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Secretome of Hypoxic Mesenchymal Stem Cells Improves Fluconazole-Induced Alopecia in Rats via Immunoregulatory Modulation of IL-15 and IFN-γ Rahardja, Carolina Kiwik; Mulyani, Sri Priyantini; Putra, Agung
Biosaintifika: Journal of Biology & Biology Education Vol. 16 No. 1 (2024): April 2024
Publisher : Universitas Negeri Semarang

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.15294/biosaintifika.v15i1.3500

Abstract

Increased IL-15 and IFN-γ characterize fluconazole-related alopecia (FRA). The hypoxia mesenchymal stem cell (hMSC) secretome has anti-inflammatory capabilities that can potentially be used as alopecia therapy. Therefore, the study aims to determine the effect of topical administration of hMSCs secretome gel on reducing IL-15 and IFN-γ gene expression and baldness in male Wistar rats, a model of FRA. MSC was collected from rat umbilical cord, cultured under hypoxia for 24 hours, and yielded a sterile secretome formulated into a water-based gel ointment for treatment. A total of 24 male Wistar rats were randomly divided into four groups: K1 for health controls with placebo administration only; K2 for negative control which contain FRA rats by applying fluconazole from day 7th to 14th and continued placebo administration until day 29th; treatments were conducted for FRA rat groups treated with 200 mg/day of topical gel contained with 10% of hMSCs secretome for K3 and 20% of hMSCs secretome for K4. Observations were made to analyze hair growth and IL-15 and INF-γ mRNA expression using qPCR. The analysis showed a significant decrease in IL-15 and IFN-γ mRNA expression (p ≤ 0.001) and a reduction in baldness of up to 60% after topical hMSCs secretome gel administration. The prominent result was that the topical gel contained 20% of hMSCs secretome. Based on research results, a topical gel dose containing 20% hMSC secretome had the best effect on improving the condition of FRA. This research may help optimize doses and treatment methods in hMSC secretome therapy.
Therapeutic Potential of Secretome Hypoxia Mesenchymal Stem Cells: Downregulation of TNF-α and HIF-2α in Metabolic Syndrome-Induced Inflammation in Wistar Rats Dewi, Alisia Martha; Trisnasi, Setyo; Putra, Agung; Chodijah , Chodijah; Sarosa, Hadi; Mulyani, Sri Priyantini; Amalina, Nur Dina; Ibrahim, Sugeng
Biosaintifika: Journal of Biology & Biology Education Vol. 16 No. 2 (2024): August 2024
Publisher : Universitas Negeri Semarang

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.15294/biosaintifika.v16i2.6613

Abstract

Background: Metabolic syndrome (MetS) has become a global health challenge with several associated issues, such as obesity, insulin resistance, dyslipidemia, and hypertension. Important proteins such as Tumor Necrosis Factor-alpha (TNF-α) and Hypoxia Inducible Factor-2 alpha (HIF-2α) regulate the inflammatory process by inducing the expression of pro-inflammatory proteins. Secretome Hypoxia Mesenchymal Stem Cells (SH-MSCs) are immunomodulatory, anti-inflammatory, and angiogenic stimulators, which can regulate various inflammatory diseases, including MetS. Objective: This study aims to determine the effect of administering SH-MSCSs on the expression of the TNF-α and Hypoxia Inducible Factor (HIF)-2α genes in the male Wistar rat model with Metabolic Syndrome. Method: This research is an experimental study with a Post-test Only Control Group Design, using a total of 24 male Wistar rats divided into four groups: T1 (Healthy control), T2 (MetS + NaCl), T3 (MetS + administration of SH-MSCs dose 150 uL), and T4 (MetS + administration of SH-MSCs dose 300 uL). SH-MSCSs were administered intraperitoneally four times over 14 days. Adipose tissue TNF-α and HIF-2α gene expression were measured on day 15 using qRT-PCR. Results: TNF-α and HIF-2α gene expression was significantly lower in T3 and T4, compared with the MetS control group (T2). Conclusion: Administration of SH-MSCs was able to reduce the expression of the Tumor Necrosis Factor (TNF-α) and Hypoxia Inducible Factor (HIF)-2α genes in fatty tissue in the male Wistar rat model with Metabolic Syndrome.
X-Ray Scanning Reduce Soluble Active Molecules of Mesenchymal Stem Cells Putra, Agung; Pasongka, Zenitalia; Widyatmoko, Agus; Prasetio, Ardi; Dirja, Bayu Tirta
International Journal of Cell and Biomedical Science Vol 1 No 1 (2022)
Publisher : Stem Cell and Cancer Research (SCCR)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.59278/cbs.v1i1.14

