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All Journal journal of internal medicine E-Journal Obstetric & Gynecology Udayana Majalah Obstetri dan Ginekologi The Indonesian Biomedical Journal Public Health of Indonesia Indonesian Journal of Obstetrics & Gynecology Science Indonesian Journal of Obstetrics and Gynecology (Majalah Obstetri dan Ginekologi Indonesia) ISM (Intisari Sains Medis) : Jurnal Kedokteran Bioscientia Medicina : Journal of Biomedicine and Translational Research Bioscientia Medicina : Journal of Biomedicine and Translational Research Indonesian Journal of Perinatology Journal of Global Pharma Technology
Anak Agung Ngurah Jaya Kusuma
Department Of Obstetrics & Gynaecology, Faculty Of Medicine, Universitas Udayana-Sanglah General Hospital, Denpasar, Bali
Biochemistry, Genetics & Molecular Biology Health Professions Immunology & microbiology Medicine & Pharmacology Neuroscience Nursing Public Health

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Lacticaseibacillus rhamnosus Probiotics Improve Fasting Blood Glucose, HOMA-IR, and Reduce Body Weight in Diabetic Rat Model Arresta Vitasatria Suastika; I Gde Raka Widiana; Anak Agung Ngurah Jaya Kusuma; Ni Nengah Dwi Fatmawati; Ketut Suastika; I Nengah Sujaya
The Indonesian Biomedical Journal Vol 17, No 1 (2025)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v17i1.3525

Abstract

BACKGROUND: Indonesian indigenous probiotics have been found to improve disruptions of tight junctions in the intestinal epithelium and reduce total cholesterol levels. Improvement in the tight junction could decrease the LPS level and further reduce the blood glucose and insulin resistance. The effects of indigenous Indonesian Lacticaseibacillus rhamnosus (Lr) probiotics on glucose metabolism and inflammatory marker levels in diabetic rats was studied to find if these probiotics are suitable as potential supplementation treatment in diabetes.METHODS: Sixteen female Wistar rats were induced with diabetes using streptozotocin and fed a high-fat, high-sucrose diet. The rats were separated into four groups: LrFBB81, LrFSMM22, LrSKG34, and a control group. Each intervention group got daily dosages of 1 mL probiotic suspensions containing 109 CFU/mL cells given orally for 14 days, whereas the control group received saline. Fasting blood glucose (FBG), insulin, homeostatic model assessment for insulin resistance (HOMA-IR), lipopolysaccharide (LPS), and body weight were evaluated.RESULTS: FBG was significantly reduced in LrFSMM22 group (Δ=120.75 mg/dL, p=0.035), while significant reduction was not observed from LrFBB81, LrSKG34, and control groups. No statistically significant differences were found in HOMA-IR before and after intervention in all groups, but Δ HOMA-IR from LrFSMM22 group was reduced more than the control group (-3.90 vs. 2.02, p=0.028). All groups showed no significant differences in LPS level, meanwhile statistically significant reduction in body weight was observed in all probiotic groups, LrFBB81 (Δ=-15.7 gram, p=0.040), LrSKG34 (Δ= -20.43 gram, p=0.006), and LrFSMM22 groups (Δ=-18.33 gram, p=0.037).CONCLUSION: The administration of L. rhamnosus could improve FBG, HOMA-IR, and reduce body weight without suppressing the LPS.KEYWORDS: diabetes, probiotic, Lacticaseibacillus rhamnosus, fasting blood glucose, HOMA-IR, lipopolysaccharide, insulin resistance
Hypomethylation of the Soluble Fms-like Tyrosine Kinase 1 (sFlt-1) Gene Promoter Region and Elevated sFlt-1 Placental Expression as Risk Factors for Preeclampsia Anak Agung Ngurah Jaya Kusuma; I Made Darmayasa; I Gede Mega Putra; Anom Suardika; Evert Solomon Pangkahila; Vidya Saraswati Putri Duarsa; William William
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.v17i4.3744

