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1.
Cell ; 178(5): 1145-1158.e20, 2019 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-31402173

RESUMO

While Mediator plays a key role in eukaryotic transcription, little is known about its mechanism of action. This study combines CRISPR-Cas9 genetic screens, degron assays, Hi-C, and cryoelectron microscopy (cryo-EM) to dissect the function and structure of mammalian Mediator (mMED). Deletion analyses in B, T, and embryonic stem cells (ESC) identified a core of essential subunits required for Pol II recruitment genome-wide. Conversely, loss of non-essential subunits mostly affects promoters linked to multiple enhancers. Contrary to current models, however, mMED and Pol II are dispensable to physically tether regulatory DNA, a topological activity requiring architectural proteins. Cryo-EM analysis revealed a conserved core, with non-essential subunits increasing structural complexity of the tail module, a primary transcription factor target. Changes in tail structure markedly increase Pol II and kinase module interactions. We propose that Mediator's structural pliability enables it to integrate and transmit regulatory signals and act as a functional, rather than an architectural bridge, between promoters and enhancers.


Assuntos
Complexo Mediador/metabolismo , RNA Polimerase II/metabolismo , Animais , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/metabolismo , Sistemas CRISPR-Cas/genética , Proteínas de Ciclo Celular/metabolismo , Células Cultivadas , Proteínas Cromossômicas não Histona/metabolismo , Microscopia Crioeletrônica , Elementos Facilitadores Genéticos , Edição de Genes , Humanos , Masculino , Complexo Mediador/química , Complexo Mediador/genética , Camundongos , Camundongos Endogâmicos C57BL , Células-Tronco Embrionárias Murinas/citologia , Células-Tronco Embrionárias Murinas/metabolismo , Regiões Promotoras Genéticas , Estrutura Quaternária de Proteína , RNA Polimerase II/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Coesinas
2.
Cell ; 173(5): 1165-1178.e20, 2018 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-29706548

RESUMO

Cohesin extrusion is thought to play a central role in establishing the architecture of mammalian genomes. However, extrusion has not been visualized in vivo, and thus, its functional impact and energetics are unknown. Using ultra-deep Hi-C, we show that loop domains form by a process that requires cohesin ATPases. Once formed, however, loops and compartments are maintained for hours without energy input. Strikingly, without ATP, we observe the emergence of hundreds of CTCF-independent loops that link regulatory DNA. We also identify architectural "stripes," where a loop anchor interacts with entire domains at high frequency. Stripes often tether super-enhancers to cognate promoters, and in B cells, they facilitate Igh transcription and recombination. Stripe anchors represent major hotspots for topoisomerase-mediated lesions, which promote chromosomal translocations and cancer. In plasmacytomas, stripes can deregulate Igh-translocated oncogenes. We propose that higher organisms have coopted cohesin extrusion to enhance transcription and recombination, with implications for tumor development.


Assuntos
Trifosfato de Adenosina/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteínas Cromossômicas não Histona/metabolismo , Genoma , Animais , Linfócitos B/citologia , Linfócitos B/metabolismo , Fator de Ligação a CCCTC/genética , Fator de Ligação a CCCTC/metabolismo , Proteínas de Ciclo Celular/química , Proteínas de Ciclo Celular/genética , Linhagem Celular , Proteoglicanas de Sulfatos de Condroitina/genética , Proteoglicanas de Sulfatos de Condroitina/metabolismo , Cromatina/metabolismo , Proteínas Cromossômicas não Histona/química , Proteínas Cromossômicas não Histona/genética , Cromossomos/metabolismo , Proteínas de Ligação a DNA , Humanos , Camundongos , Mutagênese , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Transcrição Gênica , Coesinas
3.
Cell ; 170(3): 507-521.e18, 2017 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-28735753

RESUMO

In this study, we show that evolutionarily conserved chromosome loop anchors bound by CCCTC-binding factor (CTCF) and cohesin are vulnerable to DNA double strand breaks (DSBs) mediated by topoisomerase 2B (TOP2B). Polymorphisms in the genome that redistribute CTCF/cohesin occupancy rewire DNA cleavage sites to novel loop anchors. While transcription- and replication-coupled genomic rearrangements have been well documented, we demonstrate that DSBs formed at loop anchors are largely transcription-, replication-, and cell-type-independent. DSBs are continuously formed throughout interphase, are enriched on both sides of strong topological domain borders, and frequently occur at breakpoint clusters commonly translocated in cancer. Thus, loop anchors serve as fragile sites that generate DSBs and chromosomal rearrangements. VIDEO ABSTRACT.


