Abstract: Pulmonary fibrosis induced by PM2.5 exposure is a significant public health concern. While the central role of TGF-β1 in fibrotic signaling is well established, the crosstalk among the various signaling pathways activated by PM2.5 is not yet fully understood. A literature search was conducted in the ScienceDirect and PubMed databases using keywords such as “pulmonary fibrosis,” “PM2.5,” and “TGF-β.” Recent and high-impact articles published in English were selected, and their findings were synthesized into a narrative review. The synthesized literature reveals that PM2.5 exposure drives pulmonary fibrosis through a complex signaling network. The canonical TGF-β/Smad pathway acts as a central driver, but its pro-fibrotic effects are significantly amplified and sustained by crosstalk with non-canonical pathways (e.g., MAPK, PI3K/Akt) and other key regulatory networks like Wnt/β-catenin and Hippo/YAP. Overall, PM2.5-induced pulmonary fibrosis results from an interconnected network of pro-fibrotic signals, underscoring the need for multitargeted therapeutic approaches in the future.

INTRODUCTION:Cancer is a major health concern worldwide. Common cancer treatments such as surgery, chemotherapy, and radiotherapy have not been able to completely reduce the rate of cancer-related death. Monoclonal antibodies (MAb) have been widely used for cancer treatment in the form of immunotherapy or targeted therapy. Immunotoxins are a form of targeted therapy based on monoclonal antibody-toxin conjugates. Antibodies deliver toxins to specific cancer cells and induce cell death. OBJECTIVE:This study aimed to synthesize a conjugate of bongkrekic acid (BKA), a potent mitochondrial toxin, with anti-CD3 MAb and evaluate its specificity in peripheral blood mononuclear cells (PBMC). METHODS:In silico assays were performed to predict conjugation sites and interactions between BKA and MAb. The synthesis of the conjugate was carried out chemically using EDC-HCl/Sulfo-NHS zero-length crosslinker and confirmed using a UV-Vis spectrophotometer. PBMC were used as a specificity test model. The conjugate exhibited selective cytotoxic toward CD3+ T cells without affecting other cells in PBMCs. RESULTS:In silico assays using molecular docking showed conjugation sites in the cavity of the CH2-CH3 Fc IgG2a domain and covalent interactions with lysine, asparagine, and glutamine amino acids. Measurements of absorption at wavelengths of 280 and 260 nm indicated the presence of protein and BKA in the synthesized conjugate. Incubation of PBMC with BKA and anti-CD3 MAb resulted in a significantly lower average number of cells (p< 0.05) than that observed in the group treated with the conjugate. CONCLUSION:In silico assays revealed an interaction between the carboxylic groups of BKA and the primary amine group of antibodies. The Conjugates exhibited lower cytotoxicity compared to BKA and anti-CD3 Mab individually. In vitro assays have not been able to show the specificity of the conjugate due to the anti-CD3 MAb alone exhibiting cytotoxic properties in PBMCs.

Background:The incidence of haze from Indonesian forest and peatland fires is a major concern due to its adverse health effects, particularly due to fine particulate matter (PM2.5) exposure, leading to adverse effects on the lungs. Aim:This study designed a whole-body PM2.5 exposure chamber to develop a PM2.5 exposure model with varying concentrations and durations, and then evaluated its impact on lung tissue. Methods:Thirty-six male Wistar rats were randomly divided into four groups: a control group and three treatment groups with PM2.5 exposure at concentrations of 300, 500, and 700 µg/m³ for 10, 20, and 30 days. The morphology of PM2.5 was characterized using a scanning electron microscope (SEM) equipped with an energy-dispersive X-ray spectroscopy (EDS) detector. Lung tissue histology was assessed using hematoxylin and eosin for lung injury scoring and Masson's trichrome for the percentage of fibrotic areas. Results:SEM-EDS results showed particles deposited within the alveolar cavity. The highest PM2.5 exposure group (700 µg/m³) had significantly higher lung tissue injury scores and fibrotic areas than the control group across all durations (p < 0.05). Conclusion:Exposure to PM2.5 from peat land-burning smokecauses significant lung tissue injury and fibrosis in a dose-dependent manner in Wistar rats.

