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1.
Menopause ; 2024 May 14.
Article in English | MEDLINE | ID: mdl-38743912

ABSTRACT

OBJECTIVE: Frailty may be increased by menopause. Physical activity has been proposed to reduce frailty, but poor adherence and cost limit effectiveness. We aimed to investigate both the effectiveness against the frailty burden and the adherence rate of a multicomponent physical activity scheme partially managed by the participating women themselves. METHODS: Prospective controlled study consisting of a twice-weekly group physical activity scheme divided into two consecutive periods, one supervised by a health professional (12 wk) and the other supervised by the women themselves (36 wk). Group cohesion and mutual support during the patient-only period were aided by social networking via smartphones. Community-dwelling postmenopausal women were divided into a physical activity group (PAG = 126) and a usual activity control group (UAG = 126), both assessed at baseline and at the end of the study. Participants self-assigned to one of the two study arms. RESULTS: Overall, women in the PAG were more likely to improve their frailty status (60.2% vs 42.6%, P < 0.05). The frailty reversal rate from prefrail to robust was significantly higher in the PAG than in the UAG (34.04 vs 8.00%, P < 0.05). Logistic regression confirmed that women in the PAG were more likely to improve their frailty phenotype (odds ratio [OR], 9.12; 95% confidence interval [CI], 3.45-31.52; P < 0.001). Adherence, defined by participants attending 75% of sessions, was attained by 56.35% of women at 48 wk. CONCLUSION: A physical activity scheme implemented to improve frailty proved effective and attained acceptable adherence. Conditions in the peer-supervised 36-wk phase may increase sustainability.

2.
Maturitas ; 178: 107841, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37660598

ABSTRACT

Cancer is one of the main noncommunicable diseases in terms of health impact. Factors such as a progressively aging population point to future increases in the incidence of cancer on a global level. The elevated number of affected individuals, together with continuous improvements in cancer prevention and therapy, is creating a growing population of cancer survivors, with often inadequately met needs. Lifestyle is a key modulator of cancer risk and of associated morbidity and mortality, and is included in all approaches to the long-term management of cancer. Diet is a principal component of lifestyle, and most of the available evidence is centered on the Mediterranean diet. Our objective was to provide a narrative review of the evidence on the effect of the Mediterranean diet on cancer risk and health threats related to cancer survivorship. For this purpose, we searched the PubMed database for articles published between January 1, 2000, and June 12, 2023. Current data show that the Mediterranean diet is inversely associated with risk, or is risk neutral, for most types of cancer. Tumors of the digestive system have received preferential interest, but studies have also been published on tumors in other organs. The evidence, however, is meager due to the observational nature of most studies, although it is reassuring that benefit is reproduced in studies performed in different populations and environments. Evidence related to cancer survivors is limited by the paucity of studies, yet several findings regarding survival, recurrence, and short- and long-term morbidity suggest a potential role for the Mediterranean diet that warrants further research.


Subject(s)
Cancer Survivors , Diet, Mediterranean , Neoplasms , Humans , Aged , Survivorship , Neoplasms/etiology , Neoplasms/prevention & control , Risk
3.
Reprod Health ; 20(1): 117, 2023 Aug 16.
Article in English | MEDLINE | ID: mdl-37582738