Assuntos
Fragilidade Cromossômica , Quebras de DNA de Cadeia Dupla , Neoplasias/genética , Animais , Linfócitos B/metabolismo , Fator de Ligação a CCCTC , Linhagem Celular Tumoral , DNA Topoisomerases Tipo II/metabolismo , Proteínas de Ligação a DNA/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Proteínas de Ligação a Poli-ADP-Ribose , Proteínas Repressoras/metabolismo
4.
Cell ; 171(2): 305-320.e24, 2017 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-28985562

RESUMO

The human genome folds to create thousands of intervals, called "contact domains," that exhibit enhanced contact frequency within themselves. "Loop domains" form because of tethering between two loci-almost always bound by CTCF and cohesin-lying on the same chromosome. "Compartment domains" form when genomic intervals with similar histone marks co-segregate. Here, we explore the effects of degrading cohesin. All loop domains are eliminated, but neither compartment domains nor histone marks are affected. Loss of loop domains does not lead to widespread ectopic gene activation but does affect a significant minority of active genes. In particular, cohesin loss causes superenhancers to co-localize, forming hundreds of links within and across chromosomes and affecting the regulation of nearby genes. We then restore cohesin and monitor the re-formation of each loop. Although re-formation rates vary greatly, many megabase-sized loops recovered in under an hour, consistent with a model where loop extrusion is rapid.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Núcleo Celular/genética , Proteínas Cromossômicas não Histona/metabolismo , Cromossomos/metabolismo , Genoma Humano , Proteínas Repressoras/metabolismo , Fator de Ligação a CCCTC , Linhagem Celular Tumoral , Proteínas de Ligação a DNA , Elementos Facilitadores Genéticos , Código das Histonas , Humanos , Proteínas Nucleares/metabolismo , Nucleossomos/metabolismo , Fosfoproteínas/metabolismo , Coesinas
5.
Immunity ; 54(6): 1200-1218.e9, 2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-33951416

RESUMO

Tissue macrophages self-renew during homeostasis and produce inflammatory mediators upon microbial infection. We examined the relationship between proliferative and inflammatory properties of tissue macrophages by defining the impact of the Wnt/ß-catenin pathway, a central regulator of self-renewal, in alveolar macrophages (AMs). Activation of ß-catenin by Wnt ligand inhibited AM proliferation and stemness, but promoted inflammatory activity. In a murine influenza viral pneumonia model, ß-catenin-mediated AM inflammatory activity promoted acute host morbidity; in contrast, AM proliferation enabled repopulation of reparative AMs and tissue recovery following viral clearance. Mechanistically, Wnt treatment promoted ß-catenin-HIF-1α interaction and glycolysis-dependent inflammation while suppressing mitochondrial metabolism and thereby, AM proliferation. Differential HIF-1α activities distinguished proliferative and inflammatory AMs in vivo. This ß-catenin-HIF-1α axis was conserved in human AMs and enhanced HIF-1α expression associated with macrophage inflammation in COVID-19 patients. Thus, inflammatory and reparative activities of lung macrophages are regulated by ß-catenin-HIF-1α signaling, with implications for the treatment of severe respiratory diseases.