Abstract

BACKGROUND: Preeclampsia significantly contributes to maternal and fetal morbidity and mortality worldwide, marked by an imbalance of angiogenic factors, particularly increased soluble Fms-like tyrosine kinase-1 (sFlt-1), leading to endothelial dysfunction. Epigenetic regulation, including DNA methylation of the sFlt-1 promoter, has been suggested to influence sFlt-1 expression, but the data in Indonesian population are limited. This study was perfmed to determine whether hypomethylation of the sFlt-1 promoter and elevated placental sFlt-1 expression are associated with increased risk of preeclampsia.METHODS: A case-control study was conducted involving 30 women with preeclampsia and 30 normotensive pregnant women. Subjects were selected based on eligibility criteria that included singleton pregnancy and gestational age of ≥37 weeks. DNA methylation of the sFlt-1 promoter was assessed using methylation-specific polymerase chain reaction (PCR), and sFlt-1 expression was measured by enzyme-linked immunosorbent assay (ELISA). Statistical analyses, including Mann-Whitney U, Chi-square tests, Receiver-operating characteristic (ROC) curve analysis, and multivariate logistic regression, were performed to evaluate the relationship between methylation levels, gene expression, and preeclampsia risk.RESULTS: The preeclampsia group had significantly lower methylation levels of sFlt-1 promoter and higher placental sFlt-1 expression (both p<0.001). Hypomethylation of sFlt-1 promoter (adjusted odd ratio (AOR): 21.18; 95% CI: 2.49–179.72; p=0.005), high sFlt-1 expression (AOR: 12.55; 95% CI: 1.95–80.83; p=0.008), and obesity (AOR: 11.15; 95% CI: 2.01–61.78; p=0.006) were identified as independent risk factors for preeclampsia.CONCLUSION: Hypomethylation of sFlt-1 promoter and elevated placental sFlt-1 expression are significant independent risk factors for preeclampsia. These findings suggest that hypomethylation of sFlt-1 promoter and elevated placental sFlt-1 expression may serve as potential epigenetic biomarkers for early detection and targeted intervention in preeclampsia.KEYWORDS: preeclampsia, sFlt-1, gene expression, hypomethylation, placenta, risk factor
Non-Invasive Prenatal Testing with Next Generation Sequencing Methods in Birth Defect Pregnancy: A Pilot Study Anom Suardika; Anak Agung Ngurah Jaya Kusuma; Ni Gusti Ayu Manik Ermayanti; Endang Sri Widiyanti; I Gusti Ngurah Agung Satria Wibawa; Divika Silvana; Anak Agung Gede Raka Budayasa; Ni Nyoman Ayu Dewi; I Made Jawi; H. Sunny Sun; Yen-An Tang
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.v17i4.3753

