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Ageing involves destruction on the molecular, cellular, and organ level, causing disease and death. Previous research has discovered that both diet and genetics can affect ageing. Forkhead helix box (FOXO) transcription factors are found to be the major transcription factors correlated with longevity. In addition, one of the best-known signals that are also capable to affect ageing is a dietary restriction (DR) which is evolutionary conserved. The objective of this paper is to expand our knowledge regarding the FOXO3 gene expression as anti-ageing biomarker, and how DR could impact its expression. This review was written through a rigorous searching process from various databases including Google Scholar, Science Direct, Scopus, and PubMed, by utilizing keywords such as the ‘anti-ageing’, ‘dietary restriction’ along with ‘forkhead box O3 gene’. FOXO3 exerts its essential role through the protein kinase B (Akt/PKB) signaling pathway, as well as post-translational modifications, further activating downstream target genes. This would result in cell apoptosis, cell cycle arrest, DNA repair, and other important physiological processes. Relating to diet, the FOXO3 gene is expressed when organisms face low nutrient availability. It can also be downregulated by reducing the amount of circulating insulin-like growth factor 1 (IGF-1) level which can be achieved through fasting. Meanwhile, DR can enhance the FOXO3 expression, anti-ageing effects and further establish longevity. However, the research regarding the effect of DR in humans is still limited. Future studies need to investigate the optimal type of DR along with uncovering the molecular mechanism behind the FOXO3 expression and ageing.

Background: Children under five years experience rapid growth and development, so that adequate nutritional intake is very important. Zinc is essential for child development and growth. Children’s zinc requirements are fulfilled from daily food intake that might be affected by Covid-19 pandemic. The aim of this study is to determine the correlation between zinc intake with hair zinc level and appetite in children aged 2-3 years in Jakarta. Methods: This cross-sectional study was carried out from September to October 2020 in Kampung Melayu, Jakarta. Seventy children aged 2-3 years were taken using total population sampling method. Interviews were conducted to obtain characteristic data and zinc intake using semi quantitative-food frequency questionnaire (SQ-FFQ). Appetite were assessed using VAS appetite questionnaire. Hair samples were collected to check level of hair zinc. Spearman correlation was performed using SPSS. Results: Median of zinc intake was 6 (1,2-22,5) mg/day, with 20% of the subjects had insufficient zinc intake. The median hair zinc value was 132 (30-451) µg/g, with 17,1% subjects zinc insufficient. The median of VAS appetite score was 54,5 mm. There were no significant correlation between zinc intake and hair zinc level (r = -0.077, p = 0.528). A weak positive correlation was found between appetite and hair zinc levels (r = 0,247, p = 0,039). Conclusion: Zinc intake in children aged 2-3 years had no significant correlation with hair zinc level, and appetite had a weak positive correlation with hair zinc level.

Background: Obesity modulates oxidative stress and can be detected by examining malondialdehyde (MDA) serum levels. Flavonoids are natural bioactive ingredients that can be found in various types of vegetables and fruits that function as antioxidants to suppress that oxidative stress. Objective: This study aimed to determine the correlation between flavonoid intake and MDA serum levels in obese women of reproductive age. Methods: This cross-sectional study was conducted in Kendari, Indonesia from April to October 2021. The purposive sampling method was used to obtain 88 subjects who met the research criteria. Data were collected through interviews covering flavonoids intake using validated SQ-FFQ. Anthropometric measurements were performed to assess nutritional status, and laboratory tests were applied to determine MDA serum levels. Results: The average intake of flavonoids in the subjects was 142,26 ± 56,53 mg per day. Meanwhile, the average MDA serum level in the subjects was 2.16 mol/L, ranging from 1.09 nmol/ml to 6.71 nmol/ml. There was no significant correlation between total flavonoid intake and MDA serum levels in obese women of reproductive age (r=0,188, p=0,079). However, there was a weak correlation between the intake of flavonoid subclasses, namely flavan-3-ols/flavanols and MDA serum levels (r=0.325, p=0.002). Conclusion: We conclude that there was no correlation between total flavonoid intake and MDA serum levels. However, there was a correlation between flavan-3-ols/flavanols and MDA serum levels in the subjects.

