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1.
JMIR Med Inform ; 12: e57717, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39051154

RESUMO

Background: The Hispanic community represents a sizeable community that experiences inequities in the US health care system. As the system has moved toward digital health platforms, evaluating the potential impact on Hispanic communities is critical. Objective: The study aimed to investigate demographic, socioeconomic, and behavioral factors contributing to low telehealth use in Hispanic communities. Methods: We used a retrospective observation study design to examine the study objectives. The COVID-19 Research Database Consortium provided the Analytics IQ PeopleCore consumer data and Office Alley claims data. The study period was from March 2020 to April 2021. Multiple logistic regression was used to determine the odds of using telehealth services. Results: We examined 3,478,287 unique Hispanic patients, 16.6% (577,396) of whom used telehealth. Results suggested that patients aged between 18 and 44 years were more likely to use telehealth (odds ratio [OR] 1.07, 95% CI 1.05-1.1; P<.001) than patients aged older than 65 years. Across all age groups, patients with high incomes were at least 20% more likely to use telehealth than patients with lower incomes (P<.001); patients who had a primary care physician (P=.01), exhibited high medical usage (P<.001), or were interested in exercise (P=.03) were more likely to use telehealth; patients who had unhealthy behaviors such as smoking and alcohol consumption were less likely to use telehealth (P<.001). Male patients were less likely than female patients to use telehealth among patients aged 65 years and older (OR 0.94, 95% CI 0.93-0.95; P<.001), while male patients aged between 18 and 44 years were more likely to use telehealth (OR 1.05, 95% CI 1.03-1.07; P<.001). Among patients younger than 65 years, full-time employment was positively associated with telehealth use (P<.001). Patients aged between 18 and 44 years with high school or less education were 2% less likely to use telehealth (OR 0.98, 95% CI 0.97-0.99; P=.005). Results also revealed a positive association with using WebMD (WebMD LLC) among patients aged older than 44 years (P<.001), while there was a negative association with electronic prescriptions among those who were aged between 18 and 44 years (P=.009) and aged between 45 and 64 years (P=.004). Conclusions: This study demonstrates that telehealth use among Hispanic communities is dependent upon factors such as age, gender, education, socioeconomic status, current health care engagement, and health behaviors. To address these challenges, we advocate for interdisciplinary approaches that involve medical professionals, insurance providers, and community-based services actively engaging with Hispanic communities and promoting telehealth use. We propose the following recommendations: enhance access to health insurance, improve access to primary care providers, and allocate fiscal and educational resources to support telehealth use. As telehealth increasingly shapes health care delivery, it is vital for professionals to facilitate the use of all available avenues for accessing care.

2.
J Cancer Prev ; 28(4): 175-184, 2023 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-38205359

RESUMO

This study aimed to investigate the prognostic significance of tumor mutation burden (TMB) among patients with non-small cell lung cancer (NSCLC) who received platinum-based adjuvant chemotherapy. Tumor tissue specimens after surgical resection were collected for DNA extraction. Somatic mutation detection and TMB analysis were conducted using next-generation sequencing (NGS). Recurrence status of the patients was assessed in the hospital during the adjuvant chemotherapy period, and long-term survival data of patients were obtained by telephone follow-up. Univariate analysis between TMB status and prognosis was carried out by survival analysis. A retrospective review of 78 patients with non-squamous NSCLC who received platinum-based adjuvant chemotherapy showed a median disease-free survival of 3.6 years and median overall survival (OS) of 5.3 years. NGS analysis exhibited that the most common mutated somatic genes among the 78 patients were tumor suppressor protein p53 (TP53), epidermal growth factor receptor, low-density lipoprotein receptor related protein 1B, DNA methyltransferase 3 alpha and FAT atypical cadherin 3, and their prevalence was 56.4%, 48.7%, 37.2%, 30.7%, and 25.6%, respectively. TMB status was divided into TMB-L (≤ 4.5/Mb) and TMB-H (> 4.5/Mb) based on the median TMB threshold. Relevance of TMB to prognosis suggested that the median OS of patients with TMB-L was significantly longer than that of patients with TMB-H (NR vs. 4.6, P = 0.014). Higher TMB status conferred a worse implication on OS among patients with non-squamous NSCLC who received platinum-based adjuvant chemotherapy.