BACKGROUND: Hypoxia inducible factor-1α (HIF-1α), nuclear factor erythroid 2-related factor 2 (Nrf-2), and vascular endothelial growth factor (VEGF), play a crucial role as neuroprotective factors. Currently, there is a lack of studies examining the biomolecular responses of the brain to intermittent hypoxia resulting from various pressures. This study was conducted to investigate the physiological responses, histopathological features, and cellular adaptive responses in the brains of rats that were intermittently exposed to hypobaric hypoxic conditions. METHODS: Thirty male Sprague Dawley rats were divided into six groups: a control group and five treatment groups exposed to hypobaric hypoxia. The treatment groups were placed in a hypobaric chamber simulating an altitude of 3,048 meters for 1 hour/day for 1, 7, 14, 21, and 28 days. After exposure, brain tissue was collected for histopathological analysis and protein quantification of HIF-1α, Nrf-2, cytoglobin (Cygb), neuroglobin (Ngb), VEGF, malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT). RESULTS: In the brain, intermittent hypobaric hypoxia significantly increased HIF-1α expression (p=0.000) and its downstream proteins Cygb (p=0.000), and VEGF (p=0.001), with a peak at 14x IHH exposure compared to control. This was followed by a significant increase in Nrf-2 expression (p=0.000), SOD (p=0.000), Gpx (p=0.000), and CAT activity (p=0.000), indicating an adaptive antioxidant response. Conversely, MDA levels was decreased with prolonged exposure, suggesting reduced oxidative damage. CONCLUSION: IHH elevates HIF-1α, Nrf-2, and oxidative stress markers, triggering an adaptive antioxidant response in the rat’s brains. KEYWORDS: HIF-1α, intermittent hypobaric hypoxia, Nrf-2, oxidative stress

Proteostasis, the integrated network regulating protein synthesis, folding, trafficking, and degradation, is essential for cellular function and organismal health. Reduced oxygen availability disrupts proteostasis through increased reactive oxygen species (ROS) production, endoplasmic reticulum (ER) stress, impaired ATP-dependent protein folding, and altered chaperone expression. In cancer, tumor cells exploit chronic unfolded protein response (UPR) signaling to enhance survival, angiogenesis, and therapeutic resistance. Inhibition of IRE1α and PERK pathways has shown efficacy in preclinical models, though clinical translation faces challenges including off-target toxicity. In neurodegenerative diseases—Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis—chronic hypoxia accelerates protein aggregate accumulation through oxidative modifications and impaired autophagy-lysosome function. Therapeutic strategies targeting γ-secretase, BACE1, and protein clearance pathways have demonstrated limited clinical success despite mechanistic rationale. Understanding hypoxia-induced proteostasis failure may inform therapeutic development, though significant obstacles remain in translating preclinical findings to effective treatments for cancer and neurodegenerative diseases.

BACKGROUND: Stunting due to malnutrition and soil-transmitted helminth (STH) chronic infections can cause disturbances in bone formation processes during growth. Reduced levels of insulin-like growth factor 1 (IGF-1) lead to reduced osteoblast activity which can be monitored through alkaline phosphatase (ALP) and osteocalcin (OCN). Unfortunately, studies that assessed IGF-1, OCN, and ALP together in stunted children with STH infection are still limited. Therefore, in this study, the osteoblast activity was monitored by measuring IGF-1, OCN, and ALP in stunted and normo-stature children with STH infection. METHODS: A case-control study involving 28 stunted and 33 normal-stature children was conducted. Blood plasma IGF-1 and OCN levels were measured using the enzyme linked immunosorbent assay (ELISA) method, while ALP activity was measured using the colorimetric method. STH infection was examined by direct smear method. The parameters were analyzed and compared between the stunted and normo-stature children. RESULTS: Although in stunted boys there was no significant difference, however in stunted girls with positive STH infection, a decrease in IGF-1 (<36.60 ng/mL vs. ≥36.60 ng/mL) showed an impact on the decrease of OCN levels (54.68 (42.22-144.54) ng/mL vs. 104.55 (86.14-392.73) ng/mL; p=0.047). ALP activity in children with positive STH infection showed that ALP activity in stunted children was lower than in normo-stature children (18 (10-671) U/L vs. 228.50 (16-574) U/L; p=0.005). CONCLUSION: The blood levels of IGF-1 and ALP activity in stunted and positive STH infected children tend to be lower than in normo-stature children. KEYWORDS: stunted, normo-stature, IGF-1, bone alkaline phosphatase, osteocalcin

