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1.
J Nanobiotechnology ; 22(1): 370, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38918856

RESUMO

Parkinson's disease (PD) is the second largest group of neurodegenerative diseases, and its existing drug treatments are not satisfactory. Natural cell membrane drugs are used for homologous targeting to enhance efficacy. In this study, microfluidic electroporation chip prepared mesenchymal stem cell-derived neuron-like cell membrane-coated curcumin PLGA nanoparticles (MM-Cur-NPs) was synthesized and explored therapeutic effect and mechanism in PD. MM-Cur-NPs can protect neuron from damage, restore mitochondrial membrane potential and reduce oxidative stress in vitro. In PD mice, it also can improve movement disorders and restore damaged TH neurons. MM-Cur-NPs was found to be distributed in the brain and metabolized with a delay within 24 h. After 1 h administration, MM-Cur-NPs were distributed in brain with a variety of neurotransmitters were significantly upregulated, such as dopamine. Differentially expressed genes of RNA-seq were enriched in the inflammation regulation, and it was found the up-expression of anti-inflammatory factors and inhibited pro-inflammatory factors in PD. Mechanically, MM-Cur-NPs can not only reduce neuronal apoptosis, inhibit the microglial marker IBA-1 and inflammation, but also upregulate expression of neuronal mitochondrial protein VDAC1 and restore mitochondrial membrane potential. This study proposes a therapeutic strategy provide neuroprotective effects through MM-Cur-NPs therapy for PD.


Assuntos
Apoptose , Membrana Celular , Inflamação , Células-Tronco Mesenquimais , Nanopartículas , Neurônios , Doença de Parkinson , Animais , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Camundongos , Apoptose/efeitos dos fármacos , Nanopartículas/química , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Doença de Parkinson/tratamento farmacológico , Membrana Celular/metabolismo , Membrana Celular/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Curcumina/farmacologia , Curcumina/química , Camundongos Endogâmicos C57BL , Microfluídica/métodos , Masculino , Estresse Oxidativo/efeitos dos fármacos
2.
Crit Rev Food Sci Nutr ; 63(13): 1793-1805, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36647744

RESUMO

As one of the main functional substances, carbohydrates account for a large proportion of the human diet. Conventional analysis and detection methods of dietary carbohydrates and related products are destructive, time-consuming, and labor-intensive. In order to improve the efficiency of measurement and ensure food nutrition and consumer health, rapid and nondestructive quality evaluation techniques are needed. In recent years, terahertz (THz) spectroscopy, as a novel detection technology with dual characteristics of microwave and infrared, has shown great potential in dietary carbohydrate analysis. The current review aims to provide an up-to-date overview of research advances in using the THz spectroscopy technique in analysis and detection applications related to dietary carbohydrates. In the review, the principles of the THz spectroscopy technique are introduced. Advances in THz spectroscopy for quantitative and qualitative analysis and detection in dietary carbohydrate-related research studies from 2013 to 2022 are discussed, which include analysis of carbohydrate concentrations in liquid and powdery foods, detection of foreign body and chemical residues in carbohydrate food products, authentication of natural carbohydrate produce, monitoring of the fermentation process in carbohydrate food production and examination of crystallinity in carbohydrate polymers. In addition, applications in dietary carbohydrate-related detection research using other spectroscopic techniques are also briefed for comparison, and future development trends of THz spectroscopy in this field are finally highlighted.


Assuntos
Espectroscopia Terahertz , Humanos , Espectroscopia Terahertz/métodos , Carboidratos da Dieta , Análise Espectral/métodos
3.
Int J Mol Sci ; 24(5)2023 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-36901714

