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ObjectivesTo assess the effectiveness of Neuroaspis plp10 nutritional supplement when added to interferon (IFN)-β treatment in patients with relapsing-remitting multiple sclerosis (RRMS).DesignA 30-month phase III multicentre, randomised, double-blind, placebo-controlled trial. Randomisation stratified by centre using a computer-generated procedure with Neuroaspis plp10 versus placebo in 1:1 ratio. The first 6 months were used as both the pre-entry and normalisation period.Setting3 teaching hospitals in Greece and 1 Neurology Institute in Cyprus.Participants61 patients with RRMS on IFN-β were randomly assigned to receive Neuroaspis plp10 (n=32) or placebo (n=29), 20 mL, orally, once daily, for 30 months.InterventionNeuroaspis plp10, a cocktail mixture, containing specific PUFA (12 150 mg) and γ-tocopherol (760 mg) versus virgin olive oil (placebo).Main outcome measureThe primary end point was the annual relapse rate (ARR) whereas the secondary ones were the rate of sustained progression of disability, as measured by the Expanded Disability Status Scale (EDSS) and the brain T2 and gadolinium-enhancing lesions, at 2 years.ResultsFor the intention-to-treat analyses Neuroaspis plp10 significantly reduced the ARR by 80%, (RRR, 0.20; 95% CI: 0.09 to 0.45; p=0.0001) and the risk of sustained progression of disability by 73% (HR, 0.27; 95% CI: 0.09 to 0.83; p=0.022) versus placebo, at 2 years. The number of T1 gadolinium-enhancing lesions and the number of new/enlarged T2-hyperintense lesions were significantly reduced (p=0.01 and pConclusionsNeuroaspis plp10 added to IFN-β was significantly more effective than IFN-β alone in patients with RRMS.Trial registration numberISRCTN06166891.

Obesity is one of the most serious public health problems of the 21st century. The most common method used to define obesity is the BMI (weight/height squared in meters). If a person’s BMI is 30 or above is considered to be obese. In this review we focus on the different factors that cause obesity and on the different available treatment strategies. The mechanism behind weight gain is based on the energy intake of an individual. Positive energy balance leads to gain weight. With rapid economic growth, urbanization and westernization traditional diets high in fibres were replaced by diets high in sugar and fats which are high in energy and lead to a positive energy balance and therefore gain weight. Also, energy high food prices have declined leading to increased consumption of the latter. Fast foods which sell low quality/ energy high foods for a convenient price are an example of this phenomenon. Daily choices also influence the prevalence of obesity. For instance, eating out often can expose individuals to larger portions eventually leading to the phenomenon of portion distortion. Physical activity affects the energy balance of an individual along with dietary choices. Increase in physical activity, as shown in different studies, promotes weight loss. Combining low-fat diet with either vigorous exercise or simple lifestyle activity has been proven to be the best modality for weight loss. There are three main management strategies that can be followed in order to lose weight: lifestyle changes, pharmacotherapy and surgery. The primary approach to treat obesity is weight loss through diet and exercise, supported also by behavioural therapy. The aim of the diet should be lowering the calorie intake. People should first of all inform themselves about the different macronutrients normal intake levels and consult an expert. If no adequate weight loss is achieved by lifestyle changes, medications like Orlistat may be taken. If medications and lifestyle changes aren’t successful, surgery may be considered as an option to lose weight.

Cardiac sympathetic afferent that signal the sensation of cardiac pain, ostensibly, has more underlying mechanisms than what scientists have ever been led to believe. Cardiac sympathetic afferent reflex, also known as (CSAR), has been shown to be responsive to a variety of stimuli. Many of which scientists observed in increased levels during ischemia hydrogen ion, oxygen radicals, potassium, lactate, ATP, prostaglandins bradykinin, substance p and, finally and most importantly, endogenous substances (neurohormones) such as norepinephrine (NE). In the outset of chronic heart failure (HF), it has been known for a long time, that there are abnormalities in arterial baroreceptor input which depress its sensitivity, and arterial chemoreceptors seem augmented. Therefore, they tend to not only initiate sympathetic outflow but also to sensitise cardiac afferents which are appearing to do the same thing where there are abnormalities in vagus mechano-reflexes as well. Some of these receptors are in the spinal reticulate tract and interestingly these a third pathways give off neurons to the brainstem some in the hypothalamus and trance translate through the thalamus and then ultimately up into the cortex where we have sensation of pain. Here in this essay, we aim to discuss important aspects of cardiac failure in relation to abnormal sympatho-activators through evaluation of different available studies and animal models.