Background/Objectives: Keloid treatment remains challenging due to limited effectiveness and patient dissatisfaction. Herbal-based therapy offers promising alternatives that require further investigation. Uncaria gambir (W.Hunter) Roxb., an original plant from Indonesia, possesses an antifibrotic effect. However, its potential as an antifibrotic agent in keloid management remains unclear. This study aims to bridge this gap by evaluating the bioactive compound from gambir and its effects on keloid fibroblast primary culture. Methods: The bioactive compounds of gambir extract and fractions (ethanol, hexane, and ethyl acetate fractions) were identified by using liquid chromatography–mass spectrometry (LCMS/MS) analysis. The mechanism of gambir bioactive compounds for keloid was predicted using the compound–protein interaction network and enrichment analysis, and validated using molecular docking and dynamic simulation. The experimental study results, including cytotoxic and bioactivity effects, were represented as IC50 and selectivity index (SI) values, and the ex vivo analysis of keloid tissue explants. Results: Uncariagambiriine was identified as the most potent compound with the lowest binding energy and high stability to the core protein targets: AKT1 and TGFB1. The ethanol fraction was determined to have the highest abundance of gambir’s typical bioactive compounds, with the lowest IC50 (128.76 ± 0.24 µg/mL) and the highest SI (6.32) value. Furthermore, the results of the ex vivo analysis indicated the significant inhibition of keloid fibroblast proliferation and migration by the gambir ethanolic fraction. Conclusions: This study underlines the potential of the gambir ethanolic fraction as an antifibrotic agent in keloid, warranting further investigation and development for clinical applications.

Introduction: Currently, Imatinib (IM) which is a Tyrosine Kinase Inhibitor (TKI), is the main treatment for patients with chronic myeloid leukemia (CML). Major molecular response (MMR) is used as therapeutic response. Resistance to IM may be caused by hypoxia which is regulated by hypoxia inducible factor (HIF) 2-alpha. The role of HIF2-alpha is currently not researched extensively. This study aimed to analyse the differences in HIF-2 alpha expression between chronic phase CML patients that achieved MMR and those that Methods: This study used a cross-sectional method which analysed secondary data from whole blood samples in chronic phase CML patients aged 18-60 years that received hydroxyurea (HU) before IM, aged 18-60 years, received IM therapy for more than 12 months, and were willing to participate in the study. The exclusion criteria for this study were patients who were receiving IM at a dose of more than 400 mg/day. HIF-2 alpha protein expression was examined using the enzyme-linked immunosorbent assay (ELISA) method. Differences between HIF-2 alpha protein expression in groups that achieved MMR versus not achieving MMR was analysed using the Mann-Whitney test. Results: A total of 79 subjects were obtained. The median HIF-2 alpha was 90.56 pg/mg protein (3.01-4628.74). There was no statistically significant difference in expression of HIF-2 alpha in the group that reached MMR and did not reach MMR, namely 123.45 pg/mg protein and 89.25 pg/mg protein respectively (p 0.718). Conclusion: This study found no statistically significant difference between HIF-2 alpha expression level and MMR achievement of chronic phase CML patients who received HU before IM therapy.

Objective: The goal of this study was to create vitamin E derivatives and explore their potential anticancer properties using a computational approach. Methods: The Steglich method was used for the synthesis of the vitamin E-fatty acid (pentanoic acid, heptanoic acid, and octanoic acid) derivatives, with N,N'-dicyclohexylcarbodiimide (DCC) and 4-dimethylaminopyridine (DMAP) as the catalysts. The structure of the synthesized products was determined by ultraviolet-visible (UV-Vis) spectroscopy, fourier transform infrared (FTIR) spectroscopy, and liquid chromatography-mass spectrometry (LC-MS). Molecular docking was carried out on the succinate dehydrogenase (SDH) enzyme using AutoDockTools. Results: α–Tocopherol pentanoate (α–TP), α–tocopherol heptanoate (α–TH), and α–tocopherol octanoate (α–TO) were the three vitamin E derivatives synthesized in this study. Based on the results of molecular docking, the novel compounds (α–TP, α–TH, and α–TO) generated bond energies of-10.57,-9.61, and-9.20 kcal/mol, respectively. Conclusion: All newly synthesized compounds exhibited lower binding affinity values than α–tocopherol (α–T). This confirms that these compounds might not provide greater advantages than α-tocopherol in terms of inhibitory effects on mitochondrial complex II (CII).

