Background: Technogenic and natural radionuclides (RN) along the biogeochemical chains of agrocenoses may enter the human body through irrigation water- soil- plants- agricultural animals, likewise in hydroponic systems through nutrient solution substrate plants, leading to the development of dangerous diseases. Thus, control of herbal raw material’s gross β-radioactivity and obtaining radioactively safe medicinal raw material are priority issues. Since 1996 we have carried out radio monitoring research in the Ararat valley (where the Armenian Nuclear Power Plant (ANPP) is located) in water, soil, and plant systems in zones of the ANPP with a radius of 2-15, 20 (the territory of Ashtarak city), 30 km (Yerevan, territory of Institute of Hydroponics Problems) (IHP), as well as Dilijan Forest Experimental Station (DFES) (the zone of ANPP with 90 km radius). Studies have shown that in natural waters (artesian water, Hrazdan, Qasakh, Metsamor rivers), soils and in various crops (vegetables, fruit of trees, etc.) of Ararat Valley the content of technogenic RN 90Sr (T1/2=28.6 years) and 137Cs (T1/2=30.1 years) did not exceed maximum allowable concentrations (for drinking water MAC 90Sr=5.0 Bq/L, MAC 137Cs=11.0 Bq/L; for vegetables and fruits MAC 90Sr=50 Bq/L, MAC 137Cs=130 Bq/L). Based on these studies, a complex of practical recommendations in this region will give the opportunity of obtaining ecologically pure agricultural products.Objective: Considering that the accumulation of RN in medicinal plants poses a particularly great threat to obtaining radioecologically safe medicinal raw materials, during 2017-2022 we studied the specificities of gross β-radioactivity and accumulation of controlled technogenic RN (90Sr and 137Cs) in medicinal plants under hydroponics and soil conditions in the Ararat valley (the zone of ANPP with 30 km radius). This has a specific practical significance, as it will enable to obtain the most radio-ecologically safe plant material.Methods: Gross β-radioactivity and content of 90Sr and 137Cs of samples (artesian water (irrigation water), nutrient solution, soil layers with depth of 0 - 30 cm and number of medicinal plants) in it were defined with radio-chemical extraction methods through the radiometer UMF-1500 (made in Russia) with low background. 90Sr was determined by the oxalate method with 90Y. RN were determined in dry sediments of waters, nutrient solution, the ash of plants, and soils. The following chemical reagents were used for the analysis: C2H2O4, HNO3, HCl, CH3COOH, CsCl, Y2O3, YCl3, K2SO4, KI, Sr(NO3)2, CeCl3, Ni(NO3)2, SbCl3, K4[Fe(CN)6] 3H2O and others.Results: The radio-chemical studies showed that the gross β-radioactivity of herbs in hydroponics fluctuated between 250 – 740 Bq/kg, and in soil: 140 – 690 Bq/kg. Thus, the medicinal raw material from the medicinal plants cultivated in outdoor hydroponics and soil, is radioecologically safe, since its gross β-radioactivity does not exceed the threshold of 1.0 Bq/g. Medicinal plants grown in hydroponics and soil, with a slight deviation, show the same gross β-radioactivity decreasing pattern as follows: Peucedanum caucasicum (M.Bieb.) K. Koch. > Lycium barbarum > Eleutherococcus senticosus (Rupr. & Maxim.) > Teucrium polium = Humulus lupulus, variety “Crystal” > Echinacea purpurea (L.) Moench > Humulus lupulus, variety “Chinook” > Humulus lupulus, variety “Newport” > Colchicum speciosum Stev. > Moringa oleifera Lam. Our studies have shown that the proportion of 90Sr and 137Cs together in gross β-radioactivity in different medicinal plants fluctuated between 1.0-7.4 % of dry mass in hydroponics and 1.7-10.1 % of dry mass in soil. In the gross β-radioactivity of medicinal plants the share of 90Sr and 137Cs in hydroponics was 1.2-3.0 and 1.3-2.3 times lower than that of soil plants.Conclusion: In artesian waters, gray soils and different medicinal plants grown in hydroponic settings and soil of Ararat Valley the content of controlled technogenic RN (90Sr and 137Cs) did not exceed MAC. Both medicinal raw materials grown in hydroponic settings and soil in Ararat Valley are radioecologically safe.Keywords: technogenic radionuclides, nutrient solution, herbal raw materials, 90Sr, 137Cs

