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Antibodies to citrullinated protein antigens (acpas) induce adipose tissue dysfunction impairing adipocyte differentiation, lipid accumulation and promoting macrophage polarisation. in vitro effect of biologic dmards
No full textAdipose tissue (AT) dysfunction plays a key role in inflammation- and lipid-induced metabolic complications, and rheumatoid arthritis (RA) is closely linked to metabolic comorbidities such as obesity and insulin resistance (IR). Anti-citrullinated protein antibodies (ACPAs) are implicated in the development of cardiovascular disease associated with RA, but their specific impact on AT function remains unclear. This study aimed to 1) investigate the direct effects of ACPAs on AT function—including adipocyte differentiation, macrophage polarization, and lipid accumulation—and 2) assess the ability of tocilizumab (TCZ) and infliximab (IFX) to modulate the metabolic alterations induced by ACPAs in AT. IgGs from normal human serum (IgG-NHS) and IgGs-ACPAs were isolated from the serum of 20 healthy controls and 20 RA patients. 3T3-L1 fibroblasts were treated with IgG-NHS or IgG-ACPAs, either alone or in combination with IFX or TCZ, during early (day 0) and late (day 9) stages of adipocyte differentiation, with lipid accumulation assessed by oil red O (ORO) staining. M0 macrophages derived from THP-1 cells were treated with IgG-NHS or IgG-ACPAs for 12 hours, followed by another 12-hour treatment with or without IFX and TCZ, and macrophage polarization was analyzed via flow cytometry. Visceral and subcutaneous AT samples from 8 obese patients undergoing bariatric surgery were treated ex vivo with IgG-NHS or IgG-ACPAs, alone or in combination with biological DMARDs. Across all experiments, the expression of proteins and genes involved in adipogenesis, inflammation, insulin signaling, and lipid metabolism was analyzed by RT-PCR, western blot, and ELISA.S
Dysregulation of the miRNome unveils a crosstalk between obesity and prostate cancer: miR-107 asa personalized diagnostic and therapeutic tool.
No full textProstate-specific antigen (PSA) is the gold-standard marker to screen prostate cancer (PCa) nowadays. Unfortunately, its lack of specificity and sensitivity makes the identification of novel tools to diagnose PCa an urgent medical need. In this context, microRNAs (miRNAs) have emerged as potential sources of non-invasive diagnostic biomarkers in several pathologies. Therefore, this study was aimed at assessing for the first time the dysregulation of the whole plasma miRNome in PCa patients and its putative implication in PCa from a personalized perspective (i.e., obesity condition). Plasma miRNome from a discovery cohort (18 controls and 19 PCa patients) was determined using an Affymetrix-miRNA array, showing that the expression of 104 miRNAs was significantly altered, wherein six exhibited a significant receiver operating characteristic (ROC) curve to distinguish between control and PCa patients (area under the curve [AUC] = 1). Then, a systematic validation using an independent cohort (135 controls and 160 PCa patients) demonstrated that miR-107 was the most profoundly altered miRNA in PCa (AUC = 0.75). Moreover, miR-107 levels significantly outperformed the ability of PSA to distinguish between control and PCa patients and correlated with relevant clinical parameters (i.e., PSA). These differences were more pronounced when considering only obese patients (BMI > 30). Interestingly, miR-107 levels were reduced in PCa tissues versus non-tumor tissues (n = 84) and in PCa cell lines versus non-tumor cells. In vitro miR-107 overexpression altered key aggressiveness features in PCa cells (i.e., proliferation, migration, and tumorospheres formation) and modulated the expression of important genes involved in PCa pathophysiology (i.e., lipid metabolism [i.e., FASN] and splicing process). Altogether, miR-107 might represent a novel and useful personalized diagnostic and prognostic biomarker and a potential therapeutic tool in PCa, especially in obese patients.This work was funded by MINECO/MECD (PID2019-105564RB-I00,
FPU16/06190, FPU17/00263, FPU18/02485, FPU18/06009, and PRE2
020-094225), University of Córdoba (Programa Operativo FEDER
Andalucía: 27416), Junta de Andalucía (BIO-0139, PI-0094-2020,
and P20_00442), European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement
no. 847468, and CIBERobn. CIBER is an initiative of Instituto de Salud
Carlos III, Ministerio de Sanidad, Servicios Sociales e Igualdad, SpainS
Circulating inflammatory biomarkers, adipokines and breast cancer risk-a case-control study nested within the EPIC cohort.
