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Aretha Amelia Budiman
Potensi Interaksi Senyawa Propolis dengan Toll Like Receptor 2 sebagai Agen Antiinflamasi dalam Terapi Periodontitis: Studi In Silico = Potential Interaction of Propolis Compounds with Toll Like Receptor 2 as an Anti-Inflammatory Agent in Periodontitis Therapy: In Silico Study
"Pendahuluan: Prevalensi periodontitis di Indonesia mencapai 74,1% berdasarkan data Riskesdas tahun 2018. Bakteri penyakit periodontitis dapat menembus lebih dalam ke jaringan sekitar gigi. Hal ini dapat memicu respons host dalam upaya bertahan melawan bakteri yang menyerang, salah satunya adalah respon dari TLR-2. Salah satu obat yang memiliki kandungan antiinflamasi dan saat ini sedang banyak diperhatikan oleh masyarakat adalah propolis. Tujuan: Meneliti interaksi dan afinitas antara senyawa pada propolis dengan reseptor Toll-Like Receptor 2 melalui studi penambatan molekuler. Metode: Studi in silico dengan penambatan molekuler untuk menguji interaksi molekuler dari ligan bahan aktif propolis terhadap reseptor TLR-2. Hasil interaksi yang didapat akan dianalisis dan diintrepretasikan untuk mengetahui afinitas ikatan dari interaksi antara ligan dengan reseptor. Hasil: terdapat interaksi antara ligan bahan aktif propolis terhadap reseptor TLR-2. Kesimpulan: Propolis berpotensi menjadi agen antibakteri pada terapi periodontitis yang dapat menghambat inflamasi melalui inaktivasi TLR-2. Namun, perlu dilakukan penelitian lebih lanjut secara in vitro untuk pengamatan lebih lanjut terkait interaksi yang terjadi.
Background: The prevalence of periodontitis in Indonesia reached 74.1%. (Riskesdas, 2018). Periodontitis bacteria can penetrate deep into the gum. This can trigger a host response in an effort to defend against invading bacteria, including responses from TLR-2. Propolis has been shown to have antiinflammatory properties and is currently getting a lot of attention from the public. Purpose: To examine the interaction and affinity between compounds in propolis and the Toll-Like Receptor 2 receptor through molecular docking studies. Methods: To investigate the molecular interactions of propolis active ingredient ligands on the TLR-2 receptor, a molecular docking was conducted. The interaction results obtained will be analyzed and interpreted to determine the binding affinity of the interaction between the ligand and the receptor. Results: There is an interaction between the ligand of the active ingredient of propolis and the TLR-2 receptor. Conclusions: Propolis has the potential to be an antibacterial agent in periodontitis therapy that can inhibit inflammation through inactivation of TLR-2. However, further research needs to be carried out with in vitro studies to further observe the interactions that may occur."
Jakarta: Fakultas Kedokteran Gigi Universitas Indonesia, 2023
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UI - Skripsi Membership  Universitas Indonesia Library
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Nadia Arum Ramadhani
Studi Interaksi Molekuler Senyawa Propolis Sebagai Potensi Antiinflamasi Terhadap Toll-Like Receptor 4 Pada Terapi Periodontitis Secara In Silico = Molecular Interaction of Propolis Compounds as Potential Anti-inflammatory Against Toll-Like Receptor 4 in Periodontitis Therapy: In Silico Study
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Latar Belakang: Menurut data Riset Kesehatan Dasar (Riskesdas) 2018, prevalensi penyakit periodontitis menduduki peringkat kedua terbanyak setelah karies gigi, yaitu sebesar 74,1% di Indonesia. Periodontitis merupakan penyakit inflamasi yang dihubungkan dengan kerusakan jaringan periodontal. Dalam perjalanan periodontitis, TLR-4 berperan penting dalam respon imun dan patogenesis inflamasi periodontitis karena dapat mengenali bakteri gram negatif lipopolisakarida (LPS). Propolis merupakan salah satu zat alami berupa produk resin yang memiliki banyak aktivitas biologis, salah satunya antiinflamasi. Tujuan: Mengetahui interaksi molekuler senyawa propolis yang berpotensi sebagai antiinflamasi terhadap TLR-4 pada terapi periodontitis melalui studi penambatan molekuler. Metode: Studi eksperimental komputasional secara in silico menggunakan perangkat Autodock Tools 1.5.6 dan BIOVIA Discovery Studio Visualizer 2021 untuk menguji interaksi dan afinitas ikatan dari ligan propolis terhadap reseptor target TLR-4. Hasil interaksi akan dianalisis untuk menilai konformasi terbaik dari suatu molekul dan afinitas pengikatannya. Penambatan molekuler dilakukan dengan menambatkan 7 senyawa propolis yang berpotensi sebagai antiinflamasi terhadap TLR-4 sebagai reseptor yang berperan dalam proses inflamasi. Hasil: Terdapat interaksi molekuler ikatan antara ligan propolis dengan reseptor TLR-4. Dari ketujuh ligan propolis yang diuji, senyawa Adhyperforin memiliki afinitas terbaik dibandingkan ligan propolis lainnya. Kesimpulan: Senyawa bioaktif pada propolis dapat berinteraksi terhadap reseptor TLR-4 melalui uji penambatan molekuler dan dapat berpotensi menjadi agen antiinflamasi terhadap TLR-4 yang dapat digunakan sebagai kandidat obat untuk terapi periodontitis. Namun, perlu dilakukan penelitian lebih lanjut untuk membuktikan sifat senyawa bioaktif pada propolis yang dapat bertindak sebagai agen antiinflamasi yang baik untuk terapi periodontitis.

