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1.
F S Sci ; 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38945479

RESUMO

The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of Defense, or the United States Government. This symposium was supported by Sumitomo Pharma. However, the authors received no support for the creation of this manuscript, and the manuscript was created, revised and submitted solely by the authors recognized above.

2.
Health Psychol Res ; 12: 120055, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38915786

RESUMO

Objective: The present study investigated the effectiveness of a Dragon Boat training program in women with breast cancer body image and traumatic distress processing. Methods: 29 breast cancer patients (M(SD) age= 51 (7.41)) voluntarily participated in a physical activity program. Seventeen (Intervention Group) enrolled in a Dragon Boat racing program, while 12 (the Control Group) individually performed alternative physical activities. Before and after the intervention, patients completed the Body Image Scale (BIS) and the Impact of Event Scale - Revised (IES-R). Results: The Intervention Group reported a decrease in Body Image negative perception (Pillai's trace = .352, F(1,27) = 14.111, p = .001; partial η2 = .951) and in traumatic symptoms (Pillai's trace = .283, F(1,27) = 10.682, p = .003; partial η2 = .883). Conclusions: Authors discuss the role of Dragon Boat racing in improving positive body image after the experience of breast cancer.

3.
Neurotherapeutics ; 21(3): e00346, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38493058

RESUMO

Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease influenced by genetic, epigenetic, and environmental factors, resulting in dysfunction in cellular and molecular pathways. The limited efficacy of current treatments highlights the need for combination therapies targeting multiple aspects of the disease. Niclosamide, an anthelminthic drug listed as an essential medicine, has been repurposed in clinical trials for different diseases due to its anti-inflammatory and anti-fibrotic properties. Niclosamide can inhibit various molecular pathways (e.g., STAT3, mTOR) that are dysregulated in ALS, suggesting its potential to disrupt these altered mechanisms associated with the pathology. We administered niclosamide intraperitoneally to two transgenic murine models, SOD1-G93A and FUS mice, mimicking key pathological processes of ALS. The treatment was initiated at the onset of symptoms, and we assessed disease progression by neurological scores, rotarod and wire tests, and monitored survival. Furthermore, we investigated cellular and molecular mechanisms affected by niclosamide in the spinal cord and muscle of ALS mice. In both models, the administration of niclosamide resulted in a slowdown of disease progression, an increase in survival rates, and an improvement in tissue pathology. This was characterised by reduced gliosis, motor neuron loss, muscle atrophy, and inflammatory pathways. Based on these results, our findings demonstrate that niclosamide can impact multiple pathways involved in ALS. This multi-targeted approach leads to a slowdown in the progression of the disease, positioning niclosamide as a promising candidate for repurposing in the treatment of ALS.


Assuntos
Esclerose Lateral Amiotrófica , Progressão da Doença , Fármacos Neuroprotetores , Niclosamida , Animais , Camundongos , Esclerose Lateral Amiotrófica/tratamento farmacológico , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/patologia , Modelos Animais de Doenças , Inflamação/tratamento farmacológico , Camundongos Transgênicos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Niclosamida/farmacologia , Niclosamida/uso terapêutico , Proteína FUS de Ligação a RNA/genética , Proteína FUS de Ligação a RNA/metabolismo , Superóxido Dismutase-1/genética , Superóxido Dismutase-1/metabolismo
4.
Reprod Biomed Online ; 48(4): 103737, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38342076

RESUMO

Endometriosis and adenomyosis are distinct clinical conditions that carry the same pathophysiological features. In recent years the clinical focus on assisted reproductive technology patients with either condition (E/A) has increased, in the recognition that this subgroup of patients might need special attention to obtain reproductive success. Endometriosis and adenomyosis are characterized by a disruption of progesterone and oestrogen signalling pathways, resulting in local oestrogen dominance and progesterone resistance at the receptor level. Recent scientific evidence suggests that the endometrial progesterone receptor resistance encountered in E/A patients can be overcome by a freeze-all policy, followed by down-regulating circulating oestradiol concentrations prior to frozen embryo transfer (FET), in combination with an increase in exogenous luteal phase progesterone supplementation in hormonal replacement therapy (HRT) FET cycles. Specifically, for adenomyosis patients who do not respond to gonadotrophin-releasing hormone agonist down-regulation in terms of a decrease in circulating oestradiol concentrations, a small case series has suggested that the addition of an aromatase inhibitor for 21 days prior to HRT-FET is a valid option. Endometriosis and adenomyosis are hormonally active diseases, which need to be treated by controlling local hyperoestrogenism and progesterone resistance. Based on physiology and recent preliminary clinical data, the authors of this opinion paper wish to stimulate discussion and spark interest in research in E/A patients.


