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1.
Iran J Public Health ; 53(3): 644-653, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38919298

RESUMO

Background: The regulation of p21 in the pyroptosis of cartilage cells still needs to be further clarified. We aimed to explore the regulation of p21 on the pyroptosis of cartilage cells and to reveal the improvement of osteoarthritis. Methods: Chondrocytes were collected and isolated from patients with osteoarthritis (average age 58.64 ± 4.32) in Xuzhou Third People's Hospital, China in 2019, and healthy volunteers (average age 58.23 ± 3.91) were enrolled as the control group. mRNA expression levels of p21 and pyroptosis-related proteins (NLRP3, ASC, total caspase1 and cleaved-Caspase1) were detected by Western blot and real-time PCR. Cell activity, total number of cells and number of dead cells were calculated with CCK-8, MTT. And the regulation of p21 on the pyroptosis of cartilage cells was verified with overexpression and knockdown of p21 in cartilage cells. Results: In cartilage cells of patients with osteoarthritis, the transcription and translation levels of pyrolysis-related genes (NLRP3, cleaved-caspase 1, and ASC) significantly increased (P<0.01). p21 expression was up-regulated and positively correlated with the changing trend of pyrolysis-related proteins (P<0.01). Overexpressing p21 genes in normal cartilage cells significantly increased the expression of pyrolysis-related proteins (P<0.01). Conclusion: The pyroptosis of cartilage cells is causally related to the process of osteoarthritis, and can be regulated by transcription factor p21, which is a potential therapeutic target for osteoarthritis.

2.
J Int Soc Sports Nutr ; 21(1): 2369613, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38904148

RESUMO

BACKGROUND: Despite the high risk of eating disorder (ED)-related attitudes and behaviors among female dancers, targeted scientific dietary regimens are currently inadequate. Time-restricted eating (TRE), a popular intermittent fasting protocol, has been shown to be effective in enhancing body composition and exercise performance in athletes. In this study, TRE was employed as a dietary regimen to improve body composition and exercise performance and address ED attitudes and behaviors in DanceSport dancers. METHODS: Twenty female DanceSport dancers were recruited and divided into two groups: TRE (n = 10) and normal diet (ND) (n = 10). The TRE group consumed their self-selected necessary energy intake exclusively between 11 a.m. and 7 p.m. (utilizing a 16-hour fasting and 8-hour eating window) for 6 weeks, while the ND group maintained their regular dieting patterns. The consumption of water, black tea, or coffee without added sugar or milk was not restricted. Physical activity and calorie intake were systematically recorded during the TRE intervention. Body composition, aerobic and anaerobic performance, and ED attitudes and behaviors were assessed before and after the TRE intervention. The trial was registered in the Chinese Clinical Trial Registry under the identifier ChiCTR2200063780. RESULTS: The fixed effects tests (p < 0.0001) and estimates for the intercept (p < 0.0001) of hunger level indicated a noticeable effect on the initial state of hunger during TRE. No significant differences were observed in ED attitudes or behaviors (p > 0.05). TRE resulted in a reduction in hip circumference (p = 0.039), fat mass (kg) (p = 0.0004), and body fat percentage (p = 0.0005), with no significant decrease in fat-free mass (p > 0.05). No significant improvement was observed in aerobic performance (p > 0.05). The average power (AP) (p = 0.01) and AP/Body weight ratio (p = 0.003) significantly increased. Additionally, the power drop decreased significantly (p = 0.019). Group-by-time interactions were observed for fat mass (kg) (p = 0.01), body fat percentage (p = 0.035), and AP/Body weight (p = 0.020). CONCLUSION: TRE can be considered a feasible nutritional strategy for DanceSport dancers, facilitating improvements in body composition without compromising aerobic and anaerobic exercise performance or exacerbating ED attitudes and behaviors. Moreover, TRE may facilitate more favorable physiological adaptations, potentially contributing to improved exercise performance.


