Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 61
Filtrar
Mais filtros

Bases de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
Hum Genet ; 143(3): 293-309, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38456936

RESUMO

Auditory neuropathy (AN) is a unique type of language developmental disorder, with no precise rate of genetic contribution that has been deciphered in a large cohort. In a retrospective cohort of 311 patients with AN, pathogenic and likely pathogenic variants of 23 genes were identified in 98 patients (31.5% in 311 patients), and 14 genes were mutated in two or more patients. Among subgroups of patients with AN, the prevalence of pathogenic and likely pathogenic variants was 54.4% and 56.2% in trios and families, while 22.9% in the cases with proband-only; 45.7% and 25.6% in the infant and non-infant group; and 33.7% and 0% in the bilateral and unilateral AN cases. Most of the OTOF gene (96.6%, 28/29) could only be identified in the infant group, while the AIFM1 gene could only be identified in the non-infant group; other genes such as ATP1A3 and OPA1 were identified in both infant and non-infant groups. In conclusion, genes distribution of AN, with the most common genes being OTOF and AIFM1, is totally different from other sensorineural hearing loss. The subgroups with different onset ages showed different genetic spectrums, so did bilateral and unilateral groups and sporadic and familial or trio groups.


Assuntos
Perda Auditiva Central , Mutação , Humanos , Feminino , Masculino , Perda Auditiva Central/genética , Lactente , Criança , Pré-Escolar , Estudos Retrospectivos , Adolescente , Proteínas de Membrana/genética , Estudos de Coortes
2.
J Transl Med ; 22(1): 90, 2024 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-38254099

RESUMO

BACKGROUND: Novel biomarkers are required in gastric cancer (GC) treated by immunotherapy. Epstein-Barr virus (EBV) infection induces an immune-active tumor microenvironment, while its association with immunotherapy response is still controversial. Genes underlying EBV infection may determine the response heterogeneity of EBV + GC. Thus, we screened hub genes associated with EBV infection to predict the response to immunotherapy in GC. METHODS: Prognostic hub genes associated with EBV infection were screened using multi-omic data of GC. EBV + GC cells were established and confirmed by EBV-encoded small RNA in situ hybridization (EBER-ISH). Immunohistochemistry (IHC) staining of the hub genes was conducted in GC samples with EBER-ISH assay. Infiltrating immune cells were stained using immunofluorescence. RESULTS: CHAF1A was identified as a hub gene in EBV + GC, and its expression was an independent predictor of overall survival (OS). EBV infection up-regulated CHAF1A expression which also predicted EBV infection well. CHAF1A expression also predicted microsatellite instability (MSI) and a high tumor mutation burden (TMB). The combined score (CS) of CHAF1A expression with MSI or TMB further improved prognostic stratification. CHAF1A IHC score positively correlated with the infiltration of NK cells and macrophages M1. CHAF1A expression alone could predict the immunotherapy response, but its CS with EBV infection, MSI, TMB, or PD-L1 expression showed better effects and improved response stratification based on current biomarkers. CONCLUSIONS: CHAF1A could be a novel biomarker for immunotherapy of GC, with the potential to improve the efficacy of existing biomarkers.


Assuntos
Infecções por Vírus Epstein-Barr , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/terapia , Herpesvirus Humano 4/genética , Biomarcadores , Imunoterapia , Instabilidade de Microssatélites , Microambiente Tumoral
3.
J Youth Adolesc ; 53(1): 1-20, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37991601

RESUMO

Numerous studies have explored the link between how well youth recognize emotions and their internalizing problems, but a consensus remains elusive. This study used a three-level meta-analysis model to quantitatively synthesize the findings of existing studies to assess the relationship. A moderation analysis was also conducted to explore the sources of research heterogeneity. Through a systematic literature search, a total of 42 studies with 201 effect sizes were retrieved for the current meta-analysis, and 7579 participants were included. Emotion recognition was negatively correlated with internalizing problems. Children and adolescents with weaker emotion recognition skills were more likely to have internalizing problems. In addition, this meta-analysis found that publication year had a significant moderating effect. The correlation between emotion recognition and internalizing problems decreased over time. The degree of internalizing problems was also found to be a significant moderator. The correlation between emotion recognition and internalizing disorders was higher than the correlation between emotion recognition and internalizing symptoms. Deficits in emotion recognition might be relevant for the development and/or maintenance of internalizing problems in children and adolescents. The overall effect was small and future research should explore the clinical relevance of the association.


