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"Latar Belakang: Epigenetik lingkungan merupakan faktor yang masih dapat dikontrol dalam kejadian celah bibir dan lelangit. Masyarakat diharapkan dapat mengetahui apa saja epigenetik lingkungan yang berpengaruh terhadap kejadian celah bibir dan lelangit sehingga masyarakat sadar akan pentingnya tata laksana yang baik pada penderita celah bibir dan lelangit. Tujuan: Mengetahui gambaran epigenetik lingkungan pada penderita celah bibir dan lelangit. Metode: Penelitian deskriptif dengan desain potong lintang dengan sampel 184 rekam medis pasien celah bibir dan lelangit di RSAB Harapan Kita. Data menunjukkan gambaran epigenetik lingkungan pada anak dengan celah bibir dan lelangit yang sudah selesai menjalani perawatan bedah primer di RSAB Harapan Kita. Hasil: Nilai rerata usia ibu saat hamil adalah 30,5 tahun. Terdapat riwayat konsumsi obat pada 77,7 persen subjek. Tidak diketahui adanya kebiasaan merokok pada ibu. Tingkat pendidikan ibu sedang (SMP, SMA, Diploma 1–3) dan tingkat pendidikan ayah tinggi (Sarjana 1–2) memiliki persentase terbesar. Mayoritas ibu pasien berdomisili di Jabodetabek. Nilai rerata berat badan lahir, lingkar kepala lahir, dan panjang badan lahir sebagai parameter dari nutrisi ibu termasuk dalam kategori normal. Sebanyak 79,9% subjek menjalani recall pasca perawatan primer. Kesimpulan: Epigenetik lingkungan menunjukkan gambaran yang normal pada pasien celah bibir dan lelangit di RSAB Harapan Kita.

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Background: Environmental epigenetics are controllable elements in the occurrence of cleft lip and palate. The community is expected to understand the environmental epigenetics that influence the incidence of cleft lip and palate, raising awareness of the importance of proper management in cleft lip and palate. Objective: This study aims to understand the overview of environmental in epigenetics individuals with cleft lip and palate. Methods: Descriptive research with a cross-sectional design involving a sample of 184 medical records of cleft lip and palate patients at RSAB Harapan Kita. The data illustrates the overview of environmental epigenetics in children with cleft lip and palate who have completed primary surgical treatment at RSAB Harapan Kita. Results: The average maternal age during pregnancy is 30,5 years. About 77,7% of subjects have a history of drug consumption, and smoking habits are unknown. Mothers typically have a moderate education level, while fathers have a higher education level. Most mothers reside in Jabodetabek. Birth weight, head circumference, and birth length fall within normal ranges. A recall after primary care was conducted for 79,9% of the subjects. Conclusion: The environmental epigenetics indicate a normal overview in patients with cleft lip and palate at RSAB Harapan Kita."

"Endometriosis adalah sebuah penyakit yang dicirikan dengan implantasi jaringan endometrium di luar uterus. Endometriosis disebut sebagai penyakit hormonal. Salah satu hormon yang mempengaruhi patogenesis penyakit ini adalah hormon estrogen. Estrogen diduga dapat memicu proliferasi dan pertumbuhan jaringan endometrium ektopik. Sintesis estrogen dipengaruhi oleh faktor transkripsi SF-1 (Steroidogenic Factor-1). SF-1 berperan penting dalam sintesis aromatase, enzim kunci dalam biosintesis estrogen. Penelitian sebelumnya telah menunjukkan kemungkinan peran epigenetik dalam endometriosis, salah satunya adalah metilasi DNA pada gen SF-1. Promoter gen SF-1 pada jaringan endometriosis telah ditemukan mengalami hipometilasi yang menyebabkan SF-1 lebih banyak disintesis pada jaringan endometriosis. Tujuan penelitian ini adalah untuk menganalisis tingkat metilasi dari promoter gen SF-1 pada endometriosis ovarium dan peritoneum. Penelitian ini menggunakan 11 sampel jaringan endometriosis ovarium, 11 sampel jaringan endometriosis peritoneum, dan 11 kontrol. Jaringan endometriosis didapatkan dari pasien yang melakukan laparoskopi, sedangkan kontrol didapatkan dari pasien yang melakukan mikrokuretase. DNA dari sampel kemudian diisolasi dan dilakukan konversi bisulfit, kemudian dianalisis dengan methylation-specific polymerase chain reaction (MSP). Analisis statistik yang digunakan pada penelitian ini adalah tes Kruskal-Wallis, yang dilanjutkan dengan analisis post-hoc menggunakan tes Mann-Whitney U. P-value kurang dari 0,05 dianggap signifikan. Terdapat perbedaan signifikan tingkat metilasi promoter gen SF-1 antara sampel endometriosis ovarium, endometriosis peritoneum, dan kontrol (p=0,001). Peneliti kemudian menemukan bahwa terdapat perbedaan signifikan antara kontrol dan endometriosis peritoneum (p=0,028), serta antara endometriosis ovarium dan peritoneum (p=0,028). Tidak terdapat perbedaan yang signifikan antara kontrol dan endometriosis ovarium (p=1,00). Hasil ini menunjukkan bahwa perbedaan dalam tingkat metilasi promoter gen SF-1 dapat diasosiasikan dengan perkembangan endometriosis peritoneum. Sementara itu, perbedaan pada tingkat metilasi promoter gen SF-1 antara endometriosis ovarium dan peritoneum dapat menunjukkan perbedaan patogenesis antara kedua tipe endometriosis.