Assuntos
Adenomiose , Endometriose , Endométrio/anormalidades , Doenças Uterinas , Feminino , Humanos , Progesterona , Endometriose/tratamento farmacológico , Adenomiose/tratamento farmacológico , Estrogênios , Estradiol , Técnicas de Reprodução Assistida , Fertilização in vitro , Estudos Retrospectivos
5.
Fertil Steril ; 121(3): 480-488, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38043844

RESUMO

OBJECTIVE: To prospectively examine the association between adenomyosis type, location, and severity with reproductive outcomes in patients undergoing single embryo transfer (SET) with embryos derived from donor oocytes. DESIGN: A prospective observational cohort study. SETTING: University-affiliated in vitro fertilization center. PATIENTS: Patients with infertility with (n = 114) and without (n = 114) adenomyosis who received their first donor oocyte transfer between January 2019 and January 2023 were included in this study. INTERVENTIONS: Adenomyosis was confirmed with the presence of at least one direct feature visualized by 2- or 3-dimensional transvaginal ultrasound and classified according to type (diffuse or focal), localization (inner or outer myometrium and/or junctional zone [JZ]), and uterine extension (mild, moderate, or severe). After an artificial or natural endometrial preparation cycle, patients underwent SET in the blastocyst stage. MAIN OUTCOME MEASURES: The primary outcome was the implantation rate. The secondary outcomes were the clinical pregnancy, live birth, and miscarriage rates after SET. RESULTS: The presence of adenomyosis did not significantly affect the implantation, clinical pregnancy, or live birth rates. However, women with adenomyosis had a significantly higher miscarriage rate than those without adenomyosis (35.4% vs. 18.1%, respectively). The multivariate analysis assessed possible risk factors for each clinical outcome considered in the study and showed that adenomyosis affected the risk of miscarriage. Specifically, transvaginal sonography detection of adenomyosis in the JZ was associated with over threefold higher relative risk of miscarriage (relative risk [RR], 3.28; 95% confidence interval [CI], 1.38-7.78). Conversely, adenomyosis features detected exclusively in the outer myometrium were associated with a higher ongoing pregnancy rate (RR, 0.30; 95% CI, 0.13-0.72). Diffuse adenomyosis in the JZ and severe adenomyosis increased the relative risk of miscarriage two-fold (RR, 2.29; 95% CI, 1.22-4.30 and RR, 2.20; 95% CI, 1.19-4.04, respectively). CONCLUSIONS: This study demonstrated that although adenomyosis did not significantly reduce the odds of implantation, the direct signs of adenomyosis in the JZ and disease severity are significant risk factors for miscarriage in patients receiving donor oocyte transfers. This study highlights the importance of thorough ultrasound examination and detailed adenomyosis classification in the assessment and management of patients with infertility.


Assuntos
Aborto Espontâneo , Adenomiose , Infertilidade , Gravidez , Humanos , Feminino , Adenomiose/diagnóstico por imagem , Adenomiose/terapia , Aborto Espontâneo/epidemiologia , Aborto Espontâneo/etiologia , Estudos Prospectivos , Fertilização in vitro/efeitos adversos , Taxa de Gravidez , Nascido Vivo , Infertilidade/diagnóstico , Infertilidade/terapia , Oócitos , Estudos Retrospectivos
6.
J Clin Med ; 12(21)2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-37959232

RESUMO

Ovarian endometriosis is a gynecological condition that is closely associated with infertility-from its pathogenesis to treatment modalities, this condition presents a challenge both for patients and clinicians alike when seeking conception, due to low AMH levels, peritoneal inflammation, and the inadvertent removal of healthy ovarian parenchyma at surgery. In fact, around half of endometriosis patients seeking fertility require tertiary-level assisted reproduction techniques to achieve a live birth. Oocyte cryopreservation, a procedure initially designed for oncology patients, has emerged over recent years as a very promising treatment strategy for patients who have been diagnosed with ovarian endometriosis in order to preserve their fertility and obtain a live birth at a later stage in their lives. Counseling patients about oocyte preservation techniques at an early stage in the diagnosis, ideally before the age of 35 and especially prior to any surgical treatment, provides an excellent opportunity to discuss future fertility and the benefits associated with oocyte cryopreservation.

