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1.
Reprod Biomed Online ; 48(2): 103621, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38040621

RESUMO

In recent years, increasing efforts have been made to develop advanced techniques that could predict the potential of implantation of each single embryo and prioritize the transfer of those at higher chance. The most promising include non-invasive preimplantation genetic testing for aneuploidy and artificial intelligence-based algorithms using time lapse images. The psychological effect of these add-ons is neglected. One could speculate that embarking on another transfer after one or more failures with the prospect of receiving an embryo of lower potential may be distressing for the couple. In addition, the symbolic and mental representation of an embryo with 'lower capacity to implant' is currently unknown but could affect couples' choices and wellbeing. These emotional responses may also undermine adherence to the programme and, ultimately, its real effectiveness. Future trials aimed at evaluating the validity of prioritization procedures must also consider the emotional burden on the couples.


Assuntos
Inteligência Artificial , Diagnóstico Pré-Implantação , Humanos , Feminino , Gravidez , Implantação do Embrião/fisiologia , Testes Genéticos/métodos , Aneuploidia , Emoções , Diagnóstico Pré-Implantação/métodos , Fertilização in vitro , Blastocisto
2.
Arch Gynecol Obstet ; 309(3): 887-893, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-37689593

RESUMO

Deep dyspareunia is one of the main symptoms of endometriosis. It appears to be submerged by a two-way disconnection between patients and their physicians. The aim of our review is to provide clear, ready-to-use advice on how to manage deep dyspareunia overcoming the gap in communication. Sexual history should always be taken as part of routine health care in these regards, using a patient-centered approach. An educational pelvic examination, which actively includes patients in the identification of painful areas, may prove useful to improve patients' understanding of their condition. Correlating painful pelvic areas with sexual positions and inviting patients to adopt alternative positions may represent a simple but extremely effective coping strategy to mitigate pain. Revealing and explaining to partners the nature of the pain is essential to allow them to take part in shared research of coping mechanisms, empowering the couple to make choices and changes. Couples who do not feel comfortable talking about intimacy by themselves may find that including a psychotherapist or a sexual therapist, may be a good way to start communication. Investigating and managing dyspareunia during medical encounters is a medical and ethical duty all healthcare practitioners should pursue.


Assuntos
Dispareunia , Endometriose , Feminino , Humanos , Dispareunia/etiologia , Dispareunia/terapia , Endometriose/complicações , Dor Pélvica , Comportamento Sexual , Parceiros Sexuais
3.
BMC Womens Health ; 23(1): 347, 2023 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-37391793

RESUMO

One-fourth to one-third of women with endometriosis receiving first-line hormonal treatment lacks an adequate response in terms of resolution of painful symptoms. This phenomenon has been ascribed to "progesterone resistance", an entity that was theorized to explain the gap between the ubiquity of retrograde menstruation and the 10% prevalence of endometriosis among women of reproductive age.Nevertheless, the hypothesis of progesterone resistance is not free of controversies. As our understanding of endometriosis is increasing, authors are starting to set aside the traditionally accepted tunnel vision of endometriosis as a strictly pelvic disease, opening to a more comprehensive perspective of the condition. The question is: are patients not responding to first-line treatment because they have an altered signaling pathway for such treatment, or have we been overlooking a series of other pain contributors which may not be resolved by hormonal therapy?Finding an answer to this question is evermore impelling, for two reasons mainly. Firstly, because not recognizing the presence of further pain contributors adds a delay in treatment to the already existing delay in diagnosis of endometriosis. This may lead to chronicity of the untreated pain contributors as well as causing adverse consequences on quality of life and psychological health. Secondly, misinterpreting the consequences of untreated pain contributors as a non-response to standard first-line treatment may imply the adoption of second-line medical therapies or of surgery, which may entail non-negligible side effects and may not be free of physical, psychological and socioeconomic repercussions.The current narrative review aims at providing an overview of all the possible pain contributors in endometriosis, ranging from those strictly organic to those with a greater neuro-psychological component. Including these aspects in a broader psychobiological approach may provide useful suggestions for treating those patients who report persistent pain symptoms despite receiving first-line hormonal medical treatment.


