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1.
J Nanobiotechnology ; 22(1): 575, 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39294599

RESUMO

Allergic rhinitis (AR) is a condition with limited treatment options. This study investigates the potential use of mesenchymal stem cell (MSC) nanovesicles as a novel therapy for AR. Specifically, the study explores the underlying mechanisms of MSC nanovesicle therapy by targeting dendritic cells (DCs). The researchers fabricated DC-targeted P-D2-EVs nanovesicles and characterized their properties. Transcriptomic sequencing and single-cell sequencing analyses were performed to study the impact of P-D2-EVs on AR mice, identifying core genes involved in the treatment. In vitro cell experiments were conducted to validate the effects of P-D2-EVs on DC metabolism, Th2 differentiation, and ILC2 activation. The results showed that P-D2-EVs efficiently targeted DCs. Transcriptomic sequencing analysis revealed differential expression of 948 genes in nasal tissue DCs of mice treated with P-D2-EVs. Single-cell sequencing further revealed that P-D2-EVs had inhibitory effects on DC activation, Th2 differentiation, and ILC2 activation, with Fut1 identified as the core gene. Validation experiments demonstrated that P-D2-EVs improved IL10 metabolism in DCs by downregulating Fut1 expression, thereby suppressing Th2 differentiation and ILC2 activation. Animal experiments confirmed the inhibitory effects of P-D2-EVs and their ability to ameliorate AR symptoms in mice. The study suggests that P-D2-EVs reshape DC metabolism and suppress Th2 differentiation and ILC2 activation through the inhibition of the Fut1/ICAM1/P38 MAPK signaling pathway, providing a potential therapeutic approach for AR.


Assuntos
Diferenciação Celular , Células Dendríticas , Células-Tronco Mesenquimais , Rinite Alérgica , Animais , Células Dendríticas/metabolismo , Camundongos , Rinite Alérgica/terapia , Rinite Alérgica/metabolismo , Células-Tronco Mesenquimais/metabolismo , Células Th2/imunologia , Camundongos Endogâmicos BALB C , Vesículas Extracelulares/metabolismo , Feminino , Modelos Animais de Doenças , Humanos
2.
Biomed Pharmacother ; 179: 117328, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39243435

RESUMO

Endometrial cancer is one of the three major malignant tumors of the reproductive system that threaten women's lives and health. The incidence of this disease is on the rise globally. Most cases of endometrial cancer comprise endometrioid adenocarcinomas, whose treatment is challenged by factors such as their high recurrence rate and the need to preserve fertility among young patients. Thus, oral endocrine therapy has become the main treatment modality. The main drugs used in oral endocrine therapy are progestins, selective estrogen receptor antagonists, and aromatase inhibitors. However, their clinical use is hindered by their low solubility and low oral utilization. The rapid development of nanotechnology allows the combination of these drugs with oral nano-formulations to create a good carrier. Such nanocarriers, including nanospheres, nanocapsules, and micelles can protect the drug against clearance and increase the site specificity of drug delivery. This paper reviews the pathogenesis of endometrioid endometrial cancer (EEC) and oral nano-formulations for endocrine therapy.


Assuntos
Carcinoma Endometrioide , Neoplasias do Endométrio , Humanos , Feminino , Neoplasias do Endométrio/tratamento farmacológico , Administração Oral , Carcinoma Endometrioide/tratamento farmacológico , Carcinoma Endometrioide/patologia , Nanopartículas , Animais , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/uso terapêutico
3.
Biomed Pharmacother ; 177: 117025, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38941893

RESUMO

As a broad-spectrum anticancer drug, cisplatin is widely used in the treatment of tumors in various systems. Unfortunately, several serious side effects of cisplatin limit its clinical application, the most common of which are nephrotoxicity and ototoxicity. Studies have shown that cochlear hair cell degeneration is the main cause of cisplatin-induced hearing loss. However, the mechanism of cisplatin-induced hair cell death remains unclear. The present study aimed to explore the potential role of activating transcription factor 6 (ATF6), an endoplasmic reticulum (ER)-localized protein, on cisplatin-induced ototoxicity in vivo and in vitro. In this study, we observed that cisplatin exposure induced apoptosis of mouse auditory OC-1 cells, accompanied by a significant increase in the expression of ATF6 and C/EBP homologous protein (CHOP). In cell or cochlear culture models, treatment with an ATF6 agonist, an ER homeostasis regulator, significantly ameliorated cisplatin-induced cytotoxicity. Further, our in vivo experiments showed that subcutaneous injection of an ATF6 agonist almost completely prevented outer hair cell loss and significantly alleviated cisplatin-induced auditory brainstem response (ABR) threshold elevation in mice. Collectively, our results revealed the underlying mechanism by which activation of ATF6 significantly improved cisplatin-induced hair cell apoptosis, at least in part by inhibiting apoptosis signal-regulating kinase 1 expression, and demonstrated that pharmacological activation of ATF6-mediated unfolded protein response is a potential treatment for cisplatin-induced ototoxicity.


