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Hypoxic mesenchymal stem cell‐conditioned medium accelerates wound healing by regulating IL‐10 and TGF‐β levels in a full‐thickness‐wound rat model Adi Muradi Muhar; Faizal Mukharim; Dedy Hermansyah; Agung Putra; Nurul Hidayah; Nur Dina Amalina; Iffan Alif
Indonesian Journal of Biotechnology Vol 27, No 4 (2022)
Publisher : Universitas Gadjah Mada

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.22146/ijbiotech.63914

Abstract

Full‐thickness wound healing is a complex process requiring a well‐orchestrated mechanism of various factors, including cytokines, particularly interleukin (IL)‐10 and transforming growth factor (TGF)‐β. IL‐10 and TGF‐β act as robust anti‐inflammatory cytokines in accelerating the wound healing process by regulating myofibroblasts. Hypoxic mesenchymal stem cell‐conditioned medium (hypMSC‐CM) containing cytokines potentially contribute to accelerate wound repair without scarring through the paracrine mechanism. This study aims to observe the role of hypMSC‐CM in controlling TGF‐β and IL‐10 levels to accelerate full‐thickness wound repair and regeneration. A total of 24 male Wistar rats were used in this study. Six healthy rats as a sham group and 18 rats were created as full‐thickness‐wound animal models using a 6 mm punch biopsy. The animals were randomly assigned into three groups (n = 6) consisting of two treatment groups treated with hypMSC‐CM at a low dose (200 µL hypMSC‐CM with 2 g water‐based gel added) and a high dose (400 µL hypMSC‐CM with 2 g water‐based gel added) and a control group (2 g water‐based gel only). The IL‐10 and TGF‐β levels were examined by ELISA. The results showed a significant increase in IL‐10 levels on day 3 after hypMSC‐CM treatment, followed by a decrease in platelet‐derived growth factor (PDGF) levels on days 6 and 9. In line with this finding, the TGF‐β levels also increased significantly on day 3 and then linearly decreased on days 6 and 9. HypMSC‐CM administra‐ tion may thus promote wound healing acceleration by controlling IL‐10 and TGF‐β levels in a full‐thickness‐wound rat model.
Hepatoprotective activity of Averrhoa bilimbi L. fruit extract on carbon tetrachloride-induced acute liver faiure in Wistar rats Rachellicya Ristioni Sihaloho; Chodijah Chodijah; Titiek Sumarawati; Joko Wahyu Wibowo; Siti Thomas Zulaikhah; Agung Putra; Nurul Hidayah; Shabrina Syifa Ghaissani; Mohammad Ariq Nazar
Universa Medicina Vol. 42 No. 1 (2023)
Publisher : Faculty of Medicine, Universitas Trisakti

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18051/UnivMed.2023.v42.61-69

Abstract

Background Acute liver failure (ALF) is a state of rapid and progressive deterioration of liver function. Continuous exposure to chemicals and viruses can increase reactive oxygen species (ROS) which leads to prolonged inflammation due to the production of tumor necrosis factor-alpha (TNF-á) thus inhibiting the production of platelet-derived growth factor (PDGF). The objective of this study was to evaluate the effect of administration of Averrhoa bilimbi L. fruit extract on PDGF levels and TNF-á levels in carbon tetrachloride (CCl4)-induced ALF rats. MethodsThis study used a post-test-only control group design involving 20 Wistar rats. They were randomized into 4 groups, namely sham, control, T1, and T2. Group T1 was exposed to CCl4 with the administration of A. bilimbi fruit extract at a dose of 500mg/kgBW, while, group T2 was exposed to CCl4 and given A. bilimbi fruit extract of 750 mg/kgBW. On the 15th day, the serum was analyzed to determine the levels of PDGF and TNF-á using ELISA. ResultsThe highest mean PDGF level in the control group was 146.60±15.36 pg/mL, while the highest mean TNF-á level in group T1 was 40.11±4.44 pg/mL. The One-way ANOVA test showed that there were significant differences in TNF-á (p=0.002) and PDGF (p=0.000) levels between the study groups. ConclusionThe administration of A.bilimbi L. fruit extract affected PDGF and TNF-á levels in CCl4-induced ALF rats. The present study revealed that A. bilimbi fruits have significant hepatoprotective activity in experimental Wistar rats.
Perbandingan Pemberian Mesenchymal Stem Cell Hipoksia dan Normoksia Terhadap Ekspresi IL-10 pada Tikus Model Luka Eksisi Olifiarsy Wiet Ramadhanti; Agung Putra; Nur Anna Chalimah Sadyah; Prasetyowati; Nurul Hidayah; Ardi Prasetyo
Journal of Midwifery and Health Science of Sultan Agung Vol. 1 No. 1 (2022): JMHSA
Publisher : Midwifery Department of Sultan Agung Islamic University of Semarang

