No abstract

A principal marker of brain vulnerability, stress, aging, and related pathology is represented by lipopigments (LPs)--lipofuscin, and ceroid. During ontogenesis, neuronal LP accumulations are significantly correlated with important changes in nerve cell morphology and biochemistry. In the aged neurons, LPs are present in all cellular compartments. Moreover, neuronal LP accumulations coexist with glial LP storage, especially in microglia. Owing to their transporting properties, and the migration capacity of microglia, glial cells deposit LP clusters in pericapillary areas. Thus, LP conglomerates appear in the whole nervous tissue, creating specific patterns of LP architectonics. Direct interrelations, critical LP concentrations, which generate cascades of negative subcellular events, and indirect impairment correlations determine characteristic neuropathologic aging profiles. These specific and associated negative neuropathologic consequences of LP accumulation have multiple and detrimental impacts on neuron and glia homeostasis, ranging from neuronal function to central nervous system physiology.

No abstract

In recent years, escitalopram (ESC) has been suggested to have different mechanisms of action beyond its well known selective serotonin reuptake inhibition. The aim of this study is to investigate the effects of escitalopram on oxidative stress, apoptosis, brain-derived neurotrophic factor (BDNF), Methyl-CpG-binding protein 2 (MeCP2), and oligodendrocytes number in the brain of chronic unpredictable mild stress-induced depressed rats. The animals were randomised in four groups (8 in each group): control, stress, stress + ESC 5 and stress + ESC 5/10. ESC was administered for 42 days in a fixed dose (5 mg/kg b.w.) or in an up-titration regimen (21 days ESC 5 mg/kg b.w. then 21 days ESC 10 mg/kg b.w.). Sucrose preference test (SPT) and elevated plus maze (EPM) were also performed. ESC improved the percentage of sucrose preference, locomotion and anxiety. ESC5/10 reduced the oxidative damage in the hippocampus and improved the antioxidant defence in the hippocampus and frontal lobe. ESC5/10 lowered caspase 3 activity in the hippocampus. Escitalopram had a modulatory effect on BDNF and the number of oligodendrocytes in the hippocampus and frontal lobe and also improved the MeCP2 expressions. The results confirm the multiple pathways implicated in the pathogenesis of depression and suggest that escitalopram exerts an antidepressant effect via different intricate mechanisms.

(1) Background: Recent research suggests inflammation as a factor involved in the pathophysiology of mood disorders. Neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR), platelet-to-lymphocyte (PLR), and systemic immune-inflammatory (SII) index ratios have been studied as peripheral markers of inflammation in bipolar and major depressive disorders. The purpose of this study is to comparatively analyze these inflammatory ratios among manic episodes of bipolar disorder, bipolar depression and unipolar depression. (2) Methods: 182 patients were retrospectively included in the study and divided into three groups: 65 manic patients, 34 patients with bipolar depression, and 83 unipolar depressive patients. White blood cells, neutrophils, monocytes, lymphocytes, and platelets were retrieved from the patients’ database. NLR, MLR, PLR, and SII index were calculated using these parameters. (3) Results: Patients with manic episodes had elevated NLR (p < 0.001), MLR (p < 0.01), PLR (p < 0.05), and SII index (p < 0.001) compared to unipolar depression and increased NLR (p < 0.05) and SII index (p < 0.05) when compared to bipolar depression. NLR (p < 0.01) and SII index (p < 0.05) were higher in the bipolar depression than unipolar depression. NLR is an independent predictor of the bipolar type of depression in depressive patients. (4) Conclusions: The results confirm the role of inflammation in the pathophysiology of mood disorders and suggest the ability of NLR as a marker for the differentiation of bipolar from unipolar depression.

No abstract

Innovative nanomaterials are required for the coatings of titanium (Ti) implants to ensure the activation of Ti surfaces for improved osseointegration, enhanced bone fracture healing and bone regeneration. This paper presents a systematic investigation of biomimetic composite (BC) coatings on Ti implant surfaces in a rat model of a diaphyseal femoral fracture. Methodological approaches of surface modification of the Ti implants via the usual joining methods (e.g., grit blasting and acid etching) and advanced physicochemical coating via a self-assembled dip-coating method were used. The biomimetic procedure used multi-substituted hydroxyapatite (ms-HAP) HAP-1.5 wt% Mg-0.2 wt% Zn-0.2 wt% Si nanoparticles (NPs), which were functionalized using collagen type 1 molecules (COL), resulting in ms-HAP/COL (core/shell) NPs that were embedded into a polylactic acid (PLA) matrix and finally covered with COL layers, obtaining the ms-HAP/COL@PLA/COL composite. To assess the osseointegration issue, first, the thickness, surface morphology and roughness of the BC coating on the Ti implants were determined using AFM and SEM. The BC-coated Ti implants and uncoated Ti implants were then used in Wistar albino rats with a diaphyseal femoral fracture, both in the absence and the presence of high-frequency pulsed electromagnetic shortwave (HF-PESW) stimulation. This study was performed using a bone marker serum concentration and histological and computer tomography (micro-CT) analysis at 2 and 8 weeks after surgical implantation. The implant osseointegration was evaluated through the bone–implant contact (BIC). The bone–implant interface was investigated using FE-SEM images and EDX spectra of the retrieved surgical implants at 8 weeks in the four animal groups. The obtained results showed significantly higher bone–implants contact and bone volume per tissue volume, as well as a greater amount of newly formed bone, in the BC-coated Ti implants than in the uncoated Ti implants. Direct bone–implant contact was also confirmed via histological examination. The results of this study confirmed that these biomimetic composite coatings on Ti implants were essential for a significant enhancement of osseointegration of BC-coated Ti implants and bone regeneration. This research provides a novel strategy for the treatment of bone fractures with possible orthopedic applications.

Repetitive and cumulative distress (acute and/or chronic, psychic and/or biologic) and aging processes (impairment phenomena, agglomerated, and accumulated with the passing of life and senescence periods), as well as distress <==> aging reciprocal amplification-accelerating-aggravation relationships require strong and rational (etiopathogenic) therapeutic interventions. Therefore, the drug, Antagonic-Stress (AS)--a new integrative therapy, with specific synergistic formula, being patented worldwide--becomes an important solution in distress, senescence, and their related pathologies. In acute (contention) stress, AS treatment significantly decreased rat mortality, number and surface of stomach ulcerations, nonesterified fatty acids (NEFAs), and increased superoxide dismutase (SOD) from blood. In chronic psychic stress, live nerve cells selectively isolated from rat cerebral cortex were highly protected by the administration of AS. In addition, antistress and antiaging homeostatic actions of AS were demonstrated in accelerated senescence (aging + distress) at multiple brain levels: on functional anabolism [increase in total ribonucleic acids (RNA), total proteins (TP), and water-soluble proteins (WSP)]; on functional catabolism [decrease in water-insoluble proteins (WIP)]; on structural anabolism (increased regeneration of free ribosomes, rough endoplasmic reticulum, mitochondria, and Nissl bodies); on structural catabolism (lipofuscinolysis and ceroidolysis, neurono-glial transfer of lipopigment continuously processed and dissoluted, and finally capillary elimination). Preclinical research with AS demonstrated important regenerative processes in the key organs (liver, heart, and brain), which mostly suffer due to both distress and senescence.