TGF-β and TNF-α interaction promotes the expression of MMP-9 through H3K36 dimethylation: implications in breast cancer metastasis.

Increased MMP-9 expression in the tumor microenvironment (TME) plays a crucial role in the extracellular matrix remodeling to facilitate cancer invasion and metastasis. However, the mechanism of MMP-9 upregulation in TME remains elusive. Since TGF-β and TNF-α levels are elevated in TME, we asked whether these two agents interacted to induce/augment MMP-9 expression.

IL-6R (trans-signaling) is a key regulator of reverse cholesterol transport in lipid-laden macrophages.

Atherosclerosis is a cardiovascular disease caused by cholesterol-laden arterial plaques. This study evaluated the correlation between interleukin-6 (IL-6), its receptors (IL6R/CD126), and glycoprotein 130 (gp130) alongside atherosclerosis biomarkers in a cohort of 142 subjects, equally divided between lean and obese individuals. Subsequent analyses used THP-1-derived macrophages to assess the biochemical impact of inhibiting IL-6 receptors.

Aryl hydrocarbon receptor: current perspectives on key signaling partners and immunoregulatory role in inflammatory diseases.

The aryl hydrocarbon receptor (AhR) is a versatile environmental sensor and transcription factor found throughout the body, responding to a wide range of small molecules originating from the environment, our diets, host microbiomes, and internal metabolic processes. Increasing evidence highlights AhR's role as a critical regulator of numerous biological functions, such as cellular differentiation, immune response, metabolism, and even tumor formation. Typically located in the cytoplasm, AhR moves to the nucleus upon activation by an agonist where it partners with either the aryl hydrocarbon receptor nuclear translocator (ARNT) or hypoxia-inducible factor 1β (HIF-1β).

Soybean oil-based HFD induces gut dysbiosis that leads to steatosis, hepatic inflammation and insulin resistance in mice.

High-fat diets (HFDs) shape the gut microbiome and promote obesity, inflammation, and liver steatosis. Fish and soybean are part of a healthy diet; however, the impact of these fats, in the absence of sucrose, on gut microbial dysbiosis and its association with liver steatosis remains unclear. Here, we investigated the effect of sucrose-free soybean oil-and fish oil-based high fat diets (HFDs) (SF-Soy-HFD and SF-Fish-HFD, respectively) on gut dysbiosis, obesity, steatosis, hepatic inflammation, and insulin resistance.

IL-1β-Induced CXCL10 Expression in THP-1 Monocytic Cells Involves the JNK/c-Jun and NF-κB-Mediated Signaling.

CXCL10 (IP-10) plays a key role in leukocyte homing to the inflamed tissues and its increased levels are associated with the pathophysiology of various inflammatory diseases including obesity and type 2 diabetes. IL-1β is a key proinflammatory cytokine that is found upregulated in meta-inflammatory conditions and acts as a potent activator, inducing the expression of cytokines/chemokines by immune cells. However, it is unclear whether IL-1β induces the expression of CXCL10 in monocytic cells.

PPARdelta: A key modulator in the pathogenesis of diabetes mellitus and co-morbidity.

The interplay between lipid metabolism and immune response in macrophages plays a pivotal role in various infectious diseases, notably tuberculosis (TB). Herein, we illuminate the modulatory effect of heat-killed (HKMT) on macrophage lipid metabolism and its implications on the inflammatory cascade. Our findings demonstrate that HKMT potently activates the lipid scavenger receptor, CD36, instigating lipid accumulation.

Gut Dysbiosis Shaped by Cocoa Butter-Based Sucrose-Free HFD Leads to Steatohepatitis, and Insulin Resistance in Mice.

Background: High-fat diets cause gut dysbiosis and promote triglyceride accumulation, obesity, gut permeability changes, inflammation, and insulin resistance. Both cocoa butter and fish oil are considered to be a part of healthy diets. However, their differential effects on gut microbiome perturbations in mice fed high concentrations of these fats, in the absence of sucrose, remains to be elucidated.