Patients with multiple sclerosis (MS) are characterized by, among other symptoms, impaired functional capacity and walking difficulties. Polyunsaturated fatty acids (PUFAs) have been found to improve MS patients’ clinical outcomes, however, their effect on other parameters associated with daily living activities need further investigation. The current study aimed to examine the effect of a 24-month supplementation with a cocktail dietary supplement formula, the NeuroaspisTM PLP10, containing specific omega-3 and omega-6 PUFAs and specific antioxidant vitamins on gait and functional capacity parameters of patients with MS. Fifty-one relapsing-remitting MS (RRMS) patients with low disability scores (age: 38.4 ± 7.1 years, 30 female) were randomized 1:1 to receive either a 20 mL daily dose of the dietary formula containing a mixture of omega-3 and omega-6 PUFAs (12,150 mg), vitamin A (0.6 mg), vitamin E (22 mg), and γ-tocopherol (760 mg), the OMEGA group (n = 27, age: 39 ± 8.3 years), or 20 mL placebo containing virgin olive oil, the placebo group (n = 24, age: 37.8 ± 5.3 years). The mean ± SD (standard deviation) Expanded Disability Status Scale (EDSS) score for the placebo group was 2.36 and for the OMEGA group 2.22. All enrolled patients in the study were on Interferon-b treatment. Spatiotemporal gait parameters and gait deviation index (GDI) were assessed using a motion capture system. Functional capacity was examined using various functional tests such as the six-minute walk test (6MWT), two sit-to-stand tests (STS-5 and STS-60), and the Timed Up and Go test (TUG). Isometric handgrip strength was assessed by a dynamometer. Leg strength was assessed using an isokinetic dynamometer. All assessments were performed at baseline and at 12 and 24 months of supplementation. A total of 36 patients completed the study (18 from each group). Six patients from the placebo group and 9 patients from the OMEGA group dropped out from the study or were lost to follow-up. The dietary supplement significantly improved the single support time and the step and stride time (p &lt, 0.05), both spatiotemporal gait parameters. In addition, while GDI of the placebo group decreased by about 10% at 24 months, it increased by about 4% in the OMEGA group (p &lt, 0.05). Moreover, performance in the STS-60 test improved in the OMEGA group (p &lt, 0.05) and there was a tendency for improvement in the 6MWT and TUG tests. Long-term supplementation with high dosages of omega-3 and omega-6 PUFAs (compared to previous published clinical studies using PUFAs) and specific antioxidant vitamins improved some functional capacity and gait parameters in RRMS patients.

Background and Objectives: Calcium (Ca2+) signaling is critical for the normal functioning of various cellular activities. However, abnormal changes in cellular Ca2+ can contribute to pathological conditions, including various types of cancer. The maintenance of intracellular Ca2+ levels is achieved through tightly regulated processes that help maintain Ca2+ homeostasis. Several types of regulatory proteins are involved in controlling intracellular Ca2+ levels, including the sarco/endoplasmic reticulum (SR/ER) Ca2+ ATPase pump (SERCA), which maintains Ca2+ levels released from the SR/ER. In total, three ATPase SR/ER Ca2+-transporting (ATP2A) 1-3 genes exist, which encode for several isoforms whose expression profiles are tissue-specific. Recently, it has become clear that abnormal SERCA expression and activity are associated with various types of cancer, including breast cancer. Breast carcinomas represent 40% of all cancer types that affect women, with a wide variety of pathological and clinical conditions. Materials and methods: Using cBioPortal breast cancer patient data, Kaplan–Meier plots demonstrated that high ATP2A1 and ATP2A3 expression was associated with reduced patient survival. Results: The present study found significantly different SERCA specific-type expressions in a series of breast cancer cell lines. Moreover, bioinformatics analysis indicated that ATP2A1 and ATP2A3 expression was highly altered in patients with breast cancer. Conclusion: Overall, the present data suggest that SERCA gene-specific expressioncan possibly be considered as a crucial target for the control of breast cancer development and progression.

