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1.
Skin Res Technol ; 29(7): e13416, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37522501

RESUMO

BACKGROUND: Acquired perforating dermatosis (APD) is a rare skin condition characterized by degenerated materials eliminated from the dermis. Several retrospective studies on APD have been reported; however, few data are available on Chinese APD and their features on dermoscopy and reflective confocal microscope (RCM) assays. OBJECTIVE: The aim of this study was to retrospectively evaluate the clinical and histopathologic data of 37 acquired perforating dermatosis cases, and assess their features on dermoscopy and RCM. METHODS: Thirty-seven APD patients were retrospectively enrolled in our study. We characterized the clinical histopathological features, concomitant diseases, treatment responses, and the dermoscopy and RCM findings. RESULTS: Pruritus was the most common symptom, with the lower extremities as the most predilection sites (86.5%, n = 32; 91.9%, n = 34, respectively). Concomitant diseases were found in 34 patients (92.6%), among which diabetes mellitus was the most common, followed by thyroid nodules, allergic dermatosis, and chronic renal insufficiency. Dermoscopy and RCM assays were performed in 11 patients. The typical RCM images were hyperreflective cord-like structures from the epidermis to dermis. Dermoscopy features of fully developed lesions showed central ulceration with peripheral hairpin-like or loop-like capillaries with characteristic garland arrangements. CONCLUSION: APD is an uncommon skin disorder associated with various systemic conditions in Chinese individuals. Thyroid disorders are an overlooked complication and may play an important role in the development of APD. The results of this study indicate that noninvasive dermoscopy and RCM examination are helpful in the rapid diagnosis and early intervention of APD.


Assuntos
Dermatopatias , Neoplasias Cutâneas , Humanos , Estudos Retrospectivos , Dermoscopia , Dermatopatias/patologia , Pele/patologia , Microscopia Confocal/métodos , Neoplasias Cutâneas/patologia
2.
World J Surg Oncol ; 21(1): 239, 2023 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-37542314

RESUMO

BACKGROUND: As digital medicine has exerted profound influences upon diagnosis and treatment of hepatobiliary diseases, our study aims to investigate the accuracy of three-dimensional visualization and evaluation (3DVE) system in assessing the resectability of hilar cholangiocarcinoma (hCCA), and explores its potential clinical value. MATERIALS AND METHODS: The discovery cohort, containing 111 patients from April 2013 to December 2019, was retrospectively included to determine resectability according to revised criteria for unresectability of hCCA. 3D visualization models were reconstructed to evaluate resectability parameters including biliary infiltration, vascular involvement, hepatic atrophy and metastasis. Evaluation accuracy were compared between contrast-enhanced CT and 3DVE. Logistic analysis was performed to identify independent risk factors of R0 resection. A new comprehensive 3DVE classification of hCCA based on factors influencing resectability was proposed to investigate its role in predicting R0 resection and prognosis. The main outcomes were also analyzed in cohort validation, including 34 patients from January 2020 to August 2022. RESULTS: 3DVE showed an accuracy rate of 91% (95%CI 83.6-95.4%) in preoperatively evaluating hCCA resectability, significantly higher than 81% (95%CI 72.8-87.7%) of that of CT (p = 0.03). By multivariable analysis, hepatic artery involvement in 3DVE was identified an independent risk factor for R1 or R2 resection (OR = 3.5, 95%CI 1.4,8.8, P < 0.01). New 3DVE hCCA classification was valuable in predicting patients' R0 resection rate (p < 0.001) and prognosis (p < 0.0001). The main outcomes were internally validated. CONCLUSIONS: 3DVE exhibited a better efficacy in evaluating hCCA resectability, compared with contrast-enhanced CT. Preoperative 3DVE demonstrated hepatic artery involvement was an independent risk factor for the absence of R0 margin. 3DVE classification of hCCA was valuable in clinical practice.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Tumor de Klatskin , Humanos , Tumor de Klatskin/diagnóstico por imagem , Tumor de Klatskin/cirurgia , Tumor de Klatskin/patologia , Colangiocarcinoma/diagnóstico por imagem , Colangiocarcinoma/cirurgia , Colangiocarcinoma/patologia , Imageamento Tridimensional , Estudos Retrospectivos , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/cirurgia , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/diagnóstico por imagem , Ductos Biliares Intra-Hepáticos/cirurgia , Ductos Biliares Intra-Hepáticos/patologia
3.
Radiol Med ; 128(6): 714-725, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37219740

