The Effect of Silver Nanoparticles on Antioxidant/Pro-Oxidant Balance in a Murine Model.

This study aimed to evaluate the subacute effect of two types of Ag-NPs(EG-AgNPs and PVP-EG-AgNPs) on antioxidant/pro-oxidant balance in rats. Seventy Wistar rats (35 males and 35 females) were divided in 7 groups and intraperitoneally exposed for 28 days to 0, 1, 2 and 4 mg/kg bw/day EG-Ag-NPs and 1, 2 and 4 mg/kg bw/day PVP- EG-Ag-NPs. After 28 days, the blood was collected, and the total antioxidant capacity (TAC), thiobarbituric reactive species (TBARS),protein carbonyl (PROTC) levels, reduced glutathione (GSH) levels and catalase (CAT) activity were determined. EG-Ag-NPs determined protective antioxidant effects in a dose-dependent manner. The exposure to the 4 mg/kg bw/day EG-Ag-NPs determines both in males and females a significant increase in TAC and CAT and a significant decrease in TBARS and PROTC only in females. The PVP-EG-AgNPs showed a different trend compared to EG-AgNPs. At 4 mg/kg bw/day the PVP-EG-AgNPs induce increased PROTC levels and decreased GSH (males and females) and TAC levels (males). The different mechanisms of EG-AgNPs and PVP-EG-AgNPs on antioxidant-/pro-oxidant balance can be explained by the influence of coating agent used for the preparation of the nanoparticles in the formation and composition of protein corona that influence their pathophysiology in the organism.

How does healthy aging impact on the circadian clock?

Circadian rhythms are recurring patterns in a host of physiological and other parameters that recur with periods of near 24 h. These rhythms reflect the temporal organization of an organism's homeostatic control systems and as such are key processes in ensuring optimal physiological performance. Dysfunction of circadian processes is linked with adverse health conditions. In this review we highlight the evidence that normal, healthy aging is associated with changes in the circadian system; we examine the molecular mechanisms through which such changes may arise, discuss whether more robust circadian function is a predictor of longevity and highlight the role of circadian rhythms in age-related diseases. Overall, the literature shows that aging is associated with marked changes in circadian processes, both at the behavioral and molecular levels, and the molecular mechanisms through which such changes arise remain to be elucidated, but may involve inflammatory process, redox homeostasis and epigenetic modifications. Understanding the nature of age-related circadian dysfunction will allow for the design of chronotherapeutic intervention strategies to attenuate circadian dysfunction and thus improve health and quality of life.

Vascular cognitive impairment, dementia, aging and energy demand. A vicious cycle.

To a great extent, cognitive health depends on cerebrovascular health and a deeper understanding of the subtle interactions between cerebrovascular function and cognition is needed to protect humans from one of the most devastating affliction, dementia. However, the underlying biological mechanisms are still not completely clear. Many studies demonstrated that the neurovascular unit is compromised in cerebrovascular diseases and also in other types of dementia. The hemodynamic neurovascular coupling ensures a strong increase of the cerebral blood flow (CBF) and an acute increase in neuronal glucose uptake upon increased neural activity. Dysfunction of cerebral autoregulation with increasing age along with age-related structural and functional alterations in cerebral blood vessels including accumulation of amyloid-beta (Aß) in the media of cortical arterioles, neurovascular uncoupling due to astrocyte endfeet retraction, impairs the CBF and increases the neuronal degeneration and susceptibility to hypoxia and ischemia. A decreased cerebral glucose metabolism is an early event in Alzheimer's disease (AD) pathology and may precede the neuropathological Aß deposition associated with AD. Aß accumulation in turn leads to further decreases in the CBF closing the vicious cycle. Alzheimer, aging and diabetes are also influenced by insulin/insulin-like growth factor-1 signaling, and accumulated evidence indicates sporadic AD is associated with disturbed brain insulin metabolism. Understanding how vascular and metabolic factors interfere with progressive loss of functional neuronal networks becomes essential to develop efficient drugs to prevent cognitive decline in elderly.

Neurovascular remodeling in the aged ischemic brain.

