Ekspresija hormonskih receptora i aktivnost ribocikliba u karcinomomu dojke s pozitivnim hormonskim receptorima i negativnim receptorom za humani epidermalni faktor rasta 2

In the randomized, placebo-controlled, phase 3 MONALESSA-2 trial, in patients with hormone receptor positive (HR+) [the estrogen receptor (ER) and/or progesterone receptor (PR)] and human epidermal growth factor 2 receptor negative (HER2-) advanced breast cancer (BC), progression-free survival (PFS) was signifi cantly longer among those receiving ribociclib [cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor] plus letrozole compared to patients receiving placebo plus letrozole. Additionally, ER+/PR+ cohort demonstrated higher hazard ratio for PFS than ER+/PR- cohort (0.62 vs. 0.36). Evidence from cell-line models suggests that PR signaling is tightly linked to cell-cycle regulation in terms of inhibition of CDK 4/6 activity when exposed to progestin. A possible explanation of this fi nding may be that high PR expression could interfere with ribociclib activity on the cyclin-kinase level. Furthermore, it is questionable whether PR level determines the efficacy of ribociclib administration with higher levels of this receptor being predictive of ribociclib ineffi cacy. Considering the safety profile of ribociclib, it’s necessary to perform analysis of PFS among ER+/PR+ patients receiving ribociclib, to potentially assess the cut-off value of PR expression (or ER/PR ratio) as a predictive marker of CDK4/6 efficacy.MONALESSA-2 je placebo kontrolirana randomizirana klinička studija faze 3 koja je uključila bolesnike s uznapredovalim karcinomom dojke s pozitivnim hormonskim receptorima (HR+) [estrogenski receptori (ER) i/ili progesteronski receptori (PR)] te negativnim receptorom za humani epidermalni faktor rasta 2 (eng. HER2-). Studija je pokazala kako je preživljenje bez progresije bolesti (eng. PFS) bilo značajno dulje u onih bolesnika koji su primali ribociklib [inhibitor ciklinovisne kinaze 4 i 6 (CDK4/6)] uz letrozol u usporedbi s pacijentima koji su primali placebo i letrozol. Međutim, ER+/PR+ grupa imala je viši omjer rizika (eng. hazard ratio) za preživljenje bez progresije bolesti (PFS) od ER+/PR- grupe (0.62 vs. 0.36). Dokazi iz modela staničnih linija sugeriraju kako je signalni put PR usko vezan za regulaciju staničnog ciklusa kod inhibicije aktivnosti CDK 4/6 nakon izlaganja progestinu. Moguće objašnjenje ovih saznanja može biti povezano s visokom ekspresijom PR koja interferira s aktivnošću ribocikliba na razine ciklin-kinaze. Stoga, upitno je da li razina ekspresije PR receptora utječe na učinkovitost primjene ribocikliba, tj. da li njegova veća ekspresija može uzrokovati smanjenje učinkovitosti ribocikliba. S obzirom na sigurnosni profil ribocikliba, potrebno je izvršiti analize PFS vrijednosti bolesnika koji primaju ribociklib ovisno o razinama ekspresije hormonskih receptora kako bi se potencijalno odredile vrijednosti ekspresije PR (ili ER/PR omjera) kao markera učinkovitosti inhibitora CDK4/6

Pripravci ljekovitih biljaka u liječenju kožnih bolesti

Botanical data, chemical composition and use of the most common medicinal plants preparations in the treatment of skin diseases are presented in this article. These plants include: Oenothera biennis, Borago officinalis, Avena sativa, Lavandula angustifolia, Cocos nucifera, Matricaria recutita, Hamamelis virginiana and Olea europaea, that are used for the treatment of various skin diseases such as atopic dermatitis, psoriasis vulgaris, ichtyosis non-bullosa, or eczema craquelé. Even today, in the era of highly specialized medicine, medicinal plant preparations are still used in dermatology especially in the treatment of inflammatory and itchy skin conditions. Patients trust and believe in beneficial effect of natural products, such as marigold or comfrey ointment. However, caution is needed in persons with history of allergic reactions or atopy, since plants can cause allergic or irritative inflammatory reactions in such individuals. Recent literature data confirm existing interest in the medicinal plants usage in dermatology

Određivanje količine flavonoida i fenolnih kiselina u pet vrsta roda Teucrium L.