RESUMO

BACKGROUND: To study the role of computed tomography (CT)-derived radiomics features and clinical characteristics on the prognosis of "driver gene-negative" lung adenocarcinoma (LUAD) and to explore the potential molecular biological which may be helpful for patients' individual postoperative care. METHODS: A total of 180 patients with stage I-III "driver gene-negative" LUAD in the First Affiliated Hospital of Sun Yat-Sen University from September 2003 to June 2015 were retrospectively collected. The Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression model was used to screen radiomics features and calculated the Rad-score. The prediction performance of the nomogram model based on radiomics features and clinical characteristics was validated and then assessed with respect to calibration. Gene set enrichment analysis (GSEA) was used to explore the relevant biological pathways. RESULTS: The radiomics and the clinicopathological characteristics were combined to construct a nomogram resulted in better performance for the estimation of OS (C-index: 0.815; 95% confidence interval [CI]: 0.756-0.874) than the clinicopathological nomogram (C-index: 0.765; 95% CI: 0.692-0.837). Decision curve analysis demonstrated that in terms of clinical usefulness, the radiomics nomogram outperformed the traditional staging system and the clinicopathological nomogram. The clinical prognostic risk score of each patient was calculated based on the radiomics nomogram and divided by X-tile into high-risk (> 65.28) and low-risk (≤ 65.28) groups. GSEA results showed that the low-risk score group was directly related to amino acid metabolism, and the high-risk score group was related to immune and metabolism pathways. CONCLUSIONS: The radiomics nomogram was promising to predict the prognosis of patients with "driver gene-negative" LUAD. The metabolism and immune-related pathways may provide new treatment orientation for this genetically unique subset of patients, which may serve as a potential tool to guide individual postoperative care for those patients.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Nomogramas , Estudos Retrospectivos , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Prognóstico , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia
4.
BMC Pulm Med ; 21(1): 232, 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34256739

RESUMO

BACKGROUND: Few reference equations exist for healthy adults of various races for pulmonary diffusing capacity for nitric oxide (DLNO). The purpose of this study was to collect pilot data to demonstrate that race-specific reference equations are needed for DLNO. METHODS: African Americans (blacks) were chosen as the comparative racial group. In 2016, a total of 59 healthy black subjects (27 males and 32 females) were recruited to perform a full battery of pulmonary function tests. In the development of DLNO reference equations, a white reference sample (randomly drawn from a population) matched to the black sample for sex, age, and height was used. Multiple linear regression equations for DLNO, alveolar volume (VA), and pulmonary diffusing capacity for carbon monoxide (DLCO) using a 5-6 s breath-hold were developed. RESULTS: Our models demonstrated that sex, age2, race, and height explained 71% of the variance in DLNO and DLCO, with race accounting for approximately 5-10% of the total variance. After normalizing for sex, age2, and height, blacks had a 12.4 and 3.9 mL/min/mmHg lower DLNO and DLCO, respectively, compared to whites. The lower diffusing capacity values in blacks are due, in part, to their 0.6 L lower VA (controlling for sex and height). CONCLUSION: The results of this pilot data reveal small but important and statistically significant racial differences in DLNO and DLCO in adults. Future reference equations should account for racial differences. If these differences are not accounted for, then the risk of falsely diagnosing lung disease increase in blacks when using reference equations for whites.