Assuntos
Composição Corporal , Dança , Jejum , Transtornos da Alimentação e da Ingestão de Alimentos , Humanos , Feminino , Dança/fisiologia , Adulto Jovem , Ingestão de Energia , Exercício Físico/fisiologia , Fenômenos Fisiológicos da Nutrição Esportiva , Desempenho Atlético/fisiologia , Adulto , Adolescente
3.
Foods ; 13(11)2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38890854

RESUMO

Owing to the interplay of genetic and environmental factors, obesity has emerged as a significant global public health concern. To gain enhanced control over obesity, we examined the effects of type 2 resistant starch (RS2) and its promoted microbial-derived metabolite, indole-3-propionic acid (IPA), on hepatic steatosis, antioxidant activity, and gut microbiota in obese mice. Neither RS2 nor low-dose IPA (20 mg kg-1) exhibited a reduction in body weight or improved glucose and lipid metabolism in post-obesity state mice continuously fed the high-fat diet (HFD). However, both interventions improved hepatic steatosis, with RS2 being more effective in all measured parameters, potentially due to changes in gut microbiota and metabolites not solely attributed to IPA. LC-MS/MS analysis revealed increased serum IPA levels in both RS2 and IPA groups, which positively correlated with Bifidobacterium and Clostridium. Moreover, RS2 exhibited a more significant restoration of gut dysbiosis by promoting the abundance of health-promoting bacteria including Faecalibaculum and Bifidobacterium. These findings suggest that the regulatory role of RS2 on tryptophan metabolism only partially explains its prebiotic activity. Future studies should consider increasing the dose of IPA and combining RS2 and IPA to explore their potential interventions in obesity.

4.
ACS Appl Mater Interfaces ; 16(24): 31586-31596, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38837344

RESUMO

We leveraged the potential of high χ-low N block copolymer (BCP), namely, poly[2-(perfluorobutyl) ethyl methacrylate]-block-poly(2-vinylpyridine) (P2PFBEMA-b-P2VP), and demonstrated its utility in next-generation nanomanufacturing. By combining molecular dynamics simulations with experiments, the χ value was calculated to be as high as 0.4 (at 150 °C), surpassing similar structures. Highly ordered features suitable for application were observed, ranging in periods from 19.0 nm down to 12.1 nm, with feature sizes as small as 6 nm. Transmission electron microscopy images of the BCP solutions indicated that preformed micelles in the solution facilitated the self-assembly process of the thin film. In addition, the vertical or parallel orientation of the cylindrical structure was determined by manipulating the solvent, substrate, and annealing conditions. Finally, guided by a wide topographical template, nearly defect-free directed self-assembly (DSA) lines with a resolution of 8 nm were achieved, highlighting its potential practical application in DSA lithography technology.

5.
Mar Pollut Bull ; 205: 116570, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38861798

RESUMO

The study applied a tiered ecological risk assessment method to evaluate the long-term status and trend of the ecological risks of dissolved heavy metals from 2011 to 2019 in the Yangtze River Estuary and Zhejiang coastal waters, China. The results for spring, summer, and autumn of 2019 indicated that Pb, Cd, and Zn posed no adverse ecological risk, Cu posed a potential ecological risk, and As posed an ecological risk. The annual results from 2011 to 2019 suggested that Pb, Cd, and Zn posed no adverse ecological risks, and As and Cu posed an ecological risk. The trend analysis in the nine years showed that the ecological risk of Cu is gradually decreasing, while that of As is still a concern. The overall trend is attributed to the environmental protection policies that reduced these contaminants' terrestrial sources and atmospheric sources.

6.
Heliyon ; 10(11): e32072, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38912460

RESUMO

Background: Heart failure (HF) is a severe disease threatening people's health. The aim of this study is to find a significant biomarker inducive to predicting the prognosis of HF. Methods: GSE135055 and GSE161472 datasets were reanalyzed for exploring key genes related to HF. This single-center, prospective, observational cohort study enrolled 298 patients with or without HF from the Cardiology Department of Zhongda Hospital. Levels of ADAM8 were measured using ELISA kits. Major adverse cardiovascular events (MACEs) were defined as the composite end points of the first occurrence of rehospitalization because of HF or cardiac-related death during one-year follow-up. Results: (1) Bioinformatics analysis showed that ADAM8 was a key gene in HF via mainly regulating the mechanisms of extracellular matrix (ECM) organization. (2) Levels of ADAM8 were significantly increased in the HF group, compared to the non-failing (NF) group (p < 0.001), especially in patients with HFrEF (p < 0.05), and HFmEF (p < 0.05). The prevalence of HF in the high ADAM8 group (≧472.916 pg/mL) was significantly higher than in the low ADAM8 group (<472.916 pg/mL) (41.95 % vs 30.54 %, p < 0.01). (3) Correlation analysis revealed that ADAM8 was negatively correlated to the left ventricular ejection fraction (LVEF) (r = -0.272, p < 0.001). ROC analysis showed that the AUC of ADAM8 in predicting HF and predicting the MACE were 0.701 (p < 0.0001) and 0.683 (p < 0.0001), respectively. (4) Logistic and Cox regression both indicated that high ADAM8 expression can predict adverse prognosis of HF. Conclusions: ADAM8 may be a risk factor for HF, especially in cases of HFrEF and HFmEF. High ADAM8 expression in plasma was related to the decreased heart function, and can predict the adverse prognosis of HF.

