Conserved multi-tissue transcriptomic adaptations to exercise training in humans and mice.

Physical activity is associated with beneficial adaptations in human and rodent metabolism. We studied over 50 complex traits before and after exercise intervention in middle-aged men and a panel of 100 diverse strains of female mice. Candidate gene analyses in three brain regions, muscle, liver, heart, and adipose tissue of mice indicate genetic drivers of clinically relevant traits, including volitional exercise volume, muscle metabolism, adiposity, and hepatic lipids.

Gingival Orofacial Granulomatosis Clinical and 2D/3D Microscopy Features after Orthodontic Therapy: A Pediatric Case Report.

Orofacial granulomatosis (OFG) represents a heterogeneous group of rare orofacial diseases. When affecting gingiva, it appears as a chronic soft tissue inflammation, sometimes combined with the enlargement and swelling of other intraoral sites, including the lips. Gingival biopsy highlights noncaseating granulomatous inflammation, similar to that observed in Crohn's disease and sarcoidosis.

Effects of Translucency and Thickness of Lithium Disilicate-Reinforced Glass-Ceramic Veneers on the Degree of Conversion of a Purely Light-Curing Bonding Resin: An In Vitro Study.

The objective of this study was to evaluate the variations in the degree of conversion (DC) of a light-curing composite resin when the thickness or the translucency of lithium disilicate-enriched glass-ceramic veneers are modified. IPS e. max CAD blocks of the MT-A2, LT-A2 and MO1 types were cut to obtain four slices with thicknesses ranging from 0.

Combining glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) in patients with type 2 diabetes mellitus (T2DM).

Due to their cardiovascular protective effect, glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) represent breakthrough therapies for type 2 diabetes mellitus (T2DM). In this review article, we discuss the mechanistic and clinical synergies that make the combined use of GLP-1RAs and SGLT2is appealing in patients with T2DM. Overall, the presented cumulative evidence supports the benefits of GLP-1RA plus SGLT2i combination therapy on metabolic-cardiovascular-renal disease in patients with T2DM, with a low hypoglycemia risk.

Association between physical activity, growth differentiation factor 15 and bodyweight in older adults: A longitudinal mediation analysis.

Background: Late-life aging is often associated with appetite reduction and weight loss. Physical activity (PA) may prevent these processes, but the molecular mechanisms involved remain elusive. The present study investigated the putative mediating aspect of growth differentiation factor 15 (GDF-15), a stress signalling protein involved in aging, exercise and appetite control, on the association between PA and late-life-associated weight loss.

Inactivating the lipid kinase activity of PI3KC2β is sufficient to rescue myotubular myopathy in mice.

Phosphoinositides (PIs) are membrane lipids that regulate signal transduction and vesicular trafficking. X-linked centronuclear myopathy (XLCNM), also called myotubular myopathy, results from loss-of-function mutations in the MTM1 gene, which encodes the myotubularin phosphatidylinositol 3-phosphate (PtdIns3P) lipid phosphatase. No therapy for this disease is currently available.

Endothelial DLL4 Is an Adipose Depot-Specific Fasting Sensor Regulating Fatty Acid Fluxes.

Background: Adaptation of fat depots to change in fuel availability is critical for metabolic flexibility and cardiometabolic health. The mechanisms responsible for fat depot-specific lipid sensing and shuttling remain elusive. Adipose tissue microvascular endothelial cells (AT-EC) regulates bidirectional fatty acid fluxes depending on fed or fasted state.

An integrated single cell and spatial transcriptomic map of human white adipose tissue.

To date, single-cell studies of human white adipose tissue (WAT) have been based on small cohort sizes and no cellular consensus nomenclature exists. Herein, we performed a comprehensive meta-analysis of publicly available and newly generated single-cell, single-nucleus, and spatial transcriptomic results from human subcutaneous, omental, and perivascular WAT. Our high-resolution map is built on data from ten studies and allowed us to robustly identify >60 subpopulations of adipocytes, fibroblast and adipogenic progenitors, vascular, and immune cells.

EPAC1 Pharmacological Inhibition with AM-001 Prevents SARS-CoV-2 and Influenza A Virus Replication in Cells.