Assuntos
COVID-19/imunologia , COVID-19/virologia , Autorrenovação Celular/imunologia , Interações Hospedeiro-Patógeno/imunologia , Macrófagos/imunologia , SARS-CoV-2/imunologia , Biomarcadores , COVID-19/metabolismo , Citocinas/metabolismo , Suscetibilidade a Doenças/imunologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Mediadores da Inflamação/metabolismo , Macrófagos/citologia , Macrófagos/metabolismo , Macrófagos Alveolares/imunologia , Macrófagos Alveolares/metabolismo , Transdução de Sinais
7.
Mol Cell ; 67(4): 566-578.e10, 2017 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-28803781

RESUMO

50 years ago, Vincent Allfrey and colleagues discovered that lymphocyte activation triggers massive acetylation of chromatin. However, the molecular mechanisms driving epigenetic accessibility are still unknown. We here show that stimulated lymphocytes decondense chromatin by three differentially regulated steps. First, chromatin is repositioned away from the nuclear periphery in response to global acetylation. Second, histone nanodomain clusters decompact into mononucleosome fibers through a mechanism that requires Myc and continual energy input. Single-molecule imaging shows that this step lowers transcription factor residence time and non-specific collisions during sampling for DNA targets. Third, chromatin interactions shift from long range to predominantly short range, and CTCF-mediated loops and contact domains double in numbers. This architectural change facilitates cognate promoter-enhancer contacts and also requires Myc and continual ATP production. Our results thus define the nature and transcriptional impact of chromatin decondensation and reveal an unexpected role for Myc in the establishment of nuclear topology in mammalian cells.


Assuntos
Linfócitos B/metabolismo , Ciclo Celular , Núcleo Celular/metabolismo , Montagem e Desmontagem da Cromatina , Cromatina/metabolismo , Histonas/metabolismo , Ativação Linfocitária , Proteínas Proto-Oncogênicas c-myc/metabolismo , Acetilcoenzima A/metabolismo , Acetilação , Trifosfato de Adenosina/metabolismo , Animais , Linfócitos B/imunologia , Linhagem Celular , Cromatina/química , Cromatina/genética , Metilação de DNA , Epigênese Genética , Genótipo , Histonas/química , Imunidade Humoral , Metilação , Camundongos Endogâmicos C57BL , Camundongos Knockout , Conformação de Ácido Nucleico , Fenótipo , Domínios e Motivos de Interação entre Proteínas , Processamento de Proteína Pós-Traducional , Proteínas Proto-Oncogênicas c-myc/química , Proteínas Proto-Oncogênicas c-myc/genética , Imagem Individual de Molécula , Relação Estrutura-Atividade , Fatores de Tempo , Transcrição Gênica
8.
J Cutan Pathol ; 2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39357916

RESUMO

Wolf isotopic response (WIR) is a phenomenon in which a second, unrelated skin disease arises at the same site as a previously healed dermatosis. WIR most commonly occurs in healed herpes zoster but has also been described in other conditions, such as herpes simplex virus, varicella-zoster virus, and skin tumors. Acquired perforating dermatosis (APD) is characterized by transepidermal elimination of collagen bundles that lead to the development of ulcerative papules, which are often associated with systemic conditions such as diabetes or renal failure. This report documents a rare occurrence of APD after WIR and reviews related published works.

9.
Acta Pharmacol Sin ; 45(10): 2134-2148, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38789494

RESUMO

Excessive dietary calories lead to systemic metabolic disorders, disturb hepatic lipid metabolism, and aggravate nonalcoholic steatohepatitis (NASH). Bile acids (BAs) play key roles in regulating nutrition absorption and systemic energy homeostasis. Resmetirom is a selective thyroid hormone receptor ß (THRß) agonist and the first approved drug for NASH treatment. It is well known that the THRß activation could promote intrahepatic lipid catabolism and improve mitochondrial function, however, its effects on intestinal lipid absorption and BA compositions remain unknown. In the present study, the choline-deficient, L-amino acid defined, high-fat diet (CDAHFD) and high-fat diet plus CCl4 (HFD+CCl4)-induced NASH mice were used to evaluate the effects of resmetirom on lipid and BA composition. We showed that resmetirom administration (10 mg·kg-1·d-1, i.g.) significantly altered hepatic lipid composition, especially reduced the C18:2 fatty acyl chain-containing triglyceride (TG) and phosphatidylcholine (PC) in the two NASH mouse models, suggesting that THRß activation inhibited intestinal lipid absorption since C18:2 fatty acid could be obtained only from diet. Targeted analysis of BAs showed that resmetirom treatment markedly reduced the hepatic and intestinal 12-OH to non-12-OH BAs ratio by suppressing cytochrome P450 8B1 (CYP8B1) expression in both NASH mouse models. The direct inhibition by resmetirom on intestinal lipid absorption was further verified by the BODIPY gavage and the oral fat tolerance test. In addition, disturbance of the altered BA profiles by exogenous cholic acid (CA) supplementation abolished the inhibitory effects of resmetirom on intestinal lipid absorption in both normal and CDAHFD-fed mice, suggesting that resmetirom inhibited intestinal lipid absorption by reducing 12-OH BAs content. In conclusion, we discovered a novel mechanism of THRß agonists on NASH treatment by inhibiting intestinal lipid absorption through remodeling BAs composition, which highlights the multiple regulation of THRß activation on lipid metabolism and extends the current knowledge on the action mechanisms of THRß agonists in NASH treatment.


