Eucalyptus-derived essential oils alleviate microbes and modulate inflammation by suppressing superoxide and elastase release

The Eucalyptus tree, belonging to the myrtle family, grows all over the world for its pharmaceutical and industrial benefits. In this article, we present a comparative analysis of the chemical composition of the hydrodistilled oils obtained from three different Eucalyptus species growing in Egypt viz. E. citriodora, E. camaldulensis, and E. ficifolia. Gas Chromatography-Mass Spectrometric guided analysis resulted in the identification of a total of 20 metabolites in E. citriodora oil with citronellal (54.9%) and citronellol (25.4%) being the most dominant components. β-cymene (12.7%) and 1,8-cineole (11.7%) were the major volatile constituents identified in E. camaldulensis oil, while trans-β-ocimene (22.4%), 1,8-cineole (13.5%), and L-trans-pinocarveol (12.5%) were the dominating components in the oil of E. ficifolia. The essential oils of the studied species were evaluated for their in vitro anti-inflammatory, antiviral including anti-SARS-CoV-2 (severe acute respiratory syndrome corona virus 2), antibacterial, and antifungal activities. E. citriodora oil displayed the highest inhibitory activity on the release of the superoxide radical (32%) and elastase enzyme (31%) in human neutrophils, while E. ficifolia oil had enhancing effects on elastase. The latter showed significant antiviral effects against hepatitis A, herpes simplex, and coxsackie viruses with IC50 values at 2.1, 2.5, and 5.6 μg/mL, respectively. Moderate antibacterial and antifungal activities were observed for Eucalyptus oils with Staphylococcus aureus being the most susceptible bacterial strain. E. ficifolia oil, similarly, displayed the best antibacterial activity with minimum inhibitory concentration (MIC) value at ca. 25 μg/mL (for S. aureus). On the contrary, E. camaldulensis oil was the most active against Candida albicans with an MIC value at 45 μg/mL. In silico studies were performed with a number of macromolecular drug targets for confirming the biological activities of the identified compounds and for interpreting their ADME (absorption-distribution-metabolism-elimination) parameters

The SAR analysis of dietary polyphenols and their antagonistic effects on bortezomib at physiological concentrations

Background: Bortezomib (BTZ), a primary treatment for MM, but its effectiveness can be reduced by interactions with vicinal diol moieties (VDMs) in polyphenols. Despite this, it’s debated whether BTZ therapy necessitates avoiding polyphenol-rich products, given the low bioavailability of polyphenols. Additionally, it remains unclear whether the structure of polyphenols contributes to their BTZ antagonism. Therefore, our study aims to unravel the structure-activity relationship of dietary polyphenols and their BTZ antagonism at daily diet-achievable physiological concentrations.Methods: We assessed the antagonistic effects of 25 polyphenols against BTZ using cell viability assays in RPMI 8226 cells. ChemGPS-NP helped analyze the structural similarity. Additionally, long-term cytotoxicity assays evaluated these effects at physiologically relevant concentrations.Results: By cell viability assays, we found a positive correlation between the number of VDMs in gallotannins and their BTZ antagonism. Moreover, the origin and configuration of VDMs, rather than the total VDM concentration, play a pivotal role in the combined antagonistic effects against BTZ in gallotannins. Additionally, ChemGPS-NP analysis indicated that the aromaticity and C-3 hydroxyl group in flavonoids’ C-rings enhance their BTZ antagonism. Finally, long-term cytotoxicity assays reveal that gallic acid (GA), epigallocatechin (EGC), and epigallocatechin gallate (EGCG), at their physiological concentrations—attainable through tea consumption—significantly and synergistically antagonize BTZ.Conclusion: Due to the potential for these polyphenols to reduce the effectiveness of BTZ, it is advisable for MM patients undergoing BTZ treatment to reduce their consumption of foods high in VDM-containing polyphenols

TCF/LEF Transcription Factors: An Update from the Internet Resources

T-cell factor/lymphoid enhancer-binding factor (TCF/LEF) proteins (TCFs) from the High Mobility Group (HMG) box family act as the main downstream effectors of the Wnt signaling pathway. The mammalian TCF/LEF family comprises four nuclear factors designated TCF7, LEF1, TCF7L1, and TCF7L2 (also known as TCF1, LEF1, TCF3, and TCF4, respectively). The proteins display common structural features and are often expressed in overlapping patterns implying their redundancy. Such redundancy was indeed observed in gene targeting studies; however, individual family members also exhibit unique features that are not recapitulated by the related proteins. In the present viewpoint, we summarized our current knowledge about the specific features of individual TCFs, namely structural-functional studies, posttranslational modifications, interacting partners, and phenotypes obtained upon gene targeting in the mouse. In addition, we employed several publicly available databases and web tools to evaluate the expression patterns and production of gene-specific isoforms of the TCF/LEF family members in human cells and tissues