Background: Non-alcoholic fatty liver disease (NAFLD) individuals are more prone to acquire type 2 diabetes (T2DM). However, the knowledge regarding this phenomenon is limited to individuals without diabetes mellitus (DM). Vitamin D deficiency may lead to a more pronounced shift in an individual's glucose metabolism. Moreover, hepatocytes and peripheral tissues may potentially benefit from vitamin D in terms of reducing insulin resistance induced by free fatty acids. Objective: In this study, serum vitamin D levels were examined in patients with NAFLD with T2DM, and its relationship with NAFLD without DM was evaluated.Subjects and Methods: A total of 120 subjects were included in this study, divided into three groups: Group I included 30 healthy subjects matched for sex and age, Group II included 50 patients with NAFLD who had diabetes, and Group III included 40 subjects without diabetes. Three groups were compared regarding clinical and biochemical characteristics concerning serum 25-hydroxyvitamin D levels using enzyme-linked immunosorbent assays.Results: According to this study, people with NAFLD diagnosed by ultrasound examination Group II had significantly reduced serum levels of 25(OH) vitamin D compared to patients without NAFLD diagnosed by ultrasound examination Group II. There was a statistically significant difference between groups and 25(OH) vitamin D levels than group III. In addition, a highly significant difference in serum 25(OH) vitamin D levels was observed between groups II and III and the control group. Moreover, 25(OH) vitamin D is an independent predictor of T2DM in patients with NAFLD.Conclusion: Serum 25(OH) vitamin D levels were lower in patients with NAFLD and DM, indicating that low 25(OH) vitamin D status contributes to the onset and progression of diabetes mellitus in NAFLD.Keywords:25-hydroxy vitamin D[25(OH)D)], Non-alcoholic fatty liver disease (NAFLD), diabetes mellitus.

Background: Probiotics have been used for many years to promote human health by mitigating inflammation. However, its mechanics have not been fully elucidated. During inflammation, excessive and/or prolonged production of pro-inflammatory cytokines is related with various inflammatory diseases and cancer. Several probiotics have been reported as playing a role in suppressing the level of pro-inflammatory cytokines, as the human body attempts to recover. The aim of this study was to evaluate the anti-inflammatory activity of probiotics consisting of Lactobacillus spp. and Rhodopseudomonas palustris on macrophage RAW 264.7 cells.Methods: The probiotics mixture was centrifuged to separate supernatant, i.e., the probiotics extract, from the cells. The extract was then evaluated for its effects on cell viability and anti-inflammatory activity of LPS inflammation-induced RAW264.7 cells.Results: The results showed that the extract of the probiotics was able to decrease the levels of IFN-γ, IL-1β, TNF-α, IL-8, TGF-β1 pro-inflammatory cytokines/mRNAs, and increase the level of IL-10 anti-inflammatory mRNA.Conclusion: The probiotics extract was identified to have anti-inflammatory activity, as it decreased the level of pro-inflammatory cytokines and increased the level of anti-inflammatory cytokines/mRNAs.Keywords: multi-strain probiotics, anti-inflammatory cytokine/mRNA, RAW264.7