Assuntos
Endometriose , Humanos , Feminino , Endometriose/complicações , Endometriose/tratamento farmacológico , Progesterona , Qualidade de Vida , Dor/tratamento farmacológico , Dor/etiologia
4.
Int J Mol Sci ; 24(13)2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-37445991

RESUMO

Human adipose-derived stem cells (hASCs) are commonly harvested in minimally invasive contexts with few ethical concerns, and exhibit self-renewal, multi-lineage differentiation, and trophic signaling that make them attractive candidates for cell therapy approaches. The identification of natural molecules that can modulate their biological properties is a challenge for many researchers. Oxytocin (OXT) is a neurohypophyseal hormone that plays a pivotal role in the regulation of mammalian behavior, and is involved in health and well-being processes. Here, we investigated the role of OXT on hASC proliferation, migratory ability, senescence, and autophagy after a treatment of 72 h; OXT did not affect hASC proliferation and migratory ability. Moreover, we observed an increase in SA-ß-galactosidase activity, probably related to the promotion of the autophagic process. In addition, the effects of OXT were evaluated on the hASC differentiation ability; OXT promoted osteogenic differentiation in a dose-dependent manner, as demonstrated by Alizarin red staining and gene/protein expression analysis, while it did not affect or reduce adipogenic differentiation. We also observed an increase in the expression of autophagy marker genes at the beginning of the osteogenic process in OXT-treated hASCs, leading us to hypothesize that OXT could promote osteogenesis in hASCs by modulating the autophagic process.


Assuntos
Osteogênese , Ocitocina , Animais , Humanos , Ocitocina/farmacologia , Ocitocina/metabolismo , Tecido Adiposo/metabolismo , Adipócitos , Diferenciação Celular , Células-Tronco , Células Cultivadas , Mamíferos
5.
Int J Mol Sci ; 24(21)2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37958785

RESUMO

Oxidative stress (OS) plays a key role in autism spectrum disorder (ASD), a neurodevelopmental disorder characterized by deficits in social communication, restricted interests, and repetitive behaviors. Recent evidence suggests that the TLDc [Tre2/Bub2/Cdc16 (TBC), lysin motif (LysM), domain catalytic] domain is a highly conserved motif present in proteins that are important players in the OS response and in neuroprotection. Human proteins sharing the TLDc domain include OXR1, TLDC1, NCOA7, TBC1D24, and C20ORF118. This study was aimed at understanding whether TLDc domain-containing mRNAs together with specific microRNAs (200b-3p and 32-5p) and long noncoding RNAs (TUG1), known to target TLDc proteins, contributed to regulate the OS response in ASD. Data showed a significant increase in the levels of OXR1 and TLDC1 mRNAs in peripheral blood mononuclear cells (PBMCs) of ASD children compared to their neurotypically developing (NTD) counterparts, along with an increase in TUG1 mRNA expression levels, suggesting its possible role in the regulation of TLDc proteins. A positive correlation between the expression of some TLDc mRNAs and the Childhood Autism Rating Scale (CARS) global score as well as inflammatory gene expression was found. In conclusion, our data suggest a novel biological pathway in the OS response of ASD subjects that deserves further exploration.


Assuntos
Transtorno do Espectro Autista , Criança , Humanos , Transtorno do Espectro Autista/metabolismo , Leucócitos Mononucleares/metabolismo , Estresse Oxidativo/genética , Proteínas/metabolismo , Oxirredução , Proteínas Ativadoras de GTPase/metabolismo
6.
Gynecol Endocrinol ; 38(3): 193-201, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34913798

RESUMO

OBJECTIVE: Over the past decades, an increasing number of women have been using hormonal contraception. The potential role of sex hormones in regulating vegetative, psychophysiological, and cognitive functions has been highlighted in several studies, and there is a need to further understand the impact of hormonal contraception on women's quality of life, especially as regards psychological health and sexuality. METHODS: We conducted a narrative review aimed at clarifying the mechanisms involved in the interaction between sex hormones and the brain, also focusing on the association between hormonal contraception and mood and sexual function. RESULTS: Our findings clarified that hormonal contraception may be associated with depressive symptoms, especially among adolescents, and with sexual dysfunction. However, the evidence included in this review was conflicting and did not support the hypothesis that hormonal contraception directly causes depressive symptoms, major depressive disorder, or sexual dysfunction. CONCLUSIONS: The optimal hormonal contraception should be identified in the context of shared decision making, considering the preferences and needs of each woman, as well as her physical and psychosexual conditions.