Abstract

Mesenchymal Stem Cells secrete various anti-inflammatory and regenerative SAMs-MSCs that possess immunomodulatory properties and may accelerate wound healing. As a potential agent for therapeutic, SAMs-MSCs should be stable in any condition, including under X-Ray Scanning. The previous study reveal that X-Ray Scanning may induce protein damage. However, the investigation regarding the stability of SAMs-MSCs under X-Ray Scanning is limited, thus this study aimed to investigate the stability of SAMs-MSCs after X-Ray Scanning. Mesenchymal Stem Cell medium was filtrated using the TFF method at 300 and 5 kDa filter cut off and sterilized using 0,1 um syringe. The SAMs-MSCs underwent X-ray Scanning using public Air Port X-Ray twice. The SAMs-MSCs concentration was measured using ELISA. T-test analysis was performed for the statistical analysis with P<0,05. This study revealed that X-ray scanning reduce the concentration of SAMs-MSC. A previous study found that x-ray irradiation may damage protein at 6–18 keV caused by the energy deposited by photoelectrons that are generated by the interaction of X-ray photons and the protein leading to photoelectron-induced damage.
Secretome Hypoxia-Mesenchymal Stem Cells Regulate IL-10 Concentrations in STZ-induced Type 1 Diabetes Rats Sutrisman, Intan Permatasari; Antari, Arini Dewi; Putra, Agung; Irawan, Risky Chandra; Handoyo, Frigi Eko
International Journal of Cell and Biomedical Science Vol 1 No 2 (2022)
Publisher : Stem Cell and Cancer Research (SCCR)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.59278/cbs.v1i2.18

Abstract

Background: Type 1 Diabetic Mellitus (T1DM) is a well-known autoimmune disease that is characterized by a specific adaptative immunity against β-cell antigens. Mesenchymal stem cells (MSC) have emerged as potential immunomodulators in a paracrine manner via their bioactive soluble molecules that involve inflammation-related diseases, including T1DM. Objective: This study aims to investigate the effect of S-HMSC on regulating IL-10 concentrations in STZ-induced T1DM rats. Materials and Methods: This study uses a post-only control group design and randomized system. To induce T1DM rats, an intraperitoneal injection (65 mg/kg BW) of streptozotocin (STZ) was inducted. 20 Wistar rats were subdivided into the following groups: T1DM, DM with 0,5cc S-HMSC (Low-dose), and DM with 1cc S-HMSC (High-dose). The animals received an intraperitoneal injection of S-HMSC once a week for up to 4 weeks. On day 28, the animals were terminated and IL-10 concentrations were measured by ELISA. Results: After S-HMSC administration, the concentration of IL-10 in the treated group was increased in either low-dose or high-dose groups compared with the T1DM group. Conclusion: Administration of secretome-hypoxia MSC may regulate IL-10 concentrations in STZ-induced Type 1 Diabetes Rats.
Anti-inflammation effect of Apium graveolens Extract against lead-acetate-induced brain injury in rats Sulistyo, Sona; Sarosa, Hadi; Sumarawati, Titiek; Putra, Agung; Chodidjah, Chodidjah; Amalina, Nur Dina; Ibrahim, Sugeng
International Journal of Cell and Biomedical Science Vol 2 No 6 (2023)
Publisher : Stem Cell and Cancer Research (SCCR)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.59278/cbs.v2i6.41

Abstract

Purpose: The current study investigated the protective potential of Apium graveolens extract (APE) against lead-induced brain injury in rats by exploring anti-inflammatory and antiapoptotic mechanism. Methods: Twenty male Wistar rats were randomly allocated into four groups (n=5). The control group was orally administrated with distillate water. The second group received lead acetate 200mg/kg body weight orally for 14 days, the third group were orally administered lead acetate 200 mg lead acetate/kg body weight and vitamin E 50IU/kg body weight for 14 days. The fourth group was administrated with leas acetate like second group and APE 300mg/kg body weight for 14 days. The TNF-a levels and caspase-3 expression was analyses under ELISA and flow cytometry assay, respectively. Results: The phytochemical analysis of APE indicated the presence of alkaloids, flavonoids, tannins, saponins, and steroids. Leads acetate increased the serum levels of TNF-α and caspase-3 expression, as well as altering the brain tissue architecture. Conclusion: In conclusion, the presence of APE inhibited the lead acetate toxicity by inhibition of TNF-α proinflammation protein and caspase-3 proapoptosis protein.
The Effect of Celery Extract on Caspase-3 and TNF-α Gene Expression in Lead Poisoning-Induced Renal Injury in Rats Purwaningsih, Hesti; Sumarawati, Titiek; Chodidjah, Chodidjah; Putra, Agung; Priyantini, Sri; Fasitasari, Minidian; Ibrahim, Sugeng; Amalina, Nur Dina
International Journal of Cell and Biomedical Science Vol 2 No 6 (2023)
Publisher : Stem Cell and Cancer Research (SCCR)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.59278/cbs.v2i6.42