The content of flavonoids and phenolic acids in the aerial parts of five Teucrium species (T. botrys, T. chamaedrys, T. halacsyanum, T. hyrcanicum and T. scorodonia) was determined using spectrophotometric methods. Results of quantitative analysis showed significant differences in the quantities of studied compounds. The content of flavonoids ranged from 0.12 to 0.28 %, while the quantity of phenolic acids varied between 1.19 and 9.60 %. Variations in the content of flavonoids and phenolic acids were confirmed using statistical analysis. The content of investigated compounds depended on the plant species and year of collection

Optimization of Bioactive Phenolics Extraction and Cosmeceutical Activity of Eco-Friendly Polypropylene-Glycol–Lactic-Acid-Based Extracts of Olive Leaf

Olive leaf is a rich source of phenolic compounds with numerous activities related to skin health and appearance. In this study, a green extraction method was developed using eco-friendly solvents: polypropylene glycol (PPG), lactic acid (LA), and water. The optimal extraction conditions were established, including solvent, extraction time, technique (magnetic stirrer vs. ultrasound-assisted extraction), and herbal material/solvent ratio. The composition of the solvent mixture was optimized using a mixture design. The content of phenolic compounds, including oleuropein and verbascoside, was determined using high-performance liquid chromatography (HPLC) and spectrophotometric methods. Using different extraction conditions, three extracts were prepared and their phytochemical compositions and antioxidant and skin-related bioactivities were investigated. The extracts were excellent inhibitors of elastase, collagenase, tyrosinase, and lipoxygenase. The best activity was shown by the extract richest in phenolics and prepared using magnetic-stirrer-assisted extraction for 20 min, with 0.8 g of herbal material extracted in 10 mL of PPG/LA/water mixture (28.6/63.6/7.8, w/w/w), closely followed by the extract prepared using the same extraction conditions but with 0.42 g of herbal material. The investigated PPG/LA/water mixtures contributed to the overall enzyme-inhibitory activity of the extracts. The prepared extracts were appropriate for direct use in cosmetic products, thus saving the time and energy consumption necessary for the evaporation of conventional solvents

Optimization of Two Eco-Friendly Extractions of Black Medick (Medicago lupulina L.) Phenols and Their Antioxidant, Cosmeceutical, α-Glucosidase and α-Amylase Inhibitory Properties

Medicago lupulina is an ancient edible plant from the Fabaceae family. In this work, two eco-friendly methods for extraction of bioactive phenolics from M. lupulina were developed using mixtures of water with two non-toxic, skin- and environmentally-friendly polyol solvents: glycerol and polypropylene glycol. Ultrasound-assisted extractions were optimized using a Box–Behnken design. The independent variables were the concentration of organic solvent in water (X1), extraction temperature (X2) and time (X3), while the response was phenolic content. The optimum conditions for extraction of polyphenols were (X1, X2, X3): (45%, 70 °C, 60 min) and (10%, 80 °C, 60 min) for glycerol and polypropylene glycol extraction, respectively. The extracts prepared at optimum conditions were rich in phenolic compounds, mainly derivatives of apigenin, kaempferol, luteolin, quercetin, caffeic and ferulic acid, as well as coumestrol. Their cosmeceutical and antidiabetic activity was tested. Both extracts demonstrated notable antioxidant, anti-lipoxygenase and anti-α-amylase activity. In addition to those activities, the glycerol extract efficiently inhibited protein coagulation, elastase and α-glucosidase activity. Glycerol present in the extract displayed enzyme-inhibiting activity in several assays and supported the action of the bioactive constituents. Thus, the optimized glycerol extract is a desirable candidate for direct incorporation in antidiabetic food supplements and cosmeceutical products