Background: Diabetes mellitus as a metabolic disease can have serious consequences. Due to their chemical properties,bioactive compounds can play a role in diabetes management. Squalene is a natural oil and bioactive compound. The anti-inflammatory and antioxidant effects of squalene have been discussed in recent studies. Squalene plays a role in controlling diabetes by maintaining the oxidant/antioxidant balance.Objective: The main purpose of this study was to evaluate the antioxidant effect of different doses of squalene, on different days, on the levels of some oxidative indices and the activity of antioxidant enzymes in groups of people with type 2 diabetes and compare them with each other and healthy people.Methods: 150 individuals were recruited in this study. These individuals were separated into five groups. Group one contained 30 individuals, representing the healthy control group. Groups 2, 3, 4 and 5 included subjects with type 2 diabetes. Each of the subjects in groups 3, 4 and 5 received squalene in doses of 200, 400 and 600 mg as an oral capsule (liquid filled oral), respectively for 84 days. Subjects in Group 2 did not receive squalene. Catalase, superoxide dismutase, glutathione peroxidase (as antioxidant indicators) activities and the levels of hydrogen peroxide, nitric oxide and reactive oxygen species (as oxidant indicators) were assayed.Results: In 84 days, a statistically significant difference (P value < 0.05) was observed in all the diabetic groups compared to the healthy group. In the comparison between groups receiving squalene with each other, there was a significant increase (P value < 0.05) in catalase and superoxide dismutase activity, depending on squalene dose and time. There was not a statistically significant (P value > 0.05) increase in glutathione peroxidase activity. Statistically significant changes in oxidative indices were not dose-dependent or time-dependent.Conclusion: Based on the findings of this study, a dose of 600 mg of squalene in 84 days is effective in increasing catalase and superoxide dismutase activity and reducing hydrogen peroxide levels. Squalene can play an important role in controlling and reducing the consequences of diabetes caused by changes in the oxidant/antioxidant balance.Keywords: squalene, type 2 diabetes, T2D, antioxidant enzymes, bioactive compounds, free radicals

Background: The roots of Polygonum multiflorum Thunberg (Polygonaceae) are a crude drug known as Kashu and are thought to improve blood deficiency as a Kampo concept. Kashu is added to Kampo formulas, including Tokiinshi, which is used to treat eczema and dermatitis with itchiness by facilitating blood circulation in the skin. Although anti- inflammatory effects were expected, the reports on anti-inflammatory constituents of Polygonum roots are very few. Objective: To purify pharmacologically active constituents from Polygonum roots and compare their anti- inflammatory potency using hepatocytes. Methods: Polygonum roots were extracted and fractionated based on hydrophobicity to three fractions, the ethyl acetate (EtOAc)-soluble, n-butanol-soluble, and water-soluble fractions. Constituents were purified from the EtOAc- soluble fraction, and its contents were measured using liquid chromatography-triple quadrupole mass spectrometer. The interleukin (IL)-1β-induced production of nitric oxide (NO), a proinflammatory mediator, in rat hepatocytes was monitored to assess anti-inflammatory activity. Results: The EtOAc-soluble fraction inhibited IL-1β-induced NO production, whereas the other fractions did not. Six constituents were isolated from the EtOAc-soluble fraction and identified as (E)-2,3,5,4'-tetrahydroxystilbene-2-O-β- D-glucoside, emodin, emodin-8-O-β-D-glucopyranoside, physcion, physcion-8-O-β-D-glucopyranoside, and catechin. Emodin and emodin-8-O-β-D-glucopyranoside significantly inhibited NO production in hepatocytes, and the others showed less potency in suppressing NO production. These two anthraquinones decreased the protein and mRNA levels of inducible NO synthase, as well as the mRNA levels of tumor necrosis factor α. In a search of the literature to date, the comparison of pharmacological activity of the constituents of Polygonum roots was not reported.Conclusion: These results suggest that hydrophobic constituents in the EtOAc-soluble fraction, especially anthraquinones, may exert the anti-inflammatory effects by treatment with Polygonum roots.Keywords: anthraquinone, nitric oxide, inflammation, Kampo medicine, LC–MS/MS.

