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Genotype distribution of methylenetetrahydrofolate reductase A1298C and C677T gene in Indonesian infertile men Suryandari, Dwi A.; Yurnadi, Yurnadi; Wiweko, Budi; Yunaini, Luluk
Medical Journal of Indonesia Vol 21, No 1 (2012): February
Publisher : Faculty of Medicine Universitas Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (926.764 KB) | DOI: 10.13181/mji.v21i1.470

Abstract

Background: Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme of folate and methionin metabolism, making it crucial for DNA synthesis and methylation. Variants of MTHFR C677T and A1298C gene result in reduced plasma folate levels and increase the susceptibility to spermatogenic arrest. This research aims to analyses MTHFR C677T and A1298C gene polymorphism in Indonesian infertile men with azoospermia and oligozoospermia.Methods: This cross sectional study takes 3 mL of blood from 150 infertile men with oligozoospermia and azoospermia. MTHFR gene is analyzed using polymerase chain reaction technique (PCR) with specific primers. PCR-RFLP analysis of the MTHFR gene using restriction enzymes MboII and HinfI determines allotypes, both of SNP A1298C and C677T in oligozoospermia and azoospermia in Indonesian population.Results: The results show that the distribution of allotypes of MTHFR gene SNP A1298C and A677T is not significantly different (p>0.05) between patient groups with oligozoospermia and azoospermia.Conclusion: MTHFR gene polymorphisms, both of SNP A1298C and C677T are not associated with male infertility in Indonesian men including patients with severe oligozoospermia and azoospermia. (Med J Indones 2012;21:23-7)Keywords: DNA methylation, MTHFR, spermatogenic arrest
Progesterone decrease plasma membrane in human sperm with subnormal hypoosmotic swelling test scores Sisca, Sisca; Yunaini, Luluk; Pujianto, Dwi Ari
Universa Medicina Vol 38, No 1 (2019)
Publisher : Faculty of Medicine, Trisakti University

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (607.791 KB) | DOI: 10.18051/UnivMed.2019.v38.56-62

Abstract

BackgroundProgesterone (P4) is known as a female hormone affecting oocyte maturation and developing uterine wall. A proteomic study identified several receptors including P4 receptors on human sperm. The role of P4 in human sperm cells remains unknown as to whether P4 has non-genomic effects on human sperm. The present study aims to determine the effect of progesterone (P4) on the hyperactivated motility and membrane integrity of human sperm cells.MethodsSemen from normal individuals was obtained from donors. The semen was washed by gradient density centrifugation. P4 was added to each semen sample to final concentrations of 0 (control), 250, 500, 750 and 1000 ng/mL. After the sample treatment was completed, the sperm membrane integrity was assessed with the hypoosmotic swelling test (sodium citrate dihydrate and D-fructose) and the hyperactivated sperm motility parameter was determined with the Computer Assisted Sperm Analyzer [CASA] (Hamilton Thorne, IVOS II, USA). The percentage was then compared between the treatment groups and the control group. The percentage differences were analyzed with the Sigmastat version 2.0 statistical program.ResultsAdministration of P4 increased sperm hyperactivated motility when compared with the control group at a concentration of 500 ng/mL, but the increase was statistically not signicant (p>0.05). In contrast, P4 decreased sperm membrane integrity significantly (p=0.042). And the mean of plasma membrane integrity in all groups was subnormal hypoosmotic swelling test score. ConclusionProgesterone administration tends to increase sperm hyperactivated motility. The integrity of plasma sperm membrane was affected by progesterone.
The effect of ethanolic leaves extract of soursop (Annona muricata L.) on human colorectal cancer cell line: cell viability and in silico study to cyclin D1 protein Murdani Abdullah; Debby Desmarini; Sofy Meilaini; Puji Sari; Luluk Yunaini; Fadilah Fadilah
Health Science Journal of Indonesia Vol 10 No 2 (2019)
Publisher : Sekretariat Badan Penelitian dan Pengembangan Kesehatan

