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Intermittent Hypobaric Hypoxia Preconditioning Ameliorates Kidney Damage Compared to Acute Hypoxia Sadikin, Abdul Halim; Jusman, Sri Widia Azraki; Mulyawan, Wawan; Prijanti, Ani Retno
HAYATI Journal of Biosciences Vol. 32 No. 6 (2025): November 2025
Publisher : Bogor Agricultural University, Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.4308/hjb.32.6.1437-1446

Abstract

Many studies have reported that intermittent hypobaric hypoxia (IHH) can cause oxidative stress and tissue damage in the kidneys, which can lead to impaired kidney function. However, a study using simulated intermittent hypobaric hypoxia was considered to have a protective role for the kidneys. This study aims to determine the effect of IHH on kidney adaptation to oxidative stress and kidney damage. Twenty-five rats were divided into five groups: control, one-time hypoxia (AHH), two-time hypoxia (IHH 1), three-time hypoxia (IHH 2), and four-time hypoxia (IHH 3). The intermittent interval was one week, and at the time of treatment, the rats were placed in a hypoxic chamber. At the end of treatment, the rats were sacrificed, and the kidneys, urine, and blood were collected. The kidney tissues were used for protein assay, ELISA (HIF-1α and VEGF), qPCR (cytoglobin (Cygb) and renin), SOD and GPx activity assay. Blood was used for creatinine and urea assay, and urine was used for KIM-1 ELISA. Formalin-submerged tissues were used for histopathological analysis. The level of HIF-1α and VEGF increased significantly from AHH to IHH 1. Cygb and renin expressions peaked at AHH and decreased at subsequent IHH groups. The Nrf2 level and GPx activity didn’t show any difference, but SOD activity peaked at IHH 1. The creatinine level only peaked at IHH 2; other groups remained the same as the control. Urea levels decreased with more IHH sessions, and KIM-1 didn’t show any difference. Our findings exhibit that hypoxia preconditioning by IHH treatment leads to the kidney’s adaptability to hypoxia and does not cause kidney damage.
Gastrointestinal Dysfunction after Traumatic Brain Injury: Mechanisms Linking The Gut, Inflammation, and the HPA Axis Dwi Hastuti; A Jusman, Sri Widia; Reni Paramita
EKSAKTA: Berkala Ilmiah Bidang MIPA Vol. 26 No. 04 (2025): Eksakta : Berkala Ilmiah Bidang MIPA (E-ISSN : 2549-7464)
Publisher : Faculty of Mathematics and Natural Sciences (FMIPA), Universitas Negeri Padang, Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.24036/eksakta/vol26-iss04/601

Abstract

Traumatic brain injury (TBI) is a major global health problem that often leads to systemic complications beyond neurological damage, notably gastrointestinal (GI) dysfunction. The mechanisms linking TBI to GI complications remain inconclusive. We conducted a systematic review using current clinical evidence on the pathophysiological processes underlying post-TBI GI dysfunction, focusing on two principal mechanisms: inflammatory-oxidative processes and hypothalamic–pituitary–adrenal (HPA) axis alterations. A comprehensive search was conducted through PubMed, Cochrane Library, and Scopus to identify eligible studies. Evidence indicates that surges of proinflammatory mediators and chemokines, along with reduced anti-inflammatory mediators, drive systemic immune imbalance. Moreover, iNOS upregulation and gut microbiota dysbiosis contribute to mucosal injury. Concurrently, HPA axis dysregulation exerts a bidirectional impact. Elevated ACTH and cortisol reflect an intact stress response that may stabilise metabolism if combined with early enteral nutrition, whereas critical illness-related corticosteroid insufficiency (CIRCI) and hypergastrinemia are strongly associated with gastrointestinal bleeding and mortality. Together, these findings underscore the synergistic role of inflammatory and endocrine disturbances in driving gastrointestinal vulnerability after TBI. Understanding these mechanisms is crucial for developing biomarker-based monitoring and targeted interventions to improve prognosis and reduce GI-related complications in TBI patients.
Peran Sitoglobin pada Kanker Yastani, Deasyka; H, Novi Silvia; Jusman, Sri Widia A
Jurnal Biomedika dan Kesehatan Vol 6 No 2 (2023)
Publisher : Fakultas Kedokteran Universitas Trisakti

