Obesity is associated with an increased incidence of infection, diabetes, and cardiovascular disease, which together account for most obesity-related morbidity mortality. Decreased expression leptin or functional receptors results in hyperphagia, decreased energy expenditure, obesity. It unclear, however, whether defective leptin-dependent signal transduction directly promotes any the conditions that frequently complicate Abnormalities tumor necrosis factor alpha have been noted each above...

Ob/ob mice, a model for nonalcoholic fatty liver disease (NAFLD), develop intestinal bacterial overgrowth and overexpress tumor necrosis factor α (TNF-α). In animal models alcoholic (AFLD), decontaminating the intestine or inhibiting TNF-α improves AFLD. Because AFLD NAFLD may have similar pathogenesis, treatment with probiotic (to modify flora) anti-TNF antibodies inhibit activity) improve in ob/ob mice. To evaluate this hypothesis, 48 mice were given either high-fat diet alone (ob/ob...

Obesity is associated with an increased incidence of infection, diabetes, and cardiovascular disease, which together account for most obesity-related morbidity mortality. Decreased expression leptin or functional receptors results in hyperphagia, decreased energy expenditure, obesity. It unclear, however, whether defective leptin-dependent signal transduction directly promotes any the conditions that frequently complicate Abnormalities tumor necrosis factor α have been noted each above...

Uncoupling protein 2 (UCP2) uncouples respiration from oxidative phosphorylation and may contribute to obesity through effects on energy metabolism. Because basal metabolic rate is decreased in obesity, UCP2 expression predicted be reduced. Paradoxically, hepatic of mRNA increased genetically obese (ob/ob) mice. In situ hybridization immunohistochemical analysis ob/ob livers demonstrate that are hepatocytes, which do not express lean Mitochondria isolated exhibit an H+ leak partially...

Increased intestinal permeability (IP) has emerged recently as a common underlying mechanism in the pathogenesis of allergic, inflammatory, and autoimmune diseases. The characterization zonulin, only physiological mediator known to regulate IP reversibly, remained elusive. Through proteomic analysis human sera, we have now identified zonulin precursor for haptoglobin-2 (pre-HP2). Although mature HP is scavenge free hemoglobin (Hb) inhibit its oxidative activity, no function ever been...

This study aimed to investigate the effect of circ_0000950/miR-103 network on regulating neuron apoptosis, neurite outgrowth and inflammation in Alzheimer's disease (AD). Cellular AD model rat pheochromocytoma cell line PC12 cells cellular cerebral cortex neurons were constructed, circ_0000950 both models was determined through upregulation knockdown expression by transfection. Compensation experiments luciferase assay further performed validate sponging miR-103 as well mechanisms models....

Although obesity-related fatty livers are vulnerable to damage from endotoxin, the mechanisms involved remain obscure. The purpose of this study was determine if immunologic priming might be by determining resemble normal that have been sensitized endotoxin Propionibacterium acnes infection. latter induces interleukin (IL)-12 and -18, causing a selective reduction CD4+NK T cells, diminished IL-4 production, deficient production T-helper type 2 (Th-2) cytokines ( e.g. , IL-10), excessive Th-1...

Abstract: Background: Although Kupffer cells (KCs) are capable of producing important growth‐stimulating cytokines, their role in liver regeneration following partial hepatectomy (PH) remains poorly understood. Methods: In the present study was studied after KC‐depletion by intravenous administration liposome‐encapsulated dichloromethylene‐diphosphonate (Cl 2 MDP), a method known to physically eliminate KCs. Furthermore, splenectomy performed one week prior PH exclude effect Cl MDP‐liposomes...

The growth-stimulatory actions of tumor necrosis factor alpha (TNF-alpha) after partial hepatectomy (PH) are difficult to reconcile with its well-established role in the genesis liver injury. lethal TNF thought involve induction oxidant production by mitochondria. It is not known if initiates mitochondrial PH. Furthermore, this potentially toxic response follows PH, it clear how hepatocytes defend themselves sufficiently so that replication, rather than death, occurs. These studies test...

Hepatic steatosis may have a generally benign prognosis, either because most hepatocytes are not significantly injured or mechanisms to replace damaged induced. To determine the relative importance of these mechanisms, we compared hepatocyte damage and replication in ethanol-fed ob/ob mice with very indolent fatty liver disease that healthy control PARP-1(-/-) targeted disruption DNA repair enzyme, poly(ADP-ribose) polymerase. Compared controls, both groups livers had higher serum alanine...

