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All Journal Medical Journal of Indonesia The Indonesian Biomedical Journal Molecular and Cellular Biomedical Sciences (MCBS) Indonesian Journal of Cancer 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
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 Vol. 28, No. 3
Publisher : UI Scholars Hub

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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.
Tumor Microenvironment in Colorectal Cancer Development: A Review of 3D Study Analysis Angka, Rebecca Noerjani; Sudoyo, Aru Wisaksono; Siregar, Nurjati Chairani; Jeo, Wifanto Saditya; Antarianto, Radiana Dhewayani
Indonesian Journal of Cancer Vol 18, No 1 (2024): March
Publisher : http://dharmais.co.id/

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.33371/ijoc.v18i1.1089

Abstract

Background: Colorectal cancer is the third most common cancer in 2020, with a high mortality rate. Colorectal cancer treatment has made many advances. However, many factors in the tumor microenvironment still have not been reached but significantly affect the success of treatment. This literature review was conducted to search for research articles that analyze factors in the tumor microenvironment, how they interact through studies primarily conducted in 3D, and how to prepare for 3D research on colorectal cancer will be briefly discussed. The aim of this systematic review is to study the components of the tumor microenvironment in colorectal cancer development as assessed by 3D studies. Methods: Article searches were conducted through Embase, Scopus and PubMed. From the 110 articles found at the beginning of the search, after going through several screening stages, 27 articles were determined that met the inclusion criteria. The inclusion criteria used were journals containing research articles on colorectal cancer in the last five years with topics regarding the tumor microenvironment and according to keywords. Results: Microenvironment components in colorectal cancer, consisting of cellular and noncellular components, have the most significant effect on cancer development and ultimately affect metastasis, response to treatment, and prognosis.  Conclusions: This literature review proves that the components of the tumor microenvironment are very diverse, making colorectal cancer heterogeneous. It still requires a lot of research to prove the existence of other components that affect the effectiveness of the treatment.
Andrographis paniculata Ethanol Extract Alleviates High Glucose-induced Senescence of Human Umbilical Vein Endothelial Cells via the Regulation of mTOR and SIRT1 Pathways Khatimah, Nurul Gusti; Arozal, Wawaimuli; Barinda, Agian Jeffilano; Antarianto, Radiana Dhewayani; Hardiany, Novi Silvia; Shimizu, Ippei; Fadhillah, Muhamad Rizqy
The Indonesian Biomedical Journal Vol 16, No 4 (2024)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v16i4.3067

Abstract

BACKGROUND: Chronic exposure of high glucose (HG) in endothelial cell induces senescence which may contribute to the development and progression of age-related diseases including insulin resistance. Andrographis paniculata improves insulin resistance in recent in vitro and in vivo studies. Anti-inflammatory and antioxidant properties of A. paniculata may be the new therapeutic approach to inhibiting premature senescence. However, the senolytic effect of A. paniculata on endothelial cells has not been investigated comprehensively. This study was conducted to evaluate the effect of A. paniculata extract on HG-induced endothelial cell senescence and the underlying mechanisms.METHODS: Human umbilical vein endothelial cells (HUVECs) were treated with 33 mM HG and 7.5 μg/mL A. paniculata extract for 48 hours. The expressions of p16, p21, interleukin (IL)-6, IL-8, insulin receptor substrate (IRS)-1, mammalian target of rapamycin, and sirtuin 1 (SIRT1) were measured by performing real-time quantitative polymerase chain reaction (RT-qPCR). The senescence-associated-β-galactosidase (SA-β-gal) staining was performed to observe the positive-stained senescent cells, while the cell surface expression of IL-1α was examined with flow cytometry method.RESULTS: A. paniculata extract reversed senescence in HUVECs under HG conditions by reducing mRNA expressions of p16 and p21, the number of SA-β-gal-positive-stained cells, and the expression of IL-1α on cell surface, which decreased the activation of IL-6 and IL-8. In addition, A. paniculata extract decreased the mRNA expression of mTOR and increased the mRNA expressions of IRS-1 as well as SIRT1.CONCLUSION: A. paniculata extract ameliorated senescence and improved insulin sensitivity by regulating the mTOR, SIRT1, and IRS-1 mRNA expressions on HG-treated HUVECs.KEYWORDS: Andrographis paniculata, endothelial cell, senescence, high glucose, nutrient-sensing pathways
Comparison of Maturation Stages of Natural Killer Cell Differentiation Culture from Cultured and Freshly Isolated Umbilical Cord Blood Hematopoietic Stem Cells Wijaya, Samuel Febrian; Lestari, Retno; Rahmawati, Inna; Sianipar, Imelda Rosalyn; Nuraditya, Robby; Fasha, Iqbal; Pratama, Gita; Antarianto, Radiana Dhewayani
Makara Journal of Health Research Vol. 27, No. 1
Publisher : UI Scholars Hub