Abstract

BACKGROUND: Identification of cell-free foetal DNA (cffDNA) in maternal blood, combined with next-generation sequencing (NGS) advancement, has paved the way for non-invasive prenatal screening to detect foetal aneuploidies. However, there is limited evidence on its diagnostic accuracy when compared with gold-standard invasive tests specifically in pregnancies complicated by birth defects in Indonesia. This study was conducted to evaluate the precision of non-invasive prenatal testing (NIPT) using NGS and ultrasound findings compared with the established benchmarks of amniocentesis and neonatal karyotyping through G-banding analysis, which is an invasive procedures, in a private laboratory setting for pregnancies with birth defect.METHODS: An observational cohort study involving pregnant women with foetal birth defects in central nervous system, facial, heart, gastrointestinal tract, urinary tract abnormalities and suspected Down Syndrome was conducted. The foetal birth defects were identified in the first trimester with ultrasound screening. Venous blood was drawn from the mother for NGS-based NIPT examination. As a gold standard, amniocentesis or neonatal G-banding karyotyping was conducted.RESULTS: Using G-banding karyotyping as gold standard, the results indicated that NIPT using the NGS method and ultrasound findings achieved 100% sensitivity, 100% specificity, and 100% accuracy in detecting trisomy 13, 18, and 21, as well as foetal sex chromosome abnormalities. Additionally, a case of tetrasomy 9p was identified through G-banding karyotyping, which was associated with multiple clinical abnormalities.CONCLUSION: NIPT with NGS methods and ultrasound findings demonstrated 100% accuracy for the screening of trisomy 13, 18, and 21 in birth defect pregnancy, which is comparable with G-banding analysis as a gold standard. Therefore, this suggest that these approaches offer a safe early detection, highly accurate alternative in high risk setting, compared to invasive procedure in Indonesia where access to such testing may be limited. KEYWORDS: G-banding karyotyping, next generation sequencing, non-invasive prenatal testing
Promoter Methylation and Low Placental Expression of Metalloproteinase (MMP)-9, Human Leukocyte Antigen (HLA)-G, Vascular Endothelial Growth Factor (VEGF), and Highly Soluble Endoglin (sEng) as Risk Factors for Preeclampsia Kusuma, Anak Agung Ngurah Jaya; Darmayasa, I Made; Mulyantari, Ni Kadek; Mayasari, Ni Nyoman Wistya Tri; Sutandi, Chatrine; Bay, Godefridus Paulo; Nugraha, Cokorda Gde Angga Ary
The Indonesian Biomedical Journal Vol 18, No 1 (2026)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v18i1.3921

Abstract

BACKGROUND: Dysregulated expressions of metalloproteinase (MMP)-9, human leucocyte antigen (HLA)-G, vascular endothelial growth factor (VEGF), and soluble endoglin (sEng) reflect impaired angiogenesis, immune tolerance, endothelial function, and trophoblast invasion that characterize abnormal placental development in preeclamptic (PE) pregnancies. However, the role of promoter methylation of these markers in linking the pathways to altered protein expression remains unclear. Hence, this study compared promoter methylation and placental expression of MMP-9, HLA-G, VEGF, and sEng between women with PE and normotensive pregnancies, and evaluate their diagnostic performance as potential biomarkers.METHODS: This case–control study included 30 women with PE and 30 controls. Placental tissue samples were collected within 15 minutes postpartum. Placental promoter methylation was assessed using methylation-specific polymerase chain reaction (PCR), and protein expression was measured using enzyme-linked immunosorbent assay (ELISA). Group differences were analyzed, diagnostic accuracy was evaluated using receiver operating characteristic (ROC) curves, and associations were expressed as adjusted odds ratios (AOR).RESULTS: Compared with controls, placentas from women with PE significantly showed higher methylation of HLA-G (58.9% vs. 37.3%) and sEng (6.7% vs. 4.1%), and lower methylation of VEGF (30.4% vs. 48.1%) and MMP-9 (36.1% vs. 44.9%). Expression of MMP-9, HLA-G, and VEGF was significantly reduced, while sEng expression was increased in PE. Multivariate analysis identified HLA-G hypermethylation (AOR 5.36), VEGF hypomethylation (AOR 8.55), sEng methylation (AOR 4.57), low expression of MMP-9, HLA-G, and VEGF, and high sEng expression (AOR 4.77) as independent predictors of PE. sEng expression demonstrated the best discrimination (AUC 0.835), followed by sEng methylation (AUC 0.785) and HLA-G methylation (AUC 0.774).CONCLUSION: PE is associated with distinct placental methylation–expression alterations, with sEng- and HLA-G–related markers showing the strongest diagnostic value.KEYWORDS: preeclampsia, DNA methylation, angiogenesis, MMP-9, HLA-G, sEng, placenta, epigenetics
Precision Chromosomal Surgery before Birth: Allele-Specific CRISPR-Cas9 Editing for Trisomy 21 in Perinatal Medicine Sanjaya, I Nyoman Hariyasa; Andonotopo, Wiku; Bachnas, Muhammad Adrianes; Prabowo, Wisnu; Yuliantara, Eric Edwin; Lukas, Efendi; Dewantiningrum, Julian; Pramono, Mochammad Besari Adi; Wiradnyana, Anak Agung Gede Putra; Mulyana, Ryan Saktika; Kusuma, Anak Agung Ngurah Jaya; Pangkahila, Evert Solomon; Gumilar, Khanisyah Erza; Darmawan, Ernawati; Akbar, Muhammad Ilham Aldika; Yeni, Cut Meurah; Aldiansyah, Dudy; Bernolian, Nuswil; Pribadi, Adhi; Anwar, Anita Deborah; Suryawan, Aloysius; Putra, Ridwan Abdullah; Gondo, Harry Kurniawan; Nugraha, Laksmana Adi Krista; Andanaputra, Waskita Ekamaheswara Kasumba; Dharma, Wibisana Andika Krista; Djanas, Dovy; Stanojevic, Milan
Indonesian Journal of Obstetrics & Gynecology Science Volume 9 Number 1 March 2026
Publisher : Dep/SMF Obstetri & Ginekologi Fakultas Kedokteran Universitas Padjadjaran

