Semaglutide Improves Liver Steatosis and De Novo Lipogenesis Markers in Obese and Type-2-Diabetic Mice with Metabolic-Dysfunction-Associated Steatotic Liver Disease.

Metabolic-dysfunction-associated steatotic liver disease (MASLD) is a prevalent clinical condition associated with elevated morbidity and mortality rates. Patients with MASLD treated with semaglutide, a glucagon-like peptide-1 receptor agonist, demonstrate improvement in terms of liver damage. However, the mechanisms underlaying this beneficial effect are not yet fully elucidated.

A mutual regulatory loop between miR-155 and SOCS1 influences renal inflammation and diabetic kidney disease.

Diabetic kidney disease (DKD) is a common microvascular complication of diabetes, a global health issue. Hyperglycemia, in concert with cytokines, activates the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway to induce inflammation and oxidative stress contributing to renal damage. There is evidence of microRNA-155 (miR-155) involvement in diabetes complications, but the underlying mechanisms are unclear.

Walnut inclusion in a palm oil-based atherogenic diet promotes traits predicting stable atheroma plaque in -deficient mice.

Introduction: The lower rates of cardiovascular disease in Southern Europe could be partially explained by the low prevalence of lipid-rich atheroma plaques. Consumption of certain foods affects the progression and severity of atherosclerosis. We investigated whether the isocaloric inclusion of walnuts within an atherogenic diet prevents phenotypes predicting unstable atheroma plaque in a mouse model of accelerated atherosclerosis.

The presence of activating IgG Fc receptors in macrophages aggravates the development of experimental abdominal aortic aneurysm.

Introduction: Abdominal aortic aneurysm (AAA) is a multifactorial, degenerative disease characterized by progressive aortic dilation and chronic activation of inflammation, proteolytic activity, and oxidative stress in the aortic wall. The immune response triggered by antibodies against antigens present in the vascular wall participates in the formation and progression of AAA through mechanisms not completely understood. This work analyses the function of specific IgG receptors (FcγR), especially those expressed by monocytes/macrophages, in the development of experimental AAA.

The Synthetic Flavonoid Hidrosmin Improves Endothelial Dysfunction and Atherosclerotic Lesions in Diabetic Mice.

In diabetes, chronic hyperglycemia, dyslipidemia, inflammation and oxidative stress contribute to the progression of macro/microvascular complications. Recently, benefits of the use of flavonoids in these conditions have been established. This study investigates, in two different mouse models of diabetes, the vasculoprotective effects of the synthetic flavonoid hidrosmin on endothelial dysfunction and atherogenesis.

Nephroprotective Effects of Synthetic Flavonoid Hidrosmin in Experimental Diabetic Nephropathy.

Diabetes mellitus (DM) is a high-impact disease commonly characterized by hyperglycemia, inflammation, and oxidative stress. Diabetic nephropathy (DN) is a common diabetic microvascular complication and the leading cause of chronic kidney disease worldwide. This study investigates the protective effects of the synthetic flavonoid hidrosmin (5-O-(beta-hydroxyethyl) diosmin) in experimental DN induced by streptozotocin injection in apolipoprotein E deficient mice.

Fcγ receptor activation mediates vascular inflammation and abdominal aortic aneurysm development.

Background: Abdominal aortic aneurysm (AAA), a degenerative vascular pathology characterized by permanent dilation of the aorta, is considered a chronic inflammatory disease involving innate/adaptive immunity. However, the functional role of antibody-dependent immune response against antigens present in the damaged vessel remains unresolved. We hypothesized that engagement of immunoglobulin G (IgG) Fc receptors (FcγR) by immune complexes (IC) in the aortic wall contributes to AAA development.

Cyclic mimetics of kinase-inhibitory region of Suppressors of Cytokine Signaling 1: Progress toward novel anti-inflammatory therapeutics.

Herein we investigated the structural and cellular effects ensuing from the cyclization of a potent inhibitor of JAK2 as mimetic of SOCS1 protein, named PS5. The introduction of un-natural residues and a lactam internal bridge, within SOCS1-KIR motif, produced candidates that showed high affinity toward JAK2 catalytic domain. By combining CD, NMR and computational studies, we obtained valuable models of the interactions of two peptidomimetics of SOCS1 to deepen their functional behaviors.

Ellagic Acid as a Tool to Limit the Diabetes Burden: Updated Evidence.

Oxidative stress contributes not only to the pathogenesis of type 2 diabetes (T2D) but also to diabetic vascular complications. It follows that antioxidants might contribute to limiting the diabetes burden. In this review we focus on ellagic acid (EA), a compound that can be obtained upon intestinal hydrolysis of dietary ellagitannins, a family of polyphenols naturally found in several fruits and seeds.

Protective effect of suppressor of cytokine signalling 1-based therapy in experimental abdominal aortic aneurysm.

Background And Purpose: Abdominal aortic aneurysm (AAA) is a multifactorial disease characterized by chronic inflammation, oxidative stress and proteolytic activity in the aortic wall. Targeting JAK/signal transducer and activator of transcription (JAK/STAT) pathway is a promising strategy for chronic inflammatory diseases. We investigated the vasculo-protective role of suppressor of cytokine signalling-1 (SOCS1), the negative JAK/STAT regulator, in experimental AAA.

Anti-inflammatory, antioxidant and renoprotective effects of SOCS1 mimetic peptide in the BTBR ob/ob mouse model of type 2 diabetes.