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.30659/jmhsa.v1i1.15

Abstract

Latar Belakang: Proses penyembuhan luka eksisi melibatkan rangkaian respons seluler yang kompleks untuk membalikkan pembentukan integritas jaringan kulit. Proses ini membutuhkan komunikasi parakrin yang melibatkan sitokin-sitokin antiinflamasi, terutama interleukin 10 (IL-10). Di sisi lain, sel punca mesenkimal prekondisi hipoksia (H-MSCs) dipercaya mampu meningkatkan sekresi IL-10 berkontribusi pada percepatan penyembuhan luka dibandingkan dengan sel punca mesenkimal prekondisi normoksia (N-MSCs). Tujuan: Penelitian ini bertujuan untuk membandingkan H-MSCs dan N-MSCs dalam meregulasi ekspresi serial IL-10 yang terkait dengan peningkatan kepadatan kolagen pada model hewan luka eksisi. Metode: Tiga puluh enam tikus Wistar jantan dengan luka eksisi dibuat sebagai model hewan dengan metode biopsi 6 mm. Hewan secara acak dibagi menjadi empat kelompok yang terdiri dari empat kelompok perlakuan: N-MSCs 1x106, H-MSCs 1x106, Kontrol (perlakuan PBS) dan Sham (tikus sehat yang tidak diobati). Pemberian perlakuan dilakukan 2 kali secara intra peritonial pada hari ke 0. Jaringan kulit dikoleksi pada hari ke 3, 6 dan 9 pasca injeksi. Ekspresi IL-10 diperiksa dengan qPCR. Hasil: Penelitian ini menunjukkan bahwa terjadi peningkatan IL-10 yang signifikan pada hari ke 3 dan 6 setelah perlakuan H-MSCs dan menurun pada hari ke-9 dibandingkan dengan perlakuan N-MSCs. Kesimpulan: H-MSCs dapat memperbaiki ekspresi serial IL-10 yang mengarah pada perbaikan luka model tikus luka eksisi dibandinglkan dengan N-MSCs.
Ekstrak Bunga Telang (Clitoria ternatea L.) Menghambat Peningkatan Ekspresi Gen MMP-1 pada Kulit Tikus Wistar yang Terpapar Sinar Ultraviolet B Prasetyowati Subchan; Rizka Sofyanti Putri; Christine Magdalena; Nurul Hidayah
Journal of Midwifery and Health Science of Sultan Agung Vol. 1 No. 2 (2022): JMHSA
Publisher : Midwifery Department of Sultan Agung Islamic University of Semarang