No full textInflammation has been hypothesized to play a role in the development and progression of breast cancer and might differently impact breast cancer risk among pre and postmenopausal women. We performed a nested case-control study to examine whether pre-diagnostic circulating concentrations of adiponectin, leptin, c-reactive protein (CRP), tumour necrosis factor-α, interferon-γ and 6 interleukins were associated with breast cancer risk, overall and by menopausal status. Pre-diagnostic levels of inflammatory biomarkers were measured in plasma from 1558 case-control pairs from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. We used conditional logistic regression to estimate the odds ratios (ORs) of breast cancer at blood collection, per one standard deviation increase in biomarker concentration. Cases were diagnosed at a mean age of 61.4 years on average 8.6 years after blood collection. No statistically significant association was observed between inflammatory markers and breast cancer risk overall. In premenopausal women, borderline significant inverse associations were observed for leptin, leptin-to-adiponectin ratio and CRP [OR= 0.89 (0.77-1.03), OR= 0.88 (0.76-1.01) and OR= 0.87 (0.75-1.01), respectively] while positive associations were observed among postmenopausal women [OR= 1.16 (1.05-1.29), OR= 1.11 (1.01-1.23), OR= 1.10 (0.99-1.22), respectively]. Adjustment for BMI strengthened the estimates in premenopausal women [leptin: OR = 0.83 (0.68-1.00), leptin-to-adiponectin ratio: OR = 0.80 (0.66-0.97), CRP: OR = 0.85 (0.72-1.00)] but attenuated the estimates in postmenopausal women [leptin: OR = 1.09 (0.96-1.24), leptin-to-adiponectin ratio: OR = 1.02 (0.89-1.16), CRP: OR = 1.04 (0.92-1.16)]. Associations between CRP, leptin and leptin-to-adiponectin ratio with breast cancer risk may represent the dual effect of obesity by menopausal status although this deserves further investigation.This work was funded by the French National Cancer Institute (grant number 2016-128) and the World Cancer Research Fund (grant number 2017/1614). Manon Cairat was supported by a PhD fellowship from la Ligue Nationale Contre le Cancer.
The coordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC). The national cohorts are supported by: Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer
Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology - ICO (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C8221/A29017 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk; MR/M012190/1 to EPIC-Oxford). (United Kingdom). The funders were not involved in designing the study; collecting, analyzing or interpreting the data; or in writing or submitting the manuscript for publication.S
The Contribution of Wnt Signaling to Vascular Complications in Type 2 Diabetes Mellitus.
No full textVascular complications are the leading cause of morbidity and mortality among patients with type 2 diabetes mellitus (T2DM). These vascular abnormalities result in a chronic hyperglycemic state, which influences many signaling molecular pathways that initially lead to increased oxidative stress, increased inflammation, and endothelial dysfunction, leading to both microvascular and macrovascular complications. Endothelial dysfunction represents the initial stage in both types of vascular complications; it represents "mandatory damage" in the development of microvascular complications and only "introductory damage" in the development of macrovascular complications. Increasing scientific evidence has revealed an important role of the Wnt pathway in the pathophysiology of the vascular wall. It is well known that the Wnt pathway is altered in patients with T2DM. This review aims to be an update of the current literature related to the Wnt pathway molecules that are altered in patients with T2DM, which may also be the cause of damage to the vasculature. Both microvascular complications (retinopathy, nephropathy, and neuropathy) and macrovascular complications (coronary artery disease, cerebrovascular disease, and peripheral arterial disease) are analyzed. This review aims to concisely concentrate all the evidence to facilitate the view on the vascular involvement of the Wnt pathway and its components by highlighting the importance of exploring possible therapeutic strategy for patients with T2DM who develop vascular pathologies.This research was funded by Instituto de Salud Carlos III grants (PI18-00803, PI21-01069,
and PI18-01235), co-funded by the European Regional Development Fund (FEDER) and by a Junta de
Andalucía grant (PI-0268-2019). In addition, R.S.-T. was funded by the University of Granada with
co-funding by FEDER, (grant number 8110), and C.G.-F. and S.G.-S. were funded by a postdoctoral
fellowship (CD20/00022) and a predoctoral fellowship (FI19/00118), respectively, from the Instituto
de Salud Carlos III.S
Effectiveness, implementation, and monitoring variables of intermittent hypoxic bicycle training in patients recovered from COVID-19: The AEROBICOVID study.