Abstract

Background To determine the effect of Apium graveolens L (Celery) extract in the TNF-α and caspase-3 gene expression on the lead poisoning-induced renal injury rats’ model. Methods This study is experimental research with post test only control group design. Twenty male Wistar rats were randomly allocated into four groups (n=5). The control group was orally administrated with distillate water. The second group received lead acetate 200mg/kg body weight orally for 14 days, the third group were orally administered lead acetate 200 mg lead acetate/kg body weight and vitamin E 50IU/kg body weight for 14 days. The fourth group was administrated with leas acetate like second group and celery extract 300mg/kg body weight for 14 days. The TNF-a and caspase-3 gene expression was analyses under qRT-PCR. Results The phytochemical analysis of APE indicated the presence of alkaloids, flavonoids, tannins, saponins, and steroids. Leads acetate increased the TNF-α (3.87±0.09) and caspase-3 (7.95±0.23) gene expression. The celery extract was significantly decrease in the TNF-α (3.13±0.34) and caspase-3 (2.48±1.23) gene expression. Conclusion: In conclusion, the presence of celery extract inhibited the renal injury-induced lead acetate toxicity by inhibition of TNF-α proinflammation protein and caspase-3 proapoptosis protein
Inhibitory Effects of Petai Peel Extract Gel on Tyrosinase and TRP1 Gene Expression in UVB-Exposed Mouse Skin Hutabarat, Nenny Lynda Caroline; Subchan, Prastyowati; Putra, Agung; Amalina, Nur Dina; Sitompul, Faya Nuralda
International Journal of Cell and Biomedical Science Vol 2 No 6 (2023)
Publisher : Stem Cell and Cancer Research (SCCR)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.59278/cbs.v2i6.43

Abstract

Background: UVB irradiation can induce the formation of Reactive Oxygen Species (ROS), which causes the activation of melanin synthesis through the activation of tyrosinase and tyrosinase-related protein-1 (TRP1). Secondary metabolites in stink bean peel extract inhibit ROS production due to exposure to UVB rays. This study aims to determine the effect of administering stink bean peel extract gel on the expression of the tyrosinase and TRp1 genes in mouse skin tissue exposed to UVB. Method: The research design was a posttest-only control group with a completely randomized design method. The samples studied were 24 mice exposed to UVB light with a wavelength of 302 nm and an energy of 390mJ/cm2/day 3 times a week for 2 weeks. This research was carried out in four groups: the healthy group, the negative control group, treatment 1 (T1) with 10% stink bean peel extract gel, and treatment 2 (T2) with 20% stink bean peel extract gel. Tyrosinase and TRP1 gene expression were analyzed using qRT-PCR. Results: qRT-PCR analysis showed that there was a significant decrease in tyrosinase and TRP1 gene expression between groups T1 (tyrosinase 3,19±2,12 and TRP1 4,96±3,42) and T2 (tyrosinase 0,65±0,44 and TRP1 2,22±1,18) compared to negative control (tyrosinase 17,92±3,77 and TRP1 35,91±4,52). Conclusion: The administration of stink bean peel extract gel has shown promising results in reducing the expression of tyrosinase and TRP1 genes in hyperpigmentation mice exposed to UVB light. This suggests that stink bean peel extract could be a safe and effective therapeutic approach for preventing UVB-induced hyperpigmentation.
Mesenchymal stem cells for immune modulation in systemic lupus erythematosus: From bench research to clinical applications Ginting, Andi R.; Munir, Delfitri; Amin, Mustafa M.; Darlan, Dewi M.; Putra, Agung; Rusda, Muhammad; Mutiara, Erna; Mayasari, Evita; Rozi, Muhammad F.
Narra J Vol. 4 No. 3 (2024): December 2024
Publisher : Narra Sains Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.52225/narra.v4i3.994

