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1.
Foods ; 13(17)2024 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-39272618

RESUMO

The paocai industry faces challenges related to the production of large volumes of high-salinity and acidic brine by-products. Maintaining paocai quality while reducing brine production is crucial. This study utilized high-throughput sequencing technology to analyze microbial changes throughout the fermentation process, along with the non-volatile flavor compounds and physicochemical properties, to assess the impact of hot-air and salt-pressing pre-dehydration treatments on paocai quality. The findings indicate that pre-dehydration of raw material slowed the fermentation process but enhanced the concentration of non-volatile flavor substances, including free amino acids and organic acids. Hot-air pre-dehydration effectively reduced initial salinity to levels comparable to those in high-salinity fermentation of fresh vegetables. Furthermore, pre-dehydration altered microbial community structures and simplified inter-microbial relationships during fermentation. However, the key microorganisms such as Lactobacillus, Weissella, Enterobacter, Wallemia, Aspergillus, and Kazachstania remained consistent across all groups. Additionally, this study found that biomarkers influenced non-volatile flavor formation differently depending on the treatment, but these substances had minimal impact on the biomarkers and showed no clear correlation with high-abundance microorganisms. Overall, fermenting pre-dehydrated raw materials presents an environmentally friendly alternative to traditional paocai production.

2.
Nat Commun ; 15(1): 8203, 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39313508

RESUMO

Cytotherapy is a strategy to deliver modified cells to a diseased tissue, but targeting solid tumours remains challenging. Here we design macrophages, harbouring a surface glypican-3-targeting peptide and carrying a cargo to combat solid tumours. The anchored targeting peptide facilitates tumour cell recognition by the engineered macrophages, thus enhancing specific targeting and phagocytosis of tumour cells expressing glypican-3. These macrophages carry a cargo of the TLR7/TLR8 agonist R848 and INCB024360, a selective indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor, wrapped in C16-ceramide-fused outer membrane vesicles (OMV) of Escherichia coli origin (RILO). The OMVs facilitate internalization through caveolin-mediated endocytosis, and to maintain a suitable nanostructure, C16-ceramide induces membrane invagination and exosome generation, leading to the release of cargo-packed RILOs through exosomes. RILO-loaded macrophages exert therapeutic efficacy in mice bearing H22 hepatocellular carcinomas, which express high levels of glypican-3. Overall, we lay down the proof of principle for a cytotherapeutic strategy to target solid tumours and could complement conventional treatment.


Assuntos
Exossomos , Glipicanas , Macrófagos , Animais , Glipicanas/metabolismo , Exossomos/metabolismo , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Camundongos , Humanos , Linhagem Celular Tumoral , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/metabolismo , Modelos Animais de Doenças , Receptor 7 Toll-Like/metabolismo , Receptor 7 Toll-Like/agonistas , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/metabolismo , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Indolamina-Pirrol 2,3,-Dioxigenase/antagonistas & inibidores , Terapia Baseada em Transplante de Células e Tecidos/métodos , Sistemas de Liberação de Medicamentos , Fagocitose/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Neoplasias/terapia , Neoplasias/imunologia , Neoplasias/metabolismo , Feminino
3.
Front Bioeng Biotechnol ; 12: 1421167, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39188373

RESUMO

Alanine is the most abundant chiral amino acid that exists into the D-alanine or L-alanine forms with diverse applications in the biomedical, pharmaceutical, plastics, and food industries. D/L-alanine production can be carried out through chemical, microbial fermentation, and biocatalytic methods and not much effective due to complicated processes or purification issues and is still challenging to achieve a higher yield. In the present study, biobrick method was utilized for efficient production of D/L-alanine in the recombinant Escherichia coli BL21(DE3) with tandem three-gene co-expression plasmid. Firstly, the co-expression plasmid pET-22bNS-DadX-Ald-Gdh containing three genes, alanine dehydrogenase (ald), alanine racemase (dadX), and glucose dehydrogenase (gdh) from Bacillus pseudofirmus OF4 were successfully constructed and introduced into the E. coli BL21(DE3) strain. Then, under optimized conditions in the whole-cell biocatalytic reaction [20 mM Na2CO3-NaHCO3 (pH 10.1), 200 mM D-glucose, 200 mM sodium pyruvate, and 200 mM ammonium chloride], the concentration of D-alanine and L-alanine reached the maximum value (6.48 g/L and 7.05 g/L) after 3.0 h reaction time at 37°C under 180 rpm rotation. Meanwhile, promoter replacement experiments and Western blot analysis revealed that the expression level of protein OF4Ald had a significant effect on the production of D/L-alanine, indicating that alanine dehydrogenase might be the rate-limiting enzyme for D/L-alanine synthesis. This study provides a simple, feasible, and efficient biosynthesis process of D/L-alanine, which could explore emerging applications for large-scale production of industrial bioproducts.