Restorative strategies after stroke are focused on the remodeling of cerebral endothelial cells and brain parenchymal cells. The latter, i.e., neurons, neural precursor cells and glial cells, synergistically interact with endothelial cells in the ischemic brain, providing a neurovascular unit whose components can be used as target for stroke therapies. Following focal cerebral ischemia, brain capillary cells are enabled to sprout. Neural precursor cells proliferate and migrate along cerebral microvessels to the ischemic lesion. Glial cells promote the restoration of functional microvessels and at the same time control the buildup of the extracellular matrix, creating a favorable environment to neuronal plasticity both in the ischemic and contralesional brain hemiphere. Until now, a large majority of studies have been performed in young, otherwise healthy animals. Recent behavioral, histochemical and molecular biological studies have shown that restorative brain responses differ between young and old animals, and that they are also modulated by age-related vascular risk factors, i.e., atherosclerosis, diabetes and hyperlipidemia. We claim that age aspects should more carefully be taken into consideration in translational proof-of-concept studies.

Novel putative mechanisms to link circadian clocks to healthy aging.

The circadian clock coordinates the internal physiology to increase the homeostatic capacity thereby providing both a survival advantage to the system and an optimization of energy budgeting. Multiple-oscillator circadian mechanisms are likely to play a role in regulating human health and may contribute to the aging process. Our aim is to give an overview of how the central clock in the hypothalamus and peripheral clocks relate to aging and metabolic disorders, including hyperlipidemia and hyperglycemia. In particular, we unravel novel putative mechanisms to link circadian clocks to healthy aging. This review may lead to the design of large-scale interventions to help people stay healthy as they age by adjusting daily activities, such as feeding behavior, and or adaptation to age-related changes in individual circadian rhythms.

Poststroke Cell Therapy of the Aged Brain.

During aging, many neurodegenerative disorders are associated with reduced neurogenesis and a decline in the proliferation of stem/progenitor cells. The development of the stem cell (SC), the regenerative therapy field, gained tremendous expectations in the diseases that suffer from the lack of treatment options. Stem cell based therapy is a promising approach to promote neuroregeneration after brain injury and can be potentiated when combined with supportive pharmacological drug treatment, especially in the aged. However, the mechanism of action for a particular grafted cell type, the optimal delivery route, doses, or time window of administration after lesion is still under debate. Today, it is proved that these protections are most likely due to modulatory mechanisms rather than the expected cell replacement. Our group proved that important differences appear in the aged brain compared with young one, that is, the accelerated progression of ischemic area, or the delayed initiation of neurological recovery. In this light, these age-related aspects should be carefully evaluated in the clinical translation of neurorestorative therapies. This review is focused on the current perspectives and suitable sources of stem cells (SCs), mechanisms of action, and the most efficient delivery routes in neurorestoration therapies in the poststroke aged environment.

Perfusion deficits, inflammation and aging precipitate depressive behaviour.

Major depressive disorder (MDD) is a severe psychiatric illness that is associated with significant morbidity and mortality. Despite advances in the treatment of major depression, one-third of depressed patients fail to respond to conventional antidepressant medication. One pathophysiologic mechanism hypothesized to contribute to treatment resistance in depression is inflammation. Inflammation has been linked to depression by a number of putative mechanisms involving perfusion deficits that can trigger microglial activation and subsequent neuroinflammation in the elderly. However, the pathophysiological mechanisms remain to be further elucidated. This review focusses on recent studies addressing the complex relationships between depression, aging, inflammation and perfusion deficits in the elderly. We expect that a better understanding of neuroinflammatory mechanisms associated with age-related diseases may lead to the discovery of new biomarkers of MDD and development of new therapeutic interventions.

Oxidative Stress-Induced Neurodegeneration and Antioxidative Strategies: Current Stage and Future Perspectives.

Neurodegenerative diseases (NDs) are the leading cause of neurological disorders, constituting a public health problem with an exponentially growing incidence rate [...].

Correlations of Serum Vitamin D Level with Markers of Oxidative Stress and Apoptosis in Liver Cirrhosis.