TNF-α/Stearate Induced H3K9/18 Histone Acetylation Amplifies IL-6 Expression in 3T3-L1 Mouse Adipocytes.

Extensive evidence supports the connection between obesity-induced inflammation and the heightened expression of IL-6 adipose tissues. However, the mechanism underlying the IL-6 exacerbation in the adipose tissue remains unclear. There is general agreement that TNF-α and stearate concentrations are mildly elevated in adipose tissue in the state of obesity.

Unraveling Verapamil's Multidimensional Role in Diabetes Therapy: From β-Cell Regeneration to Cholecystokinin Induction in Zebrafish and MIN6 Cell-Line Models.

This study unveils verapamil's compelling cytoprotective and proliferative effects on pancreatic β-cells amidst diabetic stressors, spotlighting its unforeseen role in augmenting cholecystokinin (CCK) expression. Through rigorous investigations employing MIN6 β-cells and zebrafish models under type 1 and type 2 diabetic conditions, we demonstrate verapamil's capacity to significantly boost β-cell proliferation, enhance glucose-stimulated insulin secretion, and fortify cellular resilience. A pivotal revelation of our research is verapamil's induction of CCK, a peptide hormone known for its role in nutrient digestion and insulin secretion, which signifies a novel pathway through which verapamil exerts its therapeutic effects.

Inflammation causes insulin resistance in mice via interferon regulatory factor 3 (IRF3)-mediated reduction in FAHFA levels.

Obesity-induced inflammation causes metabolic dysfunction, but the mechanisms remain elusive. Here we show that the innate immune transcription factor interferon regulatory factor (IRF3) adversely affects glucose homeostasis through induction of the endogenous FAHFA hydrolase androgen induced gene 1 (AIG1) in adipocytes. Adipocyte-specific knockout of IRF3 protects male mice against high-fat diet-induced insulin resistance, whereas overexpression of IRF3 or AIG1 in adipocytes promotes insulin resistance on a high-fat diet.

Neutral Sphingomyelinase 2 Inhibition Limits Hepatic Steatosis and Inflammation.

Non-alcoholic fatty liver disease (NAFLD) is manifested by hepatic steatosis, insulin resistance, hepatocyte death, and systemic inflammation. Obesity induces steatosis and chronic inflammation in the liver. However, the precise mechanism underlying hepatic steatosis in the setting of obesity remains unclear.

Differential effects of fish-oil and cocoa-butter based high-fat/high-sucrose diets on endocrine pancreas morphology and function in mice.

Introduction: A high-fat/high-sucrose diet leads to adverse metabolic changes that affect insulin sensitivity, function, and secretion. The source of fat in the diet might inhibit or increase this adverse effect. Fish oil and cocoa butter are a significant part of our diets.

Glucose intolerance induces anxiety-like behaviors independent of obesity and insulin resistance in a novel model of nutritional metabolic stress.

Objectives: Type 2 diabetes (T2D) is a metabolic disease of major public health concern. It impacts peripheral tissues and the central nervous system, leading to systemic dysmetabolism and neurocognitive impairments, including memory deficits, anxiety, and depression. The metabolic determinants of these neurocognitive impairments remain unidentified.

Verapamil chronicles: advances from cardiovascular to pancreatic β-cell protection.

Verapamil is a well-known drug used for treating angina and hypertension. Emerging data from current clinical trials suggest that this calcium channel blocker has a potential benefit for pancreatic β-cells through the elevation and sustenance of C-peptide levels in patients with diabetes mellitus (DM). This is intriguing, given the fact that the current therapeutic options for DM are still limited to using insulin and incretins which, in fact, fail to address the underlying pathology of β-cell destruction and loss.

Enhancement effect of AgO nanoparticles on fermentative cellulase activity from thermophilic Bacillus subtilis Ag-PQ.

Background: Cellulase is an important bioprocessing enzyme used in various industries. This study was conducted with the aim of improving the biodegradation activity of cellulase obtained from the Bacillus subtilis AG-PQ strain. For this purpose, AgO and FeO NPs were fabricated using AgNO and FeSO·7HO salt respectively through a hydro-thermal method based on five major steps; selection of research-grade materials, optimization of temperature, pH, centrifuge, sample washed with distilled water, dry completely in the oven at the optimized temperature and finally ground for characterization.

