White Tea extract induces lipolytic activity and inhibits adipogenesis in human subcutaneous (pre)-adipocytes

<p>Abstract</p> <p>Background</p> <p>The dramatic increase in obesity-related diseases emphasizes the need to elucidate the cellular and molecular mechanisms underlying fat metabolism. To investigate how natural substances influence lipolysis and adipogenesis, we determined the effects of White Tea extract on cultured human subcutaneous preadipocytes and adipocytes.</p> <p>Methods</p> <p>For our in vitro studies we used a White Tea extract solution that contained polyphenols and methylxanthines. Utilizing cultured human preadipocytes we investigated White Tea extract solution-induced inhibition of triglyceride incorporation during adipogenesis and possible effects on cell viability. In vitro studies on human adipocytes were performed aiming to elucidate the efficacy of White Tea extract solution to stimulate lipolytic activity. To characterize White Tea extract solution-mediated effects on a molecular level, we analyzed gene expression of essential adipogenesis-related transcription factors by qRT-PCR and determined the expression of the transcription factor ADD1/SREBP-1c on the protein level utilizing immunofluorescence analysis.</p> <p>Results</p> <p>Our data show that incubation of preadipocytes with White Tea extract solution significantly decreased triglyceride incorporation during adipogenesis in a dose-dependent manner (n = 10) without affecting cell viability (n = 10). These effects were, at least in part, mediated by EGCG (n = 10, 50 μM). In addition, White Tea extract solution also stimulated lipolytic activity in adipocytes (n = 7). Differentiating preadipocytes cultivated in the presence of 0.5% White Tea extract solution showed a decrease in PPARγ, ADD1/SREBP-1c, C/EBPα and C/EBPδ mRNA levels. Moreover, the expression of the transcription factor ADD1/SREBP-1c was not only decreased on the mRNA but also on the protein level.</p> <p>Conclusion</p> <p>White Tea extract is a natural source that effectively inhibits adipogenesis and stimulates lipolysis-activity. Therefore, it can be utilized to modulate different levels of the adipocyte life cycle.</p

Studi Efisiensi Sistem Prasedimentasi Dan Free Water Surface Wetland Dalam Menurunkan Kadar Nitrat, Fosfat, Kekeruhan, Zat Organik Dan Total Coli

Boezem Wonorejo saat ini telah dikembangkan menjadi tempat wisata yaitu Ekowisata Mangrove. Sampai saat ini pihak pengelola boezem masih kesulitan dalam penyediaan air bersihnya Sungai Jagir yang mengalir di sekitar wilayah Ekowisata tersebut merupakan sumber air permukaan yang berpotensi sebagai pemenuhan kebutuhan tersebut secara kuantitatif. Agar dapat terpenuhi secara kualitatif, maka Perlu dilakukan penelitian awal untuk mengetahui efisiensi penurunan kadar Nitrat, Fosfat, Zat Organik, Kekeruhan maupun Total Coli. Dalam penelitian ini akan digunakan rangkaian suatu sistem pengolahan Prasedimentasi dan Free Water Surface wetland skala laboratoium, Dengan variabel ukuran media pasir (16-32 mesh dan lolos 32 mesh) dan umur mangrove (3 bulan dan 6 bulan) yang akan di analisis di laboratorium Teknik Lingkungan ITS. Dari hasil analisis didapat removal maksimum untuk kekeruhan pada prasedimentasi 46,5%, sedangkan pada wetland yaitu pada media pasir mesh 16-32 dan mangrove 6 bulan yaitu 94,8%. Presentase maksimum removal nitrat pada prasedimentasi yaitu 17,8%, removal maksimum pada wetland dengan mangrove 6 bulan dan media pasir lolos 32 mesh yaitu 53,6%. Pada mangrove sendiri removal makismum terdapat pada umur 6 bulan dengan besar removal 36,5%. Removal maksimum fosfat terbesar pada prasedimentasi yaitu 64,3%, untuk Reaktor Wetland yaitu pada wetland dengan mangrove 6 bulan dan media pasir lolos mesh 32 sebesar 90,5%. Untuk . Mangrovenya sendiri mampu meremoval maksimum pada umur 6 bulan dengan besar 53,8%. Presentase removal maksimum zat organik pada prasedimentasi sebesar 35,7%, pada reaktor wetland sebesar 21,8% dengan ukuran media pasir mesh 16-32 dan umur mangrove 3 bulan