3.
Microbiol Spectr ; 10(5): e0241122, 2022 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-36125274

RESUMO

Ethylene regulates mycelial growth, primordium formation, and postharvest mushroom maturation and senescence in the white button mushroom, Agaricus bisporus. However, it remains unknown how ethylene is detected by the mushroom. In this study, we found that two hybrid histidine kinases in the mushroom, designated AbETR1 and AbETR2, showed domain structures similar to those of plant ethylene receptors. The transmembrane helices of AbETR1 and AbETR2 were expressed in yeast cells and showed ethylene-binding activities. Mushroom strains with downregulated expressions of AbETR1 and AbETR2 showed reduced sensitivity to the ethylene inhibition of mycelial growth, ethylene regulation of their own synthesis, postharvest mushroom maturation, and senescence and expression of maturation- and senescence-related genes. Therefore, AbETR1 and AbETR2 are expected to be biologically functional ethylene receptors and exhibit a different mode of action from that of the receptors of plants. Here, we fill gaps in the knowledge pertaining to higher fungus ethylene receptors, discover a novel mode of action of ethylene receptors, confirm ethylene as a novel fungal hormone, and provide a facilitated approach for preventing the maturation and senescence of postharvest button mushrooms. IMPORTANCE Ethylene regulates diverse physiological activities in bacteria, cyanobacteria, fungi, and plants, but how to perceive ethylene by fungi only remains unknown. In this study, we identify two biologically functional ethylene receptors in the basidiomycete fungus Agaricus bisporus, which fills the gaps of deficient fungal ethylene receptors. Furthermore, we found that decreased expression of the ethylene receptors facilitates preventing the maturation and senescence of postharvest button mushrooms, indicating that the two fungal ethylene receptors positively regulate the ethylene response, in contrast to that in plants.


Assuntos
Etilenos , Histidina , Histidina Quinase/genética , Etilenos/metabolismo , Hormônios
4.
Anticancer Drugs ; 33(8): 701-709, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35946537

RESUMO

An increasing number of studies have confirmed that microRNAs (miRNAs) are involved in various biological processes, including tumor growth and drug resistance. MiR-4284 has been proved to be abnormally regulated in several cancers, but the function of miR-4284 in ovarian carcinoma (OC) is unclear. Paclitaxel resistance is a key obstacle in OC treatment. Here, the role of miR-4284 in cell sensitivity to paclitaxel in OC was investigated. Two OC cell lines (SKOV3ip1 and HeyA8) were utilized for the establishment of paclitaxel-resistant cell lines. Reverse transcription-quantitative PCR (RT-qPCR) was applied to analyze the levels of miR-4284 and potential mRNAs in OC cell lines. Western blotting was performed to evaluate the levels of DNA meiotic recombinase 1 (DMC1) protein and cell cycle-associated proteins. Identification of the relationship between miR-4284 and DMC1 was achieved by luciferase reporter assay. CCK-8 and flow cytometry assays were utilized for evaluating the impact of miR-4284 on the malignant characteristics of paclitaxel-resistant OC cells. MiR-4284 was upregulated in paclitaxel-resistant OC cell lines and correlated with an adverse prognosis in OC patients. Depletion of miR-4284 suppressed cell proliferation and cell cycle progression of paclitaxel-resistant OC. MiR-4284 targeted DMC1 which was downregulated in paclitaxel-resistant cells and reversed the inhibitory influence of miR-4284 silencing on the malignant characters of paclitaxel-resistant OC cells. MiR-4284 targets DMC1 to suppress sensitivity to paclitaxel in human OC cells.


