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All Journal Molecular and Cellular Biomedical Sciences (MCBS) Indonesian Journal of Cancer eJournal Kedokteran Indonesia Makara Journal of Health Research Makara Journal of Science
Antarianto, Radiana Dhewayani
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Biochemistry, Genetics & Molecular Biology Dentistry Immunology & microbiology Medicine & Pharmacology Neuroscience Public Health

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CD34+ UCB stem cells attenuate TGF-β signaling and inhibit liver fibrosis: A new avenue for liver cirrhosis-carcinogenesis prevention Septiana, Wahyunia Likhayati; Antarianto, Radiana Dhewayani; Louisa, Melva; Jusuf, Ahmad Aulia; Barasila, Atikah Chalida; Pawitan, Jeanne Adiwinata; Fasha, Iqbal
Makara Journal of Health Research Vol. 24, No. 2
Publisher : UI Scholars Hub

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Abstract

Background: The liver microenvironment plays a key role in liver fibrosis and carcinogenesis. This study aimed to fill the gap in knowledge on the interaction between hepatic stellate cells and endothelial progenitor cells with biomarkers of liver fibrosis and/or carcinogenesis, including Col1A1, TGF-β, and tenascin-C. Methods: CD34+ stem cells were isolated from umbilical-cord-blood mononuclear cells. 2D and 3D co-culture of CD34+ UCB SCs and LX2 was performed. The cells were incubated in a CO2 incubator for three days. Morphological observation, qRT-PCR of TGF-β1 and COL1A1, and immunocytochemistry of tenascin-C were performed. Results: CD34+ UCB SCs were viable in the 2D and 3D co-culture for 24 h. 3D co-culture of CD34+ UCB SCs and LX2 inhibited in vitro liver fibrosis by lowering Col 1A1 expression as compared to control. We observed lower TGF-β expression in 3D co-culture on days 1 and 2 followed by higher expression of TGF-β on day 3. 2D co-culture of CD34+ UCB SCs and LX2 showed a different level of COL1A1 and TGF- β expression compared with 3D co-culture. Spheroids from 2D co-culture of CD34+ UCB SCs and LX-2 showed immunoreactivity against tenascin-C. Conclusion: Interaction between LX-2 and CD34+ UCB SCs in 3D co-culture inhibits in vitro liver fibrosis. The viability of CD34+ UCB SCs is essential for attenuation of TGF-β signaling in LX-2.
Effect of Calorie Restriction on the Expression of Sirtuin1 as an Antiaging Biomarker Penantian, Raya Makarim; Antarianto, Radiana Dhewayani; Hardiany, Novi Silvia
Makara Journal of Science Vol. 27, No. 3
Publisher : UI Scholars Hub

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Calorie restriction (CR) is the most effective method for delaying aging and preventing the onset of age-related diseases. Sirtuins constitute a family of nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylases. Their activity can be regulated by NAD+/NADH levels, which are influenced by nutrient intake, a variable acted upon by CR. This review elaborates on the link between CR and sirtuin1 (SIRT1). It retrieved articles from several sources, such as ClinicalKey, PubMed, and ScienceDirect. It discusses the up-to-date knowledge of how SIRT1 acts as a nutrient sensor and regulator of molecular mechanisms. These mechanisms include the control of the cell cycle, enhancing mitochondrial quality control, activating fatty acid oxidation, and stimulating anti-inflammatory effects. Disruptions in the aforementioned mechanisms are the basis of aging. CR increases the expression of SIRT1, which enhances the biogenesis and dynamics of mitochondria, resulting in an antiaging effect. In CR, SIRT1 is activated and stimulates different pathways, especially those related to mitochondrial activity and effectiveness, leading to an antiaging effect in collaboration with other antiaging biomarkers
Adipose-Derived Mesenchymal Stem Cells Extracellular Vesicles (ADMSCs-EVs) Implantation in Critical Size Bone Defect Model: Callus Formation Histology, BMP2, and Wnt Signaling Kousar, Iqra; Dilogo, Ismail Hadisoebroto; Antarianto, Radiana Dhewayani; Pawitan, Jeanne Adiwinata; Mahmood, Amer; Rahyussalim
eJournal Kedokteran Indonesia Vol. 12 No. 2 (2024): Vol. 12 No. 2 - Agustus 2024
Publisher : Faculty of Medicine Universitas Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.23886/ejki.12.803.114