4.
J Affect Disord ; 366: 44-58, 2024 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-39187180

RESUMO

BACKGROUND: This study aimed to explore the relationship between flavonoids intake and the prevalence and all-cause mortality of depressive symptoms in American adults. METHODS: Analyzing 2007-2008, 2009-2010, and 2017-2018 NHANES data, we examined the association between dietary flavonoid and depressive symptoms, including specific subclasses assessment and mortality outcomes tracking until December 31, 2019. Our methodology included weighted multivariate logistic regression, weighted cox proportional hazards regression and restricted cubic spline (RCS) models, supported by stratified and sensitivity analyses. RESULTS: Among the 12,340 participants in total, 1129 exhibited depressive symptoms. The multiple logistic regression analysis showed a significant reduction in total flavonoid and subclass intake in individuals with current depressive symptoms. Adjusted odds ratios (ORs) for the highest quartiles were 0.69 for anthocyanidins and 0.63 for flavones. Interaction effects emerged in non-hypertensive, higher-income, and normal-weight groups for flavones intake. The RCS model indicated an L-shaped association between depressive symptoms and total flavonoid intake, with inflection points at 346 mg/day. During a median follow-up of 119 months, 148 deaths occurred among patients with depressive symptoms. Hazard ratios (HRs) for all-cause mortality showed a significant positive correlation between total flavonoid intake and survival in model 1 (HR = 0.56), with an optimal intake range of 45.2-948.3 mg/day according to the RCS model. LIMITATIONS: The study relied on U.S. population survey data, potentially limiting generalizability. Unmeasured confounding factors may exist, and genetic factors were not considered. CONCLUSIONS: Adequate intake of flavonoids, especially anthocyanidins and flavones, is associated with reduced odds of depressive symptoms. Additionally, optimal intake ranges of flavonoid intake for mental health benefits were observed for all-cause mortality in population with depressive symptoms.


Assuntos
Depressão , Flavonoides , Inquéritos Nutricionais , Humanos , Masculino , Feminino , Flavonoides/administração & dosagem , Pessoa de Meia-Idade , Depressão/epidemiologia , Adulto , Prevalência , Estados Unidos/epidemiologia , Dieta/estatística & dados numéricos , Idoso , Mortalidade , Flavonas/administração & dosagem , Modelos de Riscos Proporcionais
5.
ACS Appl Mater Interfaces ; 16(31): 41659-41668, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39047062

RESUMO

Recently, metal-oxo clusters (MOCs) have attracted significant interest in fabricating nanoscale patterns in semiconductors via lithography. However, many MOCs are highly crystalline, making it difficult for them to form films and hindering subsequent nanopatterning processes. In this study, we developed a novel and simple method to enhance the film-forming ability of aromatic tetranuclear Sn-oxo clusters by adding additives. Theoretical calculations and Fourier-transform infrared (FTIR) analysis revealed the formation of intermolecular hydrogen bonds between the Sn-oxo clusters and additives, which induced a crystal-gel phase transition at -20 °C, thereby inhibiting the easy crystallization of the Sn-oxo clusters. High-quality and uniform thin films with surface roughness below 0.3 nm were prepared via spin coating. The obtained thin films exhibited good lithographic performance under deep ultraviolet (DUV), electron beam, and extreme-ultraviolet irradiation without a photo acid generator/photoinitiator, and 13- and 21 nm-wide line patterns were obtained on the films via electron-beam and extreme-ultraviolet lithographies. This study will pave the way for the further investigation of novel MOCs for advanced lithography and other thin-film applications.