RESUMO

The serine/threonine-protein kinase general control nonderepressible 2 (GCN2) is a well-known stress sensor that responds to amino acid starvation and other stresses, making it critical to the maintenance of cellular and organismal homeostasis. More than 20 years of research has revealed the molecular structure/complex, inducers/regulators, intracellular signaling pathways and bio-functions of GCN2 in various biological processes, across an organism's lifespan, and in many diseases. Accumulated studies have demonstrated that the GCN2 kinase is also closely involved in the immune system and in various immune-related diseases, such as GCN2 acts as an important regulatory molecule to control macrophage functional polarization and CD4+ T cell subset differentiation. Herein, we comprehensively summarize the biological functions of GCN2 and discuss its roles in the immune system, including innate and adaptive immune cells. We also discuss the antagonism of GCN2 and mTOR pathways in immune cells. A better understanding of GCN2's functions and signaling pathways in the immune system under physiological, stressful, and pathological situations will be beneficial to the development of potential therapies for many immune-relevant diseases.


Assuntos
Proteínas Serina-Treonina Quinases , Transdução de Sinais , Aminoácidos/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Estresse Fisiológico , Subpopulações de Linfócitos T/metabolismo , Humanos
4.
Molecules ; 28(22)2023 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-38005375

RESUMO

A facile and efficient visible-light-mediated method for directly converting 1,4-naphthoquinones into dihydrocyclo-buta[b]naphthalene-3,8-diones (DHCBNDOs) under mild and clean conditions without using any photocatalysts is reported. This approach exhibited favorable compatibility with functional groups and afforded a series of DHCBNDOs with excellent regioselectivity and high yields. Moreover, detailed mechanism studies were carried out both experimentally and theoretically. The readily accessible, low-cost and ecofriendly nature of the developed strategy will endow it with attractive applications in organic and medicinal chemistry.

5.
Proteomics ; 22(11-12): e2200027, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35297194

RESUMO

Dental stem cells isolated from oral tissues have been shown to provide with high proliferation ability and multilineage differentiation potential. Gingival mesenchymal stem cells (GMSCs) and periodontal ligament stem cells (PDLSCs), kinds of dental stem cells, can be used as substitutes for tissue repair materials because of their similar regenerative functions. In this study, we aim to explore the similarities and differences between the protein profiles of GMSCs and PDLSCs through quantitative proteomics. A total of 2821 proteins were identified and retrieved, of which 271 were upregulated and 57 were downregulated in GMSCs compared to PDLSCs. Gene Ontology (GO) analysis demonstrated that the 328 differentially abundant proteins (DAPs) were involved in the regulation of gene expression, metabolism, and signal transduction in biological process, mainly distributed in organelles related to vesicle transport, and involved in the molecular function of binding protein. And Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the DAPs were committed to regulating the synthesis of proteasome and spliceosome. Real-time quantitative polymerase chain reaction (RT-qPCR) results showed that ARPC1B, PDAP1, and SEC61B can be used as special markers to distinguish GMSCs from PDLSCs. This research contributes to explaining the molecular mechanism and promoting the clinical application of tissue regeneration of GMSCs and PDLSCs.


Assuntos
Células-Tronco Mesenquimais , Ligamento Periodontal , Diferenciação Celular/genética , Células Cultivadas , Gengiva , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Ligamento Periodontal/metabolismo , Proteômica , Células-Tronco
6.
Biochem Biophys Res Commun ; 600: 67-74, 2022 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-35196629

RESUMO

BACKGROUND: Alzheimer's disease (AD) is a progressive neurologic disorder that causes the brain to shrink and brain cells to die. Lung cancer is characterized by high morbidity and mortality, late diagnosis and poor prognosis. And there is no specific mechanism to explain the epidemiological correlation between AD and lung cancer. MATERIALS AND METHODS: Lewis lung cancer cells (LLC) were injected into the left forelimb armpit of APP/PS1 mice to establish a tumor-bearing model. After remodeling the gut microbiota by fecal microbiota transplantation (FMT), the tumor were collected and analyzed for tumor size, Western blotting, and 16S rRNA gene sequencing. RESULTS: Compared with the control group, the AD FMT group showed larger tumors, while C57 FMT group showed smaller tumors. The former group showed the inhibition of AKT/Bax/Bcl-2 pathway, while the latter showed promotion of Caspase-1/IL-1ß and AKT/Bax/Bcl-2 pathway, which induced changes in tumor size. And Prevotella, Prevotella, Mucispirillum and Halomonas in the gut lumen of LLC tumor-bearing mice are increased, and Bacteroides, Coprobacillus, Bifidobacterium, Faecalibacterium and Aggregatiacter are decreased significantly. CONCLUSION: AD and lung cancer showed a positive correlation in APP expression, which proposed a different view from epidemiology on the correlation between AD and lung cancer.