7.
Hum Reprod ; 38(8): 1621-1627, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37336546

RESUMO

STUDY QUESTION: What is the potential impact of preimplantation genetic testing for aneuploidy (PGT-A) on obstetric and neonatal outcomes? SUMMARY ANSWER: PGT-A is not associated with increased rates of adverse maternal and neonatal outcomes in singleton pregnancies following IVF/ICSI cycles. WHAT IS KNOWN ALREADY: PGT-A pregnancies may be associated with increased risks of lower birthweight, preterm delivery, and hypertensive disorders compared with natural pregnancies. In a recent meta-analysis, the overall obstetric and neonatal outcomes of PGT-A pregnancies were favorable compared with those of IVF/ICSI pregnancies, although PGT-A pregnancies were associated with a higher risk of hypertensive disorders. STUDY DESIGN, SIZE, DURATION: A multicenter retrospective cohort study was performed in University-affiliated infertility centers. Single live births following IVF/ICSI between October 2016 and January 2021 were included in the study. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 7146 live births after single embryo transfers with (n = 3296) or without (n = 3850) PGT-A were included. The primary outcome was pre-eclampsia and secondary outcomes included gestational diabetes, low birthweight and very low birthweight, cesarean section delivery, emergency cesarean section, as well as preterm birth, birthweight, congenital abnormalities, neonatal sex, Apgar score at 5 min, and neonatal intensive care unit admission. In a subgroup analysis, were included only blastocysts screened with next-generation sequencing (NGS). MAIN RESULTS AND THE ROLE OF CHANCE: Univariate analysis showed that pre-eclampsia, cesarean section incidence, and low Apgar score were higher in women undergoing PGT-A. However, after performing multivariate logistic and linear regression models accounting for many possible confounders, pregnancies that had been conceived after embryo biopsy showed no increase in adverse obstetric and neonatal outcomes. The subgroup analysis including patients with blastocysts screened by NGS showed a decreased risk of preterm birth in the group undergoing PGT-A. LIMITATIONS, REASONS FOR CAUTION: Caution should be used when interpreting the data because of its limitations, mainly related to its retrospective design. Although this is a large multicenter study, data acquisition included self-reporting questionnaires, and the deliveries occurred in different institutions with distinct protocols. WIDER IMPLICATIONS OF THE FINDINGS: The current study does not show any major adverse clinical outcomes after PGT-A. Efforts should be made to promote good quality research on embryo biopsy in terms of neonatal and obstetric outcomes, as well as its long-term consequences. STUDY FUNDING/COMPETING INTEREST(S): No specific funding was obtained for this study. The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.


Assuntos
Aneuploidia , Testes Genéticos , Resultado da Gravidez , Feminino , Humanos , Recém-Nascido , Gravidez , Testes Genéticos/métodos , Resultado da Gravidez/epidemiologia , Estudos Retrospectivos , Medição de Risco , Masculino
10.
Reprod Biomed Online ; 46(1): 150-155, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36402667