6.
Natl Sci Rev ; 11(5): nwae163, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38855727

RESUMO

China, one of the most populous countries in the world, has suffered the highest number of natural disaster-related deaths from fire. On local scales, the main causes of urban fires are anthropogenic in nature. Yet, on regional to national scales, little is known about the indicators of large-scale co-varying urban fire activity in China. Here, we present the China Fire History Atlas (CFHA), which is based on 19 947 documentary records and represents fires in urban areas of China over the twentieth century (1901-1994). We found that temperature variability is a key indicator of urban fire activity in China, with warmer temperatures being correlated with more urban fires, and that this fire-temperature relationship is seasonally and regionally explicit. In the early twentieth century, however, the fire-temperature relationship was overruled by war-related fires in large urban areas. We further used the fire-temperature relationship and multiple emissions scenarios to project fire activity across China into the twenty-first century. Our projections show a distinct increase in future urban fire activity and fire-related economic loss. Our findings provide insights into fire-climate relationships in China for densely-populated areas and on policy-relevant time scales and they contribute spatial coverage to efforts to improve global fire models.

7.
PeerJ ; 12: e17541, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38832034

RESUMO

Introduction: Oxidative and antioxidant pathways play essential roles in the development of alcohol-induced brain injury. The Nrf2 pathway is an endogenous antioxidant response pathway, but there has been little research on the role of Nrf2 in alcohol-related diseases. Thus, we examined the effects of alcohol and an Nrf2 agonist (TBHQ) on astrocyte function, mRNA expression, and metabolite content to further explore the protective mechanisms of Nrf2 agonists in astrocytes following alcohol exposure. Methods: CTX TNA2 astrocytes were cultured with alcohol and TBHQ and then subjected to transcriptome sequencing, LC-MS/MS analysis, quantitative reverse transcription polymerase chain reaction (qRT-PCR), and malondialdehyde (MDA) and superoxide dismutase (SOD) activity assays. Results: Alcohol exposure significantly increased malondialdehyde (MDA) levels while decreasing superoxide dismutase (SOD) levels in astrocytes. Treatment with TBHQ effectively reversed these effects, demonstrating its protective role against oxidative stress induced by alcohol. Transcriptome sequencing and qRT-PCR analysis revealed that TBHQ specifically upregulates genes involved in glutathione metabolism, including a notable increase in the expression of the glutathione S-transferase A5 (GSTA5) gene, which was suppressed by alcohol exposure. Additionally, metabolomic analysis showed that TBHQ regulates key components of ether lipid metabolism in alcohol-exposed astrocytes, with significant reductions in the levels of lysophosphatidylcholine (18:0) (LysoPC (18:0)) and 2-acetyl-1-alkyl-sn-glycero-3-phosphocholine, both of which are critical markers in the ether lipid metabolic pathway. Discussion: The findings underscore the role of TBHQ as an Nrf2 agonist in mitigating alcohol-induced oxidative damage in astrocytes by modulating glutathione metabolism and ether lipid metabolism. The regulation of GSTA5 gene expression emerges as a key mechanism through which Nrf2 agonists confer neuroprotection against oxidative stress and lipid oxidation. These insights pave the way for potential therapeutic strategies targeting the Nrf2 pathway to protect astrocytes from alcohol-induced damage.


Assuntos
Astrócitos , Etanol , Glutationa , Fator 2 Relacionado a NF-E2 , Animais , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Células Cultivadas , Etanol/farmacologia , Glutationa/metabolismo , Hidroquinonas/farmacologia , Malondialdeído/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/genética , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Superóxido Dismutase/genética
8.
Elife ; 132024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38722677