ABSTRACT

BACKGROUND: Once a mate choice decision has been made, couples that fail to reach a live birth in natural and/or intrauterine insemination (IUI) cycles will likely visit fertility clinics seeking assisted reproductive technology (ART) treatment. During the more or less prolonged period of infertility experienced, those couples with mild/moderate reproductive anomalies would have advantage over couples displaying more severe reproductive alterations in achieving a natural or IUI conception. Thus, we can expect to find a progressive increase in the proportion of couples with more severe reproductive anomalies as duration of infertility rises. In this study, we aim to ascertain whether there is an association between male and female infertility diagnoses and duration of infertility in couples seeking ART treatment for the first time. METHODS: A cross-sectional analysis of 1383 infertile couples that sought ART treatment for the first time. Forward-stepwise binary logistic regression analyses were applied to calculate exponentiated regression coefficients. RESULTS: Men suffering from any combination of oligo-, astheno-, and teratozoospermia (ACOAT) exhibited higher odds of having a duration of infertility > 2 years compared with non-ACOAT men [odds ratio (95% confidence interval): 1.340 (1.030-1.744)]. Women from ACOAT couples displaying a duration of infertility > 2 years presented shorter menstrual cycles (P ≤ 0.047) and lower antral follicular count (AFC) values (P ≤ 0.008) and serum anti-Müllerian hormone (AMH) levels (P ≤ 0.007) than women from non-ACOAT couples exhibiting > 2 years of infertility. Likewise, AFC values (P ≤ 0.013) and serum AMH levels (P ≤ 0.001) were decreased when compared with women from ACOAT couples displaying ≤ 2 years of infertility. A relative low but significant percentage of ACOAT couples displaying > 2 years of infertility stood out for their smoking habits. CONCLUSIONS: Couples consisting of ACOAT men and women with a relative low ovarian reserve are overrepresented in couples seeking ART treatment for the first time after experiencing > 2 years of infertility. This outcome leads us to develop a general hypothesis proposing that the origin of couple's infertility is a consequence of a process of positive assortative mating shaped by sexual selection forces.


Subject(s)
Infertility, Female , Ovarian Reserve , Pregnancy , Female , Male , Humans , Cross-Sectional Studies , Semen , Reproductive Techniques, Assisted , Infertility, Female/therapy , Live Birth
4.
Maturitas ; 171: 40-44, 2023 May.
Article in English | MEDLINE | ID: mdl-37001478

ABSTRACT

BACKGROUND: Dynapenia increases with age and in the case of women is possibly influenced by menopause, yet whether vitamin D affects this increase remains controversial. The influence of genetic variants (single nucleotide polymorphisms) of the vitamin D receptor on dynapenia is an understudied area. AIM: To analyze the association between genetic variants of the vitamin D receptor gene and dynapenia in a cohort of community-dwelling postmenopausal women. METHODS: We performed a cross-sectional study of 463 women in a university hospital. Grip strength was used as an indicator of dynapenia. Differences in grip strength among single nucleotide polymorphisms rs11568820 and rs2228570 genotypes of the vitamin D receptor gene were assessed after adjusting for confounding variables, and the percentage of phenotypic variance was estimated by linear regression. RESULTS: Dynapenia (grip strength <20 kg) was diagnosed in 178 of the women (38.45 %). A difference in grip strength, corresponding to variants of the vitamin D receptor gene single nucleotide polymorphism rs11568820, was found when using an additive model of inheritance, with lower grip strength for the TT genotype (ANOVA, p = 0.030, close to the 0.025 significance level determined by Bonferroni correction). Assuming a recessive inheritance model for allele T, the between-group difference in grip strength was significant (TT = 19.79 ± 3.10 kg vs. CC/CT = 21.58 ± 3.49 kg, p = 0.008) after adjusting for age, body mass index, comorbidities, and sociodemographic variables. More women with dynapenia had the TT genotype (60.71 %) than the CC or CT genotype (37.01 %) (p = 0.012). CONCLUSION: This study demonstrates that the TT genotype of the rs11568820 SNP of the vitamin D receptor gene was associated with decreased grip strength in community-dwelling postmenopausal women.


Subject(s)
Postmenopause , Receptors, Calcitriol , Humans , Female , Receptors, Calcitriol/genetics , Postmenopause/genetics , Cross-Sectional Studies , Vitamin D , Polymorphism, Single Nucleotide , Genotype
5.
Maturitas ; 168: 7-12, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36370490

