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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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Comparison of Two Tangential Flow Filtration Methods in Isolating CD63+/CD9+ Mesenchymal Stem Cell Exosome Putra, Agung; Alif, Iffan; Prasetio, Ardi; Prawitasari, Salindri
International Journal of Cell and Biomedical Science Vol 2 No 4 (2023)
Publisher : Stem Cell and Cancer Research (SCCR)

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

Abstract

Background: Extracellular vesicles, particularly CD63+/CD9+ Mesenchymal Stem Cell Exosome (MSC-Exo), have emerged as crucial mediators of intercellular communication and potential therapeutic agents, including regenerative medicine and immunomodulation. However, the precise isolation and purification of MSC exosomes pose critical challenges. Tangential Flow Filtration (TFF) has gained recognition as an efficient exosome isolation method, offering scalability and versatility. In this study, we address the pressing need for standardized exosome isolation methods by comparing two distinct TFF-based protocols for isolating CD63+/CD9+ MSC exosomes based on filter size pore order. Methods: MSC-Exo were conducted from the Stem Cell and Cancer Research Laboratory (SCCR Indonesia), which were then processed through TFF using different filter sizes and orders. There are two filtration methods compared, first, MSC-Exo was filtered with 1000-5-500-300-100-50-10-5 filter order. Second procedure, MSC-Exo was filtered using 1000-500-300-100-50-10-5 filter order. Result: Flow cytometry analysis revealed variations in the percentage of CD63+/CD9+ in the MSC-Exo based on filter order. The results indicate that the choice of filter order significantly influences the size range with the highest concentration of CD63+/CD9+ MSC-Exo. Conclusion: This research underscores the importance of optimizing TFF-based isolation methods for CD63+/CD9+ MSC exosomes, especially in the order of filter pore size.
The Effect of Leadership Style on Managerial Performance Through Work Engagement and Innovative Work Behavior as Mediating Variables Putra, Agung; Ng, Suwandi; Mardiana, Ana
Contemporary Journal on Business and Accounting Vol 5 No 1 (2025): Contemporary Journal on Business and Accounting (CjBA)
Publisher : Institut Transparansi dan Akuntabilitas Publik (INSPIRING)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.58792/cjba.v5i1.74

Abstract

Purpose – This study aims to analyze the influence of leadership style on managerial performance, both directly and indirectly through work involvement and innovative work behavior that act as mediators. Design/methodology/approach – The theoretical model of the study was built on the basis of goal setting theory, namely that performance is a positive function of the goal achievement process. When performance can be controlled, specific goals will reduce performance variation by reducing ambiguity of achieved performance. Findings – The results reveal that leadership style has a significant effect on work involvement and innovative behavior. Likewise, work involvement and innovative behavior have a significant effect on managerial performance, but inversely proportional to the influence of leadership style does not affect managerial performance. Originality – The data were collected from all Account Representatives in all Pratama Tax Service Offices in South Sulawesi. The respondents were selected using the purposive sampling. Keywords: leadership style, managerial performance, work involvement, innovative work behavior, account representative, goal setting theory Paper Type Research Result
Hypoxia-preconditioned mesenchymal stem cells attenuate proinflammatory cytokines in collagen loss animal model Fristiani, Yeni; Putra, Agung; Sumarawati, Titiek; Setiawan, Eko; Ibrahim, Sugeng; Pramukarso, Dodik Tugasworo Pramukarso
Universa Medicina Vol. 44 No. 2 (2025)
Publisher : Faculty of Medicine, Universitas Trisakti

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18051/UnivMed.2025.v44.131-140