Background: According to 2018 Basic Health Survey (Riskesdas) data, periodontitis is the second most frequent condition after dental caries, which reached a prevalence of 74.1% in Indonesia. Periodontitis is an inflammatory condition associated with the destruction of periodontal tissue. TLR-4, which recognizes gram-negative bacterial lipopolysaccharides (LPS), plays a crucial role in the immune response and inflammatory pathogenesis of periodontitis. Propolis is a natural product in the form of resin that has many biological activities, one of which is anti-inflammatory. Purpose: To investigate the molecular interactions of propolis compounds that have anti-inflammatory potential against TLR-4 in periodontitis therapy through molecular docking studies. Methods: In silico computational experimental study using Autodock Tools 1.5.6 and BIOVIA Discovery Studio Visualizer 2021 to test the interaction and binding affinity of propolis ligands towards the TLR-4 target receptor. The interaction results will be analyzed to assess the best conformation of a molecule and its binding affinity. Molecular docking was performed by targeting 7 propolis compounds that have anti-inflammatory potential against TLR-4 as a receptor that plays a role in the inflammatory process. Results: There is a binding interaction between propolis ligands and TLR-4 receptor. Of the seven propolis ligands tested, the compound Adhyperforin had the best affinity compared to other propolis ligand. Conclusions: Bioactive compounds in propolis can interact with TLR-4 receptors through molecular docking tests and can potentially become anti-inflammatory agents against TLR-4 that can be used as drug candidates for periodontitis therapy. However, further research is needed to prove the nature of bioactive compounds in propolis that can act as good anti-inflammatory agents for periodontitis therapy.

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Jakarta: Fakultas Kedokteran Gigi Universitas Indonesia, 2023
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UI - Skripsi Membership  Universitas Indonesia Library
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Karina Kalisa
Distribusi Polimorfisme Gen Toll-Like Receptor 2 (TLR2) pada Cheilitis Angularis = Distribution of Toll-Like Receptor 2 (TLR2) Gene Polymorphism in Angular Cheilitis
"ABSTRAK
Latar Belakang: Cheilitis angularis adalah penyakit inflamasi yang dipicu oleh faktor genetik, lingkungan dan agen infektif. Gen Toll Like Receptor 2 (TLR2) merupakan komponen penting dalam respon imun innate. Tujuan: Penelitian ini bertujuan untuk menganalisis distribusi polimorfisme gen Toll Like Receptor 2 (TLR2) pada cheilitis angularis dan non cheilitis angularis. Metode: 50 sampel cheilitis angularis dan 50 sampel non cheilitis angularis digunakan dalam penelitian ini. Campuran TLR2 16934 T/A dengan ddH2O, enzim polimerase dan DNA template dianalisis menggunakan teknik PCR RFLP, yang menggunakan HphI sebagai enzim restriksi, dilanjutkan dengan elektroforesis. Hasil: Genotip terbanyak yang ditemukan pada cheilitis angularis dan non cheilitis angularis adalah genotip TT. Jumlah genotip dan alel polimorfik paling banyak ditemukan pada cheilitis angularis (22% dan 13%) dibandingkan non-cheilitis angularis (12% dan 6%). Uji Continuity Correction menunjukkan tidak terdapat perbedaan bermakna antara cheilitis angularis dan non-cheilitis angularis. Kesimpulan: Terdapat hubungan antara polimorfisme gen TLR2-16934 T/A dan cheilitis angularis.
ABSTRACT
Background: Angular cheilitis is an inflammatory disease induced by genetic, environmental and infective agent factors. Toll Like Receptor 2 (TLR2) gene is essential components for innate immunity response. Objective: This study aimed to analyzed distribution of Toll Like Receptor 2 (TLR2) gene polymorphism in angular cheilitis and non angular cheilitis. Methods: 50 samples angular cheilitis as case group and 50 samples non angular cheilitis as control group were used in this research. TLR2-16934 T/A mixed with ddH2O, polymerase enzyme and DNA template were analyzed using PCR RFLP technique, which used HphI as restriction enzyme, then followed by electrophoresis. Subsequently assessed with statistical analysis using Continuity Corrections test. Results: The most genotype found in angular cheilitis and non angular cheilitis was TT genotype. The amount of polymorphic genotype and allele were recorded greater in angular cheilitis (22% and 13%) than non-angular cheilitis (12% and 6%). Continuity Corrections test showed no significant differences between angular cheilitis and non ngular cheilitis (p-value=0,287). Conclusion: There is an association between TLR2-16934 T/A gene polymorphism and angular cheilitis."
Jakarta: Fakultas Kedokteran Gigi Universitas Indonesia, 2019
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UI - Skripsi Membership  Universitas Indonesia Library
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Novrina Ariij Aisyti
Studi Komparatif dan Permodelan In Silico Senyawa Propolis Tetragonula biroi aff. Sulawesi sebagai Inhibitor ALK, HER2, dan BTK dalam Target Terapi Kanker = Comparative Study and In Silico Modelling of Sulawesi Tetragonula biroi aff. Propolis Compounds as ALK, HER2, and BTK Inhibitors in Cancer Targeted Therapy
"Salah satu perkembangan menarik dalam pengobatan kanker adalah target terapi kanker, yaitu pemberian obat yang ditargetkan secara molekuler untuk menginhibisi protein onkogenik tirosin kinase. Tirosin kinase adalah enzim kinase yang berperan dalam proses seluler seperti pertumbuhan, diferensiasi, migrasi, dan apoptosis sebuah sel. Mutasi atau ekspresi berlebih dari tirosin kinase dapat mengakibatkan perubahan fungsi seluler tirosin kinase yang memicu pembentukan sel tumor dan kanker, sehingga inhibisi dari protein tersebut dapat memperlambat proliferasi dan angiogenesis dari sel kanker. Pada penelitian ini, permodelan secara in silico digunakan untuk mengetahui aktivitas inhibisi senyawa propolis yang berasal dari lebah tak bersengat Tetragonula biroi aff. Indonesia pada target protein tirosin kinase penyebab non-small cell lung cancer (NSCLC), kanker payudara, dan leukemia myeloid. 18 senyawa uji propolis yang memiliki potensi antikanker diujikan sebagai inhibitor untuk menghambat aktivitas protein Anaplastic Lymphoma Kinase (ALK), Human Epidermal Growth Factor Receptor 2 (HER2), dan Brutons Tyrosine Kinase (BTK) penyebab NSCLC, kanker payudara, dan leukemia myeloid secara berturut-turut. Penambatan dikomputasikan menggunakan AutoDock Vina®, dengan LigPlot+ dan PyMOL untuk memvisualisasikan interaksi molekuler antara kompleks inhibitor-protein yang dihasilkan. Hasil menunjukkan bahwa kurarinon adalah inhibitor yang paling kuat terhadap ALK dengan skor -8,8 kkal/mol, yang berinteraksi dengan Met1199 sebagai residu utama untuk menghambat ALK. Sementara itu macarangin memiliki skor penambatan tertinggi untuk target HER2 dengan nilai sebesar -11,3 kkal/mol, dan Derrubone sebagai inhibitor paling kuat untuk BTK dengan skor -9,4 kkal/mol. Maka dari itu, studi ini menunjukkan bahwa kurarinon berpotensi untuk menjadi inhibitor ALK, dengan macarangin berpotensi sebagai inhibitor HER2, dan derrubone berpotensi untuk menjadi inhibitor BTK sehingga ketiga senyawa tersebut dapat diteliti dan dievaluasi lebih lanjut untuk studi in-vitro dan in-vivo sebagai novel inhibitor ALK, HER2, dan BTK.

