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Shirly Gunawan,1 Vivian Soetikno,2 Erni Hernawati Purwaningsih,3 Frans Ferdinal,4 Puspita Eka Wuyung,5,6 Dwi Ramadhani7 1Department of Pharmacology, Faculty of Medicine, Universitas Tarumanagara, Jakarta, Indonesia; 2Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; 3Department of Medical Pharmacy, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; 4Department of Biochemistry and Molecular Biology, Faculty of Medicine, Universitas Tarumanagara, Jakarta, Indonesia; 5Department of Anatomical Pathology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; 6Animal Research Facility, IMERI, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; 7Research Center for Radioisotope, Radiopharmaceutical, and Biodosimetry Technology, Research Organization for Nuclear Energy, National Research and Innovation Agency, Banten, IndonesiaCorrespondence: Vivian Soetikno, Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Indonesia, Salemba Raya no. 6, Jakarta, 10430, Indonesia, Tel +62 21 31930481, Email vivian.soetikno@ui.ac.idPurpose: Endoplasmic reticulum (ER) stress has a prominent role in the pathogenesis of high-fat diet-induced non-alcohol related fatty liver disease (NAFLD). The aim of this study is to investigate the effects of 6-G on the reduction of ER stress-induced NAFLD in metabolic syndrome (MetS) rats.Methods: Twenty-five male Sprague-Dawley rats were fed with a high-fat high-fructose (HFHF) diet for 16 weeks. The rats were treated orally with 6-G (50,100, and 200 mg/kgBW) once daily for eight weeks. At Week 16, all animals were sacrificed, and serum and liver tissue were harvested for biochemical and structural analysis.Results: NAFLD liver rats were shown to have elevated protein expression of GRP78, and ER-associated apoptotic protein, such as IRE1, TRAF2, p-JNK, and p-NF-κB, which were considerably reduced by the 6-G at three doses treatment. Furthermore, a significant increase in liver apoptosis and non-alcoholic steatohepatitis (NAS) score were observed in the NAFLD rat liver and which were also attenuated by the 6-G treatment at three doses. 6-G treatment also reduced ALT, AST, and ALP serum levels.Conclusion: Considering all the findings, it is suggested that the 6-G treatment could be a potential candidate therapy in treating ER stress-induced NAFLD in rats.Keywords: 6-gingerol, endoplasmic reticulum, diabetes, insulin resistance, inflammation

Penelitian ini bertujuan untuk mengetahui pengaruh yang terbaik serta mengetahui nilai organoleptik daging sapi bali hasil marinasi menggunakan madu trigona. Marinasi daging dilakukan selama 30 menit pada suhu ruang. Rancangan penelitian yang digunakan adalah Rancangan Acak Lengkap (RAL) dengan empat perlakuan dan tujuh ulangan. Keempat perlakuan tersebut adalah daging yang tidak dimarinasi (P0); daging yang dimarinasi menggunakan madu trigona 5 ml (P1); daging yang dimarinasi menggunakan madu trigona 10 ml (P2); dan daging yang dimarinasi menggunakan madu trigona 15 ml (P3). Variabel yang diamati pada penelitian meliputi warna, aroma, rasa, tekstur, keempukan, dan penerimaan keseluruhan yang dinilai oleh 15 orang panelis semi-terlatih. Hasil penelitian menunjukkan bahwa daging sapi bali yang dimarinasi menggunakan madu trigona memberikan pengaruh nyata terhadap warna, aroma, rasa, keempukan dan penerimaan keseluruhan, namun tidak memberikan pengaruh yang nyata terhadap tekstur. Simpulan dari penelitian ini adalah marinasi daging sapi bali yang paling baik adalah menggunakan madu trigona dengan level 10 ml terlihat dari peningkatan nilai aroma, rasa, tekstur, keempukan, dan penerimaan keseluruhan panelis.

This research comprehensively analyzes students’ Chemistry Learning Experience (CLE) during the COVID-19 pandemic, comparing online learning experiences with traditional face-to-face instruction in the post-pandemic phase. Employing a quantitative approach and leveraging the Rasch model, the study focuses on capturing the nuances of individual student perceptions, an aspect often overlooked in group-centric statistical analyses. One hundred students (49 males and 51 females) participated in both study phases. Segmented into behavioral tendencies, content perceptions, and specific learning needs, the evaluation tools provided insights into the students’ CLE across the two instructional modalities. Results from the stacking analysis revealed a positive shift in CLE post-pandemic, with students demonstrating a better grasp of and attitude toward chemistry in face-to-face settings. Racking analysis further underscored the changing difficulty perceptions of specific content items across the two learning environments. Gender-based patterns in CLE were also evident, with male students expressing a more favorable view of online learning during the pandemic than their female counterparts. The research findings advocate for a blended learning approach, harnessing the strengths of both online and traditional instructional methods. Furthermore, insights into gender-specific learning experiences emphasize the need for inclusive and adaptive teaching strategies, ensuring optimal learning experiences for all students. The study underscores educators’ and students’ resilience and adaptability in navigating the challenges of the pandemic. It offers valuable insights for future educational strategies in chemistry education.

Engaging students in collaborative learning fosters the expression of ideas, deepens understanding, and hones argumentation skills. Argumentation is pivotal, and instructors should facilitate opportunities for its practice. In the study on an environmental chemistry course, class conversations were recorded to analyze students’ contributions to online learning. Participants shared opinions, raised objections, and built on others’ answers. The instructor played a crucial role in harmonizing collaboration and guiding comprehensive argumentation. The study found claims and data as the most basic and common elements of argumentation. However, more complex components like rebuttal and backing warrants often need instructor intervention. While claims and data typically relied on one form of representation, such as macroscopic or symbolic, warrants demanded multiple dimensions, predominantly symbolic and submicroscopic. Toulmin’s arguments and Mahaffy’s tetrahedral ability of chemical representation were used for analysis. The findings highlighted that argumentation skills and chemical representation are intertwined, with certain argumentative components calling for specific representational dimensions. Collaborative online learning, thus, can enhance student participation and multifaceted skill development.

