Microglial pyroptosis drives neuropathic pain and targeting NLRP3 alleviates pain and neuroinflammation.

Neuropathic pain is triggered by nerve damage or disease and involves chronic neuroinflammation driven by activated microglia releasing pro-inflammatory cytokines. PANoptosis, a complex cell death program encompassing apoptosis, pyroptosis, and necroptosis, has emerged as a key player in neuroinflammation. While individual PANoptosis pathway have been linked to pain, its systemic role in neuropathic pain remains unclear.

Endothelial autophagy-related gene 7 contributes to high fat diet-induced obesity.

Objective: Obesity-associated metabolic dysfunction is a major public health concern worldwide. Endothelial dysfunction is a hallmark of metabolic dysfunction, and endothelial cells affect metabolic functions. Because autophagy-related gene 7 (ATG7) is involved in various cellular physiology, we investigated the roles of endothelial cell-ATG7 (EC-ATG7) on high-fat diet-induced obesity and its related metabolic dysfunction.

Curcumin encapsulated polylactic acid nanoparticles embedded in alginate/gelatin bioinks for in situ immunoregulation: Characterization and biological assessment.

Curcumin is a known naturally occurring anti-inflammatory agent derived from turmeric, and it is commonly used as a herbal food supplement. Here, in order to overcome the inherent hydrophobicity of curcumin (Cur), polylactic acid (PLA) nanoparticles (NPs) were synthesised using a solvent evaporation, and an oil-in-water emulsion method used to encapsulate curcumin. Polymeric NPs also offer the ability to control rate of drug release.

Subcutaneous Administration of a Nitric Oxide-Releasing Nanomatrix Gel Ameliorates Obesity and Insulin Resistance in High-Fat Diet-Induced Obese Mice.

Nitric oxide (NO) is a gaseous signaling molecule, which plays crucial roles in various biological processes, including inflammatory responses, metabolism, cardiovascular functions, and cognitive function. NO bioavailability is reduced with aging and cardiometabolic disorders in humans and rodents. NO stimulates the metabolic rate by increasing the mitochondrial biogenesis and brown fat activation.

Serum fetuin-A and Ser312 phosphorylated fetuin-A responses and markers of insulin sensitivity after a single bout of moderate intensity exercise.

Fetuin-A (Fet-A), secreted by the liver and adipose tissue, inhibits insulin receptor tyrosine kinase activity and modulates insulin action. Numerous studies have shown association of elevated serum Fet-A concentrations with obesity, non-alcoholic fatty liver disease, and type 2 diabetes. Both moderate body weight loss (5%-10%) and significant body weight loss have been shown to decrease serum Fet-A and improve insulin sensitivity.

Long-chain acyl-CoA synthetase-1 mediates the palmitic acid-induced inflammatory response in human aortic endothelial cells.

Saturated fatty acid (SFA) induces proinflammatory response through a Toll-like receptor (TLR)-mediated mechanism, which is associated with cardiometabolic diseases such as obesity, insulin resistance, and endothelial dysfunction. Consistent with this notion, TLR2 or TLR4 knockout mice are protected from obesity-induced proinflammatory response and endothelial dysfunction. Although SFA causes endothelial dysfunction through TLR-mediated signaling pathways, the mechanisms underlying SFA-stimulated inflammatory response are not completely understood.

Diurnal, metabolic and thermogenic alterations in a murine model of accelerated aging.

Senescence-Accelerated Mouse-Prone 8 (SAMP8) mice exhibit characteristics of premature aging, including hair loss, cognitive dysfunction, reduced physical activity, impaired metabolic homeostasis, cardiac dysfunction and reduced lifespan. Interestingly, circadian disruption can induce or augment many of these same pathologies. Moreover, previous studies have reported that SAMP8 mice exhibit abnormalities in circadian wheel-running behavior, indicating possible alterations in circadian clock function.

Metformin reduces saturated fatty acid-induced lipid accumulation and inflammatory response by restoration of autophagic flux in endothelial cells.

Autophagy, an integral part of the waste recycling process, plays an important role in cellular physiology and pathophysiology. Impaired autophagic flux causes ectopic lipid deposition, which is defined as the accumulation of lipids in non-adipose tissue. Ectopic lipid accumulation is observed in patients with cardiometabolic syndrome, including obesity, diabetes, insulin resistance, and cardiovascular complications.

