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All Journal HAYATI Journal of Biosciences SAINS MEDIKA : JURNAL KEDOKTERAN DAN KESEHATAN Jurnal Kedokteran Brawijaya Majalah Kedokteran Bandung Althea Medical Journal Indonesian Journal of Cancer Chemoprevention Indonesian Journal of Pharmaceutical Science and Technology Universa Medicina Molecular and Cellular Biomedical Sciences (MCBS) Jurnal Profesi Medika: Jurnal Kedokteran dan Kesehatan Narra J The Avicenna Medical Journal Indonesian Journal of Cancer Journal of Health and Nutrition Research Makara Journal of Health Research Contemporary Journal on Business and Accounting Narra X International Journal of Cell and Biomedical Science Indonesian Journal of Biomedicine and Clinical Sciences Biosaintifika: Journal of Biology & Biology Education Indonesian Journal of Medical and Pharmaceutical Science
Agung Putra
Faculty of Medicine Universitas Islam Sultan Agung, Semarang
Agriculture, Biological Sciences & Forestry Biochemistry, Genetics & Molecular Biology Chemistry Computer Science & IT Decision Sciences, Operations Research & Management Dentistry Earth & Planetary Sciences Economics, Econometrics & Finance Education Health Professions Immunology & microbiology Materials Science & Nanotechnology Medicine & Pharmacology Neuroscience Nursing Physics Public Health Social Sciences Other

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Exosome Hypoxic-MSCs, Glutathione, and Vitamin C: Effect on IL-10 Levels and CD-163 Expression Utami, Wulan Dyah; Muhar, Adi Muradi; Sumarawati, Titiek; Putra, Agung; Setiawan, Eko; Ibrahim, Sugeng; Taskworo, Dodik; Haitamy, Mohammad Nurrizki
Indonesian Journal of Pharmaceutical Science and Technology Vol 12, No 3 (2025)
Publisher : Indonesian Journal of Pharmaceutical Science and Technology

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.24198/ijpst.v12i3.60941

Abstract

Hyperpigmentation of the skin is a result of ultraviolet B (UVB) exposure, which causes oxidative stress due to increased reactive oxygen species (ROS), leading to various skin problems, including melanin accumulation. Exosomes can affect melanocyte activity. Exosomes, as small vesicles released by cells, can affect melanocyte activity and play an important role in various hyperpigmentation processes. The study aims to determine the effect of exosome mesenchymal stem cell hypoxia (EH-MSC) and glutathione with vitamin C on IL-10 levels and CD163 expression. IL-10 gene expression was measured using qRT-PCR, while CD163 expression was analyzed via immunohistochemical staining. A total of 30 male C57BL/6 mice were used and randomly assigned to five different treatment groups. The highest expression of IL-10 was observed in the EH-MSCs-treated group (K4), although the difference was not statistically significant compared to the control (p = 0.135). In contrast, the group receiving a combination of EH-MSCs with glutathione and vitamin C (K5) exhibited the highest percentage of CD163 expression, with a statistically significant difference (p = 0.00). These findings demonstrate that the administration of EH-MSC and glutathione with vitamin C significantly increased the expression of CD163, but insignificantly increased IL-10 in C57BL/6 mice with a UVB-induced hyperpigmentation model.
Potential Use of the Gel Extract of Butterfly Pea Flower as Topical Therapy to Prevent Photodamage by Downregulating TNF-α and Caspase-3 Expression Levels in UVB-Exposed Rats Cahyani, Elvana; Putra, Agung; Subchan, Prasetyowati
Makara Journal of Health Research Vol. 27, No. 1
Publisher : UI Scholars Hub

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

Abstract

Background: Prolonged exposure to UVB radiation causes DNA damage in skin cells by raising the levels of reactive oxygen species, resulting in the production of inflammatory factors and skin issues. Plant extracts are frequently used to counteract photodamage due to their antioxidant properties. One example is the floral extract of the butterfly pea plant, which contains flavonoid antioxidants. However, the effect of the extract on inflammatory factors is unknown. This study investigated how tumor necrosis factor-alpha (TNF-α) and caspase-3 expression changed when a butterfly pea flower extract gel was applied topically to UVB-exposed animals. Methods: Experimental and control groups were tested. The healthy group was not exposed to UVB. The negative controls and treatments 1 and 2 were exposed daily for 5 days at a minimal erythema dose of 160 mJ/cm2 and then treated with a gel-based extract containing 5% and 10% of the extract, respectively. A 96% ethanol solution was used during the maceration step for the extraction. Real-Time Quantitative Reverse Transcription PCR was used to examine gene expression levels in the skin tissue on day 14. Results: The expression levels of TNF-α and caspase-3 decreased in the treatment group, and higher doses of the extract had a greater effect. Conclusions: The gel extract considerably reduced the UVB-induced TNF-α and caspase-3 production in rats.
Secretome hypoxia-mesenchymal stem cells decrease tumor necrosis factor-α and interleukin-18 in kidney of type 2 diabetes mellitus model rats Irawan, Risky Chandra Satria; Putra, Agung; Setyo, Trisnadi; Ghaisani, Shabrina Syifa; Hidayah, Nurul
Universa Medicina Vol. 42 No. 3 (2023)
Publisher : Faculty of Medicine, Universitas Trisakti

