Osteoprotegerin (OPG) serum levels are associated with liver fibrogenesis and have been proposed as a biomarker for diagnosis. However, the source and role of OPG in liver fibrosis are unknown, as is the question of whether OPG expression responds to treatment. Therefore, we aimed to elucidate the fibrotic regulation of OPG production and its possible function in human and mouse livers. OPG levels were significantly higher in lysates of human and mouse fibrotic livers compared to healthy livers. Hepatic OPG expression localized in cirrhotic collagenous bands in and around myofibroblasts. Single cell sequencing of murine liver cells showed hepatic stellate cells (HSC) to be the main producers of OPG in healthy livers. Using mouse precision-cut liver slices, we found OPG production induced by transforming growth factor β1 (TGFβ1) stimulation. Moreover, OPG itself stimulated expression of genes associated with fibrogenesis in liver slices through TGFβ1, suggesting profibrotic activity of OPG. Resolution of fibrosis in mice was associated with decreased production of OPG compared to ongoing fibrosis. OPG may stimulate fibrogenesis through TGFβ1 and is associated with the degree of fibrogenesis. It should therefore be investigated further as a possible drug target for liver fibrosis or biomarker for treatment success of novel antifibrotics.
Background: Lung fibrosis is a chronic lung disease with a high mortality rate with only two approved drugs (pirfenidone and nintedanib) to attenuate its progression. To date, there are no reliable biomarkers to assess fibrosis development and/or treatment effects for these two drugs. Osteoprotegerin (OPG) is used as a serum marker to diagnose liver fibrosis and we have previously shown it associates with lung fibrosis as well. Methods: Here we used murine and human precision-cut lung slices to investigate the regulation of OPG in lung tissue to elucidate whether it tracks with (early) fibrosis development and responds to antifibrotic treatment to assess its potential use as a biomarker. Results: OPG mRNA expression in murine lung slices was higher after treatment with profibrotic cytokines TGFβ1 or IL13, and closely correlated with Fn and PAI1 mRNA expression. More OPG protein was released from fibrotic human lung slices than from the control human slices and from TGFβ1 and IL13-stimulated murine lung slices compared to control murine slices. This OPG release was inhibited when murine slices were treated with pirfenidone or nintedanib. OPG release from human fibrotic lung slices was inhibited by pirfenidone treatment. Conclusion: OPG can already be detected during the early stages of fibrosis development and responds, both in early- and late-stage fibrosis, to treatment with antifibrotic drugs currently on the market for lung fibrosis. Therefore, OPG should be further investigated as a potential biomarker for lung fibrosis and a potential surrogate marker for treatment effect.
5 September 2024 in Cellulose Chemistry and Technology
Sengon wood sawdust is a wood industry waste the quantity of which is increasing because of the high market demand of the wood. This condition demands innovation in waste processing. Microcrystalline cellulose is pure cellulose obtained from the hydrolysis of α-cellulose. This research aims to fabricate and characterize microcrystalline cellulose from Sengon wood sawdust. The initial stage was carried out to break lignocellulose bonds through the delignification process using 2% NaOH, followed by hydrolysis of α-cellulose with 4N HCl (1:40) at 80 °C. This acid treatment aims to obtain a crystalline form of cellulose by removing the amorphous part. SEM micrographs show a smooth surface with few holes and spherical fibers. XRD analysis revealed the cellulose type I structure of MCC with a crystallinity index of 33.8% due to acid hydrolysis treatment. Chemical treatment causes the loss of the hemicelluloses and lignin, as confirmed from the FT-IR analysis results, and higher thermal stability of microcrystalline cellulose, as found by the DSC analysis.
Preparasi Nanopartikel Senyawa Pentagamavunon-0 Menggunakan Matriks Polimer Kitosan Rantai Sedang dan Pengait Silang Natrium Tripolifosfat Melalui Mekanisme Gelasi Ionik Sebagai Kandidat Obat Antiinflamasi
Sistem penghantaran obat menggunakan gel mulai banyak berkembang salah satunya in situ gel. Bentuk sediaan ini menarik untuk dikembangkan karena hanya melibatkan transisi bentuk (sol-gel) sederhana tanpa adanya reaksi kimia. In situ gel termosensitif merupakan jenis sediaan in situ gel yang berbentuk larutan pada suhu ruang namun berubah menjadi gel pada suhu tubuh. Polimer basis yang digunakan pada formulasi in situ gel memiliki karakteristik khas yakni bersifat termosensitif. Artikel review ini bertujuan untuk membahas berbagai jenis polimer termosensitif dan mekanisme gelasinya serta aplikasi bidang medis dari in situ gel termosensitif. Polimer termosensitif memiliki sifat reserve gelation atau mengalami gelasi pada peningkatan suhu karena pengaruh kesetimbangan gugus hidrofil dan hidrofob dalam strukturnya. Sediaan in situ gel memberikan keleluasaan penggunaan dan modifkasi profil pelepasan obat dibandingkan sediaan konvensional. Beberapa karakteristik penting yang perlu diperhatikan pada desain sediaan ini diantaranya adalah suhu gelasi, mukoadesivitas, dan reologi. Sediaan in situ gel telah dikembangkan untuk sistem penghantaran berbagai obat seperti bukal dan sublingual, nasal, dan okular.
Kesehatan reproduksi merupakan aspek fundamental bagi kesejahteraan jangka panjang dan produktivitas mahasiswi. Namun, isu ini seringkali terabaikan, sementara kelompok ini rentan mengalami masalah seperti dismenore dan ketidakseimbangan hormonal. Pengabdian kepada masyarakat ini bertujuan untuk meningkatkan pengetahuan, kesadaran, dan keterampilan praktis santri mahasiswi di Pondok Pesantren Bil Qolam Nologaten, Yogyakarta, dalam menjaga kesehatan reproduksi melalui pendekatan yang mengintegrasikan edukasi ilmiah dengan kearifan tanaman lokal yaitu kunyit. Metode yang digunakan berupa penyuluhan dan pelatihan praktik pembuatan “Kunyit Latte”, minuman herbal inovatif berbahan dasar kunyit dan jahe yang kaya akan antioksidan dan senyawa anti-inflamasi untuk kesehatan reproduksi. Hasil penyuluhan ini membuktikan efektivitas kegiatan, ditandai dengan peningkatan pemahaman santri mahasiswa yang signifikan. Peningkatan pengetahuan ini menjadi fondasi krusial untuk membentuk sikap dan perilaku sehat. Melalui kegiatan ini, mahasiswi tidak hanya memperoleh pemahaman komprehensif tentang kesehatan reproduksi, tetapi juga terampil membuat minuman herbal yang dapat diaplikasikan dalam kehidupan sehari-hari. Kesimpulannya terdapat peningkatan pengetahuan santri dalam hal kesehatan reproduksi wanita. Dengan adanya kegiatan ini diharapkan santri mahasiswi lebih memahami mengenai kesehatan reproduksi wanita dan dapat mempraktekkan langsung pembuatan produk kunyit latte yang bermanfaat untuk kesehatan mereka.