Assuntos
Doença de Alzheimer , Neoplasias Pulmonares , Doença de Alzheimer/patologia , Animais , Fezes , Camundongos , Proteínas Proto-Oncogênicas c-akt , RNA Ribossômico 16S , Proteína X Associada a bcl-2
7.
Cytotherapy ; 24(11): 1105-1120, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35973920

RESUMO

BACKGROUND AIMS: Gingival mesenchymal stem cells (GMSCs) demonstrate high proliferation, trilineage differentiation and immunomodulatory properties. Parkinson disease (PD) is the second most common type of neurodegenerative disease. This study aimed to explore the effect and mechanism of GMSC-based therapy in 6-hydroxydopamine-induced PD rats. METHODS: RNA sequencing and quantitative proteomics technology was used to validate the neuroprotective role of GMSCs therapeutic in 6-Hydroxydopamine -induced PD model in vitro and in vivo. Western blotting, immunofluorescence and real-time quantitative PCR verified the molecular mechanism of GMSCs treatment. RESULTS: Intravenous injection of GMSCs improved rotation and forelimb misalignment behavior, enhanced the anti-apoptotic B-cell lymphoma 2/B-cell lymphoma 2-associated X axis, protected tyrosine hydroxylase neurons, decreased the activation of astrocytes and reduced the astrocyte marker glial fibrillary acidic protein and microglia marker ionized calcium-binding adaptor molecule 1 in the substantia nigra and striatum of PD rats. The authors found that GMSCs upregulated nerve regeneration-related molecules and inhibited metabolic disorders and the activation of signal transducer and activator of transcription 3. GMSCs showed a strong ability to protect neurons and reduce mitochondrial membrane potential damage and reactive oxygen species accumulation. The safety of GMSC transplantation was confirmed by the lack of tumor formation following subcutaneous transplantation into nude mice for up to 8 weeks. CONCLUSIONS: The authors' research helps to explain the mechanism of GMSC-based therapeutic strategies and promote potential clinical application in Parkinson disease.


Assuntos
Células-Tronco Mesenquimais , Doenças Neurodegenerativas , Doença de Parkinson , Animais , Cálcio/metabolismo , Gengiva , Proteína Glial Fibrilar Ácida/metabolismo , Humanos , Camundongos , Camundongos Nus , Neurônios/metabolismo , Oxidopamina/metabolismo , Oxidopamina/farmacologia , Oxidopamina/uso terapêutico , Doença de Parkinson/terapia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/farmacologia , Fator de Transcrição STAT3/uso terapêutico , Tirosina 3-Mono-Oxigenase/metabolismo , Tirosina 3-Mono-Oxigenase/farmacologia , Tirosina 3-Mono-Oxigenase/uso terapêutico
8.
Cytotherapy ; 24(11): 1095-1104, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36064533