Assuntos
Fator 6 Ativador da Transcrição , Apoptose , Cisplatino , Ototoxicidade , Resposta a Proteínas não Dobradas , Cisplatino/toxicidade , Animais , Fator 6 Ativador da Transcrição/metabolismo , Ototoxicidade/prevenção & controle , Ototoxicidade/etiologia , Ototoxicidade/patologia , Camundongos , Resposta a Proteínas não Dobradas/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Potenciais Evocados Auditivos do Tronco Encefálico/efeitos dos fármacos , Linhagem Celular , Masculino , Antineoplásicos/toxicidade , Células Ciliadas Auditivas/efeitos dos fármacos , Células Ciliadas Auditivas/metabolismo , Células Ciliadas Auditivas/patologia , Perda Auditiva/induzido quimicamente , Perda Auditiva/metabolismo , Perda Auditiva/patologia , Perda Auditiva/prevenção & controle , Camundongos Endogâmicos C57BL , Fator de Transcrição CHOP/metabolismo
4.
BMC Geriatr ; 24(1): 450, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38783172

RESUMO

OBJECTIVES: This study aimed to explore the association between ultra-processed foods and age-related hearing loss. METHODS: Cross-sectional analyses based on data from a nationally representative sample of 1075 adults aged over 50 in the US was performed. The odds ratios (ORs) and 95% confidence intervals (CIs) for hearing loss according to ultra-processed foods intake quartiles were calculated using a multiple adjusted logistic regression model. Restricted cubic spline model was used to flexibly model potential nonlinear relations between ultra-processed foods intake and possibility of hearing loss. We also explored statistical interactions and conducted subgroup analyses where they were found to be significant. RESULTS: Ultra-processed foods intake was significantly correlated with high-frequency hearing loss. After controlling for all covariables, individuals in the fourth quartile of Ultra-processed foods consumption had a 2.8 times higher chance of developing high-frequency hearing loss than individuals in the first quartile of Ultra-processed foods consumption. We also found that the association was more significant in non-Hispanic whites. CONCLUSIONS: This study discovered an association between Ultra-processed foods intake and the incidence of high-frequency hearing loss, which was more significant in non-Hispanic whites.


Assuntos
Fast Foods , Humanos , Estudos Transversais , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Fast Foods/efeitos adversos , Perda Auditiva/epidemiologia , Ingestão de Alimentos/fisiologia , Idoso de 80 Anos ou mais , Alimento Processado
5.
Sci Rep ; 14(1): 10019, 2024 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-38693171

RESUMO

Nasopharyngeal carcinoma (NPC) is a tumor that occurs in the nasopharynx. Although advances in detection and treatment have improved the prognosis of NPC the treatment of advanced NPC remains challenging. Here, we explored the effect of microRNA (miR)-122-5p on erastin-induced ferroptosis in NPC cells and the role of ferroptosis in the development of NPC. The effect of miR-122-5p silencing and overexpression and the effect of citrate synthase on erastin-induced lipid peroxidation in NPC cells was analyzed by measuring the amounts of malondialdehyde, Fe2+, glutathione, and reactive oxygen species and the morphological alterations of mitochondria. The malignant biological behavior of NPC cells was examined by cell counting kit-8, EDU, colony formation, Transwell, and wound healing assays. The effects of miR-122-5p on cell proliferation and migration associated with ferroptosis were examined in vivo in a mouse model of NPC generated by subcutaneous injection of NPC cells. We found that erastin induced ferroptosis in NPC cells. miR-122-5p overexpression inhibited CS, thereby promoting erastin-induced ferroptosis in NPC cells and decreasing NPC cell proliferation, migration, and invasion.