RESUMO

Environmental air irritants including nanosized carbon black (nCB) can drive systemic inflammation, promoting chronic obstructive pulmonary disease (COPD) and emphysema development. The let-7 microRNA (Mirlet7 miRNA) family is associated with IL-17-driven T cell inflammation, a canonical signature of lung inflammation. Recent evidence suggests the Mirlet7 family is downregulated in patients with COPD, however, whether this repression conveys a functional consequence on emphysema pathology has not been elucidated. Here, we show that overall expression of the Mirlet7 clusters, Mirlet7b/Mirlet7c2 and Mirlet7a1/Mirlet7f1/Mirlet7d, are reduced in the lungs and T cells of smokers with emphysema as well as in mice with cigarette smoke (CS)- or nCB-elicited emphysema. We demonstrate that loss of the Mirlet7b/Mirlet7c2 cluster in T cells predisposed mice to exaggerated CS- or nCB-elicited emphysema. Furthermore, ablation of the Mirlet7b/Mirlet7c2 cluster enhanced CD8+IL17a+ T cells (Tc17) formation in emphysema development in mice. Additionally, transgenic mice overexpressing Mirlet7g in T cells are resistant to Tc17 and CD4+IL17a+ T cells (Th17) development when exposed to nCB. Mechanistically, our findings reveal the master regulator of Tc17/Th17 differentiation, RAR-related orphan receptor gamma t (RORγt), as a direct target of Mirlet7 in T cells. Overall, our findings shed light on the Mirlet7/RORγt axis with Mirlet7 acting as a molecular brake in the generation of Tc17 cells and suggest a novel therapeutic approach for tempering the augmented IL-17-mediated response in emphysema.


Assuntos
Diferenciação Celular , Regulação para Baixo , MicroRNAs , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares , Enfisema Pulmonar , Células Th17 , Animais , Feminino , Humanos , Masculino , Camundongos , Interleucina-17/metabolismo , Interleucina-17/genética , Pulmão/patologia , Pulmão/metabolismo , Camundongos Endogâmicos C57BL , MicroRNAs/genética , MicroRNAs/metabolismo , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Enfisema Pulmonar/genética , Enfisema Pulmonar/metabolismo , Enfisema Pulmonar/patologia , Células Th17/imunologia , Células Th17/metabolismo
9.
Int J Immunopathol Pharmacol ; 38: 3946320241246713, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38649141

RESUMO

Purpose: This retrospective study investigates the influence of overweight and obesity status on pulmonary function, airway inflammatory markers, and airway responsiveness in elderly asthma patients. Methods: Patients with asthma older than 65 years old who completed a bronchial provocation test (BPT) or bronchial dilation test (BDT) and a fractional exhaled nitric oxide (FeNO) test between December 2015 and June 2020 were identified retrospectively for this study. All of the patients were categorized into overweight/obesity and non-obesity groups based on their BMI. Pulmonary function test (PFT) and FeNO measurements were accomplished according to the 2014 recommendations of the Chinese National Guidelines of Pulmonary Function Test and American Thoracic Society/European Respiratory Society recommendations, respectively. Results: A total of 136 patients with an average age of 71.2 ± 5.40 years were identified. The average BMI was 23.8 ± 3.63, while the value of FeNO was 42.3 ± 38.4 parts per billion (ppb). In contrast to the non-obesity group, which had a value of 48.8 ± 43.1 ppb for FeNO, the overweight/obesity group had a significant lower value of 35.4 ± 31.4 ppb. There was no significant difference in the proportion of individuals with high airway hyperresponsiveness between the overweight/obesity and non-obesity groups (96 patients in total). Multiple linear regression analysis established an inverse correlation between FeNO and Provocation concentration causing a 20% fall in FEV1(PC20) but excluded significant relationships with age and BMI. The model's R is 0.289, and its p value is 0.045. Conclusion: The elderly Chinese Han asthmatics with overweight/obesity had lower FeNO levels than those with non-obese according to our findings. In addition, the FeNO level was inversely correlated between FeNO levels and PC20 in elderly asthmatics.


Assuntos
Asma , Óxido Nítrico , Obesidade , Sobrepeso , Idoso , Feminino , Humanos , Masculino , Povo Asiático , Asma/fisiopatologia , Asma/metabolismo , Asma/diagnóstico , Índice de Massa Corporal , Testes Respiratórios , Testes de Provocação Brônquica , China/epidemiologia , Teste da Fração de Óxido Nítrico Exalado , Óxido Nítrico/metabolismo , Óxido Nítrico/análise , Obesidade/fisiopatologia , Obesidade/metabolismo , Sobrepeso/fisiopatologia , Sobrepeso/metabolismo , Testes de Função Respiratória , Hipersensibilidade Respiratória/fisiopatologia , Hipersensibilidade Respiratória/metabolismo , Hipersensibilidade Respiratória/diagnóstico , Estudos Retrospectivos
10.
Adv Sci (Weinh) ; 11(20): e2305832, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38564766