 

One of the interesting developments in cancer treatment is the use of cancer targeted therapy, a molecular targeted drugs that are given to inhibit the oncogenic protein of tyrosine kinases. The tyrosine kinases is a group of kinase enzyme that plays a role in cellular processes such as cell growth, differentiation, migration, and apoptosis. Mutation or overexpression of tyrosine kinases can result in disruption of tyrosine kinase cellular function which triggers the formation of tumor and cancerous cells, where the inhibition of these proteins can slow down the proliferation and angiogenesis of cancer cells. In this study, in-silico modeling was used to determine the inhibitory activity of propolis compounds derived from Indonesian Tetragonula biroi aff. targeting tyrosine kinase protein that causes non-small cell lung cancer (NSCLC), breast cancer, and myeloid leukemia. 18 propolis compounds that have anticancer potential are tested as inhibitors to block the activity of Anaplastic Lymphoma Kinase (ALK), Human Epidermal Growth Factor Receptor 2 (HER2), and Bruton's Tyrosine Kinase (BTK) protein that causes NSCLC, breast cancer, and myeloid leukemia respectively. Docking was computed using AutoDock Vina®, with LigPlot+ and PyMOL to visualize molecular interactions between the resulting inhibitor-protein complex. The result show that kurarinone is the most potent inhibitor towards ALK with a score -8,8 kcal/mol, interacting with Met1199 as a key residues for inhibiting ALK. Meanwhile macarangin has the highest docking score for HER2 target resulting in -11,3 kcal/mol, and derrubone as the most potent inhibitor for BTK with a score of -9,4 kcal/mol. This study suggest that kurarinone has the potential as ALK inhibitor, with macarangin has the potential to inhibit HER2, and derrubone has the potential as BTK inhibitor so that the three compounds can be further investigated and evaluated for in-vitro and in-vivo studies as novel ALK, HER2, and BTK inhibitors.

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Depok: Fakultas Teknik Universitas Indonesia, 2020
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UI - Skripsi Membership  Universitas Indonesia Library
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Lia Kusuma Dewi
Pemodelan In silico Senyawa dalam Propolis Tetragonula sapiens yang Berpotensi sebagai Inhibitor Protease Utama dan Protein Spike SARS-CoV-2 = In silico Modelling of Tetragonula sapiens Propolis Compounds Potential as an Inhibitor of SARS-CoV-2 Main Protease and Spike Protein
"COVID-19 yang disebabkan oleh SARS-CoV-2 telah menjadi isu global dan menimbulkan kasus infeksi dan korban jiwa diseluruh dunia. Penemuan obat sangat diperlukan untuk menghambat infeksi virus dan dampak yang ditimbulkannya. Namun, penelitian dan pengembangan molekul obat baru membutuhkan waktu yang sangat lama dan memakan biaya yang sangat besar.  Studi in silico merupakan salah satu alternatif solusi untuk mengatasi permasalahan tersebut. Dalam penelitian ini, uji in silico dilakukan untuk menentukan interaksi antara senyawa propolis dengan protease utama serta protein spike SARS-CoV-2 sebagai protein target. Protease utama berperan dalam replikasi virus sementara protein spike berperan penting dalam proses invasi virus ke dalam sel.  Kedua protein ini dijadikan target pengembangan obat dengan mencari inhibitor keduanya melalui proses penambatan molekuler terhadap 20 senyawa bioaktif propolis yang berasal dari lebah tanpa sengat Tetragonula sapiens. Senyawa propolis yang digunakan yaitu senyawa yang memenuhi aturan Lipinski’s Rule of Five. Adapun piranti lunak utama yang digunakan dalam metode penambatan molekuler pada penelitian ini yaitu AutoDock Vina. Hasil simulasi penambatan molekuler menunjukkan senyawa propolis yang berpotensi menghambat aktivitas protease utama adalah Sulabiroins A, Broussoflavonol F dan (2S)-5,7-dihydroxy-4'-methoxy-8-prenylflavanone dengan nilai penambatan masing-masing sebesar -8.1, -7.9, dan -7.9 kcal/mol. Sementara itu, Broussoflavonol F dan Glyasperin A merupakan senyawa propolis yang menunjukkan aktivitas inhibis terkuat terhadap protein spike SARS-CoV-2 dengan energi ikatan masing-masing sebesar -7.6 dan -7.3 kcal/mol. Senyawa-senyawa propolis tersebut juga terbukti dapat berikatan dengan asam amino kunci pada sisi aktif protein target sehingga berpotensi untuk dikembangkan lebih lanjut sebagai kandidat obat COVID-19.