Assuntos
Ácidos e Sais Biliares , Dieta Hiperlipídica , Absorção Intestinal , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica , Receptores beta dos Hormônios Tireóideos , Animais , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Ácidos e Sais Biliares/metabolismo , Masculino , Receptores beta dos Hormônios Tireóideos/agonistas , Receptores beta dos Hormônios Tireóideos/metabolismo , Absorção Intestinal/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Camundongos , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Fígado/efeitos dos fármacos , Tetracloreto de Carbono , Piridazinas , Uracila/análogos & derivados
10.
Artigo em Inglês | MEDLINE | ID: mdl-38551417

RESUMO

Context: Dilated cardiomyopathy (DCM) is the terminal manifestation of many heart diseases, and atrial fibrillation (AF) is the most common type of arrhythmia in DCM. The mutual influence of DCM and AF can ultimately lead to a poor prognosis for patients. Objective: The study intended to investigate the risk factors for DCM complicated with AF as well as the expression and clinical value of miR-499 and IL-1ß, to provide more research targets for controlling the risk of AF in clinical practice. Design: The research team conducted a retrospective, observational, case-control study. Setting: The study took place at Huai'an First People's Hospital. Participants: Participants were 79 patients with DCM who had been admitted to the hospital between January 2018 and January 2023. Groups: The study included two groups: (1) 31 participants with atrial fibrillation (AF), the AF group and (2) 48 participants without AF, the non-AF group. Outcome Measures: The research team: (1) examined the baseline characteristics of the two groups and compared the groups using single factor analysis; (2) compared the group's serum indicators and echocardiographic parameters; (3) evaluated the expression and potential relationship of microRNA (miR-499) and interleukin-1 beta (IL-1ß) to AF, using reverse transcription-polymerase chain reaction (RT-PCR) and Pearson, and compared the group's expressions of miR-499 and IL-1ß; and (4) analyzed the potential relationship between participants' characteristics and the occurrence of AF, using binary logistic regression. Results: Compared to the non-AF group, the AF group's: (1) age (P = .000) and number of participants with a high pulmonary artery pressure (P = .004) were significantly greater; (2) LVEF was significantly lower (P = .030) and LVESD (P = .000), LAD (P = .018), uric acid (P = .000), and BNP (P = .000) were significantly higher; and (3) serum miR-499 (P = .020) and IL-1ß (P = .000) were significantly higher. Also, a significant positive correlation existed between miR-499 (P = .019) and IL-1ß (P = .022) and DCM with AF. In addition, the AF group's age (P = .001), disease duration (P = .032), serum triglyceride levels (P = .036), uric acid value (P = .001), left ventricular ejection fraction (LVEF), left ventricular end systolic diameter (LVESD), left atrial anteroposterior diameter, LAD, pulmonary hypertension were significant independent risk factors DCM with AF. Conclusions: A close relationship exists between the abnormal expression of serum miR-499 and IL-1ß and DCM complicated with AF, which will be of great importance in future research. In addition, the data of patients with DCM are related to the occurrence and development of AF, and clinicians should actively perform early drug interventions to reduce myocardial remodeling, so as to reduce the incidence of AF.