ABSTRACT

BACKGROUND: Telehealth has emerged as an alternative to conventional, face-to-face visits, and the COVID pandemic has hastened its introduction. Telephone appointments make use of an easy-to-use and accessible technology. AIM: To investigate the usability of telephone-based telehealth in a women's health outpatient clinic and whether this may be affected by the severity of the COVID pandemic. METHOD: A telephone survey was prepared to explore two usability domains: interaction quality (4 items) and satisfaction, preference and future use (6 items). Women were selected from two periods during the COVID pandemic when the infection rates were high and low. RESULTS: The survey was completed by 106 women (60 when the prevalence of COVID was high, mean age 53.58 years, and 46 when it was low, mean age 48.59 years) out of the 153 women who had a telephone appointment. The severity of the COVID pandemic showed an effect on responses. Women were less enthusiastic about using the telephone during the period of low COVID prevalence, as shown by lower scores on 3 of the 4 items of the first domain [I had enough time; I would have understood better in person; I would have expressed myself better in person (p < 0.001 for comparison between groups on each of the 3 items)], and on 4 of the 6 items in the second domain [satisfied with quality of care (p < 0.001), or with the information received (p = 0.018); use of telephone in future (p < 0.001); preference to try other technologies in future (p < 0.001)]. Overall, women expressed a preference for in-person visits regardless of COVID prevalence rates. CONCLUSION: Telephone calls were a feasible alternative to face-to-face visits in a women's health outpatient clinic, but the pandemic pressure modified usability parameters. Respondents preferred in-person visits at any pandemic stage.


Subject(s)
COVID-19 , Delivery of Health Care, Integrated , Telemedicine , Humans , Female , COVID-19/epidemiology , Pandemics , Women's Health
6.
Metabolites ; 12(8)2022 Jul 24.
Article in English | MEDLINE | ID: mdl-35893245

ABSTRACT

Bone pathologies such as osteoporosis (OTP) and osteoarthritis (OA) are rising in incidence with the worldwide rise in life expectancy. The diagnosis is usually obtained using imaging techniques such as densitometry, but with both being multifactorial diseases, several molecular mechanisms remain to be understood. Metabolomics offers the potential to detect global changes which can lead to the identification of biomarkers and a better insight in the progress of the diseases. Our aim was to compare the metabolic profiles of a cohort of 100 postmenopausal women, including subcapital hip fragility fracture patients, women with severe OA of the hip that required the implantation of a hip prosthesis and controls, to find altered metabolites and networks. Nuclear magnetic resonance (NMR) spectroscopy was used to obtain the metabolomic profiles of peripheral blood derived serum, and statistical analysis was performed using MATLAB V.6.5. 30 of the 73 metabolites analysed showed statistically significant differences in a 3-way ANOVA, and 11 of them were present in the comparison between OA and controls after adjustment by covariates, including amino acids, energy metabolism metabolites and phospholipid precursors. PLS-DA analysis shows a good discrimination between controls and fracture subjects with OA patients, and ROC curve analysis demonstrates that control and fracture subjects were accurately discriminated using the metabolome, but not OA. These results point to OA as an intermediate metabolic state between controls and fracture, and suggest that some metabolic shifts that happen after a fracture are also present at weaker intensity in the OA process.

7.
Biomedicines ; 10(2)2022 Feb 21.
Article in English | MEDLINE | ID: mdl-35203710

ABSTRACT

The aim of this study was to develop and refine a heterologous mouse model of endometriosis-associated pain in which non-evoked responses, more relevant to the patient experience, were evaluated. Immunodeficient female mice (N = 24) were each implanted with four endometriotic human lesions (N = 12) or control tissue fat (N = 12) on the abdominal wall using tissue glue. Evoked pain responses were measured biweekly using von Frey filaments. Non-evoked responses were recorded weekly for 8 weeks using a home cage analysis (HCA). Endpoints were distance traveled, social proximity, time spent in the center vs. outer areas of the cage, drinking, and climbing. Significant differences between groups for von Frey response, climbing, and drinking were detected on days 14, 21, and 35 post implanting surgery, respectively, and sustained for the duration of the experiment. In conclusion, a heterologous mouse model of endometriosis-associated evoked a non-evoked pain was developed to improve the relevance of preclinical models to patient experience as a platform for drug testing.

8.
Reprod Sci ; 29(12): 3387-3393, 2022 12.
Article in English | MEDLINE | ID: mdl-35146695

ABSTRACT

Postmortem sperm retrieval for reproductive purposes is an assisted reproduction procedure that offers women an opportunity to have a child using sperm retrieved from their deceased partners. The ethical issues of this procedure have been discussed in previous works. However, an assessment of the procedure using a scientific perspective is still lacking. Here, we aim to ascertain, using a biological standpoint, whether postmortem sperm should be rescued for reproductive purposes. Data suggest that it is premature to use postmortem sperm for reproductive purposes. This procedure should not be clinically applied until appropriate and comprehensive analyses have been completed. Such analyses should be focused not only on fertilization, embryo development, and pregnancy outcomes, but also on potential postmortem alterations of sperm DNA, RNAs, and proteins. In addition, genetic and epigenetic analyses of sperm, pre-implantation embryos, and newborns, as well as mental and physical health follow-up of the resulting offspring during a whole life cycle, using appropriate non-human mammalian models, are warranted.