RESUMO

RESEARCH QUESTION: Does aromatase inhibitor improve IVF outcomes by reducing local oestrogen production in patients with adenomyosis undergoing long-term gonadotrophin-releasing hormone agonist (GnRHa) treatment? DESIGN: Four patients with severe adenomyosis who failed to improve after long-term treatment (≥3 months) with depot GnRHa received treatment with an aromatase inhibitor for 21 days. Blood oestradiol concentrations were monitored after GnRHa treatment both before and after treatment with an aromatase inhibitor. Women received a transfer of IVF autologous or donor oocytes. Pregnancy and ongoing pregnancy rates were the primary outcomes. Blood oestradiol concentration after treatment with an aromatase inhibitor was a secondary outcome. RESULTS: Patients with severe adenomyosis presented with hyperestrogenism due to local production from the lesions even after long-term treatment with GnRHa. Treatment with an aromatase inhibitor reduced hyperestrogenism and improved clinical outcomes in adenomyosis patients who have experienced previous embryo transfer failures. CONCLUSION: Women with severe adenomyosis would benefit from letrozole or a combination of GnRHa plus letrozole before receipt of treatment with assisted reproductive technology. For women with severe adenomyosis, GnRHa treatment alone may be insufficient to suppress oestrogen production by adenomyotic lesions. Thus, it should be mandatory to test for oestradiol concentrations in patients with severe adenomyosis who have received long-term GnRHa treatment. Also, GnRHa may not always be the sole strategy for medical management of adenomyotic lesions. Letrozole is safe and can improve IVF outcomes for patients with adenomyosis.


Assuntos
Adenomiose , Hormônio Liberador de Gonadotropina , Gravidez , Humanos , Feminino , Letrozol/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Adenomiose/tratamento farmacológico , Indução da Ovulação , Taxa de Gravidez , Estrogênios , Estradiol , Fertilização in vitro
11.
Endocrine ; 79(1): 200-207, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36149529

RESUMO

PURPOSE: In this study, we investigated whether metabolic dysfunction in women with Polycystic ovarian syndrome (PCOS) induces granulosa cell (GC) stress and activates in the endoplamatic reticulum and the mitochondria (UPRer and UPRmt, respectively). METHODS: Women who were diagnosed with PCOS (based on the Rotterdam criteria), were divided into two groups, PCOS with insulin resistance (PCOS-IR; n = 20) and PCOS with no insulin resistance (PCOS-nIR; n = 20), and compared to healthy oocyte donors (CONT; n = 20). Insulin resistance (IR) was assessed on the results of homeostasis model assessment (HOMA) that determines IR using the concentration of fasting plasma glucose and fasting insuline. Expression of UPRer genes (i.e., IRE1, ATF4, ATF6, XBP1, BIP, and CHOP), and UPRmt genes (i.e., HSP60, HSP10, CLPP, and HSP40) was assessed in cumulus GCs by qRT-PCR. RESULTS: We found that several genes involved in UPRer and UPRmt were overexpressed in the GCs of PCOS-IR and PCOS-nIR compared to CONT. IRE1, ATF4 and XBP1, that are activated by ER stress, were significantly overexpressed in PCOS-IR compared to CONT. BIP and CHOP were overexpressed in PCOS groups compared to CONT. HSP10 and HSP40 were upregulated in PCOS-IR and PCOS-nIR groups compared to the CONT. HSP60 and CLPP showed no statistical different expression in PCOS-IR and PCOS-nIR compared to CONT group. CONCLUSION: Our findings suggest that the GCs of women with PCOS (with or without IR) are metabolically distressed and upregulate UPRer and UPRmt genes. Our study contributes to the understanding of the molecular mechanisms underlying the pathological changes that occur in the follicular microenvironment of women with PCOS.


Assuntos
Resistência à Insulina , Síndrome do Ovário Policístico , Humanos , Feminino , Síndrome do Ovário Policístico/metabolismo , Células da Granulosa/metabolismo , Resistência à Insulina/fisiologia , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Microambiente Tumoral
12.
Reprod Biomed Online ; 46(1): 99-106, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36229390