P-class pumps are specific ion transporters involved in maintaining intracellular/extracellular ion homeostasis, gene transcription, and cell proliferation and migration in all eukaryotic cells. The present review aimed to evaluate the role of P-type pumps [Na+/K+ ATPase (NKA), H+/K+ ATPase (HKA) and Ca2+-ATPase] in cancer cells across three fronts, namely structure, function and genetic expression. It has been shown that administration of specific P-class pumps inhibitors can have different effects by: i) Altering pump function; ii) inhibiting cell proliferation; iii) inducing apoptosis; iv) modifying metabolic pathways; and v) induce sensitivity to chemotherapy and lead to antitumor effects. For example, the NKA β2 subunit can be downregulated by gemcitabine, resulting in increased apoptosis of cancer cells. The sarcoendoplasmic reticulum calcium ATPase can be inhibited by thapsigargin resulting in decreased prostate tumor volume, whereas the HKA α subunit can be affected by proton pump inhibitors in gastric cancer cell lines, inducing apoptosis. In conclusion, the present review highlighted the central role of P-class pumps and their possible use and role as anticancer cellular targets for novel therapeutic chemical agents.

Omega-3 supplements are widely used for cardiovascular (CV) protection. We performed an updated meta-analysis for omega-3 and CV outcomes.Random-effects meta-analysis including double-blind RCTs with duration ≥1 year, evaluating omega-3 supplements in 4 a priori defined categories (1, 1, 2, ≥3 of 1g capsules/day) on all-cause mortality, cardiac death, myocardial infarction and stroke, reporting the relative risk (RR) as the measure of interest. Complementary approaches were Trial Sequential Analysis (TSA) and sensitivity analyses for triglycerides, prevention setting, intention-to-treat analysis, eicosapentaenoic acid (EPA), sample size, statin use and study duration.Nineteen randomized controlled trials (RCTs) with 97,709 participants were included. Omega-3 supplements were not statistically significantly associated with reduced all-cause mortality, cardiac death, MI, or stroke, with the exception of reduced cardiac mortality only for the equivalent dose of 2 capsules/day (RR 0.55, 95%CI 0.33, 0.90, p = 0.0169, ICompared to the robust evidence for low doses, higher doses and particularly for the unique type of omega-3 icosapent ethyl ester should be further addressed.

P-class pumps are specific ion transporters involved in maintaining intracellular/extracellular ion homeostasis, gene transcription, and cell proliferation and migration in all eukaryotic cells. The present review aimed to evaluate the role of P-type pumps [Na+/K+ ATPase (NKA), H+/K+ ATPase (HKA) and Ca2+-ATPase] in cancer cells across three fronts, namely structure, function and genetic expression. It has been shown that administration of specific P-class pumps inhibitors can have different effects by: i) Altering pump function; ii) inhibiting cell proliferation; iii) inducing apoptosis; iv) modifying metabolic pathways; and v) induce sensitivity to chemotherapy and lead to antitumor effects. For example, the NKA β2 subunit can be downregulated by gemcitabine, resulting in increased apoptosis of cancer cells. The sarcoendoplasmic reticulum calcium ATPase can be inhibited by thapsigargin resulting in decreased prostate tumor volume, whereas the HKA α subunit can be affected by proton pump inhibitors in gastric cancer cell lines, inducing apoptosis. In conclusion, the present review highlighted the central role of P-class pumps and their possible use and role as anticancer cellular targets for novel therapeutic chemical agents.