7.
Extremophiles ; 28(2): 28, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38890178

RESUMO

Four halophilic archaeal strains YCN1T, YCN58T, LT38T, and LT62T were isolated from Yuncheng Salt Lake (Shanxi, China) and Tarim Basin (Xinjiang, China), respectively. Phylogenetic and phylogenomic analyses showed that these four strains tightly cluster with related species of Halobacterium, Natronomonas, Halorientalis, and Halobellus, respectively. The AAI, ANI, and dDDH values between these four strains and their related species of respective genera were lower than the proposed threshold values for species delineation. Strains YCN1T, YCN58T, LT38T, and LT62T could be differentiated from the current species of Halobacterium, Natronomonas, Halorientalis, and Halobellus, respectively, based on the comparison of diverse phenotypic characteristics. The polar lipid profiles of these four strains were closely similar to those of respective relatives within the genera Halobacterium, Natronomonas, Halorientalis, and Halobellus, respectively. The phenotypic, phylogenetic, and genome-based analyses indicated that strains YCN1T, YCN58T, LT38T, and LT62T represent respective novel species within the genera Halobacterium, Natronomonas, Halorentalis, and Halobellus, for which the names Halobacterium yunchengense sp. nov., Natronomonas amylolytica sp. nov., Halorientalis halophila sp. nov., and Halobellus salinisoli sp. nov. are proposed, respectively.


Assuntos
Lagos , Filogenia , Lagos/microbiologia , Microbiologia do Solo , Halobacterium/genética , Halobacterium/isolamento & purificação , Genoma Arqueal , Halobacteriaceae/genética , Halobacteriaceae/isolamento & purificação , Halobacteriaceae/classificação
9.
Curr Microbiol ; 81(7): 194, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38806737

RESUMO

Four halophilic archaeal strains, BCD28T, BND7T, PSR21T, and PSRA2T, were isolated from coastal and inland saline soil, respectively. The 16S rRNA and rpoB' gene sequence similarities among these four strains and current species of Halomarina were 95.9-96.6% and 86.9-90.3%, respectively. Phylogenetic and phylogenomic analyses revealed that these four strains tightly cluster with the current species of the genus Halomarina. The AAI, ANI, and dDDH values among these four strains and current species of Halomarina were 65.3-68.4%, 75.8-77.7%, and 20.3-22.0%, respectively, clearly below the threshold values for species demarcation. Strains BCD28T, BND7T, PSR21T, and PSRA2T could be differentiated from the current species of Halomarina based on the comparison of diverse phenotypic characteristics. The major polar lipids of these four strains were phosphatidylglycerol (PG), phosphatidylglycerol phosphate methyl ester (PGP-Me), and four to five glycolipids. Phosphatidylglycerol sulfate (PGS) was only detected in strain BND7T. The phenotypic, phylogenetic, and genome-based analyses suggested that strains BCD28T (= CGMCC 1.18776T = JCM 34908T), BND7T (= CGMCC 1.18778T = JCM 34910T), PSR21T (= CGMCC 1.17027T = JCM 34147T), and PSRA2T (= CGMCC 1.17214T = JCM 34148T) represent four novel species of the genus Halomarina, for which the names Halomarina litorea sp. nov., Halomarina pelagica sp. nov., Halomarina halobia sp. nov., and Halomarina ordinaria sp. nov. are proposed.


