RESUMO
INTRODUCTION: Female sexual dysfunction (FSD) is a complex issue affecting women of all ages; it involves several overlapping body systems and profoundly affects quality of life. The use of cell-based therapy, such as mesenchymal stem cells, has recently been investigated as a potential treatment for FSD. OBJECTIVES: This systematic review and meta-analysis aim to assess FSD outcomes following cell-based therapy. METHODS: We evaluated peer-reviewed articles from multiple online databases through November 2022 to identify studies that used cell-based therapy and reported sexual function outcomes in women. We performed a meta-analysis using data pooled from 3 clinical trials at our institution: CRATUS (NCT02065245), ACESO (NCT02886884), and CERES (NCT03059355). All 3 trials collected data from the Sexual Quality of Life-Female (SQOL-F) questionnaire as an exploratory outcome. RESULTS: Existing literature on this topic is scarce. Five clinical studies and 1 animal study were included in the systematic review, and only 2 clinical studies were considered good quality: 1 reported significant SQOL-F improvement in women 6 months after cell therapy, and 1 reported posttherapy sexual satisfaction in all women. When individual patient data were pooled in a meta-analysis from 29 women across 3 trials at our institution, the SQOL-F was not significantly improved. CONCLUSION: Despite growing interest in cell-based therapy for women's sexual health, this important issue is understudied in the literature. The optimal route, source, and dose of cell therapy to produce clinically meaningful change have yet to be determined, and further research is needed in larger randomized placebo-controlled clinical trials.
Assuntos
Disfunções Sexuais Fisiológicas , Disfunções Sexuais Psicogênicas , Feminino , Humanos , Disfunções Sexuais Psicogênicas/terapia , Qualidade de Vida , Comportamento Sexual , Saúde da MulherRESUMO
Inclusion of women and minorities in clinical research is critical to fully assess the safety and efficacy of innovative therapies. With inadequate representation of demography, generalizability is impaired since pharmacokinetics and pharmacodynamics differ in these patient populations. This study was designed to analyze the voluntary participation rates of different demographic groups in cell-based therapy clinical trials conducted by the Interdisciplinary Stem Cell Institute (ISCI) at the University of Miami, Miller School of Medicine. ISCI conducted eight clinical trials between 2007 and 2017. The trials enrolled patients with ischemic and non-ischemic cardiomyopathy, idiopathic pulmonary fibrosis (IPF), aging-frailty, and Type-2 Diabetes. Participants received cell-based therapy (n = 218) or placebo (n = 33). Among the 251 participants, 29.5% were Hispanic and 20% were women. The proportion of individuals participating in each trial was compared to that of the respective disease populations attending University of Miami Health System clinics to calculate the participation to prevalence ratio (PPR). Distribution of women accurately reflected the population attending the University of Miami Health System in trials for dilated cardiomyopathy (DCM) and aging-frailty but was under-represented in others. Similarly, Hispanics and whites were accurately represented in three of the five disease fields, with Hispanics under-represented in frailty and diabetes, and whites over-represented in DCM and IPF. Black patients were accurately represented in the diabetes trial but were under-represented in all others. This study provides insight into challenges of achieving representative inclusion in research. Novel community engagement strategies are necessary to improve inclusion of women and under-represented minorities in clinical research of cell-based therapy.
RESUMO
Streptococcus mutans is the main microorganism associated to dental caries; it adheres to the dental enamel by interacting with the acquired film's proteins and the cell surface adhesin, called variously antigen PAc. At least two distinct sites in PAc interact with salivary receptors in vitro, these are within residues 816-1213, the most conserved portion of PAc, and within residues 186-469, the alanine-rich sequence. Our purpose was to establish differences or similarities in PAc's peptides interactions with the salivary components of individuals with and without previous caries experience. 40 saliva samples were obtained from patients with (n=20) and without (n=20) caries. The acquired film's proteins were extracted using hydroxyapatite, and subjected to interaction with three synthetic PAc peptides (PAc (301-319), PAc (365-377), and PAc (1025-1044)) synthesized from PAc's bonding sites to the salivary components. The results show low interaction between the acquired pellicle components and the peptides in all patients. This suggests that the examined PAc's are not relevant as far as the initial adhesion of Streptococcus mutans to the tooth's surface is concerned, as defined by the similarities in the results for healthy and affected individuals.