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18051/JBiomedKes.2023.v6.250-260

Abstract

Cytoglobin (Cygb) is a new member of the globin protein family, following the discovery of other globin proteins such as hemoglobin (Hb), myoglobin (Mb), and neuroglobin (Ngb). In 2001, Kawada et al. identified Cygb in hepatic stellate cells (HSCs) that play an important role in the repair of damaged liver cell tissue, hence the name stellate cell activation-associated protein (STAP). Cygb has a more universal role than Hb, Mb, and Ngb, and is expressed throughout mammalian tissues. Cygb is a globin with 6 coordination bonds (hexacoordinate globin). Cygb has been shown to play an important role in the normal cell respiratory chain, including oxygen storage, destruction of reactive oxygen species (ROS), terminal oxidase activity, regulation of fibrogenesis, and regulation of apoptosis. The role of Cygb in the respiratory process has been studied because it is associated with the globin family, and because of the upregulation of Cygb during hypoxia, but its specific role has not been elaborated. Recent research reports that Cygb has several implications for cancer. In most cancer cells, Cygb expression is upregulated by hypermethylation, suggesting epigenetic control. In cancer cells, downregulation of Cygb occurs which indicates a possible role as a tumor suppressor gene. In some malignancies, on the contrary, Cygb upregulation may be associated with resistance to hypoxia which indicates Cygb has two sides or Janus faces related to its role in cancer cells.
The Effect of Platelet Aditive Solution In Maintaining the Quality and Function of Concentrated Platelets In The Pooling Method of Buffy Coat Leukofiltered Wido Sari Nawangsih, Idah; Widia A. Jusman, Sri; Chunaeni, Saptuti
Jurnal Health Sains Vol. 6 No. 1 (2025): Jurnal Health Sains
Publisher : Syntax Corporation Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.46799/jhs.v6i1.1537

Abstract

The availability of platelets in the Indonesian Red Cross (PMI) Blood Transfusion Unit (UDD) has been significantly high, with 767,680 bags collected in 2019, increasing to 957,397 bags in 2021. The dengue fever outbreak alongside the COVID-19 pandemic led to a nearly twofold increase in the demand for concentrated platelets (TP) in hospitals from 2021. However, platelet additive solution (PAS), which can extend platelet shelf life, is not yet utilized in Indonesia. This study aims to investigate whether TP obtained using the buffy coat leukofiltered pooling method and stored with PAS can improve platelet quality during storage. A series of laboratory tests were conducted to evaluate platelet count, pH levels, and aggregation function using ADP inspection, monitored over a storage period from day zero to day seven. The results indicate that the addition of PAS effectively maintains platelet quality, pH stability, and platelet function throughout the storage duration. This is attributed to the nutrient-rich composition of PAS, which contains glucose, sodium acetate, sodium chloride, phosphate, magnesium, and potassium, ensuring the preservation of platelet integrity. The findings highlight the potential benefits of PAS implementation in Indonesia to enhance platelet storage efficiency and availability, particularly during periods of high demand. Future research should explore the optimal PAS formulation for different storage conditions, cost-effectiveness, and clinical efficacy in transfusion settings to support broader adoption of this technology in blood banking.
Ekstrak Teh Hijau Mengurangi Luas Area Fibrosis Paru Tikus Desdiani; Iris Rengganis; Samsuridjal Djauzi; Agus Setiyono; Mohammad Sadikin; Sri Widia A. Jusman; Nurjati Chairani Siregar; Suradi; Putri C. Eyanoer
Majalah Patologi Indonesia Vol. 29 No. 1, Januari 2020
Publisher : Perhimpunan Dokter Spesialis Patologi Anatomik Indonesia (PDSPA)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.55816/mpi.v29i1.403