The cognitive aspect of arithmetic ability is a necessary aspect for students that deserves attention. This is because arithmetic cognitive ability is a tool that children will use in facing life. In addition, arithmetic cognitive ability is a basic ability for a child to solve everyday problems and is a tool for further education. Snakes and ladders can be adopted as a learning aid for kindergarten children to improve their counting ability. Teachers can consider using snakes and ladders as a teaching method, as it is considered effective for kindergartners who still have a play instinct. The purpose of this research is to understand the effectiveness of the snakes and ladders learning tool in improving children's counting ability. This research was conducted using qualitative and descriptive methodologies. The population and sample were taken from Group B of Aisyiyah Bustanul Athfal Bumi Mulyo Kindergarten with a total of 16 students. Data collection was done through several ways such as observation, interview, and documentation. The data obtained was then analyzed using several steps, namely; data reduction, data presentation, and conclusion drawing. The results showed that the use of the snakes and ladders tool can help improve arithmetic ability in Group B students of Aisyiyah Bustanul Athfal Bumi Mulyo Kindergarten in the 2021/2022 academic year

Learning activities underwent policy changes during the Covid-19 pandemic were carried out online and offline. During the Covid-19 pandemic, there were many ways that universities did to keep learning going, such as implementing online learning and online learning. Practical learning experiences changes in the teaching and learning process system due to university policies. This study aims to measure the level of mental workload and the level of student fatigue during online and offline practicums and to determine the relationship between mental workload and fatigue level. The methods used in this research are the National Aeronautics and Space Administration Task Load Index (NASA-TLX) and Subjective Self Rating Test (SSRT) methods. The results showed that the level of mental workload of students was in the high classification with the NASA-TLX dimensions of effort, mental needs, and performance. The level of student fatigue is in the moderate classification with part of the SSRT, namely the weakening of activities. The results of the correlation test show that there is a relationship between mental workload and student fatigue levels with a positive direction of relationship.

The batik industry in Kampoeng Batik Laweyan drives entrepreneurs to improve company performance for sustainability and competitiveness. SMEs can boost productivity, assessing overall performance and guiding sustainable improvements. Besides economic benefits, batik production poses environmental challenges through waste disposal. Green productivity aims to enhance productivity and environmental performance simultaneously. Research on SMEs like Batik Anugrah Purnama and Batik Tunaruntum shows productivity gains in January 2019: 172% and 610%. Material management strategies, such as reusing leftover wax and switching to gas for the lorod process, contributed to productivity enhancements. Consequently, productivity rose to 206% and 664%. Post-liquid waste treatment, Environmental Performance Indicator (EPI) indices improved from -1.415, -3.285 to 0.032, -0.77.

Background: Neck pain is pain that includes disorders of the nerves, tendons, muscles and ligaments around the neck. One of the causes of neck pain is the wrong position of the body which causes the neck in a certain position for a long time. In the use of cell phones there will be a process of changing the position of the neck, the position of the head will be bow to look at the cell phone screen and maintained for a long time, causing muscle problems which, if left unchecked, can become chronic muscle pain. Objectives: To find out relationship between the bow position when using a cell phone and neck pain. Methods: This study is an analytic-observational study with a cross-sectional design. The sampling technique used simple random sampling technique. The data will be analyze using chi-square statistical test. In which the p-value < 0.05 is significant. Results: There is a relationship between the bow position when using a cell phone to neck pain with p-value 0.045. On the other test, there is no relationship between the duration of cell phone use and neck pain, both in one use (p = 0.509) and in a day (p = 0.729). Conclusion: There is a significant relationship between the bow position when using a cell phone and neck pain. Keywords: neck pain, cell phone, bowing position Latar Belakang: Nyeri tengkuk adalah rasa nyeri yang meliputi kelainan saraf, tendon, otot dan ligamen di sekitar leher. Salah satu penyebab dari nyeri tengkuk adalah posisi tubuh yang salah sehingga membuat leher berada dalam posisi tertentu dalam jangka waktu yang lama. Pada penggunaan telepon seluler akan terjadi proses perubahan posisi leher, yang mana posisi kepala akan menunduk untuk melihat ke arah layar telepon seluler dan dipertahankan dalam waktu yang relatif lama, sehingga menimbulkan masalah otot yang apabila dibiarkan dapat menjadi nyeri otot kronis. Tujuan: Untuk mengetahui hubungan posisi menunduk saat menggunakan telepon seluler dengan nyeri tengkuk. Metode: Penelitian ini merupakan penelitian analitik-observasional dengan desain cross-sectional. Pengambilan sampel dilakukan dengan teknik simple random sampling. Hasil pengukuran akan dianalisis menggunakan uji chi-square. Nilai p < 0,05 dianggap signifikan. Hasil: Terdapat hubungan antara posisi menunduk saat menggunakan telepon seluler terhadap nyeri tengkuk dengan nilai P = 0,045. Pada uji hubungan lainnya tidak ada hubungan antara durasi penggunaan telepon seluler terhadap nyeri tengkuk baik dalam sekali penggunaan (P = 0,509) maupun dalam sehari penggunaan (P = 0,729). Kesimpulan: Terdapat hubungan yang signifikan antara posisi menunduk saat menggunakan telepon seluler dengan nyeri tengkuk. Kata Kunci: nyeri tengkuk, telepon seluler, posisi menunduk