Assuntos
Regulação Emocional , Emoções , Adolescente , Criança , Humanos
4.
Angew Chem Int Ed Engl ; 63(13): e202319728, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38285535

RESUMO

Organic molecules bearing chiral sulfur stereocenters exert a great impact on asymmetric catalysis and synthesis, chiral drugs, and chiral materials. Compared with acyclic ones, the catalytic asymmetric synthesis of thio-heterocycles has largely lagged behind due to the lack of efficient synthetic strategies. Here we establish the first modular platform to access chiral thio-oxazolidinones via Pd-catalyzed asymmetric [3+2] annulations of vinylethylene carbonates with sulfinylanilines. This protocol is featured by readily available starting materials, and high enantio- and diastereoselectivity. In particular, an unusual effect of a non-chiral supporting ligand on the diastereoselectivity was observed. Possible reaction mechanisms and stereocontrol models were proposed.

5.
J Proteome Res ; 22(8): 2558-2569, 2023 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-37432907

RESUMO

Community-acquired pneumonia (CAP) is a significant threat to human health and the leading cause of acute respiratory distress syndrome (ARDS). We aimed to reveal the metabolic profiling whether can be used for assessing CAP with or without ARDS (nARDS) and therapeutic effects on CAP patients after treatment. Urine samples were collected at the onset and recovery periods, and metabolomics was employed to identify robust biomarkers. 19 metabolites were significantly changed in the ARDS relative to nARDS, mainly involving purines and fatty acids. After treatment, 7 metabolites in the nARDS and 14 in the ARDS were found to be significantly dysregulated, including fatty acids and amino acids. In the validation cohort, we observed that the biomarker panel consisted of N2,N2-dimethylguanosine, 1-methyladenosine, 3-methylguanine, 1-methyladenosine, and uric acid exhibited better AUCs of 0.900 than pneumonia severity index and acute physiology and chronic health evaluation II (APACHE II) scores between the ARDS and nARDS. Combining L-phenylalanine, phytosphingosine, and N-acetylaspartylglutamate as biomarkers for discriminating the nARDS and ARDS patients after treatment exhibited good AUCs of 0.811 and 0.821, respectively. The metabolic pathway and defined biomarkers may serve as crucial indicators for predicting the development of ARDS in CAP patients and for assessing therapeutic effects.


Assuntos
Infecções Comunitárias Adquiridas , Pneumonia , Síndrome do Desconforto Respiratório , Humanos , Pneumonia/diagnóstico , Metabolômica , Biomarcadores , Síndrome do Desconforto Respiratório/diagnóstico , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/metabolismo , Ácidos Graxos , Purinas , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/complicações
6.
Lipids Health Dis ; 22(1): 45, 2023 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-37004014