RESUMO

BACKGROUND AIMS: Stem cells from human exfoliated deciduous teeth (SHED) play a significant role in tissue engineering and regenerative medicine. Angiogenesis is crucial in tissue regeneration and a primary target of regenerative medicine. As a first-line anti-diabetic drug, metformin demonstrates numerous valuable impacts on stem cells. This study aimed to explore metformin's impact and mechanism of action on SHED-mediated angiogenesis. METHODS: First, cell proliferation; flow cytometry; osteogenic, adipogenic and chondrogenic induction; and proteomics analyses were conducted to explore the role of metformin in SHED. Subsequently, migration and tube formation assays were used to evaluate chemotaxis and angiogenesis enhancement by SHED pre-treated with metformin under co-culture conditions in vitro, and relative messenger RNA expression levels were determined by quantitative reverse transcription polymerase chain reaction. Finally, nude mice were used for in vivo tube formation assay, and sections were analyzed through immunohistochemistry staining with anti-human CD31 antibody. RESULTS: Metformin significantly promoted SHED proliferation as well as osteogenic, adipogenic and chondrogenic differentiation. Proteomics showed that metformin significantly upregulated 124 differentially abundant proteins involved in intracellular processes, including various proteins involved in cell migration and angiogenesis, such as MAPK1. The co-culture system demonstrated that SHED pre-treated with metformin significantly improved the migration and angiogenesis of human umbilical vein endothelial cells. In addition, SHED pre-treated with metformin possessed greater ability to promote angiogenesis in vivo. CONCLUSIONS: In summary, the authors' findings illustrate metformin's mechanism of action on SHED and confirm that SHED pre-treated with metformin exhibits a strong capacity for promoting angiogenesis. This helps in promoting the application of dental pulp-derived stem cells pre-treated with metformin in regeneration engineering.


Assuntos
Metformina , Engenharia Tecidual , Animais , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Polpa Dentária , Células Endoteliais da Veia Umbilical Humana , Humanos , Metformina/farmacologia , Camundongos , Camundongos Nus , RNA Mensageiro/metabolismo , Células-Tronco , Dente Decíduo
9.
Neurochem Res ; 47(12): 3565-3582, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36309938

RESUMO

Alzheimer's disease (AD) is a central nervous system disease that can lead to cognitive impairment and progressive memory loss. An increasing number of studies have shown that intestinal flora play a crucial role in regulating the brain-gut axis. Short-chain fatty acids are metabolites of intestinal flora that regulate hormone synthesis and play an essential role in microbial-intestinal-brain communication. An imbalance of intestinal flora can promote microglia to secrete proinflammatory factors, cause nerve inflammation, and then affect cognitive and learning ability. However, the mechanism is not clear. From this, we infer that endogenous hormones may be the medium for intestinal flora to affect the process of AD. This review of the relationships among AD, endogenous hormones, and intestinal flora expounds on the critical role of various hormones in the brain-gut axis. It discusses intervention measures aimed at intestinal flora to prevent or delay AD occurrence. Finally, the potential development prospects of fecal microbiota transplantation in treating AD are put forward, which provide potential ideas for future AD research.


Assuntos
Doença de Alzheimer , Microbioma Gastrointestinal , Humanos , Microbioma Gastrointestinal/fisiologia , Doença de Alzheimer/metabolismo , Intestinos , Encéfalo/metabolismo , Hormônios/metabolismo
10.
Crit Rev Food Sci Nutr ; 62(16): 4267-4293, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34275402

RESUMO

Dehydration is one of the most widely used food processing techniques, which is sophisticated in nature. Rapid and accurate prediction of dehydration performance and its effects on product quality is still a difficult task. Traditional analytical methods for evaluating food dehydration processes are laborious, time-consuming and destructive, and they are not suitable for online applications. On the other hand, vibrational spectral techniques coupled with chemometrics have emerged as a rapid and noninvasive tool with excellent potential for online evaluation and control of the dehydration process to improve final dried food quality. In the current review, the fundamental of food dehydration and five types of vibrational spectral techniques, and spectral data processing methods are introduced. Critical overtones bands related to dehydration attributes in the near-infrared (NIR) region and the state-of-the-art applications of vibrational spectral analyses in evaluating food quality attributes as affected by dehydration processes are summarized. Research investigations since 2010 on using vibrational spectral technologies combined with chemometrics to continuously monitor food quality attributes during dehydration processes are also covered in this review.