Assuntos
Negro ou Afro-Americano , Óxido Nítrico/metabolismo , Capacidade de Difusão Pulmonar , Administração por Inalação , Adolescente , Adulto , Monóxido de Carbono/metabolismo , Feminino , Voluntários Saudáveis , Humanos , Modelos Lineares , Masculino , Óxido Nítrico/administração & dosagem , Valores de Referência , Testes de Função Respiratória , Adulto Jovem
5.
Am J Dermatopathol ; 43(12): 942-944, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34291739

RESUMO

ABSTRACT: Acquired perforating dermatoses (APDs) are a group of diverse skin disorders in patients with systemic disease, most commonly chronic renal failure and diabetes mellitus. APD induced by medication has seldom been reported. Anti-PD-1 monoclonal antibody has recently been used as a broad-spectrum, effective, durable, and relatively safe antitumor therapy for various malignancies. Thus far, known side effects involving skin have included rash, pruritus, and vitiligo. Here, we present a rare case of a unilateral linear eruption with histopathologic features of APD in a 36-year-old man during treatment with Terepril monoclonal antibody. To the best of our knowledge, APD induced by the PD-1 inhibitor has not been described in the medical literature.


Assuntos
Toxidermias/patologia , Inibidores de Checkpoint Imunológico/efeitos adversos , Dermatopatias/induzido quimicamente , Dermatopatias/patologia , Adenocarcinoma/tratamento farmacológico , Adulto , Neoplasias do Colo/tratamento farmacológico , Toxidermias/etiologia , Humanos , Masculino
6.
Neurobiol Dis ; 130: 104486, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31150793

RESUMO

Accumulated genetic evidences indicate that the contactin associated protein-like (CNTNAP) family is implicated in autism spectrum disorders (ASD). In this study, we identified genetic mutations in the CNTNAP3 gene from Chinese Han ASD cohorts and Simons Simplex Collections. We found that CNTNAP3 interacted with synaptic adhesion proteins Neuroligin1 and Neuroligin2, as well as scaffolding proteins PSD95 and Gephyrin. Significantly, we found that CNTNAP3 played an opposite role in controlling the development of excitatory and inhibitory synapses in vitro and in vivo, in which ASD mutants exhibited loss-of-function effects. In this study, we showed that the male Cntnap3-null mice exhibited deficits in social interaction, spatial learning and prominent repetitive behaviors. These evidences elucidate the pivotal role of CNTNAP3 in synapse development and social behaviors, providing mechanistic insights into ASD.


Assuntos
Transtorno do Espectro Autista/genética , Predisposição Genética para Doença/genética , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Neurogênese/genética , Comportamento Social , Animais , Comportamento Animal , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mutação , Sinapses
7.
J Exp Bot ; 70(19): 5407-5421, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31173088

RESUMO

Bacterial wilt caused by Ralstonia solanacearum is a devastating disease affecting hundreds of plant species, yet the host factors remain poorly characterized. The leucine-rich repeat receptor-like kinase gene AhRLK1, characterized as CLAVATA1, was found to be up-regulated in peanut upon inoculation with R. solanacearum. The AhRLK1 protein was localized in the plasma membrane and cell wall. qPCR results showed AhRLK1 was induced in a susceptible variety but little changed in a resistant cultivar after inoculated with R. solanacearum. Hormones such as salicylic acid, abscisic acid, methyl jasmonate, and ethephon induced AhRLK1 expression. In contrast, AhRLK1 expression was down-regulated under cold and drought treatments. Transient overexpression of AhRLK1 led to a hypersensitive response (HR) in Nicotiana benthamiana. Furthermore, AhRLK1 overexpression in tobacco significantly increased the resistance to R. solanacearum. Besides, the transcripts of most representative defense responsive genes in HR and hormone signal pathways were significantly increased in the transgenic lines. EDS1 and PAD4 in the R gene signaling pathway were also up-regulated, but NDR1 was down-regulated. Accordingly, AhRLK1 may increase the defense response to R. solanacearum via HR and hormone defense signaling, in particular through the EDS1 pathway of R gene signaling. These results provide a new understanding of the CLAVATA1 function and will contribute to genetic enhancement of peanut.