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Endometriosis is a disease characterized by implantation of endometrial-like tissues outside of uterus. Endometriosis is a hormonal disease. One of the hormones involved in its pathogenesis is estrogen. Estrogen is thought to induce proliferation and growth of ectopic endometrium tissues. Estrogen biosynthesis involved a transcription factor, SF-1 (Steroidogenic Factor-1) for synthesis of aromatase, a key enzyme in estrogen biosynthesis. Previous studies have shown the possibility of epigenetic role in endometriosis, one of them is in the DNA methylation of SF-1 gene. Promoter of SF-1 gene has found to be hypomethylated, causing an increase in the syntehsis of SF-1 in endometriotic tissues.

The purpose of this study was to analyze the methylation profile of SF-1 gene in peritoneal and ovarian endometriosis. This study used 11 samples of ovarian endometrial tissues, 11 samples of peritoneal endometrial tissues, and 11 controls. Endometrial tissues were obtained from patients underwent laparoscopy, while controls were obtained from patients underwent microcurretage. DNA from the samples were isolated, sodium bisulfite converted and then analyzed by methylation-specific polymerase chain reaction (MSP). Statistical analysis used was Kruskal Wallis and continued with post hoc analysis using Mann-Whitney U test. A two-tailed p value less than 0.05 was considered to be significant. There was a significant difference between ovarian endometriosis, peritoneal endometriosis, and control with p = 0.001.

We further discovered that there was a significant difference between control and peritoneal endometriosis (p=0.028) and between ovarian and peritoneal endometriosis (p=0.028). Meanwhile, there was no significant difference between control and ovarian endometriosis (p=1.00). Our result suggested that the difference in methylathion profile of SF-1 gene may be associated with the development of peritoneal endometriosis. The difference in methylation profile between ovarian and peritoneal endometriosis might suggest different pathogenesis of both type of endometriosis."