HIC1 Expression Distinguishes Intestinal Carcinomas Sensitive to Chemotherapy

Neoplastic growth is frequently associated with genomic DNA methylation that causes transcriptional silencing of tumor suppressor genes. We used a collection of colorectal polyps and carcinomas in combination with bioinformatics analysis of large datasets to study the expression and methylation of Hypermethylated in cancer 1 (HIC1), a tumor suppressor gene inactivated in many neoplasms. In premalignant stages, HIC1 expression was decreased, and the decrease was linked to methylation of a specific region in the HIC1 locus. However, in carcinomas, the HIC1 expression was variable and, in some specimens, comparable to healthy tissue. Importantly, high HIC1 production distinguished a specific type of chemotherapy-responsive tumors

Фітохімічне дослідження та протизапальна активність сухих екстрактів з лохини високорослої листя

All over the world, non-steroidal anti-inflammatory drugs (NSAIDs) are taken annually by about three hundred million people and this figure is constantly increasing. At the same time, NSAIDs are also one of the most common causes of side effects of drug therapy. The development and implementation of new anti-inflammatory drugs, including those of plant origin, with minimal side effects is an urgent task of modern pharmaceutical science. Vaccinium corymbosum L. (family Ericaceae), which is gaining more and more popularity among berry crops and is successfully cultivated in Ukraine, is promising in this direction for research. The aim: phytochemical analysis of dry extracts from blueberry leaves to establish the possibility of creating new drugs with anti-inflammatory activity. Materials and methods. The objects of the study were dry extracts of northern highbush blueberry leaves. The content of amino acids and phenolic compounds was determined by HPLC and spectrophotometry. The prototypal activity was studied in vivo and in vitro. Research results. 4 dry extracts were obtained from northern highbush blueberry leaves. In the extracts obtained by HPLC, 7 amino acids were identified, including 3 essential ones: arginine, histidine, and phenylalanine. As a result of the HPLC study, 7 phenolic compounds were identified in extracts from the leaves of northern highbush blueberry: 5 flavonoids - rutin, quercetin-3-O-glucoside, kaempferol-3-O-glucoside, quercetin and kaempferol and 2 hydroxycinnamic acids, chlorogenic and caffeic acid. For the first time, the anti-inflammatory effect of extracts from blueberry leaves was investigated. It was revealed that extract 1 at a dose of 50 mg/kg and extract 4 modified with arginine at a dose of 25 mg/kg have the highest anti-inflammatory activity. Conclusions. The results of the conducted studies indicate that extracts from the leaves of northern highbush blueberry in terms of the content of biologically active substances are promising sources for the creation of new drugs and dietary supplements with anti-inflammatory activityВо всем мире нестероидные противовоспалительные средства (НПВС) ежегодно принимает около трехсот миллионов человек и эта цифра постоянно увеличивается. В то же время НПВС являются также одной из наиболее частых причин возникновения побочных эффектов медикаментозной терапии. Разработка и внедрение новых противовоспалительных средств, в том числе растительного происхождения, с минимальным побочным действием является актуальной задачей современной фармацевтической науки. Перспективным в этом направлении для исследования Vaccinium corymbosum L. (семейство Ericaceae), которая среди ягодных культур набирает все большую популярность и успешно культивируется в Украине. Цель: проведение фитохимического анализа сухих экстрактов из листьев голубики высокорослой для установления возможности создания новых лекарственных средств с противовоспалительной активностью. Материалы и методы. Объектами исследования были сухие экстракты из листьев голубики высокорослой. Содержание аминокислот и фенольных соединений определяли методом ВЭЖХ и спектрофотометрически. Протизапльну активность изучали in vivo и in vitro. Результати исследований. Было получено 4 сухие экстракты из листьев голубики высокорослой. В полученных экстрактах методом ВЭЖХ было выявлено 7 аминокислот, в том числе 3 незаменимых: аргинин, гистидин и фенилаланин. В результате исследования методом ВЭЖХ, в экстрактах из листьев голубики высокорослой было выявлено 7 фенольных соединений: 5 флавоноидов - рутин, кверцетин-3-О-глюкозид, кемферол-3-O-глюкозид, кверцитина и кемферол и 2 гидроксикоричные кислоты хлорогеновая и кофейная к-ти. Впервые исследованы противовоспалительное действие экстрактов из листьев голубики высокорослой. Выявлено, что наибольшую противовоспалительную активность имеют экстракт 1 в дозе 50 мг/кг и экстракт 4, модифицированный с аргинином в дозе 25 мг/кг. Выводы. Результаты проведенных исследований указывают на то, что экстракты из листьев голубики высокорослой по содержанию БАВ являются перспективными источниками для создания новых лекарственных средств и диетических добавок с противовоспалительной активностью.У всьому світі нестероїдні протизапальні засоби (НПЗЗ) щорічно приймає близько трьохсот мільйонів людей і ця цифра постійно збільшується. Водночас НПЗЗ являються також одною із найбільш частих причин виникнення побічних ефектів медикаментозної терапії. Розробка та впровадження нових протизапальних засобів, у тому числі рослинного походження, із мінімальною побічною дією є актуальним завданням сучасної фармацевтичної науки. Перспективним у цьому напрямку для дослідження є Vaccinium corymbosum L. (родина Ericaceae), яка серед ягідних культур набирає все більшу популярність та успішно культивується в Україні. Мета: проведення фітохімічного аналізу сухих екстрактів з листя лохини високорослої для встановлення можливості створення нових лікарських засобів з протизапальною активністю. Матеріали і методи. Об'єктами дослідження були сухі екстракти з листя лохини високорослої. Вміст амінокислот та фенольних сполук визначали методом ВЕРХ та спектрофотометрично. Протизапльну активність вивчали in vivo та in vitro. Результати дослідження. Було одержано 4 сухі екстракти з листя лохини високорослої. В одержаних екстрактах методом ВЕРХ було виявлено 7 амінокислот, у тому числі 3 незамінних: аргінін, гістидин та фенілаланін. У результаті дослідження методом ВЕРХ, у екстрактах з листя лохини високорослої було виявлено 7 фенольних сполук: 5 флавоноїдів – рутин, кверцетин-3-О-глюкозид, кемферол-3-O-глюкозид, кверцитин та кемферол та 2 гідроксикоричні кислоти хлорогенова та кофейна к-ти. Вперше досліджено протизапальну дію екстрактів з листя лохини високорослої. Виявлено, що найбільшу протизапальну активність мають екстракт 1 у дозі 50 мг/кг та екстракт 4, модифікований з аргініном, у дозі 25 мг/кг. Висновки. Результати проведених досліджень вказують на те, що екстракти з листя лохини високорослої за вмістом БАР є перспективними джерелами для створення нових лікарських засобів та дієтичних добавок з протизапальною активністю

