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    Efekti upotrebe probiotika na mikroRNK povezane sa gojaznošću

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    Obesity is considered to be a chronic complex disease that increases the risk of diabetes, heart diseases and certain cancers. According to the literature, in obese people the gastrointestinal microbiota is disturbed, which could be the cause of the onset of obesity and related diseases. Moreover, there are small non-coding RNAs (microRNAs) that are disturbed in obesity, which are also considered to be a possible mechanism of probiotics’ action. Certain microRNAs are involved in the development and metabolism of adipose tissue cells, as well as the secretion and action of insulin, showing that changed expression of certain miRNAs could have a significant impact on the onset and development of obesity and obesity-related diseases. Thus, miRNAs are considered to be possible markers for the diagnosis and prognosis of various metabolic diseases, and possible therapeutic targets for the treatment of obesity and related diseases. Considering the growing need of the healthcare system for nutraceuticals and dietary supplements that present effective and safe medical nutritive therapy in obese individuals, this work aimed to assess the beneficial effects of probiotics on obesity-related microRNAs. In this review, we described the role of microRNAs and probiotics in obesity and the association between probiotics and obesity- related microRNAs. Circulating miRNAs’ profile in obese individuals significantly differs from that of normal-weight individuals. miRNAs such as miR-155, miR-221, miR-24-3p, and miR- 181a are over-expressed, while miR-26b and 125a are under-expressed in obese patients compared to non-obese individuals. It has been found that supplementation with Bifidobacterium bifidum and Lactobacillus acidophilus could downregulate the expression of miR-155 and miR- 221, and upregulate the expression of miR-26b. Supplementation with a probiotic formulation containing S. boulardii, L. plantarum 299v, and octacosanol led to the downregulation of miR- 155 and miR-24-3p expression. miR-125a and miR-181a were upregulated and downregulated, respectively, after the intervention with L. delbrueckii and L. rhamnosus. After reviewing the available literature, we can conclude that probiotics have beneficial effects on microRNAs altered in obesity, which could provide an effective strategy for the management of obesity.Gojaznost se smatra hroničnom, kompleksnom bolešću koja povećava rizik od nastanka drugih oboljenja poput dijabetesa, kardiovaskularnih oboljenja i određenih karcinoma. Prema literaturnim podacima, kod gojaznih osoba dolazi do narušavanja gastrointestinalne mikrobiote, što nadalje može biti uzrok razvoja gojaznosti i bolesti povezanih sa gojaznošću. Dodatno, postoje male nekodirajuće RNK (mikroRNK) čije su koncentracije promenjene kod gojaznih osoba u poređenju sa osobama normalne telesne mase. Takođe, mikroRNK se smatraju mogućim mehanizmom delovanja probiotika. Određene mikroRNK se smatraju ključnim u procesima razvoja i metabolizma masnog tkiva, kao i u procesima sinteze i delovanja hormona insulina, time ukazujući na to da bi promene u ekspresiji određenih miRNK mogle imati značajan uticaj na nastanak i razvoj gojaznosti i bolesti povezanih sa gojaznošću. Zbog navedenog, miRNK se smatraju mogućim markerima za dijagnozu i praćenje metaboličkih bolesti, ali se razmatraju i kao moguća terapija u tretmanu gojaznosti i oboljenja povezanih sa gojaznošću. U svetlu rastućih potreba sistema zdravstvene zaštite u pogledu dodataka ishrani i nutraceutika koji pružaju efikasnu i bezbednu podršku medicinskoj nutritivnoj terapiji kod gojaznosti, cilj ovog rada bio je da se istraže korisni efekti probiotika na mikroRNK povezane sa gojaznošću. U ovom narativnom pregledu opisali smo ulogu probiotika i mikroRNK u gojaznosti, kao i moguću povezanost probiotika sa mikroRNK koje su izmenjene kod gojaznih ljudi. Profil cirkulišućih miRNK se značajno razlikuje kod gojaznih osoba u poređenju sa osobama normalne telesne mase. Ekspresija miRNK poput miR-155, miR-221, miR-24-3p i miR-181a je značajno povišena, dok je ekspresija miR-26b i miR-125a snižena kod gojaznih osoba u poređenju sa osobama normalne telesne mase. Suplementacija sa Bifidobacterium bifidum i Lactobacillus acidophilus probiotskim sojevima snižava ekspresiju miR-155 i miR-221, dok je ekspresija miR-26b povišena nakon suplementacije ovim sojevima. Probiotska formulacija koja sadrži kombinaciju S. boulardii, L. plantarum 299v i oktakozanola dovela je do smanjenja ekspresije miR-155 i miR-24-3p. Ekspresija miR-125a je bila povećana, dok je ekspresija miR-181a bila snižena nakon suplementacije sojevima L. delbrueckii and L. rhamnosus. Nakon pregleda dostupne literature, možemo zaključiti da probiotici imaju pozitivno dejstvo na mikroRNK izmenjene kod gojaznih osoba, te da bi primena probiotika mogla biti efikasna strategija u tretmanu gojaznosti