BACKGROUND: Nutritional status is a modifiable risk factor that could support healthy ageing outcome among elderly population. OBJECTIVE: To investigate association of nutritional status indicated by Mini Nutritional Assessment short form (MNA-SF) score with domains of functional ability, cognitive state, depression, and social engagement status. METHODS: A cross-sectional study was conducted among 133 elderly aged > 60 years in five community health center across Jakarta province. MNA-SF was used to indicate nutritional status score. Functional ability measured based on activity daily living (ADL) score. Cognitive function measured based on Mini Mental State Examination (MMSE) score. Geriatric Depression Scale short form (GDS-15) was used to measure depression and social engagement status measured based on social engagement index questionnaire. Association of study variables analyzed using linear regression test by considering possible confounders including age, sex, education, income, smoking status, and disease history. RESULTS: MNA-SF score reported to have positive correlation with domains of cognitive function (r = 0.25 p = 0.00) and social engagement status (r = 0.30 p = 0.00), but inverse correlation was found with depression symptoms (r = 0.24, p = 0.00). The association was remained significant in the multivariate analyses (cognitive function adjusted β= 0.18, p = 0.01; depression adjusted β= –0.38, p = 0.00; social engagement adjusted β= 0.23, p = 0.00). MNA-SF was not associated with functional ability domain in this study. CONCLUSIONS: Higher level of nutrition status was associated with better cognition, lower depression symptoms, and better social engagement of the healthy ageing domains, but it was not associated with functional ability domain among elderly.

Introduction Despite many health benefits from dietary fiber, inadequate intake is prevalent among elderly population. This study aims to obtain the pattern of fiber intake in different socio-demographic backgrounds among elderly in Jakarta area, Indonesia and its’ associated factors. Methods: A cross-sectional study was conducted among elderly aged > 60 years in 5 community health center across Jakarta province. A total of 126 elderly were interviewed using two non-consecutive 24-h dietary recall methods to obtain dietary intake data. Socio-demographic backgrounds on age, sex, education, income, marital status, and energy intake were assessed using structured questionnaire. Mann-Whitney or independent t-test was performed to measure the different of fiber intake in each socio-demographic variable. Linear regression test was performed to analyze the variables that associated with fiber intake. Results: Majority of 98.4% of elderly have total fiber intake

Background: A keloid is a benign skin tumour characterised by excessive proliferation of fibroblasts, a process that requires a sufficient amount of energy. The energy needs are associated with adequate oxygen (O2) flow and well-functioning mitochondria. It is known that cytoglobin (CYGB) has a function in O2 distribution. The aim of the present study was to explore whether the inhibition of CYGB expression caused impaired mitochondrial function of keloid fibroblasts. Methods: An in vitro study was conducted on a keloid fibroblast derived from our previous study. The study was carried out in the laboratory of the Biochemistry & Molecular Biology Department, Faculty of Medicine, Universitas Indonesia (FMUI), from July to December 2018. CYGB expression was inhibited by small interfering ribonucleic acid (siRNA) and CYGB. Analysis of mitochondrial function was observed through peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), a mitochondrial biogenesis marker and the activity of the succinate dehydrogenase (SDH) enzyme in mitochondria. Results: The CYGB gene and protein were downregulated after treatment with CYGB siRNA. Inhibition of CYGB expression with siRNA also tended to decrease the levels of PGC-1α messenger ribonucleic acid (mRNA) and protein, as well as SDH enzyme activity. Conclusion: Inhibition of CYGB expression with siRNA tended to decrease mitochondrial biogenesis and function. This may be useful for understanding the excessive proliferation of fibroblasts in keloids and for development of treatment for keloids.

Ageing is a process of declining bodily function and a major risk factor of chronic diseases. The declining bodily function in ageing can cause loss of proteostasis (protein homeostasis), which is a balance between protein synthesis, folding, modification and degradation. For the elderly, adequate protein intake is necessary to prevent sarcopenia, frailty, fracture and osteoporosis as well as reduced resistance to infection. However, increasing the protein intake can enhance the risk of oxidized protein formation, loss of proteostasis and degenerative disorder occurrence. On the other hand, several studies show that protein restriction would increase longevity. The aim of this review was to explain the importance of determining the right amount and composition of protein intake for the elderly. Oxidative stress and molecular mechanism of proteostasis loss in ageing cells as well as its suppression pathway by protein restriction are discussed in this review. Keywords: ageing, dietary proteins, mTOR, oxidative stress, proteostasis loss