Assuntos
Carcinoma , Proteínas de Ciclo Celular , Proteínas de Ligação a DNA , MicroRNAs , Neoplasias Ovarianas , Carcinoma/genética , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células , Proteínas de Ligação a DNA/genética , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Paclitaxel/farmacologia
5.
Mol Diagn Ther ; 26(3): 309-322, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35305253

RESUMO

INTRODUCTION: Next-generation sequencing (NGS) enables simultaneous detection of actionable somatic variants and estimation of genomic signatures such as tumor mutational burden (TMB) or microsatellite instability (MSI) status, which empowers therapeutic decisions in clinical oncology. OBJECTIVE: Our retrospective study investigated the clinical performance of somatic variant detection in paired tissue and blood samples using a large targeted gene panel, the OncoScreen Plus, which interrogates 520 cancer-related genes. METHODS: We analyzed sequencing data derived from paired tissue and blood samples of 3005 patients spanning 20 solid tumor types, including lung (n = 1971), gastrointestinal (n = 625), breast (n = 120) and gynecological (n = 110), genitourinary (n = 38), and other cancers (n = 141). RESULTS: Across tumor types, the OncoScreen Plus panel achieved a high tissue detection rate, with an average of 97.9%. The average plasma detection rate was 72.2%, with an average tissue concordance rate of 36.6%. Considering all variant types, the plasma assay yielded an average sensitivity/true positive rate of 45.7%, with a positive predictive value of 64.7% relative to tissue assay. Pearson correlation analysis revealed a strong correlation in TMB estimated from blood and tissue samples (correlation coefficient 0.845, R2 = 0.756). MSI-high status was identified in five tumor types, including endometrial cancer (28.6%), colorectal cancer (2.5%), ovarian cancer (2.0%), gastric cancer (1.5%), and lung adenocarcinoma (0.2%). CONCLUSION: Paired tumor and blood samples from a large cohort of patients spanning 20 tumor types demonstrated that the OncoScreen Plus is a reliable pan-cancer panel for the accurate detection of somatic variants and genomic signatures that could guide individualized treatment strategies to improve the care of patients with advanced cancer.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Neoplasias , Biomarcadores Tumorais/genética , Genômica , Humanos , Instabilidade de Microssatélites , Mutação , Neoplasias/diagnóstico , Neoplasias/genética , Estudos Retrospectivos
6.
Bioengineered ; 12(2): 12891-12904, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34784837

RESUMO

Umbilical cord mesenchymal stem cells (UCMSCs) are regarded as an ideal source for clinical use. Increasing evidence has suggested that microRNAs (miRNAs) work as a crucial regulator in the development of plentiful diseases, including intrauterine adhesions (IUA). Herein, we investigated the specific impacts of UCMSCs overexpressing miR-455-5p in IUA. UCMSCs were cocultured with endometrial stromal cells (ESCs). Thirty-two female mice were divided into four different treated groups: sham, model, model + UCMSC-miR-NC and model + UCMSC-miR-455-5p. Mice in model groups were induced by uterine curettage. MiR-455-5p overexpressed UCMSCs facilitated the proliferation and cell cycle progression of ESCs according to 5-ethynyl-2'-deoxyuridine assay and flow cytometry analysis. Hematoxylin-eosin and Masson staining revealed that miR-455-5p upregulation in UCMSCs increased the number of endometrial glands and suppressed endometrial fibrosis in murine uterine tissues. Western blotting displayed that miR-455-5p overexpressed UCMSCs promoted the activation of Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) signaling in ESCs and murine uterine tissues. Mechanistically, miR-455-5p targeted 3' untranslated region of suppressor of cytokine signaling 3 (SOCS3), which was confirmed by luciferase reporter assay. Reverse transcription quantitative polymerase chain reaction demonstrated that miR-455-5p was lowly expressed and SOCS3 was highly expressed in murine uterine tissues of IUA model. Moreover, Pearson correlation analysis showed that their expression was inversely correlated. Rescue assays suggested that inhibiting JAK/STAT3 signaling reversed effects of miR-455-5p on the behaviors of ESCs. The results indicated that miR-455-5p overexpression in UCMSCs helps to attenuate endometrial injury and repair damaged endometrium by activating SOCS3-mediated JAK/STAT3 signaling.