Assuntos
Transtorno Depressivo Maior , Contracepção Hormonal , Adolescente , Anticoncepção/efeitos adversos , Depressão/induzido quimicamente , Feminino , Humanos , Qualidade de Vida , Sexualidade
7.
Int J Mol Sci ; 23(7)2022 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-35409178

RESUMO

Opioids are considered the oldest drugs known by humans and have been used for sedation and pain relief for several centuries. Nowadays, endogenous opioid peptides are divided into four families: enkephalins, dynorphins, endorphins, and nociceptin/orphanin FQ. They exert their action through the opioid receptors (ORs), transmembrane proteins belonging to the super-family of G-protein-coupled receptors, and are expressed throughout the body; the receptors are the δ opioid receptor (DOR), µ opioid receptor (MOR), κ opioid receptor (KOR), and nociceptin/orphanin FQ receptor (NOP). Endogenous opioids are mainly studied in the central nervous system (CNS), but their role has been investigated in other organs, both in physiological and in pathological conditions. Here, we revise their role in stem cell (SC) biology, since these cells are a subject of great scientific interest due to their peculiar features and their involvement in cell-based therapies in regenerative medicine. In particular, we focus on endogenous opioids' ability to modulate SC proliferation, stress response (to oxidative stress, starvation, or damage following ischemia-reperfusion), and differentiation towards different lineages, such as neurogenesis, vasculogenesis, and cardiogenesis.


Assuntos
Analgésicos Opioides , Peptídeos Opioides , Analgésicos Opioides/metabolismo , Humanos , Peptídeos Opioides/metabolismo , Receptores Opioides/metabolismo , Receptores Opioides kappa/metabolismo , Células-Tronco/metabolismo
8.
Int J Mol Sci ; 23(6)2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-35328576

RESUMO

We discuss emerging views on the complexity of signals controlling the onset of biological shapes and functions, from the nanoarchitectonics arising from supramolecular interactions, to the cellular/multicellular tissue level, and up to the unfolding of complex anatomy. We highlight the fundamental role of physical forces in cellular decisions, stressing the intriguing similarities in early morphogenesis, tissue regeneration, and oncogenic drift. Compelling evidence is presented, showing that biological patterns are strongly embedded in the vibrational nature of the physical energies that permeate the entire universe. We describe biological dynamics as informational processes at which physics and chemistry converge, with nanomechanical motions, and electromagnetic waves, including light, forming an ensemble of vibrations, acting as a sort of control software for molecular patterning. Biomolecular recognition is approached within the establishment of coherent synchronizations among signaling players, whose physical nature can be equated to oscillators tending to the coherent synchronization of their vibrational modes. Cytoskeletal elements are now emerging as senders and receivers of physical signals, "shaping" biological identity from the cellular to the tissue/organ levels. We finally discuss the perspective of exploiting the diffusive features of physical energies to afford in situ stem/somatic cell reprogramming, and tissue regeneration, without stem cell transplantation.


Assuntos
Transdução de Sinais , Morfogênese
9.
Reprod Biomed Online ; 43(6): 1027-1034, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34756643

RESUMO

RESEARCH QUESTION: What are the associations between endometriosis, pelvic pain symptoms, fatigue and sleep? Psychological health and quality of life in endometriosis patients with good versus bad quality of sleep were also examined. DESIGN: This matched pair case-control study included 123 consecutive endometriosis patients and 123 women without a history of endometriosis (matched to patients for age and body mass index). Endometriosis-related pelvic pain severity was rated on a 0-10 numerical rating scale. Fatigue was measured on a 1-5 Likert scale. Women also completed a set of self-report questionnaires for assessing sleep disturbances (Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, Insomnia Severity Index), psychological health (Hospital Anxiety and Depression Scale) and quality of life (Short Form-12). RESULTS: Painful endometriosis had an impact on fatigue (P = 0.006; η2p = 0.041) and sleep (P < 0.001; η2p = 0.051). Women with painful endometriosis reported significantly greater fatigue, poorer quality of sleep, higher daytime sleepiness and more severe insomnia than women without significant pain symptoms and controls. Poorer quality of sleep among endometriosis patients was associated with greater fatigue (P < 0.001; η2p = 0.130), poorer psychological health (P < 0.001; η2p = 0.135), and lower quality of life (P < 0.001; η2p = 0.240). CONCLUSIONS: Pelvic pain (rather than endometriosis in itself) is associated with fatigue and sleep disturbances, with poor sleep having a detrimental impact on women's psychological health and quality of life.