Assuntos
Aderência Bacteriana/fisiologia , Proteínas de Bactérias/metabolismo , Película Dentária/metabolismo , Glicoproteínas de Membrana/metabolismo , Proteínas e Peptídeos Salivares/metabolismo , Streptococcus mutans/química , Adesinas Bacterianas/química , Adesinas Bacterianas/metabolismo , Adolescente , Adulto , Sequência de Aminoácidos , Proteínas de Bactérias/química , Estudos de Casos e Controles , Cárie Dentária/microbiologia , Película Dentária/química , Humanos , Glicoproteínas de Membrana/química , Dados de Sequência Molecular , Peso Molecular , Ligação Proteica , Streptococcus mutans/fisiologiaRESUMO
Adhesion of microorganisms to dental surfaces is the initial step in the formation of dental bacterial plaque. Streptococcus mutans (S. mutans) is considered the main causal agent of one of the most common diseases in humans: dental caries. Adherence of these bacteria results from the interaction of adhesins that form part of their structure with salivary components, specifically those that compose the acquired pellicle. The complexity of this interaction has been the subject of studies in past years, to the extent of identifying certain salivary components related to adhesion to enamel surfaces, such as proline-rich proteins (PRSs), Staherins, Histatins, Cystatins, etc. One of the objectives of this study was to determine the adhesion capacity of S. mutans to synthetic hydroxyapatite incubated with saliva samples of caries-active and caries-inactive individuals. For the purpose of these assays, both the whole saliva samples and the salivary protein extracts were used. They were obtained by separating the proteins contained in the simple SDS-PAGE, in three ranges of molecular weight, selected in accordance with the electrophoresis profile that was usually found. The results indicated that the adhesion of this microorganism was greater in caries-inactive patients, when tested with whole saliva and proteins in the 120-159 kDa molecular weight range. This suggests that adhesion, per se, does not have a definite effect on the mechanisms that cause the disease in some individuals. However, these are interesting findings that may contribute to the design of strategies to control the adhesion of S. mutans to the tooth's surface.
Assuntos
Adesinas Bacterianas/metabolismo , Aderência Bacteriana/fisiologia , Cárie Dentária/microbiologia , Proteínas e Peptídeos Salivares/metabolismo , Streptococcus mutans/fisiologia , Adolescente , Adulto , Análise de Variância , Estudos de Casos e Controles , Película Dentária/metabolismo , Durapatita/metabolismo , Humanos , Peso Molecular , Ligação Proteica , Proteínas e Peptídeos Salivares/químicaRESUMO
La adhesión de los microorganismos a las superficies dentales, es el paso inicial en la formación de la placa dentobacteriana, Streptococcus mutans (S. mutans) es uno de los encontrados en ésta y está asociado como el principal agente causal de una delas enfermedades más comunes en los humanos, la caries dental. La adherencia de esta bacteria se da por la interacción de adhesinas que la constituyen con los componentes salivales, específicamente con los que están formando parte de la película adquirida. La complejidad de esta interacción ha sido motivo deestudio durante los últimos años, hasta el punto de identificar algunos componentes salivales relacionados con la unión a las superficies del esmalte, tales como Proteínas ricas en prolina(PRPs), staterinas,Histatinas,Cistatinas, etc. En el presente trabajo se buscó determinar la capacidad de adhesión de S. mutans a hidroxilapatita sintética incubada con muestras de salivade personas con y sin experiencia de caries. Para estos ensayos se utilizó tanto la muestra de saliva completa como extractos de proteínas salivales, obtenidos por medio de la separaciónde las proteínas contenidas en la muestra por SDS-PAGE, en tres rangos de peso molecular seleccionados de acuerdo con el perfil electroforético que fue comúnmente encontrado. Losresultados indican que la adhesión de este microorganismo es mayor en las personas sin experiencia de caries cuando se ensayó con saliva completa y con las proteínas separadas en el rangode peso molecular de 120-159 kDa. Sugiriendo que la adhesión por sí sola no tiene un efecto determinante en los mecanismos que producen la enfermedad en algunas personas. Sin embargo estos hallazgos son interesantes ya que pueden contribuir en el diseño de estrategias para intervenir en la adhesión de S. mutanssobre las superficies dentales