Assuntos
DNA Arqueal , Filogenia , RNA Ribossômico 16S , Microbiologia do Solo , RNA Ribossômico 16S/genética , DNA Arqueal/genética , DNA Arqueal/química , Halobacteriaceae/classificação , Halobacteriaceae/genética , Halobacteriaceae/isolamento & purificação , Composição de Bases , Fosfolipídeos/análise , Análise de Sequência de DNA
10.
Zhongguo Zhong Yao Za Zhi ; 49(10): 2710-2721, 2024 May.
Artigo em Chinês | MEDLINE | ID: mdl-38812171

RESUMO

Studies have reported that the hemostatic effect of Sanguisorbae Radix(SR) is significantly enhanced after processing with charcoal. However, the standard components(tannins and gallic acid) specified in the Chinese Pharmacopeia decrease in charcoal-fried Sanguisorbae Radix(CSR), which is contrast to the enhancement of the hemostatic effect. Therefore, this study aimed to optimize the charcoal-frying process of SR based on its hemostatic efficacy and comprehensively analyze the components of SR and its processed products, thus exploring the material basis for the hemostatic effect. The results indicated that SR processed at 250 ℃ for 14 min(14-min CSR) not only complied with the description in the Chinese Pharmacopeia but also demonstrated improved blood-coagulating and blood-adsorbing effects compared with raw SR(P<0.05). Moroever, 14-min CSR reduced the bleeding time in the rat models of tail snipping, liver bleeding, and muscle injury, surpassing both raw and excessively fried SR(16 min processed) as well as tranexamic acid(P<0.05). Ellagitannin, ellagic acid, methyl gallate, pyrogallic acid, protocatechuic acid, Mg, Ca, Mn, Cu, and Zn contributed to the hemostatic effect of CSR over SR. Among these substances, ellagitannin, ellagic acid, Mg, and Ca had high content in the 14 min CSR, reaching(106.73±14.87),(34.86±4.43),(2.81±0.23), and(1.21±0.23) mg·g~(-1), respectively. Additionally, the color difference value(ΔE~*ab) of SR processed to different extents was correlated with the content of the aforementioned hemostatic substances. In summary, this study optimized the charcoal-frying process as 250 ℃ for 14 min for SR based on its hemostatic effect. Furthermore, ellagic acid and/or the powder chromaticity are proposed as indicators for the processing and quality control of CSR.


Assuntos
Carvão Vegetal , Medicamentos de Ervas Chinesas , Hemostáticos , Ratos Sprague-Dawley , Sanguisorba , Animais , Ratos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Hemostáticos/farmacologia , Hemostáticos/química , Sanguisorba/química , Carvão Vegetal/química , Masculino , Culinária , Coagulação Sanguínea/efeitos dos fármacos , Humanos
11.
Front Immunol ; 15: 1349138, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38720903

RESUMO

Autoimmune diseases can damage specific or multiple organs and tissues, influence the quality of life, and even cause disability and death. A 'disease in a dish' can be developed based on patients-derived induced pluripotent stem cells (iPSCs) and iPSCs-derived disease-relevant cell types to provide a platform for pathogenesis research, phenotypical assays, cell therapy, and drug discovery. With rapid progress in molecular biology research methods including genome-sequencing technology, epigenetic analysis, '-omics' analysis and organoid technology, large amount of data represents an opportunity to help in gaining an in-depth understanding of pathological mechanisms and developing novel therapeutic strategies for these diseases. This paper aimed to review the iPSCs-based research on phenotype confirmation, mechanism exploration, drug discovery, and cell therapy for autoimmune diseases, especially multiple sclerosis, inflammatory bowel disease, and type 1 diabetes using iPSCs and iPSCs-derived cells.