    Farmakoterapija gojaznosti: danas i sutra

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    Obesity is a chronic, progressive, and recurring disease. The prevalence of obesity has reached pandemic proportions, along with overweight-related conditions like diabetes, cardiovascular diseases, and certain cancers. Reducing residual morbidity is the main goal of obesity treatment. Pharmacotherapy is intended for patients who have not responded to lifestyle interventions. There are currently six anti-obesity medications (orlistat, phentermine/topiramate, naltrexone/bupropion, liraglutide, semaglutide, and tirzepatide) approved for long-term obesity management. Most of them, except orlistat, predominantly act centrally by increasing satiety, as well as reducing appetite and food reward. The most effective anti-obesity drugs are semaglutide and tirzepatide, which might provide weight loss of more than 10% of the initial weight. Although all anti-obesity medications have been demonstrated to improve cardiometabolic risk factors, only liraglutide and semaglutide lower the risk of major cardiovascular events in patients with or without established cardiovascular disease. A personalized approach, considering both drug (weight-reducing capacity and drug safety) and patient (comorbidities, age, and the patient’s preferences) features, guarantees the best results. In this article, we will critically appraise the efficacy and safety of currently approved anti-obesity medications and those in the pipeline.Gojaznost je hronična, progresivna i recidivirajuća bolest. Prevalencija gojaznosti dostiže pandemijske razmere, baš kao i komorbiditeti povezani sa gojaznošću poput dijabetesa, kardiovaskularnih bolesti i izvesnih karcinoma. Glavni cilj lečenja gojaznosti je smanjenje rezidualnog morbiditeta. Farmakoterapija je namenjena pacijentima koji nisu odgovarajuće reagovali na izmenu životnog stila. Trenutno je šest lekova odobreno za dugoročno lečenje gojaznosti (orlistat, fentermin/topiramat, naltrekson/bupropion, liraglutid, semaglutid i tirzepatid). Većina njih, osim orlistata, pretežno deluje centralno povećanjem osećaja sitosti, kao i smanjenjem apetita i hranom izazvanog "nagrađivanja". Najveću efikasnost u redukciji povišene telesne mase (preko 10%) ostvaruju semaglutid i tirzepatid. Iako su svi lekovi za lečenje gojaznosti pokazali povoljan uticaj na kardiometaboličke faktore rizika, samo je za liraglutid i semaglutid pokazano da smanjuju rizik od velikih kardiovaskularnih događaja kod pacijenata sa ili bez potvrđene kardiovaskularne bolesti. Personalizovani pristup, koji uzima u obzir karakteristike leka (efikasnost u smanjenju telesne mase i bezbednost leka) i karakteristike pacijenta (komorbiditeti, starost i preferencije), garantuje najbolje rezultate. U ovom radu ćemo se kritički osvrnuti na efikasnost i bezbednost trenutno odobrenih lekova za lečenje gojaznosti i onih koji su u finalnoj fazi kliničkog ispitivanja

