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Alpinetin Exhibits Antioxidant and Anti-Inflammatory Effects in C57BL/6 Mice with Alcoholic Liver Disease Induced by the Lieber–DeCarli Ethanol Liquid Diet
No full textAlcohol-associated liver disease (ALD) is a common non-communicable chronic liver disease characterized by a spectrum of conditions ranging from steatosis and alcohol-associated steatohepatitis (AH) to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). The pathogenesis of ALD involves a complex interplay of various molecular, biochemical, genetic, epigenetic, and environmental factors. While the mechanisms are well studied, therapeutic options remain limited. Alpinetin, a natural flavonoid with antioxidant and anti-inflammatory properties, has shown potential hepatoprotective effects, though its efficacy in ALD remains unexplored. This study investigated the hepatoprotective effects of alpinetin using a Lieber–DeCarli ethanol liquid diet model of ALD in C57BL/6 mice. Mice were divided into three groups: the control group, the ethanol group, and the ethanol group treated with alpinetin. Serum activity of ALT, AST, γ-GT, and ALP was measured to assess liver function, along with antioxidative and oxidative/nitrosative stress markers in liver tissue. Pro-inflammatory cytokines and endoplasmic reticulum (ER) stress parameters in liver tissue were also evaluated. Histological assessment of disease activity was performed using the SALVE grading and staging system. Treatment with alpinetin significantly reduced serum levels of ALT, AST, γ-GT, and oxidative/nitrosative stress markers while increasing antioxidative markers. The levels of pro-inflammatory cytokines and ER stress parameters were significantly decreased. Histological analysis demonstrated reduced steatosis, hepatocyte ballooning, and inflammation. These findings suggest that alpinetin holds promise as a potential therapeutic agent for managing ALD
Expression Analysis of Circulating miR-21, miR-34a and miR-122 and Redox Status Markers in Metabolic Dysfunction-Associated Steatotic Liver Disease Patients with and Without Type 2 Diabetes
No full textMetabolic dysfunction-associated steatotic liver disease (MASLD), a hepatic
form of metabolic syndrome, often co-occurs with type 2 diabetes (T2D) and now affects
approximately 30% of the global population. MASLD encompasses conditions from simple
steatosis to metabolic dysfunction-associated steatohepatitis, with oxidative stress (OS)
driving progression through inflammation. This study analyzes the expression levels of
circulating miRNAs and redox status markers in MASLD patients with and without T2D,
exploring their potential as disease biomarkers. The expressions of miR-21, miR-34a, and
miR-122 were analyzed in the platelet-poor plasma of 147 participants, divided into three
groups: MASLD + T2D (48), MASLD (50), and a control group (49). Total oxidant status
(TOS), total antioxidant status (TAS), ischemia-modified albumin (IMA), and superoxide
anion radical (O2•−) were measured in serum and plasma. Logistic regression showed that
miR-21, miR-34a, TOS, TAS, O2•−, and IMA were positive predictors of MASLD, while
miR-21 and TAS were negative predictors of T2D in MASLD. Although miR-122 did not
show a significant association with either condition, in combination with miR-34a and other
markers such as lipid status and liver enzymes, a new significant predictor of MASLD was
identified. Circulating miRNAs in combination with redox status markers, lipid status and
liver enzymes show potential as MASLD biomarkers
Albuminuria in People Chronically Exposed to Low-Dose Cadmium Is Linked to Rising Blood Pressure Levels
No full textExposure to low-dose environmental pollutant cadmium (Cd) increases the risks of both albuminuria and hypertension by mechanisms which are poorly understood. Here, multiple regression and mediation analyses were applied to data from 641 Thai subjects of whom 39.8%, 16.5%, 10.8%, and 4.8% had hypertension, albuminuria, diabetes, and chronic kidney disease (CKD), defined as the estimated glomerular filtration rate (eGFR) ≤ 60 mL/min/1.73 m2, respectively. To correct for interindividual differences in urine dilution and surviving nephrons, the excretion rates of Cd (ECd), albumin (Ealb), and β2-microglobulin (Eβ2M) were normalized to the creatinine clearance (Ccr) as ECd/Ccr, Ealb/Ccr, and