A Small Molecule, UAB126, Reverses Diet-Induced Obesity and its Associated Metabolic Disorders.

Targeting retinoid X receptor (RXR) has been proposed as one of the therapeutic strategies to treat individuals with metabolic syndrome, as RXR heterodimerizes with multiple nuclear receptors that regulate genes involved in metabolism. Despite numerous efforts, RXR ligands (rexinoids) have not been approved for clinical trials to treat metabolic syndrome due to the serious side effects such as hypertriglyceridemia and altered thyroid hormone axis. In this study, we demonstrate a novel rexinoid-like small molecule, UAB126, which has positive effects on metabolic syndrome without the known side effects of potent rexinoids.

Alterations of Serum Ser312-Phosphorylated Fetuin-A from Exercise-Induced Moderate Body Weight Loss in Individuals with Obesity.

Objective: Phosphorylated fetuin-A (pFet-A) inhibits insulin action and has been shown to be associated with obesity and insulin resistance. The objective of this cohort study was to assess the effect of incremental body weight loss on alterations in serum pFet-A and indexes of insulin sensitivity.

Methods: A total of 16 men with obesity attained a targeted weight loss of 8% to 10% of their initial body weight by achieving an energy expenditure/deficit of 2,000 to 2,500 kcal/wk.

LncRNA RMST-mediated miR-107 transcription promotes OGD-induced neuronal apoptosis via interacting with hnRNPK.

The long noncoding RNA (lncRNA) rhabdomyosarcoma 2-associated transcript (RMST) silencing has been demonstrated to protect against ischemic brain injury in vivo and neuron injury in vitro. However, its underlying mechanisms in the progression of ischemic stroke have not been well explored. The expression of RMST in oxygen-glucose deprivation (OGD)-treated HT-22 hippocampal neuron cell line was examined using quantitative Real-Time PCR (qRT-PCR).

Cinnamyl O-amine functionalized chitosan as a new excipient in direct compressed tablets with improved drug delivery.

The use of chitosan as a potential excipient in pharmaceutical formulations for the delivery of drugs produced via direct compression tableting has been investigated. Chitosan, N-cinnamyl substituted O-amine functionalized chitosan (cinnamyl-chitosan) and microcrystalline cellulose (MCC) were formulated, alongside acetaminophen as the active pharmaceutical ingredient (API), and magnesium stearate (Mg-St) as lubricant in a series of formulated blends. A control blend of MCC, acetaminophen (20 wt%) and Mg-St (0.

Phosphorylation status of fetuin-A is critical for inhibition of insulin action and is correlated with obesity and insulin resistance.

Fetuin-A (Fet-A), a hepatokine associated with insulin resistance, obesity, and incident type 2 diabetes, is shown to exist in both phosphorylated and dephosphorylated forms in circulation. However, studies on fetuin-A phosphorylation status in insulin-resistant conditions and its functional significance are limited. We demonstrate that serum phosphofetuin-A (Ser312) levels were significantly elevated in high-fat diet-induced obese mice, insulin-resistant Zucker diabetic fatty rats, and in individuals with obesity who are insulin resistant.

Dynamic changes in miR-124 levels in patients with acute cerebral infarction.

Objective: To investigate the changes in serum miR-124 levels in patients with acute cerebral infarction (ACI) and elucidate the underlying mechanism by a dynamic monitor.

Methods: Fifty-four patients with ACI and 51 healthy controls were included in our study. Baseline characteristics and blood samples were collected for further analysis.

AMPK activation by pterostilbene contributes to suppression of hepatic gluconeogenic gene expression and glucose production in H4IIE cells.

Pterostilbene, a bioactive component of blueberries and grapes, shows structural similarity to resveratrol, and exhibits antioxidant, anti-inflammatory, anti-cancer, hypoglycemic, and cholesterol lowering effects. Recent evidence indicates that pterostilbene is an agonist of the nuclear receptor, peroxisome proliferator-activated receptor-alpha (PPAR-α). Since PPAR-α agonists induce peroxisomal proliferation and fatty acid oxidation, we examined gene expression of acyl CoA oxidase (ACO) and carnitine palmitoyl transferase-1 (CPT-1).