Keloid is characterized as the fibrotic tissue resulting from the increase of fibroblast activity. Uncaria gambir (Hunter) Roxb. possesses bioactive compounds that have potential as antifibrotic agents, while the mechanism of action in keloid has not yet been elucidated. The aim of this study was to investigate the interaction of gambir bioactive compounds with keloid target proteins using an epistatic and molecular simulation approach. The known bioactive compounds of gambir targets and keloid-related protein targets were screened using databases. The network was constructed and analyzed to obtain the core protein targets. The targets were enriched to describe the Gene Ontology (GO) and pathway related to the proteins. Eleven targets were defined as the main targets of gambir bioactive compounds related to keloid disease. Gambiriin C, Isogambirine, and Procyanidin B1 were identified as the most promising compounds with the highest binding energy to transforming growth factor beta 1 (TGFβ1), AKT serine/threonine kinase 1 (AKT1), and matrix metallopeptidase 1 (MMP1) as the target proteins. GO enrichment and pathway analysis found that gambir bioactive compounds may act on keloid-related target proteins to regulate cell proliferation, migration, transcription, and signal transduction activity via profibrotic cytokine and growth factor signaling pathways. This study provides a reference for potential targets, compounds, and pathways to explain the mechanism of gambir against keloid.

Since its first report in 1994, understanding of the nuclear factor erythroid 2-related factor 2 (Nrf2) has continued to grow. Initially recognized for its role in cellular response to oxidative stress, Nrf2 is now known to be involved in a variety of regulatory process, including metabolic regulation, autophagy, protein homeostasis (proteostasis), and mitochondrial biogenesis. The expression of Nrf2 target genes is highly dependent on stimulus activation and interactions with transcription factors, activators, and repressors. Nrf2 activation serves as a defense mechanism under physiological conditions, but in the context of cancer, it can trigger the development of cancer cells due to its complex roles. Nrf2 is strongly associated with the onset and development of many diseases, including those caused by metabolic disorders and inflammation. Understanding Nrf2's diverse functions offers valuable insights into disease pathogenesis and potential therapeutic approaches. This review explores the pleiotropic role of Nrf2 regulation.

Vitamin C (ascorbic acid) plays an exogenous antioxidant to protect biomolecules against cellular redox-reactive species generation, including ROS, that is involved in the development of oxidative stress-related diseases. Therefore, some ascorbic acid studies have concentrated on its ROS scavenging activity. We designed a combination of vitamin C and octanoic acid as vitamin C derivatives to evaluate their antioxidant potential in silico study using molecular docking. Compound 1 demonstrated the receptor-ligand interaction in Lipoxygenase (LO) than Zileuton-ZIL with its lower binding free energy (ΔG) and inhibition constant (Ki) value. Meanwhile, 6 exhibited lower Gibs energy (ΔG) and inhibition constant (Ki) in NADPH oxidase (NO) receptor than Dextromethorphan-DEX. The results add to the evidence supporting antioxidant activities of 1 and 6 in two receptors (LO and NO, respectively) via ROS generation. Thus, further research is warranted into their efficiency in reducing oxidative stress for possible commercial antioxidants.

This protocol introduces a streamlined and efficient method for isolating human fibroblast from skin primary cell culture with a specific focus on its application to keloid, hypertrophic scar, and normal skin biopsies. Additionally, the absence of suitable animal models for keloid and hypertrophic scar has led preclinical research to rely on in vitro studies using primary cell cultures. This approach addresses the challenges of existing protocols in terms of time, cost, equipment, and technical expertise required. The method involves derivation, culture, and characterization analysis including cell proliferation, migration, and fibroblastic marker (Vimentin, CD90, CD73, and CD105) expression. Our study yielded high amounts of fibroblast from tested skin explants while maintaining their in vivo-like characteristics and behaviour. Immunostaining assay confirmed that the cultivated fibroblast was positively expressed Vimentin. Flowcytometry results showed high expression of CD90 and CD73 while relatively showing lower expression of CD105. Fibroblast derived from keloid tissue showed the highest rate of proliferation and migration ability compared to the other samples. These findings suggest an efficient and reproducible technique to cultivate high qualified fibroblast from human skin in normal or pathological condition, particularly for keloid and hypertrophic scar. The application of this protocol provides a foundation for further studies to investigate the progression and potential intervention of aberrant fibrotic dermatological disorder, in vitro.

Telerehabilitation has the potential to help expand the reach of rehabilitation intervention. An online questionnaire-based Delphi method set out to develop a telerehabilitation guideline for patients in Indonesia with Long COVID. A Delphi panel comprised of 24 experts was selected from all relevant disciplines. Over two rounds of Delphi testing, panelists gave opinions and indicated their level of agreement with each recommendation. Key elements of consensus for a telerehabilitation guideline for patients with Long COVID includes: the benefit of telerehabilitation, types of rehabilitation intervention needed, methods of intervention, criteria for home-based self-exercise training, set-up of rehabilitation prescription, exercise monitoring, evaluation of rehabilitation intervention and duration of rehabilitation intervention. Further research is needed to determine the feasibility and effectiveness of this guideline.