RESUMO

Effective presentation of antigens by dendritic cells (DC) is essential for achieving a robust cytotoxic T lymphocytes (CTLs) response, in which cDC1 is the key DC subtype for high-performance activation of CTLs. However, low cDC1 proportion, complex process, and high cost severely hindered cDC1 generation and application. Herein, the study proposes an in situ cDC1 recruitment and activation strategy with simultaneous inhibiting cancer stemness for inducing robust CTL responses and enhancing the anti-tumor effect. Fms-like tyrosine kinase 3 ligand (FLT3L), Poly I:C, and Nap-CUM (NCUM), playing the role of cDC1 recruitment, cDC1 activation, inducing antigen release and decreasing tumor cell stemness, respectively, are co-encapsulated in an in situ hydrogel vaccine (FP/NCUM-Gel). FP/NCUM-Gel is gelated in situ after intra-tumoral injection. With the near-infrared irradiation, tumor cell immunogenic cell death occurred, tumor antigens and immunogenic signals are released in situ. cDC1 is recruited to tumor tissue and activated for antigen cross-presentation, followed by migrating to lymph nodes and activating CTLs. Furthermore, tumor cell stemness are inhibited by napabucasin, which can help CTLs to achieve comprehensive tumor killing. Collectively, the proposed strategy of cDC1 in situ recruitment and activation combined with stemness inhibition provides great immune response and anti-tumor potential, providing new ideas for clinical tumor vaccine design.


Assuntos
Apresentação de Antígeno , Vacinas Anticâncer , Células Dendríticas , Hidrogéis , Vacinas Anticâncer/imunologia , Camundongos , Animais , Células Dendríticas/imunologia , Apresentação de Antígeno/imunologia , Linfócitos T Citotóxicos/imunologia , Modelos Animais de Doenças , Células-Tronco Neoplásicas/imunologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Humanos , Camundongos Endogâmicos C57BL
11.
J Pediatr Orthop ; 44(6): e490-e495, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38533533

RESUMO

BACKGROUND: The shape of the labrum is strongly correlated with outcomes of developmental dysplasia of the hip (DDH). Magnetic resonance imaging (MRI) is the generally preferred imaging technique for observing the labrum. PURPOSE: We aimed to find a correlation between the labrum shape and anterior-posterior (AP) pelvic measurements in children with DDH. METHODS: Preoperative AP pelvic x-ray radiographs and MRI of patients with DDH from January 2019 to December 2021 were retrospectively collected and divided into three groups by labrum shape on MRI: everted, partly inverted, and inverted. The acetabular length ratio (RAL) in patients with unilateral DDH and the ratio of acetabular length to interpedicular distance (RALI) in all patients were calculated. T-tests were used to analyze differences between the groups. Receiver operating characteristic curve (ROC) analysis was performed between the everted group and the partly inverted and inverted groups. RESULTS: We found significant differences in RAL between the everted and partly inverted groups, everted and inverted groups, and everted and combined groups. The ROC analysis showed that the best cutoff value for RAL was 0.945 between the everted and combined groups, with an area under the curve (AUC) of 88.4%. The sensitivity at the best RAL value was 0.783, and the specificity was 0.887. Moreover, we observed a significant difference in RALI between the everted, partly inverted, and inverted groups, as well as between the everted and combined groups. The optimal cutoff value for RALI between the everted and combined groups was 0.575, with an AUC of 74.5%. The sensitivity at the best RALI value was 0.765, and the specificity was 0.674. CONCLUSION: The RAL or RALI values on pelvic AP radiographs can be used to predict the shape of the labrum. LEVEL OF EVIDENCE: III.


Assuntos
Acetábulo , Displasia do Desenvolvimento do Quadril , Imageamento por Ressonância Magnética , Radiografia , Humanos , Estudos Retrospectivos , Feminino , Masculino , Displasia do Desenvolvimento do Quadril/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Acetábulo/diagnóstico por imagem , Radiografia/métodos , Lactente , Pré-Escolar , Curva ROC
12.
Int J Food Sci Nutr ; 75(5): 453-462, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38356165

RESUMO

The nutritional benefits and immunological advantages of consuming nuts and seeds are well-established. However, the link between nuts and seeds consumption and the susceptibility of being overweight or obese among adolescents is not clear. This study aims to explore this relationship in adolescents aged 12-19. Using a weighted multiple logistic regression model, we analysed data of the Food Patterns Equivalents Database and the U.S. National Health and Nutrition Examination Survey (NHANES) from 2003 to 2018. We found a significant association between nuts and seeds consumption and a reduced odds of being overweight or obese in females. Specifically, females who habitually consumed nuts and seeds had lower odds of being overweight or obese (OR = 0.55, 95% CI: 0.32-0.94). Additionally, we found an L-shaped relationship between nuts and seeds consumption and appropriate waist-to-height ratio in males. The findings suggest that nuts and seeds consumption may contribute to healthier physical development in adolescents.