    Clinical Evidence on Expansion of Essential Oil-Based Formulation’s Pharmacological Activity in Bovine Mastitis Treatment: Antifungal Potential as Added Value

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    Bovine mastitis, as a significant and prevalent health problem in dairy herds, is primarily attributed to bacterial infections. Yeasts, although considered relatively rare causative agents, have also been associated with mastitis in dairy cattle. Current mastitis treatment predominantly relies on antibiotics, with limited emphasis on antifungal treatment. However, mycotic mastitis is challenging to treat, since these fungi are often resistant to antibiotics and may even utilize them for energy. In the current research, the in vivo antimicrobial activity of the essential oil-based formulation (Phyto-Bomat), as a possible alternative mastitis treatment associated with yeasts, was studied. This study involved a total of 68 animals from two dairy farms with diagnosed mastitis, and three treatment groups were established: conventional antibiotic treatment, Phyto-Bomat treatment, and the combination of both. The findings suggest significant variations in the presence of Candida samples based on the treatment administered, and the most significant difference was noted in cows treated with the combination (Phyto-Bomat and antibiotics). Yet, it is important to note that the results reveal that, regardless of the treatment type, there are statistically significant differences in the presence of Candida samples across the examined time points. These results aim to provide valuable insights into the potential of EOs as an alternative therapy in bovine mastitis, specifically targeting yeasts. Such findings could offer new strategies in the mycotic mastitis control and reducing the occurrence of secondary infections following antibiotic treatment

    Increased Odds of Metabolic Dysfunction-Associated Steatotic Liver Disease Are Linked to Reduced n-6, but Not n-3 Polyunsaturated Fatty Acids in Plasma

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    The increasing prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) underscores the need for better understanding of its complex pathogenesis. Lipid accumulation in hepatocytes is among principal mechanisms contributing to MASLD development. While routine lipid parameters are well studied, the profile of circulating fatty acids in MASLD patients remains less explored. This study aimed to assess relative proportions of individual fatty acids in plasma of MASLD patients and to explore their associations with other biochemical markers of MASLD. Ninety-one patients and 48 healthy individuals were enrolled. The relative proportions of fatty acids in plasma were determined using gas chromatography with FID detection. Proportions of total n-6 polyunsaturated fatty acids (PUFAs) and linoleic acid (LA) in plasma were lower in MASLD patients (p = 0.001 and p = 0.004, respectively), with no differences observed in n-3 PUFAs. Total plasma n-6 PUFAs correlated negatively with body mass index, hepatic steatosis indices, triglyceride concentration and coronary risk index. Decreased prevalence of n-6 PUFAs in plasma was independently associated with higher odds of MASLD (OR = 0.769; CI: 0.611–0.968; p = 0.025). Our findings indicate an altered circulatory fatty acid distribution in MASLD, characterized by a reduced amount of n-6 PUFAs, particularly LA, which may have significant implications for the prevention and treatment of MASLD

    Functionalization of silk with actinomycins from Streptomyces anulatus BV365 for biomedical applications

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    Silk, traditionally acclaimed as the “queen of fiber,” has been widely used thanks to its brilliant performance such as gentleness, smoothness and comfortableness. Owing to its mechanical characteristics and biocompatibility silk has a definitive role in biomedical applications, both as fibroin and fabric. In this work, the simultaneous dyeing and functionalization of silk fabric with pigments from Streptomyces anulatus BV365 were investigated. This strain produced high amounts of orange extracellular pigments on mannitol-soy flour agar, identified as actinomycin D, C2 and C3. The application of purified actinomycins in the dyeing of multifiber fabric was assessed. Actinomycins exhibited a high affinity towards protein fibers (silk and wool), but washing durability was maintained only with silk. Acidic condition (pH5) and high temperature (65°C) facilitated the silk dyeing. The morphologies and chemical components of the treated silk fabrics were analyzed using scanning electron microscopy and Fourier transform infrared spectroscopy. The results showed the pigments bind to the silk through interaction with the carbonyl group in silk fibroin rendering the functionalized, yet surface that does not cause skin irritation. The treated silk exhibited a remarkable antibacterial effect, while the biocompatibility test performed with 3D-reconstructed human epidermis model indicated safe biological properties, paving the way for future application of this material in medicine