RESUMO

The tumormicroenvironment (TME) plays a key role in tumor progression. Tumor-associated macrophages (TAMs), which are natural immune cells abundantin the TME, are mainly divided into the anti-tumor M1 subtype and pro-tumor M2 subtype. Due to the high plasticity of TAMs, the conversion of the M1 to M2 phenotype in hypoxic and hypoglycemic TME promotes cancer progression, which is closely related to lipid metabolism. Key factors of lipid metabolism in TAMs, including peroxisome proliferator-activated receptor and lipoxygenase, promote the formation of a tumor immunosuppressive microenvironment and facilitate immune escape. In addition, tumor cells promote lipid accumulation in TAMs, causing TAMs to polarize to the M2 phenotype. Moreover, other factors of lipid metabolism, such as abhydrolase domain containing 5 and fatty acid binding protein, have both promoting and inhibiting effects on tumor cells. Therefore, further research on lipid metabolism in tumors is still required. In addition, statins, as core drugs regulating cholesterol metabolism, can inhibit lipid rafts and adhesion of tumor cells, which can sensitize them to chemotherapeutic drugs. Clinical studies on simvastatin and lovastatin in a variety of tumors are underway. This article provides a comprehensive review of the role of lipid metabolism in TAMs in tumor progression, and provides new ideas for targeting lipid metabolism in tumor therapy.


Assuntos
Neoplasias , Macrófagos Associados a Tumor , Humanos , Macrófagos , Metabolismo dos Lipídeos/genética , Neoplasias/metabolismo , Sinvastatina/farmacologia , Microambiente Tumoral/genética
7.
BMC Ophthalmol ; 23(1): 249, 2023 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-37271801

RESUMO

BACKGROUND: Home confinement during the epidemic has a significant impact on the lifestyle and behavior of school-aged children, who have exhibited an increase in the prevalence and development of myopia. Our research will look at if home confinement will affect school-aged children on myopia control with orthokeratology. METHOD: Data on axial length was gathered from school-aged children who had received OK lenses treatment. The entire data was separated into subgroups based on gender, age, and initial refraction, and the AL changes for each period were calculated using the formula defined in our study. Finally, the acquired data will be examined using various statistical approaches, and the ideas of slow, moderate, and rapid myopia progression will be applied to our study. RESULT: A total of 258 study subjects met the requirements to be included in the study. We discovered that the percentage of rapid myopia growth increased during the epidemic. In addition, the AL changes before and during the epidemic were found to be statistically significant in 171 subjects in the overall data. (P = 0.041) In the high age group, the AL changes before and during the epidemic、(P = 0.033) before and after the epidemic (P = 0.023) were found to be statistically significant. The AL changes before and during the epidemic (P = 0.035) were shown to be statistically significant in the moderate myopia group. Finally, we did not find statistically significant results for other groups. CONCLUSION: We cannot conclude that home confinement did have a negative impact on myopia control with orthokeratology in school-aged children. But we found there was an increase in the percentage of patients with OK treatment that had fast myopia progression during the confinement. We also observed that older children with higher initial refraction were more likely to be affected by home confinement.


Assuntos
Miopia , Procedimentos Ortoceratológicos , Humanos , Criança , Adolescente , Procedimentos Ortoceratológicos/métodos , Comprimento Axial do Olho , Miopia/epidemiologia , Miopia/terapia , Refração Ocular
8.
Angew Chem Int Ed Engl ; 62(21): e202301592, 2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-36932035

RESUMO

Metal-polarized aza-ortho-quinone methides (aza-o-QMs) are a unique and efficient handle for azaheterocycle synthesis. Despite great achievements, the potential of these reactive intermediates has not yet been fully exploited, especially the new reaction modes. Herein, we disclosed an unprecedented dearomatization process of metal-polarized aza-o-QMs, affording transient dearomatized spiroaziridine intermediates. Based on this serendipity, we accomplished three sequential dearomatization-rearomatization reactions of benzimidazolines with aza-sulfur ylides, enabling the divergent synthesis of bis-nitrogen heterocycles with high efficiency and flexibility. Moreover, experimental and theoretical studies were performed to explain the proposed mechanisms and observed selectivity. Further cellular evaluation of the dibenzodiazepine products identified a hit compound for new antitumor drugs.