Suppression of adipocyte differentiation and lipid accumulation by stearidonic acid (SDA) in 3T3-L1 cells.

Background: Increased consumption of omega-3 (ω-3) fatty acids found in cold-water fish and fish oil has been reported to protect against obesity. A potential mechanism may be through reduction in adipocyte differentiation. Stearidonic acid (SDA), a plant-based ω-3 fatty acid, has been targeted as a potential surrogate for fish-based fatty acids; however, its role in adipocyte differentiation is unknown.

Influence of gamma and electron beam sterilization on the stability of a premixed injectable calcium phosphate cement for trauma indications.

Premixed calcium phosphate cements (CPC's) are becoming the material of choice for injectable cements as a result of their effective delivery to the target implantation site. For orthopaedic use, it is of vital importance that the attributes of these CPC's are not compromised by irradiation sterilization. Therefore, the aim of this study is to determine the influence of irradiation sterilization on a range of premixed CPC's, with an emphasis on improving product shelf life through the use of optimal packaging configurations and annealing steps.

Novel Mutation of the NOTCH3 Gene in a Chinese Pedigree with CADASIL.

Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) results from NOTCH3 gene mutations, which lead to the degeneration of vascular smooth muscle cells (VSMCs). The clinical presentation of CADASIL patients is dependent on the impact of other vascular risk factors and the type of NOTCH3 mutation present.

Methods: Here, we report a rare pathogenic mutation on exon 14 of the NOTCH3 gene in a Chinese family affected by CADASIL with phenotypic peculiarities.

Enhanced Thermoelectricity in High-Temperature β-Phase Copper(I) Selenides Embedded with Cu2Te Nanoclusters.

We report remarkably enhanced thermoelectric performance of Te doped Cu2Se in midtemperature range. Through ball-milling process followed by spark plasma sintering (SPS), nanoscale Cu2Te clusters were embeded in the matrix of Cu2Se, inducing a drastic enhancement of thermoelectric performance by reducing the thermal conductivity without degrading the power factor. A large ZT value of 1.

Evaluation of PPARα activation by known blueberry constituents.

Background: Anthocyanins are known to have hypolipidemic properties. It was deemed necessary to determine whether major blueberry anthocyanins and catechins are ligands for the transcription factor peroxisome proliferator activated receptor alpha isoform (PPARα), and compare activation with known PPARα agonistic constituents, pterostilbene and resveratrol. It was also considered important to investigate the effect of pterostilbene on PPARα gene expression, and relate results with hepatic mRNA PPARα expression up-regulation observed previously in hamsters fed a diet supplemented with blueberry peels extract (BBX).

[Correlation between minimal apparent diffusion coefficient and expression of Ki-67 in glioma].

Objective: To explore the correlation between minimal apparent diffusion coefficient (minADC) and expression of Ki-67 in glioma.

Methods: Findings from 78 patients with pathologically proven gliomas (grade II:n = 28, grade III: n = 21, grade IV: n = 29) were analyzed retrospectively. The minADC value of each tumor was determined on ADC maps.

Detecting community structures in networks by label propagation with prediction of percolation transition.

Though label propagation algorithm (LPA) is one of the fastest algorithms for community detection in complex networks, the problem of trivial solutions frequently occurring in the algorithm affects its performance. We propose a label propagation algorithm with prediction of percolation transition (LPAp). After analyzing the reason for multiple solutions of LPA, by transforming the process of community detection into network construction process, a trivial solution in label propagation is considered as a giant component in the percolation transition.

Classification of insular-basal ganglia gliomas based on the displacement of corticospinal tracts evaluated by diffusion tensor imaging.

Background: Resection of insula-basal ganglia (IBG) gliomas is challenging because of their deep location and vicinity to critical structures, whereas diffusion tensor tractography (DTT) can noninvasively delineate the tracks of white matter fibers. This study aims to evaluate the role of cortico-spinal tract (CST) positions in prediction of the prognosis of patients with IBG gliomas.

Methods: We retrospectively reviewed 34 patients with IBG gliomas.