    What is the Current Clinical Impact of the CYP2CTG Haplotype?

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    We read with great interest the paper by Zubiaur et al.1 on the analysis of a genotype–phenotype relationship of the CYP2C:TG haplotype. This study, including 225 patients receiving one of 6 different drugs and liver pieces from 135 children (median age 7 years), is in contrast to 2 studies by Bråten et al. using in vivo data from 875 escitalopram-treated2 and 840 sertraline-treated3 Norwegian patients, respectively, in which significantly increased rate (+20 to 25%) of CYP2C19-dependent metabolism of these drugs was found for the CYP2C:TGhaplotype

    Hepato-renal toxicity of low dose metal(oid)s mixture in real-life risk simulation in rats: Effects on Nrf2/HO-1 signalling and redox status

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    The understanding that humans are exposed to a low level of toxic metals and metalloids in their lifetime has resulted in a shift in scientific and regulatory perspectives from the traditional evaluation of single metal toxicity to complex mixtures, relevant to real-life exposure. Therefore, the aim of this study was to examine the impact of real-life, 90-days exposure to mixture of toxic metal(oid)s, Cd, Pb, Ni, Cr, As and Hg, on the nuclear factor erythroid 2–related factor 2 and hemoxygenase-1 (Nrf2/HO-1) signalling and redox status by assessing total sulfhydryl groups (SH), glutathione (GSH), superoxide dismutase activity (SOD), malondialdehyde (MDA), and ischemia modified albumin (IMA) in the liver and kidney of Wistar rats. Animals (20 males and 20 females) were randomized in 2 control and 6 treated groups that received by oral gavage mixture of metal(oid)s solutions in doses that reflect blood metal(oid) levels determined in previous human biomonitoring study as benchmark dose (F/M _BMD), median (F/M _MED), and 95th percentile (F/M _95). Our results have shown that metal(oid)s mixture impaired the activation of the Nrf2/HO-1 pathway in the kidney and liver of male rats and kidney of female rats, followed by depletion of GSH levels in males. Additionally, in males elevated levels of IMA in the liver were observed, while in both genders increased MDA levels were observed in the kidney. Interestingly, the effects were more pronounced in male than in female rats. This study is among the first that examined hepato-renal toxic mechanisms of real-life metal mixture exposure, while our results might be of immense importance for assessing the risk of exposure to mixtures of toxic substances

    Clinical decision-making in benzodiazepine deprescribing by healthcare providers vs. AI-assisted approach