Assuntos
Movimento Celular , Proliferação de Células , Ferroptose , MicroRNAs , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Piperazinas , Ferroptose/efeitos dos fármacos , Ferroptose/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/patologia , Humanos , Animais , Linhagem Celular Tumoral , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/genética , Camundongos , Proliferação de Células/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Camundongos Nus
6.
Chem Soc Rev ; 53(7): 3302-3326, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38354058

RESUMO

Secondary batteries are a core technology for clean energy storage and conversion systems, to reduce environmental pollution and alleviate the energy crisis. Oxide cathodes play a vital role in revolutionizing battery technology due to their high capacity and voltage for oxide-based batteries. However, oxygen vacancies (OVs) are an essential type of defect that exist predominantly in both the bulk and surface regions of transition metal (TM) oxide batteries, and have a crucial impact on battery performance. This paper reviews previous studies from the past few decades that have investigated the intrinsic and anionic redox-mediated OVs in the field of secondary batteries. We focus on discussing the formation and evolution of these OVs from both thermodynamic and kinetic perspectives, as well as their impact on the thermodynamic and kinetic properties of oxide cathodes. Finally, we offer insights into the utilization of OVs to enhance the energy density and lifespan of batteries. We expect that this review will advance our understanding of the role of OVs and subsequently boost the development of high-performance electrode materials for next-generation energy storage devices.

7.
Small ; 20(7): e2304277, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37806760

RESUMO

That magic-size clusters (MSCs) have their counterpart precursor compounds (PCs) has not been generally accepted by expertise circles. Here, experimental evidence to support this new concept is presented. With aqueous-phase CdSe MSCs as a model system, it is shown that when the MSCs are dispersed in water containing a certain amount of L-cysteine (Cys), the MSCs disappear slowly. Upon the addition of CdCl2 , the MSCs recover. It is proposed that after dispersing, the MSCs transform to their quasi-isomeric, non-absorbing PCs upon Cys addition. In the presence of CdCl2 , the PCs transform back to the MSCs due to Cys elimination. The surface ligand Cys of the MSCs plays a significant role in the reversible transformations. The present study provides compelling evidence that absorbing MSCs have their non-absorbing PCs. The study findings suggest that the transformation between two MSCs that display absorption spectral shifts in a stepwise pattern is assisted by their PCs.

8.
BMJ Glob Health ; 8(12)2023 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-38101937

RESUMO

INTRODUCTION: Cardiovascular disease (CVD) continues to pose a significant burden among the elderly population in China. There is a knowledge gap in the temporal trends, regional variations and socioeconomic inequalities among this vulnerable population. METHODS: This study conducted cross-sectional and cohort analyses based on four survey waves of the China Health and Retirement Longitudinal Study among adults aged ≥60 years spanning 2011-2018 across 28 provinces. Cross-sectional analyses examined temporal trends, regional variations and socioeconomic inequalities in CVD prevalence. Cohort analyses identified individuals without CVD in 2011 and followed them up until 2018 to calculate CVD incidence. Generalised estimating equations (GEE) were employed to identify associated factors. RESULTS: A total of 5451, 7258, 8820 and 11 393 participants were eligible for cross-sectional analyses, and 4392 and 5396 participants were included in cohort analyses of CVD and comorbid CVD. In 2018, the age-adjusted and sex-adjusted prevalence of CVD and comorbid CVD was 31.21% (95% CI 27.25% to 35.17%) and 3.83% (95% CI 2.85% to 4.81%), respectively. Trend analyses revealed a significant increase in the adjusted prevalence from 2011 to 2018 (p for trend <0.001). There were substantial provincial variations in the adjusted prevalence of CVD and comorbid CVD. Higher socioeconomic status (SES) participants exhibited higher prevalence, and the concentration curves and concentration indices suggested persistent but narrowing inequalities in CVD and comorbid CVD across survey waves. Cohort analyses from 2011 to 2018 yielded overall CVD and comorbid CVD incidence densities of 17.96 and 2.65 per 1000 person-years, respectively. GEE results indicated increased CVD risks among older individuals, women, higher SES participants and northern residents. CONCLUSION: More efforts should be taken to optimise strategies for high-quality CVD prevention and management in China's elderly population. Future interventions and policies should address age-specific and gender-specific, geographical, and socioeconomic disparities to ensure equitable access and outcomes for all.