Subject(s)
Premature Birth , Semen , Pregnancy , Animals , Humans , Male , Infant, Newborn , Female , Spermatozoa/metabolism , Premature Birth/metabolism , Pregnancy Outcome , Embryonic Development , Mammals
9.
Int J Mol Sci ; 23(3)2022 Feb 03.
Article in English | MEDLINE | ID: mdl-35163671

ABSTRACT

The receptor activator of nuclear factor kappa B (RANK) is becoming recognized as a master regulator of tumorigenesis, yet its role in gynecological cancers remains mostly unexplored. We investigated whether there is a gradation of RANK protein and mRNA expression in epithelial ovarian cancer (EOC) according to malignancy and tumor staging. Immunohistochemical expression of RANK was examined in a cohort of 135 (benign n = 29, borderline n= 23 and malignant n = 83) EOCs. Wild type and truncated RANK mRNA isoform quantification was performed in a cohort of 168 (benign n = 26, borderline n = 13 and malignant n = 129) EOCs. RANK protein and mRNA values were increased in malignant vs. benign or borderline conditions across serous, mucinous and endometrioid cancer subtypes. Additionally, a trend of increased RANK values with staging was observed for the mucinous and serous histotype. Thus, increased expression of RANK appears associated with the evolution of disease to the onset of malignancy in EOC. Moreover, in some EOC histotypes, RANK expression is additionally associated with clinicopathological markers of tumor aggressiveness, suggesting a role in further progression of tumor activity.


Subject(s)
Carcinoma, Ovarian Epithelial/pathology , Ovarian Neoplasms/pathology , Receptor Activator of Nuclear Factor-kappa B/metabolism , Cell Line, Tumor , Female , Gene Expression Regulation, Neoplastic , Humans , Neoplasm Grading , Neoplasm Staging , RNA, Messenger/genetics , RNA, Messenger/metabolism , Receptor Activator of Nuclear Factor-kappa B/genetics
10.
Maturitas ; 156: 60-64, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34275701

ABSTRACT

BACKGROUND: Frailty is a clinically discernible state in which decreased physiological reserve and function result in a reduced ability to cope with stressors. Information and communication technology (ICT) has been proposed as an aid to help with frailty, yet the use of ICT by older people, particularly women, is an understudied area. AIM: To analyze the association between use of ICT (specifically internet functions and social media) and frailty status in postmenopausal midlife and elderly women. METHODS: A cross-sectional study was designed to investigate whether frailty status is related to ICT use in postmenopausal midlife and older women. Community-dwelling women attending primary health care centers for health checks were invited to participate in the study. Postmenopausal status was the only inclusion criterion, whereas limitations that could interfere with use of ICT were exclusion criteria. The Fried phenotype was used to assess frailty. Four types of ICT use were examined: the internet for e-mail, the internet for other functions, and social media (WhatsApp or Facebook). Chi-square test and multivariate multinomial regression analysis were used to examine the association between frailty status and ICT use. RESULTS: We included 409 women (age = 67.45 ± 7.81 years, mean ± SD), who were frail (n = 135, 33.01%), pre-frail (n = 159, 38.87%), or robust (n  =  115, 28.11%). Frailty status was significantly and inversely associated with any ICT use, showing a strong association with use of WhatsApp (P < 0.001) and internet searches (P < 0.001). ICT non-use was a predictor of frailty, while ICT users were more likely to be robust (OR 10.62; 95% [CI], 5.34-21.10) or pre-frail (OR 9.03; [CI], 95% 5.18-15.74). CONCLUSION: Postmenopausal midlife and older women not using ICT were more likely to be frail.


