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Nelly Herfina Dahlan,1,* Irma Bernadette S Sitohang,1,* Wresti Indriatmi,1 Heri Wibowo,2 Liani Elisabeth Enggy3 1Department of Dermatology and Venereology, Faculty of Medicine, University of Indonesia, Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia; 2Department of Integrated Laboratory, Faculty of Medicine, University of Indonesia, Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia; 3Faculty of Medicine, Hasanuddin University, Makassar, Indonesia*These authors contributed equally to this workCorrespondence: Irma Bernadette S Sitohang, Department of Dermatology and Venereology, Faculty of Medicine, Universitas Indonesia, dr. Cipto Mangunkusumo Hospital, Jalan Salemba Raya No. 6, Jakarta, 10430, Indonesia, Email irma_bernadette@yahoo.comBackground: The inflammatory process in acne vulgaris (AV) is characterized by the upregulation of specific pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6, and IL-8, within sebocytes and keratinocytes. Sebocytes have been identified as target cells for bioactive vitamin D. Experimental studies on animal models have demonstrated the potent comedolytic effects of topical vitamin D. However, further research is required to specifically evaluate the impact of vitamin D on inflammatory lesions in acne vulgaris (AV).Objective: To evaluate the effectiveness of topical vitamin D in treating acne vulgaris (AV) lesions by investigating its anti-inflammatory effects on pro-inflammatory cytokine modulation, specifically assessing the correlation between IL-1β levels in acne lesions and the reduction in AV severity.Materials and Methods: This study is a double-blind, randomized, placebo-controlled clinical trial with a 2-arm design over an 8-week intervention period. Participants were randomly assigned to either the topical vitamin D group (cholecalciferol 50 mcg) or the topical placebo group, with each group comprising 32 subjects. All participants received concomitant treatment with topical adapalene 0.1%. Cytokine levels within acne lesions were assessed using Luminex Polystyrene Screening Assays to detect and quantify IL-1β levels. The effectiveness of the treatment was evaluated by monitoring the reduction in the number of inflammatory lesions, while the safety of topical vitamin D was assessed by documenting and analyzing any reported side effects.Results: The study found a significant correlation between the reduction in IL-1β levels within acne lesions and the decrease in moderate and severe inflammatory lesions in acne vulgaris (p = 0.028). The topical application of vitamin D led to a significant reduction in inflammatory AV lesions (p = 0.045). No significant topical side effects were observed in either the vitamin D or placebo groups.Conclusion: This study demonstrates that the topical administration of vitamin D in acne vulgaris (AV) lesions is effective in reducing pro-inflammatory cytokine levels within acne lesions and in decreasing the severity of AV.Trial Registration: NCT05758259. September 5, 2022.Keywords: acne vulgaris, topical vitamin D, IL-1β, Luminex

Angela Giselvania,1,2 Vetnizah Juniantito,3 Heri Wibowo,4 Trifonia Pingkan Siregar,5 Soehartati Gondhowiardjo2 1Doctoral Program in Biomedical Sciences, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia; 2Department of Radiation Oncology, Faculty of Medicine Universitas Indonesia, Dr Cipto Mangunkusumo Hospital, Jakarta, Indonesia; 3Division of Pathology, School of Veterinary Medicine and Biomedical Sciences, IPB University, Bogor, Indonesia; 4Department of Parasitology, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia; 5Department of Radiology, Faculty of Medicine Universitas Indonesia, Dr Cipto Mangunkusumo Hospital, Jakarta, IndonesiaCorrespondence: Soehartati Gondhowiardjo, Department of Radiation Oncology, Faculty of Medicine, Universitas Indonesia, Dr Cipto Mangunkusumo Hospital, Jl. Pangeran Diponegoro No. 71, Kota Jakarta Pusat, DKI, Jakarta, 10430, Indonesia, Email gondhow@gmail.comPurpose: Large animal models are still used in many studies because of their likeness to humans. It has not been documented that regular-sized conventional farm-breed pigs, generally bred for meat production, can be used to generate hepatocellular carcinoma (HCC) animal models. The goal of this study was to investigate how N-diethylnitrosamine (DENA) and phenobarbital (PB) together can generate HCC in ordinary farmed pigs.Materials and Methods: Conventional domestic swine (Sus scrofa domesticus) were used. DENA 15 mg/kg was intraperitoneally injected weekly for 12 weeks, while PB tablets (4 mg/kg) were also administered through food for 16 weeks. Blood testing and ultrasonography evaluation were performed to monitor the progress. Subsequently, computed tomography was conducted in cases with suspected nodules, followed by histopathological examination to confirm the diagnosis.Results: Ten swine (seven males, three females; age: 2 months; weight: 9– 15 kg) were included in the study and followed up for 25 months; nine were experimental, and one was control for ethical considerations. The maximum weight of animals during this study reached 162– 228 kg. The weight gain seen in the intervention swine was predominantly lower than that documented in the control. The laboratory analysis revealed no notable abnormalities in liver function markers but did demonstrate statistically significant changes in urea (p = 0.028) and creatinine (p = 0.003) levels. Ultrasonography and computed tomography showed multiple liver nodules with characteristics resembling HCC. Serial imaging screening and more extended observations revealed that all animals eventually developed tumors. Histopathological confirmation at 15– 22 weeks post-induction revealed that all intervened swine developed multiple nodules of well-differentiated HCC and some with hepatic angiosarcoma.Conclusion: This study successfully generated HCC in conventional domestic swine with a DENA and PB combination. This investigation required at least 15 months to develop tumors. This model will be beneficial for future investigations of HCC in large animals.Keywords: carcinogenesis, large animal model, hepatocellular carcinoma, domestic swine, DENA induction