Assuntos
Doenças Cardiovasculares , Adulto , Humanos , Idoso , Feminino , Doenças Cardiovasculares/epidemiologia , Estudos Longitudinais , Estudos Transversais , Classe Social , China/epidemiologia
9.
Medicine (Baltimore) ; 102(50): e36696, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38115252

RESUMO

Neurofibromatosis type 2 (NF2)-related vestibular schwannoma (NF2-VS) is a rare genetic disorder that results in bilateral acoustic neuromas. However, the exact pathogenesis of the disease is still unclear. This study aims to use bioinformatics analyses to identify potential hub genes and therapeutic. We retrieved the mRNA expression profiles (GSE108524 and GSE141801) of NF2-VS from the database, and selected the leading 25% genes with the most variance across samples for weighted correlation network analysis. Subsequently, we conducted gene ontology term and Kyoto Encyclopedia of Genes and Genomes signaling network enrichment analyses. The STRING database was employed for protein-protein interaction (PPI) axis construction. The mRNA-miRNA modulatory network was generated via the miRTarBase database. Differentially expressed genes (DEGs) were identified via the R package "limma" in both datasets, and hub genes were screened via intersection of common DEGs, candidate hub genes from the PPI axis, and candidate hub genes from the key module. Finally, common DEGs were uploaded onto the connectivity map database to determine drug candidates. Based on our observations, the blue module exhibited the most significant relation to NF2-VS, and it included the NF2 gene. Using enrichment analysis, we demonstrated that the blue modules were intricately linked to modulations of cell proliferation, migration, adhesion, junction, and actin skeleton. Overall, 356 common DEGs were screened in both datasets, and 33 genes carrying a degree > 15 were chosen as candidate hub genes in the PPI axis. Subsequently, 4 genes, namely, GLUL, CAV1, MYH11, and CCND1 were recognized as real hub genes. In addition, 10 drugs with enrichment scores < -0.7 were identified as drug candidates. Our conclusions offered a novel insight into the potential underlying mechanisms behind NF2-VS. These findings may facilitate the identification of novel therapeutic targets in the future.


Assuntos
MicroRNAs , Neurofibromatose 2 , Neuroma Acústico , Humanos , Neuroma Acústico/genética , Biologia Computacional , RNA Mensageiro
10.
Environ Sci Technol ; 57(43): 16489-16499, 2023 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-37844299

RESUMO

We analyzed two data sets of atmospheric formaldehyde (FA) at an urban site in the Shanghai megacity during the summer of 2017 and the winter of 2017/18, with the primary objective of determining the emission ratio of formaldehyde versus carbon monoxide (CO). Through the photochemical age method and the minimum R squared (MRS) method, we derived the summer urban formaldehyde release ratios of 3.37 ppbv (ppmv of CO)-1 and 4.04 ppbv (ppmv of CO)-1, respectively. The error of both estimations is within ±20%, indicating the consistency of the results. We recognized the hourly minimum emission ratios determined from the MRS method to be indicative of actual formaldehyde emission ratios. Similarly, the emission ratio in winter is determined to be 2.10 ppbv (ppmv of CO)-1 utilizing the MRS method. The findings provide significant insights into the potential impact of motor vehicle exhaust on formaldehyde emissions in urban areas. This work demonstrates that the formaldehyde emission ratio determined by the MRS method can be used to represent the emissions of the freshest air mass. Formaldehyde photolysis contributed an average of 9% to the free radical primary reaction rate (P(ROx)) as a single chemical species during the daytime in summer, which was lower than the 11% recorded in winter. Formaldehyde emission reduction positively impacts local ozone production, so models describing ozone formation in Shanghai during summer need to reflect these emissions accurately. Evidence of the crucial catalytic role of formaldehyde in particulate matter formation has been confirmed by recent research. A potentially effective way to decrease the incidence of haze days in autumn and winter in the future is therefore to focus on reducing formaldehyde emissions.