RESUMO

RESEARCH QUESTION: Do patients with adenomyosis present a dysregulated endometrial receptivity that can be reversed with personalized embryo transfer (PET) by transcriptomic-based progesterone adjustment, improving IVF outcomes? DESIGN: A multicentre, retrospective, cohort study that transcriptomically analysed the endometrial receptivity of the endometrium in patients with adenomyosis (n = 81) and healthy women (n = 231). Subsequently, implantation, biochemical and clinical miscarriage, and live birth rates between adenomyosis patients with one previous implantation failure using donor oocytes who received (n = 59) or did not receive (n = 66) PET based on endometrial receptivity, were observed to evaluate if adjusted progesterone improves reproductive outcomes of adenomyosis patients. RESULTS: Patients with adenomyosis significantly presented an altered endometrial receptivity (non-receptive) compared with healthy patients (53.1% versus 37.2%, P = 0.0179), elevating the risk of adenomyosis patients having a non-receptive endometrium 42.59% higher (95% CI 41.50 to 44.45). No significant differences were found in implantation (62.7% versus 78.8%, P = 0.0514), biochemical (13.5% versus 3.9%, P = 0.1223) and clinical (10.8% versus 15.4%, P = 0.7543) miscarriage, or live birth rates (75.7% versus 80.8%, P = 0.6066), in patients with PET compared with those without PET. CONCLUSIONS: Women with adenomyosis presented an altered expression of genes involved in decidualization, and a higher rate of non-receptive endometrial statuses than controls. Although progesterone is indispensable for implantation, adjusting progesterone before PET, using endometrial transcriptomic signatures, does not improve IVF outcomes in patients with adenomyosis. Other molecular mechanisms beyond progesterone regulation may be involved in implantation failure.


Assuntos
Aborto Espontâneo , Adenomiose , Gravidez , Humanos , Feminino , Progesterona/metabolismo , Transcriptoma , Estudos Retrospectivos , Estudos de Coortes , Adenomiose/complicações , Adenomiose/tratamento farmacológico , Adenomiose/genética , Implantação do Embrião/fisiologia , Endométrio/metabolismo
13.
Artigo em Inglês | MEDLINE | ID: mdl-35954972

RESUMO

This study explored the experience of growth related to being a cancer patient by implementing a thematic analysis. An online questionnaire was completed by 69 patients narrating their growth experience related to cancer. Collected narratives were analyzed by running a deductive thematic analysis, starting from the five domains of the Post-Traumatic Growth Inventory (PTGI) and searching for the presence or absence of topics. Descriptive statistics and correlational analysis were performed. The five factors of the PTGI were identified in the narratives. The thematic analysis we performed defined a further theme that we labeled the "time dimension", which saturated 37.7% of the entire sample. The presences of four sub-themes related to the "time dimension" were also found: "tracing a new temporal rhythm", "the value of deserved time", "facing the caducity of life" and "a view on the future". Each sub-theme significantly correlated with the theme of the "time dimension". This emergent theme does not correlate in our results with other domains of personal growth in cancer previously described in the scientific literature, emerging as an independent variable not significantly associated with other domains of post-traumatic growth. Our results suggest further investigation in the role of the time dimension in the practical and emotional experience of growth with regard to cancer.


Assuntos
Neoplasias , Crescimento Psicológico Pós-Traumático , Transtornos de Estresse Pós-Traumáticos , Adaptação Psicológica , Emoções , Humanos , Neoplasias/psicologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Inquéritos e Questionários
14.
Hum Reprod ; 37(6): 1274-1286, 2022 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-35451009