Subject(s)
Frailty , Aged , Communication , Cross-Sectional Studies , Female , Frail Elderly , Frailty/diagnosis , Geriatric Assessment , Humans , Independent Living , Postmenopause , Technology
11.
Genes (Basel) ; 12(12)2021 12 17.
Article in English | MEDLINE | ID: mdl-34946961

ABSTRACT

Much of the genetic variance associated with osteoporosis is still unknown. Bone mineral density (BMD) is the main predictor of osteoporosis risk, although other anthropometric phenotypes have recently gained importance. The aim of this study was to analyze the association of SNPs in genes involved in osteoblast differentiation and function with BMD, body mass index (BMI), and waist (WC) and hip (HC) circumferences. Four genes that affect osteoblast differentiation and/or function were selected from among the differentially expressed genes in fragility hip fracture (FOXC1, CTNNB1, MEF2C, and EBF2), and an association study of four single-nucleotide polymorphisms (SNPs) was conducted in a cohort of 1001 women. Possible allelic imbalance was also studied for SNP rs87939 of the CTNNB1 gene. We found significant associations of SNP rs87939 of the CTNNB1 gene with LS-sBMD, and of SNP rs1366594 of the MEF2C gene with BMI, after adjustment for confounding variables. The SNP of the MEF2C gene also showed a significant trend to association with FN-sBMD (p = 0.009). A possible allelic imbalance was ruled out as no differences for each allele were detected in CTNNB1 expression in primary osteoblasts obtained from homozygous women. In conclusion, we demonstrated that two SNPs in the MEF2C and CTNNB1 genes, both implicated in osteoblast differentiation and/or function, are associated with BMI and LS-sBMD, respectively.


Subject(s)
Osteoblasts/physiology , Polymorphism, Single Nucleotide , beta Catenin/genetics , Absorptiometry, Photon , Aged , Allelic Imbalance , Basic Helix-Loop-Helix Transcription Factors/genetics , Body Mass Index , Bone Density , Cell Differentiation , Cohort Studies , Female , Forkhead Transcription Factors/genetics , Genetic Association Studies , Humans , MEF2 Transcription Factors/genetics , Middle Aged , Spain , Waist Circumference
12.
Sci Rep ; 11(1): 19372, 2021 09 29.
Article in English | MEDLINE | ID: mdl-34588560

ABSTRACT

The rising incidence of bone pathologies such as osteoporosis and osteoarthritis is negatively affecting the functional status of millions of patients worldwide. The genetic component of these multifactorial pathologies is far from being fully understood, but in recent years several epigenetic mechanisms involved in the pathophysiology of these bone diseases have been identified. The aim of the present study was to compare the serum expression of four miRNAs in women with hip fragility fracture (OF group), osteoarthritis requiring hip replacement (OA group) and control women (Ctrl group). Serum expression of miR-497-5p, miR-155-5p, miR-423-5p and miR-365-3p was determined in a sample of 23 OA women, 25 OF women and 52 Ctrl women. Data shown that women with bone pathologies have higher expression of miR-497 and miR-423 and lower expression of miR-155 and miR-365 than control subjects. Most importantly, miR-497 was identified as an excellent discriminator between OA group and control group (AUC: 0.89, p < 0.000) and acceptable in distinguishing from the OF group (AUC: 0.76, p = 0.002). Our data suggest that circulating miR-497 may represent a significant biomarker of OA, a promising finding that could contribute towards future early-stage diagnosis of this disease. Further studies are required to establish the role of miR-155, miR-423 and miR-365 in bone pathologies.


Subject(s)
MicroRNAs/blood , Osteoarthritis/blood , Osteoporosis/blood , Osteoporotic Fractures/blood , Aged , Biomarkers/blood , Case-Control Studies , Female , Humans , Middle Aged
13.
Medicine (Baltimore) ; 100(23): e26216, 2021 Jun 11.
Article in English | MEDLINE | ID: mdl-34115005