Assuntos
Poluentes Atmosféricos , Ozônio , Poluentes Atmosféricos/análise , Monitoramento Ambiental/métodos , China , Emissões de Veículos/análise , Formaldeído/análise , Ozônio/análise
11.
Mol Immunol ; 162: 1-10, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37611377

RESUMO

Allergic rhinitis (AR) is characterized by various bothersome clinical symptoms of the nasal mucosa that impaired the quality of daily life. Different chemokine receptors play a crucial role in the recruitment of inflammatory cells in AR. However, the effect of CC chemokine receptor (CCR) 3 on the function of eosinophils (EOS) is still unclear. We investigated the effect of CCR3 on EOS in a murine model of OVA-mediated allergic rhinitis using CCR3-deficient (CCR3-/-) mice. In vitro, bone marrow of CCR3-/- and wild-type (WT) mice were used to investigate the induction and development of EOS. In vivo, Allergic rhinitis was initiated in CCR3-/- and wild-type (WT) mice by passive transfer OVA, followed by detecting the eosinophil infiltration of the nasal mucosa and bone marrow. Then CD34+ progenitor cells in bone marrow and blood were evaluated by IHC analysis. Furthermore, the degranulation proteins of EOS in nasal mucosa, marrow, blood and NALF were determined by IHC, real-time PCR analysis and Western blot. We found that CCR3 gene can regulate the growth and development of primary cultured eosinophils. Knockout CCR3 gene can inhibit the proliferation and degranulation of EOS. The infiltration of eosinophils in the nasal mucosa following OVA-challenged, was significantly higher in WT mice compared with those stimulated with phosphate-buffered saline (PBS) for WT, but that was not seen in similarly treated CCR3-/- mice. Besides, the number of CD34+ progenitor cells in bone marrow and blood were also suppressed in CCR3-/- mice. The degranulation proteins of EOS expressed in nasal mucosa, marrow, blood and NALF were decreased in CCR3-/- AR mice compared with WT-AR mice. And the clinical symptoms were significantly alleviated. The expression of granulation proteins in NALF were not detected in both untreated CCR3-/- mice and WT mice. These results demonstrate a contribution of CCR3 to both the growth, migration, and degranulation of EOS during allergic rhinitis.


Assuntos
Eosinófilos , Rinite Alérgica , Animais , Camundongos , Camundongos Knockout , Técnicas de Inativação de Genes , Rinite Alérgica/genética , Diferenciação Celular , Proliferação de Células
12.
J Cell Mol Med ; 27(22): 3503-3513, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37635346

RESUMO

Glioblastoma multiforme (GBM) is a highly malignant primary brain tumour with a poor prognosis in adults. Identifying biomarkers that can aid in the molecular classification and risk stratification of GBM is critical. Here, we conducted a transcriptional profiling analysis of T-cell immunity in the tumour microenvironment of GBM patients and identified two novel T cell exhaustion (TEX)-related GBM subtypes (termed TEX-C1 and TEX-C2) using the consensus clustering. Our multi-omics analysis revealed distinct immunological, molecular and clinical characteristics for these two subtypes. Specifically, the TEX-C1 subtype had higher infiltration levels of immune cells and expressed higher levels of immune checkpoint molecules than the TEX-C2 subtype. Functional analysis revealed that upregulated genes in the TEX-C1 subtype were significantly enriched in immune response and signal transduction pathways, and upregulated genes in the TEX-C2 subtype were predominantly associated with cell fate and nervous system development pathways. Notably, patients with activated T-cell activity status in the TEX-C1 subgroup demonstrated a significantly worse prognosis than those with severe T cell exhaustion status in the TEX-C2 subgroup. Finally, we proposed a machine-learning-derived novel gene signature comprising 12 TEX-related genes (12TexSig) to indicate tumour subtyping. In the TCGA cohort, the 12TexSig demonstrated the ability to accurately predict the prognosis of GBM patients, and this prognostic value was further confirmed in two independent external cohorts. Taken together, our results suggest that the TEX-derived subtyping and gene signature has the potential to serve as a clinically helpful biomarker for guiding the management of GBM patients, pending further prospective validation.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Adulto , Humanos , Perfilação da Expressão Gênica/métodos , Glioblastoma/patologia , Exaustão das Células T , Biomarcadores , Neoplasias Encefálicas/patologia , Microambiente Tumoral/genética
13.
Biomed Pharmacother ; 165: 115248, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37523980