Paddy is one of the main food-crop commodities in Indonesia. The main problem in paddy cultivation in Paser Regency is good water quality for plants. Water is the main requirement for paddy plants to grow and develop. Water quality to meet the needs of paddy plants is a very important factor. pH H2O, TDS (Total Dissolve Solid) and EC (Electrical Conductivity) are some of the water parameters used as a reference in determining land suitability for paddy plants. The purpose of this research is to spatially analyse the water parameters (pH H2O, TDS and EC) for the water needs of paddy plants in Paser Regency. Determination of sample points using stratified random sampling method and parameter measurements are carried out directly in the field in the irrigation area. Interpolation analysis used the IDW (Inverse Distance Weighted) method with a power weight of 2. RMSE values from the interpolation results for pH H2O 0.0001, TDS 0.1695 and EC 0.0003. The results of the interpolation of several parameters are then analysed by overlay to determine the spatial relationship between parameters. The results of the analysis show that the average values in Paser Regency are pH H2O 6.13, TDS 478.64 ppm and EC 0.82 mS/cm. The area of pH H2O (6.5-8.4) suitable for paddy plants is 391447.87 ha, TDS (

The purpose of this research is to know whether there is influence of learning model of Geogebra-assisted Discovery Learning to understanding mathematical concept, to know whether there is influence between learners who have cognitive style of FI and FD to understanding mathematical concept, to know whether there is interaction between learning of Discovery Learning Unity Geogebra with the cognitive style of learners towards the understanding of mathematical concepts. This research type is quasi experiment research, population in this research is all students of class VII of SMP Negeri 2 Bandar Lampung, sampling technique in this research use class random technique where class VII-8 as experiment class 1 with study of Discovery Learning assisted geogebra, Class VII-7 as a control class with Discovery Learning learning with Microsoft Power Point. Technique of data analysis in this research use two way Anova test with unequal cell. Based on the test results, the first hypothesis is indicated by the statistical price of 8,871 (p> 4,001), so that H0A is rejected with the conclusion that there is influence of Discovery Learning learning by geogebra toward the understanding of mathematical concept. For the second second hypothesis is shown with a statistical price of 5.23 (p> 4,001), so H0B is rejected with the conclusion that there is an influence between learners who have cognitive style of FI and FD on the understanding of mathematical concepts. For the third hypothesis, it is shown by the statistical price of 1.05 (p

Oxidation reactions on foods and drugs can be inhibit by using antioxidants that binding to free radicals and reactive molecules. The Ambonese banana (Musa paradisiaca) peel and orange (Citrus reticulata) peel have antioxidant activity potency. The aim of this research is knowing the antioxidant activity of combination Ambonese banana (Musa paradisiaca) peel and orange (Citrus reticulata) peel. IC50 for antioxidant activity potency between Ambonese banana (Musa paradisiaca) peel and orange (Citrus reticulata) peel is expected to increase the antioxidant activity if used as combination that can inhibit oxidation reaction. The inhibit concentration of antioxidant activity is indicated by IC50. The compound that has the highest antioxidant activity will show lowest level of IC50. The antioxidant activity test was performed by DPPH method using UV-Vis spectrophotometer on 516 nm and color change of DPPH from purple to yellow when both of them react with antioxidant compound. The results of IC50 of banana peel extract was 114 mcg / mL; IC50 of orange peel extract was22.2 mcg / mL. The greatest inhibition of the combination of both extracts was 73.53% consisting of 25 μL (0,005%) sample of tangerine orange peel extract and 75 μL (0,015%).The biggest inhibition of the combination of both extracts was 73.53% consisting of 25 μL (0.005%) samples of tangerine orange peel extract and 75 μL (0.015%).

Indonesia has governed smuggling crime in the provisions of Articles 102, 102A and 102B of Law Number 17 of 2006 about the Amendment to Law Number 10 of 1995 about customs. To lower the smuggling rate, sanction reformulation is required in the attempt of recovering the state’s financial loss and/or being partial to the state’s financial interest. Criminal sanction of smuggling is led to the attempt of recovering the state’s loss rather than sentencing imprisonment. This research aimed to find out and to analyze the reason why the reform of smuggling crime investigation system needs to be done. This study was a non-doctrinal law research; techniques of collecting data used were interview, document study, and Focus Group Discussion; data analysis was conducted using an interactive model of analysis. The result of research showed that the factors encouraging the reform of smuggling crime investigation system to be done were legal substance related to regulations about prohibited and restricted products and imprisonment criminal sanction that were ineffective, with elaborate legal structure or bureaucracy and executorial function imposed to the investigators constituting Civil Servant Officials in Directorate General of Customs, and legal culture, in which the main actor had never been found, people’s livelihood source coming from smuggling, and low support among institutions to smuggling crime overcoming.

Objective: The purpose of this study was to analyze the effect of oral administration of radioiodine (I-131) on the immune responses (interleukin 6 and 10) as biodosimetry markers and to support clinical trials of I-131 solution., Methods: The design of this study was an in vivo experimental study using twenty-seven male rats (Rattus norvegicus strain Sprague-Dawley) given 100 μL of I-131 solution at a dose of 260 μCi. Blood plasma was taken at 0.25, 0.5, 1, 3, 24, 48, 120, and 168 hours post oral I-131 administration, respectively. Rats without radioiodine administration as a control group. The levels of IL-6 and IL-10 were measured using the enzyme-linked immunosorbent assay (ELISA) method. Statistical analysis was carried out with one-way ANOVA using SPSS version 25 software., Result: IL-6 level began to significantly increase at 0.25 hours post administration of I-131 (14.4 pg/mL ± 2.52 pg/mL, p=0.02). During 7 days of observation, IL-6 levels had 2 peaks of highly significant increase at 0.5 hours (43.57 ± 5.28, p<0.001) and 120 hours (24.08 ± 2.69, p<0.001 compared to control (5.44 ± 0.95 pg/mL). IL-10 level began to significantly increase at 0.25 hours (30.32 ± 3.22 pg/mL, p=0.03) compared to controls (20.61 ± 1.59 pg/mL)., Conclusion: The highest increase in IL-6 and IL-10 levels occurred respectively in the first 0.5 hours 8 times and in the first 0.25 hours 1.47 times compared to controls. Internal irradiation with radioiodine resulted in a significant increase in immune cells in exposed blood plasma characterized by the production of the cytokines IL-6 and IL-10. This appears to be a response of immune cells to reduce or stop inflammatory reactions through the release of anti-inflammatory cytokines in an effort to prevent excessive inflammatory responses that can damage cells and tissues.