ABSTRACT

ABSTRACT: There is debate on the role of estrogens in modulating the risk for atherosclerosis in women. Our purpose was to investigate whether the size of the estrogenic impact was independently associated with variation of carotid intima-media thickness (IMT) in healthy late postmenopausal women. The levels of circulating estrogens have been used in previous studies but the influence of SNPs of the estrogen receptors (ER) α and ß have not been investigated.We performed a crossed-sectional study of 91 women in a university hospital. We used a double approach in which, in addition to the measurement of estradiol levels by ultrasensitive methods, genetic variants (SNPs) associated with differing expression of the ER α and ß genes were assessed. Multivariable analysis was used to examine the association of candidate factors with the value of IMT and plaque detection at both the carotid wall and the sinus.A genotype combination translating reduced gene expression of the ERß was directly associated with IMT at both the carotid wall (P = .001) and the sinus (P = .002). Other predictors of IMT were the levels of glucose, positively associated with IMT at both the carotid wall (P < .001) and the sinus (P = .001), age positively associated with IMT at the sinus (P = .003), and levels of vitamin D, positively associated with IMT at the carotid wall (P = .04).Poorer estrogenic impact, as concordant with a SNP variant imposing reduced expression of the ERß, was directly associated with IMT at both the carotid wall and the sinus. Glucose level, vitamin D only for the carotid wall, and age only for the sinus, also emerged as independent factors in the IMT variance.


Subject(s)
Carotid Intima-Media Thickness/statistics & numerical data , Estrogen Receptor beta/genetics , Postmenopause , Aged , Biomarkers/analysis , Biomarkers/blood , Carotid Intima-Media Thickness/instrumentation , Cross-Sectional Studies , Estrogen Receptor beta/blood , Female , Heart Disease Risk Factors , Hospitals, University/organization & administration , Hospitals, University/statistics & numerical data , Humans , Linear Models , Middle Aged , Polymorphism, Single Nucleotide/genetics , Risk Factors , Ultrasonography/methods
14.
Biomedicines ; 9(3)2021 Mar 08.
Article in English | MEDLINE | ID: mdl-33800198

ABSTRACT

Dopamine receptor 2 agonists (D2-ags) have been shown to reduce the size of tumors by targeting aberrant angiogenesis in pathological tissue. Because of this, the use of a D2-ag was inferred for endometriosis treatment. When assayed in mouse models however, D2-ags have been shown to cause a shift of the immature vessels towards a more mature phenotype but not a significant reduction in the amount of vascularization and size of lesions. These has raised concerns on whether the antiangiogenic effects of these compounds confer a therapeutic value for endometriosis. In the belief that antiangiogenic effects of D2-ags in endometriosis were masked due to non-optimal timing of pharmacological interventions, herein we aimed to reassess the antiangiogenic therapeutic potential of D2-ags in vivo by administering compounds at a timeframe in which vessels in the lesions are expected to be more sensitive to antiangiogenic stimuli. To prove our point, immunodeficient (NU/NU) mice were given a D2-ag (cabergoline), anti-VEGF (CBO-P11) or vehicle (saline) compounds (n = 8 per group) starting 5 days after implantation of a fluorescently labeled human lesion. The effects on the size of the implants was estimated by monitoring the extent of fluorescence emitted by the lesion during the three-week treatment period. Subsequently mice were sacrificed and lesions excised and fixed for quantitative immunohistochemical/immunofluorescent analysis of angiogenic parameters. Lesion size, vascular density and innervation were comparable in D2-ag and anti-VEGF groups and significantly decreased when compared to control. These data suggest that D2-ags are as powerful as standard antiangiogenic compounds in interfering with angiogenesis and lesion size. Our preliminary study opens the way to further exploration of the mechanisms beneath the antiangiogenic effects of D2-ags for endometriosis treatment in humans.

16.
Maturitas ; 147: 41-46, 2021 May.
Article in English | MEDLINE | ID: mdl-33832646

ABSTRACT

OBJECTIVE: Experimental studies suggest that lipids affect bone metabolism. We aimed to elucidate whether lipid levels are associated with bone mineral density (BMD) in a cohort of postmenopausal women. DESIGN: A cross-sectional study of participants in the Chronic Ailment Reduction after MENopause (CARMEN) cohort. Women underwent assessment of clinical and analytical parameters, including fasting lipid levels. BMD was assessed at both lumbar spine and hip. Homogeneity in the cohort was optimized by filtering out a series of confounding variables with a known impact on bone. MAIN OUTCOME MEASURES: Association of BMD at lumbar spine and femoral neck with lipid levels. RESULTS: A total of 667 of the 1304 screened women were analyzed. A strong correlation was revealed between total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) in univariate analysis. Multivariate analysis detected a significant positive association of HDL-C with BMD at both spine (p = 0.007) and femoral neck (p = 0.013). Other independent predictors of spine BMD were years since menopause (ysm, negatively associated), and body mass index (BMI) and estradiol, both positively associated with BMD. The other independent variables in the femoral neck were ysm and glucose (negatively associated) and BMI, estradiol, and phosphate, all positively associated with BMD. CONCLUSION: Levels of HDL-C, but not TC, LDL-C or triglycerides, were positively associated with BMD at both the lumbar spine and femoral neck in a homogeneous cohort of postmenopausal women.