RESUMO

STUDY QUESTION: Are transcriptomic profiles altered in ovarian granulosa cells (GCs) and peripheral blood mononuclear cells (PBMNCs) of women with polycystic ovary syndrome (PCOS) compared to young poor responders (YPR) and women with normal response to ovarian stimulation? SUMMARY ANSWER: RNA expression profiles in ovarian GCs and PBMNCs were significantly altered in patients with PCOS compared with normoresponder controls (CONT) and YPR. WHAT IS KNOWN ALREADY: PCOS is characterised by a higher number of follicles at all developmental stages. During controlled ovarian hyperstimulation, PCOS women develop a larger number of follicles as a result of an exacerbated response, with an increased risk of ovarian hyperstimulation syndrome. Despite the number of developing follicles, they are often heterogeneous in both size and maturation stage, with compromised quality and retrieval of immature oocytes. Women with PCOS appear to have a longer reproductive lifespan, with a slightly higher menopausal age than the general population, in addition to having a higher antral follicular count. As a result, the ovarian follicular dynamics appear to differ significantly from those observed in women with poor ovarian response (POR) or diminished ovarian reserve. STUDY DESIGN, SIZE, DURATION: Transcriptomic profiling with RNA-sequencing and validation using quantitative reverse transcription PCR (qRT-PCR). Women with PCOS (N = 20), YPR (N = 20) and CONT (N = 20). Five patients for each group were used for sequencing and 15 samples per group were used for validation. PARTICIPANTS/MATERIALS, SETTING, METHODS: PCOS was defined using the revised Rotterdam diagnostic criteria for PCOS. The YPR group included women <35 years old with <4 mature follicles (at least 15 mm) on the day of the trigger. According to internal data, this group represented the bottom 15th percentile of patients' responses in this age group. It was consistent with Patient-Oriented Strategies Encompassing Individualize D Oocyte Number (POSEIDON) criteria for POR (Group 3). The young CONT group included women <35 years without PCOS or anovulation, who developed >14 mature follicles (at least 15 mm on transvaginal ultrasound). According to internal data, a threshold of >14 mature follicles was established to represent the top 25% of patients in this age group in this clinic.Overall, n = 60 GCs and PBMNCs samples were collected and processed for total RNA extraction. To define the transcriptomic cargo of GCs and PBMNCs, RNA-seq libraries were successfully prepared from samples and analysed by RNA-seq analysis. Differential gene expression analysis was used to compare RNA-seq results between different groups of samples. Ingenuity pathway analysis was used to perform Gene Ontology and pathways analyses. MAIN RESULTS AND THE ROLE OF CHANCE: In PBMNCs of PCOS, there were 65 differentially expressed genes (DEGs) compared to CONT, and 16 compared to YPR. In GCs of PCOS, 4 genes showed decreased expression compared to CONT, while 58 genes were differentially expressed compared to YPR. qRT-PCR analysis confirmed the findings of the RNA-seq. The functional enrichment analysis performed revealed that DEGs in GCs of PCOS compared to CONT and YPR were prevalently involved in protein ubiquitination, oxidative phosphorylation, mitochondrial dysfunction and sirtuin signaling pathways. LARGE SCALE DATA: The data used in this study is partially available at Gene Ontology database. LIMITATIONS, REASONS FOR CAUTION: The analysis in PBMNCs could be uninformative due to inter-individual variability among patients in the same study groups. Despite the fact that we considered this was the best approach for our study's novel, exploratory nature. WIDER IMPLICATIONS OF THE FINDINGS: RNA expression profiles in ovarian GCs and PBMNCs were altered in patients with PCOS compared with CONT and YPR. GCs of PCOS patients showed altered expression of several genes involved in oxidative phosphorylation, mitochondrial function and sirtuin signaling pathways. This is the first study to show that the transcriptomic landscape in GCs is altered in PCOS compared to CONT and YPR. STUDY FUNDING/COMPETING INTEREST(S): This study was partially supported by grant PI18/00322 from Instituto de Salud Carlos III, and European Regional Development Fund (FEDER), 'A way to make Europe' awarded to S.H. M.C., S.H., S.T., L.R., M.R., I.R., A.P. and R.C. declare no conflict of interests concerning this research. E.S. is a consultant for and receives research funding from the Foundation for Embryonic Competence. TRIAL REGISTRATION NUMBER: N/A.


Assuntos
Síndrome do Ovário Policístico , Sirtuínas , Feminino , Células da Granulosa , Humanos , Leucócitos Mononucleares , Síndrome do Ovário Policístico/genética , RNA , Transcriptoma
15.
Reprod Sci ; 29(11): 3177-3193, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-34981458

RESUMO

To investigate the impact of uterine adenomyosis on in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) clinical outcomes and also to evaluate the impact of gonadotropin-releasing hormone agonist (GnRHa) and surgical treatments. Infertile women with adenomyosis undergoing conventional IVF or ICSI were compared with women without adenomyosis. Fertility outcomes were evaluated in two patients with adenomyosis untreated and treated surgically or medically therapy. The review protocol was registered in PROSPERO (CRD42020214586). We consider the live birth rate (LBR) as the primary outcome. The analysis showed that women with adenomyosis had lower LBR (OR 0.59, 95% CI 0.37-0.92, p = 0.02), clinical pregnancy rate (OR 0.66, 95% CI 0.48-0.90), and ongoing pregnancy rate (OR 0.43, 95% CI 0.21-0.88) compared to those without adenomyosis, and miscarriage rate was higher in women with adenomyosis (OR 2.11, 95% CI 1.33-3.33). Surgical treatment increases natural conception in women with adenomyosis although the paucity of data (only two studies), and conversely, treatment with GnRHa does not increase the IVF outcomes. Women with adenomyosis have decreased IVF clinical outcomes. Pretreatment with the use of long-term GnRHa could not be beneficial, even though only three studies were included in the meta-analysis. The major part of the studies has not divided focal and diffuse adenomyosis, and this represents a relevant source of bias: studies conducted with standardized diagnostic criteria for adenomyosis are still needed to determine if the different clinical presentations of such condition could compromise IVF outcomes.