11.
J Formos Med Assoc ; 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38997877

RESUMO

BACKGROUND: Social detachment includes the subjective aspect "loneliness" and the objective aspect "social isolation," but tools to assess both dimensions are limited. This study aims to develop a questionnaire, the Social Detachment Questionnaire for Older Population (SDQO), that considers multiple dimensions of social detachment simultaneously. METHODS: The study collected 600 valid samples from individuals aged 55 and above to examine the psychometric properties of the developed SDQO. Item analysis was conducted to assess the performance of each item, and exploratory factor analysis (EFA) was employed to analyze its initial structure and eliminate less ideal items. Subsequently, confirmatory factor analysis (CFA) was used to examine the model fit of the suggested structure by EFA, using different subsamples. Internal consistency, concurrent validity, and other analyses were also performed. RESULTS: The original 27-item SDQO was reduced to 17 items after removing 4 questions in item analysis and 6 questions in EFA. The Cronbach's alpha for the 17-item version of SDQO was 0.80. Both EFA and CFA supported its 6-factor structure, with factors identified as community activities, loneliness, personal resources, leisure activities, friendship, and family resources. SDQO also demonstrated expected performance in concurrent validity. CONCLUSION: The 17-item version of SDQO exhibited good reliability and validity, measuring various aspects of social detachment behavior, feelings, and resources. It holds value for future research applications.

12.
Sensors (Basel) ; 24(12)2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38931802

RESUMO

Inefficient patient transport in hospitals often leads to delays, overworked staff, and suboptimal resource utilization, ultimately impacting patient care. Existing dispatch management algorithms are often evaluated in simulation environments, raising concerns about their real-world applicability. This study presents a real-world experiment that bridges the gap between theoretical dispatch algorithms and real-world implementation. It applies process capability analysis at Taichung Veterans General Hospital in Taichung, Taiwan, and utilizes IoT for real-time tracking of staff and medical devices to address challenges associated with manual dispatch processes. Experimental data collected from the hospital underwent statistical evaluation between January 2021 and December 2021. The results of our experiment, which compared the use of traditional dispatch methods with the Beacon dispatch method, found that traditional dispatch had an overtime delay of 41.0%; in comparison, the Beacon dispatch method had an overtime delay of 26.5%. These findings demonstrate the transformative potential of this solution for not only hospital operations but also for improving service quality across the healthcare industry in the context of smart hospitals.


Assuntos
Algoritmos , Humanos , Taiwan , Hospitais , Transporte de Pacientes , Assistência ao Paciente/métodos , Eficiência Organizacional
13.
Hemoglobin ; 48(1): 60-62, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38314576

RESUMO

Patients with the genotype of ß0/ß0 for ß-thalassemia (ß-thal) usually behave as ß-thal major (ß-TM) phenotype which is transfusion-dependent. The pathophysiology of ß-thal is the imbalance between α/ß-globin chains. The degree of α/ß-globin imbalance can be reduced by the more effective synthesis of γ-globin chains, and increased Hb F levels, modifying clinical severity of ß-TM. We report a Chinese child who had homozygous ß0-thal and a heterozygous KLF1 mutation. The patient had a moderate anemia since 6 months old, keeping a baseline Hb value of 8.0-9.0 g/dL. She had normal development except for a short stature (3rd percentile) until 6 years old, when splenomegaly and facial bone deformities occurred. Although genetic alteration of KLF1 expression in ß0/ß0 patients can result in some degree of disease alleviation, our case shows that it is insufficient to ameliorate satisfactorily the presentation. This point should be borne in mind for physicians who provide the genetic counseling and prenatal diagnosis to at-risk families.