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.24198/obgynia.v9i1.965

Abstract

Objective: Trisomy 21 remains the most common live-born aneuploidy and a major contributor to perinatal morbidity. Although prenatal screening, particularly non-invasive prenatal testing (NIPT), has advanced substantially, clinical management offers no corrective options. Emerging allele-specific genome-editing approaches propose targeted removal or silencing of the extra chromosome 21. This review summarizes current evidence and evaluates the translational relevance of these technologies in perinatal medicine.Methods: A narrative review was conducted following PRISMA-aligned procedures. A structured search of PubMed, Scopus, and Web of Science (January 2000–July 2025) identified 1,242 records. After duplicate removal, title/abstract screening, and full-text assessment based on predefined inclusion criteria, 54 studies met eligibility requirements. Data were synthesized across four domains: mechanistic strategies, developmental applicability, translational feasibility, and ethical–regulatory considerations.Results: Allele-specific CRISPR-Cas9 studies demonstrated selective cleavage of the supernumerary chromosome 21 in cellular models, with partial restoration of near-euploid transcriptional patterns. Additional approaches—XIST-mediated silencing and centromere destabilization—provided alternative mechanisms with varying stability and specificity. Evidence remains limited to in vitro systems, with no validated embryo or fetal applications. Key challenges include mosaicism, delivery barriers, individualized SNP targeting, and ethical governance.Conclusions: Allele-specific chromosome editing represents a promising but still experimental direction for future perinatal therapeutics. Current findings justify continued multidisciplinary investigation while emphasizing cautious interpretation and rigorous ethical oversight prior to any clinical translation. Abstrak Tujuan: Trisomi 21 tetap menjadi aneuploidi yang paling sering ditemukan pada kelahiran hidup dan merupakan kontributor utama terhadap morbiditas perinatal. Meskipun skrining prenatal—khususnya non-invasive prenatal testing (NIPT)—telah mengalami kemajuan yang signifikan, penatalaksanaan klinis hingga kini belum menawarkan opsi korektif. Pendekatan pengeditan genom spesifik alel yang mulai berkembang mengusulkan penghilangan atau penghambatan terarah terhadap salinan ekstra kromosom 21. Tinjauan ini merangkum bukti terkini serta mengevaluasi relevansi translasional teknologi tersebut dalam kedokteran perinatal.Metode: Tinjauan naratif dilakukan dengan mengikuti prosedur yang selaras dengan PRISMA. Pencarian terstruktur terhadap PubMed, Scopus, dan Web of Science (Januari 2000–Juli 2025) mengidentifikasi 1.242 rekaman. Setelah penghapusan duplikasi, penyaringan judul/abstrak, dan penilaian teks lengkap berdasarkan kriteria inklusi yang telah ditentukan, sebanyak 54 