The Regulations of Deubiquitinase USP15 and Its Pathophysiological Mechanisms in Diseases

Deubiquitinases (DUBs) play a critical role in ubiquitin-directed signaling by catalytically removing the ubiquitin from substrate proteins. Ubiquitin-specific protease 15 (USP15), a member of the largest subfamily of cysteine protease DUBs, contains two conservative cysteine (Cys) and histidine (His) boxes. USP15 harbors two zinc-binding motifs that are essential for recognition of poly-ubiquitin chains. USP15 is grouped into the same category with USP4 and USP11 due to high degree of homology in an N-terminal region consisting of domains present in ubiquitin-specific proteases (DUSP) domain and ubiquitin-like (UBL) domain. USP15 cooperates with COP9 signalosome complex (CSN) to maintain the stability of cullin-ring ligase (CRL) adaptor proteins by removing the conjugated ubiquitin chains from RBX1 subunit of CRL. USP15 is also implicated in the stabilization of the human papillomavirus type 16 E6 oncoprotein, adenomatous polyposis coli, and IκBα. Recently, reports have suggested that USP15 acts as a key regulator of TGF-β receptor-signaling pathways by deubiquitinating the TGF-β receptor itself and its downstream transducers receptor-regulated SMADs (R-SMADs), including SMAD1, SMAD2, and SMAD3, thus activating the TGF-β target genes. Although the importance of USP15 in pathologic processes remains ambiguous so far, in this review, we endeavor to summarize the literature regarding the relationship of the deubiquitinating action of USP15 with the proteins involved in the regulation of Parkinson’s disease, virus infection, and cancer-related signaling networks

Correction: Chon-Kit Chou, et al. The Regulations of Deubiquitinase USP15 and Its Pathophysiological Mechanisms in Diseases. Int. J. Mol. Sci. 2017, 18, 483

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Correction: Chon-Kit Chou, et al. The Regulations of Deubiquitinase USP15 and Its Pathophysiological Mechanisms in Diseases. Int. J. Mol. Sci. 2017, 18, 483

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6-Paradol and 6-Shogaol, the Pungent Compounds of Ginger, Promote Glucose Utilization in Adipocytes and Myotubes, and 6-Paradol Reduces Blood Glucose in High-Fat Diet-Fed Mice

The anti-diabetic activity of ginger powder (Zingiber officinale) has been recently promoted, with the recommendation to be included as one of the dietary supplements for diabetic patients. However, previous studies presented different results, which may be caused by degradation and metabolic changes of ginger components, gingerols, shogaols and paradols. Therefore, we prepared 10 ginger active components, namely 6-, 8-, 10-paradols, 6-, 8-, 10-shogaols, 6-, 8-, 10-gingerols and zingerone, and evaluated their anti-hyperglycemic activity. Among the tested compounds, 6-paradol and 6-shogaol showed potent activity in stimulating glucose utilization by 3T3-L1 adipocytes and C2C12 myotubes. The effects were attributed to the increase in 5′ adenosine monophosphate-activated protein kinase (AMPK) phosphorylation in 3T3-L1 adipocytes. 6-Paradol, the major metabolite of 6-shogaol, was utilized in an in vivo assay and significantly reduced blood glucose, cholesterol and body weight in high-fat diet-fed mice