9.
J Am Chem Soc ; 144(43): 19932-19941, 2022 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-36270010

RESUMO

Searching for efficient strategies to access structurally novel aminoindolines is of great significance for drug discovery. However, catalytic asymmetric de novo construction of aminoindoline scaffolds with functionality primed for diversification still remains elusive. Here, we report a Cu-catalyzed asymmetric cyclization of ethynyl benzoxazinones with amines, producing chiral 3-aminoindolines in good yield and with high enantioselectivity (up to 97% yield and 98:2 er). Moreover, a radical-mediated sulfonyl migration of these products was unexpectedly found, further affording new chiral 3-aminoindolines bearing alkenyl sulfonyl groups with retained enantiopurity (up to 84% yield and 98:2 er). Bioactivity evaluations indicate that these 3-aminoindolines show notable antitumor activities and chirality is proven to have a significant impact on their antitumor activity.


Assuntos
Aminas , Ciclização , Estereoisomerismo , Catálise
10.
Nanotechnology ; 32(2): 025702, 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-32916671

RESUMO

Anode materials play an important role in the performance of rechargeable batteries and have been attracting much research interest. In this work, we have investigated the electrochemical properties of two-dimensional (2D) Janus MSSe (M = Ti or V) for potential applications as anode materials in alkali metal ion batteries from density functional theory (DFT), following the recent successful synthesis of 2D Janus MoSSe. Our DFT calculations suggest that 2D Janus TiSSe and VSSe are stable in the 1T phase and 1H phase, respectively. It is found that alkali metal atoms X (X = Li, Na or K) can be stably adsorbed on the surfaces of Janus MSSe, and have low diffusion energy barriers. Additionally, small volume changes are observed in Janus MSSe after the adsorption of alkali metal atoms. It is predicted that the MSSe-2X systems have low open circuit voltages and high capacities. Our results suggest that 2D Janus TiSSe and VSSe are potential anode materials for alkali metal ion batteries.

11.
Am J Otolaryngol ; 42(5): 103143, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34175691

RESUMO

OBJECTIVE: To analyze the clinical characteristics of patients with unilateral auditory neuropathy (UAN), and to provide guidance for future clinical diagnosis and research. METHODS: Patients who were clinically diagnosed with UAN from 2004 to 2019 were included. Clinical characteristics, audiological features, imaging findings, genetic test results and management effect were summarized and followed. RESULTS: A total of 44 patients [mean age, 4.35 ± 4.39 years; 22 (50.00%) males and 22 (50.00%) females] were enrolled for analyses. Among the 38 patients who were tested by pure-tone or behavioral audiometry, the degree of hearing loss of the affected ear was characterized as mild in 2 ears (5.26%), moderate in 5 (13.16%), severe in 9 (23.68%) and profound in 22 (57.89%). For the 44 contralateral ears, 33 (75.00%) showed normal hearing and 11 (25.00%) presented with sensorineural hearing loss. Auditory brainstem responses were absent or abnormal in all 44 affected ears, while otoacoustic emissions and/or cochlear microphonics were present. Among the 18 patients who underwent magnetic resonance imaging (MRI), 7 (38.89%) presented cochlear nerve deficiency (CND). Nineteen candidate variants were found in 12 patients among the 15 UAN patients who were conducted targeted gene capture and next generation sequencing. Thirty patients were followed up by telephone to investigate their management effect. CONCLUSIONS: Our study demonstrates comprehensive audiological features of patients with UAN to improve the clinical understanding and diagnosis. Some patients with UAN could show ipsilateral CND and MRI is essential to evaluate if the nerve is deficient. No pathogenic variants that directly related to the pathogenesis of UAN have been found in this study currently.