Batu empedu merupakan penyakit yang banyak ditemukan di Indonesia. Analisis komposisi batu empedu penting untuk mengetahui penyebab, dasar metabolisme pembentukannya, faktor risiko, serta untuk edukasi diet terhadap pasien. Komposisi batu empedu tersebut dapat dipengaruhi oleh berbagai faktor termasuk usia dan jenis kelamin. Sampai saat ini belum terdapat data analisis komposisi dan distribusi batu empedu di Jakarta. Dengan demikian, penelitian ini bertujuan untuk menganalisis komposisi dan distribusi batu empedu yang dihubungkan dengan usia dan jenis kelamin. Penelitian ini merupakan penelitian cross-sectional menggunakan 230 data sekunder hasil analisis komposisi batu empedu di Laboratorium Biokimia dan Biologi Molekuler FKUI dalam periode 3 tahun terakhir (tahun 2017 – 2019). Analisis batu dilakukan dengan uji Salkowski untuk menilai kolesterol serta uji kalsium, karbonat, Fe, pigmen empedu, dan fosfat. Hasil penelitian menunjukkan bahwa batu empedu sebesar 1,3% merupakan batu murni dan 98,7% merupakan batu campuran. Komposisi terbanyak pada batu campuran yaitu kolesterol (83,91%). Batu empedu paling banyak ditemukan pada perempuan kelompok usia 40—49 tahun (27%). Terdapat hubungan komposisi kolesterol dengan usia (p0,05) dengan jenis kelamin (p>0,05). Kesimpulan dari penelitian ini yaitu kolesterol merupakan penyusun komposisi batu empedu yang terbanyak yang berhubungan dengan usia, namun tidak berhubungan dengan jenis kelamin. Kata kunci: Batu Empedu, Distribusi, Komposisi, Kolesterol Abstract Gallstones are a disease that is commonly found in Indonesian. Analysis of the composition of gallstones is important to determine the etiology, the metabolic basis of its formation, risk factors, and to educate for the patient's diet. The composition of gallstones can be influenced by various factors including age and sex. Until now there is no data analysis of the composition and distribution of gallstones in Jakarta. Thus, this study aims to analyze the composition and distribution of gallstones that are associated with age and sex. This study is a cross-sectional study using 230 secondary data from the analysis of the composition of gallstones in the Laboratory of Biochemistry and Molecular Biology of FMUI in the last 3 years period (2017 - 2019). Stone analysis was carried out with the Salkowski test to assess cholesterol and also calcium, carbonate, Fe, bile pigment, and phosphate assays. The results showed that 1.3% gallstones were pure stones and 98.7% were mixed stones. The most composition in mixed stones is cholesterol (83.91%). Gallstones are most commonly found in women in the age group of 40-49 years (27%). There is a correlation between cholesterol composition with age (p 0.05) with gender (p> 0.05). This study concluded that cholesterol was the most common constituent of gallstone. Its levels increased with age and did not differ significantly between genders. Keywords: Gallstone, Composition, Distribution, Cholesterol