Handoko,1– 3,* Marlinda Adham,2,4,* Lisnawati Rachmadi,2,5,* Heri Wibowo,6,* Soehartati A Gondhowiardjo1,2,* 1Department of Radiation Oncology, Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia; 2Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; 3Doctoral Program in Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; 4Department of Otorhinolaryngology - Head and Neck Surgery Department, Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia; 5Department of Anatomical Pathology, Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia; 6Integrated Laboratory, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia*These authors contributed equally to this workCorrespondence: Soehartati A Gondhowiardjo, Faculty of Medicine, Universitas Indonesia, Jl. Salemba Raya No. 6, Jakarta, 10430, Indonesia, Email handoko12@ui.ac.id; gondhow@gmail.comIntroduction: Nasopharyngeal cancer (NPC) is a complex cancer due to its unique genomic features and association with the Epstein–Barr virus (EBV). Despite therapeutic advancements, NPC prognosis remains poor, necessitating a deeper understanding of its genomics. Here, we present a comprehensive whole genome sequencing (WGS) view of NPC genomics and its correlation with the phenotype.Methods: This study involved WGS of a clinical NPC biopsy specimen. Sequencing was carried out using a long read sequencer from Oxford Nanopore. Analysis of the variants involved correlation with the phenotype of NPC.Results: A loss of genes within chromosome 6 from copy number variation (CNV) was found. The lost genes included HLA-A, HLA-B, and HLA-C, which work in the antigen presentation process. This loss of the major histocompatibility complex (MHC) apparatus resulted in the tumour’s ability to evade immune recognition. The tumour exhibited an immunologically “cold” phenotype, with mild tumour-infiltrating lymphocytes, supporting the possible etiology of loss of antigen presentation capability. Furthermore, the driver mutation PIK3CA gene was identified along with various other gene variants affecting numerous signaling pathways.Discussion: Comprehensive WGS was able to detect various mutations and genomic losses, which could explain tumour progression and immune evasion ability. Furthermore, the study identified the loss of other genes related to cancer and immune pathways, emphasizing the complexity of NPC genomics. In conclusion, this study underscores the significance of MHC class I gene loss and its probable correlation with the cold tumour phenotype observed in NPC.Keywords: nasopharyngeal cancer, genomic, MHC class I, antigen processing and presentation, copy number variation, deletion

Rona Kartika,1 Dyah Purnamasari,2 Saraswati Pradipta,1 Rahma A Larasati,3 Heri Wibowo4 1Master Program in Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia; 2Division of Metabolic Endocrinology and Diabetes, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia; 3Department of Biomedicines, Faculty of Medicine, Universitas Muhammadiyah Jakarta, Jakarta, Indonesia; 4Department of Parasitology, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, IndonesiaCorrespondence: Heri WibowoDepartment of Parasitology, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, IndonesiaTel +62-812-8328-1905Email bowoheri04@gmail.comPurpose: In this study, we analyzed the production of interferon γ (IFN-γ) and interleukin 10 (IL-10) by peripheral blood mononuclear cells (PBMCs) in patients with type 2 diabetes mellitus (T2DM). We aimed to investigate the capacity of monocytes to produce tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) following IFN-γ stimulation and the associated role of IL-10 in TNF-α and IL-6 production.Patients and Methods: In vitro experiments were conducted on PBMCs obtained from 19 patients with T2DM and 17 healthy participants. PBMCs were isolated from venous blood by density gradient centrifugation, followed by 3-day phytohemagglutinin induction. In vitro production of TNF-α, IL-6, IFN-γ, and IL-10 was measured using the multiplex immunoassay. Statistical analysis was performed using IBM SPSS 23 version.Results: IFN-γ concentration in the T2DM group was significantly lower than that in control group (T2DM 7,700.86 ± 3,037.77 vs control 10,672.69 ± 5,625.50 pg/mL; p = 0.048). However, TNF-α, IL-6, and IL-10 levels showed no significant difference between the two groups. The TNF-α/IFN-γ and IL-6/IFN-γ ratios were significantly higher in T2DM than in the control group (p = 0.026 and p = 0.048, respectively). In T2DM, the high TNF-α/IFN-γ ratio was consistent, with the low baseline IL-10 level (p = 0.022).Conclusion: In T2DM, T-cell response is impaired with significantly reduced IFN-γ production, and simultaneously, circulatory monocytes show enhanced cellular responsiveness to inflammatory stimuli. The low baseline IL-10 level likely contributes to such an immune response.Keywords: type 2 diabetes mellitus, proinflammatory response, cytokines