Assuntos
Endometriose/complicações , Fadiga/complicações , Saúde Mental , Dor Pélvica/etiologia , Qualidade de Vida , Transtornos do Sono-Vigília/complicações , Adulto , Fatores Etários , Índice de Massa Corporal , Estudos de Casos e Controles , Endometriose/psicologia , Fadiga/psicologia , Feminino , Humanos , Medição da Dor , Dor Pélvica/psicologia , Transtornos do Sono-Vigília/psicologia
10.
Hum Reprod ; 34(6): 1065-1073, 2019 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-31090897

RESUMO

STUDY QUESTION: Is infertility-related distress a risk factor for impaired female sexual function in women undergoing assisted reproduction? SUMMARY ANSWER: Infertility-related distress, and especially social, sexual, and relationship concerns, is associated with female sexual dysfunction. WHAT IS KNOWN ALREADY: Women with infertility are more likely to present sexual dysfunction relative to those without infertility. Moreover, assisted reproduction is associated with increased risk for female sexual problems. To date, this higher proportion of sexual impairment in infertile women has been simplistically linked to the stress associated with the condition and investigated risk factors included mainly demographic and clinical variables. Quantitative studies aimed at identifying risk factors for sexual dysfunction that also included the evaluation of infertility-related distress are conversely lacking. STUDY DESIGN, SIZE, DURATION: This observational study was conducted at the Infertility Unit of the Fondazione Ca' Granda, Ospedale Maggiore Policlinico of Milan between 2017 and 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: We included 269 consecutive patients with infertility aged 24-45 (37.8 ± 4.0 years). Sexual function outcomes were sexual dysfunction (assessed with the Female Sexual Function Index), sexual distress (evaluated with the Female Sexual Distress Scale-Revised), dyspareunia, and number of intercourses in the month preceding ovarian stimulation. Infertility-related distress was measured with the Fertility Problem Inventory (FPI). The effects of potential confounders such as demographic variables (women's and partners' age and level of education) and infertility-related factors (type and cause of infertility, number of previous IVF cycles, and duration of infertility) were also examined. MAIN RESULTS AND THE ROLE OF CHANCE: Women with higher infertility-related distress were more likely to report sexual dysfunction (odds ratio = 1.02 per point of score; 95% CI, 1.01-1.03; P = 0.001). Three FPI domains (i.e. social, relational, and sexual concerns) were correlated with almost all sexual function outcomes (Ps < 0.05). LIMITATIONS, REASONS FOR CAUTION: Women who were not sexually active were not included, thus reasons for sexual inactivity should be further explored in future studies. Data regarding men (e.g. sexual function and infertility-related distress) were lacking, thus cross-partner effects were not examined. Recall bias (also due to the fact that questionnaires were administered on the day of oocytes retrieval) and social desirability bias may have also affected women's responses to the questionnaires. WIDER IMPLICATIONS OF THE FINDINGS: Social, relational, and sexual concerns should be assessed and addressed in psychological counselling with the infertile couple. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: Not applicable.


Assuntos
Dispareunia/epidemiologia , Infertilidade Feminina/psicologia , Técnicas de Reprodução Assistida/efeitos adversos , Disfunções Sexuais Psicogênicas/epidemiologia , Estresse Psicológico/complicações , Adulto , Coito/psicologia , Estudos Transversais , Dispareunia/etiologia , Dispareunia/psicologia , Feminino , Humanos , Infertilidade Feminina/terapia , Masculino , Pessoa de Meia-Idade , Psicometria/estatística & dados numéricos , Técnicas de Reprodução Assistida/psicologia , Fatores de Risco , Disfunções Sexuais Psicogênicas/diagnóstico , Disfunções Sexuais Psicogênicas/etiologia , Disfunções Sexuais Psicogênicas/psicologia , Parceiros Sexuais/psicologia , Estresse Psicológico/psicologia , Inquéritos e Questionários/estatística & dados numéricos , Adulto Jovem
11.
Reprod Biomed Online ; 38(5): 797-807, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30904355

RESUMO

The aim of this study was to provide a systematic narrative review of the published research articles on donor conceived offspring's subjective experiences of their donor. A systematic search of electronic databases (PsycINFO and PubMed) provided 29 published quantitative and qualitative studies matching the inclusion criteria. The analysis of the studies outcomes led to the identification of four main themes: (i) views/representations of the donor; (ii) desire to contact the donor (in terms of desire to meet the donor, reasons for wanting to contact the donor, type and frequency of contact); (iii) reactions to discovering the donor's identity and contacting the donor; (iv) identity issues. The findings revealed that genetic ties do matter to donor conceived people, especially during adolescence or adulthood. Many donor conceived people were interested in contacting the donor and all of them needed to make meaning of the role of the donor, as well as to integrate it into their family life and self-concept. Besides curiosity and medical reasons, many people reported wanting to contact the donor to see what he/she looked like, and to have access to their own ancestry and genetic history.