Adhesion of microorganisms to dental surfaces is the initial step in the formation of dental bacterial plaque. Streptococcus mutans (S. mutans) is considered the main causal agent of one of the most common diseases in humans: dental caries. Adherence of these bacteria results from the interaction of adhesins that form part of their structure with salivary components, specifically those that compose the acquired pellicle. The complexity of this interaction has been the subject of studies in past years, to the extent of identifying certain salivary components related to adhesion to enamel surfaces, such as proline-rich proteins (PRSs), Staherins, Histatins, Cystatins, etc. One of the objectives of this study was to determine the adhesion capacity of S. mutans to synthetic hydroxyapatite incubated with saliva samples of caries-active and caries-inactive individuals. For the purpose of these assays, both the whole saliva samples and the salivary protein extracts were used. They were obtained by separating the proteins contained in the simple SDS-PAGE, in three ranges of molecular weight, selected in accordance with the electrophoresis profile that was usually found. The results indicated that the adhesion of this microorganism was greater in caries-inactive patients, when tested with whole saliva and proteins in the 120-159 kDa molecular weight range. This suggests that adhesion, per se, does not have a definite effect on the mechanisms that cause the disease in some individuals. However, these are interesting findings that may contribute to the design of strategies to control the adhesion of S. mutans to the tooths surface.
Assuntos
Humanos , Adolescente , Adulto , Adesinas Bacterianas/metabolismo , Aderência Bacteriana/fisiologia , Cárie Dentária/microbiologia , Proteínas e Peptídeos Salivares/metabolismo , Streptococcus mutans/fisiologia , Suscetibilidade à Cárie Dentária/fisiologia , Análise de Variância , Estudos de Casos e Controles , Durapatita/metabolismo , Peso Molecular , Ligação Proteica , Película Dentária/metabolismo , Proteínas e Peptídeos Salivares/química , Interpretação Estatística de DadosRESUMO
Streptococcus mutans es el principal microorganismo asociadoa la caries dental, esta bacteria se une al esmalte a través de su interacción con las proteínas de la película adquirida yla proteína de superficie celular comúnmente denominada PAc. Por lo menos dos sitios de PAc interactúan in vitro con los receptores salivales, uno está dentro de la región más conservadade esta proteína que comprende los residuos de 816-1213 y el otro dentro de la secuencia rica en Alanina, residuos186-469. El objetivo del presente trabajo fue establecer similitudes o diferencias en la interacción de péptidos de PAc con los componentes salivales de individuos con y sin experienciade caries, para lo cual se tomaron muestras de saliva por salivación espontánea de 20 individuos con caries y 20 sin caries. A partir de las muestras de saliva se extrajeron las proteínas de la película adquirida (PA) utilizando hidroxilapatita sintética y fueron sometidas a la interacción con trespéptidos sintéticos de los segmentos de unión de PAc con los componentes salivales: PAc (301-319), PAc (365-377) y PAc (1024-1044). Los resultados muestran una baja interacciónentre los componentes de la PA y los péptidos en todos los individuos, sugiriendo que con base en las similitudes entre los individuos sanos y los individuos con la enfermedad lospéptidos de PAc estudiados no son relevantes en la adhesión
Streptococcus mutans is the main microorganism associated to dental caries; it adheres to the dental enamel by interacting with the acquired films proteins and the cell surface adhesin, called variously antigen PAc. At least two distinct sites in PAc interact with salivary receptors in vitro, these are within residues 816-1213, the most conserved portion of PAc, and within residues 186-469, the alanine-rich sequence. Our purpose was to establish differences or similarities in PAcs peptides interactions with the salivary components of individuals with and without previous caries experience. 40 saliva samples were obtained from patients with (n=20) and without (n=20) caries. The acquired films proteins were extracted using hydroxyapatite, and subjected to interaction with three synthetic PAc peptides (PAc (301-319), PAc (365-377), and PAc (1025-1044)) synthesized from PAcs bonding sites to the salivary components. The results show low interaction between the acquired pellicle components and the peptides in all patients. This suggests that the examined PAcs are not relevant as far as the initial adhesion of Streptococcus mutans to the tooths surface is concerned, as defined by the similarities in the results for healthy and affected individuals.