Background: Currently there is no definite cure for Alzheimer's therefore early detection is critical. Undetected Alzheimer's Disease (AD) can lead to severe accidents, neglecting to take essential medications, injury to oneself or others, and/or financial problems. Currently, biomarkers are the most promising way to detect Alzheimer's early on. Biomarkers such as beta-amyloid and tau levels taken through invasive mehods or brain scans that involve radiation are among them [20]. Objectives: Alzheimer's Disease (AD) presents itself in the body with an increase in ß-amyloid (Aß) plaque deposition, neurofibrillary tangle formation (NFT), and inflammation. As the retina is an extension of the brain and the brain structure it is possible to detect misfolded proteins via retinal examination non-invasively. One of the main objectives of this study is to determine the effectiveness of curcumin which is a phytochemical which can bind to amyloid-beta and Tau and can be used both for the diagnosis and early treatment of AD. The aim of this study was to discover the binding property of curcumin to both Tau and AB in the retina as a potential biomarker for AD.Methods: In this study, 20 patients were invited with mild AD who had undergone retinal examination within the past 2 years. All the patients had retinal imaging with curcumin which revealed misfolded proteins during the examination and then they were advised to take daily curcumin. The mean age of the patients was 71, and the patients were instructed to take Curcumin Meriva in 500 mg supplements once daily after their prior examinations. All patients had tests repeated with FAF and Heidelberg Spectralis OCT device. The regions with abnormal lesions on FAF were detected and the layer of the defect was scanned by OCT plus compared with the previous imaging of the patients. The images were examined in a masked fashion by 2 specialists.Results: The images disclosed hyperfluorescent lesions on FAF and OCT revealed accumulations in the inner layers of the retina. Some accumulations had dot shapes and others had fibril-tangle shapes. Some lesions were present in prior exams, but they were more pronounced and shinier after curcumin use. Their size and shape were in concordance with misfolded proteins in the brain [Fig.2,3,4,5,6].Conclusion: Retinal examination with curcumin revealed AB plaques in the retina in prior studies. Our study is the first that may demonstrate an easy way to detect the culprit plaque Tau inside the retina of live patients. Keywords: Alzheimer's Disease, curcumin, neurofibrillary tangle formation (NFT), inflammation, retina, ß-amyloid (Aß) plaque deposition, Misfolded proteins, Fundus Autofluorescence (FAF), Tau, amyloid-beta, treatment

Introduction: Previous studies indicated that lipids and nanostructured materials may improve the uptake of nutrients with moderate bioabsorption properties. Objectives: This study evaluated the effects of Membrane Lipid Replacement with NTFactor® Lipids (NTFL) on bioabsorption of three poorly to moderately absorbed nutrients (quercetin, curcumin and coenzyme Q10) utilizing the Caco-2 epithelial cell permeability model. Methods: Transfer across a Caco-2 epithelial cell layer has become a reference standard in the pharmaceutical and nutraceutical industries for in vitro prediction of in vivo human intestinal absorption and bioavailability of orally administered substances. The degree of bioabsorption of the test materials was assessed by monitoring the concentrations of the test materials on each side of the Caco-2 monolayers by liquid chromatography and mass spectroscopy (LCMS/MS analysis).Results: When NTFL was added to each of the three test nutrients, there was increased absorption and transfer across a Caco-2 cell layer in a dose-dependent manner for the three nutrients. When compared individually, CoQ10 with NTFL showed the most significant increase in absorption (2.01-times more compared to controls without NTFL, p=0.0011) at a concentration of NTFL of 10 mg/mL. NTFL also increased absorption and transfer across a Caco-2 cell layer of the other test nutrients, but these results did not achieve the same level of significance. Discussion: A variety of Oral membrane lipid replacement supplements with NTFL, such as various vitamins, minerals and nutrients, have been designed to reduce fatigue, improve health conditions, and protect cellular and especially mitochondrial membranes from damage. Here we used NTFL to demonstrate improvements in absorption and bioavailability of three nutrients. Conclusion: Using the Caco-2 bioabsorption and bioavailability in vitro model we found that NTFL could enhance absorption, bioavailability and uptake of nutrients while providing its own clinically demonstrated health benefits. Keywords: Phospholipids, Membrane Lipid Replacement, CoQ10, curcumin, quercetin, bioavailability, absorption, permeability, Caco2, bio-uptake, bioabsorption, glycerolphospholipids, intestinal absorption