Abstract

Background Repeated ultraviolet-B (UVB) exposure induces significant collagen degradation, primarily through overproduction of reactive oxygen species, which subsequently drives an inflammatory cascade. Hypoxia-preconditioned mesenchymal stem cells (H-MSCs) constitute a promising therapeutic approach to counteract collagen loss by modulating inflammatory pathways. This study aimed to evaluate the potential of H-MSCs in regulating NF-κB p65 and IL-1β expression in a collagen loss rat model, highlighting their therapeutic efficacy. Methods Twenty-five healthy male Wistar rats were randomly assigned to five groups: K1 (healthy controls), K2 (collagen loss), K3 (collagen loss + hyaluronic acid), K4 (collagen loss + 2.5 × 10⁵ H-MSCs), and K5 (collagen loss + 5 × 10⁵ H-MSCs). Collagen loss was induced by UVB radiation (peak wavelength: 302 nm) for 2 weeks. mRNA expression of NF-κB p65 was quantified by qRT-PCR, while IL-1β levels were assessed using ELISA. The rats were maintained for 14 days before being sacrificed, to allow the H-MSCs to exert their therapeutic effects. Data analysis was by One-way ANOVA with Tukey’s post-hoc test. Results The administration of H-MSCs significantly reduced IL-1β levels in groups K4 (633.14±63.76 pg/mL) and K5 (520.80±123.82 pg/mL) compared to group K2 (931.93±205.80 pg/mL) (p<0.05), with group K5 showing the most substantial reduction. Moreover, H-MSC injection in groups K4 and K5 effectively reduced NF-κB p65 expression levels (1.13±0.50 a.u. and 0.72±0.22 a.u., respectively), compared to group K2 (2.47±0.50 a.u.) (p<0.05), with group K5 providing optimum inhibition. Conclusion This study demonstrated that H-MSCs effectively attenuate UVB-induced inflammation and modulate key inflammatory pathways.
Mesenchymal stem cell-derived secretome accelerates third-degree burn wound healing: Effects on proliferation, angiogenesis, and fibrosis regulation Dirja, Bayu T.; Putra, Agung; Amalina, Nur D.
Narra J Vol. 5 No. 2 (2025): August 2025
Publisher : Narra Sains Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.52225/narra.v5i2.1828

Abstract

Mesenchymal stem cell-derived secretome (MSC-derived secretome) has shown promise in regenerative medicine; however, research specifically evaluating its efficacy in third-degree burn wounds remains scarce. The aim of this study was to investigate the effects of MSC-derived secretome on cellular proliferation, angiogenesis, myofibroblast activity, and collagen synthesis in a third-degree burn wound model. A total of 20 Wistar rats were randomly assigned to four groups: a healthy control group, a negative control group with untreated third-degree burn wounds, and two treatment groups receiving MSC-derived secretome at doses of 100 µL and 200 µL for 14 days. The wound healing was assessed 14 days post-treatment. Proliferating cell nuclear antigen (PCNA) protein expression was quantified via Western blot to assess cell proliferation; vascular endothelial growth factor (VEGF) gene expression was analyzed using quantitative reverse transcription polymerase chain reaction (qRT-PCR) to examine angiogenesis; alpha-smooth muscle actin (α-SMA) expression was assessed through immunohistochemistry to evaluate myofibroblast activity; and collagen density was measured using Masson's trichrome staining to determine tissue remodeling.  Our data indicated that MSC-derived secretome treatment significantly enhanced multiple aspects of the healing process in a dose-dependent manner. PCNA expression increased by 2.8-fold in the 200 µL MSC-derived secretome group compared to the negative control (p<0.05). VEGF gene expression was upregulated by 2.14-fold in the 200 µL secretome group compared to the negative control (p<0.05). α-SMA protein expression increased by 12.67% in the 200 µL secretome group, while collagen density demonstrated the most pronounced improvement at the 200 µL dose, reaching an increase of 81.26% (p<0.05). In conclusion, MSC-derived secretome significantly accelerates burn wound healing by promoting cell proliferation, enhancing angiogenesis, and increasing collagen synthesis while modulating myofibroblast activity. This highlights the potential of MSC-derived secretome as a therapeutic option for optimizing burn wound repair and reducing fibrotic complications.
Hypoxia-Induced Mesenchymal Stem Cell Exosomes Modulate Protein Kinase A and VEGFR Expression in Ultraviolet B-Induced Hyperpigmentation in Mice Andavania, Sheila Jessica; Syamsunarno, Mas Rizky; Putra, Agung; Setiawan, Eko
Molecular and Cellular Biomedical Sciences Vol 9, No 2 (2025)
Publisher : Cell and BioPharmaceutical Institute