Abstract

Critical bone defects pose a substantial healthcare burden globally. This study aimed to investigate the miRNA content ADMSCs-Evs (exosomes), which affected critical-sized bone histology, BMP2, and Wnt signalling pathways. Total RNA extraction and microarray analysis of miRNA were conducted. In-vivo experiments were performed on 16 critical-sized bone defect SD rats (eight for ADMSCs-EVs/exosomes and eight for NaCl) and four healthy control SD rats. The rats from each group were sacrificed on day 14 and day 28. Bone defect samples were collected for histology, protein, and molecular analysis. Histology analysis revealed increasing soft callus formation in the EVs ADMCs (exosomes) treated group on days 14 and 28 compared to the negative control group. Downregulation of miR-433-3p, miR-542-3p, and miR-328-3p in EVs ADMCSs (exosomes) enhances Wnt3A expression. Upregulation of miR-93-5p in ADMSCs-Evs (exosomes) inhibits BMP2 signalling, confirmed by BMP2 ELISA and higher chordin (BMP-2 antagonist) expression. Spp1 as a downstream gene of BMP-2 and Wnt signalling are indifferent. Specific miRNA inside ADMSCs-EVs (exosomes) regulates BMP-2 and Wnt signalling to enhance soft callus formation in critical size bone defect in EVs treated group than in negative control.
Stimulation Effect of Exosome From Healthy Sera to Natural Killer (NK) Cells of Hepatocellular Carcinoma Subject In Vitro Deby, Deby; Antarianto, Radiana Dhewayani; Barasila, Atikah Chalida; Irawan, Cosphiadi; Ahani, Ardhi Rahman; Jasirwan, Chyntia Olivia Maurine; Damayanti, Lia; Ritchie, Ni Ken; Aditya, Robby Nur
Indonesian Journal of Cancer Vol 18, No 4 (2024): December
Publisher : http://dharmais.co.id/

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.33371/ijoc.v18i4.1122

Abstract

Background: Hepatocellular carcinoma has a poor prognosis due to limitations of therapy such as late diagnosis, lack of specific biomarkers, and insensitivity to this tumor agent. This study aims to develop immunotherapy using autologous natural killer cells (NK cells) with exosome stimulation for hepatocellular carcinoma patients, addressing treatment limitations.Methods: Experimental research conducted from October 2022 to June 2023 at Universitas Indonesia’s Faculty of Medicine involved three hepatocellular carcinoma patients at Dr. Cipto Mangunkusumo General Hospital in Jakarta, Indonesia. NK cells from hepatocellular carcinoma patients were isolated from peripheral venous blood, and exosomes were isolated from the blood serum of healthy donors. Exosome characterization with a particle size analyzer and flow cytometry. Stimulation of exosomes on NK cells for 24 hours, then evaluation of expression of NKp44, NKp46, NKp30, NKG2D, KIR2D, and NKG2A receptors, as well as perforin and granzyme B expression. Visualization of interactions of NK cells with other mononuclear cell fractions (CD4, CD8, CD11c, and CD19) by immunofluorescence. The study compares stimulated and unstimulated NK cells, analyzing their expression of activated and inhibitory receptors, using either the One-Way Anova parametric test or the Kruskal-Wallis non-parametric test for non-normally distributed data.Results: Particle size 100 nm, negative electric charge, and CD63+CD81+ (double positive) exosome isolated results. There was increased expression of receptors NKp44, NKp46, NKp30, NKG2D, decreased expression of NKG2A, and increased expression of perforin and granzyme B in exosome-induced NK cells. There was no cell interaction in the form of immune synapses between exosome-induced NK cells and other mononuclear cell fractions in hepatocellular carcinoma patients. Conclusions: Induction of exosomes into NK cells of hepatocellular carcinoma patients restores the cytotoxic ability of NK cells
Potential Anti-Senescence Effect of Extract from Andrographis paniculata Herbal Plant and Its Bioactive Compounds: A Systematic Review Khatimah, Nurul Gusti; Arozal, Wawaimuli; Barinda, Agian Jeffilano; Antarianto, Radiana Dhewayani; Hardiany, Novi Silvia; Shimizu, Ippei; Fadhillah, Muhamad Rizqy
Molecular and Cellular Biomedical Sciences Vol 8, No 3 (2024)
Publisher : Cell and BioPharmaceutical Institute