Eβ2M/Ccr. The respective risks of having CKD and hypertension rose to 3.52 (95% CI: 1.75, 7.05) and 1.22 (95% CI: 1.12, 1.3) per doubling of the Cd body burden. The respective risk of having albuminuria increased 2.95-fold (p = 0.042) and 4.17-fold (p = 0.020) in subjects who had hypertension plus severe and extremely severe tubular dysfunction, defined according to the elevated β2M excretion rates. In multiple regression analysis, the Ealb/Ccr increased linearly with both the systolic blood pressure (SBP, β = 0.263) and diastolic blood pressure (DBP, β = 0.150), while showing an inverse association with eGFR (β = −0.180). The mediation model analyses inferred that a declining eGFR induced by Cd contributed to 80.6% of the SBP increment (p = 0.005), which then fully mediated an elevation of albumin excretion (p < 0.001). The present study provides, for the first time, evidence that causally links Cd-induced eGFR reductions to blood pressure elevations, which enhance albumin excretion
Metabolic Syndrome Spectrum in Children with Classic Congenital Adrenal Hyperplasia—A Comprehensive Review
No full textChildren with a classic form of congenital adrenal hyperplasia (CCAH) have a potentially increased risk of unfavorable cardiometabolic events due to the interplay of corticosteroid treatment, hyperandrogenism, and other factors. Although readily recognized in adults, these aspects are frequently overlooked in children and youth with CCAH; Aim: To review the evidence available from studies regarding cardiometabolic health outcomes in CCAH patients; Methods: A review of the literature was performed following PRISMA guidelines, including studies published between 2000 and 2024. We included studies reporting cardiometabolic outcomes in children and adolescents (<18 years) with CCAH. Where pediatric data were sparse, additional data were obtained from studies with older adolescents and young adults (15–25 years). Cardiometabolic outcomes included risk factors, such as obesity, insulin resistance, lipids, blood pressure, and vascular markers; Results: Twenty-five studies were analyzed. The prevalence of obesity was found to be higher in children with CCAH, as well as of increased visceral adiposity. Higher indices of insulin resistance were also a frequent finding in children with CCAH. CCAH patients had higher systolic blood pressure and more frequently loss of nocturnal blood pressure dipping, particularly among salt-wasting subtypes and in younger children. Subclinical atherosclerosis was indicated by increased carotid intima–media thickness, elevated hs-CRP, and impaired endothelial function. Other findings suggested changes in lipid profiles, particularly decreased HDL-c and increased triglycerides, although the findings were less consistent; Conclusions: Compared with the general pediatric population, children with CCAH were found to have an increase in multiple cardiometabolic risk factors. It is therefore vital to monitor these risk factors in pediatric CCAH, as well as tailoring treatment with cardiometabolic health in mind, to achieve better long-term cardiovascular and metabolic outcomes. Future research should focus on longitudinal studies of cardiometabolic outcomes and innovative therapeutic approaches to reduce these risks in patients with CCAH
Influence of patient age and sex on drug-induced liver injury caused by antiseizure medications: a disproportionality analysis of VigiBase
No full textBackground: While it has been recognised that children may be at a greater risk of developing valproic acid-induced hepatotoxicity, it is less known if age and sex represent risk factors for drug-induced liver injury (DILI) caused by other antiseizure medications (ASMs). Aim: To investigate the influence of patient age and sex on DILI caused by ASMs. Method: To estimate hepatotoxic potential of 24 ASMs, deduplicated safety reports from VigiBase were accessed and disproportionality analysis was conducted by calculating Empirical Bayesian Geometric Mean and its 90% confidence interval (EB05, EB95). For ASMs with identified signals of disproportionate reporting (EB05 > 2, N > 0) for at least one hepatotoxicity-related event, we compared reporting frequency of overall hepatotoxicity among different age groups and between males and females by combining all events of interest into one custom term “overall DILI”. The