The exceptional impact of the COVID-19 pandemic has stimulated an intense search for antiviral molecules. Host-targeted antiviral molecules have the potential of presenting broad-spectrum antiviral activity and are also considered as less likely to select for resistant viruses. In this study, we investigated the antiviral activity exerted by AM-001, a specific pharmacological inhibitor of EPAC1, a host exchange protein directly activated by cyclic AMP (cAMP).

Estrogen Actions in Placental Vascular Morphogenesis and Spiral Artery Remodeling: A Comparative View between Humans and Mice.

Estrogens, mainly 17β-estradiol (E2), play a critical role in reproductive organogenesis, ovulation, and fertility via estrogen receptors. E2 is also a well-known regulator of utero-placental vascular development and blood-flow dynamics throughout gestation. Mouse and human placentas possess strikingly different morphological configurations that confer important reproductive advantages.

The anxiolytic drug opipramol inhibits insulin-induced lipogenesis in fat cells and insulin secretion in pancreatic islets.

The antidepressant drug opipramol has been reported to exert antilipolytic effect in human adipocytes, suggesting that alongside its neuropharmacological properties, this agent might modulate lipid utilization by peripheral tissues. However, patients treated for depression or anxiety disorders by this tricyclic compound do not exhibit the body weight gain or the glucose tolerance alterations observed with various other antidepressant or antipsychotic agents such as amitriptyline and olanzapine, respectively. To examine whether opipramol reproduces or impairs other actions of insulin, its direct effects on glucose transport, lipogenesis and lipolysis were investigated in adipocytes while its influence on insulin secretion was studied in pancreatic islets.

One-year outcomes in cardiogenic shock triggered by ventricular arrhythmia: An analysis of the FRENSHOCK multicenter prospective registry.

Background: Cardiogenic shock (CS) is a life-threatening condition carrying poor prognosis, potentially triggered by ventricular arrhythmia (VA). Whether the occurrence of VA as trigger of CS worsens the prognosis compared to non-VA triggers  remains  unclear.  The  aim  of  this  study  was  to  evaluate  1-year  outcomes [mortality, heart transplantation, ventricular assist devices (VAD)] between VA-triggered and non-VA-triggered CS.

Effects of Fatty Acid Metabolites on Adipocytes Britening: Role of Thromboxane A2.

Obesity is a complex disease highly related to diet and lifestyle and is associated with low amount of thermogenic adipocytes. Therapeutics that regulate brown adipocyte recruitment and activity represent interesting strategies to fight overweight and associated comorbidities. Recent studies suggest a role for several fatty acids and their metabolites, called lipokines, in the control of thermogenesis.

Nutraceutical approaches to non-alcoholic fatty liver disease (NAFLD): A position paper from the International Lipid Expert Panel (ILEP).

Non-Alcoholic Fatty Liver Disease (NAFLD) is a common condition affecting around 10-25% of the general adult population, 15% of children, and even > 50% of individuals who have type 2 diabetes mellitus. It is a major cause of liver-related morbidity, and cardiovascular (CV) mortality is a common cause of death. In addition to being the initial step of irreversible alterations of the liver parenchyma causing cirrhosis, about 1/6 of those who develop NASH are at risk also developing CV disease (CVD).

Does housing temperature influence glucose regulation and muscle-fat crosstalk in mice?

The robustness of scientific results is partly based on their reproducibility. Working with animal models, particularly in the field of metabolism, requires to avoid any source of stress to rule out a maximum of bias. Housing at room temperature is sufficient to induce thermal stress activating key thermogenic organs such as brown adipose tissue (BAT) and skeletal muscle.

Effect of increased protein intake and exogenous ketosis on body composition, energy expenditure and exercise capacity during a hypocaloric diet in recreational female athletes.

Since low body weight is an important determinant of success in many sports such as gymnastics, martial arts and figure skating, athletes can benefit from effective weight loss strategies that preserve muscle mass and athletic performance. The present study investigates the effects of increased protein intake and exogenous ketosis on body composition, energy expenditure, exercise capacity, and perceptions of appetite and well-being during a hypocaloric diet in females. Thirty-two female recreational athletes (age: 22.