Assuntos
Filhos Adultos/psicologia , Psicologia do Adolescente , Psicologia da Criança , Doadores de Tecidos , Hereditariedade , Humanos
12.
Gynecol Obstet Invest ; 84(2): 190-195, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30380545

RESUMO

AIMS: The economic burden of endometriosis and pelvic pain involves direct and indirect healthcare costs due to work loss and decreased productivity. However, the relation between endometriosis, pelvic pain, and employment remains underinvestigated. This study aimed at providing preliminary insights into this topic. METHODS: We compared the employment status (having vs. not having a job) in 298 consecutive endometriosis patients and in 332 women without a history of endometriosis (control group). We also examined the association between pelvic pain and employment status. RESULTS: Women with endometriosis were less likely to be employed compared to women without endometriosis (OR 0.508; 95% CI 0.284-0.908; p = 0.022). Women with symptomatic endometriosis were less likely to be employed relative to controls (OR 0.345; 95% CI 0.184-0.650; p = 0.001), as well as to asymptomatic endometriosis patients (OR 0.362; 95% CI 0.167-0.785; p = 0.01). No significant differences emerged between asymptomatic endometriosis and the control group (p > 0.05). Greater severity of dysmenorrhea, dyspareunia, chronic pelvic pain, and dyschezia was found in unemployed endometriosis patients (vs. employed endometriosis participants). CONCLUSION: Endometriosis symptoms may significantly affect women's professional life, with important socioeconomic, legal, and political implications. Community-based participatory research is encouraged.


Assuntos
Emprego , Endometriose/fisiopatologia , Dor Pélvica/fisiopatologia , Adulto , Dor Crônica , Constipação Intestinal , Efeitos Psicossociais da Doença , Dismenorreia/fisiopatologia , Dispareunia/fisiopatologia , Endometriose/economia , Feminino , Humanos , Pessoa de Meia-Idade , Medição da Dor , Índice de Gravidade de Doença
13.
Int J Mol Sci ; 20(20)2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31635381

RESUMO

A wide variety of peptides not only interact with the cell surface, but govern complex signaling from inside the cell. This has been referred to as an "intracrine" action, and the orchestrating molecules as "intracrines". Here, we review the intracrine action of dynorphin B, a bioactive end-product of the prodynorphin gene, on nuclear opioid receptors and nuclear protein kinase C signaling to stimulate the transcription of a gene program of cardiogenesis. The ability of intracrine dynorphin B to prime the transcription of its own coding gene in isolated nuclei is discussed as a feed-forward loop of gene expression amplification and synchronization. We describe the role of hyaluronan mixed esters of butyric and retinoic acids as synthetic intracrines, controlling prodynorphin gene expression, cardiogenesis, and cardiac repair. We also discuss the increase in prodynorphin gene transcription and intracellular dynorphin B afforded by electromagnetic fields in stem cells, as a mechanism of cardiogenic signaling and enhancement in the yield of stem cell-derived cardiomyocytes. We underline the possibility of using the diffusive features of physical energies to modulate intracrinergic systems without the needs of viral vector-mediated gene transfer technologies, and prompt the exploration of this hypothesis in the near future.


Assuntos
Diferenciação Celular/genética , Encefalinas/genética , Encefalinas/metabolismo , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Animais , Butiratos/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Peptídeos Opioides/genética , Peptídeos Opioides/metabolismo , Organogênese/genética , Transdução de Sinais , Células-Tronco/citologia , Células-Tronco/metabolismo , Tretinoína/metabolismo
14.
Int J Mol Sci ; 20(11)2019 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-31146388