same analysis was conducted using the custom term “liver failure”. Results: Signals of disproportionate reporting were identified for 14 (58.33%) ASMs. Valproic acid and carbamazepine had the highest number of identified signals (25 and 17, respectively). Among the 14 ASMs with identified signals, seven (50%) had disproportionally higher reporting of overall DILI in children, one (7.14%) in older people, and nine (64.29%) in females. Further, six (42.86%) ASMs had disproportionally higher reporting of liver failure in children and three (21.43%) in females. Conclusion: Our study suggests the importance of considering patient age and sex when assessing the risk of DILI from specific ASMs. However, the results are mainly hypothesis-generating and the identified signals require further investigation
Combination of six compounds synergistically boosts antioxidant effects ex vivo
No full textIn this ex vivo study, we aimed to evaluate the antioxidant properties of the N-acetylcysteine, zinc, manganese, selenium, vitamin C and vitamin D in human serum, as well as the effect of their mixture present in the product BiVits® ACTIVA Recovery (Abela Pharm d.o.o. Belgrade, Serbia). The serum pool was formed by collecting samples from individuals with healthy profiles. To assess the redox status, total oxidant status (TOS), prooxidant-antioxidant balance (PAB), total antioxidant status (TAS), superoxide dismutase (SOD) activity and total sulfhydryl groups (SHG) concentration were determined. Subsequently, antioxidant score (AS), prooxidant score (PS), and general oxy score (OS), were calculated. These scores served as valuable indicators of the overall redox balance. The results of this study showed that although all components exhibited antioxidant properties individually, the mixture of these components contained in the product BiVits® ACTIVA Recovery had a much more pronounced antioxidant potential both after short-and long-term incubation in conditions that mimic physiological environment and in an oxidative stress milieu. The AS of BiVits® ACTIVA Recovery was much greater than the sum of AS of the individual components, indicating a synergistic effect of the components.În acest studiu ex vivo, ne-am propus să evaluăm proprietățile antioxidante ale N-acetilcisteinei, zincului, manganului,
seleniului, vitaminei C și vitaminei D în serul uman, precum și efectul amestecului acestora prezent în produsul BiVits®
ACTIVA Recovery. Probele de ser au fost colectate de la indivizi cu profiluri sănătoase pentru a forma un pool de ser. Pentru
a evalua statusul redox, au fost determinate nivelurile de stres oxidativ total (TOS), balanța prooxidant-antioxidantă (PAB),
statusul antioxidant total (TAS), activitatea superoxid dismutazei (SOD) și concentrația totală a grupărilor sulfhidril (SHG).
Ulterior, au fost calculați scorul antioxidant (AS), scorul prooxidant (PS) și scorul general de oxido-reducere (OS), acești
parametri servind drept indicatori ai echilibrului redox global. Rezultatele acestui studiu au demonstrat că, deși fiecare
component a manifestat proprietăți antioxidante individuale, amestecul acestor compuși, așa cum este prezent în produsul
BiVits® ACTIVA Recovery, a prezentat un potențial antioxidant semnificativ mai pronunțat, atât după incubare pe termen
scurt, cât și pe termen lung, în condiții ce imită mediul fiziologic și în prezența unui stres oxidativ. Mai mult, scorul AS al
produsului BiVits® ACTIVA Recovery a fost considerabil mai mare decât suma scorurilor AS ale componentelor individuale,
sugerând un efect sinergic al acestora
Improvement of Pharmacopeial High-Performance Liquid Chromatography Method for Determination of Enantiomeric Purity of Moxifloxacin Drug Substance