Extraction Optimization, Antioxidant, Cosmeceutical and Wound Healing Potential of <i>Echinacea purpurea</i> Glycerolic Extracts

Echinacea purpurea is a plant with immunomodulating properties, often used in topical preparations for treatment of small superficial wounds. In the presented study, the best conditions for ultrasound-assisted extraction of caffeic acid derivatives (caftaric and cichoric acid) (TPA-opt extract), as well as the conditions best suited for preparation of the extract with high radical scavenging activity (RSA-opt extract), from E. purpurea aerial parts were determined. A Box–Behnken design based on glycerol content (%, w/w), temperature (°C), ultrasonication power (W) and time (min) as independent variables was performed. Antioxidant, antiaging and wound healing effects of the two prepared extracts were evaluated. The results demonstrate that glycerol extraction is a fast and efficient method for preparation of the extracts with excellent radical scavenging, Fe2+ chelating and antioxidant abilities. Furthermore, the extracts demonstrated notable collagenase, elastase and tyrosinase inhibitory activity, indicating their antiaging properties. Well-pronounced hyaluronidase-inhibitory activities, with IC50 values lower than 30 μL extract/mL, as well as the ability to promote scratch closure in HaCaT keratinocyte monolayers, even in concentrations as low as 2.5 μL extract/mL (for RSA-opt), demonstrate promising wound healing effects of E. purpurea. The fact that the investigated extracts were prepared using glycerol, a non-toxic and environmentally friendly solvent, widely used in cosmetics, makes them suitable for direct use in specialized cosmeceutical formulations

Glycerol and Natural Deep Eutectic Solvents Extraction for Preparation of Luteolin-Rich <i>Jasione montana</i> Extracts with Cosmeceutical Activity

Jasione montana is a plant from the family Campanulaceae rich in phenols with health-beneficial properties such as luteolin (LUT) derivatives. In this work, a glycerol-based ultrasound-assisted extraction method was developed and optimized for in total phenol (TP) and LUT content, as well as antiradical activity (RSA). The best conditions (glycerol content, temperature, plant material weight, and ultrasonication power) for the preparation of J. montana extracts richest in TP (OPT-TP), LUT (OPT-LUT), and having the best RSA (OPT-RSA) were determined. Furthermore, numerous natural deep eutectic solvents (NADES), containing proline, glycerol, betaine, urea, and glucose were prepared and used for the extraction of J. montana. Contents of TP, LUT, and RSA in the prepared extracts were established. Antioxidant and cosmeceutical activity of the prepared extracts was tested. The OPT-TP, OPT-LUT, and OPT-RSA, as well as the most efficient NADES-based extract, PG-50-TP, were excellent antioxidants and Fe2+ ion chelators. In addition, they were potent inhibitors of collagenase and hyaluronidase, as well as good significant anti-elastase and -lipoxygenase activity. The observed antioxidant- and enzyme-inhibiting activity of J. montana extracts prepared using environmentally friendly methods and non-toxic solvents makes them promising ingredients of cosmeceutical products

Plants from Urban Parks as Valuable Cosmetic Ingredients: Green Extraction, Chemical Composition and Activity

The research on the possibilities of using biowaste from urban green areas is scarce. In this work, four plants, widely distributed in urban parks in Central Europe (Lotus corniculatus, Medicago lupulina, Knautia arvensis and Plantago major) were extracted using eco-friendly solvents based either on aqueous cyclodextrin solutions (hydroxypropyl-&beta;-cyclodextrin or &gamma;-cyclodextrin) or natural deep eutectic solvents based on glycerol, betaine and glucose. Metal content was determined using total reflection X-ray fluorescence (TXRF). The content of selected metabolites was determined using UV-VIS spectrophotometric methods and HPLC. Skin-related bioactivity was assessed using tyrosinase and elastase inhibition assays. The selected plants contained metals beneficial for skin health, such as zinc and calcium, while having a low content of toxic heavy metals. The extracts contained the bioactive phenolics such as quercetin, kaempferol, luteolin and apigenin. L. corniculatus was the most potent tyrosinase inhibitor, while K. arvensis showed the most pronounced elastase inhibitory activity. The employed solvents actively contributed to the observed bioactivity. The results indicate that the biowaste obtained from urban parks represents an ecologically acceptable alternative to conventional cultivation for the preparation of ecologically acceptable, high-value cosmetic products

