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1.
Artigo em Inglês | MEDLINE | ID: mdl-38929027

RESUMO

Lung cancer (LC) is the leading cause of cancer mortality in the United States. To combat this predicament, early screening and critically assessing its risk factors remain crucial. The aim of this study was to identify the value of specific factors from the National Health and Nutrition Examination Survey (NHANES) from 2001-2018, as they relate to lung cancer mortality in the US Preventive Services Task Force (USPSTF)-eligible population. A total of 3545 adults who met USPSTF criteria were extracted from 81,595 NHANES participants. The LC Death Risk Assessment Tool was used to calculate the number of deaths per 1000 individuals. The Mann-Whitney U test and one-way ANOVA determined the statistical significance of the factors involved in LC mortality. Male sex, African and Hispanic ethnicity, lower education attainment, and secondhand exposure to cigarette smoke correlated with an increased risk of LC mortality. Additionally, the factor of emotional support from NHANES data was analyzed and did not show any benefit to reducing risk. By identifying individuals at high-risk, preventative measures can be maximized to produce the best possible outcome.


Assuntos
Neoplasias Pulmonares , Inquéritos Nutricionais , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Adulto , Idoso , Fatores de Risco , Detecção Precoce de Câncer , Medição de Risco
2.
Sci Signal ; 17(838): eado6266, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38805583

RESUMO

Phosphoinositides are essential signaling molecules. The PI5P4K family of phosphoinositide kinases and their substrates and products, PI5P and PI4,5P2, respectively, are emerging as intracellular metabolic and stress sensors. We performed an unbiased screen to investigate the signals that these kinases relay and the specific upstream regulators controlling this signaling node. We found that the core Hippo pathway kinases MST1/2 phosphorylated PI5P4Ks and inhibited their signaling in vitro and in cells. We further showed that PI5P4K activity regulated several Hippo- and YAP-related phenotypes, specifically decreasing the interaction between the key Hippo proteins MOB1 and LATS and stimulating the YAP-mediated genetic program governing epithelial-to-mesenchymal transition. Mechanistically, we showed that PI5P interacted with MOB1 and enhanced its interaction with LATS, thereby providing a signaling connection between the Hippo pathway and PI5P4Ks. These findings reveal how these two important evolutionarily conserved signaling pathways are integrated to regulate metazoan development and human disease.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Via de Sinalização Hippo , Proteínas Serina-Treonina Quinases , Transdução de Sinais , Fatores de Transcrição , Proteínas de Sinalização YAP , Humanos , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Via de Sinalização Hippo/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Proteínas de Sinalização YAP/metabolismo , Proteínas de Sinalização YAP/genética , Ativação Transcricional , Fosforilação , Células HEK293 , Transição Epitelial-Mesenquimal , Fosfoproteínas/metabolismo , Fosfoproteínas/genética , Animais , Serina-Treonina Quinase 3 , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética
3.
Medicina (Kaunas) ; 60(4)2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38674269

RESUMO

Background and Objectives: Cancer, as the second leading cause of death in the United States, poses a huge healthcare burden. Barriers to access to advanced therapies influence the outcome of cancer treatment. In this study, we examined whether insurance types affect the quality of cancer clinical care. Materials and Methods: Data for 13,340 cancer patients with Purchased or Medicaid insurance from the All of Us database were collected for this study. The chi-squared test of proportions was employed to determine the significance of patient cohort characteristics and the accessibility of healthcare services between the Purchased and Medicaid insurance groups. Results: Cancer patients who are African American, with lower socioeconomic status, or with lower educational attainment are more likely to be insured by Medicaid. An analysis of the survey questions demonstrated the relationship between income and education level and insurance type, as Medicaid cancer patients were less likely to receive primary care and specialist physician access and more likely to request lower-cost medications. Conclusions: The inequities of the US healthcare system are observed for cancer patient care; access to physicians and medications is highly varied and dependent on insurance types. Socioeconomic factors further influence insurance types, generating a significant impact on the overall clinical care quality for cancer patients that eventually determines treatment outcomes and the quality of life.