No full textNew chiral isocratic HPLC conditions were proposed for investigation of moxifloxacin hydrochloride and its potential isomeric impurity (R,R)-isomer (impurity G) using the chiral additive copper (II)-sulfate and isoleucine in the mobile phase using an achiral C18 chromatographic column, 150 × 4.6 mm; 3 µm, as a significant improvement of the official European Pharmacopeia method concerning economy and baseline resolution. The mechanism of separation of enantiomers of moxifloxacin using the chiral additive copper (II)-sulfate is also elucidated. In the optimization of the experimental conditions of the chiral HPLC method, the central composite design was used, and for multiobjective optimization the desirability function with its desired value 1.00 was used. After optimization and method validation the best conditions concerning the concentration of chiral agents (0.01 M), organic solvent content in the mobile phase (30%, v/v methanol), pH value of mobile phase (3.5), and column temperature (23°C) with 10 µL injection volume, were defined. Compared to the pharmacopeial HPLC method, the analysis time was shorter and significantly lower amount of chiral agents in mobile phase was required. The optimized method was validated with respect to linearity, accuracy, precision, and robustness. The linearity of the method has been demonstrated in the range of 0.30–2.50 µg/mL (R2 > 0.998). Limit of detection and limit of quantification for moxifloxacin chiral impurity G determination were 0.098 and 0.298 µg/mL, respectively. The method was found to be suitable for quantification of moxifloxacin chiral impurity G in moxifloxacin drug substance
The effect of the two probiotic strains and policosanol combination on metabolic parameters in obese women
No full textГојазност се карактерише дисбиозом гастроинтестиналне микробиоте, те се примена пробиотика сматра обећавајућим новим приступом у третману овог обољења. Циљ наше студије је био испитати утицај нове пробиотске формулације на метаболичке, инфламаторне, епигенетске и хематолошке параметре, хормоне који утичу на апетит, као и имуномодулаторни ефекат пробиотика. У студији је коришћена комбинација пробиотика и октакозанола, једињења са хипохолестеролемијским ефектом. Истраживање је трајало 12 недеља, а спроведено је као рандомизована, двоструко слепа, плацебо-контролисана студија, у којој су учествовале испитанице са ИТМ = 30,0 – 39,9 kg m−2. Интервентна група (N = 25) је пила по 1 капсулу дневно у којој се налазило 7 x 1010 CFU Lactiplantibacillus plantarum 299v, 5 x 109 CFU Saccharomyces boulardii и 40 mg oктакозанола, док је контролна група (N = 23) пила плацебо. Примена пробиотске формулације након 12 недеља је резултовала значајно нижим концентрацијама проинфламаторних параметара, док су концентрације грелина и HDL-холестерола биле значајно више. Уочен је и регулаторни ефекат на експресију miRNA и mRNA, епигенетских маркера значајних у процесима метаболизма, инфламације и адипогенезе. Показано је да пробиотска формулација испољава позитиван ефекат на величину и облик еритроцита, као и на морфолошке карактеристике тромбоцита. Утврђен је имуномодулаторни ефекат који се огледа у смањеном проценту CD3+CD8+ и CD4+CD45RO+ Т-ћелија, као и у повећаним концентрацијама TGF-β1 након 12 недеља интервенције. Значајне промене у вредностима ИТМ између група нису забележене. Потенцијални утицај на нивое триглицерида, глукозе и инсулина захтева додатна истраживања, како би се нова дијетарна интервенција сматрала корисном адјувантном терапијом и ефикасном стратегијом у третману гојазности.Obesity is characterized by dysbiosis of the gastrointestinal microbiota, and the use of probiotics is considered a promising new approach in the treatment of this disease. The aim of this study was to examine the impact of a new probiotic formulation on metabolic, inflammatory, epigenetic and hematological parameters, appetite-related hormones, as well as the immunomodulatory effect of probiotics. Combination of probiotics and a hypocholesterolemic compound, octacosanol, was used in this study. The research lasted 12 weeks, and was conducted as a randomized, double-blind, placebo controlled study, where participated women with BMI = 30.0 - 39.9 kg m−2. Daily oral supplementation included 7 × 1010 CFU of Lactiplantibacillus plantarum 299v, 5 × 109 CFU of Saccharomyces boulardii, and 40 mg of octacosanol or placebo. After 12 weeks of the intervention significantly lower concentrations of pro-inflammatory parameters were observed, while ghrelin and HDL-cholesterol concentrations were significantly higher. A regulatory effect on the miRNA and mRNA expression, epigenetic markers important in the processes of metabolism, inflammation and adipogenesis, was also observed. It has been shown that the probiotic formulation exerts a positive effect on the size and shape of erythrocytes, as well as on the morphological characteristics of platelets. Immunomodulatory effect was was confirmed by the reduced percentage of CD3+CD8+ and CD4+CD45RO+ T-cells, as well as in increased TGF-β1 concentrations. No significant changes in BMI values between groups were noted. Potential effect on triglyceride, glucose and insulin levels requires additional research, in order to consider new dietary intervention as a useful adjuvant therapy and an effective strategy in the obesity treatment