Subject(s)
Bone Density , Cholesterol, HDL/blood , Femur Neck , Lumbar Vertebrae , Postmenopause/blood , Aged , Cohort Studies , Female , Humans , Middle Aged
17.
Gynecol Endocrinol ; 37(3): 269-272, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33480311

ABSTRACT

OBJECTIVE: Endothelial dysfunction and denudation are considered a first step in atherosclerosis. Endothelial proliferation is key for cellular repair. The effect of bazedoxifene on the vascular endothelium has not been explored. We investigated the effect of bazedoxifene on endothelial cell proliferation. METHODS: Primary cultures from human umbilical artery endothelial cells were used in dose-response experiments (0.1, 1.0, and 10.0 EC50 dose) with bazedoxifene, estradiol, raloxifene and a combination of bazedoxifene and estradiol. Proliferation was assessed with the XTT colorimetric cell-proliferation assay. The possible participation of cyclins A, B, D1 and p27Kip1 was analyzed by the measurement of their expression at both the protein and the gene levels. RESULTS: A significant increase of similar size for cell proliferation was obtained with bazedoxifene, estradiol and raloxifene, but no significant change was observed for the association of bazedoxifene and estradiol. The impact was detected at the first 0.1 EC50 dose and was not dose-dependent. Estradiol achieved a significant increase in the protein expression of cyclin A and p27Kip1, but no change was detected for the other compounds at either the gene or protein level. CONCLUSION: Bazedoxifene demonstrated a proliferative effect of similar size to estradiol in cultured human umbilical artery endothelial cells. The molecular mechanisms need further investigation.


Subject(s)
Cell Proliferation/drug effects , Endothelial Cells/drug effects , Indoles/pharmacology , Cell Proliferation/genetics , Cells, Cultured , Cyclin A/genetics , Cyclin A/metabolism , Cyclin B/genetics , Cyclin B/metabolism , Cyclin D1/genetics , Cyclin D1/metabolism , Cyclin-Dependent Kinase Inhibitor p27/genetics , Cyclin-Dependent Kinase Inhibitor p27/metabolism , Endothelial Cells/physiology , Endothelium, Vascular/cytology , Female , Gene Expression/drug effects , Humans , Infant, Newborn , Pregnancy , Umbilical Arteries/cytology
18.
Sci Rep ; 10(1): 16298, 2020 10 01.
Article in English | MEDLINE | ID: mdl-33004909

ABSTRACT

To identify new candidate genes in osteoporosis, mainly involved in epigenetic mechanisms, we compared whole gene-expression in osteoblasts (OBs) obtained from women undergoing hip replacement surgery due to fragility fracture and severe osteoarthritis. Then, we analyzed the association of several SNPs with BMD in 1028 women. Microarray analysis yielded 2542 differentially expressed transcripts belonging to 1798 annotated genes, of which 45.6% (819) were overexpressed, and 54.4% (979) underexpressed (fold-change between - 7.45 and 4.0). Among the most represented pathways indicated by transcriptome analysis were chondrocyte development, positive regulation of bone mineralization, BMP signaling pathway, skeletal system development and Wnt signaling pathway. In the translational stage we genotyped 4 SNPs in DOT1L, HEY2, CARM1 and DNMT3A genes. Raw data analyzed against inheritance patterns showed a statistically significant association between a SNP of DNMT3A and femoral neck-(FN) sBMD and primarily a SNP of CARM1 was correlated with both FN and lumbar spine-(LS) sBMD. Most of these associations remained statistically significant after adjusting for confounders. In analysis with anthropometric and clinical variables, the SNP of CARM1 unexpectedly revealed a close association with BMI (p = 0.000082), insulin (p = 0.000085), and HOMA-IR (p = 0.000078). In conclusion, SNPs of the DNMT3A and CARM1 genes are associated with BMD, in the latter case probably owing to a strong correlation with obesity and fasting insulin levels.