No full textHypoxic exposure is safely associated with exercise for many pathological conditions, providing additional effects on health outcomes. COVID-19 is a new disease, so the physiological repercussions caused by exercise in affected patients and the safety of exposure to hypoxia in these conditions are still unknown. Due to the effects of the disease on the respiratory system and following the sequence of AEROBICOVID research work, this study aimed to evaluate the effectiveness, tolerance and acute safety of 24 bicycle training sessions performed under intermittent hypoxic conditions through analysis of peripheral oxyhemoglobin saturation (SpO2), heart rate (HR), rate of perceived exertion (RPE), blood lactate concentration ([La-]) and symptoms of acute mountain sickness in patients recovered from COVID-19. Participants were allocated to three training groups: the normoxia group (GN) remained in normoxia (inspired fraction of O2 (FiO2) of ∼20.9%, a city with 526 m altitude) for the entire session; the recovery hypoxia group (GHR) was exposed to hypoxia (FiO2 ∼13.5%, corresponding to 3,000 m altitude) all the time except during the effort; the hypoxia group (GH) trained in hypoxia (FiO2 ∼13.5%) throughout the session. The altitude simulation effectively reduced SpO2 mean with significant differences between groups GN, GHR, and GH, being 96.9(1.6), 95.1(3.1), and 87.7(6.5), respectively. Additionally, the proposed exercise and hypoxic stimulus was well-tolerated, since 93% of participants showed no or moderate acute mountain sickness symptoms; maintained nearly 80% of sets at target heart rate; and most frequently reporting session intensity as an RPE of "3" (moderate). The internal load calculation, analyzed through training impulse (TRIMP), calculated using HR [TRIMPHR = HR * training volume (min)] and RPE [TRIMPRPE = RPE * training volume (min)], showed no significant difference between groups. The current strategy effectively promoted the altitude simulation and monitoring variables, being well-tolerated and safely acute exposure, as the low Lake Louise scores and the stable HR, SpO2, and RPE values showed during the sessions.S
The clinical and molecular cardiometabolic fingerprint of an exploratory psoriatic arthritis cohort is associated with the disease activity and differentially modulated by methotrexate and apremilast.
No full text(1) To evaluate clinical and molecular cardiovascular disease (CVD) signs and their relationship with psoriatic arthritis (PsA) features and (2) to identify a clinical patient profile susceptible to benefit from methotrexate (MTX) and/or apremilast regarding CVD risk. This cross-sectional study included 100 patients with PsA and 100 age-matched healthy donors. In addition, an exploratory cohort of 45 biologically naïve patients treated for 6 months with apremilast, MTX or combined therapy according to routine clinical practice was recruited. Extensive clinical and metabolic profiles were obtained. Ninety-nine surrogate CVD-related molecules were analysed in plasma and peripheral blood mononuclear cells (PBMCs). Hard cluster analysis was performed to identify the clinical and molecular phenotypes. Mechanistic studies were performed on adipocytes. Cardiometabolic comorbidities were associated with disease activity and long-term inflammatory status. Thirty-five CVD-related proteins were altered in the plasma and PBMCs of PsA patients and were associated with the key clinical features of the disease. Plasma levels of some of the CVD-related molecules might distinguish insulin-resistant patients (MMP-3, CD163, FABP-4), high disease activity (GAL-3 and FABP-4) and poor therapy outcomes (CD-163, LTBR and CNTN-1). Hard cluster analysis identified two phenotypes of patients according to the rates of cardiometabolic comorbidities with distinctive clinical and molecular responses to each treatment. (1) Novel CVD-related proteins associated with clinical features could be emerging therapeutic targets in the context of PsA and (2) the pleiotropic action of apremilast could make it an excellent choice for the management of PsA patients with high CVD risk, targeting metabolic alterations and CVD-related molecules
Awareness of venous thromboembolism among patients with cancer: Preliminary findings from a global initiative for World Thrombosis Day.