Assuntos
Arachis/genética , Nicotiana/microbiologia , Doenças das Plantas/microbiologia , Proteínas de Plantas/genética , Proteínas Serina-Treonina Quinases/genética , Ralstonia solanacearum/fisiologia , Arachis/metabolismo , Resistência à Doença , Doenças das Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Nicotiana/genética
8.
BMC Surg ; 19(1): 185, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31795997

RESUMO

BACKGROUND: As there is no consensus on the optimal surgery strategy for multiple primary lung cancer (MPLC), we conducted this study to address this issue by comparing the prognosis of MPLC patients underwent different surgical strategies including sublobar resection and the standard resection through a systemic review and meta-analysis. METHODS: Relevant literature was obtained from three databases including PubMed, Embase and Web of Science. Inclusion and exclusion criteria were set for the screening of articles to be selected for further conduction of systemic review and meta-analysis. The HRs of OS of the sublobar group compared with standard resection group were extracted directly or calculated indirectly from included researches. RESULTS: Ten researches published from 2000 to 2017 were included in this study, with 468 and 445 MPLC cases for the standard resection group and sublobar resection group respectively. The result suggested that OS of MPLC patients underwent sublobar resection (segmentectomy or wedge resection for at least one lesion) was comparable with those underwent standard resection approach (lobectomy or pneumonectomy for all lesions), with HR 1.07, 95% CI 0.67-1.71, p = 0.784. Further analysis found no difference in subgroups of synchronous and metachronous (from second metachronous lesion), different population region and dominant sex type. CONCLUSIONS: This study may reveal that sublobar resection is acceptable for patients with MPLC at an early stage, because of the equivalent prognosis to the standard resection and better pulmonary function preservation. Further research is needed to validate these findings.


Assuntos
Neoplasias Pulmonares/cirurgia , Neoplasias Primárias Múltiplas/cirurgia , Pneumonectomia/métodos , Humanos , Estadiamento de Neoplasias , Prognóstico
9.
Am J Dermatopathol ; 38(4): 305-6, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26863062

RESUMO

Angiolymphoid hyperplasia with eosinophilia (ALHE) is an uncommon, idiopathic vascular disorder. It manifests as dermal or subcutaneous red to brown papules or nodules, most commonly on the head and neck; other less common sites include the trunk, extremities, genitalia, lips, and oral mucosa. Although ALHE is a benign disease, lesions are often persistent and difficult to eradicate. ALHE occurs more frequently in Asian young and middle-aged women. Histologically, it is characterized by a florid vascular proliferation with hobnail epithelioid endothelial cells surrounding by lymphocytic and eosinophilic infiltrate. Here, we reported congenital ALHE in a 2-year-old girl. Unilateral lesions had a blaschkoid segmental distribution in the anogenital region and were successfully treated with the Nd:YAG laser.


Assuntos
Hiperplasia Angiolinfoide com Eosinofilia/congênito , Canal Anal/patologia , Hiperplasia Angiolinfoide com Eosinofilia/cirurgia , Pré-Escolar , Feminino , Genitália Feminina/patologia , Humanos , Lasers de Estado Sólido
10.
Am J Dermatopathol ; 37(8): 639-42, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25321088

RESUMO

Interdigitating dendritic cell sarcoma (IDCS) is defined as a neoplastic proliferation of spindle to ovoid cells with phenotypic features similar to those of interdigitating dendritic cells, which are present in the T cell-rich areas of lymphoid organs and participate as antigen-presenting cells responsible for initiating primary T lymphocyte immune response. IDCS usually presents with lymphadenopathy. Solitary lymph node involvement is often seen. Extra nodal presentation has been described as well. Cutaneous lesions are extremely rare, and less than 10 cases have been previously documented in medical literature. Here, the authors describe another primary cutaneous IDCS in a 42-year-old patient and review the literature.