Subject(s)
CARD Signaling Adaptor Proteins/genetics , DNA (Cytosine-5-)-Methyltransferases/genetics , Genetic Predisposition to Disease/genetics , Guanylate Cyclase/genetics , Osteoporosis/genetics , Bone Density/genetics , Case-Control Studies , DNA Methyltransferase 3A , Gene Expression Profiling/methods , Humans , Middle Aged , Oligonucleotide Array Sequence Analysis , Osteoporotic Fractures/genetics , Polymorphism, Single Nucleotide/genetics , Real-Time Polymerase Chain Reaction , Transcriptome
19.
Nutrients ; 12(10)2020 Oct 18.
Article in English | MEDLINE | ID: mdl-33081027

ABSTRACT

The rates of metabolic syndrome are increasing in parallel with the increasing prevalence of obesity, primarily due to its concomitant insulin resistance. This is particularly concerning for women, as the years around menopause are accompanied by an increase in visceral obesity, a strong determinant of insulin resistance. A fall in estrogens and increase in the androgen/estrogen ratio is attributed a determining role in this process, which has been confirmed in other physiological models, such as polycystic ovary syndrome. A healthy lifestyle, with special emphasis on nutrition, has been recommended as a first-line strategy in consensuses and guidelines. A consistent body of evidence has accumulated suggesting that the Mediterranean diet, with olive oil as a vital component, has both health benefits and acceptable adherence. Herein, we provide an updated overview of current knowledge on the benefits of olive oil most relevant to menopause-associated metabolic syndrome, including an analysis of the components with the greatest health impact, their effect on basic mechanisms of disease, and the state of the art regarding their action on the main features of metabolic syndrome.


Subject(s)
Diet, Healthy , Diet, Mediterranean , Healthy Aging , Healthy Lifestyle , Menopause , Metabolic Syndrome/etiology , Metabolic Syndrome/metabolism , Nutritional Physiological Phenomena/physiology , Olive Oil , Aged , Androgens/metabolism , Estrogens/metabolism , Female , Humans , Insulin Resistance , Metabolic Syndrome/therapy , Middle Aged , Obesity, Abdominal/etiology , Obesity, Abdominal/metabolism , Obesity, Abdominal/therapy
20.
Medicine (Baltimore) ; 99(40): e22436, 2020 Oct 02.
Article in English | MEDLINE | ID: mdl-33019425

ABSTRACT

In addition to governing key functions in bone metabolism and the immune system, the RANK/RANKL/OPG system plays a role in the vascular system, particularly in vascular calcification and atherosclerosis.Given that these 2 phenotypes are considered a major cause of high blood pressure (BP), in this study we analyzed the association of SNPs in RANK and OPG genes with blood pressure. An observational study was conducted of 2 SNPs in the RANK gene (rs884205 and rs78326403) and 1 in the OPG gene (rs4876869) with systolic (SBP) and diastolic blood pressure (DBP) in a cohort of 695 women.Data analysis revealed a statistically significant association between the SNP rs884205 and BP pressure (SBP and DBP). Analyzing this relationship by the dominant inheritance model for this SNP (allele risk: A), women of the AA/AC genotype showed higher BP than women of the CC genotype, both for SBP (P = .001) and for DBP (P = .003), and these associations both surpassed the Bonferroni threshold for multiple comparisons. Multivariate regression analysis including known predictors of BP as independent variables was performed to evaluate the strength of this association, which in the case of the SNP rs884205 of the RANK gene remained statistically significant after adjustment for both SBP (P = .0006) and DBP (P = .005), demonstrating the key role of this SNP in BP.We report a robust association between the SNP rs884205 in RANK gene and BP in women, and this SNP is validated as a candidate in cardiovascular risk studies.


Subject(s)
Blood Pressure/genetics , Receptor Activator of Nuclear Factor-kappa B/blood , Female , Genome-Wide Association Study , Humans , Middle Aged , Osteoprotegerin/blood , Polymorphism, Single Nucleotide , Spain
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