Assuntos
Adenomiose , Infertilidade Feminina , Gravidez , Humanos , Masculino , Feminino , Adenomiose/complicações , Adenomiose/terapia , Infertilidade Feminina/etiologia , Infertilidade Feminina/terapia , Sêmen , Taxa de Gravidez , Fertilização in vitro
16.
Am J Clin Hypn ; 64(2): 123-138, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34723776

RESUMO

The psychosocial genomics paradigm first proposed by Ernest Rossi established an epistemological shift in our application of hypnosis. We present original experimental research conducted within this paradigm that highlights the mind-gene relationship and, in particular, the positive health effects associated with hypnosis and mind-body integrated psychotherapy. We document that these approaches can stimulate epigenetic modifications and the expression of genes related to anti-inflammatory processes. These strategies strengthen the immune system and reduce oxidative stress both in normal and in oncological participants.


Assuntos
Hipnose , Genômica , Humanos , Psicoterapia
17.
J Neuroinflammation ; 18(1): 132, 2021 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-34118929

RESUMO

BACKGROUND: An increasing number of studies evidences that amyotrophic lateral sclerosis (ALS) is characterized by extensive alterations in different cell types and in different regions besides the CNS. We previously reported the upregulation in ALS models of a gene called fibroblast-specific protein-1 or S100A4, recognized as a pro-inflammatory and profibrotic factor. Since inflammation and fibrosis are often mutual-sustaining events that contribute to establish a hostile environment for organ functions, the comprehension of the elements responsible for these interconnected pathways is crucial to disclose novel aspects involved in ALS pathology. METHODS: Here, we employed fibroblasts derived from ALS patients harboring the C9orf72 hexanucleotide repeat expansion and ALS patients with no mutations in known ALS-associated genes and we downregulated S100A4 using siRNA or the S100A4 transcriptional inhibitor niclosamide. Mice overexpressing human FUS were adopted to assess the effects of niclosamide in vivo on ALS pathology. RESULTS: We demonstrated that S100A4 underlies impaired autophagy and a profibrotic phenotype, which characterize ALS fibroblasts. Indeed, its inhibition reduces inflammatory, autophagic, and profibrotic pathways in ALS fibroblasts, and interferes with different markers known as pathogenic in the disease, such as mTOR, SQSTM1/p62, STAT3, α-SMA, and NF-κB. Importantly, niclosamide in vivo treatment of ALS-FUS mice reduces the expression of S100A4, α-SMA, and PDGFRß in the spinal cord, as well as gliosis in central and peripheral nervous tissues, together with axonal impairment and displays beneficial effects on muscle atrophy, by promoting muscle regeneration and reducing fibrosis. CONCLUSION: Our findings show that S100A4 has a role in ALS-related mechanisms, and that drugs such as niclosamide which are able to target inflammatory and fibrotic pathways could represent promising pharmacological tools for ALS.