Assuntos
Desidratação , Vibração , Manipulação de Alimentos , Qualidade dos Alimentos , Humanos
11.
Part Fibre Toxicol ; 19(1): 64, 2022 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-36242005

RESUMO

BACKGROUND: Airborne fine particulate matter with aerodynamic diameter ≤ 2.5 µm (PM2.5) pollution is associated with the prevalence of respiratory diseases, including asthma, bronchitis and chronic obstructive pulmonary disease. In patients with those diseases, circulating asymmetric dimethylarginine (ADMA) levels are increased, which contributes to airway nitric oxide deficiency, oxidative stress and inflammation. Overexpression of dimethylarginine dimethylaminohydrolase 1 (DDAH1), an enzyme degrading ADMA, exerts protective effects in animal models. However, the impact of DDAH1/ADMA on PM2.5-induced lung injury has not been investigated. METHODS: Ddah1-/- and DDAH1-transgenic mice, as well as their respective wild-type (WT) littermates, were exposed to either filtered air or airborne PM2.5 (mean daily concentration ~ 50 µg/m3) for 6 months through a whole-body exposure system. Mice were also acutely exposed to 10 mg/kg PM2.5 and/or exogenous ADMA (2 mg/kg) via intratracheal instillation every other day for 2 weeks. Inflammatory response, oxidative stress and related gene expressions in the lungs were examined. In addition, RAW264.7 cells were exposed to PM2.5 and/or ADMA and the changes in intracellular oxidative stress and inflammatory response were determined. RESULTS: Ddah1-/- mice developed more severe lung injury than WT mice after long-term PM2.5 exposure, which was associated with greater induction of pulmonary oxidative stress and inflammation. In the lungs of PM2.5-exposed mice, Ddah1 deficiency increased protein expression of p-p65, iNOS and Bax, and decreased protein expression of Bcl-2, SOD1 and peroxiredoxin 4. Conversely, DDAH1 overexpression significantly alleviated lung injury, attenuated pulmonary oxidative stress and inflammation, and exerted opposite effects on those proteins in PM2.5-exposed mice. In addition, exogenous ADMA administration could mimic the effect of Ddah1 deficiency on PM2.5-induced lung injury, oxidative stress and inflammation. In PM2.5-exposed macrophages, ADMA aggravated the inflammatory response and oxidative stress in an iNOS-dependent manner. CONCLUSION: Our data revealed that DDAH1 has a marked protective effect on long-term PM2.5 exposure-induced lung injury.


Assuntos
Lesão Pulmonar , Óxido Nítrico , Amidoidrolases , Animais , Inflamação/induzido quimicamente , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/genética , Lesão Pulmonar/prevenção & controle , Camundongos , Camundongos Transgênicos , Óxido Nítrico/genética , Óxido Nítrico/metabolismo , Estresse Oxidativo , Material Particulado/toxicidade , Peroxirredoxinas/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transdução de Sinais , Superóxido Dismutase-1/metabolismo , Proteína X Associada a bcl-2/metabolismo
12.
J Nanobiotechnology ; 20(1): 176, 2022 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-35366889

RESUMO

Stem cells from human exfoliated deciduous teeth (SHED) can be used as a potential clinical material. But the use of xenogeneic ingredients will increase the risk of zoonotic disease transmission. Human platelet lysate (HPL) is a potential surrogate and used in human cell expansion with reliability in clinical applications. In this study, we synthesized chitosan/gelatin/gellan gum hydrogel supplemented with HPL and investigated the effect of 3D culture for SHED. TMT-tagged proteomics was used to decipher the secretome protein profiles of SHEDs and a total of 3209 proteins were identified, of which 23 were up-regulated and 192 were down-regulated. The results showed that hydrogel supplemented with HPL promoted SHED proliferation. After induction, the hydrogel coating contributed to osteogenic differentiation, adipogenic differentiation and differentiation into neural-like cells of SHED. SHED encapsulated in a hydrogel promotes migration and angiogenesis of HUVEC. In conclusion, our research found that hydrogel supplemented with HPL can be used as a method for SHED in standardized production and can contribute to the clinical application of SHED in cell therapy.