Cancer prevalence in Indonesia is 1.8 per 1000 population in 2018. Early diagnosis is needed to reduce the mortality rate and one of which is by examining vanillylmandelic acid (VMA) level as tumor markers. VMA is a catecholamine metabolite whose level will increase in several neuroendocrine tumors. This study was conducted to determine the proportion of positive VMA in urine of patients with suspected neuroendocrine tumors in Jakarta and its association with age and gender. This study was a cross-sectional design using secondary data of urinary VMA laboratory examination from 295 patients who suspected neuroendocrine tumors period 2010 to 2019 in Laboratory of Department of Biochemistry and Molecular Biology, Faculty of Medicine Universitas Indonesia. Qualitative examination of urinary VMA used spot test. Positive examination result showed levels of VMA in urine >8mg/24 hours, while negative result showed 8mg/24 hours. Inclusion criteria were subject data with a provisional diagnosis of neuroblastoma, pheochromocytoma, and paraganglioma. The proportion of positive VMA in urine of suspected neuroendocrine tumor patients was 14,2%. There was a significant association between VMA in urine with age (p 0,023), while gender was not significant (p 0,885). In conclusion, there was an association between urinary VMA of suspected neuroendocrine tumor patients with age, however no association with gender. Keywords: neuroendocrine tumors; urinary vanillylmandelic acid; age; gender Abstrak Prevalensi kanker di Indonesia pada 2018 adalah 1,8 per 1000 penduduk. Diagnosis dini dibutuhkan untuk mengurangi angka mortalitas, salah satunya melalui pemeriksaan penanda tumor berupa vanillylmandelic acid (VMA). VMA termasuk metabolit katekolamin yang meningkat produksinya pada beberapa tumor neuroendokrin. Penelitian dilakukan untuk mengetahui proporsi VMA positif dalam urin pasien dugaan tumor neuroendokrin di Jakarta serta hubungannya dengan usia dan jenis kelamin. Penelitian ini menggunakan desain cross-sectional yang menggunakan data sekunder hasil pemeriksaan laboratorium VMA urin dari 295 pasien dugaan tumor neuroendokrin periode 2010 hingga 2019 di Laboratorium Departemen Biokimia dan Biologi Molekuler, Fakultas Kedokteran Universitas Indonesia. Data VMA kualitatif yang diperoleh, diperiksa dengan metode spot test. Hasil positif menunjukkan kadarnya > 8 mg/24 jam, sedangkan hasil negatif menunjukkan kadarnya 8 mg/24 jam. Kriteria inklusi berupa diagnosis sementara neuroblastoma, pheochromocytoma, dan paraganglioma. Proporsi VMA positif dalam urin pasien dugaan tumor neuroendokrin adalah 14,2%. Terdapat hubungan bermakna antara kadar VMA dalam urin dengan usia (p 0,023), sedangkan dengan jenis kelamin menunjukkan hasil yang tidak bermakna (p 0,885). Dengan demikian dapat disimpukan bahwa terdapat hubungan antara VMA urin pasien dugaan tumor neuroendokrin dengan usia, namun tidak terdapat hubungan dengan jenis kelamin. Kata kunci: tumor neuroendokrin; vanillylmandelic acid urin; usia; jenis kelamin

Objective: This is an in vitro experimental study designed to analyze the role of alternative splicing of mRNA in the apoptotic process of the cancer cells. Here we induced apoptosis in the glioblastoma multiforme (GBM) T-98G cell line to obtain a better understanding in the regulation of mRNA expression of the soluble Tumor Necrosis factor-related Apoptosis-Inducing Ligand (sTRAIL) gene. Methods: Cells were induced to undergo apoptosis by treatment with rotenone at 10, 20 and 40 µM for 6 h. Dimethylsulphoxide (DMSO) was used to dissolve rotenone and as a negative control. The morphology of the GBM-T98G cells was viewed with an inverted microscope. DNA, RNA and protein extractions were performed to analyse apoptotic DNA fragmentation by a DNA laddering assay, a quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) for TRAIL mRNA expression and ELISA for caspase-9 protein expression. Electrophoresis was also performed on TRAIL complementary DNA (cDNA) produced from TRAIL qRT-PCR mRNA. Results: Nucleosomal DNA degradation was confirmed by DNA laddering, whereas the TRAIL melting curve and the cDNA electrophoresis showed a shift in the balance of the TRAIL mRNA isoform to the pro-apoptotic mRNA isoform, in conjunction with a significant increase in expression of TRAIL mRNA and caspase-9 protein. Conclusion: These findings indicate the regulation of apoptotic events at the level of TRAIL mRNA expression, as indicated by the shift in the balance of mRNA expression of the TRAIL isoform towards the pro-apoptotic isoform.