Waste steel from used ship propeller shafts is reused for the keel structures of InaTEWS buoys. Because of the application of waste material, fatigue life assessment is critical. The purpose of this study is to assess the mechanical and fatigue properties of the waste material and to estimate the fatigue life of the keel structure as a result of sea wave loading. Material tests, fatigue tests and model tests were performed to obtain the parameters required for the estimation of the fatigue life, together with application of the spectral analysis method, including the effects of spectral band width. Chemical and tensile tests identified the material as low-carbon steel, with mechanical properties comparable to AISI 1035 steel. The fatigue tests resulted in an S-N curve (NSm = K) with m = 7.7 and K = 3.2×1024, showing a lower fatigue strength than AISI 1035 steel. The observed reduction in fatigue strength is ascribed to the previous use of the shaft. The calculated fatigue life based on the experimental S-N curve and the observed in-situ wave data is approximately 9.5 years, with a safety factor of 5.

Jeremiah Suryatenggara,1,2 Heri Wibowo,2 Wahyuni Lukita Atmodjo,3 George Mathew1,3 1Mochtar Riady Institute for Nanotechnology and Medical Science Group, Pelita Harapan University, Tangerang, 2Biomedical Science Graduate Programme, Faculty of Medicine, University of Indonesia, Jakarta, 3Faculty of Medicine, Pelita Harapan University, Tangerang, Indonesia Abstract: Tumor antigen alpha-fetoprotein (AFP) can promote immune tolerance toward tumor cells by inducing regulatory functions of the immune system. The purpose of this study was to characterize the effects of AFP on dendritic cells (DC) in their antitumor immune response stimulation and subsequent immune tolerance toward tumor cells. Monocytes were cultured in medium with GM-CSF and IL-4 and incubated for 6 days to generate immature DC (imDC). AFP was added into the treatment group at the beginning of the monocyte-derived DC culture. Mature DC (mDC) were generated by an addition of lipopolysaccharide (LPS) into the culture and incubation for another 48 hours. We observed that the addition of AFP in early DC culture was able to decrease the binding of LPS onto imDC surface, which lowered the strength of stimulation and consequently the maturity of DC. As expected, the expression of mDC surface markers, which are known to be crucial in effector cell proliferation and activation such as HLA-DR, CD40, CD80, CD83, and CD86, were confirmed to be reduced on AFP-exposed DC. DC potential in stimulating proliferation of CD4+ T cells was decreased, in line with the reduction of surface markers’ expression. Additionally, an increased secretion of cytokine TGF-β by DC was observed. In summary, AFP inhibited the effector immune responses while increasing the regulatory immune responses in DC. This might lead to tolerance toward antigens and tumor cell survival, such as in cases of hepatocellular carcinoma patients with high levels of AFP. Keywords: alpha-fetoprotein, dendritic cells, antigen-presenting cells, hepatocellular carcinoma, lipopolysaccharide, tumor immunoescape

Although live load is well known to have a dynamic effect on bridge response in addition to its self-weight, the significance of these effects on seismic response is unclear. In addition, most bridge design specifications have few requirements concerning the inclusion of live load in their seismic design provisions. The main objective of this study is therefore to investigate and obtain insight into the effect of vehicle-bridge interaction during earthquake shaking. The study consists of both experimental and analytical investigations. This paper focuses on the experimental work, which includes shake table testing of a 2/5-scale model of a horizontally curved steel girder bridge loaded with a series of representative vehicles. Preliminary experimental results show that the presence of the live load had a clear beneficial effect on performance for small amplitude motions, but that this improvement diminished with increasing amplitude of shaking. Parameters used to measure performance include column displacements, abutment shear forces, abutment uplift, and concrete spalling.