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.

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.

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 [...].

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.

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.

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.

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.

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.

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.

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.

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.

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.

Reversal of brain aging by targeting telomerase: A nutraceutical approach.

Telomeres, the protective caps of chromosomes, shorten with age, as telomerase, the enzyme responsible for the compensation of telomere erosion, is inactive in the majority of cells. Telomere shortening and subsequent cell senescence lead to tissue aging and age­related diseases. Neurodegenerative disorders, characterized by the progressive loss of neurons among other hallmarks of aged tissue, and poor cognitive function, have been associated with a short telomere length. Thus, telomerase activity has emerged as a therapeutic target, with novel agents being under investigation. The present study aimed to examine the effects of a novel natural telomerase activator, 'Reverse™', containing Centella asiatica extract, vitamin C, zinc and vitamin D3 on the brains of 18­month­old rats. The administration of the 'Reverse™' supplement for 3 months restored telomerase reverse transcriptase (TERT) expression in the brains of rats, as revealed by ELISA and immunohistochemistry. In addition, the findings from PCR­ELISA demonstrated an enhanced telomerase activity in the cerebellum and cortex cells in the brains of rats treated with the 'Reverse™' supplement. The histopathological findings confirmed a structural reversibility effect close to the differentiation observed in the young control group of rats treated with two capsules/kg body weight of the 'Reverse™' supplement. On the whole, the findings of the present study provide a strong indication that an increased telomerase activity and TERT expression may be achieved not only in the postnatal or embryonic period, but also in the brains of middle­aged rats through nutraceutical supplementation. The use of the 'Reverse™' supplement may thus contribute to the potential alleviation of a number of central nervous system diseases.

Interrelation of inflammation and oxidative stress in liver cirrhosis.

Recently, the trend of research has been focused on the role of hematological indicators in assessing the activities of various diseases. The aim of the present study was to determine the usefulness of such hematological indicators for assessment of the relationship between inflammation and oxidative stress in order to provide new predictive tools for a non-invasive investigation of disease outcome for liver cirrhosis patients. A total of 35 subjects with compensated or decompensated liver cirrhosis and 10 age-matched healthy volunteers were included in this study. The patients were divided into two groups: Group 1, patients with toxic metabolic cirrhosis due to ethanol consumption; group 2, patients with liver cirrhosis following hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. Using hematological data obtained after the complete counting of peripheral blood cells, the monocyte/lymphocyte (MLR), neutrophil/lymphocyte (NLR) and platelet/lymphocyte (PLR) ratios as well as systemic immune inflammation biomarkers were determined. The erythrocyte sedimentation ratio (ESR), C-reactive protein (CRP), fibrinogen and biochemical parameters related to liver function were also registered. Thiobarbituric acid reactive substances (TBARS), protein carbonyl content (PCARB), and total antioxidant capacity (TAC) were also investigated in the peripheral blood samples of healthy subjects and liver cirrhosis patients. The results revealed that NLR, MLR and PLR were significantly increased in group 2. PLR was significantly increased in group 1 compared with that noted in the control group. TBARS and PCARB were increased in patients from group 1 compared to patients from group 2 and the control group. However, no difference in TAC was found between the liver cirrhosis groups and the control. We showed that the pro-inflammatory status of liver cirrhosis patients can be easily appreciated by NLR, MLR but not PLR. However, the increase in these ratios was not significantly associated with a decrease in the antioxidant capacity and an augmentation of oxidative stress markers for the patients diagnosed with cirrhosis included in the two groups of study.

Crosstalk between vitamin D axis, inflammation and host immunity mechanisms: A prospective study.

Tuberculosis (TB) remains a public health burden, after many years at attempts for its eradication. Vitamin D (VD) status has been suggested to be related to TB susceptibility because it has the ability to regulate multiple axes of the innate and adaptive host immune response. VD mediates cathelicidin (LL-37) synthesis, a cationic bactericidal peptide, through the expression of vitamin D receptor (VDR). Host innate defense mechanisms include autophagy and apoptosis of alveolar macrophages. The present study aimed to assess the relationship between VD status, inflammation and host defense mechanisms before and after two months of first-line anti-TB pharmacotherapy. The study included newly diagnosed individuals with pulmonary TB without co-morbidities (HIV infection, diabetes, cancer) and without VD supplementation or other therapies interfering with VD serum levels. We measured serum levels of 25-hydroxyvitamin D (25-(OH)-D), the major circulating form of vitamin D, VDR, LL-37, beclin-1 (an autophagy marker) and M30 (an apoptosis biomarker) before and after two months of anti-TB treatment. Individuals presented lower levels of 25-(OH)-D before receiving first-line anti-TB treatment (T0) in comparison with its plasmatic levels after two-months of therapy (T2). At T2, patients were divided in two subgroups according the results of sputum-culture conversion. After two-months of therapy, decreased values of LL-37, beclin-1 and M30 were observed in the culture-negative patients compared to the culture-positive patients. Control of anti-TB treatment outcome could be improved by appraisal of VD status and host defense mechanisms such as autophagy and apoptosis.

A Novel Nutraceutical Formulation Can Improve Motor Activity and Decrease the Stress Level in a Murine Model of Middle-Age Animals.