COVID-19 caused by SARS-CoV-2 is a global health issue and resulting in morbidity and mortality across the world. There is an urgent need to find the treatments to inhibit the virus infections and its consequences. However, research and development of new drug molecules takes years and is very expensive. In silico research is an alternative solution to overcome these problems. Here we conducted in silico study to examine the interaction between propolis compounds with SARS-CoV-2 main protease and spike protein as target proteins. Main protease is responsible for the virus replication while spike protein mediates viral entry. Their important roles makes it an interesting target for developing SARS-CoV-2 potential drugs by developing the inhibitor using molecular docking toward 20 propolis active compounds from Tetragonula sapiens. Those propolis compounds then selected based on Lipinski’s Rule of Five (Lipinski’s RO5). The main software that used to conduct molecular docking in this research are AutoDock Vina. Docking results showed that propolis compound which has the high potential to inhibit SARS-CoV-2 main protease activity was Sulabiroins A, following by broussoflavonol F and (2S)-5,7-dihydroxy-4'-methoxy-8-prenylflavanone with docking score -8.1, -7.9, dan -7.9 kcal/mol, respectively. Broussoflavonol F and Glyasperin A were the most promising compounds that showed inhibition activity towards SARS-CoV-2 spike protein with binding affinity  -7.6 dan -7.3 kcal/mol. Those compounds were able to bind with the key residu on the active site of the target protein so that they could be potential to be further developed as COVID-19 drug candidates."
Depok: Fakultas Teknik Universitas Indonesia, 2022
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UI - Tesis Membership  Universitas Indonesia Library
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Rafidha Irdiani
Studi in silico interaksi molekuler antara propolis tetragonula aff. biroi dengan target protein penyebab covid-19 = Molecular interaction in silico study between tetragonula aff. biroi propolis and covid-19 therapeutic protein targets
"Coronavirus disease 2019 (Covid-19) merupakan penyakit saluran pernapasan yang disebabkan oleh virus severe acute respiratory syndrome 2 (SARS-CoV-2). Saat ini, Covid-19 menjadi masalah kesehatan global dan ditetapkan sebagai pandemic pada Maret 2020. Kompleksitas dan mutasi ssRNA virus yang sangat cepat menyebabkan dibutuhkan waktu lama untuk menghasilkan vaksin yang efektif. Sementara itu, angka kematian yang terus meningkat mengiringi peningkatan angka kasus setiap harinya membuat tingginya urgensi penemuan obat. Terdapat dua target pengobatan Covid-19 yang menjanjikan, yaitu protease SARS-CoV-2 dan ACE-2. Penelitian ini bertujuan untuk mengetahui potensi propolis Tetragonula aff. biroi sebagai obat Covid-19 melalui studi in silico. Dalam penelitian ini, penambatan molekuler antara senyawa propolis dengan masing-masing protease SARS-CoV-2 dan ACE-2 dilakukan. Melalui penelitian ini, dapat disimpulkan bahwa senyawa yang berpotensi menghambat aktivitas protease SARSCoV-2 adalah glyasperin A dan broussoflavonol F, dengan docking score -7,8 kcal/mol dan dengan persentase kemiripan profil interaksi masing-masing dibandingkan dengan inhibitor 13b sebagai kontrol positif sebesar 63% dan 75%. Sementara itu, senyawa yang berpotensi menghambat aktivitas ACE-2 adalah glyasperin A, broussoflavonol F, dan sulabiroins A dengan docking score secara berurutan -10,8 kcal/mol, -9,9 kcal/mol, dan -9,5 kcal/mol serta persentase kemiripan profil interaksi dibandingkan dengan inhibitor MLN-4760 sebagai kontrol positif secara berurutan sebesar 77%, 23%, dan 38%.
Coronavirus disease 2019 (COVID-19), a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global health concern, as the World Health Organization declared this outbreak to be a global pandemic in March 2020. The need for an effective treatment is urgent because the development of an effective vaccine may take years given the complexity of the virus and its rapid mutation. Two promising treatment targets for COVID-19 are SARS-CoV-2 main protease and ACE-2. Thus, this study examined whether Sulawesi propolis compounds produced by Tetragonula aff. biroi can inhibit the enzymatic activity of both proteins. In this study, molecular docking was performed to analyze the interaction profiles of propolis compounds with SARS-CoV-2 main protease and ACE-2 severally. Based on the research, two compounds, namely glyasperin A and broussoflavonol F, are potential inhibitor for SARS-CoV-2 protease with docking score -7.8 kcal/mol and binding similarities compared to inhibitor 13b as positive control 63% and 75% respectively. Furthermore, glyasperin A, broussoflavonol F and sulabiroins A are also considered as potential inhibitors for ACE-2 with docking score -10.8 kcal/mol, -9.9 kcal/mol and -9.5 kcal/mol respectively, and binding similarity compared to inhibitor MLN-4760 as positive control 77%, 23% and 38% respectively."
Depok: Fakultas Teknik Universitas Indonesia, 2020
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UI - Skripsi Membership  Universitas Indonesia Library
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Andhika Alwan Rasyhad
Studi In Silico senyawa syzygium aromaticum sebagai inhibitor SGLT2 untuk terapi diabetes melitus tipe 2 = In Silico study of syzygium aromaticum compounds as SGLT2 inhibitor for type 2 diabetes melitus therapy
"Latar Belakang
Diabetes Melitus (DM) merupakan penyebab kematian terbesar ke-3 di Indonesia. Terdapat berbagai opsi pengobatan diabetes Melitus, salah satunya golongan inhibitor SGLT2. Bunga cengkeh atau Syzygium aromaticum sebagai spesies tumbuhan yang umum digunakan sebagai obat herbal, memiliki senyawa dengan aktivitas down regulation SGLT dan GLUT2. Penelitian ini bertujuan untuk mengetahui efek antidiabetes senyawa Syzygium aromaticum dengan aktivitas inhibitor SGLT2 secara in silico menggunakan prediksi nilai IC50 dan molecular docking.
Metode
Penelitian analitik observasional in silico menggunakan metode prediksi nilai IC50 dengan perangkat lunak DataWarrior dan molecular docking dengan perangkat lunak Molegro Virtual Docker (MVD).
Hasil
Senyawa yang terdapat dalam Syzygium aromaticum memiliki aktivitas inhibitor SGLT2 melalui prediksi nilai IC50. Tiga senyawa yang dipilih karena memiliki potensi inhibitor SGLT2 adalah Astilbin, HPEA, dan Strictinin (IC50: 3,2 μM; 31,189 μM; 0,315 μM) Ketiga senyawa memiliki nilai IC50 dengan kategori excellent, good, dan moderate activity serta nilai LELP mendekati 6. Validasi molecular docking dengan protein SGLT2 (7VSI) menunjukkan ketiga senyawa Rerank Score negatif, mengindikasikan ikatan yang spotan dan kuat. Selain itu, Strictinin memiliki nilai Rerank Score positif terhadap protein SGLT1, mengindikasikan selektivitas yang rendah terhadap protein tersebut.