studi memenuhi persyaratan kelayakan. Data disintesis ke dalam empat domain: strategi mekanistik, aplikabilitas perkembangan, kelayakan translasional, serta pertimbangan etika dan regulasi.Hasil: Studi CRISPR-Cas9 spesifik alel menunjukkan pemotongan selektif terhadap kromosom 21 supernumerari pada model seluler, dengan pemulihan parsial pola transkripsi menuju profil ekspresi gen yang menyerupai kondisi euploid. Pendekatan lain—seperti penghambatan berbasis XIST dan destabilisasi sentromer—menyediakan mekanisme alternatif dengan tingkat kestabilan dan spesifisitas yang bervariasi. Bukti saat ini terbatas pada sistem in vitro, tanpa aplikasi yang tervalidasi pada embrio maupun janin. Tantangan utama meliputi mosaikisme, hambatan pengantaran, kebutuhan penargetan SNP individual, serta tata kelola etis.Kesimpulan: Pengeditan kromosom spesifik alel merupakan arah yang menjanjikan, namun masih bersifat eksperimental bagi terapi perinatal di masa mendatang. Temuan saat ini mendukung keberlanjutan penelitian multidisipliner, sekaligus menekankan perlunya interpretasi yang hati-hati dan pengawasan etika yang ketat sebelum penerapannya dalam praktik klinis.Kata Kunci: Bedah genom janin; CRISPR-Cas9; Penyuntingan gen perinatal; Terapi kromosom; Trisomi 21
Co-Authors Adhi Pribadi Aldiansyah, Dudy Aldika Akbar, Muhammad Ilham Aloysius Suryawan Anak Agung Gede Raka Budayasa Andanaputra, Waskita Ekamaheswara Kasumba Andonotopo, Wiku Anita Deborah Anwar Anom Suardika Anom Suardika Anom Suardika Arresta Vitasatria Suastika Bachnas, Muhammad Adrianes Bay, Godefridus Paulo Cut Meurah Yeni Darmawan, Ernawati DARMAYASA, K. Dharma, Wibisana Andika Krista Divika Silvana Djanas, Dovy Duarsa, Dyah Paramita Efendi Lukas Endang Sri Widiyanti Eric Edwin Yuliantara Evert Solomon Pangkahila Evert Solomon Pangkahila Gde Bagus Rizky Kornia GUNUNG, K. H. Sunny Sun Harry Kurniawan Gondo I Dewa Made Sukrama I Gde Raka Widiana I Gede Mega Putra I Gede Mega Putra I Gusti Bagus Indrajaya I Gusti Ngurah Agung Satria Wibawa I Gusti Putu Mayun Mayura I Ketut Suwiyoga I Made Bakta I Made Darmayasa I Made Darmayasa I Made Jawi I Nengah Sujaya I Nyoman Gede Budiana I Nyoman Hariyasa Sanjaya I Wayan Artana Putra I Wayan Megadhana Julian Dewantiningrum KARKATA, M. K. Ketut Suastika Khanisyah Erza Gumilar Leony Lim LUH MERTASARI . Luh Seri Ani Mantik AN Marta, Kadek Fajar Mayasari, Ni Nyoman Wistya Tri Mona Mariana Muhammad Freddy Candra Sitepu Ni Gusti Ayu Manik Ermayanti Ni Kadek Mulyantari Ni Nengah Dwi Fatmawati Ni Nyoman Ayu Dewi Nugraha, Cokorda Gde Angga Ary Nugraha, Laksmana Adi Krista Nuswil Bernolian Pradnyana, I Wayan Agus Surya Pramono, Mochammad Besari Adi Putra, Ridwan Abdullah Putra, Wayan Artana Putu Doster Mahayasa Ryan Saktika Mulyana Stanojevic, Milan Sutandi, Chatrine Vidya Saraswati Putri Duarsa Widi, Made Yudha Ganesa Wikantyas William William Wiradnyana, Anak Agung Gede Putra Wiradnyana, Anak Agung Putra WISNU PRABOWO Yen-An Tang