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.21705/mcbs.v9i2.594

Abstract

Background: Hyperpigmentation is often exacerbated by ultraviolet-B (UVB) exposure through oxidative stress and activation of pathways like mitogen-activated protein kinase (MAPK) and vascular endothelial growth factor receptor (VEGFR). Current treatments carry risks and necessitate safer alternatives. This study investigated the therapeutic potential of hypoxia-induced mesenchymal stem cell (MSC) exosomes in reducing protein kinase-A (PKA) and VEGFR expression in UVB-induced hyperpigmentation.Materials and methods: A post-test-only control group design was used with 30 male C57BL/6 mice divided into five groups: Healthy group, 0,9% NaCl-treated group, retinol-treated group, and two treatment groups (200 µL Exosomes-treated group and 300 µL Exosomes-treated group. UVB-induced hyperpigmentation was established with 180 mJ/cm² exposures over two weeks. Treatment was administered via subcutaneous injections for seven days. PKA and VEGFR mRNA levels were analyzed using qRT-PCR.Results: PKA expression was significantly lower in the 200 µL Exosomes-treated group (0.34±0.05) and 300 µL Exosomes-treated group (0.21±0.04) groups compared with the 0,9% NaCl-treated group (1.12±0.08) (p<0.001). VEGFR expression similarly decreased in 200 µL Exosomes-treated group (0.32±0.05) and 300 µL Exosomes-treated group (0.18±0.04) versus the 0,9% NaCl-treated group (1.48±0.09) (p<0.001). Both exosome doses achieved reductions comparable to baseline levels observed in the Healthy group.Conclusion: Hypoxia-induced MSC exosomes reduced PKA and VEGFR expression in UVB-induced hyperpigmentation, with the 300 µL dose showing greater efficacy. These findings suggested exosome therapy as a promising alternative for hyperpigmentation treatment. Keywords: hyperpigmentation, MSC, PKA, VEGFR, melanin
Mesenchymal Stem Cell-Derived Exosomes Enhance FGF-1 and SDF-1 Expression in Rats with Second Degree Burns Hariani, Nova Putri; Putra, Agung; Subchan, Prasetyowati; Setiawan, Eko
Molecular and Cellular Biomedical Sciences Vol 9, No 2 (2025)
Publisher : Cell and BioPharmaceutical Institute

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.21705/mcbs.v9i2.635

Abstract

Background: Second-degree burns cause extensive damage to the skin and pose significant health challenges, with current treatments facing limitations such as donor skin shortages and complications. Fibroblast growth factor 1 (FGF-1) and stromal-derived growth factor 1 (SDF-1) are critical for tissue repair. Emerging evidence suggests that mesenchymal stem cell-derived exosomes (E-MSCs) are a promising cell-free therapeutic option for enhancing wound healing through the modulation of FGF-1 and SDF-1. This study investigated the effect of E-MSCs on the expression of FGF-1 and SDF-1 genes in rats with second-degree burns.Materials and methods:  This experimental study used a second-degree burn model in Wistar rats, treated with subcutaneous injections of E-MSCs at doses of 100 µL and 200 µL. Gene expression of FGF-1 and SDF-1 was quantified using qRT-PCR. Histological validation confirmed burn severity, and flow cytometry was used to characterize E-MSCs and exosomes.Results: An increase in FGF-1 and SDF-1 expression was observed in exosome-treated groups compared to the NaCL-treated group. The 200 µL E-MSCs-treated group showed the most significant enhancement in both growth factors, with statistically significant differences (p<0.05). These findings underline the efficacy of E-MSCs in modulating critical genes involved in wound healing.Conclusion: E-MSCs significantly upregulate FGF-1 and SDF-1 expression, promoting tissue repair and regeneration in second-degree burn models. This study highlights the potential of E-MSCs as a non-invasive therapeutic approach.  Keywords: exosomes, FGF-1, mesenchymal stem cells, SDF-1
Correlation between haemoglobin, leukocytes, HbA1c, and albumin levels with diabetic foot ulcer severity: a cross-sectional study Sadyah, Nur Anna Chalimah; Nugroho, Heri; Putra, Agung; Riwanto, Ignatius
Sains Medika: Jurnal Kedokteran dan Kesehatan Vol 16, No 1 (2025): June 2025
Publisher : Faculty of Medicine, Universitas Islam Sultan Agung (UNISSULA), Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.30659/sainsmed.v16i1.41423