Abstract

Systemic lupus erythematosus (SLE) is a prevalent autoimmune disease affecting multiple organ systems. Disease progression is inevitable as part of its natural course, necessitating aggressive therapeutic strategies, particularly with the use of immunosuppressants. Long-term use of steroids and other immunosuppressants is associated with significant adverse effects. Mesenchymal stem cells (MSCs) have been shown to modulate the immune response, leading to immunosuppressive effects against self-antigens. MSCs have demonstrated the ability to modulate several immune cell populations, contributing to favorable outcomes in controlling immune and inflammatory conditions. Recent evidence has shown an increase in Treg and Breg cell subsets following MSC administration, along with modulation of other immune cells, including dendritic cells, B cells, and T cells. However, the balance between MSC pro-inflammatory and anti-inflammatory phenotypic activation remains a critical factor in determining therapeutic outcomes. Various covariates also influence the efficacy of MSC therapy. The aim of this study was to provide a comprehensive overview of the utilization of mesenchymal stem cells (MSCs) in SLE treatment, leveraging their immunomodulatory and immunosuppressive capabilities. Understanding the fundamental preclinical effects of MSCs and recent findings from clinical studies may enhance the potential of MSC therapy in the management of SLE patients.
Secretome from hypoxic mesenchymal stem cells as a potential therapy for ischemic stroke: Investigations on VEGF and GFAP expression Silvana, Sisca; Japardi, Iskandar; Rusda, Muhammad; Daulay, Rini S.; Putra, Agung; Mangunatmadja, Irawan; Darlan, Dewi M.; Sofyani, Sri; Andreas, Yana
Narra J Vol. 4 No. 3 (2024): December 2024
Publisher : Narra Sains Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.52225/narra.v4i3.1181

Abstract

Ischemic stroke is a sudden onset of neurological deficit resulting from a blockage in cerebral blood vessels, which can lead to brain tissue damage, chronic disability, and increased risk of mortality. Secretome from hypoxic mesenchymal stem cells (SH-MSC) is a potential therapy to improve neurological deficit by increasing the expression of vascular endothelial growth factor (VEGF) and reducing glial fibrillary acidic protein (GFAP). These effects can reduce the infarction area of ischemic stroke. Therefore, the aim of this study was to analyze the effect of 150 μL and 300 μL SH-MSC injection on VEGF and GFAP expression as well as the improvement of infarction area in ischemic stroke animal model. A post-test-only experimental design with consecutive sampling was used, with Rattus norvegicus as subjects. Stromal mesenchymal stem cells (S-MSCs) were isolated from the umbilical cords of rats at 21 days of gestation. Secretome production by the S-MSCs was induced under a hypoxic condition, and subsequently isolated. The resultant secretome was administered to rats subjected to middle cerebral artery occlusion (MCAO) at doses of 150 μL (P1 group) and 300 μL (P2 group). The results showed that the infarction area was reduced in P1 (p<0.001) and P2 groups (p<0.001). SH-MSC at a dose of 300 μL increased the expression of VEGF (p=0.028) and reduced the expression of GFAP (p=0.001). In conclusion, secretome from hypoxic S-MSC could potentially improve ischemic stroke by upregulating VEGF expression and downregulating GFAP expression.
Hypoxic mesenchymal stem cell secretome upregulates IL-10 and STAT3 gene expressions in mice model with polycystic ovary syndrome Lusiana, Lusiana; Darlan, Dewi M.; Trisnadi, Setyo; Putra, Agung; Amalina, Nur D.; Husain, Sofian A.
Narra X Vol. 2 No. 3 (2024): December 2024
Publisher : Narra Sains Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.52225/narrax.v2i3.176

Abstract

Polycystic ovary syndrome (PCOS) is a condition characterized by chronic anovulation and hyperandrogenism, which often leads to infertility. It is closely associated with chronic inflammation triggered by glucose and saturated fat, contributing to hyperandrogenism and negatively impacting a patient’s quality of life. Effective therapeutic approaches are essential to address these issues. The secretome of mesenchymal stem cells (MSCs) have demonstrated the ability to suppress pro-inflammatory cytokine secretion and regulate growth factors. The aim of this study was to investigate the effect of hypoxic mesenchymal stem cell secretome (MHSSCs) on the expression of interleukin-10 (IL-10) and signal transducer and activator of transcription 3 (STAT3) genes in a PCOS-induced mouse model. An in vivo experimental study was conducted using a post-test-only control group design. A total of 24 female C57BL/6 mice were divided into four groups: healthy control, negative control (PCOS mice injected with 0.9% NaCl), T1 (PCOS mice administered 200 μL of MHSSCs), and T2 (PCOS mice administered 400 μL of MHSSCs) for 33 days. Gene expression of IL-10 and STAT3 were quantified using quantitative reverse transcription polymerase chain reaction (qRT-PCR), normalized to the expression of the housekeeping β-actin gene. Statistical analysis using one-way ANOVA followed by the least significant difference (LSD) post-hoc test was then performed. The results showed a significant increase in IL-10 expression in the T2 group compared to the negative control group (p<0.001). STAT3 expression was also significantly higher in the T2 group compared to the negative control group (p=0.035). A dose-dependent effect was observed, with the T2 group demonstrating the highest upregulation of both IL-10 and STAT3 expression levels. The study highlights that the administration of MHSSCs effectively increased IL-10 and STAT3 gene expression, suggesting their potential as a therapeutic strategy to alleviate inflammation in PCOS.
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