In the event of a radiological incident, a fast and accurate biological dosimetry (biodosimetry) method for evaluating people who have been potentially exposed to ionising radiation is crucial. Among the many biodosimetry methods available, the immunodetection of phosphorylated H2AX (γ-H2AX) stands as a promising method to be used in the triage of patients exposed to radiation. Currently, the most common way to measure γ-H2AX levels is through fluorescence microscopy. In this pilot study, we assessed the feasibility of using an enzyme-linked immunosorbent assay (ELISA) for quantifying γ-H2AX for biodosimetry purposes. Moreover, the usefulness of measuring phosphorylated ATM (pATM) levels through ELISA for biodosimetry was also evaluated. Blood samples were obtained from three male donors (38 y) and were irradiated with 60Co (0, 1, 2 and 6 Gy). Peripheral blood mononuclear cells (PBMCs) were isolated and lysed before measuring γ-H2AX, total H2AX protein and pATM using ELISA kits. The dicentric chromosome assay (DCA) using whole blood was also performed for comparison. Data from all donors at each dose were pooled before statistical analysis. The ratio of γ-H2AX/total H2AX and pATM levels increased in a radiation-dose-dependent manner. The average γ-H2AX/total H2AX ratios were 0.816 ± 0.219, 0.830 ± 0.685, 1.276 ± 1.151 and 1.606 ± 1.098, whereas the average levels of pATM were 59.359 ± 3.740, 63.366 ± 0.840, 66.273 ± 2.603 and 69.936 ± 4.439, in PBMCs exposed to 0, 1, 2 and 6 Gy, respectively. The linear-quadratic dose-response calibration curve for DCA was Y = 0.0017 (±0.0010) + 0.0251 (±0.0142) × D + 0.0342 (±0.0039) × D2  $\boldsymbol{Y}=\mathbf{0.0017}\left(\pm \mathbf{0.0010}\right)+\mathbf{0.0208}\left(\pm \mathbf{0.0218}\right)\times \boldsymbol{D}+\mathbf{0.0350}\left(\pm \mathbf{0.0050}\right)\times{\boldsymbol{D}}^{\mathbf{2}}$. Overall, despite a large variability in the ratio of γ-H2AX/total H2AX among donors, the present study revealed the suitability of using the ratio of γ-H2AX/total H2AX and pATM for biodosimetry. Still, more research with a larger group of subjects is necessary to construct a reliable calibration curve for the ratio of γ-H2AX/total H2AX and pATM levels for biodosimetry., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

On Earth, there are significant variations in terms of exposure to naturally occurring radiation among different areas. Radon, a naturally-occurring radioactive gas that is the primary cause of lung cancer in nonsmokers and the second most prevalent cause among smokers, poses a considerable risk. Indoor radon, in particular, constitutes the most substantial source of natural radiation to which individuals are exposed. This study assessed the immune status of a population chronically exposed to high indoor radon concentration in Indonesia. Fifty-seven subjects from the Tande-Tande sub-village (high indoor radon concentration area) were compared to fifty-three participants living in the Topoyo village (low concentration area). We contrasted the immunological conditions of these two populations by measuring levels of tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-4 (IL-4), and IL-10 in serum. Moreover, we also measured levels of the nuclear factor kappa B (NF-κB), superoxide dismutase (SOD), glutathione peroxidase (GPX), and protein kinase B in its phosphorylated (pAkt) and non-phosphorylated form (Akt) in peripheral blood mononuclear cells (PBMCs) of a subset of participants (31 from each population). TNF-α, IFN-γ, and IL-4 levels in Tande-Tande sub-village inhabitants were significantly lower than those in the control group living in the Topoyo village (p = 0.001, p = 0.017, and p = 0.002). The concentration of IL-10 also tended to be lower in people living in the high indoor radon concentration area, but it did not differ significantly between Tande-Tande sub-village inhabitants and Topoyo inhabitants (p = 0.106). Protein levels of NF-κB, pAkt, and Akt in Tande-Tande sub-village inhabitants also did not differ significantly between Tande-Tande sub-village inhabitants and Topoyo inhabitants (p = 0.234, p = 0.210, and p = 0.657). Similarly, activities of SOD and GPX did not differ significantly between the two populations (p = 0.569 and p = 0.949). Overall, despite their chronic exposure to high indoor radon concentrations, our study revealed no increase in the levels of TNF-α, IFN-γ, IL-10, IL-4, SOD, and GPX in the inhabitants of Tande-Tande sub-village compared with people living in the Topoyo village. Furthermore, our study demonstrated no activation in the Akt pathway, as indicated by the pAkt/Akt ratio observed in PBMC lysates of individuals residing in the Tande-Tande sub-village., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The frequencies of unstable and stable chromosome aberrations and micronuclei were examined in peripheral blood samples from 10 individuals living in elevated radon concentration areas (Takandeang Village, Mamuju, Indonesia). Blood samples from 10 people living in Topoyo Village were used as a control group. For unstable chromosome aberration analysis, a dicentric chromosome assay was conducted using conventional Giemsa staining. Chromosomal painting of chromosomes 1 and 4 using the fluorescence in situ hybridisation technique was also applied to four subjects to assess the stable chromosome aberration. Our study showed no significant increases across all groups in dicentric and other unstable chromosome aberrations, such as rings and acentric fragments. Translocations were found in one person from Takandeang Village and two Topoyo Village inhabitants. The translocations found in the subjects from Takandeang Village were due more to aging factors than to radon exposure. The number of micronuclei per 1000 binucleus cells in Takandeang Village inhabitants was not significantly different than that in the control group (p = 0.943). A more comprehensive analysis should be conducted in a subsequent study by increasing the number of study donors and the number of metaphases to be analysed in both dicentric chromosome assay and fluorescence in situ hybridisation assays. Such research could provide valid information on the cytogenetic effects of elevated indoor radon exposure., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Purpose: To deepen our knowledge on the effects of high levels of indoor radon exposure, we assessed the frequencies of unstable and stable chromosome aberrations and micronucleus (MN), as well as the concentration of an endogenous antioxidant (catalase, CAT), in blood samples of individuals chronically exposed to high indoor radon concentrations in Indonesia (Tande-Tande sub-village, Mamuju, West Sulawesi). Moreover, we also investigated the occurrence of a radio-adaptive response (RAR) in Tande-Tande sub-village inhabitants using the G 2 MN assay., Materials and Methods: The frequencies of dicentric (DC), acentric (AF), ring (R), and translocation (Tr) chromosomes in Tande-Tande inhabitants were compared to those in people living in a reference area with low levels of indoor radon levels (Topoyo village, Indonesia). The number of MN per 1000 binucleated cells (BNC) and CAT concentration per total protein was quantified and compared between groups. Lastly, we irradiated (2 Gy) phytohemagglutinin-stimulated samples in vitro and measured the frequency of MN to verify the occurrence of a RAR in Tande-Tande sub-village inhabitants., Results and Conclusion: The frequencies of DC, AF, and Tr did not differ between Tande-Tande inhabitants and control subjects ( p  = 0.350, 0.521, 0.597). The frequency of MN in Tande-Tande inhabitants was significantly lower than that in the control group ( p  = 0.006). Similarly, CAT concentration in Tande-Tande inhabitants was also significantly lower than that in the control population ( p  < 0.001). Significant negative correlations were identified for MN number and CAT concentration versus indoor radon concentration, annual effective dose, or cumulative dose both within groups and when all data were analyzed together. Our findings indicate that, despite the high indoor radon levels, Tande-Tande inhabitants are not under oxidative stress, since this group had lower CAT concentration and MN frequency than those in the control group. The negative correlation between MN frequency and indoor radon concentration, annual effective dose, and cumulative dose suggests the occurrence of an RAR phenomenon in Tande-Tande sub-village inhabitants. This interpretation is also supported by the results of the G 2 MN assay, which revealed lower MN frequencies after in vitro irradiation of samples from Tande-Tande sub-village inhabitants than those in samples from the control group ( p  = 0.0069, for cumulative MN frequency; p =  0.0146, for radiation-induced MN only).