Mitochondrial generation of reactive oxygen species (ROS) is increased in mice with fatty livers induced by genetic obesity, chronic consumption ethanol, or methionine/choline-deficient diets. Both nuclear and mitochondrial (mt) DNA are targets for ROS-induced damage accumulate hydroxylated bases, such as 8-hydroxy-2'-deoxyguanosine (8-oxoG) base substitution adenine 8-oxoG (A*8-oxoG), that introduce mutations promote cancer well cell death. The mammalian homolog the bacterial mismatch...

Bacterial lipopolysaccharide (LPS) is a key mediator in the vascular leak syndromes associated with Gram-negative bacterial infections. LPS opens paracellular pathway pulmonary endothelia through protein tyrosine phosphorylation. We now have identified protein-tyrosine kinases (PTKs) and their substrates required for LPS-induced phosphorylation opening of human lung microvascular endothelial cells (HMVEC-Ls). disrupted barrier integrity dose- time-dependent manner, prior broad spectrum PTK...

Increases in monocyte/macrophage production of the proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), parallel evolution liver injury rats and humans with alcoholic disease. However, possibility that TNF-alpha expression may be induced other cell populations before serious disease develops has not been evaluated. To clarify this issue, mRNAs and/or protein levels cytokines [interleukin (IL)-6, IL-10, transforming growth factor-beta (TGF)-beta, IL-12, interferon-gamma]...

Although previous work suggests that tumor necrosis factor-alpha (TNF) promotes liver regeneration after partial hepatectomy (PH), the source of TNF is unknown. If Kupffer cells release PH, then cell depletion by gadolinium chloride (GdCl) should inhibit regeneration. To test this hypothesis, cytokine expression and regenerative events were compared in GdCl-treated control rats. Functional assays Northern blot analysis a cell-specific mRNA confirmed GdCl depleted cells. Despite this,...

It is not known why natural killer T (NKT) cells, which modulate liver injury by regulating local cytokine production, are reduced in leptin-deficient ob/ob mice. NKT cells express adrenoceptors. Thus, we hypothesize that the low norepinephrine (NE) activity of mice promotes depletion thereby sensitizing livers to lipopolysaccharide (LPS) toxicity. To evaluate this hypothesis, hepatic were quantified wild-type before and after treatment with NE inhibitors, dopamine β-hydroxylase knockout...

Recovery from liver damage might be enhanced by encouraging repopulation of the endogenous hepatic progenitor cells. Oval cells are resident stem that promote regeneration and repair. Little is known about mediators regulate accumulation these in liver. Parasympathetic nervous system inhibition reduces number oval injured livers. The effect sympathetic (SNS) on cell not known. Adrenergic mobilizes hematopoietic precursors into circulation has also been shown to regeneration. Thus, we...

Abstract Background The development of diabetes vascular calcification (VC) is tightly associated with the inhibition smooth muscle cell (VSMC) autophagy. Previously, our team found that miR-32-5p (miR-32) promotes macrophage activation, and miR-32 expressed at higher level in plasma patients coronary calcification. However, whether mediates function macrophages type 2 (T2D) VC still unclear. Methods Wild-type (WT) −/− mice were used this study. qRT-PCR western blotting to analyze gene...

Fibrotic diseases pose a significant burden on health care, yet the key pathogenic fibroblasts involved remain unclear. We developed fibrotic disease fibroblast atlas (FDFA), which comprises 394 single-cell and 38 spatial transcriptomic samples from 11 common diseases. To perform cell-type phenotype association study in large-scale heterogeneous datasets, we research kit for dataset exploration (SPARKLE). SPARKLE handles heterogeneity by incorporating confounding information into its...

Fatty livers are sensitive to lipopolysaccharide (LPS) damage. This study tests the hypothesis that this vulnerability occurs because protective, antiapoptotic mechanisms not upregulated appropriately. Genetically obese, leptin-deficient ob/ob mice, a model for nonalcoholic fatty liver disease, and their lean litter mates were treated with small dose of LPS. General measures injury, early (i.e., cytochrome c release) late activation caspase 3) events occur during hepatocyte apoptosis,...

Purpose: Immune checkpoint inhibitors (ICIs) and sonodynamic therapy (SDT) are types of immunotherapy. In order to combine soluble programmed cell death protein 1 (sPD-1)-mediated immune chlorin e6 (Ce6)-assisted SDT, nanobubbles (NBs) were generated simultaneously load sPD-1 Ce6. Materials Methods: The sPD-1/Ce6-NBs, which prepared by thin-film hydration mechanical oscillation, had a stable physical condition, delivered Ce6 in targeted manner. NBs could strengthen tumor suppression...