Kesimpulan
Terdapat aktivitas inhibitor SGLT2 pada senyawa Syzygium aromaticum untuk senyawa Astilbin, HPEA, dan Strictinin. Senyawa tersebut memiliki selektivitas tinggi terhadap protein SGLT2. Strictinin memiliki selektivitas rendah terhadap protein SGLT1, sehingga berpotensi untuk terapi antidiabetes dengan efek samping minimal.
Introduction
Diabetes Melitus (DM) is the third leading cause of death in Indonesia. There are various treatment options for diabetes Melitus, one of which is the SGLT2 inhibitor class. Clove flower or Syzygium aromaticum is a plant species commonly used as an herbal medicine, contains compounds that exhibit downregulation of SGLT and GLUT2. This study aims to investigate the antidiabetic effects of compounds in Syzygium aromaticum with SGLT2 inhibitory activity in silico using IC50 prediction and molecular docking.
Method
This observational analytic in silico study used the IC50 value prediction method with DataWarrior software and molecular docking with Molegro Virtual Docker (MVD) software.
Results
The compounds found in Syzygium aromaticum exhibited SGLT2 inhibitory activity through IC50 value prediction. Three compounds identified as having SGLT2 inhibitor potential were Astilbin, HPEA, and Strictinin (IC50: 3,2 μM; 31,189 μM; 0,315 μM). These compounds had IC50 values classified as excellent, good, and moderate activity, with LELP values approaching 6. Upon validation of molecular docking with the SGLT2 protein (7VSI), all three compounds showed negative Rerank Scores, indicating strong and spontaneous binding. Additionally, Strictinin exhibited a positive Rerank Score with the SGLT1 protein, indicating low selectivity for that protein.
Conclusion
There is SGLT2 inhibitory activity in compounds from Syzygium aromaticum, specifically in Astilbin, HPEA, and Strictinin. These compounds have high selectivity for the SGLT2 protein. Strictinin shows low selectivity for the SGLT1 protein, making it a potential candidate for antidiabetic therapy with minimal side effects."
Jakarta: Fakultas Kedokteran Universitas Indonesia, 2024
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UI - Skripsi Membership  Universitas Indonesia Library
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Dicky Fakhri
Peran polimorfisme toll like receptor 2 dan toll interacting protein terhadap kejadian sepsis dan respons imun pada anak di bawah 1 tahun yang menjalani operasi jantung terbuka = Role of toll like receptor 2 and toll interacting protein polymorphism in the development of sepsis and immunology response in children less than 1 year old undergoing open heart surgery
"[ABSTRAK
Latar Belakang: Pada anak dengan penyakit jantung bawaan (PJB) yang
menjalani operasi jantung terbuka, sepsis merupakan salah satu komplikasi
pascaoperasi. Lama prosedur pintas jantung paru, usia, status gizi, timektomi, dan
variasi genetik, seperti polimorfisme toll-like receptor (TLR) 2 dan tollinteracting
protein (TOLLIP) dapat memengaruhi respons imun. Informasi
mengenai peran faktor tersebut terhadap kejadian sepsis dan respons imun
pascaoperasi jantung terbuka masih terbatas.
Tujuan: Mengetahui peran polimorfisme TLR2, TOLLIP, dan faktor lainnya
terhadap kejadian sepsis dan respons imun pascaoperasi jantung terbuka untuk
memperoleh strategi paling tepat dalam penanganan kasus bedah jantung pada
anak.
Metodologi: Studi longitudinal dengan non-probability consecutive sampling
dilakukan pada anak <1 tahun yang menjalani operasi jantung terbuka.
Pemeriksaan polimorfisme TLR2 Arg677Trp, TLR2 N199N, TOLLIP rs5743867,
sel CD4 dan CD8 yang menyekresikan IFN-γ intraselular, sel Dendritik yang
mengekspresikan TLR2, dan sel NK. Pasien menjalani operasi jantung terbuka.
Setelah operasi, pasien dimonitor untuk menilai sepsis dan respons imun
pascaoperasi.
Hasil: Dari 108 subjek yang terlibat, 21,3% diantaranya mengalami sepsis.
Seluruh subjek adalah mutan TLR2 Arg677Trp, 92,6% pasien adalah mutan TLR2
N199N, dan 52,8% pasien adalah mutan TOLLIP rs5743867. Polimorfisme TLR2
N199N dan timektomi total tidak diikutkan dalam model analisis multivariat.
Polimorfisme TOLLIP rs5743867 (p = 0,358) menurunkan resiko sepsis, lama
prosedur pintas jantung paru ≥90 menit (p = 0,002), usia neonatus (p = 0,032), dan
gizi buruk (p = 0,558) meningkatkan risiko sepsis pascaoperasi. Jumlah respons
imun bervariasi antara kategori, namun secara umum komponen respons imun
lebih rendah pada pasien yang mengalami sepsis dibanding pada pasien yang tidak
mengalami sepsis.
Simpulan: Lama prosedur pintas jantung paru dan usia neonatus secara signifikan
memengaruhi risiko dan kecepatan sepsis pascaoperasi. Peran polimorfisme TLR2
N199N dan TOLLIP rs5743867 terhadap kejadian sepsis dan respons imun
pascaoperasi memerlukan studi komprehensif lebih lanjut.
ABSTRACT
Background: Sepsis is one of the complications in children with congenital heart
defect who underwent open heart surgery. Cardiopulmonary bypass (CPB) time,
age, nutritional status, thymectomy, and genetic variants, such as toll-like receptor
(TLR) 2 and toll-interacting protein (TOLLIP) polymorphism affect immune
response. Information regarding those factors in the development of sepsis and
immune response after open heart surgery is still limited.