Assuntos
Sarcoma de Células Dendríticas Interdigitantes/patologia , Neoplasias Cutâneas/química , Neoplasias Cutâneas/patologia , Adulto , Feminino , Humanos , Antígenos Comuns de Leucócito/análise , Proteínas S100/análise , Vimentina/análise
11.
Am J Dermatopathol ; 36(12): 965-71, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24698942

RESUMO

Panfolliculoma (PF) is an uncommon benign follicular neoplasm exhibiting differentiation toward all components of a hair follicle. Several pathologic manifestations have been described in a limited number of cases. We studied 19 cases of PF to summarize the clinical parameters and to classify this unique neoplasm histopathologically. A study of the largest sample series of PF has been performed here. The lesions affect both genders after age 20. The head is the most common site of PF of all types. On microscopic examination, all cases demonstrated advanced follicular differentiation by showing cell components of infundibulum, isthmus, stem, bulb, and mesenchymal papilla. Based on the findings and various patterns in histopathology, we classified PF into 3 subtypes: nodular, superficial, and cystic. The superficial and cystic variants account for most of the cases in our study. The histopathologic differential diagnosis is also discussed for each subtype.


Assuntos
Doenças do Cabelo/patologia , Folículo Piloso/patologia , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias Cutâneas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Diferenciação Celular , Diagnóstico Diferencial , Feminino , Doenças do Cabelo/classificação , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Cutâneas/classificação , Adulto Jovem
12.
Am J Dermatopathol ; 36(6): 510-2, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24366197

RESUMO

Sclerosing lipogranuloma is a granulomatous reaction to the injection of a high-viscosity fluid in the tissues for the cosmetic purpose of improving body contour; lesions on the extremities and buttocks are commonly the results of injections of therapeutic agents in oily vehicles. Exenatide, once-weekly injection, is a therapeutic method for patients with type 2 diabetes. Here, we describe a case of exenatide once weekly induced eosinophilic sclerosing lipogranuloma at the injection site of a 62-year-old patient. To the best of our knowledge, the histopathologic features of this adverse event have not been reported in the medical literature.


Assuntos
Eosinofilia/induzido quimicamente , Granuloma/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Paniculite/induzido quimicamente , Peptídeos/efeitos adversos , Dermatopatias/induzido quimicamente , Peçonhas/efeitos adversos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Eosinofilia/patologia , Exenatida , Granuloma/patologia , Humanos , Hipoglicemiantes/administração & dosagem , Injeções Subcutâneas/efeitos adversos , Masculino , Pessoa de Meia-Idade , Paniculite/patologia , Peptídeos/administração & dosagem , Dermatopatias/patologia , Peçonhas/administração & dosagem
13.
Zookeys ; 1214: 35-57, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39391534

RESUMO

Four species of the cosmopolitan genus Asaphes Walker, 1834 (Hymenoptera: Chalcidoidea: Asaphesinae, family incerta sedis) are recorded from Xinjiang Uyghur Autonomous Region, China, bringing the number of known species in China to eight. In addition to Asaphessuspensus (Nees ab Esenbeck), 1834 and A.vulgaris Walker, 1834, A.fuyunis Li & Zhang, sp. nov. is newly described based on females and A.californicus Girault, 1917, previously known only from North and South America, is newly recorded from China. These four species are differentiated using an integrative taxonomic approach that includes COI barcode data and morphometrics, and are illustrated using macrophotography. Additionally, the 13 described world species of Asaphes are tabulated and females of the eight recognized Chinese species are keyed.

