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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.
The Effect of secretome-hypoxia mesenchymal-stem-cells and vitamin-d3 in type-2 diabetes-mellitus induced periodontitis rats Muchaeroni, Isa Anshori; Rochmah, Yayun Siti; Putra, Agung
Odonto : Dental Journal Vol 10, No 1 (2023): July 2023
Publisher : Faculty of Dentistry, Universitas Islam Sultan Agung

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.30659/odj.10.1.125-131

Abstract

Background: A systemic metabolic disorder by insulin resistance, type-2 diabetes mellitus (T2DM), is characterised by an increased level of reactive oxygen species (ROS) and decreased superoxide dismutase (SOD), which is associated with the activation of proinflammatory cytokine pathways such as tumor necrosis (TNF)-α. This condition usually stimulates inflammation of the periodontal tissue (periodontitis). Vitamin-D3 can inhibit the release of inflammatory mediator and reduce the risk of chronic periodontitis. Purpose this study to determine the effect of the secretome-hypoxia mesenchymal-stem-cells (SH-MSCs)-Vitamin-D3 combination on the expression of SOD, IL-10, and TNF-α genes in T2DM periodontitis-induced rats. Method: 30 rats were randomly divided into five groups; normal sham condition, positive control, SH-MSCs group, vitamin-D3 group, and combination of SH-MSCs and vitamin D3 group. SH-MSCs were injected at doses of 150 uL in the gingival. In addition, vitamin D3 5000 IU 2.25 mcg were administrated orally. After 35 days, all rats were sacrificed, and qRT-PCR from gingival tissue was performed to identify the expression of SOD, IL-10 and TNF-α genes Results: The results a significant increase in SOD and IL-10 gene expression (p
The Effect of secretome-hypoxia mesenchymal-stem-cells and vitamin-d3 in type-2 diabetes-mellitus induced periodontitis rats Muchaeroni, Isa Anshori; Rochmah, Yayun Siti; Putra, Agung
Odonto : Dental Journal Vol 10, No 1 (2023): July 2023
Publisher : Faculty of Dentistry, Universitas Islam Sultan Agung

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.30659/odj.10.1.125-131

Abstract

Background: A systemic metabolic disorder by insulin resistance, type-2 diabetes mellitus (T2DM), is characterised by an increased level of reactive oxygen species (ROS) and decreased superoxide dismutase (SOD), which is associated with the activation of proinflammatory cytokine pathways such as tumor necrosis (TNF)-α. This condition usually stimulates inflammation of the periodontal tissue (periodontitis). Vitamin-D3 can inhibit the release of inflammatory mediator and reduce the risk of chronic periodontitis. Purpose this study to determine the effect of the secretome-hypoxia mesenchymal-stem-cells (SH-MSCs)-Vitamin-D3 combination on the expression of SOD, IL-10, and TNF-α genes in T2DM periodontitis-induced rats. Method: 30 rats were randomly divided into five groups; normal sham condition, positive control, SH-MSCs group, vitamin-D3 group, and combination of SH-MSCs and vitamin D3 group. SH-MSCs were injected at doses of 150 uL in the gingival. In addition, vitamin D3 5000 IU 2.25 mcg were administrated orally. After 35 days, all rats were sacrificed, and qRT-PCR from gingival tissue was performed to identify the expression of SOD, IL-10 and TNF-α genes Results: The results a significant increase in SOD and IL-10 gene expression (p
Non-contact electro capacitive cancer therapy (ECCT) modulate the mRNA expression of p53, Apaf-1, survivin, NF-κB, TSP-1 and bFGF in DMBA-induced breast cancer rat Hidayah, Nurul; Putra, Agung; Alamsyah, Firman; Pratiwi, Rarastoeti
Indonesian Journal of Biomedicine and Clinical Sciences Vol 58 No 1 (2026)
Publisher : Published by Universitas Gadjah Mada