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Abstract

Background: Natural killer (NK) cells originate from the differentiation of hematopoietic stem cells (HSCs) in the common lymphoid progenitor pathway, and HSCs can be obtained from umbilical cord blood (UCB). Comparative studies of NK cell differentiation between cultured and freshly isolated HSCs are important in the development of NK cell therapy for cancer. This study aimed to compare the maturation stages of NK cell differentiation between cultured and newly isolated HSC samples using interleukin-2 in the absence of feeder cells. Methods: Differentiation cultures were divided into two groups according to HSC source. Giemsa staining and flow cytometry were performed to determine the maturation stages and the presence of NKp46 receptors, respectively. Results: Giemsa staining revealed that the cultured HSC samples produce a higher number and more mature (stage 5) NK cells than the freshly isolated HSC samples. Flow cytometry showed that the NKp46 mean fluorescence intensity significantly differed between the two samples, and a high level of NKp46 activation receptor was found in the isolated samples on day 35. Conclusions: The cultured HSC samples could produce more mature NK cell populations than the freshly isolated HSCs, which will be beneficial for the therapy applications of NK cells derived from UCB HSCs.
Adipose-derived mesenchymal stem cells enhance regeneration in a chronic peripheral sciatic nerve injury Sprague-Dawley rat model Widodo, Wahyu; Dilogo, Ismail Hadisoebroto; Kamal, Achmad Fauzi; Antarianto, Radiana Dhewayani; Wuyung, Puspita Eka; Siregar, Nurjati Chairani; Octaviana, Fitri; Kekalih, Aria; Suroto, Heri; Aprilya, Dina; Canintika, Anissa Feby
Medical Journal of Indonesia Vol. 34 No. 3 (2025): September
Publisher : Faculty of Medicine Universitas Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.13181/mji.oa.257780

Abstract

BACKGROUND Obtaining optimal functional outcomes in patients with chronic peripheral nerve injuries (PNIs) remains challenging due to the limited regeneration of the neuromuscular junction (NMJ). Adipose-derived mesenchymal stem cells (AD-MSCs) can differentiate into Schwann-like cells, secrete neurotrophic factors, and recruit native Schwann cells. This study aimed to analyze the effects of AD-MSCs on functional outcomes in a chronic PNI model. METHODS An in vivo study was performed using 20 male Sprague-Dawley rats with chronic PNI of the right sciatic nerve. Rats were divided into two groups: the AD-MSC group (n = 10), receiving human AD-MSC injections in the NMJ; and the control group (n = 10), receiving normal saline injections. Walking track analysis and electrophysiological assessments were performed 8 weeks after the nerve repair. Postmortem gastrocnemius muscle weights and immunohistochemical examinations were also performed. RESULTS The AD-MSCs showed significantly larger fiber diameters than the control group (45.54 [13.1] versus 35.46 [6.64]; p = 0.011). While clinical, electrophysiological, and gastrocnemius muscle weight data suggested a trend toward improved outcomes in the AD-MSCs group, the differences were not statistically significant. CONCLUSIONS AD-MSC implantation may enhance nerve regeneration, as demonstrated by a better outcome profile in the AD-MSCs group.
Co-Authors Achmad Fauzi Kamal Aditya, Robby Nur Agian Jeffilano Barinda Ahani, Ardhi Rahman Ahmad Aulia Angka, Rebecca Noerjani Aprilya, Dina Aria Kekalih Asrinda, Indria Barasila, Atikah Chalida Canintika, Anissa Feby Chyntia Olivia Maurine Jasirwan, Chyntia Olivia Maurine Cosphiadi Irawan Deby Deby Fadhillah, Muhamad Rizqy Fasha, Iqbal Fitri Octaviana Gita Pratama Heri Suroto Imelda Rosalyn Sianipar Ismail Hadisoebroto Dilogo Jeo, Wifanto Saditya Khatimah, Nurul Gusti Kousar, Iqra Lia Damayanti Mahmood, Amer Melva Louisa Ni Ken Ritchie, Ni Ken Novi Silvia Hardiany Nur Aditya, Robby Nuraditya, Robby Nurjati Chairani Siregar Pawitan, Jeanne Adiwinata Pawitan, Jeanne Adiwinata Penantian, Raya Makarim Puspita Eka Wuyung Rahmawati, Inna Rahyussalim Rahyussalim, Rahyussalim Retno Lestari Shimizu, Ippei Sudoyo, Aru Wisaksono Wahyu Widodo Wahyunia Likhayati Septiana Wawaimuli Arozal Wijaya, Samuel Febrian