Abstract

BackgroundPulmonary fibrosis is often found in infectious diseases and chemical exposure in the work environment. Antifibrotic effects can befibropreventive and fibrolysis. Bleomycin can cause inflammation and pulmonary fibrosis. Catechin is proven can repair liverdamages due to alcohol induction. The aim of this study is to examine the effect of antifibrotic green tea catechin on reducing thearea of rat lung fibrotic.MethodsThis research was carried out in vivo experimentally in the Laboratory Animal Management Unit at Faculty of Veterinary MedicineIPB in 4 groups of rat experiments, consisting of 3 rats in the negative control group, 3 rats in the positive control group, 3 rats in thegroup of rats given bleomycin on the 8th day and 28thwith green tea extract every day from day 0 to 49 days (fibropreventive), 3groups of rats given bleomycin days 0 and 21 with green tea extract every day from day 15 to 49 (fibrolysis). Histopathologicalexamination was performe for all groups of rats.ResultsThis study showed that administration of green tea extract in fibropreventive groups and fibrolysis groups could reduce the fibrosisarea in rat lungs based on Aschroft's modified scale.ConclusionBased on the results of this study it was found that the anti-fibrotic activity of green tea extract was proven to be able to suppressthe development of pulmonary fibrosis both by fibropreventive and fibrolysis
Lower IGF-1 and Alkaline Phosphatase Activity Blood Levels in Stunted Children with Soil-Transmitted Helminth Infections Tiara Mayang Pratiwi Lio; Heri Wibowo; Mohamad Sadikin; Sri Widia A. Jusman
The Indonesian Biomedical Journal Vol 17, No 2 (2025)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v17i2.3454

Abstract

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
Intermittent Exposure to Hypobaric Hypoxia Increases VEGF, HIF-1α, and Nrf-2 Expressions in Brain Tissue Wardaya Wardaya; Dewi Sukmawati; Nurhadi Ibrahim; Frans Ferdinal; Ninik Mudjihartini; Mohamad Sadikin; Sri Widia A. Jusman; Irawan Satriotomo; Wawan Mulyawan
The Indonesian Biomedical Journal Vol 17, No 2 (2025)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v17i2.3519

Abstract

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
Hyperbaric Oxygen Therapy for Traumatic Brain Injury: A Review Of History, Development, Current Techniques, and Future Directions Wiwoho, Yudi Yuwono; Sadikin, Abdul Halim; Jusuf, Ahmad Aulia; Mulyawan, Wawan; Mudjihartini, Ninik; Ibrahim, Nurhadi; Jusman, Sri Widia A.; Sadikin, Mohamad
Proceedings Book of International Conference and Exhibition on The Indonesian Medical Education Research Institute Vol. 9 No. - (2025): Proceedings Book of International Conference and Exhibition on The Indonesian M
Publisher : Writing Center IMERI FMUI

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.69951/proceedingsbookoficeonimeri.v9i-.321

Abstract

Hyperbaric oxygen therapy (HBOT) has gained increasing attention as a potential adjunctive treatment for traumatic brain injury (TBI) patients. This narrative review discusses the historical background, current preclinical and clinical studies, and explores its underlying mechanisms from biomolecular, histological, and clinical perspectives. HBOT promotes neural recovery by improving oxygenation, preserving mitochondrial integrity, enhancing neurotrophic support and synaptic connectivity, mitigating secondary injury pathways (including oxidative stress, inflammation, and apoptosis), and promoting angiogenesis and vascular stability. These mechanisms have demonstrated improvements of motor, cognitive, and memory functions both in preclinical and clinical studies, although outcomes and treatment protocols vary. However, challenges remain regarding optimal protocols, patient selection, and adverse effects. Further high-quality clinical trials are required to define the optimal HBOT regimen are required.
Proteostasis disruption under hypoxia: therapeutic targets in cancer and neurodegenerative diseases Susi Rahmiyati; Ani Retno Prijanti; Sri Widia A Jusman; Syarifah Dewi
Acta Biochimica Indonesiana Vol. 8 No. 2 (2025): Acta Biochimica Indonesiana
Publisher : Indonesian Society for Biochemistry and Molecular Biology

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.32889/actabioina.142

Abstract

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.
Gastrointestinal Dysfunction after Traumatic Brain Injury: Mechanisms Linking The Gut, Inflammation, and the HPA Axis Dwi Hastuti; Sri Widia A Jusman; Reni Paramita
EKSAKTA: Berkala Ilmiah Bidang MIPA Vol. 26 No. 04 (2025): Eksakta : Berkala Ilmiah Bidang MIPA (E-ISSN : 2549-7464)
Publisher : Faculty of Mathematics and Natural Sciences (FMIPA), Universitas Negeri Padang, Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.24036/eksakta/vol26-iss04/601