"Sindrom koroner akut (SKA) merupakan masalah kesehatan nasional karena tingginya angka morbiditas dan mortalitas serta beban biaya yang dibutuhkan. Intervensi koroner perkutan (IKP) dan terapi antiplatelet seperti klopidogrel merupakan tata laksana yang direkomendasikan oleh organisasi kardiologi internasional. Meskipun demikian, pasien SKA masih dapat mengalami kejadian kardiovaskular mayor (KKM). Kemungkinan, resistensi klopidogrel berperan pada KKM sedangkan resistensi klopidogrel mungkin dipengaruhi oleh faktor genetik dan epigenetik. Penelitian ini bertujuan untuk mengetahui hubungan faktor genetik yaitu polimorfisme gen CYP2C19 dan P2Y12, serta epigenetik yaitu metilasi DNA gen CYP2C19 dan P2Y12 serta ekspresi miRNA-26a dengan resistensi klopidogrel dan pengaruhnya terhadap KKM pada pasien SKA pasca IKP.Untuk menganalisis hubungan faktor genetik dan epigenetik dengan resistensi klopidogrel, penelitian dilakukan dengan desain potong lintang, sedangkan untuk analisis hubungan faktor genetik dan epigenetik dengan KKM dilakukan dengan desain kohort prospektif. Subjek penelitian meliputi 201 pasien SKA pasca IKP dan mendapat terapi klopidogrel di Rumah Sakit Jantung dan Pembuluh Darah Harapan Kita dari bulan September 2018 sampai dengan Juni 2020. Resistensi klopidogrel ditentukan dengan pemeriksaan light transmission aggregometry (LTA) apabila hasilnya lebih besar dari 59% dengan agonis ADP 20 mM. Deteksi polimorfisme gen CYP2C19 dan P2Y12 serta ekspresi miRNA-26a dilakukan dengan metode qRT-PCR, sedangkan metilasi DNA gen CYP2C19 dan P2Y12 dikerjakan dengan metode konversi bisulfit. Pasien diobservasi selama satu tahun dan jika ada angina pektoris, infark miokard akut (IMA) rekuren, stroke, atau kematian, dicatat sebagai KKM.Dari 201 subjek, terdapat 45,8% carrier mutant polimorfisme *2 dan *3 gen CYP2C19, 36,8% carrier mutant polimorfisme rs3679479 gen P2Y12, 10% hipometilasi DNA gen P2Y12, 80,1% hipometilasi DNA gen CYP2C19, dan 66,2% ekspresi miRNA-26a up regulated. Proporsi resisten klopidogrel adalah 49,8% dan proporsi KKM adalah 14,9% (kematian 7,5%). Terdapat hubungan antara merokok (p = 0,001; OR 0,37 [IK 95%; 0,20–0,68]), hipometilasi DNA gen CYP2C19 (p = 0,037; OR 2,13 [IK 95%; 1,04–4,37]), dan ekspresi miRNA-26a up regulated (p = 0,020; OR 2,03 [IK 95%; 1,12–3,68]) dengan resistensi klopidogrel. Terdapat hubungan antara jenis kelamin perempuan (p = 0,040; HR 2,73 [IK 95%; 1,05–7,14]), usia ≥ 60 tahun (p = 0,035; HR 2,17 [IK 95%; 1,06–4,48]), eGFR rendah (p = 0,001; HR 3,29 [IK 95%; 1,59–6,84]), dan polimorfisme *2 dan *3 gen CYP2C19 (p = 0,047; HR 2,12 [IK 95%; 1,01–4,46]) dengan KKM dalam satu tahun.Hanya faktor epigenetik berupa metilasi DNA gen CYP2C19 dan ekspresi miRNA-26a yang berhubungan dengan resistensi klopidogrel. Walaupun resistensi klopidogrel tidak berhubungan dengan KKM, terdapat hubungan antara faktor genetik polimorfisme *2 dan *3 gen CYP2C19 dengan KKM.

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Acute coronary syndrome (ACS) is a national health problem due to high morbidity and mortality, and cost burden as well. Percutaneous coronary intervention (PCI) and antiplatelet therapy such as clopidogrel are recommended. However, ACS patients could still experience major adverse cardiovascular events (MACE). Clopidogrel resistance possibly plays a role in MACE whereas it may be affected by genetic and epigenetic factors. Therefore, the objective of this study was to determine the relationship between genetic factors which are CYP2C19 and P2Y12 polymorphisms, as well as epigenetic factors which are DNA methylation of CYP2C19 and P2Y12, and miRNA-26a expression and their effects on MACE in post-PCI patients.

To analyze the association between genetic and epigenetic factors and clopidogrel resistance, the study design was cross-sectional, while the study design of relationship between genetic and epigenetic factors and MACE was prospective cohort. The subjects were 201 post-PCI ACS patients who received clopidogrel therapy at Harapan Kita Hospital from September 2018 to June 2020. Clopidogrel resistance was determined by light transmission aggregometry (LTA) if the result was greater than 59% with agonist ADP 20 µM. The detection of CYP2C19 and P2Y12 gene polymorphisms and miRNA-26a expression were carried out by qRT-PCR method, while the DNA methylation of the CYP2C19 and P2Y12 genes were carried out by bisulfite conversion method. Patients were observed for one year and angina pectoris, recurrent acute myocardial infarction (AMI), stroke, or death, were recorded as MACE.

From 201 subjects, 45.8% were CYP2C19*2 and CYP2C19*3 polymorphism mutant carrier, 36.8% were rs3679479 P2Y12 polymorphism mutant carrier, 10% were hypomethylated of P2Y12, 80.1% were hypomethylated of CYP2C19, and 66.2% were up regulated in miRNA-26a expression. 49.8% of subjects were clopidogrel resistant and 14.9% of subjects experienced MACE (death was 7.5%). Smoking (p = 0.001; OR 0.37 [CI 95%; 0.20–0.68]), hypomethylated of CYP2C19 (p = 0.037; OR 2.13 [CI 95%; 1.04–4.37]), and up regulated miRNA-26a expression (p = 0.020; OR 2.03 [CI 95%; 1.12–3.68]) were associated with clopidogrel resistance. Female gender (p = 0.040; HR 2.73 [CI 95%; 1.05–7.14]), age over 60 years old (p = 0.035; HR 2.17 [CI 95%; 1.06–4.48]), low eGFR (p = 0.001; HR 3.29 [CI 95%; 1.59–6.84]), and CYP2C19*2 and CYP2C19*3 polymorphisms (p = 0.047; HR 2.12 [CI 95%; 1.01–4.46]) were associated with MACE in one year.

