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Abstrak :
Pendahuluan: Proses penyembuhan luka merupakan proses biologi yang kompleks dan dinamis yang melibatkan peran seluler, molekuler dan humoral yang terdiri atas fase inflamasi, fase proliferasi dan fase maturasi. Proses penyembuhan luka yang lambat akan menyebabkan luka kronis sehingga berbagai penelitian dikembangkan untuk mempercepat proses penyembuhan. Tingginya biaya ekonomi dan sosial bagi pemerintah dan pasien terkait dengan perawatan luka adalah motivasi penting untuk pencarian alternatif terapi baru baik sebagai obat alternatif maupun sebagai komplementer. Penelitian ini bertujuan untuk membuktikan percepatan proses penyembuhan luka berbahan dasar alami, yaitu ekstrak daun Jatropha multifida L. yang dinilai dengan pemeriksaan secara histologi dan imunohistokimia. Metode: Penelitian dilakukan pada 54 ekor tikus putih jantan galur Spraque dawley yang dibuat luka sayat pada enam kelompok masing-masing 3 ekor per periode dekapitasi. Tikus diperlakukan dengan ekstrak metanol 1%, ekstrak etil asetat 1% dan ekstrak n-heksan 1% daun J. multifida L. dibandingkan dengan kelompok kontrol positif (senyawa steroid), pelarut (alkohol 70%) dan negatif (tanpa perlakuan). Pemeriksaan histologi dilakukan untuk mempelajari parameter penyembuhan luka yaitu jumlah leukosit PMN, fibroblas, pembuluh darah baru, re-epitelialisasi dan kerapatan serabut kolagen. Ekspresi Vascular Endothelial Growth Factor (VEGF), Fibroblast Growth Factor (FGF) dan Epidermal Growth Factor (EGF) dinilai dengan analisis imunohistokimia. Uji sensitifitas dilakukan untuk menilai keamanan pemakaian ekstrak daun J. multifida L. terhadap kulit hewan coba. Hasil: Semua parameter yang diukur menunjukkan bahwa ekstrak metanol 1% daun J. multifida L. dapat mempercepat proses penyembuhan luka dengan hasil yang lebih baik dan lebih cepat dibanding semua kelompok kontrol. Terdapat korelasi yang sangat kuat dan bermakna antara angiogenesis dan fibroblas dengan ekspresi VEGF, fibroblas dengan ekspresi FGF dan re-epitelialisasi dengan ekspresi EGF. Uji sensitifitas menunjukkan bahwa ekstrak daun J. multifida L. tidak menimbulkan edema dan eritema. Kesimpulan: Ekstrak metanol daun J. multifida L., dapat mempercepat proses penyembuhan luka dengan mempersingkat fase inflamasi dan fibroproliferasi dengan adanya senyawa metabolit sekunder yang dikandungnya sehingga dapat menstimulasi ekspresi VEGF, FGF dan EGF dserta tidak bersifat iritatif.

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Introduction: Wound healing is a complex biological process involving the dynamic role of cellular, molecular and humoral pathways in the phases of inflammation, proliferation and maturation. Various studies have been conducted to accelerate the wound healing process, because slow healing can lead to complications. The high economic and social costs for governments and patients related to wound care is an important motivation for the search of new therapeutic intervention including complementary and alternative medicine. This study aims to accelerate the process of wound healing with natural compounds, namely Jatropha multifida L. leaf extracts assessed by histological and immunohistochemical examination. Methods: The study was conducted with 54 male white rats, Spraque Dawley strain injured by equally sized skin cuts and divided into six groups of 3 animals each. Rats were treated with methanol, ethyl acetate or n-hexane extracts of J. multifida L. leaves (3 treatment groups) and compared with steroid-treated positive controls, organic solvent (methanol 70%) and negative (no treatment) control groups. Histology examined wound healing parameters, e.g., polymorphonuclear leukocyte and fibroblast numbers, re-vascularisation, re- epithelialisation and density of collagen fibers. Expression of vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF) and epidermal growth factor (EGF) was determined by immunohistochemistry. Sensitivity tests were conducted to assess the safety of the application of J. multifida L. leaf extracts towards the animal skin. Results: All measured parameters showed that the methanol extract of J. multifida L. leaves accelerates the wound healing process with better results compared to all other groups. There were strong correlations of VEGF expression with angiogenesis and fibroblast numbers, between FGF expression and fibroblast numbers and between EGF expression and re-epithelialisation. Conclusion: The methanol extract of J. multifida L. leaves can accelerate the wound healing process by shortening the inflammatory phase and reducing fibroblast proliferation through stimulation of VEGF, FGF and EGF expression.