RESUMO

Oxaliplatin, as a third-generation platinum-based anticancer drug, is widely used in tumor therapy of many systems. Clinically, oxaliplatin has a number of serious side effects, most notably neuropathy and ototoxicity. The degeneration of cochlear hair cells is the main reason for the hearing loss caused by platinum-based drugs. However, the mechanism of oxaliplatin-induced cochlear hair cell death remains unclear. Ferroptosis is a novel cell injury pattern triggered by the accumulation of iron hydroperoxides in lipids and dependent on the participation of iron ions, which plays an important role in a variety of diseases. Whether ferroptosis is involved in oxaliplatin-induced ototoxicity has not been reported. In this study, we observed that oxaliplatin treatment resulted in lipid peroxidation and reactive oxygen species (ROS) accumulation in OC1 cells, which may be an early alteration in the occurrence of ferroptosis. Additional treatment with ferroptosis inducer or inhibitor significantly aggravated or ameliorated oxaliplatin-induced cytotoxicity. Similarly, inhibition of ferroptosis also protected cochlear hair cells against oxaliplatin-induced injury. In addition, the expression of nuclear factor erythroid 2-related factor2 (Nrf2) and heme oxygenase-1 (HO-1) was significantly increased after oxaliplatin treatment, and treatment with the Nrf2 agonist, resveratrol, dramatically attenuated cochlear hair cell damage induced by oxaliplatin. Activation of Nrf2 significantly decreased the expression of iron regulatory protein 2 (IRP-2) and reversed the expression of glutathione peroxidase 4 (GPX4). Collectively, our results demonstrated that activation of Nrf2 alleviates oxaliplatin-induced cochlear hair cell damage by inhibiting ferroptosis, which may be a new mechanism of oxaliplatin-induced ototoxicity.


Assuntos
Antineoplásicos , Ferroptose , Fator 2 Relacionado a NF-E2 , Ototoxicidade , Oxaliplatina , Antineoplásicos/toxicidade , Ferro/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Ototoxicidade/prevenção & controle , Oxaliplatina/efeitos adversos , Espécies Reativas de Oxigênio/metabolismo , Animais , Camundongos , Linhagem Celular
14.
Immunol Invest ; 52(4): 499-512, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37129115

RESUMO

This article aimed to explore whether the regulation of Th1/Th2 immune responses by FOXD3-AS1 is associated with dendritic cells (DCs) in allergic rhinitis (AR). HE staining was performed to assess the pathological changes in the nasal mucosa; ELISA was performed to measure the levels of Th1/Th2-related cytokines; flow cytometry was performed to analyze Th1/Th2 cells and MHC-II-, CD80-, and CD86-positive DCs; and qRT‒PCR and western blotting were performed to measure mRNA and protein expression levels, respectively. Our data revealed that LV-FOXD3-AS1 improved AR and increased the Th1/Th2 cell ratio in AR model mice. LV-FOXD3-AS1 further inhibited DC maturation both in vivo and in vitro. Moreover, the coculture system of DCs and CD4+ T cells demonstrated that LV-FOXD3-AS1 increased the Th1/Th2 cell ratio by inhibiting the maturation of DCs. In addition, LV-FOXD3-AS1 reduced the level of phosphorylated STAT6 in DCs derived from healthy mice, and STAT6 overexpression eliminated the inhibitory effect of LV-FOXD3-AS1 on the maturation of DCs. In summary, LV-FOXD3-AS1 ameliorated AR by increasing the Th1/Th2 cell ratio by inhibiting DC maturation via the inhibition of STAT6 phosphorylation. Our data confirmed the protective effect of FOXD3-AS1 in AR and provided a novel idea for the treatment of this disease.


Assuntos
RNA Longo não Codificante , Rinite Alérgica , Camundongos , Animais , RNA Longo não Codificante/metabolismo , Citocinas/metabolismo , Células Th2 , Células Dendríticas , Modelos Animais de Doenças
15.
Angew Chem Int Ed Engl ; 62(28): e202304329, 2023 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-37188865

RESUMO

Colloidal semiconductor II-VI metal chalcogenide (ME) magic-size clusters (MSCs) exhibit either an optical absorption singlet or doublet. In the latter case, a sharp photoluminescence (PL) signal is observed. Whether the PL-inactive MSCs transform to the PL-active ones is unknown. We show that PL-inactive CdS MSC-322 transforms to PL-active CdS MSC-328 and MSC-373 in the presence of acetic acid (HOAc). MSC-322 displays a sharp absorption at ≈322 nm, whereas MSC-328 and MSC-373 both have broad absorptions respectively around 328 and 373 nm. In a reaction of cadmium myristate and S powder in 1-octadecene, MSC-322 develops; with HOAc, MSC-328 and MSC-373 are present. We propose that the MSCs evolve from their relatively transparent precursor compounds (PCs). The PC-322 to PC-328 quasi-isomerization involves monomer substitution, while monomer addition occurs for the PC-328 to PC-373 transformation. Our findings suggest that S dominates the precursor self-assembly quantitatively, and ligand-bonded Cd mainly controls MSC optical properties.