Introduction: Diabetic nephropathy (DN) is the leading cause of chronic kidney disease worldwide. The Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway participates in the development and progression of DN. Among the different mechanisms involved in JAK/STAT negative regulation, the family of suppressor of cytokine signaling (SOCS) proteins has been proposed as a new target for DN.

Targeting NF-κB by the Cell-Permeable NEMO-Binding Domain Peptide Improves Albuminuria and Renal Lesions in an Experimental Model of Type 2 Diabetic Nephropathy.

Diabetic nephropathy (DN) is a multifactorial disease characterized by hyperglycemia and close interaction of hemodynamic, metabolic and inflammatory factors. Nuclear factor-κB (NF-κB) is a principal matchmaker linking hyperglycemia and inflammation. The present work investigates the cell-permeable peptide containing the inhibitor of kappa B kinase γ (IKKγ)/NF-κB essential modulator (NEMO)-binding domain (NBD) as therapeutic option to modulate inflammation in a preclinical model of type 2 diabetes (T2D) with DN.

Pathogenic Pathways and Therapeutic Approaches Targeting Inflammation in Diabetic Nephropathy.

Diabetic nephropathy (DN) is associated with an increased morbidity and mortality, resulting in elevated cost for public health systems. DN is the main cause of chronic kidney disease (CKD) and its incidence increases the number of patients that develop the end-stage renal disease (ESRD). There are growing epidemiological and preclinical evidence about the close relationship between inflammatory response and the occurrence and progression of DN.

Chimeric Peptidomimetics of SOCS 3 Able to Interact with JAK2 as Anti-inflammatory Compounds.

The immunomodulatory effects of Suppressor of Cytokine Signaling (SOCS) proteins, that control the JAK/STAT pathway, indicate them as attractive candidates for immunotherapies. Recombinant SOCS3 protein suppresses the effects of inflammation, and its deletion in neurons or in immune cells increases pathological blood vessels growth. Recently, on the basis of the structure of the ternary complex among SOCS3, JAK2, and gp130, we focused on SOCS3 interfacing regions and designed several interfering peptides (IPs) that were able to mimic SOCS3 biological role in triple negative breast cancer (TNBC) models.

Lipotoxicity and Diabetic Nephropathy: Novel Mechanistic Insights and Therapeutic Opportunities.

Lipotoxicity is characterized by the ectopic accumulation of lipids in organs different from adipose tissue. Lipotoxicity is mainly associated with dysfunctional signaling and insulin resistance response in non-adipose tissue such as myocardium, pancreas, skeletal muscle, liver, and kidney. Serum lipid abnormalities and renal ectopic lipid accumulation have been associated with the development of kidney diseases, in particular diabetic nephropathy.

The Coming Age of Flavonoids in the Treatment of Diabetic Complications.

Diabetes mellitus (DM), and its micro and macrovascular complications, is one of the biggest challenges for world public health. Despite overall improvement in prevention, diagnosis and treatment, its incidence is expected to continue increasing over the next years. Nowadays, finding therapies to prevent or retard the progression of diabetic complications remains an unmet need due to the complexity of mechanisms involved, which include inflammation, oxidative stress and angiogenesis, among others.

Role of complement system in pathological remodeling of the vascular wall.

Cardiovascular diseases (CVD) remain the major cause of morbidity and mortality in Europe. The clinical complications associated to arterial wall rupture involve intimal cap rupture in complicated atherosclerotic plaques and medial rupture in abdominal aortic aneurysm (AAA). The mechanisms underlying pathological vascular remodeling include lipid accumulation, cell proliferation, redox imbalance, proteolysis, leukocyte infiltration, cell death, and eventually, thrombosis.

SOCS1-Derived Peptide Administered by Eye Drops Prevents Retinal Neuroinflammation and Vascular Leakage in Experimental Diabetes.

Current treatments for diabetic retinopathy (DR) target late stages when vision has already been significantly affected. Accumulating evidence suggests that neuroinflammation plays a major role in the pathogenesis of DR, resulting in the disruption of the blood-retinal barrier. Suppressors of cytokine signaling (SOCS) are cytokine-inducible proteins that function as a negative feedback loop regulating cytokine responses.

Diabetes-mediated promotion of colon mucosa carcinogenesis is associated with mitochondrial dysfunction.

Type 2 diabetes mellitus (T2DM) has been associated with an increased risk of cancer, including colon cancer (CC). However, we recently reported no influence of T2DM on CC prognosis, suggesting that any effect might be at the early stages of tumor development. We hypothesized that T2DM may create an environment in the healthy tissue, which acts as a carcinogenesis driver in agreement with the field of cancerization concept.

Molecular evidence of field cancerization initiated by diabetes in colon cancer patients.

The potential involvement of type 2 diabetes mellitus (T2DM) as a risk factor for colon cancer (CC) has been previously reported. While several clinical studies show a higher incidence of CC and a lower survival rate in diabetics, others report no association. Our own experience indicates that diabetes does not seem to worsen the prognosis once the tumor is present.

Targeting inflammation in diabetic nephropathy: a tale of hope.

Introduction: Diabetic nephropathy (DN) is the leading cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD). Beyond the new anti-diabetic drugs that possess markedly cardiovascular and renal protective effects, no novel direct therapies for DN have become available on the market in the last twenty years. Recently well-designed clinical trials for the treatment of DN, with attractive pathogenetic rationale, e.