Mitochondria-targeted hydrogen sulfide donor reduces atherogenesis by changing macrophage phenotypes and increasing UCP1 expression in vascular smooth muscle cells.

Atherosclerosis is a leading cause of morbidity and mortality in the Western countries. Mounting evidence points to the role of mitochondrial dysfunction in the pathogenesis of atherosclerosis. Recently, it has been shown that mitochondrial hydrogen sulfide (HS) can complement the bioenergetic role of Krebs cycle leading to improved mitochondrial function.

Mitochondria-targeted hydrogen sulfide donor reduces fatty liver and obesity in mice fed a high fat diet by inhibiting de novo lipogenesis and inflammation via mTOR/SREBP-1 and NF-κB signaling pathways.

Metabolic diseases that include obesity and metabolic-associated fatty liver disease (MAFLD) are a rapidly growing worldwide public health problem. The pathogenesis of MAFLD includes abnormally increased lipogenesis, chronic inflammation, and mitochondrial dysfunction. Mounting evidence suggests that hydrogen sulfide (HS) is an important player in the liver, regulating lipid metabolism and mitochondrial function.

The antiatherosclerotic action of 1G244 - An inhibitor of dipeptidyl peptidases 8/9 - is mediated by the induction of macrophage death.

Background: Targeting cell death to induce favorable functional and morphological changes within atherosclerotic plaques has long been postulated as a promising anti-atherosclerotic strategy. In this regard, inhibition of dipeptidyl peptidases 8/9 has received special attention in the context of chronic inflammatory diseases due to its regulatory role in macrophage death in vivo.

Methods: The present study investigates the influence of prolonged treatment with 1G244 - an inhibitor of dipeptidyl peptidases 8/9 - on the development of the advanced atherosclerosis plaque in apoE-knockout mice, using morphometric and molecular methods.

The Influence of the FFAR4 Agonist TUG-891 on Liver Steatosis in ApoE-Knockout Mice.

Background: Nonalcoholic fatty liver disease (NAFLD) constitutes an independent risk factor for the development of coronary heart disease. Low-grade inflammation has been shown to play an important role in the development of atherosclerosis and NAFLD. Free fatty acid receptor 4 (FFAR4/GPR120), which is involved in damping inflammatory reactions, may represent a promising target for the treatment of inflammatory diseases.

Changes in the liver proteome in apoE knockout mice exposed to inhalation of silica nanoparticles indicate mitochondrial damage and impairment of ER stress responses associated with microvesicular steatosis.

The adverse effects of air pollution on the cardiovascular system have been well documented. Nonalcoholic fatty liver disease (NAFLD) is an independent risk factor for cardiovascular events. However, the influence of exposure to airborne particles on the development of NAFLD is less recognised.

Inhaled silica nanoparticles exacerbate atherosclerosis through skewing macrophage polarization towards M1 phenotype.

Background And Aims: Exposure to environmental nanoparticles is related to the adverse impact on health, including cardiovascular system. Various forms of nanoparticles have been reported to interact with endothelium and induce inflammation. However, the potential role of nanoparticles in the pathogenesis of atherosclerosis and their mechanisms of action are still unclear.

The Anti-Atherosclerotic Action of FFAR4 Agonist TUG-891 in ApoE-Knockout Mice Is Associated with Increased Macrophage Polarization towards M2 Phenotype.

Over the past few years, a better understanding of the biology of G-protein coupled receptors (GPRs) has led to the identification of several receptors as novel targets for free fatty acids (FFAs). FFAR4 has received special attention in the context of chronic inflammatory diseases, including atherosclerosis, obesity and NAFLD, through to its anti-inflammatory effect. The present study investigates the influence of prolonged treatment with TUG-891-FFAR4 agonist on the development of atherosclerosis plaque in apoE-knockout mice, using morphometric and molecular methods.

Decrease of the pro-inflammatory M1-like response by inhibition of dipeptidyl peptidases 8/9 in THP-1 macrophages - quantitative proteomics of the proteome and secretome.