16.
Front Neurol ; 14: 1142459, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37144001

RESUMO

Sudden sensorineural hearing loss (SSNHL) is defined as an abrupt hearing loss of more than 30 dB in three contiguous frequencies within 72 h. It is an emergency disease requiring immediate diagnosis and treatment. The incidence of SSNHL in Western countries' population is estimated between 5 and 20 per 1,00,000 inhabitants. The etiology of SSNHL remains unknown. Due to the uncertainty of the cause of SSNHL, at present, no specific treatment targets the cause of SSNHL, resulting in poor efficacy. Previous studies have reported that some comorbidities are risk factors for SSNHL, and some laboratory results may provide some clues for the etiology of SSNHL. Atherosclerosis, microthrombosis, inflammation, and the immune system may be the main etiological factors for SSNHL. This study confirms that SSNHL is a multifactorial disease. Some comorbidities, such as virus infections, are suggested to be the causes of SSNHL. In summary, by analyzing the etiology of SSNHL, more targeting treatments should be used to achieve a better effect.

17.
Animals (Basel) ; 13(9)2023 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-37174596

RESUMO

The objective of this study was to determine the effect of high-concentrate diets on the blood parameters and liver transcriptome of goats. Eighteen goats were allocated into three dietary treatments: the high level of concentrate (HC) group, the medium level of concentrate (MC) group, and the low level of concentrate (LC) group. The blood parameters and pathological damage of the gastrointestinal tract and liver tissues were measured. In hepatic portal vein blood, HC showed higher LPS, VFAs, and LA; in jugular vein blood, no significant differences in LPS, VFAs, and LA were recorded among groups (p > 0.05). Compared to the LC and MC groups, the HC group showed significantly increased interleukin (IL)-1ß, IL-10, TNF-α, and diamine oxidase in jugular vein blood (p < 0.05). Liver transcriptome analysis discovered a total of 1269 differentially expressed genes (DEGs) among the three groups and most of them came from the HC vs. LC group. There were 333 DEGs up-regulated and 608 down-regulated in the HC group compared to the LC group. The gene ontology enrichment analysis showed that these DEGs were mainly focused on the regulation of triacylglycerol catabolism, lipoprotein particle remodeling, and cholesterol transport. The Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the liver of the HC group enhanced the metabolism of nutrients such as VFAs through the activation of AMPK and other signaling pathways and enhanced the clearance and detoxification of LPS by activating the toll-like receptor signaling pathway. A high-concentrate diet (HCD) can significantly promote the digestion of nutrients; the liver enhances the adaptability of goats to an HCD by regulating the expression of genes involved in nutrient metabolism and toxin clearance.

18.
BMC Med Educ ; 23(1): 237, 2023 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-37046240

RESUMO

BACKGROUND: Investigating students' learning styles can generate useful information that can improve curriculum design. This study adopts diverse measures to identify the learning styles of students despite limited literature related to clinical medical students in China. We utilized Felder's Index of Learning Styles to examine the learning style characteristics of clinical medical students at Inner Mongolia Minzu University. METHODS: Cluster sampling (probability sampling) was used. This cross-sectional study investigated clinical medicine students with regard to their learning style preference and the difference across genders. This study also analysed data collected from other published studies. A total of 411 students from the medical school at Inner Mongolia Minzu University completed the Index of Learning Styles Questionnaire. The questionnaire assessed the learning styles of students in four dimensions: visual-verbal learning, sequential-global learning, active-reflective leaning, and sensing-intuitive learning. RESULTS: The analysis results show that clinical medicine students choose to receive visual information (73.97% of the student sample) instead of verbal information. These students prioritize sensory information (67.15%) rather than intuitive information and process reflective information (51.82%) rather than active information. They prefer to process information sequentially (59.85%) instead of globally. Our results also show that male students present a higher preference for an active learning style over a reflective learning style, while female students seem to present a higher preference for a reflective learning style over an active learning style. These preferences vary between cohorts (gender), but the difference is not statistically significant. Compared to data collected from other published studies, active, visual, sensing, and sequential are the most popular styles of learning adopted by medical science students. CONCLUSIONS: The identification of medical students' learning style in China provides information that medical educators and others can use to make informed choices about modification, development and strengthening of medical educational programs. Our outcomes may potentially improve motivation, engagement and deep learning in medical education when used as a supplement to teaching/learning activities.


