Quantitative proteomics in rat saliva stimulated with pilocarpine and isoprenaline.

Objective: Saliva is increasingly being recognized as a convenient and informative reservoir of proteins that could serve as indicators of various diseases. As the literature remains taciturn with regard to saliva collection methods in rodents, our objective was to provide the protocol for a comprehensive quantitative proteomic assessment of stimulated rat saliva.

Design: We applied the next-generation proteomic methodology (directDIA) to compare qualitatively and quantitatively stimulated rat saliva specimens obtained from pilocarpine alone and pilocarpine in combination with isoprenaline.

Alterations in plasma proteome during acute COVID-19 and recovery.

Background: The severe course of COVID-19 causes cardiovascular injuries, although the mechanisms involved are still not fully recognized, linked, and understood. Their characterization is of great importance with the establishment of the conception of post-acute sequelae of COVID-19, referred to as long COVID, where blood clotting and endothelial abnormalities are believed to be the key pathomechanisms driving circulatory system impairment.

Methods: The presented study investigates temporal changes in plasma proteins in COVID-19 patients during hospitalization due to SARS-CoV-2 infection and six months after recovery by targeted SureQuant acquisition using PQ500 panel.

Multi-layered metabolic effects of trehalose on the liver proteome in apoE-knockout mice model of liver steatosis.

Background: Metabolic dysfunction-associated fatty liver disease has been well documented as a key independent risk factor for the development of atherosclerosis. A growing body of evidence suggests that due to its numerous favorable molecular effects, trehalose may exert beneficial effects in counteracting liver steatosis. In our previous study, we described the antiatherosclerotic and antisteatotic properties of trehalose, which we attributed to the induction of autophagy.

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.

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.

Comparative two time-point proteome analysis of the plasma from preterm infants with and without bronchopulmonary dysplasia.

Background: In this study, we aimed to analyze differences in plasma protein abundances between infants with and without bronchopulmonary dysplasia (BPD), to add new insights into a better understanding of the pathogenesis of this disease.

Methods: Cord and peripheral blood of neonates (≤ 30 weeks gestational age) was drawn at birth and at the 36th postmenstrual week (36 PMA), respectively. Blood samples were retrospectively subdivided into BPD(+) and BPD(-) groups, according to the development of BPD.

An iTRAQ-Based Quantitative Proteomic Analysis of Plasma Proteins in Preterm Newborns With Retinopathy of Prematurity.

Purpose: Retinopathy of prematurity (ROP) is a vision-threatening complication of a premature birth, in which the etiology still remains unclear. Importantly, the molecular processes that govern these effects can be investigated in a perturbed plasma proteome composition. Thus, plasma proteomics may add new insights into a better understanding of the pathogenesis of this disease.

Prospective plasma proteome changes in preterm infants with different gestational ages.

Background: In this study, we aimed to analyze time-resolved plasma proteome changes in preterm neonates stratified by their gestational age to detect malfunctioning pathways that derive from the systemic immaturity of the neonate and to highlight those that are differentially regulated during the early development.

Methods: Preterm newborns were enrolled in three subgroups with different gestational ages: before 26 weeks of gestation (group 1), between 27 and 28 weeks of gestation (group 2), and between 29 and 30 (group 3) weeks of gestation. Plasma protein abundances were assessed at two time points (at preterm delivery and at the 36th week of post-menstrual age) by quantitative proteomics.

The influence of AICAR - direct activator of AMP-activated protein kinase (AMPK) - on liver proteome in apoE-knockout mice.

There is a growing body of evidence that altered functioning of apoE may aggravate cellular energy homeostasis and stress response, leading to oxidative stress, mitochondrial dysfunction, endoplasmic reticulum (ER) stress and inflammation, leading to hypercholesterolemia, dyslipidemia, liver steatosis and neurodegeneration. One of the key cellular responses to mitochondria and ER-stress related processes and cellular energy imbalance is AMP-activated protein kinase (AMPK), considered as a cellular master energy sensor and critical regulator of mitochondrial homeostasis. The aim of our study was to use differential proteomics and transcriptomics approach to elucidate the effect of direct AMPK activator AICAR on liver proteome in apoE mice - experimental model of atherosclerosis and moderate nonalcoholic steatosis.

Influence of metformin on mitochondrial subproteome in the brain of apoE knockout mice.

Neurodegenerative diseases are the set of progressive, age-related brain disorders, characterized by an excessive accumulation of mutant proteins in the certain regions of the brain. Such changes, collectively identified as causal factors of neurodegeneration, all impact mitochondria, imminently leading to their dysfunction. These observations predestine mitochondria as an attractive drug target for counteracting degenerative brain damage.

Mitochondrial aldehyde dehydrogenase activation by Alda-1 inhibits atherosclerosis and attenuates hepatic steatosis in apolipoprotein E-knockout mice.

Background: Mitochondrial dysfunction has been shown to play an important role in the development of atherosclerosis and nonalcoholic fatty liver disease (NAFLD). Mitochondrial aldehyde dehydrogenase (ALDH2), an enzyme responsible for the detoxification of reactive aldehydes, is considered to exert protective function in mitochondria. We investigated the influence of Alda-1, an activator of ALDH2, on atherogenesis and on the liver steatosis in apolipoprotein E knockout (apoE(-/-)) mice.