Assuntos
Perda Auditiva Central , Audiometria de Tons Puros , Criança , Pré-Escolar , Potenciais Evocados Auditivos do Tronco Encefálico , Feminino , Seguimentos , Perda Auditiva Central/complicações , Perda Auditiva Central/diagnóstico , Perda Auditiva Central/genética , Perda Auditiva Central/fisiopatologia , Perda Auditiva Neurossensorial/etiologia , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Índice de Gravidade de Doença , Doenças do Nervo Vestibulococlear/diagnóstico por imagem , Doenças do Nervo Vestibulococlear/etiologia
12.
Neural Plast ; 2020: 5625768, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32684920

RESUMO

To decipher the genotype-phenotype correlation of auditory neuropathy (AN) caused by AIFM1 variations, as well as the phenotype progression of these patients, exploring the potential molecular pathogenic mechanism of AN. A total of 36 families of individuals with AN (50 cases) with AIFM1 variations were recruited and identified by Sanger sequencing or next-generation sequencing; the participants included 30 patients from 16 reported families and 20 new cases. We found that AIFM1-positive cases accounted for 18.6% of late-onset AN cases. Of the 50 AN patients with AIFM1 variants, 45 were male and 5 were female. The hotspot variation of this gene was p.Leu344Phe, accounting for 36.1%. A total of 19 AIFM1 variants were reported in this study, including 7 novel ones. A follow-up study was performed on 30 previously reported AIFM1-positive subjects, 16 follow-up cases (53.3%) were included in this study, and follow-up periods were recorded from 1 to 23 years with average 9.75 ± 9.89 years. There was no hearing threshold increase during the short-term follow-up period (1-10 years), but the low-frequency and high-frequency hearing thresholds showed a significant increase with the prolongation of follow-up time. The speech discrimination score progressed gradually and significantly along with the course of the disease and showed a more serious decline, which was disproportionately worse than the pure tone threshold. In addition to the X-linked recessive inheritance pattern, the X-linked dominant inheritance pattern is also observed in AIFM1-related AN and affects females. In conclusion, we confirmed that AIFM1 is the primary related gene among late-onset AN cases, and the most common recurrent variant is p.Leu344Phe. Except for the X-linked recessive inheritance pattern, the X-linked dominant inheritance pattern is another probability of AIFM1-related AN, with females affected. Phenotypical features of AIFM1-related AN suggested that auditory dyssynchrony progressively worsened over time.


Assuntos
Fator de Indução de Apoptose/genética , Frequência do Gene , Perda Auditiva Central/genética , Mutação , Linhagem , Adolescente , Adulto , Alelos , Criança , China , Feminino , Estudos de Associação Genética , Humanos , Masculino , Fenótipo , Adulto Jovem
13.
Zhongguo Zhong Yao Za Zhi ; 45(1): 92-97, 2020 Jan.
Artigo em Zh | MEDLINE | ID: mdl-32237416

RESUMO

Pyrrolizidine alkaloids(PAs) are a kind of natural toxins, which can cause severe hepatotoxicity, pulmonary toxicity, genotoxicity, neurotoxicity, embryotoxicity and even death. Therefore, international organizations and countries such as World Health Organization have paid great attention to herbal medicines and preparations containing PAs. PAs are widely distributed in Chinese herb medicines and contained in hundreds of traditional Chinese medicine preparations. The content of adonifoline, the main PAs in Senecionis Scandentis Herba, shall be less than 0.004% in herbal medicines as described in Chinese pharmacopeia. However, there is no guidance in preparations which contain Senecionis Scandentis Herba. In this study, 14 preparations were analyzed by an UPLC-MS method. Among them, 8 preparations were found to contain adonifoline much higher than the content limits of such countries as Germany, Netherlands and New Zealand. And the highest contents of adonifoline were found in Qianbai Biyan Tablets and Qianbai Biyan Capsules, which are officially recorded in Chinese Pharmacopeia. The contents of adonifoline varied in different batches of the same preparations. The highest content was 156.10 µg·g~(-1) Qianbai Biyan Tablets, whose daily intake of adonifoline was up to 1 030.26 µg according to the recommended dosage of the preparation. Our results showed the potential risk of these preparations, and the content limit of adonifoline shall be inspected Chinese medicine preparations containing Senecionis Scandentis Herba.