Assuntos
Endométrio/patologia , Janus Quinases/metabolismo , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/genética , Regeneração , Fator de Transcrição STAT3/metabolismo , Cordão Umbilical/citologia , Regulação para Cima/genética , Animais , Sequência de Bases , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Endométrio/efeitos dos fármacos , Feminino , Humanos , Células-Tronco Mesenquimais/efeitos dos fármacos , Camundongos , MicroRNAs/metabolismo , Fenótipo , Regeneração/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Proteína 3 Supressora da Sinalização de Citocinas/genética , Proteína 3 Supressora da Sinalização de Citocinas/metabolismo , Tirfostinas/farmacologia , Regulação para Cima/efeitos dos fármacos
7.
Kaohsiung J Med Sci ; 35(1): 39-48, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30844146

RESUMO

An association between genetic polymorphisms in encoding X-ray repair cross complementing group 1 (XRCC1) and encoding xeroderma pigmentosum group D (XPD) and risks of non-small-cell lung cancer (NSCLC) in East Chinese Han population has been observed. Herein we hypothesized that genetic polymorphisms in these two DNA repair genes are likely to be important in the NSCLC in Chinese nonsmoking female patients. We recruited 327 nonsmoking female patients with NSCLC and 342 individuals with benign lung diseases or healthy controls. Genotype frequencies of XRCC1 T-77C, Arg194Trp, Arg280His and Arg399Gln, Pro206Pro, and XPD Asp312Asn and Lys751Gln were calculated after Polymerase Chain Reaction amplification and sequencing. Generalized multifactor dimensionality reduction (GMDR) was used to detect the interactive effect of XRCC1 and XPD gene polymorphisms. The ratio of cooking oil mist exposure history and soot exposure history, and the gene frequencies of XRCC1 T-77C TC + CC, XRCC1 AG + GG, XRCC1 399Gln/Gln, and XPD 751Gln/Gln were higher in female patients with NSCLC than those with benign lung diseases or healthy controls. The haplotypes of XRCC1 T-Arg-Arg-Gln and XRCC1 C-Arg-Arg-Arg were positively associated with the NSCLC occurrence in nonsmoking female patients. GMDR discovered that there was an interactive model of XRCC1 and XPD genes in multiple gene loci. Logistic regression analysis showed that XRCC1 T-77C, XRCC1 Pro206Pro polymorphism, cooking oil mist and soot exposure history and tumor-node-metastasis (TNM) stage were related to NSCLC occurrence for nonsmoking female patients. Taken together, XRCC1 and XPD polymorphisms, cooking oil mist, and soot exposure history may be interactively correlated with NSCLC incidence for nonsmoking female patients.


Assuntos
Povo Asiático/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Interação Gene-Ambiente , Predisposição Genética para Doença , Neoplasias Pulmonares/genética , Polimorfismo de Nucleotídeo Único/genética , Proteína 1 Complementadora Cruzada de Reparo de Raio-X/genética , Xeroderma Pigmentoso/genética , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Haplótipos/genética , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Modelos Genéticos , Fatores de Risco , Fumar , Fuligem
8.
Genet Test Mol Biomarkers ; 21(5): 305-311, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28287835

