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1.
Artigo em Inglês | MEDLINE | ID: mdl-36612845

RESUMO

Purpose: Stress urinary incontinence (SUI) refers to involuntary leakage from the urethra, synchronous with exertion/effort, sneezing or coughing, which has a negative effect on quality of life. Studies have shown that mild-to-moderate physical activities reduce the risk of SUI by multiple mechanisms. The objective of this study was to determine whether the Rumba dance combined with breathing training (RDBT) can reduce the severity of incontinence and improve the quality of life of patients with SUI. Methods: A randomized clinical trial was conducted with women who were sedentary, were postmenopausal, reported mild-to-moderate SUI on a 1-h pad test, were not already engaged in Rumba dance and did not receive estrogen replacement therapy. The patients were randomly assigned to the RDBT group (n = 13) or the control group (n = 11). The intervention included 90 min of RDBT three times per week for 16 weeks, and the vaginal resting pressure (VRP), pelvic floor muscle (PFM) strength and endurance, 1-h pad test, International Consultation on Incontinence Questionnaire­Urinary Incontinence Short Form (ICIQ­UI SF), and the Incontinence Quality of Life Questionnaire (I­QOL) were measured or completed at baseline and 16 weeks. None of the participants reported adverse events. Results: The mean (±SD) age of the participants was 55.75 ± 5.58 years. After 16 weeks, in the RDBT group, the urine leakage on the 1-h pad test was significantly decreased −2.91 ± 0.49 from the baseline (p = 0.000). The VRP increased from 76.00 ± 16.23 cmH2O to 95.09 ± 18.90 cmH2O (p = 0.000), the PFM endurance of class I (−3.15 ± 1.99% vs. −0.46 ± 0.97%, p = 0.000) and class II (−0.69 ± 0.95% vs. −0.23 ± 0.44%, p = 0.065) increased, and the grades of PFM strength of class I and class II were significantly enhanced (p < 0.01). Finally, the severity of self-reported incontinence (ICIQ­UI SF) significantly decreased from 6.12 ± 2.15 to 3.81 ± 1.68 (p = 0.000), and quality of life (I­QOL) improved from 75.73 ± 11.93 to 83.48 ± 7.88 (p = 0.005). Conclusion: A 16-week RDBT program can increase PFM strength and endurance to reduce the severity of incontinence symptoms and improve the quality of life in patients with SUI, demonstrating the feasibility of recruiting and retaining postmenopausal women with SUI into a RDBT therapeutic program.


Assuntos
Dança , Incontinência Urinária por Estresse , Incontinência Urinária , Humanos , Feminino , Pessoa de Meia-Idade , Incontinência Urinária por Estresse/terapia , Qualidade de Vida , Terapia por Exercício , Pós-Menopausa , Diafragma da Pelve , Resultado do Tratamento
2.
J Biol Chem ; 296: 100426, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33609526

RESUMO

Birt-Hogg-Dubé (BHD) syndrome is a multiorgan disorder caused by inactivation of the folliculin (FLCN) protein. Previously, we identified FLCN as a binding protein of Rab11A, a key regulator of the endocytic recycling pathway. This finding implies that the abnormal localization of specific proteins whose transport requires the FLCN-Rab11A complex may contribute to BHD. Here, we used human kidney-derived HEK293 cells as a model, and we report that FLCN promotes the binding of Rab11A with transferrin receptor 1 (TfR1), which is required for iron uptake through continuous trafficking between the cell surface and the cytoplasm. Loss of FLCN attenuated the Rab11A-TfR1 interaction, resulting in delayed recycling transport of TfR1. This delay caused an iron deficiency condition that induced hypoxia-inducible factor (HIF) activity, which was reversed by iron supplementation. In a Drosophila model of BHD syndrome, we further demonstrated that the phenotype of BHD mutant larvae was substantially rescued by an iron-rich diet. These findings reveal a conserved function of FLCN in iron metabolism and may help to elucidate the mechanisms driving BHD syndrome.


Assuntos
Antígenos CD/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Receptores da Transferrina/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Animais , Antígenos CD/genética , Antígenos CD/fisiologia , Síndrome de Birt-Hogg-Dubé/metabolismo , Síndrome de Birt-Hogg-Dubé/fisiopatologia , Citoplasma/metabolismo , Proteínas de Drosophila , Drosophila melanogaster , Células HEK293 , Homeostase , Humanos , Ferro/metabolismo , Modelos Animais , Proteínas Proto-Oncogênicas/fisiologia , Receptores da Transferrina/genética , Receptores da Transferrina/fisiologia , Proteínas Supressoras de Tumor/fisiologia , Proteínas rab de Ligação ao GTP/metabolismo
3.
Nat Commun ; 11(1): 4860, 2020 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-32978381

RESUMO

Despite remarkable recent advances in transition-metal-catalyzed C(sp3)-C cross-coupling reactions, there remain challenging bond formations. One class of such reactions include the formation of tertiary-C(sp3)-C bonds, presumably due to unfavorable steric interactions and competing isomerizations of tertiary alkyl metal intermediates. Reported herein is a Ni-catalyzed migratory 3,3-difluoroallylation of unactivated alkyl bromides at remote tertiary centers. This approach enables the facile construction of otherwise difficult to prepare all-carbon quaternary centers. Key to the success of this transformation is an unusual remote functionalization via chain walking to the most sterically hindered tertiary C(sp3) center of the substrate. Preliminary mechanistic and radical trapping studies with primary alkyl bromides suggest a unique mode of tertiary C-radical generation through chain-walking followed by Ni-C bond homolysis. This strategy is complementary to the existing coupling protocols with tert-alkyl organometallic or -alkyl halide reagents, and it enables the expedient formation of quaternary centers from easily available starting materials.

4.
Chem Sci ; 10(37): 8701-8705, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31803445

RESUMO

A strategically novel single C-F bond functionalization of CF3-derived molecules, which shows a prominent advantage for the expedient construction of difluoromethylene-bridged organic scaffolds, is disclosed. The reported protocol consists of SN2' amination, N-alkylation and palladium-catalyzed allylic substitution reactions, which enables straightforward arylation and alkenylation of vinyltrifluoromethane derivatives. Furthermore, this strategy is characterized by its broad substrate scope with respect to both CF3-alkene and arylboronic acid derivatives.

5.
Chem Sci ; 10(27): 6721-6726, 2019 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-31367327

RESUMO

The catalytic C-F bond carboxylation of organofluorines with CO2 gas remains a challenging problem in synthetic chemistry. Here, we describe a selective defluorinative carboxylation of gem-difluoroalkenes through photoredox/palladium dual catalysis. The C-F bond activation is enabled by single electron reduction through photoredox catalysis to generate a fluorovinyl radical, which subsequently participates in an unprecedented palladium-catalyzed carboxylation. This novel C-F functionalization proved applicable to a wide range of substituted gem-difluoroalkenes, providing a rapid access to valuable α-fluoroacrylic acids.

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