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Untranslated region-5' and viral protein 1-based genetic stability analysis of bulk polio in Indonesia 2010-2019 Andi Yasmon; Normasari Normasari; Fithriyah Fithriyah; Fadilah Fadilah
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) Vol 53, No 4 (2021)
Publisher : Journal of the Medical Sciences (Berkala Ilmu Kedokteran)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.19106/JMedSci005304202106

Abstract

Cases of vaccine-associated paralytic poliomyelitis (VAPP) continued increasingly from 2010-2019 in the world. Oral polio vaccine (OPV) is the live attenuated virus-based vaccine that could genetically revert to neurovirulent during the vaccine production process or when the virus replicates in the human body. The poliovirus neurovirulence is determined by the UTR-5' region and VP1 coding region. UTR-5' played a role in protein translation and VP1 was responsible for the immunogenicity of the virus. Some reported mutations in UTR-5' and VP1 could affect the neurovirulence of poliovirus. In this study, we analyzed the genetic stability of the UTR-5' and VP1 in the bulk of OPV types -1 and -3 produced in 2010 - 2019. The results of the analysis of UTR-5' sequences in Sabin strain types-1 and -3 and VP1 sequences on Sabin virus type 1 did not show any mutations. Meanwhile, the VP1 sequences in Sabin strain type 3 showed nucleotide mutation C2493U that caused the substitution amino acid Thr6Ile amino acid in all samples of the type 3 bulk polio test. Based on the results of in silico analysis, this mutation in VP1 did not contribute significantly to the neurovirulence of the virus.
Penentuan Aktivitas Gabungan Ekstrak Etanol Pulosari (Alyxia reinwardtii) dan Secang (Sappan Lignum) Sebagai Inhibitor Tirosinase Yang Potensial Untuk Bahan Kosmetik Melalui Pendekatan In Silico dan In Vitro Fadilah Fadilah; Aryo Tedjo; Rudi Heryanto
Jurnal Jamu Indonesia Vol. 1 No. 1 (2016): Jurnal Jamu Indonesia
Publisher : Tropical Biopharmaca Research Center, IPB University

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (974.021 KB) | DOI: 10.29244/jji.v1i1.4

Abstract

Tirosinase atau fenol oksidase adalah enzim utama yang terlibat dalam biosintesis melanin. Untuk menghindari produksi melanin secara berlebihan pada lapisan epidermal, maka dicari senyawa yang mampu menghambat tirosinase sehingga dapat digunakan sebagai bahan pemutih kulit. Inhibitor enzim tirosinase dapat diperoleh dari senyawa bahan alam diantaranya, polifenol, kumarin, stilben sebagai pengganti senyawa sintetik. Tirosinase telah diketahui struktur molekular sehingga dapat diketahui mekanisme kerjanya melaui uji in-silico dan pembuktian secara in-vitro. Penelitian ini digunakan untuk mendeteksi keefektifan gabungan dari ekstrak etanol pulosari (Alyxia reinwardtii) dan secang (Sappan lignum) sebagai inhibitor tirosinase. Dari hasil in-silico pengujian aktivitas inhibisi tirosinase menggunakan software MOE 2008 menunjukkan bahwa dalam ekstrak etanol dari secang yaitu senyawa brazilin dan rhamnitin berturut-turut memiliki nilai ∆G -15.6582 kkal/mol, -13.3378 kkal/mol dengan inhibisi 10.021 μM, 8.331 μM dan Hdon-acc 6, 8. Sedangkan dalam ektrak etanol dari pulosari dengan senyawa scopoletin dan zhebeiresinol berturut-turut memiliki nilai ∆G -12.1661 kkal/mol; -13.8982 kkal/mol dengan inhibisi 7.279 μM; 9.104 μM dan Hdon-acc 5 dan 6. Sedangkan senyawa parameter L-DOPA dan pembanding asam kojat berturut-turut memiliki nilai ∆G -9.8247 kkal/mol; -8.8047 kkal/mol dengan inhibisi 5.592 μM; 4.976 μM dan Hdon-acc 3; 3. Dari pembuktian secara in-vitro menunjukkan bahwa uji aktivitas inhibisi tirosinase berturut-turut dari secang (Sl), pulosari (Ar), gabungan Sl dan Ar dengan pembanding asam kojat memiliki nilai IC50 berturut-turut 797.090 ppm, 1962.934 ppm, 571.352 ppm dan 93.557 ppm. Sehingga dari hasil in-silico dan in-vitro disimpulkan bahwa penggabungan antara pulosari dan secang memiliki tingkat IC50 lebih baik dibandingkan pemberian masing-masing ekstrak.
In-Silico Study: Potential Inhibitor of Cyclin-Dependent Kinase 6 (CDK6) from Natural Plant Compounds for Melanoma Treatment Putri Aliya Ahadini; Adhyatma Ismu Reihan; Muhamad Bagus Wira Utama; Siti Khaerunnisa; Fadilah Fadilah
JUXTA: Jurnal Ilmiah Mahasiswa Kedokteran Universitas Airlangga Vol. 13 No. 2 (2022): Jurnal Ilmiah Mahasiswa Kedokteran Universitas Airlangga
Publisher : Faculty of Medicine Universitas Airlangga