In this study we investigated the relationship between vitamin D and markers of oxidative stress and apoptosis in patients with liver cirrhosis stratified according serum GGT activity. Forty-eight patients with liver cirrhosis of various aetiology were selected, among which 58% cases (n=28) diagnosed with alcoholic liver cirrhosis and 42% (n=20) with cirrhosis after hepatitis virus infection. Each group was divided into three quartiles according GGT activity. 25-hydroxyvitamin D [25-(HO) vit D], markers of oxidative stress (catalase, superoxide dismutase) and apoptosis (M30) were compared. Higher levels of GGT were correlated with elevated AST, ALT and ALP values in both groups. A statistically significant difference was observed when comparing 25-(OH) vit D levels of patients suffering from ethanol-induced liver cirrhosis versus control group for all the quartiles as well as for those from the first quartile of viral-induced liver cirrhosis. For SOD, statistically significant differences were noticed between all cirrhosis subgroups and the control group. CAT values in all cirrhosis subgroups were lower than in control, but significant differences were only between Q2.2 and Q1.3 quartiles and Q2.2 and control. Correlation of 25-(OH) vit D versus SOD yields statistically significant results in ethanol-induced cirrhosis patients. M30 activity was increased in patients with alcoholic cirrhosis compared to controls and those with virus-induced cirrhosis, being correlated with the degree of GGT activity. Our results emphasized that vitamin D deficiency is associated with enhanced liver dysfunction regardless of the trigger responsible for disease onset. Furthermore, vitamin D deficiency augments liver injury by promoting oxidative stress which influence the survival mechanisms of parenchymal liver cells.

The Gut-Brain Axis as a Therapeutic Target in Multiple Sclerosis.

The CNS is very susceptible to oxidative stress; the gut microbiota plays an important role as a trigger of oxidative damage that promotes mitochondrial dysfunction, neuroinflammation, and neurodegeneration. In the current review, we discuss recent findings on oxidative-stress-related inflammation mediated by the gut-brain axis in multiple sclerosis (MS). Growing evidence suggests targeting gut microbiota can be a promising strategy for MS management. Intricate interaction between multiple factors leads to increased intra- and inter-individual heterogeneity, frequently painting a different picture in vivo from that obtained under controlled conditions. Following an evidence-based approach, all proposed interventions should be validated in clinical trials with cohorts large enough to reach significance. Our review summarizes existing clinical trials focused on identifying suitable interventions, the suitable combinations, and appropriate timings to target microbiota-related oxidative stress. Most studies assessed relapsing-remitting MS (RRMS); only a few studies with very limited cohorts were carried out in other MS stages (e.g., secondary progressive MS-SPMS). Future trials must consider an extended time frame, perhaps starting with the perinatal period and lasting until the young adult period, aiming to capture as many complex intersystem interactions as possible.

Is There a Potential Link between Gastroesophageal Reflux Disease and Recurrent Respiratory Tract Infections in Children?

BACKGROUND: The implications of gastroesophageal reflux disease in respiratory tract infections have been investigated over time. The aim of our study was to evaluate the relationship between these two pathologic entities and the outcome after proper antireflux treatment. METHODS: A group of 53 children with recurrent respiratory tract infections admitted in the gastroenterology clinic of a children's hospital in North-East Romania was investigated for gastroesophageal reflux disease through 24 h pH-metry. Those with a Boix-Ochoa score higher than 11.99 received proton pump inhibitor treatment and were reevaluated after 2 months. RESULTS: A total of 41 children were found with a positive Boix-Ochoa score. After 2 months of antireflux therapy, eight patients still had a positive Boix-Ochoa score. CONCLUSIONS: Recurrent respiratory tract infections with symptoms resistant to treatment should be considered a reason to investigate for gastroesophageal reflux, because the symptoms may be due to micro- or macro-aspiration of the gastric refluxate or to an esophageal-bronchial reflex mediated through the vagal nerve.

Quality of life three months post­stroke among stroke patients and their caregivers in a single center study from Romania during the COVID­19 pandemic: A prospective study.

The aim of the present study was to determine the health-related quality of life of stroke patients and their caregivers during the fifth wave of the COVID-19 pandemic. A total of 70 patients who had been diagnosed with stroke between October 2021 and March 2022 and 70 caregivers were included in the present study. A prospective follow-up study assessing the quality of life at baseline was conducted after 3 months for both patients and their caregivers. A linear regression analysis was performed to evaluate potential associations between quality of life and assessed factors. The results revealed that age, sex, employment status, hospitalization period, type of stroke, Barthel index for activities of daily living (ADL) and discharge Modified Rankin Scale (mRS), were significant determinants of the 90-day Health-Related Quality of Life (HRQoL). An important clinical change in the QoL score was estimated for both post-stroke patients and their caregivers. The decrease of the HRQoL of patients was statistically influenced by a higher value of ADL (P=0.014), whereas, in the case of their caregivers, the decrease of HRQoL was primarily influenced by the QoL of patients after 3 months (P=0.043). The present study identified some important key factors with direct consequences on HRQoL regarding stroke survivors and their caregivers.