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.22435/hsji.v12i2.2441

Abstract

Latar Belakang: Kanker kolorektal merupakan transformasi patologis dari epitel kolon dan rektum normal menjadi massa jaringan abnormal, perubahan ini terjadi karena ekspresi berlebih dari protein cyclin D1 yang menginduksi proliferasi sel kolorektal secara berlebihan. Pengobatan dan pencegahan kanker kolorektal dapat dilakukan secara alami dengan mengonsumsi ekstrak daun Annona muricata L. (sirsak). Sirsak dikenal karena banyak komponen fitokimia yang berfungsi sebagai anti kanker. Metode: Penelitian ini menggunakan sel kanker kolorektal HT-29 yang diberi ekstrak etanol daun sirsak dan 5 Fluorourasil (5-FU). Tujuannya untuk menemukan konsentrasi sitotoksisitas yang dapat menghambat 50% populasi sel HT-29 (CC50) dan konsentrasi yang didapat sebelumnya akan diuji dengan metode uji MTT. Analisis docking molekuler dilakukan antara molekul-molekul dari ekstrak etanol daun sirsak terhadap protein Cyclin D1 menggunakan perangkat lunak molecular operating environment (MOE) 2013.08. Hasil: CC50 ekstrak etanol daun sirsak adalah 278 μg / mL dan 5-FU adalah 88 μg / mL. Persentase terendah sel HT-29 yang layak adalah 2 x CC50 setelah perlakuan ekstrak etanol daun sirsak (40,4 ± 1,3%) dibandingkan dengan 5-FU (52,8 ± 4,3%), kontrol pelarut ( 97,2 ± 1,4%), dan kontrol sel (100%). Analisis docking molekuler untuk protein cyclin D1 diperoleh asam N-hexadecanoic dan molekul phytol sebagai kandidat yang baik untuk menghambat protein cyclin D1. Kesimpulan: Ekstrak etanol daun sirsak dapat menurunkan viabilitas sel kultur kanker kolon HT-29 dan berdasarkan analisis molekular docking dilihat dari energi bebas gibbs (ΔG) dan afinitas tertinggi (pKi) diperoleh N-hexadecanoic dan molekul phytol sebagai penghambat protein cyclin D1. (Health Science Journal of Indonesia 2019;10(2):96-102) Kata Kunci: Kanker kolorektal HT-29, ekstrak etanol daun sirsak, viabilitas sel, molecular docking, cyclin D1 Abstract Introduction: Colorectal cancer is a pathological transformation of normal colon and rectum epithelial that becomes an abnormal tissue mass, due to the overexpression of cyclin D1 protein that inducing excessive proliferation of colorectal cell. The treatment and prevention of colorectal cancer could be done naturally by consuming leaves extract of Annona muricata L. (soursop). Soursop is known for many phytochemical components that serve as an anti-cancer. Methods: This study was used HT-29 colorectal cancer cell that treated with ethanolic leaves extract of soursop and 5-Fluorourasil (5-FU) to find the cytotoxicity concentration that can inhibit 50% of HT-29 cell population (CC50) and the next concentrations of them were treated for next treatment with MTT assay. Molecular docking analysis of the compounds of ethanolic leaves extract of soursop to cyclin D1 protein used molecular operating environment (MOE) 2013.08 software. Results: CC50 of ethanolic leaves extracts of soursop was 278 μg/mL dan 5-FU was 88 μg/mL. The lowest percentage of viable HT-29 cell was 2 x CC50 after ethanolic leaves extract of soursop treatment (40,4±1,3%) was compared to 5-FU (52,8±4,3%), solvent control (97,2±1,4%), and cells control (100%). Analysis of molecular docking to cyclin D1 protein was obtained N-hexadecanoic acid and phytol molecules as good candidates to inhibit cyclin D1 protein. Conclusions: The ethanolic leaves extract of soursop could be a good alternative treatment for colorectal cancer and its compounds had ability to inhibit cyclin D1 protein (the highest gibbs free energy (ΔG) and affinity (pKi)). (Health Science Journal of Indonesia 2019;10(2):96-102) Keywords: Colorectal cancer, ethanolic leaves extract of soursop, cell viability, molecular docking, cyclin D1
HUBUNGAN KADAR SERUM AMH DENGAN JUMLAH MUTASI PADA GEN PROMOTER AMH (ANTI-MULLERIAN HORMONE) PADA PASIEN SOPK (SINDROM OVARIUM POLIKISTIK) Mala Kurniati; Dwi Anita Suryandari; Budi Wiweko; Pudji Sari; Luluk Yunaini; Roselina Panghiyangani
Jurnal Ilmu Kedokteran dan Kesehatan Vol 9, No 1 (2022): Volume 9 Nomor 1
Publisher : Prodi Kedokteran Fakultas Kedokteran Universitas Malahayati