Latar belakang: Malondialdehida (MDA) merupakan petanda stres oksidatif yang merupakan produk akhir dari reaksi berantai proksidasi lipid. Untuk mencegah stres oksidatif, tubuh mensintesis katalase, suatu enzim antioksidan endogen yang mengkatalisis hidrogen peroksida (H2O2) menjadi air dan oksigen. Sampai saat ini kadar MDA dan katalase pada populasi usia lanjut (usila) masih memberikan hasil yang bervariasi dan kadar tersebut pada kelompok usia yang berbeda dalam populasi usila belum pernah dilaporkan. Dengan demikian, penelitian ini bertujuan untuk menganalisis profil kadar MDA dan aktivitas spesifik katalase pada plasma populasi usila berdasarkan peningkatan usia. Metode: Penelitian ini menggunakan 60 subjek wanita usila sehat yang tinggal di Jakarta. Subjek dibagi dalam 2 kelompok berdasarkan kategori usia, kelompok yang lebih muda (60 – 70 tahun) dan kelompok yang lebih tua (> 70 tahun). Kadar MDA dan aktivitas spesifik katalase dianalisis pada plasma dengan spektrofotometer. Hasil: Kadar MDA pada kelompok yang lebih muda (60 – 70 tahun) sedikit lebih tinggi dibandingkan kelompok yang lebih tua (> 70 tahun) namun tidak bermakna secara statistik. Selain itu, akitivitas spesifik katalase pada kelompok yang lebih muda lebih rendah bermakna dibandingkan dengan kelompok yang lebih tua. Kesimpulan: Tidak ada perbedaan bermakna kadar MDA plasma pada populasi usila. Namun, aktivitas spesifik katalase meningkat bermakna seiring dengan pertambahan usia. (Health Science Journal of Indonesia 2019;10(2):132-6) Kata kunci: Malondialdehida, katalase, wanita usila Abstract Background: Malondialdehyde (MDA) is a marker of oxidative stress as an end product from the chain reaction of lipid peroxidation. In order to prevent oxidative stress, our body synthesizes catalase, an endogenous antioxidant enzyme that catalyzes hydrogen peroxide (H2O2) into water and oxygen. Until now, the level of MDA and catalase in aging population were still varied and those level at different age in elderly population has not been yet reported. Therefore, the purpose of this study was to analyse the profile of MDA level and catalase specific activity in plasma of elderly women based on increasing age. Methods: This research used 60 healthy elderly women as the subjects living in Jakarta. The subjects were divided into 2 groups based on age category, the younger group (60 – 70 years old) and the older group (>70 years old). MDA and specific activity of catalase were analyzed in plasma using spectrophotometer. Results: MDA level in the younger group (60-70 years old) was slightly higher than MDA levels in the older group (>70 years old) but it was not significant. Moreover, specific activity of catalase in the younger group was significantly lower than the older group. Conclusions: There was no difference in MDA level of elderly woman between younger and older group. However, catalase specific activity significantly increased with increasing age. (Health Science Journal of Indonesia 2019;10(2):132-6) Keywords: Malondialdehyde, Catalase, elderly woman

A glioma, especially a grade IV glioblastoma, is a malignant tumour with a poor prognosis despite growing medical advancements. Researchers have been looking for better and more effective treatments targeting the molecular pathways of gliomas due to glioblastomas' ability to develop resistance to chemotherapies. Moreover, glioma stem cells (GSC) contribute to maintaining the glioma population, which benefits from its ability to self-renew and differentiate. Recent research has reported that through the introduction of umbilical cord mesenchymal stem cells (UCMSC) into glioma cells, the growth and development of the glioma cells can be downregulated. It has more currently been found out that UCMSC release extracellular vesicles (EVs) containing miRNA that are responsible for this phenomenon. Therefore, this review analyses literature to discuss all possible miRNAs contained within the UCMSC's EVs and to elaborate on their molecular mechanisms in halting gliomas and GSC growth. This review will also include the challenges and limitations, to account for which more in vivo research is suggested. In conclusion, this review highlights how miRNAs contained within UCMSC's EVs are able to downregulate multiple prominent pathways in the survival of gliomas.

This study aimed to analyse the expression pattern of FOXO3a in leucocytes of elderly women according to their lifespans.It was a cross-sectional study involving 60 healthy elderly female subjects living in Jakarta. Women were classified based on age as younger (60-70 years of age) and older (70 years of age). Blood samples were taken for the preparation of leucocyte cells for RNA isolation. FOXO3a mRNA expression was analysed using quantitative polymerase chain reaction (qPCR).The relative mRNA expression of FOXO3a in leucocytes was significantly higher in the younger group (60-70 years of age) than in the older group (70 years of age).FOXO3a mRNA expression decreased with increasing age in elderly female subjects. Further research is required to evaluate FOXO3a expression at the protein level.

Oxidative stress is a state of imbalance of free radicals in the cells and is one of the causes of various diseases in humans. One method that is thought to reduce oxidative stress is calorie restriction or fasting. However, its effects remain unclear. This study was conducted to determine the effect of intermittent fasting and prolonged fasting on the levels of malondialdehyde (MDA) as an oxidative stress marker in the liver and plasma of New Zealand White rabbits. Fifteen of New Zealand White rabbits were divided into three groups (intermittent fasting (IF), prolonged fasting (PF), and control). MDA was measured in plasma and liver homogenate using spectrophotometry. The results were analyzed using One-way ANOVA test. The liver MDA level was decreased in the IF group, but not significant. However, there was a significant increase in plasma MDA levels both in the IF and PF groups. Moreover, liver MDA level was increased in PF group, although it was not significant. In conclusion, intermittent and prolonged fasting could increase plasma MDA levels significantly.