Difficulties in Adaptation of the Mother and Newborn via Cesarean Section versus Natural Birth-A Narrative Review.

Birth is a physiological act that is part of the morpho-functional economy of the maternal body. Each stage in the act of birth has a predetermined pathway that is neurohormonally induced and morpho-functionally established through specific and characteristic adaptations. Like maternity, childbirth also has an important impact on the maternal body as a biological structure and psycho-emotional behavior. Cesarean section performed at the request of the mother with no medical underlying conditions besides the prolonged hospitalization risk can also cause breathing problems in children, delayed breastfeeding, and possible complications in a future pregnancy. Vaginal birth remains the path of choice for a physiological evolution pregnancy. Although erroneously considered safe and easy today, cesarean section delivery must remain an emergency procedure or a procedure recommended for pregnancies where birth is a risk to the mother and to the child, as cesarean section itself is a risk factor for negative outcomes for both mother and baby. This review summarizes the impact that both cesarean section and natural birth have on mother and newborn in their attempt to adapt to postpartum events and extrauterine life.

A novel nutraceutical formulation increases telomere length and activates telomerase activity in middle­aged rats.

Telomeres are major contributors to cell fate and aging through their involvement in cell cycle arrest and senescence. The accelerated attrition of telomeres is associated with aging­related diseases, and agents able to maintain telomere length (TL) through telomerase activation may serve as potential treatment strategies. The aim of the present study was to assess the potency of a novel telomerase activator on TL and telomerase activity in vivo. The administration of a nutraceutical formulation containing Centella asiatica extract, vitamin C, zinc and vitamin D3 in 18­month­old rats for a period of 3 months reduced the telomere shortening rate at the lower supplement dose and increased mean the TL at the higher dose, compared to pre­treatment levels. TL was determined using the Q­FISH method in peripheral blood mononuclear cells collected from the tail vein of the rats and cultured with RPMI­1640 medium. In both cases, TLs were significantly longer compared to the untreated controls (P≤0.001). In addition, telomerase activity was increased in the peripheral blood mononuclear cells of both treatment groups. On the whole, the present study demonstrates that the nutraceutical formulation can maintain or even increase TL and telomerase activity in middle­aged rats, indicating a potential role of this formula in the prevention and treatment of aging­related diseases.

Relationship between Serum Gamma-Glutamyltransferase and Glutathione Antioxidant System in Patients with Liver Cirrhosis of Various Etiology.

Oxidative stress involvement in liver diseases has been extensively studied. A direct assessment of the reactive species incriminated is avoided due to their short lifespan and high cost. For these reasons an inexpensive and easy to perform test for whole body oxidative stress is highly desired. This pilot study was conducted to assess the relationship between γ-glutamyl transferase (GGT) activity and markers of oxidative stress: reduced glutathione (GSH), glutathione peroxidase (GPx) activity and lipid peroxidation in patients with liver cirrhosis due to chronic ethanol consumption and viral hepatitis. Forty-eight patients with alcoholic liver cirrhosis and cirrhosis developed after HBV and HCV infection were included in this study.Blood GSH andGPxand serum GGT and MDAwere assayed and the results were statistically analyzed. The activity of serum GGT was significantly higher in the alcoholic group. The relationship between GGT activity, GSH and MDA levels was different between groups.A strong significant positive correlation between GGT and GSH was noticed for the patients from GGT Q3 and Q4 quartiles in the group of viral liver cirrhosis, while for alcoholics the relationship between GGT and GSH showed the trend for a negative correlation.The values of serum MDA differ significantly between groups (p<0.015); a very significant variation was observed at low levels of GGT activity (p<0.006). Our study demonstrates that the GSH antioxidant defense system is more compromisedin alcoholic cirrhosisand tends to correlate negatively with GGT. Even in its normal range GGT might be an early and sensitive marker of oxidative stress.

Iron Deficiency Anemia in Pediatric Gastroesophageal Reflux Disease.

