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1.
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.

2.
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.

3.
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
4.
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
5.
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
6.
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
7.
Neoplasma ; 70(6): 761-776, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38247332

RESUMO

Nasopharyngeal carcinoma (NPC) is a common malignant tumor of the head and neck. A number of studies have confirmed that coiled-coil domain-containing protein 86 (CCDC86) plays an important role in the pathogenesis of lymphoma but the role of CCDC86 in NPC has not yet been reported. Here, in vivo and in vitro experiments were conducted to explore whether CCDC86 plays a role in the pathogenesis of NPC and to identify the specific mechanism. We found that CCDC86 was highly expressed in NPC tissues and cells, and the expression level of CCDC86 was correlated with the prognosis of patients with advanced NPC. CCDC86 promoted the proliferation, invasion, and migration of NPC cells in vivo and in vitro by promoting the EMT process and upregulating the expression of MMPs. Then, we confirmed that EGFR is a downstream target gene of CCDC86 and that CCDC86 can promote the proliferation, invasion, and migration of NPC cells by upregulating the expression of EGFR and activating downstream PI3K/Akt. Furthermore, we confirmed that CCDC86 did not directly bind to EGFR but positively regulated EGFR by binding to NPM1. CCDC86 is expected to be used as a novel biomarker and therapeutic target for predicting the prognosis of NPC.


Assuntos
Receptores ErbB , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Receptores ErbB/metabolismo , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo
8.
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
9.
J Environ Sci (China) ; 123: 327-340, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36521996

RESUMO

A compilation of new advances made in the research field of laboratory reaction kinetics in China's Key Development Project for Air Pollution Formation Mechanism and Control Technologies was presented. These advances are grouped into six broad, interrelated categories, including volatile organic compound (VOC) oxidation, secondary organic aerosol (SOA) formation, new particle formation (NPF) and gas-particle partitioning, ozone chemistry, model parameters, and secondary inorganic aerosol (SIA) formation, highlighting the laboratory work done by Chinese researchers. For smog chamber applications, the current knowledge gained from laboratory studies is reviewed, with emphasis on summarizing the oxidation mechanisms of long-chain alkanes, aromatics, alkenes, aldehydes/ketones in the atmosphere, SOA formation from anthropogenic emission sources, and oxidation of aromatics, isoprene, and limonene, as well as SIA formation. For flow tube applications, atmospheric oxidation mechanisms of toluene and methacrolein, SOA formation from limonene oxidation by ozone, gas-particle partitioning of peroxides, and sulfuric acid-water (H2SO4-H2O) binary nucleation, methanesulfonic acid-water (MSA-H2O) binary nucleation, and sulfuric acid-ammonia-water (H2SO4-NH3-H2O) ternary nucleation are discussed.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Ozônio , Cinética , Limoneno , Aerossóis/análise , Ozônio/química , Poluição do Ar/prevenção & controle , Água , China , Poluentes Atmosféricos/análise
10.
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.

11.
Acta Biochim Biophys Sin (Shanghai) ; 54(3): 332-339, 2022 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-35538041

RESUMO

Oxidative stress is one of the important mechanisms of inner ear cell damage, which can lead to age-related hearing loss (ARHL). LncRNA H19 is significantly downregulated in the cochlea of old mouse, however, the role of H19 in the development of ARHL remains unclear. In this study, we aim to investigate the expression and function of H19 in oxidative stress injury of cochlear hair cells induced by HO. RT-qPCR and western blot analysis confirms that HEI-OC1 cells stimulated with HO decreases the expressions of H19 and SIRT1, but increases the expression of miR-653-5p. Overexpression of H19 could increase cell viability, ATP level and mitochondrial membrane potential, but reduce mitochondrial ROS generation and cell apoptosis ratio in HO-stimulated HEI-OC1 cells. MiR-653-5p is a target of H19, which can bind to the 3'-UTR of SIRT1. H19 is found to regulate the expression of SIRT1 through miR-653-5p. Further experiments demonstrates that H19 regulates HEI-OC1 cell viability, ATP level, mitochondrial membrane potential, mitochondrial ROS generation, and cell apoptosis ratio via the miR-653-5p/SIRT1 axis. In conclusion, lncRNA H19 inhibits oxidative stress injury of cochlear hair cells via the miR-653-5p/SIRT1 axis.