Abstract

Traumatic brain injury (TBI) is a major global health problem that often leads to systemic complications beyond neurological damage, notably gastrointestinal (GI) dysfunction. The mechanisms linking TBI to GI complications remain inconclusive. We conducted a systematic review using current clinical evidence on the pathophysiological processes underlying post-TBI GI dysfunction, focusing on two principal mechanisms: inflammatory-oxidative processes and hypothalamic–pituitary–adrenal (HPA) axis alterations. A comprehensive search was conducted through PubMed, Cochrane Library, and Scopus to identify eligible studies. Evidence indicates that surges of proinflammatory mediators and chemokines, along with reduced anti-inflammatory mediators, drive systemic immune imbalance. Moreover, iNOS upregulation and gut microbiota dysbiosis contribute to mucosal injury. Concurrently, HPA axis dysregulation exerts a bidirectional impact. Elevated ACTH and cortisol reflect an intact stress response that may stabilise metabolism if combined with early enteral nutrition, whereas critical illness-related corticosteroid insufficiency (CIRCI) and hypergastrinemia are strongly associated with gastrointestinal bleeding and mortality. Together, these findings underscore the synergistic role of inflammatory and endocrine disturbances in driving gastrointestinal vulnerability after TBI. Understanding these mechanisms is crucial for developing biomarker-based monitoring and targeted interventions to improve prognosis and reduce GI-related complications in TBI patients.
Co-Authors . Rusdi Abdul Halim Agus Setiyono Ahmad A Jusuf Ahmad Aulia Andi Arus Victor Andriani Andriani Angelina Stevany Regina Masengi Ani R Prijanti Ani Retno Prijanti Cindy Fawwaz Roviqoh Damar Prasmusinto Deasyka Yastani Desdiani Dewi Sukmawati Dwi Hastuti DWI HASTUTI Dwi Retna Lestari Ernie Purwaningsih Evy Ayu Arida Fadilah Fadilah Fanny Septiani Farhan Febriana Catur Iswanti Ferdiana Yunita Frans D Suyatna Frans Ferdinal Frans Ferdinal H, Novi Silvia Helmi Rizal Hendrik Kurniawan Heri Wibowo Ika Superti Daruningrum Indriati P Harahap Irawan Satriotomo Iris Rengganis Joedo Prihartono Joedo Prihartono Johannes Cornelius Mose K Kartini Kenny Cantika Abadi Labibah Qotrunnada Lailan Safina Nasution Lindi G Haritsyah Lis Rosmanah M Ekawati Maftuhatun Fista Amalia Mohamad Sadikin Mohamad Saekhu Mohammad Sadikin Mohammad Sadikin Muhammad Yamin Murdani Abdullah Ninik Mudjihartini Noroyono Wibowo Novi Resistantie Novi Silvia Hardiany Novianti, Titta Noza Hilbertina Nur Ita Margyaningsih Nurhadi Ibrahim Nurhadi Ibrahim Nurjati Chairani Siregar Nurjati Chairani Siregar Putri C. Eyanoer Rahayuningsih Dharma Raisa Nauli Reni Paramita Reni Paramita Ressa Yuneta Retno Kuntarti Rizqa Febriliany Putri Sadikin, Abdul Halim Saidah Rauf Samsuridjal Djauzi Saptuti Chunaeni, Saptuti Sarsanti, Pungguri Ayu Nega Septelia I. Wanandi Siregar, Fajri Marindra Siti Rahmawati Achyat Sri Sukmaniah Suhendro Suhendro Suradi Susi Rahmiyati Syarifah Dewi Tiara Mayang Pratiwi Lio Tjahjono Darminto Gondhowiardjo Vetnizah Juniantito Wardaya Wardaya Wawaimuli Arozal Wawan Mulyawan Wawan Mulyawan Werdhasari, Asri Wido Sari Nawangsih, Idah Wiji Lestari Wiwoho, Yudi Yuwono