Assuntos
Doenças Autoimunes , Células-Tronco Pluripotentes Induzidas , Humanos , Doenças Autoimunes/imunologia , Doenças Autoimunes/terapia , Animais , Descoberta de Drogas , Terapia Baseada em Transplante de Células e Tecidos/métodos
12.
Artigo em Inglês | MEDLINE | ID: mdl-38758376

RESUMO

PURPOSE: To compare the accuracy of 14 formulas in calculating intraocular lens (IOL) power in extremely long eyes with axial length (AL) over 30.0 mm. METHODS: In this retrospective study, 211 eyes (211 patients) with ALs > 30.0 mm were successfully treated with cataract surgery without complications. Ocular biometric parameters were obtained from IOLMaster 700. Fourteen formulas were evaluated using the optimized A constants: Barrett Universal II (BUII), Kane, Emmetropia Verifying Optical (EVO) 2.0, PEARL-DGS, T2, SRK/T, Holladay 1, Holladay 2, Haigis and Wang-Koch AL adjusted formulas (SRK/Tmodified-W/K, Holladay 1modified-W/K, Holladay 1NP-modified-W/K, Holladay 2modified-W/K, Holladay 2NP-modified-W/K). The mean prediction error (PE) and standard deviation (SD), mean absolute errors (MAE), median absolute errors (MedAE), and the percentage of prediction errors (PEs) within ± 0.25 D, ± 0.50 D, ± 1.00 D were analyzed. RESULTS: The Kane formula had the smallest MAE (0.43 D) and MedAE (0.34 D). The highest percentage of PE within ± 0.25 D was for EVO 2.0 (37.91%) and the Holladay 1NP-modified-W/K formulas (37.91%). The Kane formula had the highest percentage of PEs in the range of ± 0.50, ± 0.75, ± 1.00, and ± 2.00 D. There was no significant difference in PEs within ± 0.25, ± 0.50 ± 0.75 and ± 1.00 D between BUII, Kane, EVO 2.0 and Wang-Koch AL adjusted formulas (P > .05) by using Cochran's Q test. The Holladay 2modified-W/K formula has the lowest percentage of hyperopic outcomes (29.38%). CONCLUSIONS: The BUII, Kane, EVO 2.0 and Wang-Koch AL adjusted formulas have comparable accuracy for IOL power calculation in eyes with ALs > 30.0 mm.

13.
Breast Cancer ; 31(4): 684-694, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38643430

RESUMO

BACKGROUND: Guideline recommendations for the application of neoadjuvant chemotherapy (NACT) in T2N1M0 stage hormone receptor-positive, HER2-negative (HR + /HER2-) breast cancer are ambiguous. The debate continues regarding whether NACT or adjuvant chemotherapy (ACT) offers superior survival outcomes for these patients. MATERIALS AND METHODS: Female patients diagnosed with HR + /HER2- breast cancer at T2N1M0 stage between 2010 and 2020, were identified from the Surveillance, Epidemiology, and End Results database and divided into two groups, the NACT group and the ACT group. Propensity score matching (PSM) was utilized to establish balanced cohorts between groups, considering baseline features. Kaplan-Meier (K-M) analysis and the Cox proportional hazards model were executed to assess the efficacy of both NACT and ACT in terms of overall survival (OS) and breast cancer-specific survival (BCSS). A logistic regression model was employed to examine the association between predictive variables and response to NACT. RESULTS: After PSM, 4,682 patients were finally included. K-M curves showed that patients receiving NACT exhibited significantly worse OS and BCSS when compared with patients undergoing ACT. Multivariable Cox analysis indicated that not achieving pathologic complete response (non-pCR) after NACT (versus ACT), was identified as an adverse prognostic factor for OS (HR 1.58, 95% CI 1.36-1.83) and BCSS (HR 1.70, 95% CI 1.44-2. 02). The logistic regression model revealed that low tumor grade independently predicted non-pCR. CONCLUSION: Among T2N1M0 stage HR + /HER2- patients, OS and BCSS of NACT were inferior to ACT. Patients who attained non-pCR after NACT demonstrated significantly worse survival outcomes compared with those who received ACT.


Assuntos
Neoplasias da Mama , Terapia Neoadjuvante , Receptor ErbB-2 , Receptores de Progesterona , Programa de SEER , Humanos , Feminino , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Quimioterapia Adjuvante/métodos , Terapia Neoadjuvante/métodos , Pessoa de Meia-Idade , Estudos Retrospectivos , Receptor ErbB-2/metabolismo , Receptores de Progesterona/metabolismo , Adulto , Idoso , Estadiamento de Neoplasias , Receptores de Estrogênio/metabolismo , Estimativa de Kaplan-Meier , Pontuação de Propensão , Modelos de Riscos Proporcionais
14.
Artigo em Inglês | MEDLINE | ID: mdl-38682858