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18051/UnivMed.2023.v42.320-328

Abstract

Background Type 2 diabetes mellitus (T2DM) is a chronic disease that affects millions of people worldwide and associated with an increased risk of kidney damage caused by prolonged inflammation. Secretome hypoxia- mesenchymal stem cells (SH-MSCs) have been investigated as a potential therapy for kidney inflammation in T2DM, due to their immunomodulatory properties and ability to promote tissue repair. In this study, we investigated the effects of SH-MSCs on tumor necrosis α (TNF-á) and interleukin-18 (IL-18) in the kidney of the T2DM model rats. MethodsA post-test-only control group involving 24 male Wistar rats. The rats were treated with a high-fat diet (HFD) for 4 weeks and streptozotocin-nicotinamide with sucrose solution for 5 days to induce T2DM animal models. Rats were randomly divided into four groups: healthy, control, and groups treated with SH-MSCs T1 and T2, with doses of 250 µL and 500 µL, respectively. TNF-α and IL-18 gene expression was measured by real time polymerase chain reaction (RT-PCR). One Way ANOVA and post-hoc LSD tests were used to determine the significant difference against all groups based on their quantitative measurement. ResultsAdministration of the SH-MSCs at a dose of 500µL (T2) was able to significantly reduce TNF-α and IL-18 gene expression when compared to control (T2DM rat without treatment) (p<0.05), but not significantly when compared to healthy and SH-MSC at a dose of 250µL (T1) group (p>0.05). ConclusionThis study demonstrated that the SH-MSCs decreased the levels of proinflammatory cytokines TNF-α and IL-18 gene expression in the kidney of T2DM model rats.
The Role of Hypoxic Mesenchymal Stem Cells Conditioned Medium in Increasing Vascular Endothelial Growth Factors (VEGF) Levels and Collagen Synthesis to Accelerate Wound Healing Sunarto, Hadi; Trisnadi, Setyo; Putra, Agung; Sa'dyah, Nur Anna Chalimah; Tjipta, Arya; Chodidjah, Chodidjah
Indonesian Journal of Cancer Chemoprevention Vol 11, No 3 (2020)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev11iss3pp134-143

Abstract

Full-thickness wound are areas damage of skin associated with loss of epidermis and dermis. The wound healing mechanism consists proliferation, migration and remodeling. Hypoxic conditional medium of mesenchymal stem cells (HMSCs-CM) contains lots of soluble molecules, such as protein growth factor and cytokine anti-inflammation. The soluble molecule of HMSCs-CM plays a critical role in wound healing by upregulation of VEGF and collagen synthesis. The objective of this study was to evaluate the effect of HMSCs-CM on VEGF and collagen concentrations in rats with incised wounds. The methods of this study were an experimental animal study with post-test only control group design was performed involving 24 Wistar rats. The rats were randomized into four groups consisting of sham, control and two treatment groups (gel of HMSCs-CM at doses of 200 μL and 400 μL). The VEGF levels and collagen density were analyses using ELISA assay and Masson-trichome specific staining, respectively. One-way ANOVA and Post Hoc LSD were used to analyses the data. The results of this study showed that a VEGF levels was significant increased on day 6 with doses-dependent manner. Interestingly, the VEGF levels gradual decrease on day 9. In addition, the decreased of VEGF levels on day 9 in this study in line with our findings in which we found there was a trend in the decreased of collagen density, it indicated the completion of remodeling phase and there has been an acceleration in wound healing. This study demonstrated that HMSCs-CM were able to regulate VEGF levels and collagen synthesis in accelerate wound healing. The role of HMSCs-CM stimulate cutaneous wound healing should be clarified further.Keywords: hypoxic conditional medium of mesenchymal stem cells (HMSCs-CM), vascular endothelial growth factor, collagen synthesis, paracrine factors
Hypoxia-Exosome Mesenchymal Stem Cells Therapy Reduces Interleukin-6 Levels and CD86 Expression Isfandiari, Adelia Bayu; Putra, Agung; Setiawan, Eko
Molecular and Cellular Biomedical Sciences Vol 9, No 3 (2025)
Publisher : Cell and BioPharmaceutical Institute