14.
Brain Behav ; 14(2): e3399, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38340139

RESUMO

OBJECTIVE: To explore the impact of inflammatory factors on the incidence of cerebral small vessel disease (CSVD), we performed a mendelian randomization (MR) study to analyze the causal relationship between multiple inflammatory factors and CSVD imaging markers and utilized summary-data-based mendelian randomization (SMR) analysis to infer whether the impact of instrumental variables (IVs) on disease is mediated by gene expression or DNA methylation. METHODS: Using public databases such as UKB and IEU, and original genome-wide association studies, we obtained IVs related to exposure (inflammatory factors) and outcome (CSVD imaging markers). We performed the inverse variance weighted, weighted median, and MR-Egger methods to assess causal effects between exposure and outcome in univariate MR analysis. To evaluate their heterogeneity, a series of sensitivity analyses were conducted, including the Cochrane Q test, MR-Egger intercept test, MR-Presso, and leave-one-out analysis. We also applied mediation and multivariate MR analysis to explore the interactions between positive exposures on the same outcome. Additionally, we conducted the SMR, which utilizes instruments within or near relevant genes in blood or brain tissues, to elucidate the causal associations with CSVD markers. RESULTS: ABO Univariate MR of multiple cohorts revealed that the risk of small vessel stroke (SVS) increases with elevated levels of TNF-related apoptosis-inducing ligand (TRAIL, OR, 1.23, 95% CI, 1.08-1.39) and interleukin-1 receptor-like 2, (IL-1RL2, OR, 1.29, 95% CI, 1.04-1.61). IL-18 was a potential risk factor for extensive basal ganglia perivascular space burden (BGPVS, OR, 1.02, 95% CI, 1.00-1.05). Moreover, the risk of extensive white matter perivascular space burden (WMPVS) decreased with rising levels of E-selectin (OR, .98, 95% CI, .97-1.00), IL-1RL2 (OR, .97, 95% CI, .95-1.00), IL-3 receptor subunit alpha (IL-3Ra, OR, .98, 95% CI, .97-1.00), and IL-5 receptor subunit alpha (IL-5Ra, OR, .98, 95% CI, .97-1.00). Mediation and multivariate MR analysis indicated that E-selectin and IL-3Ra might interact during the pathogenesis of WMPVS. SMR estimates showed that TRAIL-related IVs rs5030044 and rs2304456 increased the risk of SVS by increasing the expression of gene Kininogen-1 (KNG1) in the cerebral cortex, particularly in the frontal cortex (ßsmr = .10, Psmr = .003, FDR = .04). Instruments (rs507666 and rs2519093) related to E-selectin and IL-3Ra could increase the risk of WMPVS by enhancing DNA methylation of the gene ABO in blood tissue (ßsmr = .01-.02, Psmr = .001, FDR = .01-.03). CONCLUSION: According to MR and SMR analysis, higher levels of TRAIL increased the risk of SVS by upregulating gene expression of KNG1 in brain cortex tissues. In addition, protective effects of E-selectin and IL-3a levels on WMPVS were regulated by increased DNA methylation of gene ABO in blood tissue.


Assuntos
Doenças de Pequenos Vasos Cerebrais , Selectina E , Humanos , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Fatores de Risco , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Doenças de Pequenos Vasos Cerebrais/genética
15.
Nat Neurosci ; 27(1): 116-128, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38012399

RESUMO

Whole-brain genome editing to correct single-base mutations and reduce or reverse behavioral changes in animal models of autism spectrum disorder (ASD) has not yet been achieved. We developed an apolipoprotein B messenger RNA-editing enzyme, catalytic polypeptide-embedded cytosine base editor (AeCBE) system for converting C·G to T·A base pairs. We demonstrate its effectiveness by targeting AeCBE to an ASD-associated mutation of the MEF2C gene (c.104T>C, p.L35P) in vivo in mice. We first constructed Mef2cL35P heterozygous mice. Male heterozygous mice exhibited hyperactivity, repetitive behavior and social abnormalities. We then programmed AeCBE to edit the mutated C·G base pairs of Mef2c in the mouse brain through the intravenous injection of blood-brain barrier-crossing adeno-associated virus. This treatment successfully restored Mef2c protein levels in several brain regions and reversed the behavioral abnormalities in Mef2c-mutant mice. Our work presents an in vivo base-editing paradigm that could potentially correct single-base genetic mutations in the brain.