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.20473/juxta.V13I22022.93-99

Abstract

Highlights:1. Melanoma is the most aggressive and dangerous type of skin cancer. 2. Cyclin-dependent kinase 6 (CDK6) had a role in melanoma progression.3. Chlorogenic acid, guattegaumerine, luteolin, and acronycine were potential natural compounds in plants as CDK6 inhibitors. AbstractIntroduction: Melanoma is the most aggressive and dangerous type of skin cancer. It usually occurs in the skin because melanocytes originate from the neural crest cells that migrate. A previous study stated misregulation of cyclin-dependent kinase 6 (CDK6) had a role in melanoma progression. This study aimed to identify the potential natural compound targeting and modulating the CDK6.Methods: This was an investigative study using in-silico docking analysis to search for compatible ligands and potential inhibitors to CDK6 protein. This study screened 46 natural compounds based on the drug-likeliness based on Lipinski’s rules of five and used PyRx (AutoDock Vina) software for the initial screening. 10 compounds with the highest binding energy underwent docking simulation using Molecular Operating Environment (MOE) software.Results: Chlorogenic acid, guattegaumerine, luteolin, and acronycine were potential natural compounds in plants as CDK6 inhibitors.Conclusion: This study found that chlorogenic acid was the most potential to be an inhibitor of CDK6 compared to other compounds screened.
Phytochemical Analysis and In Vitro Cytotoxicity of n-Hexane Extract of Kaempferia pandurata and its Nanoparticle to Breast Cancer MCF-7 Cells Fadilah Fadilah
Journal of Global Pharma Technology Volume 11 Issue 05.
Publisher : Journal of Global Pharma Technology

Show Abstract | Download Original | Original Source | Check in Google Scholar

Abstract

Background: Finger root (Kaempferia pandurata) is a medicinal herb which has shown anticancer activity as potential targeted-therapy towards estrogen receptor positive breast cancer. Objective: This research was conducted to analyze the phytochemical contents of n-hexane extract of Kaempferia pandurata and its nanoparticle to the growth of estrogen positive breast cancer MCF-7 cells. Methods: Kaempferia pandurata rhizome was extracted in n-hexane, and its phytochemical contents was analyzed by simple phytochemical test and thin layer chromatography. Nanoparticle was then synthesized from n-hexane extract of Kaempferia pandurata. Finally, the n-hexane extract of Kaempferia pandurata and its nanoparticle were then tested using MTT Assay to MCF-7 cells in order to determine their inhibition rate and IC50. Results:. The extraction of Kaempferia pandurata rhizome in n-hexane extract was conducted successfully. Through simple phytochemical testing, n-hexane extract of Kaempferia pandurata contained flavonoids, triterpenoids, and tannins. Thin layer chromatography using non-polar eluent (n-hexane : ethyl acetate = 5 :1) showed eight spots with Rf values of 0,12; 0,18; 0,23; 0,29; 0,41; 0,55; 0,62; 0,80. MTT assay resulted in IC50 value of 94.387 ± 11.667 μg/mL and 31,298 ± 0,242 μg/mL for n-hexane extract of Kaempferia pandurata and its nanoparticle respectively. Discussion: The phytochemical contents of n-hexane extract of Kaempferia pandurata (flavonoid, triterpenoid, tannin) was shown to have anticancer activities on breast cancer cells n-hexane extract of Kaempferia pandurata and its nanoparticle has moderately active anticancer activities towards estrogen positive breast cancer MCF-7 cells. Nanoparticle enhances n-hexane extract of Kaempferia pandurata’s entry to cancer cells. Conclusion: N-hexane extract of Kaempferia pandurata and its nanoparticle can be a potenial anticancer agent towards estrogen positive breast cancer.
Spirulina platensis effect on oxidative stress of rat’s offspring brain exposed to cigarette smoke during pregnancy and lactation Kenny Cantika Abadi; Febriana Catur Iswanti; Sri Widia A Jusman; Fadilah Fadilah; Ani Retno Prijanti
Acta Biochimica Indonesiana Vol. 5 No. 1 (2022): Acta Biochimica Indonesiana
Publisher : Indonesian Society for Biochemistry and Molecular Biology