Objectives: To understand the role of TLR 2 and TOLLIP polymorphism, as well
as other risk factors, in the development of sepsis and immune response following
open heart surgery to develop the best strategy in open heart surgery in children.
Methods: Longitudinal study with consecutive sampling were done in children <1
year old who underwent open heart surgery. Blood sample was obtained to check
for TLR2 Arg677Trp polymorphism, TLR2 N199N polymorphism, TOLLIP
rs5743867 polymorphism, the numbers of intracellular interferon γ CD4 and CD8,
TLR2 expression in Dendritic cells, and NK cells. Patient then underwent open
heart surgery. Thymectomy was done as indicated and CPB time was recorded.
After surgery, patient was monitored for signs of sepsis and immune response was
checked.
Results: Out of 108 patients involved in this study, 21.3% developed
postoperative sepsis. TLR2 Arg677Trp polymorphism was found in all patients,
TLR2 N199N polymorphism was found in 92.6% of the patients, and TOLLIP
rs5743867 polymorphism was found in 52.8% of the patients. TLR2 N199N
polymorphism and thymectomy were not included in multivariate analysis.
TOLLIP rs5743867 polymorphism (p = 0.358) reduced the risk of sepsis, CPB
time ≥90 menit (p = 0.002), neonates (p = 0.032), and severe malnutrition (p =
0.558) increased the risk of postoperative sepsis. Immune response?s counts vary
in each category, but were generally lower in patients who developed
postoperative sepsis.
Conclusion: Cardiopulmonary bypass time and neonates significantly influenced
the risk and hazard of postoperative sepsis. Further investigation on the role of
TLR2 N199N and TOLLIP rs5743867 polymorphism are necessary to provide
more comprehensive explanation on the development of postoperative sepsis and
the immune response after open heart surgery;Background: Sepsis is one of the complications in children with congenital heart
defect who underwent open heart surgery. Cardiopulmonary bypass (CPB) time,
age, nutritional status, thymectomy, and genetic variants, such as toll-like receptor
(TLR) 2 and toll-interacting protein (TOLLIP) polymorphism affect immune
response. Information regarding those factors in the development of sepsis and
immune response after open heart surgery is still limited.
Objectives: To understand the role of TLR 2 and TOLLIP polymorphism, as well
as other risk factors, in the development of sepsis and immune response following
open heart surgery to develop the best strategy in open heart surgery in children.
Methods: Longitudinal study with consecutive sampling were done in children <1
year old who underwent open heart surgery. Blood sample was obtained to check
for TLR2 Arg677Trp polymorphism, TLR2 N199N polymorphism, TOLLIP
rs5743867 polymorphism, the numbers of intracellular interferon γ CD4 and CD8,
TLR2 expression in Dendritic cells, and NK cells. Patient then underwent open
heart surgery. Thymectomy was done as indicated and CPB time was recorded.
After surgery, patient was monitored for signs of sepsis and immune response was
checked.
Results: Out of 108 patients involved in this study, 21.3% developed
postoperative sepsis. TLR2 Arg677Trp polymorphism was found in all patients,
TLR2 N199N polymorphism was found in 92.6% of the patients, and TOLLIP
rs5743867 polymorphism was found in 52.8% of the patients. TLR2 N199N
polymorphism and thymectomy were not included in multivariate analysis.
TOLLIP rs5743867 polymorphism (p = 0.358) reduced the risk of sepsis, CPB
time ≥90 menit (p = 0.002), neonates (p = 0.032), and severe malnutrition (p =
0.558) increased the risk of postoperative sepsis. Immune response?s counts vary
in each category, but were generally lower in patients who developed
postoperative sepsis.
Conclusion: Cardiopulmonary bypass time and neonates significantly influenced
the risk and hazard of postoperative sepsis. Further investigation on the role of
TLR2 N199N and TOLLIP rs5743867 polymorphism are necessary to provide
more comprehensive explanation on the development of postoperative sepsis and
the immune response after open heart surgery;Background: Sepsis is one of the complications in children with congenital heart
defect who underwent open heart surgery. Cardiopulmonary bypass (CPB) time,
age, nutritional status, thymectomy, and genetic variants, such as toll-like receptor
(TLR) 2 and toll-interacting protein (TOLLIP) polymorphism affect immune
response. Information regarding those factors in the development of sepsis and
immune response after open heart surgery is still limited.
Objectives: To understand the role of TLR 2 and TOLLIP polymorphism, as well
as other risk factors, in the development of sepsis and immune response following
open heart surgery to develop the best strategy in open heart surgery in children.
Methods: Longitudinal study with consecutive sampling were done in children <1
year old who underwent open heart surgery. Blood sample was obtained to check
for TLR2 Arg677Trp polymorphism, TLR2 N199N polymorphism, TOLLIP
rs5743867 polymorphism, the numbers of intracellular interferon γ CD4 and CD8,
TLR2 expression in Dendritic cells, and NK cells. Patient then underwent open
heart surgery. Thymectomy was done as indicated and CPB time was recorded.
After surgery, patient was monitored for signs of sepsis and immune response was
checked.
Results: Out of 108 patients involved in this study, 21.3% developed
postoperative sepsis. TLR2 Arg677Trp polymorphism was found in all patients,
TLR2 N199N polymorphism was found in 92.6% of the patients, and TOLLIP
rs5743867 polymorphism was found in 52.8% of the patients. TLR2 N199N
polymorphism and thymectomy were not included in multivariate analysis.
TOLLIP rs5743867 polymorphism (p = 0.358) reduced the risk of sepsis, CPB
time ≥90 menit (p = 0.002), neonates (p = 0.032), and severe malnutrition (p =
0.558) increased the risk of postoperative sepsis. Immune response?s counts vary
in each category, but were generally lower in patients who developed
postoperative sepsis.
Conclusion: Cardiopulmonary bypass time and neonates significantly influenced
the risk and hazard of postoperative sepsis. Further investigation on the role of
TLR2 N199N and TOLLIP rs5743867 polymorphism are necessary to provide
more comprehensive explanation on the development of postoperative sepsis and
the immune response after open heart surgery;Background: Sepsis is one of the complications in children with congenital heart
defect who underwent open heart surgery. Cardiopulmonary bypass (CPB) time,
age, nutritional status, thymectomy, and genetic variants, such as toll-like receptor
(TLR) 2 and toll-interacting protein (TOLLIP) polymorphism affect immune
response. Information regarding those factors in the development of sepsis and
immune response after open heart surgery is still limited.