Abstract

Diabetic foot ulcers (DFUs) represent a serious complication of diabetes mellitus, associated with significant morbidity and healthcare costs. The progression of DFUs is influenced by systemic and local factors, including haemoglobin levels, leukocyte count, glycated haemoglobin (HbA1c), and serum albumin. This study aims to explore the relationship between these clinical parameters and the severity of DFUs. We enrolled 62 patients with DFUs and classified ulcer severity as mild, moderate, or severe according to the Wagner classification system. Using Spearman’s rank correlation, we found significant associations: lower hemoglobin and albumin levels correlated with more severe ulcers (ρ = -0.34, p= 0.0065; ρ = -0.41, p = 0.00084, respectively), while higher HbA1c and leukocyte counts were associated with increased ulcer severity (ρ = 0.62, p = 0.000; ρ = 0.40, p = 0.0013, respectively). These findings suggest that hematologic and biochemical markers may serve as valuable indicators of DFU progression, potentially guiding clinical decision-making and improving patient outcomes. Further research is needed to elucidate the underlying mechanisms and evaluate targeted interventions for this high-risk population.
Effector Cytokine Profiles of Ex Vivo Expanded CTLs in Colorectal Cancer HCT-116 Cells Co-Culture Models Ibrahim, Sugeng; Putra, Agung; Hidayah, Nurul; Cahyani, Dini
Indonesian Journal of Medical and Pharmaceutical Science Vol. 4 No. 2 (2025)
Publisher : Sultan Agung Islamic University of Semarang

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.30659/ijmps.v4i2.450

Abstract

Background: Colorectal cancer (CRC) remains a major cause of cancer-related mortality worldwide, with limited benefit from conventional therapies in advanced disease. Cytotoxic T lymphocytes (CTLs, CD8⁺ T cells) are critical mediators of anti-tumor immunity, primarily through direct cytotoxicity and cytokine secretion. However, the dual roles of CTL-derived cytokines, particularly interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6), in CRC progression remain incompletely understood. This study aims to analyze the cytokine profile (IFN-γ, TNF-α, and IL-6) in a CTL–CRC cell direct co-culture model. Methods: CD8⁺ T cells were isolated from peripheral blood mononuclear cells (PBMCs) of CRC patients using magnetic negative selection and activated for 5 days with anti-CD3/CD28 beads and IL-2. Purity and viability were assessed by flow cytometry and morphology. Activated CTLs were co-cultured with the HCT116 CRC cell line at effector-to-target (E:T) ratios of 1:1, 5:1, and 10:1 under direct contact for 48 h. Supernatants were collected and cytokine levels (IFN-γ, TNF-α, and IL-6) were quantified using validated sandwich ELISA kits. Results: Direct co-culture with HCT116 cells significantly increased cytokine secretion in an E:T ratio-dependent manner. IFN-γ secretion rose from 3044.6±120 pg/mL at 1:1 to 4882.1±198 pg/mL at 5:1, plateauing thereafter. TNF-α levels remained relatively constant (628.6±67 pg/mL at 1:1 vs. 674.0±91 pg/mL at 10:1). IL-6, nearly undetectable at 1:1 (0.4±0.1 pg/mL), increased dose-dependently to 5.1±0.9 pg/mL at 10:1. Conclusion: Ex vivo expanded CTLs from CRC patients exhibit a distinct cytokine secretion profile characterized by robust IFN-γ release, stable TNF-α production, and a dose-dependent increase in IL-6 across different effector-to-target ratios.
Protective Effect of Black Rice Extract Cream on Ultraviolet B-Induced Skin Hyperpigmentation in Mice Maryanti, Maryanti; Putra, Agung; Subchan, Prasetyowati
Althea Medical Journal Vol 12, No 3 (2025)
Publisher : Faculty of Medicine Universitas Padjadjaran