Assuntos
Inquéritos Nutricionais , Nozes , Obesidade Infantil , Sementes , Humanos , Adolescente , Masculino , Feminino , Obesidade Infantil/epidemiologia , Criança , Dieta , Adulto Jovem , Fatores Sexuais , Estados Unidos , Comportamento Alimentar , Estudos Transversais , Sobrepeso/epidemiologia
14.
bioRxiv ; 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-37905101

RESUMO

Environmental air irritants including nanosized carbon black (nCB) can drive systemic inflammation, promoting chronic obstructive pulmonary disease (COPD) and emphysema development. The let-7 family of miRNAs is associated with IL-17-driven T cell inflammation, a canonical signature of lung inflammation. Recent evidence suggests the let-7 family is downregulated in patients with COPD, however, whether this repression conveys a functional consequence on emphysema pathology has not been elucidated. Here we show that overall expression of the let-7 miRNA clusters, let-7b/let-7c2 and let-7a1/let-7f1/let-7d, are reduced in the lungs and T cells of smokers with emphysema as well as in mice with cigarette smoke (CS)- or nCB-elicited emphysema. We demonstrate that loss of the let-7b/let-7c2-cluster in T cells predisposed mice to exaggerated CS- or nCB-elicited emphysema. Furthermore, ablation of the let-7b/let-7c2-cluster enhanced CD8+IL17a+ T cells (Tc17) formation in emphysema development in mice. Additionally, transgenic mice overexpressing let-7 in T cells are resistant to Tc17 and CD4+IL17a+ T cells (Th17) development when exposed to nCB. Mechanistically, our findings reveal the master regulator of Tc17/Th17 differentiation, RAR-related orphan receptor gamma t (RORγt), as a direct target of let-7 miRNA in T cells. Overall, our findings shed light on the let-7/RORγt axis with let-7 acting as a molecular brake in the generation of Tc17 cells and suggests a novel therapeutic approach for tempering the augmented IL-17-mediated response in emphysema.

15.
Chron Respir Dis ; 20: 14799731231210559, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37889184

RESUMO

OBJECTIVE: Recently, a type 2 inflammation (T2) high endotype in bronchiectasis was identified. The fraction of exhaled nitric oxide (FeNO) and blood eosinophil count (BEC) are recognized as representative biomarkers of T2 inflammation. Herein, we investigate the clinical characteristics of T2-high endotype in non-cystic fibrosis bronchiectasis patients classified by FeNO and BEC. METHODS: This retrospective study included 164 bronchiectasis patients treated in the First Affiliated Hospital of Sun Yat-sen University from December 2017 to July 2022. Clinical characteristics were analyzed after classifying patients into four groups according to T2 inflammation biomarkers (FeNO ≥25 ppb; BEC ≥200/µL). RESULTS: Among the 164 bronchiectasis patients, 35.3% (58/164) presented with high FeNO, 30.5% (50/164) presented with high BEC, and 10.4% (17/164) had high FeNO and BEC. Patients with high FeNO and low BEC presented with better lung function, fewer affected lobes, and lower dyspnea prevalence compared with the three other groups. Moreover, decreased FeNO, instead of decreased BEC, is revealed to be an independent predictor for disease severity and airflow obstruction in bronchiectasis. CONCLUSIONS: Simultaneous evaluation of FeNO and BEC proposed different endotypes of bronchiectasis established that patients with low BEC and high FeNO had better lung function, fewer affected lobes, lower dyspnea prevalence, and less disease severity. This result will contribute to a more comprehensive assessment of the disease severity and lead to more precise treatment of T2 inflammation in bronchiectasis patients.