Phytochemical Properties, Antioxidant Capacity, and Hypoglycemic Potential of Goji Berry Juice from Serbia
No full textGoji berry is a rich source of polyphenols, carotenoids and polysaccharides, contributing to its diverse biological activities. Due to their high water content and perishability, the berries are often processed into dried forms or juices. This study hypothesized that juice obtained from Serbian-grown goji berries would exhibit a distinctive phytochemical composition and significant in vitro antioxidant and hypoglycemic potential. Antioxidant activity was assessed using DPPH, ABTS, CUPRAC, FRAP and β-carotene bleaching assays, while hypoglycemic potential was evaluated via α-amylase and α-glucosidase inhibition. The analyzed goji juice exhibited mild acidity and moderate sweetness. In terms of bioactive composition, the juice contained high levels of polyphenols (194.50 ± 3.88 mg GAE/100 mL) exceeding the values reported for most commercial fruit juices, as well as notable levels of flavonoids (70.30 ± 5.11 mg CE/100 mL), carotenoids (289.53 ± 0.65 µg/100 mL) and polysaccharides (375.20 ± 12.46 mg Glu/100 mL), along with minerals, particularly potassium and copper. It also showed strong antioxidant capacity and concentration-dependent inhibition of α-amylase (IC50 = 5.28 ± 0.26 mg/mL) and α-glucosidase (IC50 = 10.12 ± 0.23 mg/mL). This study provides the first comprehensive characterization of Serbian-grown goji berry juice, confirming its potential as a functional ingredient
Biljni lekoviti proizvodi kod respiratornih infekcija u pedijatrijskoj populaciji
No full textCough and cold represent some of the most prevalent indications for using herbal medicinal
products in pediatric care across European countries. These herbal medicines are generally
regarded as safe, with their efficacy predominantly classified as good to very good. Traditional
herbal medicinal products based on mucilaginous herbal drugs like Althaeae radix, Malvae
folium, Lichen islandicus and Plantaginis lanceolatae folium are used in the treatment of oral and
pharyngeal inflammations and associated dry cough. For productive coughs, herbal medicinal
products with well-established use, based on Hederae folium, or a range of traditional herbal
medicinal products containing Primulae radix, Thymi herba, and other aromatic drugs and
essential oils are administered. It is important to note that products containing essential oils and
certain aromatic herbal drugs are contraindicated in children under 2 to 2.5 years of age due to
the risk of laryngospasm. In the pediatric population, products derived from Matricariae flos,
Pelargonii radix, Tiliae flos and Sambuci flos are used to relieve various cold symptoms. Use is
restricted to children over a certain age, mostly due to lack of safety data, and in some cases due
to the possibility of certain adverse effects.Najčešće indikacije za upotrebu biljnih lekovitih proizvoda u pedijatriji u evropskim zemljama su kašalj i prehlada. Ovi biljni proizvodi se generalno smatraju bezbednim i njihov efekat se uglavnom klasifikuje kao dobar ili veoma dobar. Tradicionalni biljni lekovi na bazi biljnih droga sa sluzima poput Althaeae radix, Malvae folium, Lichen islandicus i Plantaginis lanceolatae folium koriste se u lečenju upala usne duplje i ždrela i pratećeg suvog kašlja. Kod produktivnog kašlja primenjuju se biljni lekovi na bazi Hederae folium, ili niz tradicionalnih biljnih lekova na bazi Primulae radix, Thymi herba, i drugih aromatičnih droga i etarskih ulja. Važno je napomenuti da su proizvodi na bazi etarskih ulja, kao i nekih aromatičnih droga, kontraindikovani kod dece mlađe od 2 ili 2,5 godina, zbog rizika od laringospazma. U pedijatrijskoj populaciji, za ublažavanje različitih simptoma prehlade, primenjuju se i proizvodi na bazi Matricariae flos, Pelargonii radix, Tiliae flos i Sambuci flos. Primena je ograničena na decu određenog uzrasta, najčešće zbog nedostatka dokaza o bezbednosti, a u pojedinim slučajevima zbog mogućnosti pojave određenih neželjenih efekata