Assuntos
Células-Tronco Mesenquimais , Osteogênese , Diferenciação Celular , Humanos , Hidrogéis/farmacologia , Reprodutibilidade dos Testes
13.
Int J Mol Sci ; 23(6)2022 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-35328696

RESUMO

Human gingival mesenchymal stem cells (GMSCs) are derived from migratory neural crest stem cells and have the potential to differentiate into neurons. Metformin can inhibit stem-cell aging and promotes the regeneration and development of neurons. In this study, we investigated the potential of metformin as an enhancer on neuronal differentiation of GMSCs in the growth environment of chitosan hydrogel. The crosslinked chitosan/ß-glycerophosphate hydrogel can form a perforated microporous structure that is suitable for cell growth and channels to transport water and macromolecules. GMSCs have powerful osteogenic, adipogenic and chondrogenic abilities in the induction medium supplemented with metformin. After induction in an induction medium supplemented with metformin, Western blot and immunofluorescence results showed that GMSCs differentiated into neuron-like cells with a significantly enhanced expression of neuro-related markers, including Nestin (NES) and ß-Tubulin (TUJ1). Proteomics was used to construct protein profiles in neural differentiation, and the results showed that chitosan hydrogels containing metformin promoted the upregulation of neural regeneration-related proteins, including ATP5F1, ATP5J, NADH dehydrogenase (ubiquinone) Fe-S protein 3 (NDUFS3), and Glutamate Dehydrogenase 1 (GLUD1). Our results help to promote the clinical application of stem-cell neural regeneration.


Assuntos
Quitosana , Células-Tronco Mesenquimais , Metformina , Diferenciação Celular , Células Cultivadas , Quitosana/química , Gengiva , Humanos , Hidrogéis/química , Células-Tronco Mesenquimais/metabolismo , Metformina/metabolismo , Metformina/farmacologia , Neurônios
14.
J Sci Food Agric ; 101(14): 5956-5962, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33838057

RESUMO

BACKGROUND: Plastic film mulch is widely used to improve crop yield and water use efficiency (WUE, yield per unit evapotranspiration) in semi-arid regions. It is commonly applied as partial-film mulch (PM: at least 50% soil cover) or full-film mulch (FM: complete soil cover). The PM has lower economic and environmental cost; hence it would be a superior technology provided it delivers similar gains in yield and WUE in relation to FM. RESULTS: To solve contradictory results from individual studies, we compared FM and PM in a meta-analysis of 100 studies with 1881 comparisons (685 for wheat; 1196 for maize). Compared with bare ground, FM and PM both increased yield of wheat (20-26%) and maize (37-52%), and WUE of wheat (16-20%) and maize (38-48%), with statistically undistinguishable differences between PM and FM. The increases in crop yield and WUE were stronger at elevation > 1000 m, with annual precipitation<400 mm, and on loess soil, especially for maize. CONCLUSIONS: We concluded that partial-film mulch could replace full-film mulch to return similar yield and WUE improvement, with reduced cost and environmental pollution. © 2021 Society of Chemical Industry.


Assuntos
Agricultura/métodos , Plásticos/economia , Triticum/crescimento & desenvolvimento , Água/metabolismo , Zea mays/crescimento & desenvolvimento , Agricultura/economia , Poluição Ambiental/prevenção & controle , Solo/química , Triticum/metabolismo , Água/análise , Zea mays/metabolismo
15.
J Allergy Clin Immunol ; 144(4): 1091-1105, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31121187