Introduction: Hyperglycemia in people with diabetes mellitus and its lack of control are associated with irreversible consequences. Glycation of proteins and enzymes, especially antioxidant enzymes in uncontrolled diabetes mellitus, affects these consequences. Consumption of bioactive compounds containing antioxidants and minerals as well as the use of adjunct therapies, such as cold atmospheric plasma therapy, can be effective in preventing and controlling the consequences of diabetes mellitus.Objective: In this research, we investigated whether cold plasma treatment of diabetic samples was effective in altering the activity of oxidative enzymes, some biochemical elements, and biochemical parameters.Methods: Thirty individuals with type 2 diabetes mellitus and 30 healthy individuals, as controls, participated in the study. The samples were exposed to cold argon plasma jet for 10 minutes (by a 10 kHz pulsed DC power supply with an amplitude up to 20.0 kV). The following contents of the serum samples of all participants were evaluated according to the instructions of the used kits before and after the cold argon plasma jet treatment: the activity of catalase, superoxide dismutase, and glutathione peroxidase enzymes; the concentration of glucose, hydrogen peroxide, and selenium binding protein 1 (as an indicator of blood selenium); and the concentration of copper, zinc, iron, and magnesium.Results: The activity of antioxidant enzymes and minerals significantly increased in diabetic samples treated with cold plasma (P value < 0.05). No significant changes were observed in the concentrations of glucose, hydrogen peroxide, or selenium binding protein 1 in diabetic samples treated with cold plasma.Conclusions: Using cold argon plasma jet as an adjunct method, which will reduce the glycation of enzymes and improve some minerals, can reduce the risk of diabetes complications in patients with diabetes mellitus.Keywords:Antioxidant enzymes, Cold plasma, Diabetes mellitus, Minerals.

Membrane Lipid Replacement (MLR) is the use of functional dietary supplements containing cell membrane glycerolphospholipids and antioxidants to safely replace and remove damaged essential membrane phospholipids that accumulate during aging and in various chronic and acute illnesses. Most, if not all, clinical conditions and aging are characterized by cellular membrane phospholipid free radical oxidative damage, resulting in loss of membrane and cellular functions. In particular, loss of mitochondrial function, the key organelle responsible for over 90% of cellular energy production, can result in excess fatigue and other symptoms, and this is a common problem in almost all, if not all, age-related chronic diseases. Clinical trials have shown the benefits of MLR supplements in replenishing damaged membrane phospholipids and restoring mitochondrial function, resulting in reductions in fatigue and other symptoms in aged subjects and patients with a variety of clinical diagnoses. Here we have specifically reviewed the beneficial results of MLR on subjects older than 60 years. MLR provides general membrane and nutritional support during aging and illnesses to improve membrane function and overall health without risk of adverse effects. The case reports here and elsewhere and published clinical trials demonstrate that this is a safe and effective alternative or addition to pharmaceutical approaches for alleviating fatigue, pain, gastrointestinal and other symptoms associated with normal aging and age-related chronic illnesses.Keywords: Aging, Fatigue, Pain, Gastrointestinal symptoms, Phospholipids, Clinical trials, Case reports, Cellular membranes

Background: Carvacrol is an aromatic phenolic terpenoid widely existing in the volatile oils of thyme, oregano, and some other aromatic plants. Recent studies have found that carvacrol possesses excellent antibacterial activity. In order to provide an updated information about the antibacterial potentials of carvacrol, herein, we summarized recent publications about the antibacterial activity of carvacrol, with special attention paid to its antibacterial molecular mechanisms, including desrupting cell membrane, depleting intracellular ATP, inducing reactive oxygen species, inhibiting efflux pumps, as well as suppressing two important virulence factors, biofilm and quorum sensing. In conclusion, carvacrol is a promising natural antibacterial compound with potential application in food preservation and infection.Keywords：Carvacrol, antibacterial mechanisms, biofilm, quorum sensing