The aim of the study is to examine the role of hypoxia-inducible factor-1a (HIF-1a) and intercellular adhesive molecule (ICAM-1) in clinical findings found in patients with rhegmatogenous retinal detachment (RRD). The clinical findings are; the duration of retinal detachment, retinal quadrants involvement, and the severity of proliferative vitreoretinopathy (PVR). A cross sectional study was conducted, with 34 consecutive vitreous sample were obtained from dr. Cipto Mangunkusumo National General Hospital (RSCM), from October 2015 to October 2016. The samples were taken from RRD patient who received vitrectomy in the hospital. There were no significant difference between the ICAM-1 and HIF-1a levels to the clinical findings that is measured; duration of retinal detachment (p>0.05), extent of retinal detachment area (p>0.05) and severity of PVR (p>0.05). However, there is a significant mean difference of ICAM-1 level on the duration of retinal detachment, where < 1 week group has higher mean 49.71, (SD 49.54) than the other group, as well as in the retinal quadrants groups (2nd quadrant 19.42 (SD 2.49) and also in severity of PVR groups (PVR B 35.42, SD 30.13). The results from HIF-1a level on each sub group were insignificant. The level of ICAM-1 and HIF-1a cannot be used as predictor of the clinical findings found in the patients. ICAM-1 levels tend to be high on patients whose diagnosed with retinal detachment early, with smaller area of detachment (2nd quadrant) and lower PVR levels (PVR B). The level of HIF-1a shows a consistent pattern with minimal difference in between the sub groups.

Topical keloid therapy is performed with triamcinolone acetonide (TA) intralesional injection. However, the recurrence rate is high with various side effects. Mesenchymal stem cells (MSCs) have high proliferative abilities and reduce the activity and proliferation of fibroblast cells in keloids. To overcome the costs and limitations, conditioned medium (CM) is used. This study aims to evaluate feasibility of intralesional injection of umbilical cord MSC (UC-MSC) and conditioned medium (UC-CM) compared to TA for keloid therapy. Twenty-four patients with keloids who met the inclusion criteria were included, randomized into three treatment groups and then got assessed for the sociodemographic data, keloid volume, histopathology (type 1:3 collagen ratio), interleukin-10 (IL-10) levels and Patient and Observer Scar Assessment Scale (POSAS) score during visits. Largest volume regression occurred in the UC-MSC group, followed by UC-CM and then the TA group (UC-MSC: 45.32% ± 2.61%; UC-CM: 43.61% ± 3.67%; TA: 28.34% ± 3.81%; p  = 0.003). Similar pattern was also observed in increase in IL-10 levels, the decrease in POSAS scores and the reduction of type 1:3 collagen ratio. Hence, UC-MSC and UC-CM are promisingly more effective than TA for keloid therapy, showcasing their superiority in reducing keloid volume, symptoms and type 1:3 collagen ratio, as well as increasing the levels of IL-10.

Background: Current keloid treatment involves intralesional injection of triamcinolone acetonide (TA), which, despite its usage, is associated with high recurrence rates and adverse effects. Mesenchymal stem cells (MSCs) exhibit potent proliferative abilities and can curb fibroblast activity and proliferation within keloids. It is now known that umbilical cord mesenchymal stem cells (UC-MSCs) have been shown to have greater proliferative potential than bone marrow-derived MSCs (BM-MSCs), and other advantages of UC-MSCs include being easily accessible and less immunogenic. To assess the viability of administering umbilical cord MSC (UC-MSC) and its conditioned medium (UC-CM) via intralesional injection compared to TA in reducing macroscopic keloid volume and type 1:3 collagen ratio.Methods: This randomized controlled trial enrolled twenty-four keloid patients by consecutive sampling. Eligible patients were required to have keloids on the chest, back, abdomen, or extremities. Patients with hypertrophic scars, a history of kidney failure, hypertension, blood disorders, malignancy, pregnancy, breastfeeding, or keloid treatment were excluded. Sociodemographic data, keloid size, and tissue biopsies were collected during scheduled visits. Bivariate analyses applied were considered significant at a p-value of <0.05.Results: The study revealed that the most significant decrease in macroscopic volume occurred within the UC-MSC group, followed by the UC-CM group, and then the TA group (UC-MSC: 50.24% +/- 3.58%; UC-CM: 43.97% +/- 3.04%; TA: 33.53% +/- 2.64; p = 0.004. The UC-CM group exhibited the most substantial decrease in the type 1:3 collagen ratios (4.80 +/- 0.26), with UC-MSC (4.60(4.15-8.05)) and TA (3.96(1.63-4.14)) following in sequence (p=0.002).Conclusion: The findings of this study indicate that the use of UC-MSC and UC-CM exhibits promising superiority over TA in terms of reducing macroscopic keloid volume and type 1:3 collagen ratio.