An integrative metabolomics and transcriptomics study to identify metabolic alterations in aged skin of humans in vivo

Background Aging human skin undergoes significant morphological and functional changes such as wrinkle formation, reduced wound healing capacity, and altered epidermal barrier function. Besides known age-related alterations like DNA-methylation changes, metabolic adaptations have been recently linked to impaired skin function in elder humans. Understanding of these metabolic adaptations in aged skin is of special interest to devise topical treatments that potentially reverse or alleviate age-dependent skin deterioration and the occurrence of skin disorders. Results We investigated the global metabolic adaptions in human skin during aging with a combined transcriptomic and metabolomic approach applied to epidermal tissue samples of young and old human volunteers. Our analysis confirmed known age-dependent metabolic alterations, e.g. reduction of coenzyme Q10 levels, and also revealed novel age effects that are seemingly important for skin maintenance. Integration of donor-matched transcriptome and metabolome data highlighted transcriptionally-driven alterations of metabolism during aging such as altered activity in upper glycolysis and glycerolipid biosynthesis or decreased protein and polyamine biosynthesis. Together, we identified several age-dependent metabolic alterations that might affect cellular signaling, epidermal barrier function, and skin structure and morphology. Conclusions Our study provides a global resource on the metabolic adaptations and its transcriptional regulation during aging of human skin. Thus, it represents a first step towards an understanding of the impact of metabolism on impaired skin function in aged humans and therefore will potentially lead to improved treatments of age related skin disorders.ISSN:1471-216

Modulation of Coenzyme Q10 content and oxidative status in human dermal fibroblasts using HMG-CoA reductase inhibitor over a broad range of concentrations. From mitohormesis to mitochondrial dysfunction and accelerated aging

Coenzyme Q10 (CoQ10) is an endogenous lipophilic quinone, ubiquitous in biological membranes and endowed with antioxidant and bioenergetic properties, both crucial to the aging process. In fact, coenzyme Q10 synthesis is known to decrease with age in different tissues including skin. Moreover, synthesis can be inhibited by 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors such as statins, that are widely used hypocholesterolemic drugs. They target a key enzymatic step along the mevalonate pathway, involved in the synthesis of both cholesterol and isoprenylated compounds including CoQ10.In the present study, we show that pharmacological CoQ10 deprivation at concentrations of statins > 10000 nM triggers intracellular oxidative stress, mitochondrial dysfunction and generates cell death in human dermal fibroblasts (HDF). On the contrary, at lower statin concentrations, cells and mainly mitochondria, are able to partially adapt and prevent oxidative imbalance and overt mitochondrial toxicity. Importantly, our data demonstrate that CoQ10 decrease promotes mitochondrial permeability transition and bioenergetic dysfunction leading to premature aging of human dermal fibroblasts in vitro

A potent SARS-CoV-2 neutralising nanobody shows therapeutic efficacy in the Syrian golden hamster model of COVID-19

SARS-CoV-2 remains a global threat to human health particularly as escape mutants emerge. There is an unmet need for effective treatments against COVID-19 for which neutralizing single domain antibodies (nanobodies) have significant potential. Their small size and stability mean that nanobodies are compatible with respiratory administration. We report four nanobodies (C5, H3, C1, F2) engineered as homotrimers with pmolar affinity for the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. Crystal structures show C5 and H3 overlap the ACE2 epitope, whilst C1 and F2 bind to a different epitope. Cryo Electron Microscopy shows C5 binding results in an all down arrangement of the Spike protein. C1, H3 and C5 all neutralize the Victoria strain, and the highly transmissible Alpha (B.1.1.7 first identified in Kent, UK) strain and C1 also neutralizes the Beta (B.1.35, first identified in South Africa). Administration of C5-trimer via the respiratory route showed potent therapeutic efficacy in the Syrian hamster model of COVID-19 and separately, effective prophylaxis. The molecule was similarly potent by intraperitoneal injection