Only DNA methylation of CYP2C19 and miRNA-26a expression were associated with clopidogrel resistance. Although clopidogrel resistance was not associated with MACE, there was association between CYP2C19*2 and CYP2C19*3 polymorphisms and MACE."

"Kanker merupakan penyebab kematian utama di seluruh dunia. Salah satu faktor terjadinya kanker adalah modifikasi epigenetik yang abnormal (hipermetilasi). Hipermetilasi yang terjadi pada gen diyakini bahwa yang berperan besar dalam proses karsinogenesis adalah enzim DNA metiltransferase (DNMT). Penelitian-penelitian yang dilakukan saat ini untuk menemukan senyawa inhibitor DNMT dari bahan alam. Salah satu metode yang mendukung untuk analisis ini adalah metode in silico. Dalam penelitian ini, diteliti beberapa senyawa pilihan dari basis data herbal Indonesia hasil penapisan virtual terhadap aktivitasnya sebagai inhibitor DNMT. Hasil penambatan molekuler senyawa Cassiamin C, Procyanidin B2, Ent-epicatechin-4alpha-8-ent-epicatechin, Epicatechin-4beta-8-epicatechin-3-O-gallate, Neorhusflavanone, 3-O-galloylepigallocatechin-4beta-6-epicatechin-3-O-gallate, Withanolide, 3-O-galloylepigallocatechin-4beta-6-epigallocatechin-3-O-gallate, Cyanidin-3-6''-caffeylsophoroside-5-glucoside, Epifriedelinol, Gallo-catechin-4alpha-8-epicatechin, Scutellarein-7-glucosyl-1-4-rhamnoside, Epigallo-catechin-3-gallate (EGCG) (kontrol positif), dan sinefungin (kokristal) didapatkan nilai ΔG secara berturut-turut, -9.34, -10.95, -7.95, -11.01, -8.78, -8.87, -11.49, -7.98, -5.92, -8.92, -9.17, -8.76, -9.70, dan -9.11 kkal/mol. Senyawa cassiamin C, procyanidin B2, epicatechin-4beta-8-epicatechin-3-O-gallate, withanolide, dan gallocatechin-4alpha-8-epicatechin memiliki ΔG lebih rendah dari senyawa sinefungin (kokristal) dan EGCG (kontrol positif). Sehingga, tahap selanjutnya akan dilakukan simulasi dinamika molekuler terhadap tujuh ligan tersebut. Hasil simulasi dinamika molekuler menunjukkan aktivitas terbaik secara keseluruhan yaitu pada senyawa procyanidin B2, epicatechin-4beta-8-epicatechin-3-O-gallate, dan gallocatechin-4alpha-8-epicatechin. Residu asam amino yang penting bagi aktivitas inhibitor DNMT1 adalah Phe1145, Glu1168, Met1169, Cys1191, Glu1266, Ala1579, dan Val1580.