Smoking and Diabetes: Sex and Gender Aspects and Their Effect on Vascular Diseases.

Smoking and diabetes mellitus (DM) have been identified as 2 major cardiovascular risk factors for many years. In the field of cardiovascular diseases, considering sex differences, or gender differences, or both has become an essential element in moving toward equitable and quality health care. We reviewed the effect of sex or gender on the link between smoking and DM.

Impact of 3D-printed models in meetings with parents of children undergoing interventional cardiac catheterisation.

Background: Paediatric interventional catheterisation has consistently improved in recent decades, with often highly successful outcomes. However, progress is still required in terms of the information delivered to parents and how parental anxiety is managed.

Aim: To investigate the impact of cardiac printed models on improving parental understanding and alleviating anxiety before interventional catheterisation.

Plasma inflammation-related biomarkers are associated with intrinsic capacity in community-dwelling older adults.

Background: How inflammation relates to intrinsic capacity (IC), the composite of physical and mental capacities, remains undefined. Our study aimed to investigate the cross-sectional and longitudinal associations between plasma inflammation-related biomarkers and IC in older adults.

Methods: This secondary analysis of the Multidomain Alzheimer Preventive Trial (MAPT) included 1238 community-dwelling older individuals with IC assessments from 12 to 60 months.

Inhibition of the endocannabinoid system reverses obese phenotype in aged mice and partly restores skeletal muscle function.

Sarcopenia, the age-related loss of skeletal muscle mass, is associated with lipid accumulation and anabolic resistance; phenomena also observed in obesity and worsen when obesity and aging are combined. The endocannabinoid system (ECS) is overactivated in obesity, but its role in aging obesity-related muscle dysfunction is unknown. The aims of this study were to evaluate the effect of inhibition of the ECS by rimonabant (RIM) on the metabolic alterations induced by a high-fat high-sucrose diet and on skeletal muscle mass/function in aged mice.

Adipose tissue is a source of regenerative cells that augment the repair of skeletal muscle after injury.

Fibro-adipogenic progenitors (FAPs) play a crucial role in skeletal muscle regeneration, as they generate a favorable niche that allows satellite cells to perform efficient muscle regeneration. After muscle injury, FAP content increases rapidly within the injured muscle, the origin of which has been attributed to their proliferation within the muscle itself. However, recent single-cell RNAseq approaches have revealed phenotype and functional heterogeneity in FAPs, raising the question of how this differentiation of regenerative subtypes occurs.

Glycaemic Control in People with Type 2 Diabetes Mellitus Switching from Basal Insulin to Insulin Glargine 300 U/ml (Gla-300): Results from the REALI Pooled Database.

Introduction: Using pooled data from the REALI European database, we evaluated the impact of previous basal insulin (BI) type on real-life effectiveness and safety of switching to insulin glargine 300 U/ml (Gla-300) in people with suboptimally controlled type 2 diabetes.

Methods: Patient-level data were pooled from 11 prospective, open-label, 24-week studies. Participants were classified according to the type of prior BI.

TNFR-1 and GDF-15 Are Associated With Plasma Neurofilament Light Chain and Progranulin Among Community-Dwelling Older Adults: A Secondary Analysis of the MAPT Study.

There is growing evidence that cognitive decline can be affected by both nutritional aspects and inflammation. Plasma neurodegenerative biomarkers stand out as minimally invasive useful measures to monitor the potential risk of cognitive decline. This study aimed to investigate the associations between biomarkers of neurodegeneration, nutrition, and inflammation among community-dwelling older adults, and to verify if associations differed according to apolipoprotein E (APOE) ε4 status.

Impact of Pre-Existing History of Heart Failure on Patient Profile, Therapeutic Management, and Prognosis in Cardiogenic Shock: Insights from the FRENSHOCK Registry.

There is a large heterogeneity among patients presenting with cardiogenic shock (CS). It is crucial to better apprehend this heterogeneity in order to adapt treatments and improve prognoses in these severe patients. Notably, the presence (or absence) of a pre-existing history of chronic heart failure (CHF) at time of CS onset may be a significant part of this heterogeneity, and data focusing on this aspect are lacking.