Objectives: To understand the role of TLR 2 and TOLLIP polymorphism, as well
as other risk factors, in the development of sepsis and immune response following
open heart surgery to develop the best strategy in open heart surgery in children.
Methods: Longitudinal study with consecutive sampling were done in children <1
year old who underwent open heart surgery. Blood sample was obtained to check
for TLR2 Arg677Trp polymorphism, TLR2 N199N polymorphism, TOLLIP
rs5743867 polymorphism, the numbers of intracellular interferon γ CD4 and CD8,
TLR2 expression in Dendritic cells, and NK cells. Patient then underwent open
heart surgery. Thymectomy was done as indicated and CPB time was recorded.
After surgery, patient was monitored for signs of sepsis and immune response was
checked.
Results: Out of 108 patients involved in this study, 21.3% developed
postoperative sepsis. TLR2 Arg677Trp polymorphism was found in all patients,
TLR2 N199N polymorphism was found in 92.6% of the patients, and TOLLIP
rs5743867 polymorphism was found in 52.8% of the patients. TLR2 N199N
polymorphism and thymectomy were not included in multivariate analysis.
TOLLIP rs5743867 polymorphism (p = 0.358) reduced the risk of sepsis, CPB
time ≥90 menit (p = 0.002), neonates (p = 0.032), and severe malnutrition (p =
0.558) increased the risk of postoperative sepsis. Immune response?s counts vary
in each category, but were generally lower in patients who developed
postoperative sepsis.
Conclusion: Cardiopulmonary bypass time and neonates significantly influenced
the risk and hazard of postoperative sepsis. Further investigation on the role of
TLR2 N199N and TOLLIP rs5743867 polymorphism are necessary to provide
more comprehensive explanation on the development of postoperative sepsis and
the immune response after open heart surgery, Background: Sepsis is one of the complications in children with congenital heart
defect who underwent open heart surgery. Cardiopulmonary bypass (CPB) time,
age, nutritional status, thymectomy, and genetic variants, such as toll-like receptor
(TLR) 2 and toll-interacting protein (TOLLIP) polymorphism affect immune
response. Information regarding those factors in the development of sepsis and
immune response after open heart surgery is still limited.
Objectives: To understand the role of TLR 2 and TOLLIP polymorphism, as well
as other risk factors, in the development of sepsis and immune response following
open heart surgery to develop the best strategy in open heart surgery in children.
Methods: Longitudinal study with consecutive sampling were done in children <1
year old who underwent open heart surgery. Blood sample was obtained to check
for TLR2 Arg677Trp polymorphism, TLR2 N199N polymorphism, TOLLIP
rs5743867 polymorphism, the numbers of intracellular interferon γ CD4 and CD8,
TLR2 expression in Dendritic cells, and NK cells. Patient then underwent open
heart surgery. Thymectomy was done as indicated and CPB time was recorded.
After surgery, patient was monitored for signs of sepsis and immune response was
checked.
Results: Out of 108 patients involved in this study, 21.3% developed
postoperative sepsis. TLR2 Arg677Trp polymorphism was found in all patients,
TLR2 N199N polymorphism was found in 92.6% of the patients, and TOLLIP
rs5743867 polymorphism was found in 52.8% of the patients. TLR2 N199N
polymorphism and thymectomy were not included in multivariate analysis.
TOLLIP rs5743867 polymorphism (p = 0.358) reduced the risk of sepsis, CPB
time ≥90 menit (p = 0.002), neonates (p = 0.032), and severe malnutrition (p =
0.558) increased the risk of postoperative sepsis. Immune response’s counts vary
in each category, but were generally lower in patients who developed
postoperative sepsis.
Conclusion: Cardiopulmonary bypass time and neonates significantly influenced
the risk and hazard of postoperative sepsis. Further investigation on the role of
TLR2 N199N and TOLLIP rs5743867 polymorphism are necessary to provide
more comprehensive explanation on the development of postoperative sepsis and
the immune response after open heart surgery]"
2015
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UI - Disertasi Membership  Universitas Indonesia Library
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Ika Widiawati
Penapisan In Silico Dan Konfirmasi In Vitro Senyawa Bahan Alam Sebagai Modulator Reseptor Progesteron Dalam Perbaikan Reseptivitas Endometrium = In Silico Screening and In Vitro Confirmation of Natural Compounds as Progesterone Receptor Modulators in Improving Endometrial Receptivity
"Kondisi infertilitas yang dialami oleh Wanita memiliki prevalensi yang tinggi. Kegagalan implantasi salah satu penyebab rendahnya keberhasilan IVF sebagai teknologi reproduksi berbantuan. Defek pada reseptivitas endometrium menyebabkan perkembangan kurang adekuat untuk proses implantasi. Progesteron berperan dalam peningkatan reseptivitas endometrium sehingga perlu dilakukan eksplorasi potensi senyawa bahan alam sebagai dasar pengembangan alternatif terapi alternatif infertilitas. Tujuan dari penelitian ini yaitu melakukan penapisan dan evaluasi senyawa bahan alam yang berpotensi sebagai kandidat modulator reseptor progesteron. Metode yang digunakan adalah penapisan virtual berbasis literatur secara sistematis, simulasi penambatan molekuler; analisis prediksi absorbsi, distribusi, metabolism, ekskresi dan toksisitas (ADMET), simulasi dinamika molekuler dan uji ikatan kompetitif reseptor progesteron secara in vitro. Berdasarkan hasil skrinig literatur informasi terkait 12 senyawa yang memiliki kemampuan modulasi reseptor progesteron. Hasil simulasi penambatan molekuler, analisis ADMET dan simulasi dinamika molekuler diperoleh kandidat 6 senyawa potensial dalam hal pengikatan dengan reseptor progesteron pada situs aktif dan stabil dengan reseptor progesteron serta memiliki profil farmakokinetika yang baik. Senyawa tersebut yaitu apigenin, kaempferol, naringenin, baicalein, paeoniflorin dan e-Guggulsterone. Uji konfirmasi ikatan dengan reseptor progesteron manusia secara in vitro menunjukkan senyawa yang memiliki nilai IC50 paling mendekati dengan kontrol progesteron yaitu apigenin (1,10 μM) dan e-guggulsterone (1,35 μM). Selanjutnya yaitu senyawa Baicalein (13,85 μM), Kaempferol (16 μM) dan Naringenin (47,97 μM). Paeoniflorin (0,98 μM) memiliki nilai IC 50 paling rendah dibandingkan dengan senyawa lainnya akan tetapi grafik menunjukkan tidak adanya perubahan nilai polarisasi terhadap perubahan konsentrasi senyawa sehingga data dianggap tidak valid (R= 0,18). Dapat ditarik kesimpulan kandidat senyawa yang berpotensi untuk dikembangkan sebagai fitoprogestin untuk alternatif terapi pada infertilitas melalui reseptor progesteron yaitu apigenin dan e-guggulsterone.