Assuntos
Esclerose Lateral Amiotrófica/tratamento farmacológico , Niclosamida/farmacologia , Niclosamida/uso terapêutico , Proteína A4 de Ligação a Cálcio da Família S100/antagonistas & inibidores , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/metabolismo , Animais , Animais Geneticamente Modificados , Modelos Animais de Doenças , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibrose/tratamento farmacológico , Fibrose/prevenção & controle , Humanos , Inflamação/tratamento farmacológico , Inflamação/prevenção & controle , Camundongos , Mutação , NF-kappa B/metabolismo , Proteína FUS de Ligação a RNA/genética , Proteína A4 de Ligação a Cálcio da Família S100/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo
18.
J Assist Reprod Genet ; 38(7): 1799-1807, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33851314

RESUMO

OBJECTIVE: To investigate whether minimal ovarian stimulation (mOS) is as effective as conventional ovarian stimulation (cOS) for older women belonging to different groups according to the Poseidon criteria. MATERIAL AND METHODS: Observational retrospective multicentre cohort including women from Poseidon's groups 2 and 4 that underwent in vitro fertilization (IVF). We performed a mixed-effects logistic regression model, adding as a random effect the patients and the stimulation cycle considering the dependence of data. Survival curves were employed as a measure of the cumulative live birth rate (CLBR). The primary outcomes were live birth rate per embryo transfer and CLBR per consecutive embryo transfer and oocyte consumed until a live birth was achieved. RESULTS: A total of 2002 patients underwent 3056 embryo transfers (mOS = 497 and cOS = 2559). The live birth rates per embryo transfer in mOS and cOS showed no significant difference in both Poseidon's groups. Likewise, the logistic regression showed similar live birth rates between the two protocols in Poseidon's groups 2 (OR 1.165, 95% CI 0.77-1.77; p = 0.710) and 4 (OR 1.264 95% CI 0.59-2.70; p = 0.387). However, the survival curves showed higher CLBR per oocyte in women that received mOS (Poseidon group 2: p < 0.001 and Poseidon group 4: p = 0.039). CONCLUSIONS: Minimal ovarian stimulation is a good alternative to COS as a first-line treatment for patients belonging to Poseidon's groups 2 and 4. The number of oocytes needed to achieve a live birth seems inferior in mOS strategy than cOS.


Assuntos
Coeficiente de Natalidade , Indução da Ovulação/métodos , Adulto , Custos de Medicamentos , Transferência Embrionária/estatística & dados numéricos , Feminino , Fertilização in vitro , Hormônio Foliculoestimulante/uso terapêutico , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Gonadotropinas/administração & dosagem , Gonadotropinas/economia , Gonadotropinas/uso terapêutico , Humanos , Idade Materna , Reserva Ovariana , Gravidez , Estudos Retrospectivos
19.
Rev. bras. ginecol. obstet ; 43(4): 304-310, Apr. 2021. graf
Artigo em Inglês | LILACS | ID: biblio-1280037

RESUMO

Abstract Hydrosalpinx is a disease characterized by the obstruction of the salpinx, with progressive accumulation in the shape of a fluid-filled sac at the distal part of the tuba uterina, and closed to the ovary. Women with hydrosalpinges have lower implantation and pregnancy rates due to a combination of mechanical and chemical factors thought to disrupt the endometrial environment. Evidence suggests that the presence of hydrosalpinx reduces the rate of pregnancy with assisted reproductive technology. The main aim of the present is review to make an overview of the possible effects of hydrosalpinx on in vitro fertilization (IVF).We conducted a literature search on the PubMed, Ovid MEDLINE, and Google Scholar data bases regarding hydrosalpinx and IVF outcomes. Hydrosalpinx probably has a direct toxic effect on sperm motility and on the embryos. In addition, the increasing liquid inside the salpinges could alter the mechanisms of endometrial receptivity. The window of endometrial receptivity is essential in the implantation of blastocysts, and it triggers multiple reactions arising from the endometrium as well as the blastocysts. Hydrosalpinx could influence the expression of homeobox A10 (HOXA10) gene, which plays an essential role in directing embryonic development and implantation. Salpingectomy restores the endometrial expression of HOXA10; therefore, it may be one mechanism by which tubal


Assuntos
Humanos , Feminino , Gravidez , Implantação do Embrião , Fertilização in vitro , Falha de Tratamento , Doenças das Tubas Uterinas/complicações , Salpingectomia , Infertilidade Feminina/terapia , Blastocisto/fisiologia , Expressão Gênica , Endométrio/fisiopatologia , Doenças das Tubas Uterinas/cirurgia , Doenças das Tubas Uterinas/fisiopatologia , Proteínas Homeobox A10/genética , Infertilidade Feminina/etiologia
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