Assuntos
Medicamentos de Ervas Chinesas/análise , Lactonas/análise , Alcaloides de Pirrolizidina/análise , Senécio/química , Cromatografia Líquida , Medicamentos de Ervas Chinesas/normas , Medicina Tradicional Chinesa , Espectrometria de Massas em Tandem
14.
J Am Chem Soc ; 140(47): 16190-16197, 2018 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-30360620

RESUMO

GeTe experiences phase transition between cubic and rhombohedral through distortion along the [111] direction. Cubic GeTe shares the similarity of a two-valence-band structure (high-energy L and low-energy Σ bands) with other cubic IV-VI semiconductors such as PbTe, SnTe, and PbSe, and all show a high thermoelectric performance due to a high band degeneracy. Very recently, the two valence bands were found to switch in energy in rhombohedral GeTe and to be split due to symmetry-breaking of the crystal structure. This enables the overall band degeneracy to be manipulated either by the control of symmetry-induced degeneracy or by the design of energy-aligned orbital degeneracy. Here, we show Sb-doping for optimizing carrier concentration and manipulating the degree of rhombohedral lattice distortion to maximize the band degeneracy and then electronic performance. In addition, Sb-doping significantly promotes the solubility of PbTe, enhancing the scattering of phonons by Ge/Pb substitutional defects for minimizing the lattice thermal conductivity. This successfully realizes a superior thermoelectric figure of merit, zT of >2 in both rhombohedral and cubic GeTe, demonstrating these alloys as top candidates for thermoelectric applications at T < 800 K. This work further sheds light on the importance of crystal structure symmetry manipulation for advancing thermoelectrics.

15.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 34(2): 164-168, 2017 Apr 10.
Artigo em Zh | MEDLINE | ID: mdl-28397210

RESUMO

OBJECTIVE: To identify pathogenic mutations of TSC1 and TSC2 genes in two familial and one sporadic cases with tuberous sclerosis complex (TSC). METHODS: For five patients and their family members, potential mutations of the TSC1 and TSC2 genes were detected by direct sequencing. RESULTS: For one family, a novel missense mutation c.1964C>T (p.S655F) was detected in the exon 19 of the TSC2 gene. For the sporadic patient, a repeat substitution with deletion mutation c.5238-5255delCATCAAGCGGCTCCGCCA (p.His1746GlnfsX56) was detected in the exon 40 of the TSC2 gene, which led to a stop codon TGA after the 56th amino acids. No mutation was found in another family. CONCLUSION: The missense mutation c.1964C>T(P.S655F) and the substitution with deletion mutation 5238-5255delCATCAAGCGGCTCCGCCA(p.His1746GlnfsX56) of the TSC2 gene probably underlie the disease in the first family and the sporadic case.


Assuntos
Mutação de Sentido Incorreto , Esclerose Tuberosa/genética , Proteínas Supressoras de Tumor/genética , Adolescente , Adulto , Sequência de Bases , Pré-Escolar , Análise Mutacional de DNA , Feminino , Humanos , Masculino , Linhagem , Fenótipo , Proteína 1 do Complexo Esclerose Tuberosa , Proteína 2 do Complexo Esclerose Tuberosa
16.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 33(2): 173-6, 2016 Apr.
Artigo em Zh | MEDLINE | ID: mdl-27060309

RESUMO

OBJECTIVE: To identify potential mutation of the ADAR1 gene in a Chinese family and a sporadic case affected with dyschromatosis symmetrica hereditaria(DSH). METHODS: Clinical data and peripheral blood samples from the pedigree and the sporadic patient were collected. Following extraction of genomic DNA, all 15 exons and exon-intron flanking sequences of the ADAR1 gene were amplified by polymerase chain reaction and subjected to direct sequencing. RESULTS: A novel frame-shift mutation c.2638delG (p.Asp880ThrfsX15) from the patients of the pedigree was detected in exon 8 of the ADAR1 gene. And a novel nonsense mutation c.2867C>A (p.Ser956X) was detected in exon 10 of the ADAR1 gene from the sporadic case. Neither mutation was identified among the unaffected family members nor 100 unrelated healthy controls. CONCLUSION: The frame-shift mutation c.2638delG (p.Asp880ThrfsX15) and the nonsense mutation c.2867C>A (p.Ser956X) in the ADAR1 gene probably underlie the DSH in our patients.