RESUMO

BACKGROUND: TH9 cells have emerged as important mediators of allergic airway inflammation. There is evidence that general control nonderepressible 2 (GCN2) affects the immune response under some stress conditions. However, whether GCN2 regulates CD4+ T-cell differentiation during allergic inflammation remains unknown. OBJECTIVE: We sought to clarify the regulatory roles of GCN2 in CD4+ T-cell subset differentiation and its significance in patients with allergic airway inflammation. METHODS: The effects of GCN2 in differentiation of TH cell subsets were detected by using the in vitro induction system. GCN2 knockout mice, ovalbumin-induced allergic airway inflammation, and adoptive transfer mouse models were used to determine the significance of GCN2 in TH9 differentiation and allergic airway inflammation in vivo. RNA sequencing, real-time PCR, Western blotting, and other molecular approaches were used to identify the molecular mechanisms relevant to regulation of GCN2 in TH9 cell differentiation. RESULTS: GCN2 deficiency significantly inhibited differentiation of TH9 cells but not TH1, TH2, and regulatory T cells. GCN2 knockout mice and recombination-activating gene 2 knockout (Rag2KO) mice that received adoptively transferred GCN2-deficient CD4+ T cells exhibited reduced TH9 differentiation and less severe allergic airway inflammation. Furthermore, the isolated GCN2-deficient TH9 cells also mediated less severe allergic airway inflammation on adoptive transfer. Mechanistically, GCN2 deficiency inhibits TH9 cell differentiation through a hypoxia-inducible factor 1α-dependent glycolytic pathway. CONCLUSION: Our results reveal a novel role of GCN2 in TH9 cell differentiation. Our findings indicate that new strategies to inhibit GCN2 activity might provide novel approaches to attenuate allergic airway inflammation.


Assuntos
Diferenciação Celular/imunologia , Proteínas Serina-Treonina Quinases/imunologia , Hipersensibilidade Respiratória/imunologia , Subpopulações de Linfócitos T/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Animais , Feminino , Interleucina-9/imunologia , Ativação Linfocitária/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
16.
J Evid Based Dent Pract ; 20(3): 101468, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32921388

RESUMO

OBJECTIVE: Oral lichen planus (OLP) is a chronic inflammatory immune disease, recognized as an oral potentially malignant disorder by the World Health Organization. There is considerable controversy over the standardized treatment of OLP, with great diversities in the outcome measures in clinical trials. This methodological study aimed to estimate the degree of consensus on outcome measures in randomized controlled trials (RCTs) for OLP treatment. METHODS: PubMed, Embase, and Cochrane databases were searched to identify RCTs published from 2004 to 2018 about OLP treatment. All the outcome measures and measurement methods mentioned in the trials were extracted and analyzed. RESULTS: After identification of 1087 articles, 88 RCTs were included. A total of 193 single-outcome measures and 119 composite outcome measures were classified into 11 different domains, the chief of which consisted of clinical symptom (78 trials; 88.6%) and clinical score (58 trials; 65.9%). Visual analog scale (65 trials; 73.9%) and Thongprasom scoring system (38 trials; 43.2%) were the predominant measurement methods. Oral health-related quality of life (except for clinical symptoms) accounted for 4.8% of all the outcome measures. CONCLUSIONS: There was high heterogeneity in outcome measures of RCTs for OLP treatment, making it difficult to make valid comparisons between different clinical trials. A core outcome set should be developed and adopted in future trials for OLP treatment.


Assuntos
Líquen Plano Bucal , Avaliação de Resultados em Cuidados de Saúde , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Líquen Plano Bucal/tratamento farmacológico , Qualidade de Vida
17.
Biochim Biophys Acta Mol Basis Dis ; 1864(5 Pt A): 1744-1753, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29499325