Assuntos
Células Ciliadas Auditivas , MicroRNAs , RNA Longo não Codificante , Sirtuína 1 , Trifosfato de Adenosina/metabolismo , Animais , Apoptose/genética , Células Ciliadas Auditivas/metabolismo , Células Ciliadas Auditivas/patologia , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Estresse Oxidativo/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Sirtuína 1/genética , Sirtuína 1/metabolismo
12.
Eur Arch Otorhinolaryngol ; 278(5): 1355-1364, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-32651676

RESUMO

PURPOSE: To investigate optimal approaches for appropriate removal of the parotid gland in the management of squamous cell carcinoma (SCC) of the external auditory canal (EAC) at different tumor stages. METHODS: In total, 39 patients with SCC of EAC treated at the Second Affiliated Hospital of Nanchang University between September 2003 and April 2019 were enrolled in this study. All patients underwent lateral temporal bone resection or subtotal temporal bone resection. Total parotidectomy was performed in patients with direct parotid invasion. Superficial parotidectomy was performed in patients with parotid node metastasis and patients with advanced stages without evidence of parotid involvement. RESULTS: The mean follow-up period was 68.7 months. Local recurrences or distant metastases occurred in five patients (12.8%). The 5-year overall survival rate was 78.4%. The 5-year survival rate was 100% in early stage (T1 and T2) patients, and 58.9 and 50.0% in patients staged III and IV, respectively. Direct parotid invasion was observed in only advanced-stage patients, while parotid node metastasis was noted in both early and advanced-stage patients preoperatively. There were no significant differences (χ2 = 0.1026; p = 0.749) between different tumor primary locations. However, soft tissue or preauricular organs became vulnerable once the anterior wall was infiltrated or eroded. CONCLUSION: Parotid management is important for achieving safer and wider tumor-free margins. Total parotidectomy should be mandatory for all advanced-staged (T3 and T4) patients. An optimal decision for parotid management in early stages depends on the infiltration or erosion of the anterior wall of the EAC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias da Orelha , Neoplasias Parotídeas , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Meato Acústico Externo/patologia , Meato Acústico Externo/cirurgia , Neoplasias da Orelha/patologia , Neoplasias da Orelha/cirurgia , Humanos , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasias Parotídeas/patologia , Neoplasias Parotídeas/cirurgia , Estudos Retrospectivos
13.
Mol Cell Biochem ; 473(1-2): 239-246, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32671514

RESUMO

Long non-coding RNA FOXD3-AS1 is associated with allergic rhinitis (AR). This article aims to demystify the role of FOXD3-AS1 in AR. We compared FOXD3-AS1 expression in nasal mucosas between AR patients and healthy control. Next, nasal epithelial cells (NECs) were incubated with lipopolysaccharide or recombinant IL-25, and then the supernatant of the NECs was incubated with CD4+ T cells. Th2 cell proportions were assessed by flow cytometry. The levels of gene and cytokines were detected by real-time quantitative PCR or enzyme linked immunosorbent assay. FOXD3-AS1 was downregulated in nasal mucosas of AR patients, whereas Th2 cell proportions and the levels of IL-25, IL-4, and IL-13 were enhanced in peripheral blood of AR patients. FOXD3-AS1 overexpression inhibited the expression and secretion of IL-25 in NECs. The levels of IL-4 and IL-13 and Th2 cell proportions in CD4+ T cells were enhanced by recombinant IL-25, which was effectively abolished by the supernatant of FOXD3-AS1-overexpressed NECs treatment. Our study demonstrates that FOXD3-AS1 is downregulated in nasal mucosas of AR patients, and FOXD3-AS1 represses the expression and secretion IL-25 in NECs, thereby inhibiting Th2 type immunoreaction in AR. Thus, our data provide a novel target gene for AR treatment.


Assuntos
Células Epiteliais/imunologia , Regulação da Expressão Gênica/imunologia , Interleucina-17/imunologia , Mucosa Nasal/imunologia , RNA Longo não Codificante/imunologia , Rinite Alérgica/imunologia , Células Th2/imunologia , Células Epiteliais/patologia , Feminino , Humanos , Masculino , Mucosa Nasal/patologia , Rinite Alérgica/patologia , Células Th2/patologia
14.
J Org Chem ; 84(6): 3419-3430, 2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30807154

RESUMO

Structurally complex 2(5 H)-furanones are potentially challenging targets for ring-closing metathesis (RCM). A hydrogen bonding-guided RCM strategy was developed in this study to provide 3-substituted and 3,4-disubstituted 2(5 H)-furanones in moderate to high yields with broad functional group tolerance. A workup procedure using ethylenediamine-derived polyamines such as tetraethylenepentylamine was also established to effectively remove Ru residues in products.

16.
Org Biomol Chem ; 14(45): 10705-10713, 2016 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-27805220

RESUMO

An efficient hydrogen bonding-guided ring-closing metathesis (RCM) reaction of sterically demanding homoallyl 2-(hydroxymethyl)acrylates catalyzed by the Hoveyda-Grubbs 2nd generation catalyst was developed and the reaction mechanism was explored. Adding a substituent to the hydroxymethyl group in this scaffold resulted in a class of challenging RCM substrates, although usable yields could be obtained. However, substrates bearing a 1-oxygenated alkyl group on the homoallylic carbon gave excellent RCM yields, providing a practical solution. Experimental and computational evidence indicated an unusual directing effect of OHCl hydrogen bonding between the substrate and Ru catalyst, which guides Ru to interact with the electron-deficient, more hindered acrylic C[double bond, length as m-dash]C bond and thus triggers the RCM process.

17.
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
18.
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
19.
J Orthop Sci ; 18(4): 599-604, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23661178

RESUMO

BACKGROUND: Giant cell tumors of the distal radius at Campanacci grade III are particularly challenging to treat. We have treated 15 cases of giant cell tumor of the distal radius by en bloc excision and osteoarticular allograft reconstruction with locking compression plate (LCP). The purpose of this study was to assess the intermediate outcomes of all patients treated with this surgery. METHODS: From July 2002 to January 2009, we followed up 15 patients with giant cell tumors of the distal radius who were treated with en bloc excision and osteoarticular allograft reconstruction with LCPs that were long enough to approach the distal end of the allograft. All of the cases were evaluated based on clinical and radiologic examinations, the passive range of motion of the wrist joint, complications, Mayo wrist score, and short form (SF)-36. RESULTS: The clinical follow-up time after reconstruction averaged 5.2 years. The mean resected length of the radius was 8.1 cm. One patient had tumor recurrence in the soft tissues after 3 years (recurrence rate 6.67 %). No patient had allograft bone fracture, nonunion, or metastases. Subchondral bone alterations and joint narrowing were present in all cases, with 1 patient suffering from the pain, but the pain could be endured without the need for analgesics. The average range of motion of the wrist was 46.7° of dorsiflexion, 33.3° of volar flexion, 61.3° of supination, and 72.3° of pronation. The mean Mayo wrist score was 70 and the mean modified SF-36 score was 71. CONCLUSIONS: En bloc excision and osteoarticular allograft reconstruction with an appropriate LCP for a Campanacci grade III giant cell tumor of the distal radius result in a reasonable functional outcome at intermediate follow-up evaluation. This method can excise the tumor integrally with a low rate of recurrence, good function, and a satisfactory range of motion.


Assuntos
Neoplasias Ósseas/cirurgia , Placas Ósseas , Transplante Ósseo , Tumor de Células Gigantes do Osso/cirurgia , Rádio (Anatomia)/cirurgia , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Ortopédicos/métodos , Estudos Retrospectivos , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
20.
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
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