Assuntos
Transtorno do Espectro Autista , Edição de Genes , Animais , Camundongos , Masculino , Transtorno do Espectro Autista/genética , Encéfalo , Mutação/genética , Fatores de Transcrição MEF2/genética
16.
Hepatol Res ; 43(11): 1199-210, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23607749

RESUMO

AIM: Serum Golgi protein 73 (sGP73) is a novel biomarker for hepatocellular carcinoma (HCC). However, there are few reports on the pattern of GP73 expression in the progression of benign liver diseases to precancerous lesions and HCC. This study aimed to investigate GP73 expression and its correlation with clinicopathological parameters. METHODS: Tissue GP73 (tGP73) levels were detected in specimens of group A (n = 186) including HCC, peritumoral tissue (PTL), high/low-grade hepatic atypical hyperplasia (AH), chronic hepatitis B (CHB) and normal controls (NC) by immunohistochemistry, and GP73 expression in group B (n = 159) and group C (n = 16) were detected by reverse transcription polymerase chain reaction and western blot, respectively. sGP73 levels were detected in subjects of group D (n = 287) by enzyme-linked immunoassay. RESULTS: GP73 expression increased gradually from NC, CHB, PTL to high-grade AH and HCC at both protein and mRNA levels (P < 0.05), while sGP73 in the HCC group was lower than in the liver cirrhosis (LC) group (P < 0.001). Both tGP73 and sGP73 levels were negatively associated with tumor size and tumor-node-metastasis stage, and tGP73 levels were positively associated with tumor differentiation. The high-tGP73 group showed significantly better overall and disease-free survival than the low-tGP73 group (P = 0.008, P = 0.018). Multivariate analysis revealed that the tGP73 level was an independent prognostic factor for HCC, but not sGP73. CONCLUSION: GP73 expression pattern suggests that the regulatory mechanism of GP73 is related to the progression of chronic liver diseases. Furthermore, a high level of tGP73 is a favorable prognostic factor for HCC.

17.
Mol Oncol ; 17(2): 365-377, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36221911

RESUMO

The improvement of treatment for patients with 'driver-gene-negative' lung adenocarcinoma (LUAD) remains a critical problem to be solved. We aimed to explore the role of methylation of N6 adenosine (m6A)-related long noncoding RNA (lncRNA) in stratifying 'driver-gene-negative' LUAD risk. Patients negative for mutations in EGFR, KRAS, BRAF, HER2, MET, ALK, RET, and ROS1 were identified as 'driver-gene-negative' cases. RNA sequencing was performed in 46 paired tumors and adjacent normal tissues from patients with 'driver-gene-negative' LUAD. Twenty-three m6A regulators and relevant lncRNAs were identified using Pearson's correlation analysis. K-means cluster analysis was used to stratify patients, and a prognostic nomogram was developed. The CIBERSORT and pRRophetic algorithms were employed to quantify the immune microenvironment and chemosensitivity. We identified two clusters highly consistent with the prognosis based on their unique expression profiles for 46 m6AlncRNAs. A risk model constructed from nine m6A lncRNAs could stratify patients into high- and low-risk groups with promising predictive power (C-index = 0.824), and the risk score was an independent prognostic factor. The clusters and risk models were closely related to immune characteristics and chemosensitivity. Additional pan-cancer analysis using the nine m6AlncRNAs showed that the expression of DIO3 opposite strand upstream RNA (DIO3OS) is closely related to the immune/stromal score and tumor stemness in a variety of cancers. Our results show that m6AlncRNAs are a reliable prognostic tool and can aid treatment decision-making in 'driver-gene-negative' LUAD. DIO3OS is associated with the development of various cancers and has potential clinical applications.