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.32889/actabioina.64

Abstract

Background: Maternal exposure to cigarette smoke during pregnancy and lactation might harmful for the fetus. The smoke contains many free radicals that could be eliminated by antioxidant. This study aimed to investigate the effect of Spirulina platensis ethanol extract as antioxidant against cigarette smoke exposure during pregnancy until lactation by assessing oxidative stress markers in neonatal brain tissues. Methods: The experimental study used 26 offspring divided into four groups: (C) = offspring of maternal control group; (Cg) = offspring of maternal exposed to cigarette smoke; (CgSp) = offspring of maternal given spirulina and exposed to cigarette smoke; and (Sp) = offspring of maternal given spirulina only group, during gestation and 9 days lactation (30 days). Each group consisted of 6 offspring obtained from 2 adult females mated with male Sprague-Dawley rats. The exposure of cigarette smoke was 4 burn cigarettes/day for 30 days. The dose of extract was 200 mg/kg BW. The offspring were sacrificed, and the brain tissues were taken for MDA, MnSOD activity, as well as catalase activity, carbonyl, and GSH. Results: There was no significant differences in MDA level between groups. The carbonyl, SOD, and catalase activity did not differ between the control and smoked group. Conclusion: Exposure of four burned cigarettes smoke per day during pregnancy, and 9 days of lactation did not trigger oxidative stress. However, the effect of Spirulina platensis administration on rat offspring brain could not be analyzed.
Molecular Simulation for Screening Bioactive Compounds as Potential Candidate for Alzheimer’s Disease Immanuelle Kezia; Linda Erlina; Ninik Mudjihartini; Fadilah Fadilah
EKSAKTA: Berkala Ilmiah Bidang MIPA Vol. 24 No. 02 (2023): Eksakta : Berkala Ilmiah Bidang MIPA (E-ISSN : 2549-7464)
Publisher : Faculty of Mathematics and Natural Sciences (FMIPA), Universitas Negeri Padang, Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.24036/eksakta/vol24-iss02/401

Abstract

Alzheimer’s disease is one of the neurodegenerative diseases that afflict the elderly. One of the symptoms is a loss cognitive ability due to neuronal death caused by amyloid plaque accumulation. Alzheimer’s disease is one of the most expensive diseases to treat. Drugs for Alzheimer’s treatment only treat the symptoms, not the disease itself. Several pathways, including the mitochondrial cascade, can be used to develop drugs for Alzheimer’s disease, according to NIH guidelines. Caspase3 is a protein that involved in the mitochondrial cascade, specifically in apoptosis. Alzheimer’s therapy may be more effective if caspase3 is targeted. Indonesia is a rich country, particularly in medicinal plants. We used the Structure-Based Drug Design approaches to screen bioactive compounds in Indonesian medicinal plant to find the best compound candidate. In addition, we performed ADMETOX prediction, molecular docking, and molecular dynamic simulation on forty 3D structures of bioactive compounds and donepezil as an FDA approved Alzheimer’s drug. We discovered Miraxanthin-V had a higher binding affinity than donepezil using molecular simulation. As a result, we can conclude that Miraxanthin-V has a high potential of neuroprotective by inhibiting apoptosis.
FOXO1 and FYN Expression Trends in Breast Cancer Stem Cells: An Integrative Study of Single Nucleotide Polymorphism (SNP) Array and Quantitative PCR (qPCR) Analysis Ay Ly Margaret; Septelia Inawati Wanandi; Fadilah Fadilah; Rafika Indah Paramita
The Indonesian Biomedical Journal Vol 17, No 4 (2025)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v17i4.3656