Assuntos
Globinas beta , Talassemia beta , Criança , Feminino , Humanos , Lactente , alfa-Globinas/genética , Globinas beta/genética , Talassemia beta/genética , China , Seguimentos , Genótipo , Mutação
14.
Clin Gerontol ; 47(5): 996-1007, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38967355

RESUMO

OBJECTIVES: This study investigated the impact of social activities on cognitive functioning and psychopathological symptoms. METHODS: Participants aged 55 or older were enrolled through communities. Initial measures assessed demographic data, neuropsychological functioning, psychopathological state, and happiness. Social activities were evaluated using a modified 12-item tool, with 3-4 activities as the cutoff. Follow-up after 6-9 months included Mini-Mental State Examination (MMSE), Beck Depression Inventory - II (BDI-II), Beck Anxiety Inventory (BAI), Health Assessment Questionnaire (HAQ), and Patient Health Questionnaire-15 (PHQ-15) measurements. Predictive models for psychiatric and cognitive statuses were built using multiple linear regression, adjusting for baseline conditions. RESULTS: Initially, 516 older individuals enrolled, with 403 undergoing follow-up. During follow-up, the low participation group reported lower MMSE scores, higher BAI scores, and increased PHQ-15 risk. Negative correlations between social activity numbers and PHQ-15 results were found. Engagement in social clubs correlated positively with higher MMSE scores, while regular interactions with one's adult child(ren) were linked to decreased BAI scores. CONCLUSIONS: The quantity of social activities was associated with lower somatic distress. Social club engagement positively influenced cognition, and regular interactions with one's adult child(ren) mitigated anxiety among older individuals. CLINICAL IMPLICATIONS: Enough types of social activities, participating in social clubs, and adequate interactions with children protected against psychopathologies.


Assuntos
Cognição , Vida Independente , Participação Social , Humanos , Masculino , Feminino , Idoso , Participação Social/psicologia , Vida Independente/psicologia , Pessoa de Meia-Idade , Estudos Prospectivos , Cognição/fisiologia , Ansiedade/psicologia , Ansiedade/epidemiologia , Depressão/psicologia , Depressão/epidemiologia , Inquéritos e Questionários , Idoso de 80 Anos ou mais , Escalas de Graduação Psiquiátrica , Testes Neuropsicológicos , Disfunção Cognitiva/psicologia , Disfunção Cognitiva/epidemiologia
15.
Nicotine Tob Res ; 25(10): 1641-1647, 2023 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-37279967

RESUMO

INTRODUCTION: The increased growth of older adults has generated demand for home care aides (HCAs). Occupational tobacco smoke exposure (OTSE) may risk their health which should be paid attention to. AIMS AND METHODS: This study explored the HCAs' perspectives of OTSE to inform health promotion programs catering to individual needs. A two-stage Q methodology was employed for data collection and analysis. Thirty-nine Q statements were extracted in the first stage and then 51 HCAs with OTSE were recruited to complete Q sorting in the second stage. PQ Method software was used for data analysis. Principal component analysis was performed to determine the most appropriate number of factors. RESULTS: The five factors identified from HCAs' perspective of OTSE explained 51% of the variance. The HCAs agreed that OTSE could increase cancer risk. The HCAs with factor I did not care about OTSE, tending to complete their work. The HCAs with factor II agreed with the health hazards of OTSE, but did not know how to help their clients stop smoking. The HCAs with factor III cared about OTSE but were afraid of disrupting the client-provider relationship. The HCAs with factor IV regarded OTSE as a priority for occupational interventions whereas the HCAs with factor V did not think OTSE was an issue and believed that they could balance work and OTSE health hazards. CONCLUSIONS: Our findings will inform the design of home care pre-service and on-the-job training courses. Long-term care policies should be developed to promote smoke-free workplaces. IMPLICATIONS: There are five types of HCAs' perspectives on OTSE. The tailor interventions can be developed to help them avoid the OTSE (eg, opening windows for ventilation or using air purification equipment) and have an OTSE-free space.


Assuntos
Serviços de Assistência Domiciliar , Visitadores Domiciliares , Poluição por Fumaça de Tabaco , Humanos , Idoso , Poluição por Fumaça de Tabaco/efeitos adversos , Local de Trabalho , Coleta de Dados
16.
Acta Pharmacol Sin ; 44(3): 596-609, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36085523