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.22146/inajbcs.v58i1.24954

Abstract

Breast cancer is the most common cancer that causes death in women in the world. Cancer development is facilitated by the inhibition of apoptosis and induction of angiogenesis. Current cancer therapy still encounters problems in the form of recurrence, resistance, and side effects of drugs. Non-contact static electric field therapy, electro capacity cancer therapy (ECCT) with medium frequency, is a therapy developed to inhibit the proliferation of tumor cells. This study aimed to determine the mRNA expression of p53, Apaf-1, survivin related to apoptosis and NF-κB, bFGF and TSP-1 related to angiogenesis in rat breast tumor tissue after ECCT frequency of 150 kHz. Breast tissue samples and rat breast tumor nodules stored in RNA later at -20°C were used. The tissue was obtained from the non-induction non-therapy (NINT) group, induction non-therapy (INT), non-induction therapy (NIT), and induction therapy (IT). mRNA expression of p53, Apaf-1, NF-κB, bFGF and TSP-1 were analyzed using qRT-PCR and calculated with the Livak formula. Data were analyzed using one-way Anova and post-hoc LSD. The results showed that, mRNA expression of p53, Apaf-1 and TSP-1 in the IT group increased significantly, and mRNA expression of survivin and bFGF decreased significantly compared to the INT group. However, the expression of NF-κB mRNA in the IT group remained the same as in the INT group. In conclusion, ECCT with a frequency of 150 kHz upregulates p53, Apaf-1 and TSP-1 mRNA expression and downregulates survivin and bFGF mRNA expression but have no effect on NF-κB mRNA expression in rat breast tumor tissue.
In vivo study on the effect of noni leaf extract cream (Morinda Citrifolia L) on PDGF and TNF-α levels in cut wounds Sari, Shintia Devi Arum; Mulyani, Sri Priyantini; Putra, Agung; Setiawan , Eko
MEDISAINS: Jurnal Ilmiah Ilmu-Ilmu Kesehatan Vol. 23 No. 3 (2025)
Publisher : Universitas Muhammadiyah Purwokerto

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.30595/medisains.v23i3.25252

Abstract

ABSTRACT Background: Skin wounds damage the structure and epithelial tissue, resulting in scar tissue formation. Prolonged wound healing or excessive body response will inhibit the normal process and produce unaesthetic scar tissue. Many plant extracts and their active components can accelerate the wound healing process, Noni leaf extract has antioxidant activity and accelerates wound healing. Objective: This study aims to determine the effect of noni leaf extract cream (Morinda Citrifolia L) on TNF-α and PDGF levels in Wistar rats with incised wounds. Method: A laboratory experimental study with a post-test only control group design. Consisting of five treatment groups, namely the healthy rat group (KS), Negative group (KN) rats with incised wounds without treatment, positive group (KP) rats with incised wounds that were smeared with povidone-iodine cream, treatment group 1 (P1) rats that were smeared with 20% noni leaf extract cream, and treatment group 2 (P2) rats that were smeared with 40% noni leaf extract cream, treatment for 3 days then examined the levels of TNF-α and PDGF skin tissue using the ELISA method. Results: The average TNF-α levels showed a significant difference between groups p of 0.000 (p <0.05) with the One way anova test, the highest average in group (KN) 220.68 pg / mL, there was a decrease in all treatment groups with the lowest TNF-α levels in group (KP) 76.59 pg / mL. The average results of TNF-α levels showed a significant difference of p 0.000 (<0.05) with the One-way ANOVA test, the group without intervention (KP) had the lowest PDGF levels while the group (P2) experienced the highest increase in PDGF levels. Conclusion: Administration of noni leaf extract cream with doses of 20% and 40% had an effect on reducing TNF-α levels and increasing PDGF levels in Wistar rats with incised wounds.
Hypoxic MSCs Reduce UV-B Collagen Loss by Modulating CD68 and TNF-α Expression Ati, Sri Umi; Putra, Agung; Sumarawati, Titiek; Setiawan, Eko; Ibrahim, Sugeng; Taskworo, Dodik
Indonesian Journal of Pharmaceutical Science and Technology Vol 13, No 1 (2026)
Publisher : Indonesian Journal of Pharmaceutical Science and Technology

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.24198/ijpst.v13i1.63650

Abstract

Ultraviolet-B (UV-B) radiation-induced skin photoaging is marked by collagen degradation and chronic inflammation, with limited effective treatments currently available. Hypoxic-preconditioned mesenchymal stem cells (H-MSCs) offer a novel therapeutic approach due to their immunomodulatory capabilities. This study evaluated the effects of H-MSCs at two doses (2.5×105 and 5×105 cells) on UVB-induced collagen loss, focusing on CD68 expression and TNF-α levels in a rat model. Male Wistar rats were divided into five groups: healthy controls, UV-B-exposed negative controls (saline), positive controls (hyaluronic acid), and two H-MSC-treated groups. After UV-B exposure (160 mJ/cm², five times per week for two weeks), validated H-MSCs were administered subcutaneously. Collagen content was assessed histologically, while CD68 gene expression and TNF-α levels were measured by qRT-PCR and ELISA, respectively. UVB exposure led to significant reductions in collagen and increased levels of inflammatory markers. H-MSC treatment showed dose-dependent anti-inflammatory effects, with the higher dose (5×105 cells) optimally reducing CD68 expression and TNF-α levels, nearly matching healthy controls. These results suggest that H-MSCs, particularly at higher doses, may be a promising therapy for UVB-induced skin damage and collagen loss.
Pentagamavunone-1 and its derivative, Chemoprevention Curcumin Analog-1.1, modulate PD-L1 and CD80 expression in breast cancer stem cells Alif, Iffan; Putra, Agung; Jenie, Riris Istighfari; Ikawati, Muthi'
Indonesian Journal of Biotechnology Vol 31, No 2 (2026)
Publisher : Universitas Gadjah Mada