Introduction: it is needed the innovative interventions to promote smoking cessation behavior. This research analyzed the influence of comic as the communication media to the knowledge and attitude of the respondent in the various determinant of smoking behavior., Methods: this research measured the knowledge and attitude of the respondent after they have been given comic as the educational media. It also explored the information about smoking status and social context of the smokers, such as smoker parents, friends, and teachers. The population was the students. The sample size was 1000 students of junior high school. The research aimed to find out the difference of knowledge and attitude based on the smoking status, social context, and training experience., Results: the mean score of knowledge between the respondents who had trained was higher than respondents who had no trained was significantly different (p<0.05). There was also significantly different of the mean score of knowledge and attitude (p<0.05) between the respondents whose family were smoker and non-smoker. The mean score of knowledge and attitude between the smoker and non-smoker respondents was also significantly different (p<0.05)., Conclusion: the comic is more effective as an educational media for non-smoker adolescents, adolescents who have not smoker family, and health educated adolescent., Competing Interests: The authors declare no competing interests., (Copyright: Abduh Ridha et al.)

Cyclic peptides have been widely reported to have therapeutic abilities in the treatment of cancer. This has been proven through in vitro and in vivo studies against breast, lung, liver, colon, and prostate cancers, among others. The multitude of data available in the literature supports the potential of cyclic peptides as anticancer agents. This review summarizes the findings from previously reported studies and discusses the different cyclic peptide compounds, the sources, and their modes of action as anticancer agents. The prospects and future of cyclic peptides will also be described to give an overview on the direction of cyclic peptide development for clinical applications.

It has been considered difficult to detect the biological effects of low-dose radiation exposure below approximately 100 mSv in humans. Serum proteomic analysis and oxidative modification profiling were conducted with blood samples collected from residents of a newly discovered high-level natural background radiation area (annual effective dose approximately 50 mSv y -1 ) and normal-level area (1.22 mSv y -1 ) in Mamuju, Indonesia, where many people have been living for generations. Dose-dependent oxidative modifications in amino acid sequences of human serum albumin, especially the 162 nd and 356 th tyrosine residues and 111 th and 470 th methionine residues, were found. None of these findings have been reported in humans exposed to chronic low-dose radiation. It can be used as a biomarker not only for the assessment of the presence or absence of radiation exposure but also for dose prediction in living organisms for chronic radiation. These results suggest that traces of radiation exposure are recorded in serum albumin and that there is a possibility of a new methodology that can evaluate biological responses below 100 mSv., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The objective of this study was to assess the effect of radon exposure on the modulation of endogenous antioxidants in a population chronically exposed to high levels of radon indoors. To do so, we measured the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPX) in peripheral blood mononuclear cells (PBMCs) of people living in an area with high indoor radon concentration (Tande-Tande sub-village, Indonesia). The activities of SOD and GPX in Tande-Tande inhabitants were compared with those in subjects living in the Topoyo village (Indonesia), an area with low indoor radon levels. The activities of SOD and GPX in Tande-Tande sub-village inhabitants did not differ from those in people living in the Topoyo village (0.37 ± 0.021  versus 0.28 ± 0.018 U/mg protein and 8.46 ± 1.48 versus 8.34 ± 1.65 U/mg protein, p  > .05). For both populations, there was a significant positive correlation between SOD and GPX activities ( p  < .001). No significant effects of gender, age, smoking habit, and body mass index on SOD and GPX activities were found for both groups. Although no significant modulation of SOD and GPX activities in PBMCs was detected, further studies should expand the sample size and also assess antioxidant levels in the serum. This study provides a first picture of endogenous antioxidant systems in Tande-Tande sub-village inhabitants, but a more comprehensive analysis, including the measurement of catalase (CAT) activity, might provide additional insight into the effects of chronic exposure to high indoor radon concentrations.