RESUMO

Stem cells undergo senescence both in vivo, contributing to the progressive decline in self-healing mechanisms, and in vitro during prolonged expansion. Here, we show that an early developmental zebrafish embryo extract (ZF1) could act as a modulator of senescence in human mesenchymal stem cells (hMSCs) isolated from both adult tissues, including adipose tissue (hASCs), bone marrow (hBM-MSCs), dental pulp (hDP-MSCs), and a perinatal tissue such as the Wharton's Jelly (hWJ-MSCs). In all the investigated hMSCs, ZF1 decreased senescence-associated ß-galactosidase (SA ß-gal) activity and enhanced the transcription of TERT, encoding the catalytic telomerase core. In addition, it was associated, only in hASCs, with a transcriptional induction of BMI1, a pleiotropic repressor of senescence. In hBM-MSCs, hDP-MSCs, and hWJ-MSCs, TERT over-expression was concomitant with a down-regulation of two repressors of TERT, TP53 (p53), and CDKN1A (p21). Furthermore, ZF1 increased the natural ability of hASCs to perform adipogenesis. These results indicate the chance of using ZF1 to modulate stem cell senescence in a source-related manner, to be potentially used as a tool to affect stem cell senescence in vitro. In addition, its anti-senescence action could also set the basis for future in vivo approaches promoting tissue rejuvenation bypassing stem cell transplantation.


Assuntos
Senescência Celular , Embrião não Mamífero/química , Células-Tronco Mesenquimais/efeitos dos fármacos , Extratos de Tecidos/farmacologia , Animais , Células Cultivadas , Inibidor de Quinase Dependente de Ciclina p21/genética , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Complexo Repressor Polycomb 1/genética , Complexo Repressor Polycomb 1/metabolismo , Telomerase/genética , Telomerase/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Peixe-Zebra
15.
Int J Med Sci ; 15(13): 1486-1501, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30443170

RESUMO

Human Mesenchymal Stem Cells (hMSCs) undergo senescence in lifespan. In most clinical trials, hMSCs experience long-term expansion ex vivo to increase cell number prior to transplantation, which unfortunately leads to cell senescence, hampering post-transplant outcomes. Hydrogen peroxide (H2O2) in vitro represents a rapid, time and cost-effective tool, commonly used as oxidative stress tantalizing the stem cell ability to cope with a hostile environment, recapitulating the onset and progression of cellular senescence. Here, H2O2 at different concentrations (ranging from 50 to 400 µM) and time exposures (1 or 2 hours - h), was used for the first time to compare the behavior of human Adipose tissue-derived Stem Cells (hASCs) and human Wharton's Jelly-derived MSCs (hWJ-MSCs), as representative of adult and perinatal tissue-derived stem cells, respectively. We showed timely different responses of hASCs and hWJ-MSCs at low and high subculture passages, concerning the cell proliferation, the cell senescence-associated ß-Galactosidase activity, the capability of these cells to undergo passages, the morphological changes and the gene expression of tumor protein p53 (TP53, alias p53) and cyclin dependent kinase inhibitor 1A (CDKN1A, alias p21) post H2O2 treatments. The comparison between the hASC and hWJ-MSC response to oxidative stress induced by H2O2 is a useful tool to assess the biological mechanisms at the basis of hMSC senescence, but it could also provide two models amenable to test in vitro putative anti-senescence modulators and develop anti-senescence strategies.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Senescência Celular/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Células Cultivadas , Humanos , Peróxido de Hidrogênio/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Geleia de Wharton/citologia , beta-Galactosidase/metabolismo
16.
Int J Med Sci ; 15(14): 1631-1639, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30588186

RESUMO

Melatonin, that regulates many physiological processes including circadian rhythms, is a molecule able to promote osteoblasts maturation in vitro and to prevent bone loss in vivo, while regulating also adipocytes metabolism. In this regard, we have previously shown that melatonin in combination with vitamin D, is able to counteract the appearance of an adipogenic phenotype in adipose derived stem cells (ADSCs), cultured in an adipogenic favoring condition. In the present study, we aimed at evaluating the specific phenotype elicited by melatonin and vitamin D based medium, considering also the involvement of epigenetic regulating genes. ADSCs were cultured in a specific adipogenic conditioned media, in the presence of melatonin alone or with vitamin D. The expression of specific osteogenic related genes was evaluated at different time points, together with the histone deacetylases epigenetic regulators, HDAC1 and Sirtuins (SIRT) 1 and 2. Our results show that melatonin and vitamin D are able to modulate ADSCs commitment towards osteogenic phenotype through the upregulation of HDAC1, SIRT 1 and 2, unfolding an epigenetic regulation in stem cell differentiation and opening novel strategies for future therapeutic balancing of stem cell fate toward adipogenic or osteogenic phenotype.