Background: Cellular peptidases are an emerging target of novel pharmacological strategies in inflammatory diseases and cancer. In this context, the dipeptidyl peptidases 8 and 9 (DPP8/9) have gained special attention due to their activities in the immune cells. However, in spite of more than hundred protein substrates identified to date by mass spectrometry-based analysis, the cellular DPP8/9 functions are still elusive.

Effect of thyrotropin-releasing hormone on the locomotor and sensitizing effects of cocaine in rats.

The present study was designed to find out whether single and repeated treatment with thyrotropin-releasing hormone (TRH) changed the cocaine-evoked hyperactivation or sensitization, and whether cross-sensitization occurred between TRH and cocaine. Like cocaine (10 mg/kg), TRH (10 mg/kg) increased the basal activation of rats; however, when given in combination with cocaine (10 mg/kg), TRH (5-10 mg/kg) did not change the locomotor effect of cocaine. On day 10, cocaine challenge of rats treated repeatedly with the psychostimulant (days 1-5) significantly enhanced locomotor hyperactivity compared to the effect of acute cocaine injection in saline-treated (days 1-5) animals.

Withdrawal from chronic cocaine up-regulates 5-HT1B receptors in the rat brain.

In the present study we examined the effect of prolonged treatment with cocaine (a sensitization and discrimination paradigm) on the expression of serotonin (5-HT)(1B) receptors in rat brain structures using a quantitative autoradiographic analysis. To estimate the distribution of 5-HT(1B) receptors in several brain coronal sections, we used [N-methyl-(3)H]GR 125743, a 5-HT(1B/1D) receptor antagonist, in the presence of ketanserin (a drug used to block 5-HT(1D) receptors). The binding of [N-methyl-(3)H]GR 125743 in the areas containing dopamine cell bodies (the ventral tegmental area, the substantia nigra) and terminals (the nucleus accumbens shell and core, but not in the caudate-putamen) and in the subiculum of the hippocampus was increased after withdrawal from repeated cocaine in both the discrimination and the sensitization paradigms, either being effective as confirmed by behavioral experiments.

Different pattern of brain c-Fos expression following re-exposure to ethanol or sucrose self-administration environment.

Exposure of alcohol addicts to alcohol-related environmental cues may elicit alcohol-seeking behavior and lead to relapse to heavy drinking. The aim of the present study was to identify brain regions activated by alcohol (ethanol)-related stimuli in Wistar rats trained to lever press for 8% ethanol solution in operant self-administration cages. Ethanol self-administration was stabilized in a maintenance phase, which lasted for 30 days.

Serotonin 5-HT1A receptors might control the output of cortical glutamatergic neurons in rat cingulate cortex.

The present study was designed to investigate the distribution of serotonin 5-HT1A receptor protein (5-HT1A-immunoreactivity) and its localization within cortical pyramidal neurons of the rat cingulate cortex. This experimental direction was inspired by recent data showing the role of 5-HT1A receptors in the pathology of schizophrenia, and in the mechanism of action of novel antipsychotic drugs as well as by the importance of the cingulate cortex in regulation of cognitive functions. It was found that 5-HT1A-immunoreactivity was densely distributed in neuronal eyelash-like elements, and their size, shape and spatial orientation may suggest concentration of 5-HT1A-immunopositive material in the proximal fragments of axons of cortical neurons.

Role of dopamine D3 receptors in controlling the expression of cocaine sensitization in rats.

It is established that dopamine (DA) is an important brain mediator of the behavioral (i.e. sensitizing) effects of cocaine in rodents.

Effects of 5-HT1B receptor ligands microinjected into the ventral tegmental area on cocaine discrimination in rats.

Some recent data indicate a significant interaction between serotonin (5-hydroxytryptamine; 5-HT) and dopamine in mesolimbic brain structures (e.g. the ventral tegmental area) which modulate the behavioral effects of cocaine in rats.