Purpose: Our previous study indicated that sodium orthovanadate (vanadate), a strong inhibitor of p53, effectively suppressed the lethality from the hematopoietic (HP) and gastrointestinal (GI) syndromes after 12 Gy total-body irradiation (TBI) in mice. This conclusion, however, was inconsistent with the fact that p53 plays a radioprotective role in the intestinal epithelium. The death after TBI of around 12 Gy was attributed to a combined effect of HP and GI syndromes. To verify the effect from prophylactic administration of p53 inhibitor on protection of HP and GI syndromes, in this study, the radioprotective effects from vanadate were investigated in TBI and lower half-body irradiation (partial-body irradiation: PBI) mouse models., Methods: Female ICR mice were given a single injection of vanadate or vehicle, followed by a lethal dose of TBI or PBI. Radioprotective effects of vanadate against the irradiations were evaluated by analyzing survival rate, body weight, hematopoietic parameters, and histological changes in the bone marrow and intestinal epithelium., Results: TBI-induced HP syndrome was effectively suppressed by vanadate treatment. After TBI, the vanadate-treated mice retained better bone marrow cellularity and showed markedly higher survival rate compared to the vehicle-treated animals. In contrast, vanadate did not relieve loss of intestinal crypts and failed to rescue mice from GI death after PBI., Conclusion: Vanadate is a p53 inhibitor that has been shown to be beneficial as a radiation protective agent against HP but was not effective in protecting against acute GI radiation injury.

The alkaline comet assay, or single cell gel electrophoresis, is one of the most popular methods for assessing DNA damage in human population. One of the open issues concerning this assay is the identification of those factors that can explain the large inter-individual and inter-laboratory variation. International collaborative initiatives such as the hCOMET project - a COST Action launched in 2016 - represent a valuable tool to meet this challenge. The aims of hCOMET were to establish reference values for the level of DNA damage in humans, to investigate the effect of host factors, lifestyle and exposure to genotoxic agents, and to compare different sources of assay variability. A database of 19,320 subjects was generated, pooling data from 105 studies run by 44 laboratories in 26 countries between 1999 and 2019. A mixed random effect log-linear model, in parallel with a classic meta-analysis, was applied to take into account the extensive heterogeneity of data, due to descriptor, specimen and protocol variability. As a result of this analysis interquartile intervals of DNA strand breaks (which includes alkali-labile sites) were reported for tail intensity, tail length, and tail moment (comet assay descriptors). A small variation by age was reported in some datasets, suggesting higher DNA damage in oldest age-classes, while no effect could be shown for sex or smoking habit, although the lack of data on heavy smokers has still to be considered. Finally, highly significant differences in DNA damage were found for most exposures investigated in specific studies. In conclusion, these data, which confirm that DNA damage measured by the comet assay is an excellent biomarker of exposure in several conditions, may contribute to improving the quality of study design and to the standardization of results of the comet assay in human populations., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Chromosome aberration is a biomarker that has been used as a standard tool in biological dosimetry (biodosimetry) of individuals after exposure to ionizing radiation. It is based mainly on the induction of dicentric chromosomes - one of the radiation-induced biological effects, in order to correlate them with radiation dose. In this study, a dose calibration curve for X-rays was generated by using the dicentric assay and by fitting the data to both Chromosomal Aberration Calculation Software and Dose Estimate programs to compare the output of each method. Peripheral blood samples from four nonsmoker healthy donors were irradiated with various doses ranging from 0 to 4 Gy with 250 kV or 122 keV X-rays at a dose rate of 0.17 Gy/min. The irradiated blood was cultured, harvested, and analyzed according to the standard procedure as described by the International Atomic Energy Agency with slight modifications. The dose-response calibration data for dicentrics were fitted with the linear-quadratic model (Y dic = 0.03987D 2 + 0.00651D). The dose-response calibration curve obtained in this research was comparable to other estimations with similar radiation quality and dose rates. The results in this research convinced us in sustaining a biodosimetry using a dose-response calibration curve in our laboratory., Competing Interests: There are no conflicts of interest.

High expression of phospho histone γ-H2AX, a sensitive marker of double stranded DNA damage, is believed to be an indication of defective DNA repair pathway or genomic instability that may cause mutations and ultimately cancer. DNA damage can be caused by ionizing radiation exposure. Beside in medical treatment/diagnosis or industry, ionizing radiation exposure can also be found in naturally in regions of high natural back ground radiation. In this study we collect the blood from 45 volunteers living in Mamuju, a region with highest natural radiation in Indonesia (dose of ∼7 mSv/year). Subjects were grouped as high natural background area (HNBA) (n = 37) and control area (n = 8). The expression γ-H2AX foci were evaluated by one of researcher fluorescence microscope examination. Our results show that the average foci numbers per cell were in the normal range. While not statistical different, the average of γ-H2AX foci in exposed area higher in the exposed compared to the control area, 0.31 versus 0.13 (p > 0.05), respectively. Moreover, there was also no statistical difference of average γ-H2AX foci between man and woman, old and young people in exposed and control area (p > 0.05). In this preliminary study we find that γ-H2AX foci (and thus DNA double strand break) frequency in residents living in the HNBA of Mamuju, West Sulawesi, show a trend towards higher (albeit not significant) average values relative to the control area. More research is needed to further scrutinize these observations., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The extracellular matrix (ECM) is important in creating cellular environments in tissues. Recent studies have demonstrated that ECM components are localized in anterior pituitary cells and affect cell activity. Thus, clarifying the mechanism responsible for ECM maintenance would improve understanding of gland function. Tissue inhibitors of metalloproteinases (TIMPs) are endogenous inhibitors of matrix metalloproteinases and participate in ECM degradation. In this study, we investigated whether cells expressing TIMPs are present in rat anterior pituitary gland. Reverse transcription polymerase chain reaction was used to analyze expression of the TIMP family (TIMP1-4), and cells producing TIMPs in the gland were identified by using in situ hybridization. Expression of TIMP1, TIMP2, and TIMP3 mRNAs was detected, and the TIMP-expressing cells were located in the gland. The TIMP-expressing cells were also investigated by means of double-staining with in situ hybridization and immunohistochemical techniques. Double-staining revealed that TIMP1 mRNA was expressed in folliculostellate cells. TIMP2 mRNA was detected in folliculostellate cells, prolactin cells, and thyroid-stimulating hormone cells. TIMP3 mRNA was identified in endothelial cells, pericytes, novel desmin-immunopositive perivascular cells, and folliculostellate cells. These findings indicate that TIMP1-, TIMP2-, and TIMP3-expressing cells are present in rat anterior pituitary gland and that they are involved in maintaining ECM components.