Assuntos
Adenocarcinoma , Neoplasias Pulmonares , RNA Longo não Codificante , Humanos , Metilação , RNA Longo não Codificante/genética , Proteínas Tirosina Quinases , Proteínas Proto-Oncogênicas , Adenosina , Pulmão , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Microambiente Tumoral
18.
Biomedicines ; 11(6)2023 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-37371723

RESUMO

Prostate cancer (PCa) is a critical global public health issue with its incidence on the rise. Radiation therapy holds a primary role in PCa treatment; however, radiation resistance has become increasingly challenging as we uncover more about PCa's pathogenesis. Our review aims to investigate the multifaceted mechanisms underlying radiation therapy resistance in PCa. Specifically, we will examine how various factors, such as cell cycle regulation, DNA damage repair, hypoxic conditions, oxidative stress, testosterone levels, epithelial-mesenchymal transition, and tumor stem cells, contribute to radiation therapy resistance. By exploring these mechanisms, we hope to offer new insights and directions towards overcoming the challenges of radiation therapy resistance in PCa. This can also provide a theoretical basis for the clinical application of novel ultra-high-dose-rate (FLASH) radiotherapy in the era of PCa.

19.
Cancer Med ; 11(11): 2259-2270, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35246970

RESUMO

OBJECTIVE: Examining the role of immune-related genes (IRGs) in "driver gene negative" lung adenocarcinoma (LUAD) may provide new ideas for the treatment and study for this LUAD subgroup. We aimed to find the hub immune-related gene pairs can stratify the risk of "driver-gene-negative" LUAD. MATERIALS AND METHODS: IRGs were identified according to ImmPort database based on RNA sequencing results of tumors and normal tissues from 46 patients with "driver gene negative" LUAD at The First Affiliated Hospital of Sun Yat-sen University and cyclically singly paired as immune-related gene pairs (IRGPs). Multivariate Cox analysis was used to construct an immune risk model and a prognostic nomogram combining was also been developed. Immune microenvironment landscape described by CIBERSORT and drug sensitivity calculated by pRRophetic algorithm were used to explore possible treatment improvements. RESULTS: A novel immune risk model with 5-IRGPs (CD1A|CXCL135, CD1A|S100A7L2, IFNA7|CMTM2, IFNA7|CSF3, CAMP|TFR2) can accurately distinguish patients in the high- and low-risk groups. Risk score act as an independent prognostic factor and is related to clinical stage. There are significant differences in tumor immune microenvironment and PD-1/PD-L1/CTLA-4 expression between groups. The low-risk patient may benefit more from the commonly used chemotherapy regimens such as gemcitabine and paclitaxel. CONCLUSION: This study constructed 5-IRGPs as a reliable prognostic tool and may represent genes pairs that are potential rationale for choice of treatment for "driver gene negative" LUAD.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/metabolismo , Biomarcadores Tumorais/genética , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Nomogramas , Prognóstico , Microambiente Tumoral/genética
20.
Food Chem ; 386: 132838, 2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-35509171

RESUMO

A novel method for benzo(α)pyrene (Bαp) enrichment from an oil matrix was developed by using magnetic nanoparticles (Fe3O4@dopamine/graphene oxide, Fe3O4@DA/GO) as extraction absorbents, and the chemical properties of the synthesized nanoparticles were characterized. Various parameters were investigated to optimize the extraction of Bαp from oils. Under optimal conditions (pH, 4; extraction time, 0.5 min; elution solvent, 1 mL; absorbent weight, 20 mg; elution time, 0.5 min), these nanoparticles showed excellent abilities to enrich Bαp from the saponified oil solution and were easily separated by a magnet. High-performance liquid chromatography plus fluorescence detection (HPLC-FLD) was then applied to determine the Bαp content with excellent linearity (R2 = 0.999). The detection limit was 0.13 µg/kg, while the limit of quantification was 0.42 µg/kg. The spiked recoveries of Bαp in oils ranged from 73.5% to 121%. Compared with previous reports, the proposed method displayed many advantages, including a high efficiency of oil matrix removal, short extraction time, and convenient extraction procedure.


Assuntos
Benzo(a)pireno , Nanopartículas de Magnetita , Cromatografia Líquida de Alta Pressão/métodos , Limite de Detecção , Magnetismo , Óleos , Extração em Fase Sólida/métodos
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