RESUMO

Promotion of hepatic glycogen synthesis and inhibition of hepatic glucose production are effective strategies for controlling hyperglycemia in type 2 diabetes mellitus (T2DM), but agents with both properties were limited. Herein we report coronarin A, a natural compound isolated from rhizomes of Hedychium gardnerianum, which simultaneously stimulates glycogen synthesis and suppresses gluconeogenesis in rat primary hepatocytes. We showed that coronarin A (3, 10 µM) dose-dependently stimulated glycogen synthesis accompanied by increased Akt and GSK3ß phosphorylation in rat primary hepatocytes. Pretreatment with Akt inhibitor MK-2206 (2 µM) or PI3K inhibitor LY294002 (10 µM) blocked coronarin A-induced glycogen synthesis. Meanwhile, coronarin A (10 µM) significantly suppressed gluconeogenesis accompanied by increased phosphorylation of MEK, ERK1/2, ß-catenin and increased the gene expression of TCF7L2 in rat primary hepatocytes. Pretreatment with ß-catenin inhibitor IWR-1-endo (10 µM) or ERK inhibitor SCH772984 (1 µM) abolished the coronarin A-suppressed gluconeogenesis. More importantly, we revealed that coronarin A activated PI3K/Akt/GSK3ß and ERK/Wnt/ß-catenin signaling via regulation of a key upstream molecule IRS1. Coronarin A (10, 30 µM) decreased the phosphorylation of mTOR and S6K1, the downstream target of mTORC1, which further inhibited the serine phosphorylation of IRS1, and subsequently increased the tyrosine phosphorylation of IRS1. In type 2 diabetic ob/ob mice, chronic administration of coronarin A significantly reduced the non-fasting and fasting blood glucose levels and improved glucose tolerance, accompanied by the inhibited hepatic mTOR/S6K1 signaling and activated IRS1 along with enhanced PI3K/Akt/GSK3ß and ERK/Wnt/ß-catenin pathways. These results demonstrate the anti-hyperglycemic effect of coronarin A with a novel mechanism by inhibiting mTORC1/S6K1 to increase IRS1 activity, and highlighted coronarin A as a valuable lead compound for the treatment of T2DM.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Camundongos , Ratos , Animais , Gluconeogênese , Glicogênio Hepático/metabolismo , beta Catenina/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Insulina/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Glucose/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Homeostase , Fosforilação
17.
Altern Ther Health Med ; 29(8): 97-101, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37535923

RESUMO

Objective: This study aims to compare patient data from two different surgical approaches for minimally invasive valve surgery: hemi-sternotomy and right anterolateral thoracotomy. The primary objective is to determine the safety and efficacy of both surgical incisions. Methods: Between December 2019 and December 2022, a total of 90 patients underwent minimally invasive valve surgery at our center. Among them, 36 patients received the hemi-sternotomy incision with an average age of 45.86 ± 14.83, and 54 patients received the right anterolateral thoracotomy with an average age of 56.77 ± 14.83 years. In the hemi-sternotomy group, 21 patients underwent aortic valve surgery, and 15 had mitral valve surgery, while in the right anterolateral thoracotomy group, 30 patients underwent aortic valve surgery, and 15 patients had mitral valve surgery. Results: No deaths or significant bleeding occurred in the hemi-sternotomy group. However, in the right anterolateral thoracotomy group, one patient died from continuous low cardiac output syndrome after surgery, and one patient suffered a femoral artery dissection. All other patients were discharged without complications. The aortic clamp time and the cardiopulmonary bypass time were significantly lower in the hemi-sternotomy group compared to the right anterolateral thoracotomy group. Conversely, the two groups had no significant differences in intubation time, 24-hour drainage, hospitalization time, and blood transfusion. On the second day after surgery, serum c-TNT and NT-PROBNP levels significantly increased in both groups, but they were significantly higher in the right anterolateral thoracotomy group than in the hemi-sternotomy group. However, on the fifth day after surgery, serum c-TNT and NT-PROBNP levels decreased significantly in both groups, with no significant differences between them. Conclusions: Minimally invasive valve surgery, whether performed with right anterolateral thoracotomy or hemi-sternotomy, is safe and effective after the learning curve. Patients can benefit from these advances in minimally invasive cardiac surgery, and surgeons can easily master these techniques.