Laminin, a major basement membrane component, is important in structural support and cell proliferation and differentiation. Its 19 isoforms are assemblies of α, β, and γ chains, and the α chains (α1-5) determine the isoform characteristics. Although our previous studies showed alterations in α chain expressions during anterior pituitary development, their expressions in pituitary tumors yet to be determined. The present study used a rat model of diethylstilbestrol (DES)-induced prolactinoma to examine α chain expressions during prolactinoma tumorigenesis (0-12 weeks of DES treatment) by in situ hybridization and immunohistochemistry. mRNA of α1, α3, and α4 chains was detected in control and after 4 weeks of DES treatment. These expressions were undetectable after 8 weeks of DES treatment and in prolactinoma (12 weeks of DES treatment). Immunohistochemistry showed that the α1 chain was localized in some anterior pituitary cells in control and after 4 weeks of treatment and in endothelial cells after 8 weeks of treatment. The α3 and α4 chains were expressed in endothelial cells, and immunoreactivity and the number of immunopositive cells decreased during DES treatment. These findings suggest that alteration of laminin α chains is related to abnormal cell proliferation and neovascularization during development of DES-induced prolactinoma.

Midkine (MK) belongs to a family of secreted heparin-binding growth factors and is highly expressed in various tissues during development. MK has multiple functions, such as regulation of cell proliferation, migration, survival and differentiation. We recently reported that MK mRNA is strongly expressed in the developing rat pituitary gland. In the adult pituitary, however, expression of MK and its receptor and the characteristics of the cells that produce them, have not been determined. Therefore, in this study, we investigate whether MK and its receptor, protein tyrosine phosphatase receptor-type Z (Ptprz1), are present in the adult rat pituitary. In situ hybridization, real-time reverse transcription-PCR and immunoblotting were performed to assess MK and Ptprz1 expression. We also characterize MK- and Ptprz1-expressing cells by double-staining with in situ hybridization and immunohistochemical techniques for each pituitary hormone or S100 protein [a marker of folliculostellate (FS) cells]. MK-expressing cells were located in the anterior and posterior lobes but not in the intermediate lobe. Double-staining and immunoblotting revealed that MK mRNA and protein were only expressed in FS cells in the anterior pituitary. Regarding Ptprz1 expression, Ptprz1 mRNA was detected in adrenocorticotropic hormone (ACTH) cells and growth hormone (GH) cells but not in prolactin cells, thyroid-stimulating hormone cells, luteinizing hormone cells, or FS cells. These findings suggest that MK produced in FS cells acts locally on ACTH cells and GH cells via Ptprz1 in the adult rat anterior pituitary.

Pituitary gland development is controlled by numerous signaling molecules, which are produced in the oral ectoderm and diencephalon. A newly described family of heparin-binding growth factors, namely midkine (MK)/pleiotrophin (PTN), is involved in regulating the growth and differentiation of many tissues and organs. Using in situ hybridization with digoxigenin-labeled cRNA probes, we detected cells expressing MK and PTN in the developing rat pituitary gland. At embryonic day 12.5 (E12.5), MK expression was localized in Rathke's pouch (derived from the oral ectoderm) and in the neurohypophyseal bud (derived from the diencephalon). From E12.5 to E19.5, MK mRNA was expressed in the developing neurohypophysis, and expression gradually decreased in the developing adenohypophysis. To characterize MK-expressing cells, we performed double-staining of MK mRNA and anterior pituitary hormones. At E19.5, no MK-expressing cells were stained with any hormone. In contrast, PTN was expressed only in the neurohypophysis primordium during all embryonic stages. In situ hybridization clearly showed that MK was expressed in primitive (immature/undifferentiated) adenohypophyseal cells and neurohypophyseal cells, whereas PTN was expressed only in neurohypophyseal cells. Thus, MK and PTN might play roles as signaling molecules during pituitary development.

The anterior pituitary gland is organized tissue comprising hormone-producing cells and folliculostellate (FS) cells. FS cells interconnect to form a meshwork, and their cytoplasmic processes are anchored by a basement membrane containing laminin. Recently, we developed a three-dimensional (3D) cell culture that reproduces this FS cell architecture. In this study of the novel function of FS cells, we used transgenic rats that express green fluorescent protein in FS cells for the 3D culture. Anterior pituitary cells were cultured with different proportions of FS cells (0%, 5%, 10%, and 20%). Anterior pituitary cells containing 5-20% FS cells formed round/oval cell aggregates, whereas amorphous cell aggregates were formed in the absence of FS cells. Interestingly, immunohistochemistry showed laminin-immunopositive cells instead of extracellular laminin deposition in FS cell-deficient cell aggregates. Double-immunostaining revealed that these laminin-immunopositive cells were gonadotrophs. Laminin mRNA expression did not differ in relation to the presence or absence of FS cells. When anterior pituitary cells with no FS cells were cultured with FS cell-conditioned medium, the proportion of laminin-immunopositive cells was lower than in control. These results suggest that a humoral factor from FS cells is required for laminin release from gonadotrophs.