Hydroxypropyl-β-Cyclodextrin-Based <i>Helichrysum italicum</i> Extracts: Antioxidant and Cosmeceutical Activity and Biocompatibility

Two Helichrysum italicum extracts, OPT-1 (rich in phenolic acids) and OPT-2 (rich in total phenols and flavonoids), were prepared using hydroxypropyl-β-cyclodextrin (HP-β-CD)-assisted extraction. The prepared extracts were rich in phenolic compounds, including flavonoids and phenolic acids. GC-MS analysis of the extracts identified neryl acetate, neo-intermedeol, β-selinene, γ-curcumene, italidione I, and nerol as the main volatile components of the extracts, as well as plant sterols, γ-sitosterol, campesterol, and stigmasterol. The antioxidant (DPPH radical scavenging, reducing power, and a carotene linoleic acid assay) and cosmeceutical (anti-hyaluronidase, anti-tyrosinase, anti-lipoxygenase, ovalbumin anti-coagulation, and a UV-absorption assay) activity of the extracts in most of the assays was better than the activity of the applied positive controls. Especially low were the IC50 values of the extracts in the anti-hyaluronidase (14.31 ± 0.29 μL extract/mL and 19.82 ± 1.53 μL extract/mL for OPT-1 and OPT-2, respectively) and the anti-lipoxygenase (0.96 ± 0.11 μL extract/mL and 1.07 ± 0.01 μL extract/mL for OPT-1 and OPT-2, respectively) assays. The extracts were non-toxic to HaCaT cells in concentrations of up to 62.5 µL extract/mL assuring their status as excellent candidates for cosmeceutical product development appropriate for direct use in cosmetic products without solvent evaporation

Effect of timing of levothyroxine administration on the treatment of hypothyroidism : a three-period crossover randomized study

Aim Hypothyroidism is a common clinical problem that is successfully treated with hormone substitutes in the form of levothyroxine (LT4). LT4 is a drug with a narrow therapeutic index and is usually administered by strict rules, standardly at least half an hour before breakfast. The aim of this study was to investigate a possible effect of different timings of administration on thyroid function status and lipid profile. Methods The study included patients with the diagnosis of primary hypothyroidism, which were using a stable dose of levothyroxine. They were randomized into three different groups regarding the timing of LT4 administration in a crossover fashion. Each timing regimen lasted for at least 8 weeks ; timing regimen A—half an hour before breakfast ; timing regimen B—an hour before the main meal of the day ; timing regimen C—at bedtime (minimally 2 h after dinner). The hormones (TSH, fT3, fT4) and lipid profile (triglycerides, HDL-, LDL-, and total cholesterol) were measured before the study, at the beginning of every timing regimen and at the end of the study. Results Altogether, 84 patients finished the study. Different timings of LT4 administration were non-inferior in comparison to the standard one and between each other. Median differences in TSH level between baseline and timing regimens were: baseline vs. A = −0.017 95% C.I. (−0.400– 0.192) ; baseline vs. B = −0.325 95% C.I. (−0.562– 0.023) ; baseline vs. C = −0.260 95% C.I. (−0.475–0.000). There were no statistically significant differences in either TSH, fT4, or fT3 when compared between all three timing regimens of LT4 administration and the baseline. There were no statistically significant differences in any of the lipid profile parameters (triglycerides, HDL-, LDL-, and total cholesterol) when compared between all three timing regimens of LT4 administration and the baseline. Conclusion The three investigated timing regimens of LT4 administration were equally efficient and offer additional options regarding the treatment individualization