Assuntos
Adenosina Desaminase/genética , Códon sem Sentido , Mutação da Fase de Leitura , Transtornos da Pigmentação/congênito , Proteínas de Ligação a RNA/genética , Adulto , Povo Asiático/genética , Sequência de Bases , China , Éxons , Feminino , Humanos , Masculino , Dados de Sequência Molecular , Linhagem , Transtornos da Pigmentação/enzimologia , Transtornos da Pigmentação/genética
17.
Int Immunopharmacol ; 127: 111412, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38160567

RESUMO

There is a lack of reliable biomarkers to predict and identify the risk of immune-related adverse events (irAEs) in non-small cell lung cancer (NSCLC) patients undergoing immune checkpoint inhibitor (ICI) treatment. This study aims to explore potential biomarkers using lipidomics to identify and predict the risk of irAEs in NSCLC patients receiving ICI treatment. This prospective study enrolled 94 NSCLC patients with IIIB/IV stage NSCLC who underwent first-line chemotherapy in combination with ICI treatment. The prediction cohort consisted of plasma samples collected from 60 patients before ICI treatment, and the occurrence of irAE was monitored within 6 months of initiating first-line ICI therapy. The validation cohort comprised 34 patients, with plasma samples obtained from 15 patients who did not develop irAE at 6 months of ICI treatment and plasma samples collected from 19 irAE patients at the onset of irAE. Through non-targeted lipidomics and semi-targeted lipid quantification analysis, we identify 11 differentially metabolized lipids and further screened these lipids with the area under the curve (AUC) > 0.7 to predict the occurrence of irAEs in NSCLC patients following ICI treatment. The results showed that the biomarker panel consisting of 9 lipids (LPC-18:2, PC-40:6, LPC-22:6, LPC-O-18:0, PS-38:0, PC-38:6, PC-37:6, PC-36:5,LPC-17:0) exhibited a good AUC of 0.859 in the prediction and 0.940 in the validation cohort phase of the receiver operating characteristic curve; The study utilizes plasma lipidomics to develop a rapid and effective prediction model for identifying irAEs in advanced NSCLC patients who treatment with first-line chemotherapy combined with immunotherapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Lipidômica , Estudos Prospectivos , Neoplasias Pulmonares/tratamento farmacológico , Biomarcadores , Lipídeos , Estudos Retrospectivos
18.
Oncoimmunology ; 13(1): 2303195, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38235318

RESUMO

Many biological processes related to cell function and fate begin with chromatin alterations, and many factors associated with the efficacy of immune checkpoint inhibitors (ICIs) are actually downstream events of chromatin alterations, such as genome changes, neoantigen production, and immune checkpoint expression. However, the influence of genes as chromatin regulators on the efficacy of ICIs remains elusive, especially in gastric cancer (GC). In this study, thirty out of 1593 genes regulating chromatin associated with a favorable prognosis were selected for GC. CHAF1A, a well-defined oncogene, was identified as the highest linkage hub gene. High CHAF1A expression were associated with microsatellite instability (MSI), high tumor mutation burden (TMB), high tumor neoantigen burden (TNB), high expressions of PD-L1 and immune effector genes, and live infiltration of immune cells. High CHAF1A expression indicated a favorable response and prognosis in immunotherapy of several cohorts, which was independent of MSI, TMB, TNB, PD-L1 expression, immune phenotype and transcriptome scoring, and improved patient selection based on these classic biomarkers. In vivo, CHAF1A knockdown alone inhibited tumor growth but it impaired the effect of an anti-PD-1 antibody by increasing the relative tumor proliferation rate and decreasing the survival benefit, potentially through the activation of TGF-ß signaling. In conclusion, CHAF1A may be a novel biomarker for improving patient selection in immunotherapy.