Abstrak :
Latar Belakang : FGF2 merupakan ligan bagi Fibroblast Growth Factor Receptor2(FGFR2). Interaksi dengan reseptor ini memediasi dimerisasi reseptor, fosforilasi, dan aktivasi jalur pensinyalan, seperti jalur Ras-MAPK dan PI3K. Mutasi yang berlebihan melalui sumbu FGF / FGFR dapat menginduksi proliferasi sel kanker, memicu angiogenesis dan limfogenesis, yang mendorong terjadinya metastasis. Penelitian ini mencoba mengevaluasi peran FGF2 pada metastasis kelenjar getah bening aksila pada pasien kanker payudara stadium dini. Tujuan : Mengetahui hubungan nilai ekspresi FGF 2 pada tumor primer terhadap kejadian metastasis kelenjar getah bening aksila. Metode : Digunakan studi potong lintang dengan mengevaluasi ekspresi FGF2 pada 47 pasien kanker payudara stadium dini yang menjalani mastektomi di Rumah Sakit Umum Pusat Nasional Cipto Mangunkusumo (RSCM) pada periode Januari 2014 sampai Desember 2018. Ekspresi FGF2 diperiksa dengan pemeriksaan imunohistokimia, kemudian dievaluasi dan dihubungkan antara ekspresi FGF2 dengan metastasis kelenjar getah bening aksila. Hasil : Uji Chi Square memperlihatkan nilai p=0.044 (p<0.05) yang menunjukkan bahwa terdapat hubungan yang signifikan antara nilai FGF2 pada tumor payudara dengan kejadian metastasis kelenjar getah bening aksila. Odds ratio 4,22 (CI 95% 0,983-18,1). Kesimpulan : Peran FGF2 dalam metastasis kelenjar getah bening berhubungan dengan interaksi antara berbagai faktor limfangiogenik dalam mempromosikan limfangiogenesis dan metastasis limfatik. Ekspresi FGF2 yang tinggi memiliki korelasi signifikan dengan angka kejadian metastasis kelenjar getah bening aksila. ......Background : FGF2 is a ligand for Fibroblast Growth Factor Receptor 2 (FGFR2). Interaction with this receptor mediate dimerization of receptor, phosphorilation, and activation of signaling pathway, such as Ras-MAPK and PI3K. Overmutation through FGF/FGFR induced proliferation of cancer cells, promoted angiogenesis, lymphogenesis, and metastasis. This study tried to evaluate the role of FGF2 in axillary lymph node metastasis in early-stage breast cancer patients. Aim : To determined the relationship of FGF 2 expression values in primary tumors to the incidence of axillary lymph node metastases. Methods :A cross-sectional study was used by evaluating the expression of FGF2 in 47 early-stage breast cancer patients who underwent a mastectomy at the Cipto Mangunkusumo National Center General Hospital (RSCM) from January 2014 to Desember 2018. FGF2 expression was examined by immunohistochemistry, then evaluated and linked between expression FGF2 with axillary lymph node metastases. Results : The Chi Square test had a value of p=0.044 (p<0.05) that showed there was a significant relationship between FGF2 value in breast tumors with the incidence of axillary lymph node metastasis. Odds ratio 4.22 (95% CI 0.983-18.1). Conclusions The role of FGF2 in lymph node metastasis is related to the interaction between various lymphangiogenic factors in promoting lymphangiogenesis and lymphatic metastasis. High expression of FGF2 has a significant correlation with the incidence of axillary lymph node metastasis.