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.30659/jmhsa.v1i2.22

Abstract

Background: Photoaging increases MMP-1 and damages collagen by forming ROS. Antioxidant compounds in Clitoria ternatea L. have been studied to reduce ROS, thereby inhibiting the emergence of MMP-1 and regulating collagen deposition. This study aimed to analyze the effect of Clitoria ternatea L. extract gel on the inhibition of MMP-1 increase and collagen decrease in male Wistar rat skin exposed to UV-B light. Methods: A randomized control group post-test-only design was conducted on 30 male Wistar rats aged 8-10 weeks with a body weight of 150-250 grams. Rats were divided into four groups: untreated group, placebo group, Clitoria ternatea L. extract gel group 5% and Clitoria ternatea L. 10% extract gel group. Rats were exposed to UVB for 5 consecutive days and administrated with gel every day for two weeks. At week 3, their skin was checked for MMP-1 levels using q-RTPCR. Results: Comparative analysis showed that the lowest mean MMP-1 levels were seen in the untreated grou, followed by the Clitoria ternatea L. 10% gel extract group, 5% Clitoria ternatea L. extract gel group and placebo group. Comparative analysis showed significant differences between groups (p < 0.05). Conclusion: Clitoria ternatea L. 10% extract gel was proven to inhibit the increase in MMP-1 levels in the skin of Wistar rats exposed to UV-B rays.
Cooperative Impact of Curcuma longa and Phyllanthus niruri Extracts on Cytotoxicity in HCT-116 Cells Ibrahim, Sugeng; Hidayah, Nurul; Rifai, Fauziah Novita Putri; Ginanto, Dede
International Journal of Cell and Biomedical Science Vol 2 No 5 (2023)
Publisher : Stem Cell and Cancer Research (SCCR)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.59278/cbs.v2i5.36

Abstract

Background: The combination of herbal extracts has the potential to enhance cytotoxic effects against cancer cells. This study explores the combined cytotoxic effects of Curcuma longa and Phyllanthus niruri extracts on HCT-116 colorectal cancer cells. Objective: To assess the cytotoxic effects of Curcuma longa and Phyllanthus niruri extracts when used in combination and to determine the most effective ratio for inhibiting HCT-116 cell growth. Methods: HCT-116 cells were treated for 24 hours with varying concentrations of Curcuma longa and Phyllanthus niruri extracts based on the IC50 values of each extract administered individually. The concentrations for Phyllanthus niruri were 164 µg/mL (one part), 82 µg/mL (half part), and 41 µg/mL (quarter part), while for Curcuma longa the concentrations were 47 µg/mL (one part), 24 µg/mL (half part), and 12 µg/mL (quarter part). Cytotoxicity was assessed using the MTT assay. Results: The combination of Phyllanthus niruri and Curcuma longa extracts demonstrated varied cytotoxic effects. The most effective combination was identified as Phyllanthus niruri to Curcuma longa ratio of 1:0.25, resulting in a 13.5% cell viability rate. Interaction studies using the Chou-Talalay method indicated that the combination index (CI) revealed the most synergistic effect at a ratio of 0.25:0.50. Conclusion: The study identifies that the combination of Phyllanthus niruri and Curcuma longa extracts exhibits synergistic cytotoxic effects on HCT-116 cells, with the optimal combination showing significant inhibition of cell growth. These findings support further investigation into the synergistic potential of these extracts for colorectal cancer therapy.
Non-Contact Electro Capacitive Cancer Therapy (ECCT) Modulate the mRNA Expression of PDGF and IL-1 in DMBA-induced Breast Cancer Rat Hidayah, Nurul; Sakinah, Feby Nur; Annisa, Dyah Retno
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.v2i6.44