Assuntos
Antígeno B7-H1 , Neoplasias Gástricas , Humanos , Antígeno B7-H1/genética , Cromatina , Imunoterapia , Neoplasias Gástricas/patologia , Oncogenes/genética
19.
Environ Monit Assess ; 185(8): 6713-8, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23307100

RESUMO

Extracellular polymeric substances (EPS) were extracted from Aspergillus fumigatus using cationic exchange resin technique. The EPS were mainly composed of polysaccharide and low quantities of protein and nucleic acid. Biosorption of Cd(II), Pb(II), and Cu(II) of EPS was investigated as a function of pH using differential pulse polarography and the Ruzic model. Results showed that the EPS biosorption capacity determined using either the direct titration curves i = f(C M) or the method proposed by Ruzic (Analytica Chimica Acta 140:99-113, 1982) were coincident. Cu(II) had the highest affinity with EPS followed by Pb(II) and Cd(II). The total number of binding sites for Cu(II) and Cd(II) increased with pH in the range of 4.0-7.0. Similar trend was observed for Pb(II) at pH 4.0-5.0, while precipitates were observed at pH 6.0 and 7.0. The conditional binding constants of these three metals displayed low levels of fluctuation with pH and ranged from 4.02 ± 0.02 to 5.54 ± 0.05.


Assuntos
Aspergillus fumigatus/química , Cádmio/análise , Cobre/análise , Chumbo/análise , Polarografia/métodos , Aspergillus fumigatus/metabolismo , Cádmio/metabolismo , Cátions Bivalentes/análise , Cátions Bivalentes/metabolismo , Cobre/metabolismo , Poluentes Ambientais/análise , Poluentes Ambientais/metabolismo , Resinas de Troca Iônica , Chumbo/metabolismo
20.
J Affect Disord ; 341: 319-328, 2023 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-37659615

RESUMO

BACKGROUND: Frontline nurses suffered unprecedented mental distress during the COVID-19 pandemic. It's essential to explore new and more accessible alternatives to improve the availability of psychological treatments. This study aimed to investigate the influence of online self-help iACT linear intervention and iACT loop intervention on sleep quality (SQ), obsessive-compulsive symptoms (OCS), and psychological flexibility (PF) in nurses. METHODS: A randomized controlled trial was conducted at a hospital in China. 602 participants were randomly assigned to the iACT linear intervention, iACT loop intervention, or wait list control group, and required to complete the questionnaires of OCS, PF and SQ. The linear mixed effects analysis (LMM) was used to analyze the impact of the intervention on outcome variables. RESULTS: LMM analyses demonstrated that both two intervention had significant improvement on OCS (t = -38.235, p < 0.001), PF (t = 28.156, p < 0.001), as well as SQ (t = -16.336, p < 0.001). There were significant differences between the linear group and loop group on the PF in T2 (t = -8.271, p < 0.001), T3 (t = -8.366, p < 0.001), T4 (t = -8.302, p < 0.001), with the iACT loop model (Cohen's d = 1.652) showing a slight advantage over the iACT linear model (Cohen's d = 1.134). CONCLUSIONS: The findings indicate that two interventions positively impact OCS, PF, and SQ. Compared to the iACT linear psychotherapy model, the iACT loop model shows greater effectiveness in enhancing PF, making it helpful to promote significant improvements in psychotherapy planning.


Assuntos
Terapia de Aceitação e Compromisso , COVID-19 , Enfermeiras e Enfermeiros , Transtorno Obsessivo-Compulsivo , Humanos , Qualidade do Sono , Seguimentos , Pandemias , Internet , Transtorno Obsessivo-Compulsivo/terapia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA