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BACKGROUND: Obesity represents a global health crisis, yet a dichotomy is emerging with classification according to the metabolic state into metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO). This study aimed to identify distinctive systemic clinical/endocrinological parameters between MHO individuals, employing a comprehensive comparative analysis of 50 biomarkers. Our emphasis was on routine analytes, ensuring cost-effectiveness for widespread use in diagnosing metabolic health. SUBJECTS/METHODS: The study included 182 women diagnosed with obesity referred for bariatric surgery at the Endocrinology, Diabetes, and Metabolism Service of São João Hospital and University Centre in Portugal. MUO was defined by the presence of at least one of the following metabolic disorders: diabetes, hypertension, or dyslipidemia. Patients were stratified based on the diagnosis of these pathologies. RESULTS: Significantly divergent health-related parameters were observed between MHO and MUO patients. Notable differences included: albumin (40.1 ± 2.2 vs 40,98 ± 2.6 g/L, p value = 0.017), triglycerides (110.7 ± 51.1 vs 137.57 ± 82.6 mg/dL, p value = 0.008), glucose (99.49 ± 13.0 vs 119.17 ± 38.9 mg/dL, p value < 0.001), glycated hemoglobin (5.58 ± 0.4 vs 6.15 ± 1.0%, p value < 0.001), urea (31.40 ± 10.0 vs 34.61 ± 10.2 mg/dL, p value = 0.014), total calcium (4.64 ± 0.15 vs 4.74 ± 0.17 mEq/L, 1 mEq/L = 1 mg/L, p value < 0.001), ferritin (100.04 ± 129.1 vs 128.55 ± 102.1 ng/mL, p value = 0.005), chloride (104.68 ± 1.5 vs 103.04 ± 2.6 mEq/L, p value < 0.001), prolactin (13.57 ± 6.3 vs 12.47 ± 7.1 ng/mL, p value = 0.041), insulin (20.36 ± 24.4 vs 23.87 ± 19.6 µU/mL, p value = 0.021), c peptide (3.78 ± 1.8 vs 4.28 ± 1.7 ng/mL, p value = 0.003), albumin/creatinine ratio (15.41 ± 31.0 vs 48.12 ± 158.7 mg/g creatinine, p value = 0.015), and whole-body mineral density (1.27 ± 0.1 vs 1.23 ± 0.1 g/cm2, p value = 0.016). CONCLUSIONS: Our findings highlight potential additional parameters that should be taken into consideration alongside the commonly used biomarkers for classifying metabolic health in women. These include albumin, urea, total calcium, ferritin, chloride, prolactin, c-peptide, albumin-creatinine ratio, and whole-body mineral density. Moreover, our results also suggest that MHO may represent a transitional phase preceding the development of the MUO phenotype.
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Biomarcadores , Obesidad Metabólica Benigna , Humanos , Femenino , Adulto , Persona de Mediana Edad , Biomarcadores/sangre , Portugal/epidemiología , Obesidad/metabolismo , Glucemia/metabolismo , Glucemia/análisisRESUMEN
Biosynthetic gold nanoparticles (bAuNPs) present a promising avenue for enhancing bio-compatibility and offering an economically and environmentally responsible alternative to traditional production methods, achieved through a reduction in the use of hazardous chemicals. While the potential of bAuNPs as anticancer agents has been explored, there is a limited body of research focusing on the crucial physicochemical conditions influencing bAuNP production. In this study, we aim to identify the optimal growth phase of Pseudomonas aeruginosa cultures that maximizes the redox potential and coordinates the formation of bAuNPs with increased efficiency. The investigation employs 2,6-dichlorophenolindophenol (DCIP) as a redox indicator. Simultaneously, we explore the impact of temperature, pH, and incubation duration on the biosynthesis of bAuNPs, with a specific emphasis on their potential application as antitumor agents. Characterization of the resulting bAuNPs is conducted using ATR-FT-IR, TEM, and UV-Vis spectroscopy. To gain insights into the anticancer potential of bAuNPs, an experimental model is employed, utilizing both non-neoplastic (HPEpiC) and neoplastic (PC3) epithelial cell lines. Notably, P. aeruginosa cultures at 9 h/OD600 = 1, combined with biosynthesis at pH 9.0 for 24 h at 58 °C, produce bAuNPs that exhibit smaller, more spherical, and less aggregated characteristics. Crucially, these nanoparticles demonstrate negligible effects on HPEpiC cells while significantly impacting PC3 cells, resulting in reduced viability, migration, and lower IL-6 levels. This research lays the groundwork for the development of more specialized, economical, and ecologically friendly treatment modalities.
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Antineoplásicos , Nanopartículas del Metal , Neoplasias de la Próstata , Humanos , Masculino , Antibacterianos/química , Oro/química , Espectroscopía Infrarroja por Transformada de Fourier , Nanopartículas del Metal/uso terapéutico , Nanopartículas del Metal/química , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Neoplasias de la Próstata/tratamiento farmacológico , Tecnología Química Verde/métodos , Extractos Vegetales/químicaRESUMEN
INTRODUCTION: Obesity and breast cancer are two major pathologies closely associated with increasing incidence and mortality rates, especially amongst women. The association between both diseases have been thoroughly discussed but much is still to uncover. AIM: The aim of this study is to analyse tumour characteristics and clinical outcomes of overweight and obese women to disclosure potential associations and better understand the impact of obesity in breast cancer. MATERIALS AND METHODS: Clinicopathological information of 2246 women were extracted from the institutional database of comprehensive cancer centre in Portugal diagnosed between 2012 and 2016. Women were stratified according to body mass index as normal, overweight, and obese. Patients' demographic information and tumour features (age, family history, topographic localization, laterality, histological type, and receptor status) were taken as independent variables and overall survival, tumour stage, differentiation grade and bilaterality were considered clinical outcomes. RESULTS: The main results reveal that overweight and obesity are predominantly associated with worse outcomes in breast cancer patients. Obese patients present larger (p-value: 0.002; OR 1.422; 95% CI 1.134-1.783) and more poorly differentiated tumours (p-value: 0.002; OR 1.480; 95% CI 1.154-1.898) and tend to have lower overall survival although without statistical significance (p-value: 0.117; OR 1.309; 95% CI 0.934-1.833). Overweighted women are more likely to have bilateral breast cancer (p-value: 0.017; OR 3.076; 95% CI 1.225-7.722) than obese women. The results also reveal that overweight women present less distant metastasis (p-value: 0.024; OR 0.525; 95%CI 0.299-0.920). Topographic localization and laterality did not achieve statistical significance.
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Neoplasias de la Mama , Sobrepeso , Humanos , Femenino , Sobrepeso/complicaciones , Sobrepeso/epidemiología , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/terapia , Estudios Retrospectivos , Obesidad/complicaciones , Obesidad/epidemiología , Obesidad/diagnóstico , Índice de Masa CorporalRESUMEN
Epidemiological studies support the association of coffee-specific diterpenes, with various beneficial health effects. Although anti-antiangiogenic properties of free cafestol and kahweol have been recently described, available data regarding their esterified form, in particular palmitate esters as the main diterpene esters present in coffee, are still rare. Given that angiogenesis plays an important role in many pathological conditions, including cancer growth and metastasis, this study aimed to assess and compare the potential anti-angiogenic effects of cafestol palmitate (CP) and kahweol palmitate (KP) in an in vitro angiogenesis model. According to our findings, both compounds inhibited angiogenesis steps on human microvascular endothelial cells (HMVECs), although a more significant effect was observed for KP. Compared to control, HMVECs viability decreased in a dose-dependent manner upon incubation either with CP or KP. Concentrations of 75 and 100 µM of each compound were cytotoxic. Cell proliferation was also dramatically reduced by both diterpene esters at 50 µM, although KP had a stronger inhibitory effect. However, CP and KP did not induce apoptosis on HMVECs. Both compounds reduced cell migration, but this effect was only statistically significant after KP incubation. Inhibition of VEGFR2 expression and its downstream effector Akt, but not Erk, was also observed in CP- and KP-treated HMVECs. These findings were confirmed using ELISA assay for phosphorylated (active) VEGFR-2. Taken together, these data indicate that both CP and KP can be considered potent compounds against angiogenesis-dependent disorders. Our findings further indicate that KP exerts more potent anti-angiogenic effects than CP, in most of assays. J. Cell. Biochem. 117: 2748-2756, 2016. © 2016 Wiley Periodicals, Inc.
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Inhibidores de la Angiogénesis/farmacología , Diterpenos/farmacología , Ésteres/farmacología , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Neovascularización Fisiológica/efectos de los fármacos , Apoptosis/efectos de los fármacos , Western Blotting , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Fosforilación/efectos de los fármacos , Células Tumorales Cultivadas , Factor A de Crecimiento Endotelial Vascular/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismoRESUMEN
It is well established that tumour cells undergo metabolic changes to acquire biological advantage over normal cells with activation of the glycolytic pathway, a process termed "Warburg effect". Enzyme isoforms are alternative enzymatic forms with the same function but with different biochemical or epigenetic features. Moreover, isoforms may have varying impacts on different metabolic pathways. We challenge ourselves to analyse the glycolytic and gluconeogenic enzymes and isoforms in breast cancer, a complex and heterogeneous pathology, associated with high incidence and mortality rates especially among women. We analysed epithelial and tumour cell lines by RT-PCR and compared values to a publicly available database for the expression profile of normal and tumour tissues (Gepia) of enzymes and enzymatic isoforms from glycolytic and gluconeogenic pathways. Additionally, GeneMANIA was used to evaluate interactions, pathways, and attributes of each glycolytic/gluconeogenic steps. The findings reveal that the enzymes and enzymatic isoforms expressed in cell culture were somewhat different from those in breast tissue. We propose that the tumor microenvironment plays a crucial role in the expression of glycolytic and gluconeogenic enzymes and isoforms in tumour cells. Nonetheless, they not only participate in glycolytic and gluconeogenic enzymatic activities but may also influence other pathways, such as the Pentose-Phosphate-Pathway, TCA cycle, as well as other carbohydrate, lipid, and amino acid metabolism.
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Neoplasias de la Mama , Gluconeogénesis , Glucólisis , Humanos , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Neoplasias de la Mama/enzimología , Femenino , Línea Celular Tumoral , Isoenzimas/metabolismo , Isoenzimas/genéticaRESUMEN
INTRODUCTION: Sarcopenic obesity (SO) is characterised by the confluence of muscle deterioration and high adiposity. When non-surgical interventions prove insufficient, bariatric surgery (BS) becomes the primary approach. This study aimed to address BS effects on SO outcomes 1 year post-surgery among middle-aged women, also considering physical exercise's impact. METHODS: Prospective single-centre study of 140 patients who underwent Roux-en-Y gastric bypass or sleeve gastrectomy between November 2019 and December 2022. Participants were categorised into tertiles according to SO's diagnosis and severity (group 1-patients with the most severe SO; group 2-intermediate; group 3-the least severe or without SO), calculated considering the consensus issued by ESPEN and EASO in 2022. Evaluations of clinical and biochemical parameters were conducted before and 12 months after BS, and the variation was used for comparative purposes. Body composition was assessed using bone density scans. Linear regression analysis accounted for both surgery type and baseline body mass index (BMI). RESULTS: Before BS, SO prevalence in the overall sample was 89.3%, decreasing to 2.9% after BS. Group 1 had more body fat mass (56.9 vs 54.8 vs 50.7 kg, p < 0.001), total, trunk and leg fat at baseline and a significantly lower total skeletal muscle mass (47.2 vs 49.4 vs 51.8 kg, p < 0.001). One year post-BS, group 1 presented more weight loss (- 39.8 ± 11.4 kg, p = 0.031), BMI reduction (- 15.9 ± 4.6 kg/m2, p = 0.005) and lost more fat mass (- 32.6 vs - 30.5 vs - 27.9 kg, p = 0.005), but not total skeletal muscle mass (- 5.8 vs - 5.9 vs - 6.8 kg, p = 0.130). Remission rates for comorbidities were substantial among all groups, but more marked among patients within group 1 (type 2 diabetes mellitus 75%, hypertension 47.1% and dyslipidemia 52.8%). Engagement in physical exercise of any kind has increased post-BS (33.1% vs 79.1%). CONCLUSION: Despite concerns about malabsorptive mechanisms potentially worsening muscle loss, patients with the most severe SO undergoing BS lost more fat mass while experiencing the smallest reduction in total skeletal muscle mass. Remission rates for comorbidities following BS were notable among all groups.
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Cirugía Bariátrica , Diabetes Mellitus Tipo 2 , Derivación Gástrica , Obesidad Mórbida , Sarcopenia , Persona de Mediana Edad , Humanos , Femenino , Obesidad Mórbida/cirugía , Estudios Prospectivos , Sarcopenia/complicaciones , Sarcopenia/epidemiología , Diabetes Mellitus Tipo 2/cirugía , Obesidad/complicaciones , Obesidad/cirugía , Pérdida de Peso , Gastrectomía , Estudios RetrospectivosRESUMEN
Cancer is a major health problem worldwide and the second leading cause of death following cardiovascular diseases. Breast cancer is the leading cause of mortality and morbidity among women and one of the most common malignant neoplasms prompt to metastatic disease. In the present review, the mechanisms of the major cell adhesion molecules involved in tumor invasion are discussed, focusing on the case of breast cancer. A non-systematic updated revision of the literature was performed in order to assemble information regarding the expression of the adhesion cell molecules associated with metastasis.
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Neoplasias de la Mama , Femenino , Humanos , Neoplasias de la Mama/genética , Moléculas de Adhesión Celular/genéticaRESUMEN
BACKGROUND: In type 2 diabetes, insulin resistance is observed, and ß-cells are incapable of responding to glycemia demands, leading to hyperglycemia. Although the nature of ß-cells dysfunction in this disease is not fully understood, a link between the induction of pancreatic ß-cell premature senescence and its metabolic implications has been proposed. This study aimed to understand the relationship between diabetes and pancreatic senescence, particularly at the beginning of the disease. METHODS: C57Bl/6 J mice were fed two different diets, a normal diet and a high-fat diet, for 16 weeks. Pancreatic histomorphology analysis, insulin quantification, inflammation parameters, and senescence biomarkers for the experimental animals were assessed at weeks 12 and 16. RESULTS: The results proved that diabetes onset occurred at week 16 in the High Fat Diet group, supported by glycaemia, weight and blood lipid levels. Increased ß-cells size and number accompanied by increased insulin expression were observed. Also, an inflammatory status of the diabetic group was noted by increased levels of systemic IL-1ß and increased pancreatic fibrosis. Finally, the expression of galactosidase-beta 1 (GLB1) was significantly increased in pancreatic ß-cells. CONCLUSION: The study findings indicate that senescence, as revealed by an increase in GLB1 expression, is a key factor in the initial stage of diabetes.
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Diabetes Mellitus Tipo 2 , Células Secretoras de Insulina , Animales , Ratones , Glucemia/metabolismo , Dieta Alta en Grasa , Galactosidasas/metabolismo , Insulina , Células Secretoras de Insulina/metabolismo , Ratones Endogámicos C57BLRESUMEN
Obesity is a relevant risk factor in breast cancer (BC), but little is known about the effects of overweight and obesity in surgical outcomes of BC patients. The aim of this study is to analyse surgical options and associated overall survival (OS) in overweight and obese women with BC. In this study, 2143 women diagnosed between 2012 and 2016 at the Portuguese Oncology Institute of Porto (IPO-Porto) were included, and the clinicopathological information was retrieved from the institutional database. Patients were stratified by body mass index (BMI). Statistical analysis included Pearson's chi-squared test with statistical significance set at p < 0.05. Multinomial, binary logistic regression and cox proportional-hazards model were also performed to calculate odd ratios and hazard ratios with 95% confidence intervals for adjusted and non-adjusted models. The results revealed no statistical difference in histological type, topographic localization, tumour stage and receptor status and in the number of surgical interventions. Overweight women have increased probability to be subjected to sentinel node biopsy. Obese and overweight women are more likely to be submitted to conservative surgery and contrariwise, less likely to undergo total mastectomy. Patients submitted to conservative surgery and not submitted to total mastectomy had a favourable OS although without statistical significance. No significant differences were observed in OS when stratified by BMI. Our results revealed significant variations regarding the surgical options in overweight and obese patients, but these were not translated in OS difference. More research is recommended to better address treatment options in overweight and obese BC patients.
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Neoplasias de la Mama , Humanos , Femenino , Sobrepeso/complicaciones , Índice de Masa Corporal , Mastectomía , Obesidad/complicacionesRESUMEN
Breast cancer is a heterogeneous entity, where different molecular subtypes (MS) exhibit distinct prognostic and therapeutic responses. A series of 62 breast cancer samples stratified by MS was obtained from the tumor biobank of IPO-Porto. The expression of glycolysis and gluconeogenesis-regulating enzymes was investigated by immunohistochemistry. Data analysis included stratification according to MS, body mass index (BMI), and BMI with MS (mBMI). We observed significant differences in pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PCK), and fructose-1,6-bisphosphatase (FBP) tumor cell expression when stratified by MS and mBMI. The expression of these enzymes was also statistically dependent on hormonal receptors and HER2 status and correlated with pathological stage and histological grade. Obesity tended to attenuate these differences, particularly in PC expression, although these were not affected by adipocyte deposition or inflammatory infiltration at the tumor microenvironment. Nonetheless, PCK and FBP expression was also modified by the presence of obesity-associated disorders like diabetes, hypertension, and dyslipidemia. Taken together, these findings identify metabolic fingerprints for breast cancer as distinct histological types, which are affected by the presence of obesity and obesity-associated conditions. Despite the biological role of the differential expression of enzymes remaining unknown, the current study highlights the need to identify the expression of gluconeogenic-regulating enzymes as a tool for personalized medicine.
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Molecular subtype (MS) is one of the most used classifications of breast cancer (BC). Four MSs are widely accepted according to receptor expression of estrogen, progesterone, and HER2. The impact of adipose tissue on BC MS metabolic impairment is still unclear. The present work aims to elucidate the metabolic alterations in breast cancer cell lines representing different MSs subjected to adipocyte associated factors. Preadipocytes isolated from human subcutaneous adipose tissue were differentiated into mature adipocytes. MS representative cell lines were exposed to mature adipocyte secretome. Extracellular medium was collected for metabolomics and RNA was extracted to evaluate enzymatic expression by RT-PCR. Adipocyte secretome exposure resulted in a decrease in the Warburg effect rate and an increase in cholesterol release. HER2+ cell lines (BT-474 and SK-BR-3) exhibited a similar metabolic pattern, in contrast to luminal A (MCF-7) and triple negative (TN) (MDA-MB-231), both presenting identical metabolisms. Anaplerosis was found in luminal A and TN representative cells, whereas cataplerotic reactions were likely to occur in HER2+ cell lines. Our results indicate that adipocyte secretome affects the central metabolism distinctly in each BC MS representative cell line.
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Neoplasias , Secretoma , Humanos , Células MCF-7 , Adipocitos , Tejido Adiposo , EstrógenosRESUMEN
The COVID-19 pandemic has disrupted daily life, impacting relationships, work, and education. This has led to increased stress, anxiety, and depression, along with altered sleep patterns and eating behaviors. Quarantine and isolation have worsened mental health, especially in children and the elderly, due to the loss of activities and physical contact. Sleep disorders and negative dreams perpetuate poor sleep quality, increasing the risk of health issues. Sedentary lifestyles and emotional effects contribute to unhealthy eating patterns and obesity, exacerbated by disrupted routines and limited outdoor activities. Addressing these challenges requires prioritizing mental health, promoting healthy sleep habits, and addressing obesity factors. The pandemic has profoundly affected human well-being, but resilience, mental health, sleep, and nutrition can enhance overall well-being and adaptability in the post-COVID era. This comprehensive opinion aims to raise awareness of the wide-ranging impacts of this pandemic on various aspects of human well-being and to emphasize the importance of implementing strategies that prioritize mental health, improve sleep habits, address eating behaviors, and foster resilience to navigate and thrive in the face of future challenges.
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Inflammation may play a significant role in Keratoconus (KC), but the relationship between inflammatory markers and choroidal thickness (CT) is unknown. The purpose of this study was to evaluate serum inflammatory markers and correlate them with the choroidal profile of KC patients and control subjects. Forty patients with KC and 26 age-matched control subjects were enrolled in a cross-sectional case-control study. Choroidal profile was studied with a Spectralis Heidelberg apparatus and venous blood samples were collected. Neutrophil/lymphocyte ratio (NLR), monocyte/HDL ratio (MHR), platelet/lymphocyte ratio (PLR) and systemic immune inflammation index (SII) were calculated. Serum inflammatory biomarkers IL-1, IL-6 and TNF-alfa were also analyzed. KC group presented thicker choroids in each evaluated point when compared to the control group (subfoveal CT 417.38 ± 79.79 vs 299.61 ± 76.13, p < 0.001 for all measured locations). Mean values of NLR, PLR and SII were significantly higher in patients with KC (NLR p = 0.001; PLR p = 0.042; SII p = 0.007). Although KC patients presented higher mean levels of MHR, IL-1, IL-6 and TNF-α than control group, no significant differences were achieved. Positive correlations were found between subfoveal CT and NLR and SII (0.408, p = 0.001 and 0.288, p = 0.019 respectively). The results presented are in favor of a relationship between the increased CT and inflammatory mechanisms in KC patients. The elevated serum inflammatory indices NLR, SII and PLR provide additional evidence of a role for systemic inflammation in the pathophysiology of KC.