Hypertriglyceridemia is a common problem in adults in the developed world. It is associated with increased levels of triglycerides within the blood, which subsequently promote the development of other diseases such as cardiovascular disease and pancreatitis. Triglycerides are mostly consumed through the diet and act as a source of energy in between meals. However, the levels of triglycerides increase proportionally with the number of calories consumed. This only leads to a problem if the total daily energy expenditure is exceeded.

Humans have a symbiotic relationship with gut microbiota, normally comprised of greater amount of the phyla firmicutes as opposed to Bacteroidetes. Which are respectfully categorized as gram-positive bacteria (GPB) and gram-negative bacteria (GNB). Their gut microbiome facilitates metabolism of substances which are otherwise indigestible to humans. Relevant literature reiterates their vital role to our daily life. Amongst individuals with metabolic disease syndrome (MetS) or/and obesity have shown to have disproportionate microbiome compared to healthy individuals. Giving rise to therapeutic options such as, prebiotics, probiotics and synbiotics as well as an educated diet. GPB, which have been shown to be a protective factor against lipopolysaccharide (LPS) induced gut-barrier dysfunctions and gut inflammation that are considered to be risk factors against MetS and obesity. In turn, the amount of GNB have a positive correlation with LPS. Relevant research supports dietary effects on microbiome and by extension on MetS and obesity. The authors acknowledge the need for more research and increased education to the general population, as well as to specialists about these implications.

The aim of the present study was to examine the effects of a high-dose omega-3 and omega-6 fatty acids supplementation, in combination with antioxidant vitamins, on cognitive function and functional capacity of older adults with mild cognitive impairment (MCI), over a 6-month period in a randomized, double-blind, placebo-controlled trial. Forty-six older adults with MCI (age: 78.8 &plusmn, 7.3 years) were randomized 1:1 to receive either a 20 mL dose of a formula containing a mixture of omega-3 (810 mg Eicosapentaenoic acid and 4140 mg Docosahexaenoic acid) and omega-6 fatty acids (1800 mg gamma-Linolenic acid and 3150 mg Linoleic acid) (1:1 w/w), with 0.6 mg vitamin A, vitamin E (22 mg) plus pure &gamma, tocopherol (760 mg), or 20mL placebo containing olive oil. Participants completed assessments of cognitive function, functional capacity, body composition and various aspects of quality of life at baseline and following three and six months of supplementation. Thirty-six participants completed the study (eighteen from each group). A significant interaction between supplementation and time was found on cognitive function (Addenbrooke&rsquo, s Cognitive Examination -Revised (ACE-R), Mini-Mental State Examination (MMSE) and Stroop Color and Word Test (STROOP) color test, p &lt, 0.001, p = 0.011 and p = 0.037, respectively), functional capacity (6-min walk test and sit-to-stand-60, p = 0.028 and p = 0.032, respectively), fatigue (p &lt, 0.001), physical health (p = 0.007), and daily sleepiness (p = 0.007)&mdash, showing a favorable improvement for the participants receiving the supplement. The results indicate that this nutritional modality could be promising for reducing cognitive and functional decline in the elderly with MCI.

In the present study, we investigated whether Neuroaspis PLP10™, a well-designed intervention, rich in omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFAs) with specific antioxidant vitamins, may exert positive action in the improvement of Parkinson’s disease symptoms and perhaps delay the progression of the disease when used as an adjuvant to the conventional treatment. Forty patients were randomized 1:1 to receive either 20 ml dose, once daily, of control (pure virgin olive oil) or Neuroaspis PLP 10™, a formula containing a mixture of omega-3 (810 mg Eicosapentaenoic acid and 4140 mg Docosahexaenoic acid) and omega-6 fatty acids (1800 mg gamma-Linolenic acid and 3150 mg Linoleic acid) (1:1 w/w), with 0.6 mg vitamin A, vitamin E (22 mg) plus pure gamma (γ)-tocopherol (760 mg), for a total of 30 months in a randomized double-blind, placebo-controlled trial. Participants completed assessments based on the Hoehn and Yahr Staging Scale of Parkinson’s Disease (HY scale) and the Unified Parkinson's Disease Rating Scale (UPDRS) III. Overall, for this small sample size clinical trial, Neuroaspis PLP10™ supplementation as an adjuvant treatment for 30 months in PD patients significantly delayed disease progression according to UPDRS (p ≤ 0.05) Vs placebo.