Assuntos
Estudantes de Medicina , Humanos , Masculino , Feminino , Universidades , Estudos Transversais , Cognição , Inquéritos e Questionários , China
19.
Medicine (Baltimore) ; 102(14): e33470, 2023 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-37026948

RESUMO

Vestibular schwannomas are the most common tumors of the cerebellopontine angle, but their pathogenesis is still unclear. This study aimed to explore the molecular mechanisms and potential therapeutic target biomarkers in vestibular schwannoma. Two datasets (GSE141801 and GSE54934) were downloaded from the Gene Expression Omnibus database. Weighted gene coexpression network analysis was performed to find the key modules associated with vestibular schwannoma (VS). Functional enrichment analysis was applied to evaluate the gene enrichment signaling pathway in key modules. Protein-protein interaction networks in key modules were constructed using the STRING website. Hub genes were identified by intersecting candidate hub genes in protein-protein interaction network and candidate hub genes in key modules. Single-sample gene set enrichment analysis was utilized to quantify the abundance of tumor-infiltrating immune cells in VSs and normal control nerves. A Random forest classifier was developed based on hub genes identified in this study and validated on an independent dataset (GSE108524). Results of immune cell infiltration were also validated on GSE108524 by gene set enrichment analysis. Eight genes from coexpression modules were identified as hub genes, that is, CCND1, CAV1, GLI1, SOX9, LY86, TLR3, TREM2, and C3AR1, which might be potential therapeutic targets for VS. We also found that there were distinct differences in the infiltration levels of immune cells between VSs and normal control nerves. Overall, our findings may be useful for investigating the mechanisms underlying VS and provide noteworthy directions for future research.


Assuntos
Neuroma Acústico , Humanos , Neuroma Acústico/genética , Ângulo Cerebelopontino , Bases de Dados Factuais , Perfilação da Expressão Gênica , Redes Reguladoras de Genes
20.
Front Neurol ; 14: 1138354, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37090982

RESUMO

Objectives: This study aimed to investigate the efficacy and safety of intratympanic or postauricular subperiosteal glucocorticoid injection combined with systemic glucocorticoid in the treatment of sudden sensorineural hearing loss (SSNHL). Methods: This study is a prospective randomized controlled study. This study included unilateral SSNHL patients who were hospitalized in our department between January 2020 and June 2021. Patients were randomly divided into three groups (groups A, B, and C). Patients in group A were treated with an intratympanic corticosteroid injection combined with systemic corticosteroid treatment, and patients in group B received a postauricular corticosteroid injection combined with systemic corticosteroid treatment. Patients in group C (control group) were treated with systemic corticosteroid alone. The case number of groups A, B, and C was 311, 375, and 369, respectively. Results: There was no significant difference in gender distribution, the proportion of left and right affected ears, and the average interval from onset to treatment among the three groups (P > 0.05). However, there were significant differences in their average age, distribution of audiogram type, and hearing loss levels among them (P < 0.01). Our study shows that there was no significant difference in average hearing threshold improvement before and after treatment in the three groups (P > 0.05). Regarding the complications, in group A, 33 patients (10.6%) had a transient vertigo attack during tympanic injection, which lasted for ~1-3 min. In group B, 20 patients (6.43%) complained of pain at the injection site, which disappeared after 1-3 days. No other complications occurred in all the other patients. Conclusion: The addition of intratympanic or postauricular corticosteroid to systemic steroids did not result in a significant effect on hearing recovery in SSNHL. No obvious complications occur in SSNHL patients treated with intratympanic injection or postauricular injection of corticosteroid. Clinical trial registration: [chictr.org.cn], registration number: ChiCTR2100048762.

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