The Proinflammatory Role of ANGPTL8 R59W Variant in Modulating Inflammation through NF-κB Signaling Pathway under TNFα Stimulation.

Background: Angiopoietin-like protein 8 (ANGPTL8) is known to regulate lipid metabolism and inflammation. It interacts with ANGPTL3 and ANGPTL4 to regulate lipoprotein lipase (LPL) activity and with IKK to modulate NF-κB activity. Further, a single nucleotide polymorphism (SNP) leading to the ANGPTL8 R59W variant associates with reduced low-density lipoprotein/high-density lipoprotein (LDL/HDL) and increased fasting blood glucose (FBG) in Hispanic and Arab individuals, respectively.

Endoplasmic Reticulum Stress Promotes the Expression of TNF-α in THP-1 Cells by Mechanisms Involving ROS/CHOP/HIF-1α and MAPK/NF-κB Pathways.

Obesity and metabolic syndrome involve chronic low-grade inflammation called metabolic inflammation as well as metabolic derangements from increased endotoxin and free fatty acids. It is debated whether the endoplasmic reticulum (ER) stress in monocytic cells can contribute to amplify metabolic inflammation; if so, by which mechanism(s). To test this, metabolic stress was induced in THP-1 cells and primary human monocytes by treatments with lipopolysaccharide (LPS), palmitic acid (PA), or oleic acid (OA), in the presence or absence of the ER stressor thapsigargin (TG).

Technique for insertion of a Scheker prosthesis for failed Sauve-Kapandji with a well fixed ulnar stem: A case report.

Introduction: The Scheker prosthesis is a distal radioulnar joint (DRUJ) arthroplasty used as a salvage option for many DRUJ pathologies.

Presentation Of Case: We report the case of a patient who underwent insertion of a Scheker prosthesis for continued pain and limited motion at the wrist in the setting of a failed Sauve-Kapandji with a well fixed ulnar stem and DRUJ pseudo-arthrosis.

Discussion: This report aims to provide a technique for ulnar stem removal without compromising the bone needed for the Scheker prosthesis and for describing the location of a DRUJ osteotomy without compromising radio-lunate stability.

TNFα induces matrix metalloproteinase-9 expression in monocytic cells through ACSL1/JNK/ERK/NF-kB signaling pathways.

Studies have established the association between increased plasma levels of matrix metalloproteinase (MMP)-9 and adipose tissue inflammation. Tumor necrosis factor α (TNFα) was elevated in obesity and is involved in the induction of MMP-9 in monocytic cells. However, the underlying molecular mechanism was incompletely understood.

Glycerol 3-phosphate phosphatase/PGPH-2 counters metabolic stress and promotes healthy aging via a glycogen sensing-AMPK-HLH-30-autophagy axis in C. elegans.

Metabolic stress caused by excess nutrients accelerates aging. We recently demonstrated that the newly discovered enzyme glycerol-3-phosphate phosphatase (G3PP; gene Pgp), which operates an evolutionarily conserved glycerol shunt that hydrolyzes glucose-derived glycerol-3-phosphate to glycerol, counters metabolic stress and promotes healthy aging in C. elegans.

Metabolomics: a promising tool for deciphering metabolic impairment in heavy metal toxicities.

Heavy metals are the metal compounds found in earth's crust and have densities higher than that of water. Common heavy metals include the lead, arsenic, mercury, cadmium, copper, manganese, chromium, nickel, and aluminum. Their environmental levels are consistently rising above the permissible limits and they are highly toxic as enter living systems via inhalation, ingestion, or inoculation.

Wharton's jelly mesenchymal stem cells: a concise review of their secretome and prospective clinical applications.

Accumulating evidence indicates that most primary Wharton's jelly mesenchymal stem cells (WJ-MSCs) therapeutic potential is due to their paracrine activity, i.e., their ability to modulate their microenvironment by releasing bioactive molecules and factors collectively known as secretome.