RESUMO

The orexin system is closely related to the pathogenesis of Alzheimer's disease (AD). Orexin-A aggravates cognitive dysfunction and increases amyloid ß (Aß) deposition in AD model mice, but studies of different dual orexin receptor (OXR) antagonists in AD have shown inconsistent results. Our previous study revealed that OX1R blockade aggravates cognitive deficits and pathological progression in 3xTg-AD mice, but the effects of OX2R and its potential mechanism in AD have not been reported. In the present study, OX2R was blocked by oral administration of the selective OX2R antagonist MK-1064, and the effects of OX2R blockade on cognitive dysfunction and neuropsychiatric symptoms in 3xTg-AD mice were evaluated via behavioral tests. Then, immunohistochemistry, western blotting, and ELISA were used to detect Aß deposition, tau phosphorylation, and neuroinflammation, and electrophysiological and wheel-running activity recording were recorded to observe hippocampal synaptic plasticity and circadian rhythm. The results showed that OX2R blockade ameliorated cognitive dysfunction, improved LTP depression, increased the expression of PSD-95, alleviated anxiety- and depression-like behaviors and circadian rhythm disturbances in 3xTg-AD mice, and reduced Aß pathology, tau phosphorylation, and neuroinflammation in the brains of 3xTg-AD mice. These results indicated that chronic OX2R blockade exerts neuroprotective effects in 3xTg-AD mice by reducing AD pathology at least partly through improving circadian rhythm disturbance and the sleep-wake cycle and that OX2R might be a potential target for the prevention and treatment of AD; however, the potential mechanism by which OX2R exerts neuroprotective effects on AD needs to be further investigated.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Modelos Animais de Doenças , Progressão da Doença , Camundongos Transgênicos , Antagonistas dos Receptores de Orexina , Animais , Doença de Alzheimer/metabolismo , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/patologia , Camundongos , Antagonistas dos Receptores de Orexina/farmacologia , Disfunção Cognitiva/tratamento farmacológico , Receptores de Orexina/metabolismo , Peptídeos beta-Amiloides/metabolismo , Masculino , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Hipocampo/metabolismo
15.
Eur J Med Chem ; 271: 116433, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38678826

RESUMO

PD-1/PD-L1 pathway blockade is a promising immunotherapy for the treatment of cancer. In this manuscript, a series of triaryl compounds containing ester chains were designed and synthesized based on the pharmacophore studies of the lead BMS-1. After several SAR iterations, 22 showed the best biochemical activity binding to hPD-L1 with an IC50 of 1.21 nM in HTRF assay, and a KD value of 5.068 nM in SPR analysis. Cell-based experiments showed that 22 effectively promoted A549 cell death by restoring T-cell immune function. 22 showed significant in vivo antitumor activity in a 4T1 mouse model without obvious toxicity, with a TGI rate of 67.8 % (20 mg/kg, ip). Immunohistochemistry data indicated that 22 activates the immune activity in tumors. These results suggest that 22 is a promising compound for further development of PD-1/PD-L1 inhibitor for cancer therapy.


Assuntos
Antineoplásicos , Antígeno B7-H1 , Ésteres , Receptor de Morte Celular Programada 1 , Humanos , Animais , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/metabolismo , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/metabolismo , Camundongos , Relação Estrutura-Atividade , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Estrutura Molecular , Ésteres/química , Ésteres/farmacologia , Ésteres/síntese química , Ensaios de Seleção de Medicamentos Antitumorais , Relação Dose-Resposta a Droga , Proliferação de Células/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Feminino , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/química , Inibidores de Checkpoint Imunológico/síntese química
16.
Int Immunopharmacol ; 133: 112070, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38640716