Introduction: Breast cancer is one of the highest causes of death from cancer in women in Indonesia. This is partly due to the resistance of ROS-based therapies such as radiotherapy and chemotherapy. Breast cancer stem cells (cancer stem cells, CSCs) have a role in this resistance mechanism. Previous studies demonstrated the ability of CSC to survive oxidative stress conditions due to rotenone administration. Therefore, in this study an analysis was carried out on the transcription factor NF-kB in breast cancer cells, both CSCs and Non CSCs, related to the role of NF-kB in maintaining the survival of cancer cells under conditions of oxidative stress. Methods: The study was conducted on human breast cancer stem cells (CD24-/CD44+) and non stem cells (CD24-/CD44-) which were given H2O2 at concentrations of 1.1µM, 11µM, and 110µM with control cells not given H2O2. Assessment was carried out on the parameters of NF-kB mRNA expression, and cell viability. Results: Administration of H2O2 at a concentration of 11µM showed a significant increase in the expression of NFk-B CSCs mRNA compared to non CSCs (p<0.05). As for the viability test results, at all concentrations of H2O2 it appears that CSCs was able to maintain its viability compared to non CSCs which experienced a decrease in viability (p<0.05). Conclusion: In this study, conditions of oxidative stress due to the administration of H2O2 led to an increase in the expression of NF-kB mRNA in CSCs so that cell viability could be maintained.

The aim of this study was to analyze the effect of heme synthesis inhibition on cytoglobin expression and its correlation with keloid fibroblast viability and proliferation. The study was conducted on primary culture of keloid fibroblasts. Heme synthesis in keloid fibroblasts was inhibited using succinyl acetone. We measured ALAD enzyme activity using a colorimetric method; cytoglobin mRNA expression using qRT PCR; cytoglobin protein expression using ELISA and immunocytochemistry; fibroblast viability using the MTT test; and fibroblast proliferation using BrdU test. The results showed that the ALAD enzyme activity level was lower in the keloid fibroblasts treated with SA (1, 2.5, and 5 mM) than in the control. The CYGB mRNA and protein expressions level were significantly lower in the keloid fibroblasts cultured with 2.5 mM and 5 mM SA than in the control and 1 mM SA. The viability and proliferation of the keloid fibroblasts decreased when the SA concentration was increased. In conclusion, the use of succinyl acetone at a concentration of 1; 2.5; and 5 mM caused decrease ALAD enzyme activity which indicated the inhibition of the heme synthesis. Inhibition of heme synthesis can affect cytoglobin expression, which correlates with the viability and proliferation of keloid fibroblasts.

Hypobaric hypoxia is situation that might occur to helicopter pilots in Indonesia who must fly at an altitude of more than 3,048 m such as in Papua. It can be dangerous because hypoxic condition can affect person's performance. So far, the heart is known as an aerobic organ and very sensitive to hypoxic conditions. Hitherto, the effects of hypobaric hypoxia exposure on biomolecular aspects of the heart are still unclear. Therefore, this study assessed cardiac response in rats exposed to intermittent hypobaric hypoxia (IHH) (equivalent to 3,048 meters/10,000 feet). Sprague-Dawley rats were divided into six groups: control; acute hypobaric hypoxia (AHH); and IHH, for 7; 14; 21; and 28 days. We measured super oxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities, reduced glutathione (GSH), malondialdehyde (MDA), cytoglobin, myoglobin, HIF-1α, and Nrf2 level as our parameters. Activities of SOD, CAT, GPx and GSH increased while the levels of MDA, cytoglobin, myoglobin, HIF-1α, and Nrf2 decreased in all IHH groups compared with the AHH group. A biphasic pattern was observed as IHH sessions increased from 14 to 21 or 28. Where the IHH treatment for more than 14 sessions caused a decrease in endogenous antioxidants, but the response to hypoxia and oxidative stress increased. Our findings presented the molecular alterations of cardiac rats exposed to intermittent hypobaric hypoxia.