Assuntos
Implante de Prótese de Valva Cardíaca , Ferida Cirúrgica , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Esternotomia/métodos , Toracotomia/métodos , Implante de Prótese de Valva Cardíaca/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Resultado do Tratamento , Estudos Retrospectivos
18.
J Formos Med Assoc ; 122(7): 612-620, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36788044

RESUMO

INTRODUCTION: Social participation activities have a close association with health aging. However, the clinical significance of numbers of social participation activities and its cutoff value has not been defined. METHODS: We recruited 516 people aged ≥55 years. Twelve social participation behaviors modified according to Taiwanese culture were investigated, and the adequacy of cutoff number was determined by the area under the receiver operating characteristic curve (AUC) according to the results of cluster analysis of individual activities and scores of the Brief Symptom Rating Scale-5 (BSRS-5) and the Chinese Happiness Inventory (CHI). Demographic, BSRS-5 and CHI data were then compared according to the candidate cutoff numbers. RESULTS: The distribution of the numbers of social activities suggested that the highest partition of numbers of social activities was 3 in women and 4 in men. The AUC regarding the cluster of activity types was 0.917, with the highest Youden's J value located between 3 and 4. The AUC regarding the cluster of activity types and scores of the BSRS-5 and the CHI was 0.929, with similar cutoffs. If 3 and 4 were used as cutoffs, the between-group differences of both the CHI and the BSRS-5 were significant. More types of social activities had a different engaging frequency with the 3 and 4 cutoffs. CONCLUSION: Our findings found an adequate cutoff with better differential power in the psychopathology and happiness of older people that provided a basis for application in intervention and policy formation.


Assuntos
Participação Social , Masculino , Humanos , Feminino , Idoso , Curva ROC
19.
Chem Soc Rev ; 51(19): 8351-8377, 2022 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-36107012

RESUMO

Sulfur-containing compounds have attracted considerable interest due to their wide-ranging applications in pharmaceuticals, agriculture, natural products, and organic materials. The development of efficient and rapid methods for the construction and transformation of sulfur-containing compounds is of great importance. Since nickel is inexpensive and has a variety of valence states, strong nucleophilicity and low energy barriers for oxidative addition, the construction and transformation of sulfur-containing compounds by nickel-catalyzed cross-coupling have become important strategies. In addition, sulfur-containing compounds have also been playing increasingly important roles in the field of cross-coupling due to their thermodynamically stable but dynamic activity. This review will focus on nickel-catalyzed construction and transformation of various sulfide-containing compounds, such as sulfides, disulfides, and hypervalent sulfur-containing compounds.


Assuntos
Produtos Biológicos , Níquel , Catálise , Dissulfetos , Níquel/química , Preparações Farmacêuticas , Sulfetos/química , Enxofre/química , Compostos de Enxofre
20.
Sensors (Basel) ; 23(16)2023 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-37631704

RESUMO

The current study aimed to investigate the relationship between body parameters and the current-time product (mAs) in chest digital radiography using a non-contact infrared thickness-measurement sensor. An anthropomorphic chest phantom was first used to understand variations in mAs over multiple positionings during chest radiography when using the automatic exposure control (AEC) technique. In a human study, 929 consecutive male subjects who underwent regular chest examinations were enrolled, and their height (H), weight (W), and body mass index (BMI) were recorded. In addition, their chest thickness (T) was measured at exhalation using a non-contact infrared sensor, and chest radiography was then performed using the AEC technique. Finally, the relationship between four body parameters (T, BMI, T*BMI, and W/H) and mAs was investigated by fitting the body parameters to mAs using three curve models. The phantom study showed that the maximum mAs was 1.76 times higher than the lowest mAs during multiple positionings in chest radiography. In the human study, all chest radiographs passed the routine quality control procedure and had an exposure index between 100 and 212. In curve fitting, the comparisons showed that W/H had a closer relationship with mAs than the other body parameters, while the first-order power model with W/H fitted to mAs performed the best and had an R-square of 0.9971. We concluded that the relationship between W/H and mAs in the first-order power model may be helpful in predicting the optimal mAs and reducing the radiation dose for chest radiography when using the AEC technique.


Assuntos
Intensificação de Imagem Radiográfica , Tórax , Masculino , Humanos , Radiografia , Tórax/diagnóstico por imagem , Índice de Massa Corporal , Expiração
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