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.33024/jikk.v9i1.6482

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Anti-Mullerian Hormone (AMH) adalah anggota dari kelompok Transforming Growth Factor-β yang berperan penting dalam regulasi folikulogenesis reproduksi wanita. Peningkatan kadar AMH 2-3 kali lipat ditemukan pada pasien SOPK (Sindrom Ovarium Polikistik) dibandingkan dengan wanita dengan ovulasi normal. Tujuan dari penelitian ini adalah untuk mengetahui hubungan kadar serum AMH dengan jumlah mutasi pada gen promoter AMH (Anti-Mullerian Hormone) pada pasien SOPK (Sindrom Ovarium Polikistik). Besar sampel adalah 114 pasien yang terdiri dari 60 pasien SOPK dan 54 pasien bukan SOPK sebagai kontrol. Kadar AMH didapatkan dari rekam medis pasien di Klinik Yasmin IVF RSCM Kencana Hospital, Jakarta. Analisis molekuler dan genotipe dilakukan dengan PCR dan sekuensing dilanjutkan dengan analisis bioinformatika. Terdapat 60 mutasi titik pada varian promotor gen AMH. Jenis mutasi varian tertinggi yang ditemukan adalah -674 G/A (100%), diikuti oleh -245 C/CT (88,2%), dan -444 A/G (17,9%) di seluruh sampel. Berdasarkan hasil uji Wilcoxon Signed Rank test, jumlah mutasi pada kelompok SOPK berpengaruh nyata terhadap AMH serum (p<0,05). Pada kelompok kontrol, jumlah mutasi tidak berpengaruh nyata terhadap kadar AMH (p>0,05). Jumlah mutasi pada promotor gen mempengaruhi kadar serum AMH pada PCOS.
Gene Expression of Sperm Associated Antigen 8 and Ran-Binding Protein 9 on Azoospermic Male : Its Association with Spermatogenic Arrest Christina Agusta Deviana Tanifan; Dwi Anita Suryandari; Luluk Yunaini
Jurnal Health Sains Vol. 3 No. 9 (2022): Jurnal Health Sains
Publisher : Syntax Corporation Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.46799/jhs.v3i9.591

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Proteins that play an  important role in the transcription process during spermatogenesis are CREMs that bind to their ACT activators that are suspected to be regulated by SPAG8 and RANBP9. Until now the role of both genes in the spermatogenic arrest process is not known. This study aims to determine the relative expression of Spag8 and RanBP9 on spermatogenic arrest and to analyze the correlation of expression of both genes. This study is a cross sectional study using a sample of testicular biopsy with Johnsen 2 to 8 score. Relative expression analysis of Spag8 and RanBP9 using qRT-PCR technique with Livak calculation. The data obtained were analyzed statistically using ANOVA one way test for Spag8 and Kruskal Wallis test for RanBP9 with significance value p <0,05. The results of this study show that the relative expression of Spag8 and RanBP9 is highest on Johnsen 3 scores and is statistically significantly different (p <0.05). There is a positive correlation with a very strong correlation strength between SPAG8 and RANBP9 expressions. Based on the results of this study shows that both of these genes are candidates for spermatogenic arrest.
THE EFFECT OF STATIC MAGNETIC FIELD EXPOSURE ON BODY WEIGHT AND ADIPOSE CELLS DENSITY OF OBESE MICE Puji Sari; luluk yunaini; Widia Bela Oktaviani; Umiatin Umiatin; Anita Dwi Suryandari
Jurnal Neutrino:Jurnal Fisika dan Aplikasinya Vol 15, No 1 (2022): October
Publisher : Department of Physics, Maulana Malik Ibrahim State Islamic University of Malang

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18860/neu.v15i1.16302

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Obesity is a mojar public health problem in worldwide, especially in Indonesia. Obesity in addition to affecting productivity, is also trigger for other chronic disease such as diabetes and cardiac disease. Body mass index is an assessment tool used to assess degree of individual adiposity to define overweight, obesity, and severe obesity.The determination of obesity is based on the calculation of Body Mass Index (BMI), which devide body weight (kg) by height (cm2). In addition to the method of regulating diet, exercise, and bariatric surgery for weight loss, it was reported that the biophysical therapy tool, that is static magnetic field (SMF) became a modality for weight loss. Based on research reports, it proves that the static magnetic field affects weight loss in the group of obese mice after 30 days of exposure. Therefore, in this study, we carried out static magnetic field exposure to obese mice with a field intensity of 2 mT for 1 hour/day. Mice were exposed gradually to SMF on 2, 7, 14, and 21 days to determine the effectiveness of SMF to obesity in mice in terms of weight loss and cellular adipose cell density. The results showed that the weight of mice decreased significantly on 2nd and 7th days of exposure, the trend showed a decrease in body weight until the 14th day. The density of adipose tissue is increased after exposure to SMF on the 14th and 21st days of exposure. It showed that early exposure to SMF (2 and 7 days) could induce weight loss in mice, while cellularly SMF increased adipose cell density on late exposure (14 and 21 days).
DNA METHYLATION IN THYROID-STIMULATING HORMONE GENE: PREDICTOR OF GRAVE’S DISEASE RECURRENCE IN INDONESIA Luluk yunaini; Dwi Anita Suryandari; Trisia Lusiana Amir; Dwi Yanti; Fatimah Eliana
Journal of Global Pharma Technology Volume 10 Issue 06: (2018) June 2018
Publisher : Journal of Global Pharma Technology