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Interleucina-6 , Queratocono , Humanos , Estudios de Casos y Controles , Estudios Transversales , Coroides , Inflamación , Neutrófilos , Factor de Necrosis Tumoral alfa , Interleucina-1 , Estudios Retrospectivos , Biomarcadores , LinfocitosRESUMEN
BACKGROUND: Breast cancer (BC) and obesity are two closely associated pathologies with increasing incidence and mortality rates. Bilateral Breast Cancer (BBC) displays a low incidence rate within BC and obesity represents a major risk factor. OBJECTIVE: The aim of this study is to analyzed BBC clinicopathological features distribution and determine the potential influence of obesity in BBC in these same features and overall survival. METHODS: Clinicopathological information was obtained from 42 cases of women with BBC diagnosed in IPO-Porto. To evaluate the frequency distribution of the clinicopathological data, a chi-square goodness of fit test was performed for BBC cases. A chi-square test of independence was applied for BMI stratification. Cox regression was performed for overall survival. Statistical significance was set at p-value < 0.05. RESULTS: Distribution of BBC clinicopathological features was found to be statistically significant in family history (p-value < 0.001), BBC type (p-value < 0.001), stage (p-value = 0.005), differentiation grade (p-value < 0.001), receptor expression (p-value < 0.001) and histological type (p-value = 0.031). In comparison to the statistical expected results, we observed an increased cases of absence of family history and less cases of metachronous BBC. Histological types between tumours of BBC were mostly concordant. All cases presented concordant receptor expression. Analysis stratified by BMI revealed that obese women were diagnosed later, although without statistical significance. All obese women presented poor differentiation grade (n = 6). Overweight patients display a tendency to a better overall survival with lower tumour stages and lower differentiation grades. CONCLUSIONS: Our results reveal the same receptor expression between contralateral tumours. Also, most tumours share the same histological type. When stratified by BMI, we observed a tendency for overweight women to have improved overall survival.
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Neoplasias de la Mama , Humanos , Femenino , Índice de Masa Corporal , Sobrepeso/complicaciones , Obesidad/complicaciones , Expresión GénicaRESUMEN
Type 2 Diabetes (T2D) is currently one of the fastest growing health challenging, a non-communicable disease result of the XXI century lifestyle. Given its growing incidence and prevalence, it became increasingly imperative to develop new technologies and implement new biomarkers for early diagnosis in order to promote lifestyle changes and thus cause a setback of the disease. Promising biomarkers have been identified as predictive of T2D development; however, none of them have yet been implemented in clinical practice routine. Moreover, many prediabetic biomarkers can also represent potential therapeutical targets in disease management. Previous studies have identified the most popular biomarkers, which are being thoroughly investigated. However, there are some biomarkers with promising preliminary results with limited associated studies; hence there is still much to be understood about its mechanisms and associations in T2D pathophysiology. This work identifies and discusses the promising results of Galectin-3, Ophthalmate and Fetuin-A.
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Diabetes Mellitus Tipo 2 , Estado Prediabético , Biomarcadores , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiología , Humanos , Incidencia , Estilo de Vida , Estado Prediabético/diagnóstico , Estado Prediabético/epidemiologíaRESUMEN
Aging is a natural physiological process, but one that poses major challenges in an increasingly aging society prone to greater health risks such as diabetes, cardiovascular disease, cancer, frailty, increased susceptibility to infection, and reduced response to vaccine regimens. The loss of capacity for cell regeneration and the surrounding tissue microenvironment itself is conditioned by genetic, metabolic, and even environmental factors, such as nutrition. The senescence of the immune system (immunosenescence) represents a challenge, especially when associated with the presence of age-related chronic inflammation (inflammaging) and affecting the metabolic programming of immune cells (immunometabolism). These aspects are linked to poorer health outcomes and therefore present an opportunity for host-directed interventions aimed at both eliminating senescent cells and curbing the underlying inflammation. Senotherapeutics are a class of drugs and natural products that delay, prevent, or reverse the senescence process - senolytics; or inhibit senescence-associated secretory phenotype - senomorphics. Natural senotherapeutics from food sources - nutritional senotherapeutics - may constitute an interesting way to achieve better age-associated outcomes through personalized nutrition. In this sense, the authors present herein a framework of nutritional senotherapeutics as an intervention targeting immunosenescence and immunometabolism, identifying research gaps in this area, and gathering information on concluded and ongoing clinical trials on this subject. Also, we present future directions and ideation for future clinical possibilities in this field.