Assuntos
Acessibilidade aos Serviços de Saúde , Seguro Saúde , Neoplasias , Humanos , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Acessibilidade aos Serviços de Saúde/normas , Neoplasias/terapia , Estados Unidos , Masculino , Feminino , Pessoa de Meia-Idade , Seguro Saúde/estatística & dados numéricos , Qualidade da Assistência à Saúde/estatística & dados numéricos , Qualidade da Assistência à Saúde/normas , Medicaid/estatística & dados numéricos , Adulto , Idoso , Bases de Dados Factuais , Fatores Socioeconômicos
4.
Front Cell Infect Microbiol ; 13: 1167827, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37457959

RESUMO

Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection has claimed millions of lives since late 2019, yet there are still many unexplored areas in its pathogenesis and clinical outcomes. COVID-19 is a disease that can affects multiple systems, some of which are overlapped with those modulated by gut microbiota, especially the immune system, thus leading to our concentration on analyzing the roles of microbiota in COVID-19 pathogenesis through the gut-lung axis. Dysbiosis of the commensal intestinal microbes and their metabolites (e.g., SCFAs) as well as the expression and activity of ACE2 in the gut could influence the host's immune system in COVID-19 patients. Moreover, it has been known that the elderly and individuals diagnosed with comorbidities (e.g., hypertension, type 2 diabetes mellitus, cardiovascular disease, etc.) are more susceptible to gut flora alterations, SARS-CoV-2 infection, and death. Thus, in this review we will focus on analyzing how the gut microbiota regulates the immune system that leads to different responses to SARS-CoV-2 infection. Since diet is a major factor to modulate the status of gut microbiota, dietary influence on COVID-19 pathogenesis will be also discussed, aiming to shed light on how diet-modulated gut microbiota regulates the susceptibility, severity, and treatment of SARS-CoV-2 infection.


Assuntos
COVID-19 , Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Idoso , Humanos , SARS-CoV-2 , Dieta , Disbiose
5.
Dev Cell ; 56(11): 1661-1676.e10, 2021 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-33984270

RESUMO

PI5P4Ks are a class of phosphoinositide kinases that phosphorylate PI-5-P to PI-4,5-P2. Distinct localization of phosphoinositides is fundamental for a multitude of cellular functions. Here, we identify a role for peroxisomal PI-4,5-P2 generated by the PI5P4Ks in maintaining energy balance. We demonstrate that PI-4,5-P2 regulates peroxisomal fatty acid oxidation by mediating trafficking of lipid droplets to peroxisomes, which is essential for sustaining mitochondrial metabolism. Using fluorescent-tagged lipids and metabolite tracing, we show that loss of the PI5P4Ks significantly impairs lipid uptake and ß-oxidation in the mitochondria. Further, loss of PI5P4Ks results in dramatic alterations in mitochondrial structural and functional integrity, which under nutrient deprivation is further exacerbated, causing cell death. Notably, inhibition of the PI5P4Ks in cancer cells and mouse tumor models leads to decreased cell viability and tumor growth, respectively. Together, these studies reveal an unexplored role for PI5P4Ks in preserving metabolic homeostasis, which is necessary for tumorigenesis.


Assuntos
Carcinogênese/genética , Mitocôndrias/genética , Neoplasias/metabolismo , Peroxissomos/metabolismo , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Animais , Linhagem Celular Tumoral , Metabolismo Energético/genética , Feminino , Homeostase/genética , Humanos , Gotículas Lipídicas/metabolismo , Metabolismo dos Lipídeos/genética , Masculino , Camundongos , Mitocôndrias/metabolismo , Mitocôndrias/ultraestrutura , Neoplasias/genética , Neoplasias/patologia , Peroxissomos/genética
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