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Abstract

Thyroid-stimulating hormone receptor (TSHR) has a critical role in Graves’ disease (GD). GD is an autoimmune disease which is multifactorial. Environmental factors can affect the epigenetic, a changes in gene expression without any changes in base sequence of the DNA. One of the epigenetic types is methylation. This study aims to determine the status of DNA methylation in TSHR gene in patients with GD to be one of the predictors of recurrence. This study used a case control design with 58 samples of GD patients divided into 29 groups of recurrence and 29 groups of non-recurrence. DNA methylation examination used methylation-specific PCR (MSP) method. Our result found that DNA methylation profile of GD in Indonesia were 5% with complete DNA methylation, 17% complete DNA unmethylation and 78 partial DNA methylation. Statistical analysis showed no significant different between recurrence and non-recurrence group (p>0.05). Nevertheless, our result showed no patient with complete status DNA methylation was found in recurrence group. This shows that in recurrence occur a reduction of DNA methylation resulting in increasing of TSHR production. Thus, DNA methylation in TSHR gene might be has a role in the risk of recurrence GD.
Expression relative of RANK, RANKL and OPG gene on Rat Femoral Fracture Healing Process in Delayed Union Model after Pulsed Electromagnetic Field exposure Luluk yunaini
Journal of Global Pharma Technology Volume 11 Issue 04.
Publisher : Journal of Global Pharma Technology

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Abstract

Pulsed electromagnetic field (PEMF) is application medical devices in healing bone fracture. Osteoblast and osteoclast cells have regulation in femoral fracture healing process. PEMF exposure has effect in cell nucleus activity. Genes that have critical role in bone remodelling are Receptor activator of nuclear factor kappa-B (RANK), receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG).This research aimed to analysis effect PEMF exposure in improve bone fracture healing process with delay union model, which its expression level in RANK, RANKL and OPG gene. Our research used experimental design. Sample for this research was callus from rat femoral fracture with delay union. qRT-PCR technique with Livak’s measurement were used to detection expression relative. Statistic analysis used two way ANOVA with a significant differences value p <0.05. The result showed that relative expression on RANK, RANKL and OPG have significance different in PEMF group and times (days) group. We found that the PEMF group can expedite the higher expression relative of RANK, RANKL and OPG than non PEMF group. The result has concluded using PEMF can improve the healing to normal union process on rat with delay union model.
RELA mRNA Expression in Epithelial Ovarian Cancer: Correlation with rs11820062 Gene Variant: Ekspresi mRNA RELA pada Kanker Ovarium Epitelial : Korelasinya dengan Varian Gen rs11820062 Benedikta D. Saraswati; Dwi A. Suryandari; Ria Kodariah; Dewi Sukmawati; Luluk Yunaini; Primariadewi Rustamadji; Puji Sari
Indonesian Journal of Obstetrics and Gynecology Volume 11 No. 2 April 2023
Publisher : Indonesian Socety of Obstetrics and Gynecology