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Ageing is a risk factor for chronic diseases including cancer, cardiovascular diseases, neurodegenerative disorders, and metabolic syndrome. Among others, senescence mechanisms have become a target of huge research on the topic of the ageing process. Cellular senescence is a state of an irreversible growth arrest that occurs in response to various forms of cellular stress and is characterized by a pro-inflammatory secretory phenotype. Multiple studies showed that cellular senescence occurs in both physiological and pathophysiological conditions. Senescent cells accumulate with ageing and can contribute to age-related decline in tissue function. Obesity is a metabolic condition that can accelerate the ageing process by promoting a premature induction of the senescent state of the cells. In contrast, caloric restriction without malnutrition is currently the most effective non-genetic intervention to delay ageing, and its potential in decreasing the cellular senescent burden is suggested. Here, it will be highlighted the cellular and molecular mechanisms involved in cellular senescence and discussed some of the research that is being done about how environmental conditions such as diet can affect the accumulation of senescent cells.
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During the pathophysiological course of type 2 diabetes (T2D), several metabolic imbalances occur. There is increasing evidence that metabolic dysfunction far precedes clinical manifestations. Thus, knowing and understanding metabolic imbalances is crucial to unraveling new strategies and molecules (biomarkers) for the early-stage prediction of the disease's non-clinical phase. Lifestyle interventions must be made with considerable involvement of clinicians, and it should be considered that not all patients will respond in the same manner. Individuals with a high risk of diabetic progression will present compensatory metabolic mechanisms, translated into metabolic biomarkers that will therefore show potential predictive value to differentiate between progressors/non-progressors in T2D. Specific novel biomarkers are being proposed to entrap prediabetes and target progressors to achieve better outcomes. This study provides a review of the latest relevant biomarkers in prediabetes. A search for articles published between 2011 and 2021 was conducted; duplicates were removed, and inclusion criteria were applied. From the 29 studies considered, a survey of the most cited (relevant) biomarkers was conducted and further discussed in the two main identified fields: metabolomics, and miRNA studies.
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Diabetes Mellitus Tipo 2 , Humanos , Metabolómica , MicroARNsRESUMEN
Metabolic syndrome is a complex and heterogeneous pathology characterized by a cluster of biochemical, clinical, and metabolic factors that came together in raising the risk of cardiovascular diseases, type 2 diabetes mellitus, and all-cause mortality. Some of these features are well defined in this syndrome like: obesity, inflammation, hypertension, insulin resistance, atherosclerotic dyslipidemias, endothelial dysfunction, and inflammation. This circuit is intermediated by a complex network of hormones, cytokines, transcription factors, and adipokines, among others. Some like leptin, adiponectin, Plasminogen activator inhibitor-1, interleukin-6, Tumor necrosis factor, and their influence on the metabolic syndrome are well described in the literature and new players are described continuously. One novel player was described in 2016 by Romere et al as a fasting-induced glycogenic protein hormone named asprosin. In order to perform a state-of-the-art, nonsystematic review of asprosin, a study of the available literature was carried out in the main database (Pubmed) and the results were studied and correlated to better understand the mechanism of action of this hormone. Asprosin is not only associated with the metabolic syndrome features like glucose and lipid metabolism, insulin resistance, obesity and inflammation but also in other pathologies metabolic syndrome related like diabetic retinopathy, polycystic ovary syndrome and anorexia nervosa. A limited number of pathways were already unveiled although much more research is needed to better understand the therapeutical potential of asprosin in the metabolic syndrome.
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There is increasing attention on the complex interactions occurring between schistosome parasites and their hosts. However, little is known about the occurrence, epidemiology, and mechanisms of schistosomiasis-associated infertility. In this article, we argue that an in-depth understanding of the interplay between parasites and the host endocrine system may significantly enhance current knowledge of infertility in infected individuals. We discuss the basic hormonal mechanisms that may lead to the discovery of entirely novel anthelmintic interventions against schistosomiasis.