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.15850/amj.v12n3.4192

Abstract

Background: Hyperpigmentation is a common sign of skin aging caused by prolonged ultraviolet B (UVB) exposure. Black rice (Oryza sativa L. var glutinosa), known for its high antioxidant content, has moisturizing and regenerative properties that may support skin health. This  study aimed to evaluate the effect of black rice extract cream on transforming growth factor beta (TGF-β) and tumor necrosis factor alpha (TNF-α) expression in a UVB-induced hyperpigmentation mouse model.Method: An in vivo experimental study with post test only control group design was conducted in 2024 at the Stem Cell and Cancer Research Laboratory, Semarang, Indonesia. Twenty-eight male C57BL/6 mice were randomly divided into four groups: healthy control (K1),  UVB-exposed negative control group (K2), UVB-exposed group treated with  7.5% (K3) and 15 % (K4) black rice extract cream  for14 days. On day 15, TGF-β and TNF-α expression levels were analyzed using the RTq-PCR,  normalized to GAPDH. Data were analyzed using One-way ANOVA followed by post-hoc testing.Results: TGF-β gene expression was the highest in K4 (1.87±0.23), followed by K3 (1.52±0.42l) which was statistically significant different between groups (p=000); whereas TNF-α gene expression was the lowest in K4 (1.92±1.02) compared with K3 (5.40±2.28), and the difference between groups was also statistically significant (p=000).  Conclusion: Black rice extract cream increase TGF-β expression and reduces TNF-α expression in UVB-induced hyperpigmentation. These findings suggests its potential as a natural topical agent to mitigate UVB-induced skin damage and premature aging.
Time-Dependent Secretion of IFN-γ, TNF-α, Perforin, and Granzyme-B in CTL-Conditioned Medium from Colorectal Cancer Patient Ibrahim, Sugeng; Putra, Agung; Hidayah, Nurul; Khan, Ahmed Faheem; Nugraha, Dendi Krisna
The Avicenna Medical Journal Vol. 6 No. 1 (2025): The Avicenna Medical Journal
Publisher : Faculty of Medicine, UIN Syarif Hidayatullah Jakarta

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.15408/avicenna.v6i1.46889

Abstract

Background: Cytotoxic T lymphocytes (CTLs) are key effectors of adaptive immunity, exerting their functions through the release of pro-inflammatory cytokines and cytotoxic molecules. Conditioned medium (CM) derived from CTLs has emerged as a potential cell-free immunotherapeutic strategy; however, the temporal dynamics of its secreted mediators remain poorly defined. Methods: Human CTLs were isolated, activated, and cultured in vitro. CM was harvested at defined intervals (days 5, 10, and 15). Concentrations of interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), perforin, and granzyme-B were quantified by enzyme-linked immunosorbent assay (ELISA). Temporal secretion profiles were evaluated using ANOVA with post-hoc analysis. Results: IFN-γ and TNF-α exhibited peak secretion at day 5, followed by a decline at later time points. In contrast, perforin and granzyme-B increased progressively, reaching maximal levels at day 15. All four mediators demonstrated significant time-dependent variation (p < 0.05). Conclusion: CTL-derived CM displays distinct time-dependent secretion patterns, with cytokines predominating during early activation and cytotoxic molecules dominating later phases. These findings underscore the importance of optimizing CM collection timing to maximize its immunomodulatory and therapeutic potential, and provide a rationale for further translational development of CTL-CM in immunotherapy.
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