Comestíveis/química , Agregação Plaquetária/efeitos dos fármacos , Glicoproteínas da Membrana de Plaquetas/metabolismo , Trombose/prevenção & controle , Proteínas Adaptadoras de Transdução de Sinal/sangue , Adulto , Idoso , Animais , Antocianinas/farmacologia , Antocianinas/uso terapêutico , Antígenos CD/sangue , Aterosclerose/sangue , Aterosclerose/dietoterapia , Aterosclerose/etiologia , Colágeno/sangue , Feminino , Glucosídeos/farmacologia , Glucosídeos/uso terapêutico , Hemostasia/efeitos dos fármacos , Humanos , Masculino , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Selectina-P/sangue , Fosfoproteínas/sangue , Extratos Vegetais/uso terapêutico , Ativação Plaquetária/efeitos dos fármacos , Transdução de Sinais , Trombose/sangue , Trombose/etiologia
20.
Nutr Metab (Lond) ; 13: 86, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27933092

RESUMO

BACKGROUND: It is becoming increasingly evident that platelet chemokines are involved in distinct aspects of atherosclerosis. The aim of this study was to examine the effects of long-term supplementation with purified anthocyanins on platelet chemokines in hypercholesterolemic individuals and to identify correlations of decreased platelet chemokine levels with serum lipid and inflammatory marker levels. METHODS: A total of 146 hypercholesterolemic individuals were recruited and treated with 320 mg of purified anthocyanins (n = 73) or a placebo (n = 73) daily for 24 weeks in this randomized, double-blind, placebo-controlled trial. RESULTS: Anthocyanin supplementation for 24 weeks significantly decreased the plasma CXCL7 (-12.32% vs. 4.22%, P = 0.001), CXCL5 (-9.95% vs. 1.93%, P = 0.011), CXCL8 (-6.07% vs. 0.66%, P = 0.004), CXCL12 (-8.11% vs. 5.43%, P = 0.023) and CCL2 levels (-11.63% vs. 12.84%, P = 0.001) compared with the placebo. Interestingly, the decreases in the CXCL7 and CCL2 levels were both positively correlated with the decreases in the serum low-density lipoprotein-cholesterol (LDL-C), high-sensitivity C-reactive protein (hsCRP) and interleukin-1ß (IL-1ß) levels after anthocyanin supplementation for 24 weeks. The decrease in the CXCL8 level was negatively correlated with the increase in the how-density lipoprotein-cholesterol (HDL-C) level and was positively correlated with the decrease in the soluble P-selectin (sP-selectin) level in the anthocyanin group. In addition, a positive correlation was observed between the decreases in the CXCL12 and tumornecrosis factor-α (TNF-α) levels after anthocyanin supplementation. However, the plasma CXCL4L1, CXCL1, macrophage migration inhibitory factor (MIF) and human plasminogen activator inhibitor 1 (PAI-1) levels did not significantly change following anthocyanin supplementation. CONCLUSIONS: The present study supports the notion that platelet chemokines are promising targets of anthocyanins in the prevention of atherosclerosis. TRIAL REGISTRATION: ChiCTR-TRC-08000240. Registered: 10 December 2008.

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