Assuntos
Asma , Bronquiectasia , Humanos , Eosinófilos , Teste da Fração de Óxido Nítrico Exalado , Asma/epidemiologia , Estudos Retrospectivos , Óxido Nítrico , Inflamação , Fibrose , Dispneia , Biomarcadores , Testes Respiratórios
16.
Acta Pharm Sin B ; 13(10): 4305-4317, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37799382

RESUMO

Chemoimmunotherapy has been approved as standard treatment for triple-negative breast cancer (TNBC), but the clinical outcomes remain unsatisfied. Abnormal epigenetic regulation is associated with acquired drug resistance and T cell exhaustion, which is a critical factor for the poor response to chemoimmunotherapy in TNBC. Herein, macrophage-camouflaged nanoinducers co-loaded with paclitaxel (PTX) and decitabine (DAC) (P/D-mMSNs) were prepared in combination with PD-1 blockade therapy, hoping to improve the efficacy of chemoimmunotherapy through the demethylation of tumor tissue. Camouflage of macrophage vesicle confers P/D-mMSNs with tumor-homing properties. First, DAC can achieve demethylation of tumor tissue and enhance the sensitivity of tumor cells to PTX. Subsequently, PTX induces immunogenic death of tumor cells, promotes phagocytosis of dead cells by dendritic cells, and recruits cytotoxic T cells to infiltrate tumors. Finally, DAC reverses T cell depletion and facilitates immune checkpoint blockade therapy. P/D-mMSNs may be a promising candidate for future drug delivery design and cancer combination therapy in TNBC.

17.
J Hum Nutr Diet ; 36(5): 1845-1856, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37448140

RESUMO

BACKGROUND: Limited literature has addressed the impact of nut consumption in mitigating frailty. This study aimed to investigate the association between nut consumption and frailty among Americans aged above 60 years, employing two 24-h dietary recalls for analysis. METHODS: The data sets of the National Health and Nutrition Examination Survey (NHANES) (2003-2018) and the Food Patterns Equivalents Database were utilised for a weighted multiple logistic regression model to evaluate the association between nut consumption and frailty in elderly adults. Furthermore, a restricted cubic spline model was employed to investigate the nonlinear relationship between nut intake and frailty. Besides, stratified and interaction analyses were conducted to explore the sensitivity of nut consumption in reducing the risk of frailty in diverse subgroups. RESULTS: The research study comprised 10,033 individuals aged 60 years or above, of whom 3591 were classified as frailty and 5302 consumed nuts. In the multivariate logistic regression analysis that adjusted for covariates, the weighted multivariate adjusted odds ratios demonstrated that the prevalence of frailty was lower in the nut intake group than in nonconsumers. The stratified analysis indicated that nearly all subgroups who consumed nuts had a significantly lower risk of frailty compared to nonconsumers, and an interaction was observed between nut intake and nonhypertensive populations. The optimal threshold for nut intake to decrease the risk of frailty was identified as 1.02 ounces. CONCLUSIONS: The study concluded that nut consumption has a constructive impact on averting frailty in elderly adults, particularly in nonhypertensive individuals. Nut intake of ~1.02 ounces per day is advantageous in improving the quality of life in elderly adults.


Assuntos
Fragilidade , Nozes , Adulto , Idoso , Humanos , Estados Unidos , Inquéritos Nutricionais , Estudos Transversais , Fragilidade/epidemiologia , Fragilidade/prevenção & controle , Qualidade de Vida , Dieta
18.
Nutrients ; 15(9)2023 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-37432150