RESUMO

Skin, the largest organ of body, is a highly immunogenic tissue with a diverse collection of immune cells. Highly polymorphic human leukocyte antigen (HLA) molecules have a central role in coordinating immune responses as recognition molecules. Nevertheless, HLA gene expression patterns among diverse cell types within a specific organ, like the skin, have yet to be thoroughly investigated, with stromal cells attracting much less attention than immune cells. To illustrate HLA expression profiles across different cell types in the skin, we performed single-cell RNA sequencing (scRNA-seq) analyses on skin datasets, covering adult and fetal skin, and hair follicles as the skin appendages. We revealed the variation in HLA expression between different skin populations by examining normal adult skin datasets. Moreover, we evaluated the potential immunogenicity of multiple skin populations based on the expression of classical HLA class I genes, which were well represented in all cell types. Furthermore, we generated scRNA-seq data of developing skin from fetuses of 15 post conception weeks (PCW), 17 PCW, and 22 PCW, delineating the dynamic expression of HLA genes with cell type-dependent variation among various cell types during development. Notably, the pseudotime trajectory analysis unraveled the significant variance in HLA genes during the evolution of vascular endothelial cells. Moreover, we uncovered the immune-privileged properties of hair follicles at single-cell resolution. Our study presents a comprehensive single-cell transcriptomic landscape of HLA genes in the skin, which provides new insights into variation in HLA molecules and offers a clue for allogeneic skin transplantation.


Assuntos
Perfilação da Expressão Gênica , Antígenos HLA , Análise de Célula Única , Pele , Transcriptoma , Humanos , Pele/imunologia , Pele/metabolismo , Antígenos HLA/genética , Antígenos HLA/imunologia , Folículo Piloso/imunologia , Folículo Piloso/metabolismo , Feto/imunologia , Adulto , Privilégio Imunológico
17.
BMC Microbiol ; 24(1): 131, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38643098

RESUMO

BACKGROUND: Exposure to extreme cold or heat temperature is one leading cause of weather-associated mortality and morbidity in animals. Emerging studies demonstrate that the microbiota residing in guts act as an integral factor required to modulate host tolerance to cold or heat exposure, but common and unique patterns of animal-temperature associations between cold and heat have not been simultaneously examined. Therefore, we attempted to investigate the roles of gut microbiota in modulating tolerance to cold or heat exposure in mice. RESULTS: The results showed that both cold and heat acutely change the body temperature of mice, but mice efficiently maintain their body temperature at conditions of chronic extreme temperatures. Mice adapt to extreme temperatures by adjusting body weight gain, food intake and energy harvest. Fascinatingly, 16 S rRNA sequencing shows that extreme temperatures result in a differential shift in the gut microbiota. Moreover, transplantation of the extreme-temperature microbiota is sufficient to enhance host tolerance to cold and heat, respectively. Metagenomic sequencing shows that the microbiota assists their hosts in resisting extreme temperatures through regulating the host insulin pathway. CONCLUSIONS: Our findings highlight that the microbiota is a key factor orchestrating the overall energy homeostasis under extreme temperatures, providing an insight into the interaction and coevolution of hosts and gut microbiota.


Assuntos
Microbioma Gastrointestinal , Temperatura Alta , Animais , Camundongos , Temperatura , Microbioma Gastrointestinal/fisiologia , Temperatura Baixa , Adaptação Fisiológica/fisiologia
18.
Food Chem ; 449: 139246, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38604035

RESUMO

The levels of metabolites in honey are influenced by floral origin, production region, and bee species. However, how environmental factors affect honey quality remains unclear. Based on untargeted metabolomics and using UPLC Q-Orbitrap MS, we analyzed 3596 metabolites in 51 honey samples from Yunnan and Shennongjia. Comparative analysis revealed that geniposidic acid, kynurenic acid and caffieine accumulated at significantly different levels between Shennongjia and Yunnan honey. Based on cluster structure analysis, 36 Yunnan honey samples were divided into two distinct groups by altitude. Notably, quercetin, hyperoside, taxifolin, rutin, tryptophan, astragalin and phenylalanine were higher levels in high-altitude honey (>1700 m), whereas abscisic acid was higher levels in low-altitude honey (≤1700 m). Among these, significantly elevated levels of hyperoside, taxfolin, astragalin, and tryptophan were observed in honey collected from high-altitude areas in Shennongjia. Our findings highlight the effect of altitude on honey health-promoting components, providing valuable insights into honey quality.