Abstract

Background: Breast cancer remains the most prevalent cancer among women globally, with significant mortality rates. Traditional therapies, such as surgery, chemotherapy, and radiotherapy, are associated with severe side effects and resistance, highlighting the need for alternative treatments. Electro-Capacitive Cancer Therapy (ECCT) is a promising non-invasive approach that uses low-intensity electric fields to selectively target cancer cells. Objective: This study aims to investigate the molecular mechanisms of ECCT, particularly its effects on key molecules such as PDGF and IL-1 in a DMBA-induced rat breast cancer model. Materials and Methods: The study used a post-test-only control group design with four groups: NINT (normal tissue), NIT (untreated tumor tissue), INT (DMBA-induced tumor tissue), and IT (ECCT-treated tumor tissue). ECCT was applied at 150 kHz for 21 days. mRNA expressions of PDGF and IL-1 were quantified using quantitative RT-PCR. Results: ECCT significantly reduced the mRNA expression of PDGF and IL-1 in treated tumor tissues (IT) compared to untreated tumor tissues (INT), bringing their levels closer to those observed in normal tissue (NINT). This suggests that ECCT downregulates key pro-angiogenic and pro-inflammatory molecules involved in tumor progression. Conclusion: In conclusion, the non-contact ECCT with a frequency of 150 kHz might downregulate PDGF and IL-1 mRNA expression in rat breast tumor tissue.
Temporal Dynamics of TNF-α Expression and Cell Viability in LPS-Stimulated Peripheral Blood Mononuclear Cells Cahyani, Dini; Hidayah, Nurul; Sari, Fikriya Novita
International Journal of Cell and Biomedical Science Vol 3 No 7 (2024)
Publisher : Stem Cell and Cancer Research (SCCR)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.59278/cbs.v3i7.49

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Background: Lipopolysaccharide (LPS), a key component of Gram-negative bacterial membranes, activates innate immune responses through Toll-like receptor 4 (TLR4) signaling in peripheral blood mononuclear cells (PBMCs). This study aimed to evaluate the temporal dynamics of TNF-α expression and cell viability in LPS-stimulated PBMCs to understand the inflammatory and cytotoxic effects of prolonged LPS exposure. Methods: Human PBMCs were treated with increasing concentrations of LPS (10, 30, and 50 ng/mL) for 4, 8, 12, and 24 hours. TNF-α mRNA expression was analyzed using quantitative PCR, while cell viability was assessed via CCK-8 assay and microscopic imaging. Results: LPS stimulation induced a robust, dose-dependent upregulation of TNF-α expression, peaking at 4 hours and gradually declining over time. Concurrently, PBMC viability remained stable up to 12 hours post-stimulation but significantly decreased at 24 hours, particularly at higher LPS concentrations (30–50 ng/mL). Microscopic analysis revealed increased cellular aggregation and morphological changes consistent with immune activation and cytotoxic stress. Conclusion:LPS triggers early TNF-α expression in PBMCs through TLR4-mediated activation of the NF-κB pathway. However, prolonged exposure to LPS results in decreased cell viability, likely due to sustained inflammatory signaling and oxidative stress. These findings provide insight into the dual-phase response of PBMCs to LPS and underscore the importance of tightly regulated inflammation in innate immunity.
Cytotoxic and Antiproliferative Effects of Gynura divaricata Ethanolic Extract on HCT-116 Colorectal Cancer Cells In Vitro Putri Rifai, Fauziah Novita; Hidayah, Nurul; Sakinah, Feby Nur; Adityani, Resanti
International Journal of Cell and Biomedical Science Vol 3 No 8 (2024)
Publisher : Stem Cell and Cancer Research (SCCR)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.59278/cbs.v3i8.50