Abstrak :
Obesitas menyebabkan resistensi FGF21 yang berperan dalam proses pencokelatan dan termogenesis. Resistensi FGF21 disebabkan karena penurunan ekspresi reseptor, sehingga berkurangnya ikatan antara FGF21 dan reseptornya di jaringan adiposa. Penurunan ekspresi reseptor tersebut dipengaruhi oleh miR-34a yang meningkat pada kondisi obesitas. Beberapa penelitian menunjukkan bahwa miR-34a dapat menghambat persinyalan FGF21 yang berperan pada proses pencokelatan. Pendekatan terapetik berbasis FGF21 telah banyak diteliti namun potensi ekstrak Hibiscus sabdariffa Linn (H. sabdariffa)terhadap miR-34a belum diketahui. Penelitian ini bertujuan untuk mengetahui pengaruh pemberian ekstrak H. sabdariffa terhadap ekspresi miR-34a dan FGF21 di jaringan adiposa putih. Penelitian eksperimen ini menggunakan dua puluh empat tikus jantan (Rattus norvegicus L) jantan galur Sprague-Dawley usia 6-10 minggu yang diinduksi diet tinggi lemak (19,09% lemak, 24,00% protein). Tikus dikelompokkan menjadi empat kelompok yaitu kelompok kontrol normal (N), kelompok kontrol obese (Ob), kelompok perlakuan dosis 200 mg/kgBB/hari (Ob-hib200), dan kelompok perlakuan dosis 400 mg/kgBB/hari (Ob-hib4000). H. sabdariffa diberikan setiap hari selama 5 minggu. Pemeriksaan ekspresi miR-34a menggunakan qRT-real time PCR dan protein FGF21 dari jaringan adiposa putih menggunakan uji ELISA. Hasil uji statistik ANOVA menunjukkan ekspresi miR-34a lebih rendah pada kelompok tikus obese yang diberikan ekstrak dosis 400 mg/kgBB/hari (p < 0,001) sehingga kadarnya tidak berbeda bermakna dengan keadaan normal (p>0,05). Di samping itu,  kadar FGF21 pada tikus obese yang diberikan ekstrak H. sabdariffa dosis 400 mg/kgBB/hari (p < 0,001) lebih tinggi bahkan berbeda bermakna dibandingkan keadaan normal (p < 0,001). Dengan demikian, ekstrak H. sabdariffa berpengaruh terhadap penurunan ekspresi miR-34a diikuti dengan peningkatan kadar FGF21 jaringan adiposa putih yang berpotensi memperbaiki resistensi FGF21. ......Obesity increase  FGF21 in circulation and caused the FGF21 resistance. This resistant lead to decrease expressions of FGF21 receptor in white adipose tissue of obese rats. The downregulation its receptor and co-receptor is altered by miR-34a which elevate in obesity. Several studies show miR-34a can inhibit signal cascade of beiging process. The therapeutic approach using FGF21 has been approved to improve obesity but the potential natural extracts of  Hibiscus sabdariffa Linn (H. sabdariffa) has an effect to miR-34a and FGF21 remains unclear. This study aimed to determine alteration of miR-34a expressions of white adipose tissue and FGF21 of obese rats given to H. sabdariffa extracts. In vivo experimental study using twenty-four males of Sprague-Dawley rats (Rattus norvegicus L), age 6-10 weeks. Rats is administered high fat diet (19,09% lemak, 24,00% protein) to induce obesity. Rats divided by four groups as follows : normal control group (N), obese control group (Ob), obese group is given 200 mg/kgWB/day extracts (Ob-hib200), and obese group is given 400 mg/kgWB/day extracts (Ob-hib4000). H. sabdariffa extracts is given daily for five weeks. Quantification of miR-34a expressions using qRT-real time PCR and  FGF21 levels of white adipose using ELISA assay. Statistical analysis using ANOVA showed  miR-34a expressions of white adipose tissue decrease in obese group is given 400 mg/kgWB/day extracts (p < 0,001) but not significantly differ from normal control group (p>0,05). In addition, FGF21 levels in white adipose tissue of obese rats given H. sabdariffa 400 mg/kgWB/day extracts (p < 0,001) increase differ from normal control group (p < 0,001). In brief,  H. sabdariffa extracts can alter the decrease of miR-34a expressions and increasing FGF21  levels in white adipose tissue of obese rats that has potential improve FGF21 resistance.

Abstrak :
Human dental pulp of exfoliated deciduous teeth contains the population of cells that exhibited mesenchymal stem cell (MSC) characters. Though, a cell amplification process is indeed required to secure and adequate cell number for such a potential employment. Several publications suggested the alteration of MSCs upon in vitro culture, for example, the decrease in proliferation and the loss of stem cell characters. Here, we investigated an influence of basic fibroblast growth factor (bFGF) on stem cells isolated from human exfoliated deciduous teeth (SHEDs) with respect to cell proliferation, colony forming unit efficiency and stem cell marker expression in both short- and long-term cultures. For short-term bFGF treatment, SHEDs were treated with bFGF for 48h. While, in long-term bFGF supplementation, SHEDs were maintained in culture and continuous passage upon confluence in medium supplemented witg bFGF. Cells at passage (P) 5 and 10 were employed for characterization. Our result showed that short-term bFGF treatment enhanced OCT4, REX1, and NANOG mRNA expression as well as colony forming unit ability. The FGFR inhibitor pretreatment was able to attenuate the influence of bFGF on pluripotent stem cell marker expression, confirming bFGF function. In addition, cells cultured in high passage number had decreased in cell proliferation, colony forming unit capacity, and pluripotent stem cell marker mRNA expression. However, bFGF supplementation in culture medium enhanced both pluripotent stem cell marker expression and colony forming unit capacity in later passage, though the effect was not robust. Together, these results indicate that high passage number may attenuate pluripotent properties of SHEDs and bFGF supplementation could be the beneficial approach to maintain SHEDs' stemness properties.

Abstrak :
Fibroblast growth factors (FGFs) have been recognized primarily as autocrine/paracrine factors that regulate embryonic development and organogenesis. However, recent studies have revealed that some FGFs function as endocrine factors and regulate various metabolic processes in adulthood. Such FGFs, collectively called endocrine FGFs, are comprised of three members (FGF15/19, FGF21, and FGF23: FGF15 is the mouse ortholog of human FGF19). These endocrine FGFs share a common structural feature that enables the endocrine mode of action at the expense of the affinity to FGF receptors. To restore the affinity to FGF receptors in their target organs, the endocrine FGFs have designated the Klotho family of transmembrane proteins as obligate co-receptors. By expressing Klothos in a tissue-specific manner, this unique co-receptor system also enables the endocrine FGFs to specify their target organs among many tissues that express FGF receptors.