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.22146/ijbiotech.114332

Abstract

Breast cancer stem cells (bCSCs) exhibit high plasticity, therapeutic resistance and immune evasion, making them critical targets for effective cancer immunotherapy. Pentagamavunone-1 (PGV-1), a curcumin analog, and its derivative, Chemoprevention Curcumin Analog-1.1 (CCA-1.1), possess cytotoxic and reactive oxygen species (ROS)-modulating properties. However, their potential role in modulating immune-related phenotypes in bCSCs remains unclear. In the study, bCSCs derived from the MDA-MB-231 cell line were treated with PGV-1 or CCA-1.1 to evaluate cytotoxicity, apoptosis, cell cycle distribution, stemness-associated markers and immune checkpoint expression. Cell viability was assessed using the CCK-8 assay. Apoptotic, stemness and immune-checkpoint profiles were analyzed using flow cytometry. PGV-1 exhibited stronger cytotoxicity against bCSCs than CCA-1.1, characterized by lower IC50 values (10.70 and 28.78 µM for PGV-1 and CCA-1.1 respectively at 24 h) and greater induction of apoptosis in a dose-dependent manner. Both compounds at concentrations of 2.67 and 7.19 µM significantly (p < 0.001) induced G2/M cell cycle arrest and reduced the CD44+CD24– stem-like population, indicating loss of stemness and enhanced differentiation. Importantly, PGV-1 significantly downregulated PD-L1 while upregulating CD80, suggesting a shift toward immunophenotypic alterations associated with a potentially more immunogenic profile. These dual effects of cytotoxic and preliminary immunophenotypic modulation highlight the ability of PGV-1 to overcome immune resistance in bCSCs. Further investigation using immune cell–based functional assays or in vivo models is required to validate whether the observed immunophenotypic modulation translates into functional immune activation and to assess the potential of PGV-1 in a co-immunotherapy setting.
Co-Authors Agus Widyatmoko, Agus Alif, Iffan Amalina, Nur D. Amalina, Nur Dina Amin, Mustafa M. Andavania, Sheila Jessica Andreas, Yana Antari, Arini Dewi Ati, Sri Umi Azizah Retno Kustiyah Cahyani, Dini Cahyani, Elvana Cahyono, Erwin Budi Candra Satria Irawan, Risky Catharina Suharti Chodidjah Chodidjah Darlan, Dewi M. Daulay, Rini S. Delfitri Munir 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 Firman Alamsyah 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 HS, Zakariya Husain, Sofian A. Hutabarat, Nenny Lynda Caroline Hutagalung, Ananta Ibrahim, Sugeng Ignatius Riwanto, Ignatius Ikawati, Muthi' Intan, Yulice Soraya Nur Irawan Mangunatmadja Irawan, Risky Chandra Irawan, Risky Chandra Satria Isfandiari, Adelia Bayu Iskandar Japardi Kuntardjo, Novalia Lusiana Lusiana Mardiana, Ana Maryanti Maryanti Minidian Fasitasari Muchaeroni, Isa Anshori Muhar, Adi Muradi Noka, Isara Abda Nur Anna Chalimah Sadyah NURUL HIDAYAH Nurul Hidayah Pasongka, Zenitalia Pramukarso, Dodik Tugasworo Pramukarso Prasetio, Ardi Prasetyowati Subchan, Prasetyowati Prawitasari, Salindri Purwaningsih, Hesti Rarastoeti Pratiwi Riris Istighfari Jenie Rozi, Muhammad F. Rusda, Muhammad Sa’dyah, Nur Anna C Sari, Shintia Devi Arum Selamat Budijitno Setiawan , Eko Setyo Trisnadi Setyo, Trisnadi 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 Utami, Wulan Dyah Yasmine Azzahara, Salma Yayun Siti Rochmah Yustianingsih, Vivi