Ageing is a genetically programmed physiological process that is modulated by numerous environmental factors, associated with decreasing physiological function, decreasing reproductive rate and increasing age-related mortality rate. Maintaining mobility performance and physical function in the elderly is the main objective of the successful ageing concept. In this study, we aimed to evaluate the beneficial effect of a novel nutraceutical formulation containing Centella asiatica L. extract, vitamin C, zinc and vitamin D3 (as cholecalciferol) on motor activity and anxiety with the use of a murine model of old animals, as a means of providing proof for clinical use in the elderly, for enhancing physical strength and improving life quality. Eighteen Sprague Dawley 18 months old male rats were divided into three groups and received corn oil (the control group) or 1 capsule/kg bw Reverse supplement (treatment group 1) or 2 capsules/kg bw Reverse supplement (treatment group 2), for a period of 3 months. The Reverse supplement (Natural Doctor S.A, Athens, Greece) contains 9 mg Centella asiatica L. extract, vitamin C (200 mg as magnesium ascorbate), zinc (5 mg as zinc citrate), vitamin D3 (50 µg as cholecalciferol) per capsule. Before and after the treatment, the motor function and behavioral changes for anxiety and depression were evaluated using the open-field test, elevated plus-maze test and rotarod test. The supplementation with Reverse (Natural Doctor S.A) supplement can improve the locomotor activity in old rats in a dose-dependent manner, as demonstrated by an increase in the latency to leave from the middle square, in the number of rearings in the open field test, in the time spent in the open arms and time spent in the center in the elevated plus-maze test and the latency to all in all three consecutive trials in the rotarod test. Stress also decreased significantly in a dose-dependent manner, following the treatment with Reverse supplement, as was demonstrated by the decrease in the number of groomings at the open field test and time spent in the dark and the number of groomings at the elevated plus-maze test.

Prediction of Autoimmune Diseases by Targeted Metabolomic Assay of Urinary Organic Acids.

Autoimmune diseases (ADs) are chronic disorders characterized by the loss of self-tolerance, and although being heterogeneous, they share common pathogenic mechanisms. Self-antigens and inflammation markers are established diagnostic tools; however, the metabolic imbalances that underlie ADs are poorly described. The study aimed to employ metabolomics for the detection of disease-related changes in autoimmune diseases that could have predictive value. Quantitative analysis of 28 urine organic acids was performed using Gas Chromatography-Mass Spectrometry in a group of 392 participants. Autoimmune thyroiditis, inflammatory bowel disease, psoriasis and rheumatoid arthritis were the most prevalent autoimmune diseases of the study. Statistically significant differences were observed in the tricarboxylate cycle metabolites, succinate, methylcitrate and malate, the pyroglutamate and 2-hydroxybutyrate from the glutathione cycle and the metabolites methylmalonate, 4-hydroxyphenylpyruvate, 2-hydroxyglutarate and 2-hydroxyisobutyrate between the AD group and the control. Artificial neural networks and Binary logistic regression resulted in the highest predictive accuracy scores (66.7% and 74.9%, respectively), while Methylmalonate, 2-Hydroxyglutarate and 2-hydroxybutyrate were proposed as potential biomarkers for autoimmune diseases. Urine organic acid levels related to the mechanisms of energy production and detoxification were associated with the presence of autoimmune diseases and could be an adjunct tool for early diagnosis and prediction.

Functional Recovery in Parkinson's Disease: Current State and Future Perspective.

Parkinson's disease (PD) is one of the most frequent neurodegenerative disorders, affecting not only the motor function but also limiting the autonomy of affected people. In the last decade, the physical exercises of different intensities carried out by kinetic therapeutic activities, by robotic technologies or with the participation of sensory cues, have become increasingly appreciated in the management of Parkinson's disease impairments. The aim of this paper was to evaluate the impact of physical exercises with and without physical devices on the motor and cognitive variables of PD patients. In order to achieve our objectives, we performed a systematic review of available original articles based on the impact of kinetic therapeutic activity. Through the search strategy, we selected original papers that were laboriously processed using characteristics related to physical therapy, or the tools used in physiological and psychological rehabilitation strategies for PD patients. In this study, we presented the most current intervention techniques in the rehabilitation programs of patients with Parkinson's disease, namely the use of assisted devices, virtual imagery or the performing of physical therapies that have the capacity to improve walking deficits, tremor and bradykinesia, to reduce freezing episodes of gait and postural instability, or to improve motor and cognitive functions.

The Treatment of Cognitive, Behavioural and Motor Impairments from Brain Injury and Neurodegenerative Diseases through Cannabinoid System Modulation-Evidence from In Vivo Studies.

Neurological disorders such as neurodegenerative diseases or traumatic brain injury are associated with cognitive, motor and behavioural changes that influence the quality of life of the patients. Although different therapeutic strategies have been developed and tried until now to decrease the neurological decline, no treatment has been found to cure these pathologies. In the last decades, the implication of the endocannabinoid system in the neurological function has been extensively studied, and the cannabinoids have been tried as a new promising potential treatment. In this study, we aimed to overview the recent available literature regarding in vivo potential of natural and synthetic cannabinoids with underlying mechanisms of action for protecting against cognitive decline and motor impairments. The results of studies on animal models showed that cannabinoids in traumatic brain injury increase neurobehavioral function, working memory performance, and decrease the neurological deficit and ameliorate motor deficit through down-regulation of pro-inflammatory markers, oedema formation and blood-brain barrier permeability, preventing neuronal cell loss and up-regulating the levels of adherence junction proteins. In neurodegenerative diseases, the cannabinoids showed beneficial effects in decreasing the motor disability and disease progression by a complex mechanism targeting more signalling pathways further than classical receptors of the endocannabinoid system. In light of these results, the use of cannabinoids could be beneficial in traumatic brain injuries and multiple sclerosis treatment, especially in those patients who display resistance to conventional treatment.