Assuntos
Diferenciação Celular/genética , Epigênese Genética/fisiologia , Melatonina/metabolismo , Células-Tronco/fisiologia , Vitamina D/metabolismo , Adipócitos/fisiologia , Adipogenia/genética , Tecido Adiposo/citologia , Adulto , Células Cultivadas , Histona Desacetilase 1/metabolismo , Humanos , Pessoa de Meia-Idade , Osteoblastos/fisiologia , Osteogênese/genética , Cultura Primária de Células , Sirtuína 1/metabolismo , Sirtuína 2/metabolismo , Regulação para Cima
17.
J Obstet Gynaecol Can ; 40(6): 726-749.e10, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-28988744

RESUMO

Endometriosis management seems to be influenced by outcome-independent biomedical, pharmacological, and technological developments. The propensity towards doing more affects several aspects of care, sometimes translating into proposals that are not based on sound epidemiological principles and robust evidence. Different stakeholders share the interest for doing more testing and using novel and costly drugs or devices in patients with endometriosis. Although some women may benefit from such an approach, the majority do not, and some may be harmed. Moreover, an uncontrolled increase in expenditures for endometriosis management without demonstrated and proportional health benefits would waste the finite resources of national health care services and would risk cost-related non-adherence. Cost-effectiveness analyses should be systematically pre-planned in future trials on endometriosis, and the concept of "value" of medical interventions should guide investigators and health care policymakers. Reducing low-value care, financial toxicity, and the burden of treatment is respectful not only of endometriosis patients, but also of the entire society. Whenever possible, long-term therapeutic strategies should be tailored to each woman's needs, and high-value tests and treatments should be chosen based on her priorities and preferences. Moreover, listening to patients, understanding their concerns, avoiding disease labelling, explaining plainly what is known and what is unknown, and giving constant reassurance and encouragement may be exceedingly important for the successful management of endometriosis and may change the patient's perception of her clinical condition. Physician empathy has no untoward effects, does not cause harms, and may determine whether a woman successfully copes or desperately struggles with her disease during reproductive life.


Assuntos
Análise Custo-Benefício , Custos e Análise de Custo , Endometriose/terapia , Adolescente , Conflito de Interesses , Endometriose/diagnóstico , Endometriose/fisiopatologia , Feminino , Fertilização in vitro , Prioridades em Saúde , Terapia de Reposição Hormonal , Humanos , Infertilidade Feminina/terapia , Menopausa , Neoplasias Ovarianas/prevenção & controle , Ovariectomia , Manejo da Dor , Preferência do Paciente , Resultado do Tratamento
18.
Molecules ; 23(2)2018 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-29385685

RESUMO

In this review, we described different factors that modulate pluripotency in stem cells, in particular we aimed at following the steps of two large families of miRNAs: the miR-200 family and the miR-302 family. We analyzed some factors tuning stem cells behavior as TGF-ß, which plays a pivotal role in pluripotency inhibition together with specific miRNAs, reactive oxygen species (ROS), but also hypoxia, and physical stimuli, such as ad hoc conveyed electromagnetic fields. TGF-ß plays a crucial role in the suppression of pluripotency thus influencing the achievement of a specific phenotype. ROS concentration can modulate TGF-ß activation that in turns down regulates miR-200 and miR-302. These two miRNAs are usually requested to maintain pluripotency, while they are down-regulated during the acquirement of a specific cellular phenotype. Moreover, also physical stimuli, such as extremely-low frequency electromagnetic fields or high-frequency electromagnetic fields conveyed with a radioelectric asymmetric conveyer (REAC), and hypoxia can deeply influence stem cell behavior by inducing the appearance of specific phenotypes, as well as a direct reprogramming of somatic cells. Unraveling the molecular mechanisms underlying the complex interplay between externally applied stimuli and epigenetic events could disclose novel target molecules to commit stem cell fate.