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.21705/mcbs.v9i3.660

Abstract

Background: UVB exposure activates type 1 macrophages (CD86) and increases IL-6, both contributing to collagen loss. exosome hypoxia mesenchymal stem cells (EH-MSC) has anti-inflammatory properties, suggesting its potential role in modulating CD86 activation and IL-6 secretion. This study examines the effects of EH-MSC injections on CD86 and IL-6 levels in UVB-exposed skin with collagen loss.Materials and methods: Experimental research post-test only control group design was conducted with 30 male Wistar rats (Rattus norvegicus, strain: Wistar Han) divided into five groups. G1: healthy rats, G2: UVB-exposed with a subcutaneous injection of 0.9% NaCl, G3: UVB-exposed with Hyaluronic Acid, and G4 & G5: UVB-exposed with EH-MSC injections of 200 µL and 300 µL, respectively. IL-6 and CD86 levels were analysed using ELISA and qRT-PCR at 14 days post-treatment continue with statistical analysis.Results: IL-6 analysis showed that levels in G4 (107.70±47.86 pg/mL) and G5 (58.68±25.37 pg/mL) were notably lower than in G2 and G3 (p<0.05). Compared to G1 (32.28±14.65 pg/mL), G4 exhibited a statistically distinct increase (p<0.05), whereas G5 showed no significant difference (p>0.05). Meanwhile, CD86 data analysis showed that G4 (0.53±0.14 pg/mL) were lower than in G1 (1.03±0.01 pg/mL) and G2 (1.47±0.43 pg/mL), but not significantly different from G3 (0.87±0.1 pg/mL) and G5 (0.36±0.08 pg/mL). Similarly, CD86 expression in G5 decreased relative to G1 and G2 (p<0.05) but remained similar to G3 and G4.Conclusion: EH-MSC injections (200 µL and 300 µL) significantly reduced IL-6 and CD86 levels in collagen loss rats, supporting its potential as a therapeutic approach for UVB-induced skin damage.Keywords: collagen loss, CD86, EH-MSC, IL-6, UVB
Exosome Therapy from Hypoxia-treated Mesenchymal Stem Cells Reduces TNF-α and Increases VEGF Levels in Fluconazole-Induced Alopecia Model Sulistami, Siska Marlina; Mulyani, Sri Priyantini; Putra, Agung; Setiawan, Eko
Molecular and Cellular Biomedical Sciences Vol 9, No 3 (2025)
Publisher : Cell and BioPharmaceutical Institute

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.21705/mcbs.v9i3.642

Abstract

Background: Alopecia is a condition with partial or complete hair loss, leading to psychological distress. Current treatments, such as minoxidil and finasteride, have limited efficacyand side effects. Recent studies suggest that mesenchymal stem cells (MSCs)-derived exosomes offer regenerative potential by modulating inflammation and enhancing hair follicle regeneration, though optimal dosage remains unclear. Tumor necrosis factor-alpha (TNF-α)  inhibits hair follicle growth, while vascular endothelial growth factor (VEGF) promotes hair regrowth. This study evaluates  exosome therapy from hypoxia (Hypo-Exo)-treated MSCs in modulating TNF-α and VEGF in a fluconazole-induced alopecia-like model..Materials and methods: An experimental post-test only control group design was used with 30 male Wistar rats, divided into five groups:  Healthy group, 0.9% NaCl-treated group, 5% Minoxidil-treated group, 100 μg/mL Hypo-Exo MSCs-treated group, and 200 μg/mL Hypo-Exo MSCs-treated group. TNF-α and VEGF levels were analyzed using ELISA on day 14 post-treatment. Results: The highest TNF-α level was found in the 0.9% NaCl-treated group (307.46 ± 20.68 pg/mL) and significantly reduced (p<0.05) in 100 μg/mL Hypo-Exo MSCs-treated group (65.38±15.05 pg/mL) and 200 μg/mL Hypo-Exo MSCs-treated group (37.16±7.14 pg/mL). VEGF levels were the highest in the 200 μg/mL Hypo-Exo MSCs-treated group (189.11±9.75 pg/mL) and 100 μg/mL Hypo-Exo MSCs-treated group (158.50±5.33 pg/mL), compared to the 0.9% NaCl-treated group (69.60±15.39 pg/mL). Conclusion: Hypo-Exo MSCs significantly reduced TNF-α and increased VEGF levels, supporting their potential as a novel regenerative therapy for alopecia. Keywords: alopecia, TNF-α, VEGF, exosome, hypoxia, mesenchymal stem cells 
Hypoxic mesenchymal stem cell-derived secretome and alkaline water synergistically reduce apoptosis and insulin resistance in type 2 diabetes mellitus rat model Mawarini, Melisa Septi; Setiawan, Eko; Putra, Agung
Universa Medicina Vol. 44 No. 3 (2025): Ahead Of Print
Publisher : Faculty of Medicine, Universitas Trisakti