Abstract

Background: Colorectal cancer is a major cause of cancer-related morbidity and mortality worldwide. The limitations of conventional treatments such as chemotherapy and radiotherapy have driven the search for alternative therapies with fewer side effects. Objective: This study aimed to investigate the cytotoxic effects of Gynura divaricata extract on HCT-116 colorectal cancer cells and evaluate its potential as a complementary anticancer agent. Methods: Gynura divaricata was extracted using ethanol through a maceration process. HCT-116 cells were cultured and treated with various concentrations of the extract. Cell viability was measured using the MTT assay, and the IC50 value was calculated through linear regression analysis. Results: Treatment with Gynura divaricata extract resulted in a dose-dependent decrease in cell viability. The IC50 value was determined to be 62.09 µg/mL, indicating significant cytotoxic activity against HCT-116 cells. Conclusion: Gynura divaricata exhibits potential as an alternative or adjunctive therapy for colorectal cancer due to its ability to reduce cancer cell viability.
Hypoxia-Induced Modulation of OCT-4, SOX-2, NANOG, and KLF-4 Expression in Mesenchymal Stem Cells Irawan, Risky Chandra Satria; Hidayah, Nurul; Wilaksono, Bhirau
International Journal of Cell and Biomedical Science Vol 3 No 9 (2024)
Publisher : Stem Cell and Cancer Research (SCCR)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.59278/cbs.v3i9.62

Abstract

Background: Mesenchymal stem cells (MSCs) possess remarkable regenerative and immunomodulatory capabilities, largely attributed to their intrinsic stemness properties regulated by transcription factors such as OCT-4, SOX-2, NANOG, and KLF-4. However, in vitro culture under normoxia often leads to stemness decline. Hypoxic preconditioning has been proposed to preserve stemness, though the optimal duration of exposure remains unclear. This study aimed to evaluate the time-dependent effects of hypoxia on the expression of core stemness-related transcription factors in human umbilical cord Wharton’s jelly-derived MSCs. Methods: MSCs (passage 5) obtained from the Stem Cell and Cancer Research (SCCR) Laboratory were cultured under hypoxia (5% O₂) for 0, 4, 6, 10, 12, and 24 hours. Gene expression of OCT-4, SOX-2, NANOG, and KLF-4 was quantified by qRT-PCR using GAPDH as a reference. Morphological changes were observed via phase-contrast microscopy. Statistical analysis was performed using one-way ANOVA with Tukey’s post hoc test. Results: Hypoxic exposure induced a significant, time-dependent upregulation of OCT-4, SOX-2, and NANOG, with peak expression at 12 hours (approximately 13-, 7-, and 5-fold increases, respectively; p < 0.05). KLF-4 expression showed a modest elevation but was not statistically significant. Prolonged hypoxia (24 hours) resulted in a marked decline in all gene expressions toward baseline levels, accompanied by cell rounding and detachment. These findings indicate that short-term hypoxia enhances MSC stemness, while extended exposure triggers stress-related responses. Conclusion: Controlled short-term hypoxia (approximately 12 hours at 5% O₂) optimally enhances MSC stemness gene expression without compromising morphology or viability. This duration represents an effective preconditioning window for maintaining MSC multipotency and may improve the consistency and therapeutic efficacy of MSC-based applications.
Synergistic Effects of Honey and Herbal Bioactives in Cancer Suppression Aprilia, Waheni Rizki; Hidayah, Nurul; Ari, Psn Masruri Sulistiyanto
International Journal of Cell and Biomedical Science Vol 4 No 11 (2025)
Publisher : Stem Cell and Cancer Research (SCCR)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.59278/cbs.v4i11.73

Abstract

Natural bioactives from medicinal plants and honey possess remarkable antioxidant and anticancer properties. However, limited studies have evaluated their synergistic efficacy as combination formulations. This study aimed to develop and characterize a honey–herbal formulation with potential anticancer activity against human breast cancer cells (MDAMB) while ensuring minimal cytotoxicity toward non-cancerous mesenchymal stem cells (MSCs). The formulation was prepared by blending ethanolic herbal extract with pure natural honey in optimized ratios. Organoleptic characteristics were assessed by sensory evaluation. Antioxidant capacity was determined by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. Organoleptic analysis showed acceptable color, aroma, texture, and pH profiles. The honey exhibited strong antioxidant (IC₅₀ = 60 ± 0.7 ppm) compared with external honey and others sample. The formulation demonstrates potential as a functional nutraceutical or adjunctive natural therapy for breast cancer management, warranting further in vivo and molecular pathway investigations.