Assuntos
Epigênese Genética/fisiologia , MicroRNAs/metabolismo , Células-Tronco Pluripotentes/metabolismo , Animais , Humanos , MicroRNAs/genética , Células-Tronco Pluripotentes/citologia
19.
Acta Obstet Gynecol Scand ; 96(6): 668-687, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27687240

RESUMO

INTRODUCTION: Endometriosis is associated with an increased risk of dyspareunia, therefore this chronic gynecologic disease should be considered as a major cause of sexual dysfunctions. The aims of this study were to review the literature on the effects of surgical and pharmacological treatments for endometriosis on female sexual functioning, and to provide suggestions for future treatment strategies. MATERIAL AND METHODS: We followed the PRISMA guidelines to conduct this systematic review, which involved an electronic database search of studies on the association between endometriosis and sexuality published between 2000 and 2016. RESULTS: As a result of the screening process, 22 studies were included in this systematic review. The 22 studies included were divided into two categories: (a) surgical intervention studies (n = 17), examining postoperative sexual outcomes of surgery for endometriosis; (b) pharmacological intervention studies (n = 5), evaluating the effects of pharmacological endometriosis treatments on sexual functioning. The studies considered showed that overall surgical and pharmacological interventions for endometriosis can lead to medium-/long-term improvement, but not necessarily to a definitive resolution of female sexual dysfunctions due to endometriosis. CONCLUSIONS: Sexual functioning is a multidimensional phenomenon and the ideal treatment for endometriosis-related sexual dysfunctions should be conducted by a multidisciplinary team that involves not only gynecologists, but also sexologists and psychologists/psychotherapists. Improving global sexual functioning, and not just reducing pain at intercourse, should be considered as a major clinical goal of endometriosis treatment.


Assuntos
Endometriose/cirurgia , Comportamento Sexual/estatística & dados numéricos , Disfunções Sexuais Fisiológicas/terapia , Endometriose/complicações , Feminino , Humanos , Dor Pélvica/etiologia , Disfunções Sexuais Fisiológicas/etiologia , Doenças Vaginais/complicações , Saúde da Mulher
20.
Hum Reprod ; 31(7): 1515-21, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27165626

RESUMO

STUDY QUESTION: Is pelvic pain due to endometriosis associated with temperament and character dimensions? SUMMARY ANSWER: Women with endometriosis and pelvic pain do not clearly exhibit a specific personality profile; however, personality is associated with pelvic pain perception. WHAT IS KNOWN ALREADY: There is research evidence suggesting that endometriosis patients with pelvic pain are more likely to present psychological disruption. Little is known about the association between subjective factors, such as personality traits, and pelvic pain. STUDY DESIGN, SIZE, DURATION: This cross-sectional study (N = 133) is part of a larger research on the association between endometriosis and several psychological variables carried out between 2012 and 2014. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: The participants were 82 endometriosis patients and 51 healthy controls. Endometriosis patients indicated on a dichotomous scale (yes/no) whether they were suffering from pelvic pain and were divided in two study groups: painful endometriosis group (N = 58) and pain-free endometriosis group (N = 24). The severity of pelvic pain (chronic pelvic pain, dysmenorrhoea, dyspareunia, and dyschezia) was rated on a 0-10 point numerical rating scale. All participants completed a 240-item psychometric test (TCI-R) evaluating personality in terms of temperament and character dimensions. MAIN RESULTS AND THE ROLE OF CHANCE: Women with painful endometriosis had lower novelty seeking compared with the control group (P = 0.017) and higher harm avoidance (P = 0.007) and lower exploratory excitability (P = 0.034) and responsibility (P = 0.027) compared with the pain-free endometriosis group, as well as higher fatigability compared with the pain-free endometriosis group (P = 0.001) and the control group (P = 0.032). Higher harm avoidance (B = 0.081; P = 0.002) and lower self-directedness (B = -0.053; P = 0.015) were associated with a greater severity of chronic pelvic pain. LIMITATIONS, REASONS FOR CAUTION: These study findings should be taken cautiously for several methodological reasons such as small sample size, differences in group sizes and cultural homogeneity. More research is needed to further investigate the association between personality and pelvic pain related to endometriosis. WIDER IMPLICATIONS OF THE FINDINGS: Our findings suggest new avenues for future research and treatment of endometriosis. The association between the severity of chronic pelvic pain and personality may help clarify the lack of a direct correlation between pain severity and the type and stage of endometriosis, as well as the inconsistencies in patients' response to medical and/or surgical treatment. Therapeutic strategies should be specifically targeted on individual women and involve an integrated approach to the treatment of chronic pelvic pain related to endometriosis. STUDY FUNDING/COMPETING INTERESTS: There was no external funding for this study and the authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: Not applicable to this study.


Assuntos
Endometriose/complicações , Percepção da Dor , Dor/etiologia , Personalidade , Feminino , Humanos , Dor/psicologia , Medição da Dor
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