RESUMO

The transcriptional co-activator Yes-associated protein (YAP) has been implicated as an oncogene and is found to promote breast cancer metastasis. However, the pro-metastatic mechanism of YAP remains unclear. Here, we demonstrated that YAP functions as a transcriptional repressor of growth differentiation factor-15 (GDF15), a divergent member of the transforming growth factor superfamily, in several breast cancer cell lines. Functionally, knockdown of YAP decreased, whereas knockdown of GDF15 increased, the metastatic potential of breast cancer cells. More than that, the reduced metastasis in YAP-depleted cells could be reversed by simultaneous knockdown of GDF15. Mechanistically, the repressive effect of YAP on GDF15 requires its transcriptional factor TEAD (TEA domain family). In addition, YAP recruits polycomb repressive complex 2 (PRC2) to tri-methylate histone H3 lysine 27 in the promoter region of GDF15. Co-immunoprecipitation experiments demonstrated that YAP and enhancer of zeste 2 PRC2 subunit (EZH2) physically interact with each other. In conclusion, our data reveal that YAP promotes metastasis of breast cancer cells by repressing GDF15 transcription and present a novel molecular mechanism underlying the pro-metastasis function of YAP oncoprotein, with the implication of a therapeutic avenue for breast cancer treatment.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Neoplasias da Mama/metabolismo , Regulação Neoplásica da Expressão Gênica , Fator 15 de Diferenciação de Crescimento/biossíntese , Fosfoproteínas/metabolismo , Transcrição Gênica , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Feminino , Fator 15 de Diferenciação de Crescimento/genética , Humanos , Camundongos , Metástase Neoplásica , Fosfoproteínas/genética , Complexo Repressor Polycomb 2/genética , Complexo Repressor Polycomb 2/metabolismo , Fatores de Transcrição , Proteínas de Sinalização YAP
19.
Int J Biol Macromol ; 256(Pt 2): 128308, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37992921

RESUMO

Neurodegenerative diseases (NDs) are characterized by nervous system damage, often influenced by genetic and aging factors. Pathological analysis frequently reveals the presence of aggregated toxic proteins. The intricate and poorly understood origins of these diseases have hindered progress in early diagnosis and drug development. The development of novel in-vitro and in-vivo models could enhance our comprehension of ND mechanisms and facilitate clinical treatment advancements. Microfluidic chips are employed to establish three-dimensional culture conditions, replicating the human ecological niche and creating a microenvironment conducive to neuronal cell survival. The incorporation of mechatronic controls unifies the chip, cells, and culture medium optimizing living conditions for the cells. This study provides a comprehensive overview of microfluidic chip applications in drug and biomarker screening for neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, and amyotrophic lateral sclerosis. Our Lab-on-a-Chip system releases toxic proteins to simulate the pathological characteristics of neurodegenerative diseases, encompassing ß-amyloid, α-synuclein, huntingtin, TAR DNA-binding protein 43, and Myelin Basic Protein. Investigating molecular and cellular interactions in vitro can enhance our understanding of disease mechanisms while minimizing harmful protein levels and can aid in screening potential therapeutic agents. We anticipate that our research will promote the utilization of microfluidic chips in both fundamental research and clinical applications for neurodegenerative diseases.


Assuntos
Doença de Alzheimer , Doenças Neurodegenerativas , Humanos , Doenças Neurodegenerativas/metabolismo , Microfluídica , Peptídeos beta-Amiloides
20.
BMC Psychol ; 12(1): 35, 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38238861

RESUMO

BACKGROUND: One noteworthy concern within the realm of education is the level of engagement demonstrated by students. Among the factor that can have a crucial role in this domain is teacher support, especially emotional support which has an impact on several aspects of learners' education. Furthermore, various studies have investigated the relationship between Emotional Intelligence (EI) and learners' engagement. METHODS: Accordingly, this study investigated the possible role of trait EI and the emotional support of teachers and how these constructs may work to associate learners' engagement. For this objective, a total of 309 Chinese students across different colleges and universities in 5 provinces of Beijing, Shanghai, Jiangsu, Hubei, and Shaanxi were enrolled. They were 126 females and 183 males, with ages ranging from 18 to 30 years old (Mean = 24.6). RESULTS: The results of this research through running Structural Equation Modeling (SEM) demonstrated that teachers' emotional support and trait EI both can associate students' learning engagement. The final measurement model shows that about 73% of changes in learners' engagement can be associated by their trait EI and teachers' emotional support. CONCLUSIONS: This study underscores the importance of emotional support from teachers and the trait of EI in relation to students' engagement in learning. Both factors were shown to play a significant role in associating student engagement. Moreover, this study could potentially have wider impacts on members of academic teams.


Assuntos
Aconselhamento , Pessoal de Educação , Inteligência Emocional , Adolescente , Adulto , Feminino , Humanos , Masculino , Adulto Jovem , China , População do Leste Asiático , Aprendizagem
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