(1) Background: Gastroesophageal reflux disease (GERD) can cause several complications as a result of the acidic pH over various cellular structures, which have been demonstrated and evaluated over time. Anemia can occur due to iron loss from erosions caused by acidic gastric content. In children, anemia has consequences that, in time, can affect their normal development. This study evaluates the presence of anemia as a result of pediatric gastroesophageal reflux disease. (2) Methods: 172 children were diagnosed with gastroesophageal reflux in the gastroenterology department of a regional children's hospital in northeast Romania by esophageal pH-metry and they were evaluated for presence of anemia. (3) Results: 23 patients with GERD from the studied group also had anemia, showing a moderate correlation (r = -0.35, p = 0.025, 95% confidence interval) and lower levels of serum iron were found in cases with GERD, with statistical significance (F = 8.46, p = 0.012, 95% confidence interval). (4) Conclusions: The results of our study suggest that there is a relationship between anemia or iron deficiency and gastroesophageal reflux due to reflux esophagitis in children, which needs to be further studied in larger groups to assess the repercussions on children's development.

The Impact of Chronic Suppurative Otitis Media with and without Cholesteatoma in Patients from Northeastern Romania.

Quality of life is a widely used concept that tends to become an important part of clinical management. The present study performs an analysis of the impact of suppurative chronic otitis media with and without cholesteatoma on quality of life, using the COMQ-12 questionnaire. It was applied to a group of 40 healthy people and to 40 patients before surgery, and the answers to the questions were analyzed and correlated with socioeconomic factors. After the confirmation of the diagnosis based on clinical and imaging information, the patients completed the COMQ-12 questionnaire. It was observed that the chronic ear problems had negative impacts of varying degrees on daily and long-term activities. The evaluation and analysis of information can be used in setting therapeutic targets.

The Gut Microbiome and Its Implication in the Mucosal Digestive Disorders.

The gastrointestinal (GI) tract is one of the most studied compartments of the human body as it hosts the largest microbial community including trillions of germs. The relationship between the human and its associated flora is complex, as the microbiome plays an important role in nutrition, metabolism and immune function. With a dynamic composition, influenced by many intrinsic and extrinsic factors, there is an equilibrium maintained in the composition of GI microbiota, translated as "eubiosis". Any disruption of the microbiota leads to the development of different local and systemic diseases. This article reviews the human GI microbiome's composition and function in healthy individuals as well as its involvement in the pathogenesis of different digestive disorders. It also highlights the possibility to consider flora manipulation a therapeutic option when treating GI diseases.

Vitamin Status as Predictors in Rheumatoid Arthritis.

Musculoskeletal disorders are the leading cause of long term disability in EU with a significant impact on health care system and with increased social and economic costs. Despite of recent advances in Rheumatoid arthritis (RA) research field, here is still lacking of specific biomarkers that can be used in order to distinguish between different RA patterns and the clinical criteria are still the main tool used only for classification of diseases. Our hypothesis is that the vitamin deficiency associated with chronic inflammation can lead to a mild increase in Hcy level in blood that can act as predictor of increased risk of complication in RA patients. The aim of our study was to identify a correlation between level of Hcy in peripheral blood samples collected from RA patients and to establish if the Hcy level can be validate as potential predictive biomarker in RA patients treated with different DMARDs. Our findings suggest that Hcy level in plasma and CRP are independent predictors of chronic inflammatory status and are useful biomarkers in order to estimate the risk of complication in RA patients. To our knowledge to date, studies before had a controversial findings regarding the efficiency of folate and B12 vitamins supplements on decreasing the cardiovascular events risk. We showed that the folic acid and B12 supplements are important.

Homocysteine as a Predictor Tool in Multiple Sclerosis.

Multiple sclerosis (MS) is a progressive and irreversible disease which affects the central nervous system (CNS) with still unknown etiology. Our study aimes to establish the homocysteine pattern that can predict the MS diseases progression and to identify a potential disease progression marker that can be easy to perform and non-invasive, in order to predict the diseases outcome. In order to achieve this goal, we included 10 adult RRMS subjects, 10 adult SPMS subjects and 10 age-matched healthy subjects. The homocysteine plasma level was measured using automated latex enhanced immunoassay and the cobalamin and folate measurements were performed using automated chemiluminescence immunoassay (CLIA). HCR was calculated by dividing the homocysteine plasma level by cobalamin plasma level. We found that the homocysteine level in plasma of both RRMS patients and SPMS group are significantly increased compared with the control group. There is a significantly higher concentration of homocysteine in SPMS group compared with the RRMS group. In addition, the HCR is significantly increased in SPMS compared with the RRMS group and is a very good index of disease severity.