The influence of angiotensin-(1-7) Mas receptor agonist (AVE 0991) on mitochondrial proteome in kidneys of apoE knockout mice.

Excessive action of angiotensin II on mitochondria has been shown to play an important role in mitochondrial dysfunction, a common feature of atherogenesis and kidney injury. Angiotensin-(1-7)/Mas receptor axis constitutes a countermeasure to the detrimental effects of angiotensin II on AT1 receptors. The aim of the study was to assess the effects of angiotensin-(1-7) peptidomimetic AVE0991 on the kidney mitochondrial proteome in widely used animal model of atherosclerosis (apoE(-/-) mice).

Influence of atorvastatin on angiotensin I metabolism in resting and TNF-α -activated rat vascular smooth muscle cells.

Introduction: Vascular smooth muscle cells (VSMCs) are essential for maintaining vasculature homeostasis and function. By influence on its growth and activation both proinflammatory cytokines and peptides of the renin-angiotensin system (RAS) are potent regulators of VSMCs. Interestingly, angiotensin (Ang) II and Ang-(1-7) elicit opposite effects on VSMC activation, differentiation and proliferation.

Elevated interleukin-1β serum level after chronic peripheral salsolinol administration.

The catechol isoquinoline derivatives are endogenous compounds present in the mammalian brain and the representative one is referred to as salsolinol. It may be formed from aromatic amines leading to neurotoxic N-methyltetrahydroquinolinium ions that may play a role in the etiology of Parkinson's disease (PD). Neuroinflammation and apoptosis is thought to be a major contributor to the neuronal degeneration in PD.

Proteomic analysis of liver mitochondria of apolipoprotein E knockout mice treated with metformin.

Nonalcoholic fatty liver disease (NAFLD) is strongly associated with insulin resistance. Metformin, a widely known anti-diabetic drug, used for patients with type 2 diabetes mellitus, is also claimed to be useful in treatment of NAFLD. However, both the clinical efficacy and the putative mechanisms underlying the clinical effects of metformin in treating NAFLD are unclear.

Beneficial effect of amantadine on postoperative pain reduction and consumption of morphine in patients subjected to elective spine surgery.

Objective: To analyze the effect of coadministration of morphine and amantadine on postoperative pain reduction and morphine consumption in patients after elective spine surgery.

Methods: In double-blinded study, 60 patients (ASA physical status I-II) were randomized into two groups. Group A was given oral amantadine 50 or 100 mg 1 hour before surgery and 8, 20, 32 hours after operation.

The influence of salsolinol on basic rat metabolism.

Parkinson's disease (PD) is associated with a broad spectrum of non-motor symptoms, which are poorly understood and foremost, may precede motor impairment. These symptoms include weight changes and gastrointestinal dysregulation. In our experiment, we applied salsolinol given peripherally and continuously in rats to induce changes in the enteric nervous system, which might be similar to those observed in PD patients.

Metabolism of bradykinin in aorta of hypertensive rats.

Alterations in the formation and metabolism of bradykinin (Bk) are hypothesized to play a role in the pathophysiology of hypertension, atherosclerosis and vascular complications of diabetes. However, despite its prominent role in cardiovascular regulation, studies on bradykinin have been limited by various difficulties in accurate measurements of this peptide in biological samples. In this study, using the LC-ESI-MS method we estimated the conversion of exogenous Bk to its main metabolites - Bk-(1-5) and Bk-(1-7) - in endothelial cell culture and in fragments of aorta of normotensive (WKY) and hypertensive rats (SHR).

Proteomic analysis of changes in protein expression in liver mitochondria in apoE knockout mice.

The involvement of both apolipoprotein E (apoE) and mitochondria in lipid metabolism is widely recognized, however there is surprisingly scarce data about the putative mitochondrial action(s) of this protein. The aim of the study was to screen the alterations in liver mitochondrial proteome caused by apoE deficiency. We applied 2DE-LC-MS/MS methodology to investigate the changes in liver mitochondrial protein expression in 6-months old apoE(-/-) mice as compared to C57BL/6J controls.

Co-administration of dextromethorphan and morphine: reduction of post-operative pain and lack of influence on morphine metabolism.

We investigated co-analgesic effect of dextromethorphan in adolescent post-operative patients with idiopathic scoliosis. In a double-blind study, 60 patients with ASA physical status I-II were randomised into two groups. Group dextromethorphan (n = 30; age: 15.

[Metformin--an inhibitor of early stages of protein glycation].

Nonenzymatic glycation of proteins is associated with the long-term diabetes complication. The aim of this work was to examine in vitro the infuence of metformin on glycated proteins formation by mass spectrometry (ESI/MS, LC/MS/MS) and spectrofluorimetric method. Obtained results suggest that metformin dose-dependently inhibits early stage of Maillard reaction, although with the weaker potency than known glycation inhibitor aminoguanidine.

[Evaluation of morphine metabolism in presence of amantadine and dextromethorphan in human serum by high performance liquid chromatography coupled with mass spectrometry (LC/MS) method].

In the present study we assessed by LC/MS method the influence of amantadine and dextromethorphan on morphine metabolism in humans in order to explain clinically observed phenomenon of amplification of analgesic action of morphine by these drugs. Neither dextromethorphan nor amantadine influenced the rate of morphine degradation and concentration of morphine metabolites. Thus, our results suggest pharmacodynamical, not pharmacokinetic mechanism of interaction.