No full textCancer-associated venous thromboembolism (CAT) has detrimental impact on patients' clinical outcomes and quality of life. Data on CAT education, communication, and awareness among the general cancer population are scanty. We present the preliminary results of an ongoing patient-centered survey including 27 items covering major spheres of CAT. The survey, available in 14 languages, was promoted and disseminated online through social networks, email newsletters, websites, and media. As of September 20, 2022, 749 participants from 27 countries completed the survey. Overall, 61.8% (n = 460) of responders were not aware of their risk of CAT. Among those who received information on CAT, 26.2% (n = 56) were informed only at the time of CAT diagnosis. Over two thirds (69.1%, n = 501) of participants received no education on signs and symptoms of venous thromboembolism (VTE); among those who were educated about the possible clinical manifestations, 58.9% (n = 119) were given instructions to seek consultation in case of VTE suspicion. Two hundred twenty-four respondents (30.9%) had a chance to discuss the potential use of primary thromboprophylaxis with health-care providers. Just over half (58.7%, n = 309) were unaware of the risks of bleeding associated with anticoagulation, despite being involved in anticoagulant-related discussions or exposed to anticoagulants. Most responders (85%, n = 612) valued receiving CAT education as highly relevant; however, 51.7% (n = 375) expressed concerns about insufficient time spent and clarity of education received. This ongoing survey involving cancer patients with diverse ethnic, cultural, and geographical backgrounds highlights important patient knowledge gaps. These findings warrant urgent interventions to improve education and awareness, and reduce CAT burden
Risk-based versus GFR threshold criteria for nephrology referral in chronic kidney disease.
No full textChronic kidney disease (CKD) and kidney failure are global health problems associated with morbidity, mortality and healthcare costs, with unequal access to kidney replacement therapy between countries. The diversity of guidelines concerning referral from primary care to a specialist nephrologist determines different outcomes around the world among patients with CKD where several guidelines recommend referral when the glomerular filtration rate (GFR) is
Association between ultra-processed food consumption and gut microbiota in senior subjects with overweight/obesity and metabolic syndrome.
No full textThe production and consumption of ultra-processed foods (UPF) has increased considerably during the last years worldwide. Collective evidence shows the association between UPF consumption and adverse health outcomes, including inflammatory gastro-intestinal disorders and obesity. The gut microbiota has been suggested as potential mediator of the effects of UPF consumption on metabolism and health. However, few studies have been conducted in order to elucidate these aspects. Therefore, the aim of the present study was to assess the cross-sectional associations between UPF consumption and gut microbiota in a population of senior subjects (n = 645) within the frame of the PREDIMED-Plus trial. Eligible participants were men and women (aged 55-75 years), without documented history of cardiovascular disease at enrollment, with overweight/obesity (body mass index ≤ 27 and <40 kg/m2) and metabolic syndrome. Using the information of food frequency questionnaires, the consumption of UPF, expressed as a percentage of total dietary energy intake in kcal/day, was calculated considering those food items classified in group 4 of NOVA system. Population was categorized according to tertiles of UPF consumption. Taxonomic fecal microbiota information, along with blood biochemical parameters, anthropometric measurements and clinical data were obtained. Bioinformatics analysis was performed to study the association between fecal microbiota composition and UPF consumption. We observed that subjects allocated in the highest tertile of UPF consumption (21.4 ± 5.0 % kcal/day) presented lower adherence to MedDiet (p < 0.001) and higher total energy intake (p < 0.001). The taxonomic analysis of the fecal microbiota revealed a significant (Benjamini-Hochberg adjusted p < 0.2) positive association between specific taxa and tertiles (T) of UPF consumption: Alloprevotella (p = 0.041 vs. T2; p = 0.065 vs. T3), Negativibacillus (p = 0.096 vs. T3), Prevotella (p = 0.116 vs. T3), and Sutterella (p = 0.116 vs. T2). UPF consumption was positively associated with lower adherence to MedDiet and higher total energy intake in senior subjects with overweight obesity and metabolic syndrome. In addition, positive association with specific fecal microbiota taxa related to inflammatory gastro-intestinal diseases and low consumption of fruits and vegetables, was observed.S
Respiratory symptoms and their determinants in the general Spanish population: changes over 20 years
No full textBackground Few large epidemiological studies have analysed the prevalence of respiratory symptoms and their determinants in the general adult population. We investigated the prevalence and determinants of respiratory symptoms and compared their prevalence with that of two previous studies conducted in 1999 and 2009.Method EPISCAN II was a multicentre, cross-sectional, population-based epidemiological study in individuals older than 40 years.Results A total of 9092 individuals were included. Up to 47.5% reported at least one respiratory symptom, being more frequent in women than in men (49.4% versus 45.5%, p=0.0002) and with wheezing being the most frequent (33.7%) followed by dyspnoea (26.8%). The presence of any symptom was associated with female sex, higher body mass index (BMI), lower forced expiratory volume in 1 s (FEV1 % pred), reduced physical activity, a higher Charlson index and the presence of anxiety and depression. Smoking was also significantly associated with having at least one respiratory symptom in a dose-response fashion (OR: 1.415, 1.916, 2.192 and 2.987 for 0-10, 10-20, 20-30 and >30 pack-years, respectively, all p30 pack-years, respectively, all