Abstract

BACKGROUND: Currently, identification of breast cancer stem cells (BCSCs) commonly relies on CD24-/CD44+ expression profiles. However, few studies have integrated genomic mutation data with experimental gene expression validation in CSC and non-CSC populations. Genotyping results of CD24-/CD44+ MDAMB-231 cells revealed 36 mutations in BCSCs compared to non-BCSCs, with upregulated FOXO1 and FYN that might represent promising candidate biomarkers for this subpopulation. Therefore, in this study, single nucleotide polymorphism (SNP) and quantitative polymerase chain reaction (qPCR) analysis were performed to assess the association between mutations and expression trends of FOXO1 and FYN in MDAMB-231 cell, as breast cancer cell model with stem-like traits and well-characterized profile.METHODS: Genomic DNA was isolated from BCSC and non-BCSC DNA from the MDAMB-231 cell line. Mutation analysis was conducted using PLINK, while gene expressions of FOXO1 and FYN were quantified by one-step SYBR Green-based qPCR, using 18s rRNA as a reference. Data was then analyzed with the Livak (2−∆∆Ct) method.RESULTS: Among 36 mutations found in BCSCs of the MDAMB-231 cell line, PTEN (rs786204914) and CHEK2 (rs587782401) were identified as pathogenic. While FOXO1 (2.989±2.817 vs. 1.072±0.388) and FYN (1.405±0.072 vs. 0.855±0.140) mRNA levels were found to be higher in CSCs compared to non-CSCs, though these differences was not statistically significant.CONCLUSION: Pathogenic mutations in CHEK2 and PTEN were detected within BCSC population, implying a potential influence on the expression of FOXO1 and FYN, though not statistically significant. These findings suggest a possible, but as yet unverified, association between gene mutations and expression patterns, emphasizing the importance of further functional studies to validate FOXO1 and FYN as biomarkers for BCSCs.KEYWORDS: breast cancer stem cells, FOXO1, FYN, PTEN, CHEK2, mutation, biomarker
In Silico Study: Metabolite Compounds of Zingiber Officinale Var. Rubrum as Potential E2F2 Inhibitor Agents in Breast Cancer Signaling Pathway Khoirunnisa Purwamita Budiutami; Aryo Tedjo; Fadilah Fadilah; Surya Dwira; Ajeng M. Fajrin
Eduvest - Journal of Universal Studies Vol. 6 No. 1 (2026): Eduvest - Journal of Universal Studies
Publisher : Green Publisher Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.59188/eduvest.v6i1.52614

Abstract

Breast cancer ranks among the leading causes of death in women, linked to disruptions in signaling pathways regulating cell proliferation and survival, particularly E2F2 gene activity. E2F2 regulation falters when pRB is phosphorylated by Cyclin D–CDK4/6 or Cyclin E–CDK2 complexes, freeing E2F2 to activate cell cycle genes. This study, "In Silico Study: Metabolite Compounds of Zingiber officinale var. rubrum as Potential E2F2 Inhibitor Agents in Breast Cancer Signaling Pathway," assesses red ginger (Zingiber officinale var. rubrum) metabolites as CDK4/CDK6 inhibitors via molecular docking in silico. Target protein structures came from the Protein Data Bank; metabolites were chosen for reported anticancer effects and 3D-modeled. Docking used Molegro Virtual Docker to gauge ligand affinity and interactions at active sites. Results highlighted [12]-shogaol, (E,E)-α-farnesene, and 1-dehydro-[6]-gingerdione as CDK4 inhibitors; azafrin, [8]-shogaol, and [12]-shogaol for CDK6. These exhibit strong binding via hydrogen bonds and hydrophobic interactions at key residues. Red ginger metabolites show promise as CDK4/CDK6 inhibitors for breast cancer therapy, pending in vitro/in vivo validation.
Doxycycline Suppresses Hypertension through Renin– Angiotensin System (RAS) Regulation: Insights from Molecular Docking and Renal Gene Expression Ariski Fajarido; Fadilah Fadilah; Wawaimuli Arozal; Jaka Fajar Fatriansyah; Agrin Febrian Pradana; Edwina Rugayah Monayo
Molecular and Cellular Biomedical Sciences Vol 10, No 1 (2026)
Publisher : Cell and BioPharmaceutical Institute