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.21705/mcbs.v8i3.432

Abstract

The rapid aging of the global population is a major worldwide issue because of the close relationship between age and the development of several diseases. Aging or senescence is among the most widely studied topics at the moment. However, no pharmaceuticals have been developed that claim to possess anti-senescence properties. Andrographis paniculata, is a medicinal plant found widely throughout tropical and subtropical Asia. This review aims to identify the potential anti- senescence effect of A. paniculata extract and its bioactive compounds. By following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, five databases were used and in vivo and in vitro studies were included in this review. A. paniculata extracts and their bioactive compounds exert anti-senescence properties through their anti-inflammatory and antioxidant properties. This herb and its compounds enhanced memory, cognitive function and behaviour in Alzheimer's disease. The extract also promoted cell cycle progression and proliferation in the skin. In addition, andrographolide exhibited anti-senescence effects in endothelial cells through the activation of PI3K/Akt/Nrf and PI3K/Akt/AP-1 pathways. A. paniculata along with its bioactive compounds including andrographolide and 14-deoxyandrographolide, may have the potential to be used as anti-senescence through anti-inflammatory and antioxidant properties. However, the specific markers to evaluate the senescence are necessary to be conducted. Any clinical trials should be done to establish these findings. Since in clinical settings this potential herbal may be used for long-life time, the safety profile and toxicity of A. paniculata should be considered. Keywords: herbal plants, Andrographis paniculata, andrographolide, bioactive compounds, senescence
Histodynamics of Natural Killer Cells from a Healthy Donor Exposed to Exosomes from the Blood of Hepatocellular Carcinoma Patients Asrinda, Indria; Antarianto, Radiana Dhewayani; Jusuf, Ahmad Aulia; Ahani, Ardhi Rahman; Jasirwan, Chyntia Olivia Maurine; Ritchie, Ni Ken; Nur Aditya, Robby; Irawan, Cosphiadi
Makara Journal of Health Research
Publisher : UI Scholars Hub

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Abstract

Background: Hepatocellular carcinoma (HCC) is the leading form of liver cancer and the second leading cause of cancer-related deaths globally. Exosomes in the HCC microenvironment can induce significant changes in natural killer (NK) cells during endocytosis. The present study aimed to distinguish exosomes in the blood of HCC patients, analyze changes in NK cell phenotype, and evaluate peroxidase and toluidine blue staining as alternative methods for observing the changes. Methods: NK cells were collected from healthy donors, and exosomes were extracted from the blood of HCC patients. The exosomes were characterized in accordance with MISEV 2018 guidelines, and NK cells were incubated with HCC-derived exosomes. NK cell phenotype changes were assessed using immunofluorescence, toluidine blue staining, and peroxidase staining. Results: The identified exosomes measured 34.7 nm, had a charge of −4.33 mV, and were positive for CD81+. Changes in NK cell receptor expression following exposure to HCC exosomes were not significant (p > 0.05). Immunofluorescence confirmed exosome endocytosis by NK cells, toluidine blue staining revealed negative metachromasia and peroxidase staining indicated morphological NK cell changes. Conclusions: This study demonstrates that peroxidase and toluidine blue staining are effective for observing exosome endocytosis in NK cells, enhancing our understanding of HCC exosome-NK cell interactions and beneficial in developing future therapeutic strategies targeting the HCC microenvironment.
Co-Authors Aditya, Robby Nur Agian Jeffilano Barinda Ahani, Ardhi Rahman Ahmad Aulia Asrinda, Indria Barasila, Atikah Chalida Chyntia Olivia Maurine Jasirwan, Chyntia Olivia Maurine Cosphiadi Irawan Deby Deby Fadhillah, Muhamad Rizqy Fasha, Iqbal Ismail Hadisoebroto Dilogo Khatimah, Nurul Gusti Kousar, Iqra Lia Damayanti Mahmood, Amer Melva Louisa Ni Ken Ritchie, Ni Ken Novi Silvia Hardiany Nur Aditya, Robby Pawitan, Jeanne Adiwinata Pawitan, Jeanne Adiwinata Penantian, Raya Makarim Rahyussalim Shimizu, Ippei Wahyunia Likhayati Septiana Wawaimuli Arozal