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.32771/inajog.v11i2.1872

Abstract

and its correlation to i mRNA expression in low-grade and high-grade EOC’s patients from Dr. Cipto Mangunkusumo General hospital, Indonesia. Methods: This study is cross-sectional with a total of 65 healthy subjects and 80 ovarian biopsies (15 ovarian cysts as expression calibrators, 36 low-grade EOC, and 29 high-grade EOC) were used in this study. The distribution of genotypes and alleles was analyzed using ARMS PCR. The mRNA expressions of RELA were determined by real-time polymerase chain reaction (qPCR) analysis.Results: There was no significant difference between genotype and allele distributions for RELA rs11820062 in normal and case group. RELA relative mRNA expression was significantly higher in low-grade and high-grade EOC compared to in ovarian cysts (p<0.01). RELA rs11820062 CC genotype correlated to higher RELA mRNA relative expression and the TT genotype of RELA rs11820062 correlated with lower RELA mRNA relative expression in low-grade and high-grade EOC.Conclusion: C allele in rs11820062 caused an increased expression of RELA mRNA, which individuals with CC genotype correlated with higher RELA expression in low-grade and high-grade EOC. In contrast, individuals with the T allele of RELA rs11820062 had a protective effect against EOC risk because the RELA TT genotype tended to have a lower RELA mRNA expression in EOC.Keywords: epithelial ovarian cancer, NF-kB, RELA, rs11820062.AbstrakTujuan: Mengetahui distribusi RELA rs11820062 dan korelasinya dengan ekspresi mRNA RELA pada pasien EOC low-grade dan high-grade di Rumah Sakit Dr. Cipto Mangunkusumo, Indonesia.Metode: Penelitian ini merupakan peneliatan potong lintang terhadap 65 sampel darah perempuan normal dan total 80 biopsi kanker ovarium dengan rincian: 15 kista ovarium sebagai kalibrator ekspresi, 36 EOC low-grade, dan 29 EOC high-grade. Distribusi genotipe dan alel dianalisis menggunakan ARMS PCR dan ekspresi mRNA RELA dikuantifikasi menggunakan teknik qPCR. Hasil: Tidak terdapat perbedaan distribusi genotipe dan alel antara kelompok normal dengan kasus EOC. Ekspresi relatif mRNA RELA meningkat secara signifikan pada kelompok EOC low-grade dan high-grade. Individu dengan genotipe RELA rs11820062 homozigot CC memiliki ekspresi mRNA yang lebih tinggi dibandingkan genotipe lain. Sebaliknya individu dengan genotipe TT memiliki korelasi dengan ekspresi mRNA RELA yang lebih rendah pada tipe low-grade dan high-grade EOC. Kesimpulan: Alel C pada RELA rs11820062 menyebabkan peningkatan ekspresi mRNA RELA pada pasien EO yang dilihat dari individu dengan genotipe CC cenderung memiliki ekspresi mRNA RELA yang lebih tinggi pada tipe EOC low-grade dan high-grade. Sebaliknya, individu dengan alel T RELA rs11820062 diduga memiliki efek protektif terhadap risiko EOC karena adanya korelasi antara genotipe TT dengan ekspresi mRNA RELA yang lebih rendah pada EOC.Kata kunci: kanker ovarium epitelial, NF-kB, RELA, rs11820062.
Molecular Insights into Propylthiouracil as a Thyroid Peroxidase Inhibitor: A Computational Study Approach Suryandari, Dwi Anita; Yunaini, Luluk; Sunaryo, Hadi; Istiadi, Khaerunissa Anbar; Pratomo, Irandi Putra
Indonesian Journal of Medical Chemistry and Bioinformatics
Publisher : UI Scholars Hub

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Abstract

Thyroid peroxidase (TPO) is a crucial enzyme in the biosynthesis of thyroid hormones, catalyzing the iodination of tyrosine residues in thyroglobulin and the coupling of iodotyrosines to form thyroxine (T4) and triiodothyronine (T3). Propylthiouracil (PTU) is an antithyroid drug commonly used to manage hyperthyroidism by inhibiting TPO. Understanding the molecular interactions between TPO and PTU can provide insights into the inhibitory mechanisms and guide the design of more effective antithyroid medications. Objective: This study aims to elucidate the binding interactions between TPO and PTU through molecular docking, providing a detailed understanding of how PTU inhibits TPO activity. Methods: The three-dimensional structure of TPO was obtained from Prosite and modelling by swissmodel and prepared for docking. The structure of PTU was optimized, and molecular docking was performed using AutoDock. The binding affinity, binding poses, and key interactions between TPO and PTU were analyzed. Visualization of the docking results was performed using PyMOL to identify critical residues involved in PTU binding. Results: The docking analysis revealed that PTU binds effectively to the active site of TPO with a binding affinity of -5.45 kcal/mol. The interaction involves coordination with the heme group and several key residues, including His239, which coordinates the heme, and Ser314, which forms hydrogen bonds with PTU. Additionally, hydrophobic interactions with residues Phe241 and Ile399 stabilize the binding of PTU in the active site. Conclusion: The docking study highlights the significant interactions between PTU and TPO, elucidating the molecular basis of TPO inhibition by PTU. The binding affinity and key interactions identified in this study provide a foundation for the design of more potent antithyroid drugs.