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18051/UnivMed.2025.v44.310-317

Abstract

BACKGROUNDType 2 Diabetes Mellitus (T2DM) is characterized by chronic inflammation and insulin resistance. These factors contribute to pancreatic β-cell apoptosis, reducing insulin production and impairing glucose homeostasis. This study aims to evaluate the protective effects of hypoxic mesenchymal stem cell-derived secretome (HMSCS) and alkaline water on inflammation, apoptosis, and insulin resistance in a T2DM rat model. METHODSAn experimental study was conducted involving 24 male Wistar T2DM model rats (aged 6-8 weeks, 200-250g). They were randomized into four groups: T2DM rats only as negative control (K-), T2DM rats with metformin as positive control (K+), HMSCS treatment (P1), and HMSCS plus alkaline water group (P2). Caspase-3 expression was measured to assess apoptosis levels using RT-PCR, while homeostatic model assessment for insulin resistance (HOMA-IR) was measured using ELISA. One way ANOVA followed by a post hoc LSD test were used to analyse the data. RESULTSThe P1 group (3.03 ± 1.26 a.u) and P2 group (2.93 ± 0.52 a.u.) had significantly lower caspase-3 expression compared to K- group (6.66 ± 2.76 a.u.) (p<0.05), but were not significantly different from K+ group (3.83 ± 1.61 a.u.) (p>0.05). Additionally, P2 group (6.76 ± 0.96) had a significantly lower HOMA-IR than K- group (18.92 ± 2.63) and K+ group (10.85 ± 1.39) (p<0.05), and similarly the P1 (7.71 ± 0.53) group also showed significant difference from K- and K+ groups (p<0.05). CONCLUSIONHigher doses of HMSCS and alkaline water are associated with reduced pancreatic β-cell apoptosis and improved insulin sensitivity, highlighting its potential as a novel therapeutic approach for T2DM.
Modulation of GLUT4 and FOXO1 Expression by SH-MSC and Alkaline Water in Experimental Type 2 Diabetes Mellitus Fatmawati, Dian; Putra, Agung; Setiawan, Eko
Journal of Health and Nutrition Research Vol. 4 No. 3 (2025)
Publisher : Media Publikasi Cendekia Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.56303/jhnresearch.v4i3.562

Abstract

Type 2 Diabetes Mellitus (T2DM) is a metabolic disorder characterized by insulin resistance, which is associated with the dysregulation of glucose transporter 4 (GLUT4) and forkhead box protein O1 (FOXO1). The secretome from hypoxia-preconditioned mesenchymal stem cells (SH-MSC) and alkaline water have been proposed as potential therapies to modulate these molecular targets and improve glycemic control; however, their combined effects remain unexplored.  Using an experimental post-test-only control group design, this study aimed to assess the possible additive effect of SH-MSC and alkaline water on the expression of GLUT4 and FOXO1 in Wistar rats with type 2 diabetes. Twenty-five male Wistar rats were split into five groups: healthy control (G1), T2DM control (G2), T2DM with metformin (G3), T2DM with SH-MSC (G4), and T2DM with SH-MSC and alkaline water (G5).  Streptozotocin and nicotinamide were utilized to induce T2DM, and qRT-PCR was used to measure the expression of GLUT4 and FOXO1 in pancreatic tissue. One-way ANOVA and a post hoc LSD test were used for statistical analysis. The findings recognized that while GLUT4 expression was decreased, T2DM induction markedly increased fasting blood glucose levels and FOXO1 expression. SH-MSC treatment significantly upregulated GLUT4 and downregulated FOXO1 equated to the control T2DM group, and while the addition of alkaline water showed a further trend of improvement, this difference was not statistically significant. These findings suggest that SH-MSC therapy effectively improves glucose metabolism by modulating GLUT4 and FOXO1 expression, with the potential for alkaline water as an adjunctive therapy in T2DM management
Modulation of inflammatory pathways in ischemic stroke rats by hypoxia-primed umbilical cord mesenchymal stem cells (UC-MSCs): Implications for IFN-γ and IL-10 signaling Fahreza, Rakha; Setiawan, Eko; Trisnadi, Setyo; Putra, Agung; Hidayah, Nurul; Fikriya Novita Sari; Ibrahim, Sugeng
Indonesian Journal of Biomedicine and Clinical Sciences Vol 57 No 4 (2025)
Publisher : Published by Universitas Gadjah Mada