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Cancer is the leading cause of death worldwide. Factors of cancer is an abnormal epigenetic modifications (hypermethylation). Hypermethylation that occur in genes believed that played a major role in process of carcinogenesis is DNA methyltransferase (DNMT) enzyme. Recent studies is conducted to find DNMT inhibitor compounds from natural materials. Method that support for this analysis is in silico studies. In this study, several selected compounds from herbal database Indonesia results of virtual screening will be studying for the activity as an inhibitor DNMT. Results molecular docking of Cassiamin C, Procyanidin B2, Epicatechin-4alphaent-8-ent-epicatechin, Epicatechin-4beta-8-epicatechin-3-O-gallate, Neorhusflavanone, 3-O-galloylepigallocatechin-4beta-6-epicatechin-3-O-gallate, Withanolide, 3-O-galloylepigallocatechin-4beta-6-epigallocatechin-3-O-gallate, Cyanidin-3-6''-caffeylsophoroside-5-glucoside, Epifriedelinol, Gallocatechin-4alpha-8-epicatechin, Scutellarein-7-glucosyl-1-4-rhamnoside, Epigallocatechin-3-gallate (EGCG) (positive control), and Sinefungin (co-crystal) compounds, ΔG values obtained -9.34, -10.95, -7.95, -11.01, -8.78, -8.87, -11.49, -7.98, -5.92, -8.92, -9.17, -8.76, -9.70, and -9.11 kcal/mol, respectively. Cassiamin C, Procyanidin B2, Epicatechin-4beta-8-epicatechin-3-O-gallate, Withanolide, and Gallocatechin-4alpha-8-epicatechin compounds had lower ΔG than Sinefungin (co-crystal) and EGCG (positive control) compounds. Therefore, molecular dynamic simulation of seven selected compounds will be performed. The results of molecular dynamic simulation shows the best overall activity is Procyanidin B2, Epicatechin-4beta-8-epicatechin-3-O-gallate, and Gallocatechin-4alpha-8-epi-catechin compounds. Amino acid residues which are important for the activity of DNMT1 inhibitor is Phe1145, Glu1168, Met1169, Cys1191, Glu1266, Ala1579, and Val1580."

"ABSTRAKKanker payudara merupakan jenis kanker dengan prevalensi yang tinggi di dunia yang umumnya terjadi pada wanita. Kanker payudara memiliki angka tertinggi yang mencapai hingga 40 per 100.000 kasus setiap tahunnya, dan sebnayak 12,9 diantaranya dapat menyebabkan kematian. Perubahan epigenetik berperan penting dalam proses pembentukan dan penyebaran sel kanker. Metilasi DNA merupakan salah satu jenis dari perubahan epigenetik yang sering terjadi yang dapat memicu terjadinya pertumbuhan sel kanker. Metilasi DNA dikatalisis oleh enzim DNA Metiltransferase 1 DNTM1 yang dapat memindahkan gugus metil dari S-adenosil metionin SAM ke sitosin pada dinukleotida CpG. Pada penelitian ini, dilakukan penapisan virtual senyawa bahan alam sebagai inhibitor enzim DNMT1. Penapisan dilakukan terhadap 26.731 senyawa bahan alam yang diperoleh dari NCBI Pubchem databsase. Simulasi penambatan molekul dilakukan dengan menggunakan Molecular Operating Environment MOE 2014.09 untuk mendapatkan 10 ligan terbaik berdasarkan interaksi kompleks ligan-enzim dan energi bebas Gibbs. Karakteristik farmakologi meliputi sifat fsikokimia, toksisitas, karsinogenisitas-mutagenisitas serta bioaktivitas menggunakan online software maupun offline software. Uji farmakologi dilakukan untuk mengetahui karakteristik fisikokimia, toksisitas, karsinogenisitas-mutagenisitas dan bioaktivitas menggunakan software DataWarrior 4.7.2., Toxtree, Molinspiration, admetSAR dan SWISSADME. Hasil dari penelitian ini ialah terdapat 3 ligan terbaik yang berasal dari kelompok senyawa bahan alam fenolik yang terpilih berdasarkan karakteristik farmakologi yang dapat dijadikan sebagai kandidat obat untuk terapi kanker payudara.

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ABSTRACTBreast cancer is the most prevalent cancer in woman worldwide. It has the highest number of new cases which amounted to 40 per 100,000 cases per year, 12,9 of which leads to death. Epigenetic alteration plays a vital role in the process of cancer cell formation and propagation. DNA methylation is one of the most common types of epigenetic alteration which generally leads to breast cancer DNA Methylation, a transfer the methyl group from S adenosyl methionin SAM to cytosine in the CpG dinucleotide, is catalyzed by DNMT1 enzyme. In the present study, we performed a virtual screening of natural product compounds as an inhibitors of DNMT1 enzyme. Virtual screening was conducted on 26,731 natural products obtained from the NCBI PubChem database. Three steps of rigid and one step of flexible molecular docking simulations were performed using MOE 2014.09. Through the simulations, 10 ligands based on the Gibbs free binding energies Gbinding and the ligand enzyme complex interactions were identified. Pharmacological test was conducted to observe the psychochemical, toxicity, carcinogenicity mutagenicity, and bioactivity properties by employing DataWarrior 4.7.2., Toxtree, Molinspiration, admetSAR and SWISSADME software. The results revealed that three best ligands from phenolic group were selected due to their exceptional pharmacological characteristics as the drug candidate for breast cancer therapy. "