Assuntos
Altitude , Mel , Mel/análise , Animais , Abelhas/metabolismo , China , Metabolômica , Cromatografia Líquida de Alta Pressão
19.
J Biomater Sci Polym Ed ; : 1-22, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38652755

RESUMO

Titanium (Ti) implants are widely used in orthopedic and dental applications due to their excellent biocompatibility and mechanical properties. However, bacterial adhesion and subsequent biofilm formation on implant surfaces pose a significant risk of postoperative infections and complications. Conventional surface modifications often lack long-lasting antibacterial efficacy, necessitating the development of novel coatings with enhanced antimicrobial properties. This study aims to develop a novel Ag-TiO2-OTS (Silver-Titanium dioxide-Octadecyltrichlorosilane, ATO) nanocomposite coating, through a chemical plating method. By employing a 'resist-killing-disintegrate' approach, the coating is designed to inhibit bacterial adhesion effectively, and facilitate pollutant removal with lasting effects. Characterization of the coatings was performed using spectroscopy, electron microscopy, and contact angle analysis. Antibacterial efficacy, quantitatively evaluated against E. coli and S. aureus over 168 h, showed a significant reduction in bacterial adhesion by 76.6% and 66.5% respectively, and bacterial removal rates were up to 83.8% and 73.3% in comparison to uncoated Ti-base material. Additionally, antibacterial assays indicated that the ratio of the Lifshitz-van der Waals apolar component to electron donor surface energy components significantly influences bacterial adhesion and removal, underscoring a tunable parameter for optimizing antibacterial surfaces. Biocompatibility assessments with the L929 cell line revealed that the ATO coatings exhibited excellent biocompatibility, with minimal cytotoxicity and no significant impact on cell proliferation or apoptosis. The ATO coatings provided a multi-functionality surface that not only resists bacterial colonization but also possesses self-cleaning capabilities, thereby marking a substantial advancement in the development of antibacterial coatings for medical implants.

20.
Front Neurol ; 15: 1365465, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38682033

RESUMO

Objective: This retrospective study aimed to investigate the clinical features of optic neuritis associated with COVID-19 (COVID-19 ON), comparing them with neuromyelitis optica-associated optic neuritis (NMO-ON), myelin oligodendrocyte glycoprotein-associated optic neuritis (MOG-ON), and antibody-negative optic neuritis (antibody-negative ON). Methods: Data from 117 patients (145 eyes) with optic neuritis at the Shantou International Eye Center (March 2020-June 2023) were categorized into four groups based on etiology: Group 1 (neuromyelitis optica-related optic neuritis, NMO-ON), Group 2 (myelin oligodendrocyte glycoprotein optic neuritis, MOG-ON), Group 3 (antibody-negative optic neuritis, antibody-negative ON), and Group 4 (optic neuritis associated with COVID-19, COVID-19 ON). Characteristics of T2 and enhancement in orbital magnetic resonance imaging (MRI) were assessed. Best-corrected visual acuity (BCVA) was compared before treatment, at a short-term follow-up (14 days), and at the last follow-up after treatment. Results: The COVID-19-associated optic neuritis (COVID-19 ON) group exhibited 100% bilateral involvement, significantly surpassing other groups (P < 0.001). Optic disk edema was observed in 100% of COVID-19 ON cases, markedly differing from neuromyelitis optica-related optic neuritis (NMO-ON) (P = 0.023). Orbital magnetic resonance imaging (MRI) revealed distinctive long-segment lesions without intracranial involvement in T1-enhanced sequences for the COVID-19 ON group compared to the other three groups (P < 0.001). Discrepancies in optic nerve sheath involvement were noted between the COVID-19 ON group and both NMO-ON and antibody-negative optic neuritis (antibody-negative ON) groups (P = 0.028). Before treatment, no significant difference in best-corrected visual acuity (BCVA) existed between the COVID-19 ON group and other groups. At the 14-day follow-up, BCVA in the COVID-19 ON group outperformed the NMO-ON (P < 0.001) and antibody-negative ON (P = 0.028) groups, with no significant difference observed compared to the myelin oligodendrocyte glycoprotein optic neuritis (MOG-ON) group. At the last follow-up after treatment, BCVA in the COVID-19 ON group significantly differed from the NMO-ON group (P < 0.001). Conclusion: Optic neuritis associated with COVID-19 (COVID-19 ON) predominantly presents with bilateral onset and optic disk edema. Orbital magnetic resonance imaging (MRI) demonstrates that COVID-19 ON presents as long-segment enhancement without the involvement of the intracranial segment of the optic nerve in T1-enhanced images. Glucocorticoid therapy showed positive outcomes.

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