In the healthcare sector, phytocompounds are known to be beneficial by contributing or alleviating a variety of diseases. Studies have demonstrated the progressive effects of phytocompounds on immune-related diseases and to exhibit anticancer effects. Graviola tree is an evergreen tree with its extracts (leafs and seeds) been reported having anticancer properties, but the precise target of action is not clear. Using an in silico approach, we predicted that annonacin, an Acetogenin, the active agent found in Graviola leaf extract (GLE) to potentially act as a novel inhibitor of both sodium/potassium (NKA) and sarcoplasmic reticulum (SERCA) ATPase pumps. We were able to validate and confirm the in silico studies by showing that GLE inhibited NKA and SERCA activity in intact cells. In the present study, we also demonstrated the antiproliferative and anticancer effects of GLE in a variety of cancer cell lines with limited toxic effects on non-transformed cells. Moreover, our results revealed that known inhibitors of both NKA and SERCA pumps could also promote cell death in several cancer cell lines. In addition, a mouse xenograft cancer model showed GLE as able to reduce tumor size and progression. Finally, bioprofiling studies indicated a strong correlation between overexpression of both NKA and SERCA gene expression vs. survival rates. Overall, our results demonstrated that GLE can promote selective cancer cell death via inhibiting NKA and SERCA, and thus can be considered as a potential novel treatment for cancer. After molecular analysis of GLE by liquid chromatography–mass spectrometry and ESI–QTOF–MS analysis, it was found that the MS spectrum of the high abundant chromatographic peak purified sample highly consisted of annonacin.

The present work focuses on the characterization of molecules formed when virgin olive oil is heated at 130 °C for 24 h open in air, which are found to be strong agglutinins. The hemagglutinating activity of the newly formed molecule isolated from the heated virgin olive oil sample was estimated against human red blood cells (RBCs). Dimers and polymers (high molecular weight molecules) were identified through thin layer chromatography (TLC) of the oil mixture. (1)H and (13)C nuclear magnetic resonance (NMR) and gas chromatography-mass spectroscopy (GC-MS) were the methods used for structural characterization. Among others, oligomerization of at least two monounsaturated fatty acids (FA) by an ether linkage between the hydrocarbon chains is involved. Light microscopy was used to characterize and visualize the agglutination process. Agglutination without fusion or lysis was observed. It was concluded that the heating of virgin olive oil open in air, among other effects, produces oligomerization as well as polymerization of unsaturated FA, possibly of monohydroxy, monounsaturated FA that is associated with strong hemagglutinating activity against human RBCs. The nutritional value and the effects on human health of such oligomers are not discussed in the literature and remain to be investigated.

Objective To assess whether three novel interventions, formulated based on a systems medicine therapeutic concept, reduced disease activity in patients with relapsing–remitting multiple sclerosis (MS) who were either treated or not with disease-modifying treatment. Design A 30-month randomised, double-blind, placebo-controlled, parallel design, phase II proof-of-concept clinical study. Settings Cyprus Institute of Neurology and Genetics. Participants 80 participants were randomised into four groups of 20 each. A total of 41 (51%) patients completed the 30-month trial. The eligibility criteria were an age of 18–65; a diagnosis of relapsing–remitting MS according to the McDonald criteria; a score of 0.0–5.5 on the Expanded Disability Status Scale (EDSS); MRI showing lesions consistent with MS; at least one documented clinical relapse and either receiving or not a disease-modifying treatment within the 24-month period before enrolment in the study. Patients were excluded because of a recent (