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.22146/inajbcs.v57i4.24529

Abstract

Ischemic stroke is a major global cause of disability and mortality. Inflammation plays a central role in its pathogenesis, characterized by elevated pro-inflammatory cytokines such as IFN-γ and reduced anti-inflammatory cytokines like IL-10. Mesenchymal stem cells (MSCs), especially those derived from the umbilical cord (UC-MSCs), exhibit enhanced immunomodulatory potential when preconditioned under hypoxia. This study aims to evaluate the effect of hypoxic-preconditioned UC-MSCs administration on IFN-γ and IL-10 levels in an ischemic stroke rat model. This in vivo experimental study employed a randomized posttest-only control group design with four groups of male Wistar rats (n=6 each), ranging from healthy controls, untreated group to stroke-induced groups treated with hypoxic UC-MSCs at different doses (1.5x106 and 3x106). IFN-γ and IL-10 levels in brain tissue of each group were measured via ELISA. Significant reduction in IFN-γ and elevation in IL-10 were observed in UC-MSC-treated groups, particularly at the 3×10⁶ cell dose compared to the untreated ischemic group (p<0.05). Hypoxic UC-MSCs reduce post-stroke inflammation by lowering IFN-γ and enhancing IL-10, indicating a promising immunomodulatory potential.
Co-Authors Agus Widyatmoko, Agus Alif, Iffan Amalina, Nur D. Amalina, Nur Dina Amin, Mustafa M. Andavania, Sheila Jessica Andreas, Yana Antari, Arini Dewi Azizah Retno Kustiyah Cahyani, Dini Cahyani, Elvana Cahyono, Erwin Budi Candra Satria Irawan, Risky Catharina Suharti Chodidjah Chodidjah Chodijah , Chodijah Darlan, Dewi M. Daulay, Rini S. Delfitri Munir Dewi, Alisia Martha Dirja, Bayu T. Dirja, Bayu Tirta Djannah, Durrotul Edi Dharmana Eko Setiawan Eko Setiawan Erna Mutiara Evita Mayasari Fahreza, Rakha Fatmawati, Dian Fikriya Novita Sari Fristiani, Yeni Ghaisani, Shabrina Syifa Ginting, Andi R. Hadi Sarosa Haitamy, Mohammad Nurrizki Handoyo, Frigi Eko Hariani, Nova Putri Hasanal, Ihdina Hanifa Hasannuri, Tarrayuana Rhamadia Heri Nugroho HS, Zakariya Husain, Sofian A. Hutabarat, Nenny Lynda Caroline Hutagalung, Ananta Ibrahim, Sugeng Ignatius Riwanto, Ignatius Intan, Yulice Soraya Nur Irawan Mangunatmadja Irawan, Risky Chandra Irawan, Risky Chandra Satria Isfandiari, Adelia Bayu Iskandar Japardi Jessika, Cleveria Khan, Ahmed Faheem Kuntardjo, Novalia Lusiana Lusiana Mardiana, Ana Maryanti Maryanti Mawarini, Melisa Septi Minidian Fasitasari Muhar, Adi Muradi Nugraha, Dendi Krisna Nur Anna Chalimah Sadyah NURUL HIDAYAH Pasongka, Zenitalia Pramukarso, Dodik Tugasworo Pramukarso Prasetio, Ardi Prasetyowati Subchan, Prasetyowati Prawitasari, Salindri Purwaningsih, Hesti Rahardja, Carolina Kiwik Rozi, Muhammad F. Rusda, Muhammad Sa’dyah, Nur Anna C Selamat Budijitno Setyo Trisnadi Setyo, Trisnadi Shafia, Arina Sisca Silvana, Sisca Sitompul, Faya Nuralda Sri Priyantini Sri Priyantini Mulyani Sri Sofyani, Sri Subchan, Prastyowati Sulistami, Siska Marlina Sulistyo, Sona Sunarto, Hadi Sutrisman, Intan Permatasari Suwandi Ng Syamsunarno, Mas Rizky Syamsunarno, Mas Rizky A.A Taskworo, Dodik Taufiq R Nasihun, Taufiq R Titiek Sumarawati Tjipta, Arya Trisnasi, Setyo Utami, Wulan Dyah Yasmine Azzahara, Salma Yustianingsih, Vivi