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.21705/mcbs.v10i1.744

Abstract

Background: Doxycycline, a tetracycline antibiotic known for inhibiting matrix metalloproteinases, has shown potential antihypertensive effects. However, its role in modulating the renin–angiotensin system remains poorly understood. This study aims to specifically evaluate Doxycycline’s effects on key RAS components and blood pressure responses to clarify its underlying mechanism and support its development as a targeted antihypertensive therapeutic candidate.Materials and Methods: This study integrated an in-silico and experimental approach to assess the antihypertensive effects of doxycycline. Bioinformatics analyses were first conducted, including target prediction, gene ontology enrichment, hub-gene identification, PPI network construction, and KEGG pathway analysis, followed by molecular docking and molecular dynamics simulations to predict doxycycline’s interactions with key RAS targets. To validate these computational findings, qRT-PCR was performed to measure the expression of selected genes in kidney tissues from hypertensive rats.Results: Bioinformatics analysis identified six key target genes, including AGT, AGTR1, AGTR2, REN, ACE, and ACE2. Molecular docking showed that doxycycline exhibited stronger binding affinity to AGTR1 (-8.346 kcal/mol) than its native ligand. Molecular dynamics confirmed the stability of the doxycycline–AGTR1 complex at 20 ns. Gene expression analysis of kidney tissues from hypertensive rats revealed a significant reduction in AGTR1 expression in the group treated with doxycycline 15 mg/kg (p<0.05), while no significant change was observed at 30 mg/kg.Conclusion: Low-dose doxycycline may modulate the renin–angiotensin pathway through AGTR1 inhibition, indicating its potential as a candidate for further antihypertensive research and warranting more comprehensive in vivo evaluation.Keywords: Hypertension, doxycycline, molecular docking, gene expression, Renin-Angiotensin System
In Silico Analysis of Centella asiatica Phytochemicals Targeting the KEAP1–NRF2 Pathway as Potential Radioprotective Agents Aghisna Binurillah Sulaeman; Dwi Anita Suryandari; Luluk Yunaini; Fadilah Fadilah
Jurnal Locus Penelitian dan Pengabdian Vol. 5 No. 6 (2026): JURNAL LOCUS: Penelitian dan Pengabdian
Publisher : Riviera Publishing

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.58344/locus.v5i6.5759

Abstract

Ionising radiation induces excessive oxidative stress and cellular damage, necessitating the discovery of effective radioprotective agents. The KEAP1–NRF2 pathway plays a central role in antioxidant defence, making KEAP1 inhibition a promising strategy for enhancing NRF2 activation. Centella asiatica contains diverse bioactive compounds with reported antioxidant and cytoprotective properties; yet their potential as direct KEAP1 inhibitors remains underexplored. This study aimed to evaluate the molecular interactions of Centella asiatica phytochemicals with KEAP1 using in silico approaches, in order to identify potential natural radioprotective candidates. Thirty-six bioactive compounds from Centella asiatica were subjected to molecular docking against the KEAP1 Kelch domain (PDB ID: 4L7B) using AutoDockTools 1.5.7. Ligand–protein interactions were visualised using LigPlot+ and PyMOL. Pharmacokinetic and toxicity profiles were predicted using DeepPK and admetSAR, including assessments of drug-likeness, intestinal absorption, CYP inhibition, and toxicity endpoints. Three compounds demonstrated strong binding affinities below –8 kcal/mol: acetylursolic acid (–8.88 kcal/mol), campesterol (–8.55 kcal/mol), and ursolic acid (–8.15 kcal/mol). All three interacted with the key KEAP1 residue Arg415, with additional interactions involving Ser363 (acetylursolic acid and ursolic acid) and Ser508 (campesterol). ADME–Tox analysis indicated favourable pharmacokinetic profiles, good intestinal absorption, non-mutagenic and non-carcinogenic predictions, and overall compliance with Lipinski's Rule of Five, notwithstanding a single LogP violation. Acetylursolic acid, campesterol, and ursolic acid exhibit strong binding to critical KEAP1 residues and demonstrate favourable pharmacokinetic and safety profiles, suggesting their potential as natural radioprotective agents through modulation of the KEAP1–NRF2 pathway. Further in vitro and in vivo studies are warranted to validate their radioprotective efficacy.