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    Aims: The aim of this study was to compare the clinical decision-making for benzodiazepine deprescribing between a healthcare provider (HCP) and an artificial intelligence (AI) chatbot GPT4 (ChatGPT-4). Methods: We analysed real-world data from a Croatian cohort of community-dwelling benzodiazepine patients (n = 154) within the EuroAgeism H2020 ESR 7 project. HCPs evaluated the data using pre-established deprescribing criteria to assess benzodiazepine discontinuation potential. The research team devised and tested AI prompts to ensure consistency with HCP judgements. An independent researcher employed ChatGPT-4 with predetermined prompts to simulate clinical decisions for each patient case. Data derived from human-HCP and ChatGPT-4 decisions were compared for agreement rates and Cohen's kappa. Results : Both HPC and ChatGPT identified patients for benzodiazepine deprescribing (96.1% and 89.6%, respectively), showing an agreement rate of 95% (κ=.200,P=.012). Agreement on four deprescribing criteria ranged from 74.7% to 91.3%(lack of indicationκ=.352,P< .001; prolonged useκ=.088,P=.280; safety concernsκ=.123,P=.006; incorrect dosageκ=.264,P=.001). Important limitationsof GPT-4 responses were identified, including 22.1% ambiguous outputs, genericanswers and inaccuracies, posing inappropriate decision-making risks.Conclusions : While AI-HCP agreement is substantial, sole AI reliance poses a risk forunsuitable clinical decision-making. This study's findings reveal both strengths andareas for enhancement of ChatGPT-4 in the deprescribing recommendations within areal-world sample. Our study underscores the need for additional research on chatbot functionality in patient therapy decision-making, further fostering the advance-ment of AI for optimal performance

    The effect of nasal douching by hypertonic 2.3% sea water with algae extracts on the concentration of epidermal growth factor, transforming growth factor-α and interleukin-8 in nasal secretions of patients with nasal polyposis following endoscopic surgical treatment

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    Objective. To investigate epidermal growth factor (EGF), transforming growth factor (TGF)- a and interleukin (IL)-8 production in nasal mucosa irrigated with hypertonic 2.3% solution with algae extracts, in comparison to 0.9% NaCl during the first two weeks after surgery for nasal polyposis (NP), in relation to symptoms and local findings. Methods. This prospective study included 20 NP patients postoperatively irrigated with hypertonic and 20 with isotonic solution. We evaluated symptoms (NSS), endoscopic findings (ES) and mediator levels in nasal secretions before and after irrigation. Results. Following treatment, NSS and ES were significantly lower in the hypertonic solution group (p = 0.023; p < 0.001, respectively). The increase in the EGF and the decrease in the TGF-a and IL-8 concentration were higher in the hypertonic group (p < 0.001 for all mediators). Conclusion. Irrigation with a hypertonic solution was found to be more effective than an isotonic solution in nasal mucosa reparation.This is peer-reviewed version of the folowing article: Perić, A., Gaćeša, D., Vezmar-Kovačević, S., Perić, A. V., Vojvodić, D., Georgiou, S., Protopapadakis, E.,& Alevizopoulos, K.. The effect of nasal douching by hypertonic 2.3% sea water with algae extracts on the concentration of epidermal growth factor, transforming growth factor-α and interleukin-8 in nasal secretions of patients with nasal polyposis following endoscopic surgical treatment. in Journal of Laryngology and Otology Cambridge University Press.. 2024, 138 (5), 520 - 526 [https://doi.org/10.1017/S0022215123001974

    Antioxidative and anti-inflammatory activities of Erica spiculifolia extracts and fractions

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    There is little data on the phytochemical/pharmacological properties of Erica spiculifolia Salisb. (syn. Bruckentalia spiculifolia (Salisb.) Rchb.). This study examines the antioxidative and anti-inflammatory activities of different extracts and fractions of E. spiculifolia in vitro on isolated rat peritoneal macrophages, in the carrageenan-induced rat paw oedema test, BSA test, and two complementary antioxidant assays. Ethanolic extracts of leaves, flowers, and aboveground parts, and petroleum ether, ether, ethyl acetate, and water fractionations of the ethanol extract of E. spiculifolia applied at doses of 50–200 mg/kg p.o. exhibited dose-dependent anti-inflammatory activity comparable with indomethacin. All tested samples, except for the petroleum ether fraction, exerted excellent in vitro antioxidant activity, and all of them exhibited significant and similar inhibition of BSA denaturation comparable with diclofenac. Ethanolic extract of the aboveground parts obtained by percolation, ethyl acetate and water fractions had the highest efficiency, attenuating inflammation by more than 50% in the lowest applied concentration alongside exceptional radical scavenging activity

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