The prevalence of infertility conditions is high in women. Implantation failure is one of the causes of the low success of IVF as an assisted reproductive technology. Defects in endometrial receptivity result in inadequate development for the implantation process. Progesterone plays a role in increasing endometrial receptivity, therefore it is necessary to explore the potential of natural compounds as a basis for developing alternative infertility therapies. The aim of this study is to screen and evaluate natural compounds that potentially to be candidates for progesterone receptor modulators. The methods used are systematic literature screening, molecular docking, absorption, distribution, metabolism, excretion, and toxicity (ADMET) prediction analysis, molecular dynamics simulation, and competitive binding assay of progesterone receptors. Based on the results of the literature screening, information related to 12 compounds that have the ability to modulate progesterone receptors. The results of molecular docking simulations, ADMET analysis, and molecular dynamics simulations obtained six potential candidate compounds in terms of binding to the progesterone receptor in the active site, being stable with the progesterone receptor, and having a good pharmacokinetic profile. These compounds are apigenin, kaempferol, naringenin, baicalein, paeoniflorin and e-guggulsterone. The result of assay in confirming the binding to the human progesterone receptor showed that the compound with an IC50 value closest to the control progesterone was apigenin (1.10 μM) and e-guggulsterone (1.35 μM). The next compounds are Baicalein (13.85 μM), Kaempferol (16 μM) and Naringenin (47.97 μM). Paeoniflorin (0.98 μM) has the lowest IC50 value compared to other compounds, but the graph shows no change in polarization value to changes in compound concentration so that the data is considered invalid (R = 0.18). In conclusion, the candidate compounds which have the potential to be developed as a phytoprogestin for alternative therapy for infinfertility via the progesterone receptor are apigenin and e-guggulsterone."
Depok: Fakultas Farmasi Universitas Indonesia, 2024
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UI - Tesis Membership  Universitas Indonesia Library
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Saras Aulia Rahmiati
Studi interaksi berbagai new psychoactive substances terhadap reseptor cannabinoid-1 secara in silico = In silico interaction study of various new psychoactive substances on cannabinoid-1 receptor
"Zat-zat serupa narkotika dan psikotropika baru yang dikenal sebagai New Psychoactive Substances (NPS) telah berkembang di pasaran dalam beberapa tahun terakhir di dunia Internasional maupun di Indonesia. Telah teridentifikasi sebanyak 27 NPS diantara 74 jenis yang beredar di Indonesia pada tahun 2019 yang merupakan turunan kanabinoid dan sudah diatur dalam Peraturan Menteri Kesehatan No. 50 Tahun 2018. Prediksi terhadap NPS perlu dilakukan dan dapat dilakukan menggunakan metode in silico. Penelitian ini bertujuan memperoleh model interaksi dan afinitas penambatan molekuler dari New Psychoactive Substances (NPS) terhadap reseptor Cannabinoid-1 (CB1) dilakukan secara in silico. Penambatan molekuler dilakukan menggunakan AutoDock melalui program PyRx serta dilakukan visualisasi interaksi hasil penambatan molekuler menggunakan Ligplot dan PyMOL. Parameter optimasi yang didapatkan untuk penambatan molekuler CB1 adalah menggunakan grid box 50x50x50 unit dengan energi evaluasi medium (2.500.000). Golongan NPS yang termasuk pada rentang energi ikatan -9,00 hingga -11,00 kkal/mol adalah kanabinoid (62%), fentanil (70%) dan plant-based substances (50%). Pada rentang -7,00 hingga -9,00 kkal/mol yaitu arilsikloheksilamin (70%). Sedangkan pada rentang -4,00 hingga -7,00 kkal/mol yakni katinon (58%), fenetilamin (84%), piperazin (81%) dan triptamin (64%).
New narcotic and psychotropic substances known as New Psychoactive Substances (NPS) have evolved on the market in recent years both in Indonesia and internationally. As many as 27 NPS have been identified among 74 type in Indonesia in 2019 which are cannabinoid derivatives and have been regulated in Ministry of Health Republic of Indonesia Regulation No. 50 of 2018. Prediction of NPS needs to be done and can be done using the method in silico. This study aims to obtain a model of interaction and molecular binding affinity of the New Psychoactive Substances (NPS) on Cannabinoid-1 (CB1) receptor using in silico method. Molecular docking is done using AutoDock in PyRx program and visualize molecular docking interactions using Ligplot and PyMOL. Optimization parameter obtained for molecular docking of CB1 is using 50x50x50 unit grid box with medium energy evaluation (2.500.000). The NPS group included in the binding energy range of -9.00 to -11.00 kcal/mol are cannabinoids (62%), fentanyl (70%) and plant-based substances (50%). In the range of -7.00 to -9.00 kcal/mol, namely arylcyclohexylamine (70%). Whereas in the range of -4.00 to -7.00 kcal/mol are cathinone (58%), phenethylamine (84%), piperazine (81%) and tryptamine (64%)."
Depok: Fakultas Farmasi Universitas Indonesia, 2020
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UI - Skripsi Membership  Universitas Indonesia Library
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