Cell-matrix interaction is required for tissue development. Laminin, a major constituent of the basement membrane, is important for structural support and as a ligand in tissue development. Laminin has 19 isoforms, which are determined by combinational assembly of five α, three β, and three γ chains (eg, laminin 121 is α1, β2, and γ1). However, no report has identified the laminin isoforms expressed during pituitary development. We used in situ hybridization to investigate all laminin chains expressed during rat anterior pituitary development. The α5 chain was expressed during early pituitary development (embryonic day 12.5-15.5). Expression of α1 and α4 chains was noted in vasculature cells at embryonic day 19.5, but later diminished. The α1 chain was re-expressed in parenchymal cells of anterior lobe from postnatal day 10 (P10), while the α4 chain was present in vasculature cells from P30. The α2 and α3 chains were transiently expressed in vasculature cells and anterior lobe, respectively, only at P30. Widespread distribution of β and γ chains was also observed during development. These findings suggest that numerous laminin isoforms are involved in anterior pituitary gland development and that alteration of the expression pattern is required for proper development of the gland.

In the anterior pituitary gland, folliculo-stellate cells and five types of hormone-producing cells are surrounded by an extracellular matrix (ECM) essential for these cells to perform their respective roles. Syndecans-type I transmembrane cell-surface heparan sulfate proteoglycans act as major ECM coreceptors via their respective heparan sulfate chains and efficiently transduce intracellular signals through the convergent action of their transmembrane and cytoplasmic domains. The syndecans comprise four family members in vertebrates: syndecan-1, -2, -3 and -4. However, whether syndecans are produced in the pituitary gland or whether they have a role as a coreceptor is not known. We therefore used (1) reverse transcription plus the polymerase chain reaction to analyze the expression of syndecan genes and (2) immunohistochemical techniques to identify the cells that produce the syndecans in the anterior pituitary gland of adult rat. Syndecan-2 mRNA expression was clearly detected in the corticotropes of the anterior pituitary gland. Moreover, the expression of syndecan-2 in the developing pituitary gland had a distinct temporospatial pattern. To identify the cells expressing syndecan-2 in the developing pituitary gland, we used double-immunohistochemistry for syndecan-2 and the cell markers E-cadherin (immature cells) and Ki-67 (proliferating cells). Some E-cadherin- and Ki-67-immunopositive cells expressed syndecan-2. Therefore, syndecan-2 expression occurs in developmentally regulated patterns and syndecan-2 probably has different roles in adult and developing anterior pituitary glands.

The anterior pituitary gland comprises 5 types of hormone-producing cells and non-endocrine cells, such as folliculostellate (FS) cells. The cells form a lobular structure surrounded by extracellular matrix (ECM) but are not randomly distributed in each lobule; hormone-producing cells have affinities for specific cell types (topographic affinity), and FS cells form a homotypic meshwork. To determine whether this cell and ECM organization can be reproduced in vitro, we developed a 3-dimensional (3D) model that utilizes hanging drop cell culture. We found that the topographic affinities of hormone-producing cells were indeed maintained (ie, GH to ACTH cells, GH to TSH cells, PRL to LH/FSH cells). Fine structures in hormone-producing cells retained their normal appearance. In addition, FS cells displayed well-developed cytoplasmic protrusions, which interconnected with adjacent FS cells to form a 3D meshwork. In addition, reassembly of gap junctions and pseudofollicles among FS cells was observed in cell aggregates. Major ECM components-collagens and laminin-were deposited and distributed around the cells. In sum, the dissociated anterior pituitary cells largely maintained their in vivo anterior pituitary architectures. This culture system appears to be a powerful experimental tool for detailed analysis of anterior pituitary cell organization.

Proteoglycans are components of the extracellular matrix and comprise a specific core protein substituted with covalently linked glycosaminoglycan chains. Small leucine-rich proteoglycans (SLRPs) are a major family of proteoglycans and have key roles as potent effectors in cellular signaling pathways. Research during the last two decades has shown that SLRPs regulate biological functions in many tissues such as skin, tendon, kidney, liver, and heart. However, little is known of the expression of SLRPs, or the characteristics of the cells that produce them, in the anterior pituitary gland. Therefore, we have determined whether SLRPs are present in rat anterior pituitary gland. We have used real-time reverse transcription with the polymerase chain reaction to analyze the expression of SLRP genes and have identified the cells that produce SLRPs by using in situ hybridization with a digoxigenin-labeled cRNA probe. We have clearly detected the mRNA expression of SLRP genes, and cells expressing decorin, biglycan, fibromodulin, lumican, proline/arginine-rich end leucine-rich repeat protein (PRELP), and osteoglycin are located in the anterior pituitary gland. We have also investigated the possible double-staining of SLRP mRNA and pituitary hormones, S100 protein (a marker of folliculostellate cells), desmin (a marker of capillary pericytes), and isolectin B4 (a marker of endothelial cells). Decorin, biglycan, fibromodulin, lumican, PRELP, and osteoglycin mRNA have been identified in S100-protein-positive and desmin-positive cells. Thus, we conclude that folliculostellate cells and pericytes produce SLRPs in rat anterior pituitary gland.

Laminin is a key component of the basement membrane and is involved in the structural scaffold and in cell proliferation and differentiation. Research has identified 19 laminin isoforms, which are assemblies of α, β, and γ chains (eg, the α1, β1, and γ1 chains form the laminin 111 isoform). Although laminin is known to be present in the anterior pituitary, the specific laminin isoforms have not been identified. This study used molecular biological and histochemical techniques-namely, RT-PCR, immunohistochemistry, and in situ hybridization-to identify the laminin isoforms and laminin-producing cells in rat anterior pituitary. RT-PCR showed that laminin α1, α3, and α4 genes were expressed in anterior pituitary. Immunohistochemistry revealed laminin α1 in gonadotrophs and laminin α4 in almost all vascular endothelial cells. Laminin α3 was seen in a subset of vascular endothelial cells. We then performed in situ hybridization to localize β and γ chains in these cells and found that laminin β1, β2, and γ1 were expressed in gonadotrophs and that laminin β1 and γ1 were expressed in endothelial cells. In conclusion, we identified gonadotroph-type (laminin 111 and 121) and vascular-type (laminin 411 and 311) laminin isoforms in rat anterior pituitary.