RESUMO

Ecological approaches can help to correct oral microbial dysbiosis and drive the advent and persistence of a symbiotic oral microbiome, which benefits long-term dental caries control. The aim of this study was to investigate the impact of the prebiotic Galacto-oligosaccharide (GOS) on the growth of probiotics L. plantarum 14,917 and its effect on the inhibitory ability of L. plantarum 14,917 against the growth of Streptococcus mutans and Candida albicans in an in vitro model. Single-species growth screenings were conducted in TSBYE broth with 1% glucose and 1-5% GOS. Interaction experiments were performed using duo- and multi-species models with inoculation of 105 CFU/mL S. mutans, 103 CFU/mL C. albicans, and 108 CFU/mL L. plantarum 14,917 under 1%, 5% GOS or 1% glucose. Viable cells and pH changes were measured. Real-time PCR was utilized to assess expression of C. albicans and S. mutans virulence genes. Six replicates were used for each group. Student's t-test, one-way ANOVA, and Kruskal-Wallis were employed to compare the outcomes of different groups. GOS significantly inhibited the growth of C. albicans and S. mutans in terms of growth quantity and speed when the two strains were grown individually. However, GOS did not affect the growth of L. plantarum 14,917. Moreover, 1% and 5% GOS enhanced the anti-fungal performance of L. plantarum 14,917 in comparison to 1% glucose. GOS as the carbon source resulted in a less acidic environment in the C. albicans and S. mutans duo-species model and multispecies model where L. plantarum 14,917 was added. When GOS was utilized as the carbohydrate substrate, S. mutans and C. albicans had a significant reduction in the expression of the HWP1, ECE1, atpD, and eno genes (p < 0.05). To our knowledge, this is the first study that reported the ability of GOS to neutralize S. mutans-C. albicans high caries of medium pH and to disrupt virulence gene expression. Moreover, as a prebiotic, GOS augmented the inhibitory ability of L. plantarum against C. albicans in vitro. The current study revealed the anti-caries potential of prebiotics GOS and shed light on novel caries prevention strategies from the perspective of prebiotics and probiotics. These findings provide a rationale for future biofilm or clinical studies to elucidate the effect of GOS on modulating oral microbiota and caries control.


Assuntos
Cárie Dentária , Lactobacillus plantarum , Humanos , Cariostáticos , Cárie Dentária/prevenção & controle , Prebióticos , Oligossacarídeos/farmacologia , Candida albicans , Glucose
19.
Int Orthop ; 2023 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-37442823

RESUMO

PURPOSE: Hip vessel examination provides key information on many hip-related pediatric diseases, and it has an important role in the evaluation of femoral head (FH) blood supply and diagnosis of avascular necrosis (AVN). The aim of this study was to investigate the feasibility of MR-enhanced high-resolution three-dimensional water-selective cartilage (3D-WATSc) sequence in visualizing the vessels of the hip joint in children. PATIENTS AND METHODS: Children with hip disease were randomly enrolled prospectively at our hospital from January 2021 to August 2022. We performed our institution's hip MRI protocol and enhanced high-resolution 3D-WATSc sequence. The 3D-WATSc images were reconstructed and analyzed, and images of the normal hip were categorized into grades 0-3. The abnormal hip images were compared with those of the normal side using the χ2 test. RESULTS: Twenty-four patients with unilateral hip abnormalities were included in this study. The cartilaginous vascular canal and ossification centre vessels of normal FHs were observed in 18 patients (75%) and met the grade 3 standard. An abnormal cartilaginous canal was observed in 16 patients (67%); meanwhile, 18 patients (75%) had abnormal extrachondral vessels. Comparison of high-resolution 3D-WATSc images with those of the normal side provided effective abnormal vascular information in 95.8% of patients. CONCLUSIONS: Enhanced high-resolution 3D-WATSc can visualize the blood vessels of the hip in children. This may provide a new method for the vascular study of various pediatric hip diseases.

20.
PeerJ ; 11: e15494, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37304877

RESUMO

Alcohol dependence is a chronic, relapsing encephalopathy characterized by compulsive craving for alcohol, loss of control over alcohol use, and the presence of negative emotions and physical discomfort when alcohol is unavailable. Harmful use of alcohol is one of the greatest risk factors for death, illness, and disability. Rho kinase inhibitors have neuroprotective effects. This study used metabonomics analysis to assess untreated astrocytes, astrocytes exposed to 75 mmol/L of alcohol, and astrocytes exposed to 75 mmol/L of alcohol and treated with 15 µg/mL fasudil for 24 h. One of the clearest differences between the alcohol-exposed and fasudil-treated alcohol-exposed groups was the abundance of lipids and lipid-like molecules, although glycerophospholipid metabolism was comparable in both groups. Our findings show that fasudil may alleviate alcohol-induced astrocyte damage by modifying lipid metabolism, providing a new approach for preventing and treating alcohol dependence.


Assuntos
Alcoolismo , Astrócitos , Humanos , Alcoolismo/complicações , Metabolismo dos Lipídeos , Etanol/efeitos adversos , Metabolômica
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