RESUMO

OBJECTIVE: This case-control study investigated the association of single nucleotide polymorphisms in the PTPN1 gene with susceptibility to esophageal squamous cell carcinoma (ESCC) in Inner Mongolia, China. METHODS: A total of 302 patients living in Inner Mongolia China who were pathologically diagnosed with ESCC between April 2012 and 2016 were selected for the ESCC group; 373 healthy individuals were selected for the control group. The rs2904268 C>G, rs2230605 A>G, and rs16995309 C>T polymorphisms in the PTPN1 gene were detected by bidirectional polymerase chain reaction amplification of specific alleles. The haplotype frequencies were analyzed by SHEsis software. Binary logistic regression analysis was conducted to analyze risk factors associated with ESCC. RESULTS: Statistical differences between the ESCC and control groups were observed for history of smoking, drinking, and poor eating habits (all p < 0.05). Both the rs2904268 C>G CG and GG genotype frequencies were markedly higher in the ESCC group relative to the control group (both p < 0.05). However, the genotype frequencies of rs2230605 A>G and rs16995309 C>T were similar between the ESCC and control groups (all p > 0.05). Compared with the control group, the ESCC group had notably elevated frequencies of the GGC and GAT haplotypes and significantly reduced frequencies of CGC and GGT haplotypes (all p < 0.05). A history of smoking, drinking, poor eating habits, the rs2904268 C>G CG+GG genotypes, and the GAT haplotype were all identified as risk factors for ESCC (all p < 0.05). CONCLUSION: These results indicated that the PTPN1 gene polymorphism rs2904268 is associated with susceptibility to ESCC in Inner Mongolia.


Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Proteína Tirosina Fosfatase não Receptora Tipo 1/genética , Adenocarcinoma/genética , Adulto , Alelos , Sequência de Bases/genética , Estudos de Casos e Controles , China , Carcinoma de Células Escamosas do Esôfago , Feminino , Frequência do Gene/genética , Estudos de Associação Genética , Predisposição Genética para Doença/genética , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Fatores de Risco , Neoplasias Gástricas/genética
9.
Tumour Biol ; 37(11): 15241-15252, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27696291

RESUMO

The present study aims to investigate the effects of microRNA-218 (miR-218) on the proliferation, migration, invasion, and apoptosis of gastric cancer (GC) cells by targeting LIM and SH3 domain protein 1 (LASP1). The GC cells in the logarithmic phase were selected and divided into five groups: the blank group, negative control (NC) group, miR-218 inhibitors group, miR-218 inhibitors + siLASP1 group, and miR-218 mimics + siLASP1 group. The miR-218 expression in each group was also detected by qRT-PCR. The CCK8 assay, Transwell migration, and invasion assays and flow cytometry were performed to determine the effects of miR-218 on cell proliferation, migration, invasion, and apoptosis of GC cells. Western blotting was conducted to measure LASP1 protein expression in GC cells after transfection. The qRT-PCR revealed that the transfection of miR-218 mimics could upregulate the miR-218 expression, and the transfection of miR-218 inhibitors could downregulate the miR-218 expression in the GC cells. Compared with the blank and NC groups, the proliferation, migration, and invasion of GC cells were significantly reduced in the miR-218 mimics, miR-218 inhibitors + siLASP1, and miR-218 mimics + siLASP1 groups but enhanced in the miR-218 inhibitors group. Similarly, compared with the blank and NC groups, the cell apoptosis rates in the miR-218 mimics, miR-218 inhibitors + siLASP1, and the miR-218 mimics + siLASP1 groups were significantly increased, while the miR-218 inhibitors group had a lower apoptosis rate. In conclusion, these results indicate that miR-218 could inhibit the proliferation, migration, and invasion and promote apoptosis of GC cells by downregulating LASP1 expression.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adenocarcinoma/secundário , Apoptose , Movimento Celular , Proliferação de Células , Proteínas do Citoesqueleto/metabolismo , Proteínas com Domínio LIM/metabolismo , MicroRNAs/genética , Neoplasias Gástricas/patologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Western Blotting , Estudos de Casos e Controles , Ciclo Celular , Proteínas do Citoesqueleto/genética , Feminino , Citometria de Fluxo , Regulação Neoplásica da Expressão Gênica , Humanos , Técnicas Imunoenzimáticas , Proteínas com Domínio LIM/genética , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Células Tumorais Cultivadas
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