Covid 19 pandemic has caused changes in the socioeconomic conditions, affects parents' ability to sustain their children nutritious food. If nutrients are insufficient for a long term is causing growth to be stunted.

Background: Keloid is an abnormal wound healing process that extends beyond the site of injury. Keloid and tumor’s shared similarity of recurrence suggesting a shared underlying mechanism that involves stemness. Octamer-binding transcription factor-4 (Oct-4) and aldehyde dehydrogenase-1 (ALDH1) are stem cell stemness markers. This study aimed to analyze Oct-4 and ALDH1 expressions in keloid tissues.Methods: Samples were obtained from keloid tissue excisions from three keloid patients and post-circumcision preputial skin from three healthy donors (normal control) in accordance with the local ethical committee regulation. Total RNA was isolated using TriPure Isolation kit (Ameritech), and expressions of Oct4 and ALDH1 mRNA in keloid and preputial skin were determined by quantitative reverse transcription–polymerase chain reaction (qRT-PCR) using Livak method.Results: The qRT-PCR analysis revealed the expressions of Oct4 and ALDH1 in keloid and preputial skin tissues. Keloid tissues exhibited lower expression levels of Oct-4 and ALDH1 than the preputial skin. The difference was statistically insignificant.Conclusion: Keloid tissues express Oct-4 and ALDH1 as stemness markers, and the stemness characteristics of keloid might be similar to a normal skin.

Hypobaric hypoxia is basically a hypoxia condition experienced in high altitude commonly during flight, that increase reactive oxygen species (ROS). When hypoxia hypobaric does not undergo continuation or in other word, intermittent, it will cause adaptation response in a form of protection mode into ROS. Moreover, ROS could be eliminated by reduced-glutathione (GSH) as an endogenous non enzymatic antioxidant. Therefore, the aim of this study was to analyze the effects of intermittent hypobaric hypoxia exposure on GSH level in rat lung and renal tissue. Lung and renal samples were collected from 6–8 weeks old male Sprague-Dawley rats weighing 150–200 g, previously exposed 1–4 times to intermittent hypobaric hypoxia in 35,000 ft (1 minute), 25.000 ft (5 minute) and 18,000 ft altitude (25 minute). Afterwards, GSH level was calculated from lung and renal extracts using the Ellman’s method. In lung tissues, GSH level was decreased in hypoxia 1×, 2×, 3×, 4× treatment, and were significant between the control–hypoxia 3×, control–hypoxia 4×, hypoxia 1×–hypoxia 3× and hypoxia 1×–hypoxia 4×. On the contrary, GSH level was increased in renal tissues on hypoxia 1× and hypoxia 2× treatment compared to control. Nevertheless, GSH level was decreased after 3× treatment and found almost stabilized at 4× treatment of hypoxia in renal tissues. Intermittent hypobaric hypoxia exposure affect GSH in rat lung and renal tissues with varying level as an adaptive response system.

BACKGROUND: Keloids are characterized by an overabundance of collagen deposition due to elevated activity and proliferation of fibroblasts, which lead to hypoxic conditions. Adaptation to these conditions is regulated by the transcription factor hypoxia inducible factor-1α (HIF-1α). Cytoglobin (Cygb), a reactive oxygen species scavenger, is a target gene of HIF-1α. In our previous study, we showed that Cygb expression in keloid tissue was correlated with HIF-1α expression. However, whether HIF-1α regulates Cygb expression and the proliferation of keloid fibroblasts remained unclear. Therefore, this study aimed to determine the role of HIF-1α in Cygb expression and fibroblast proliferation of keloids. METHODS: This was an in vitro study using a primary culture of keloid fibroblasts in which ibuprofen was used to inhibit HIF-1α expression. The expression of HIF-1α and Cygb mRNA were analyzed using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) methods, and their protein levels were analyzed using an enzyme-linked immunosorbent assay (ELISA). Fibroblast proliferation was analyzed using a Trypan blue exclusion assay. RESULTS: Inhibition of HIF-1α by ibuprofen decreased Cygb mRNA expression but not in all the samples, followed by a decrease in the protein level of Cygb. There was a positive correlation between the HIF-1α protein and Cygb mRNA, probably due to the regulation of Cygb by HIF-1α at the mRNA level, but not the protein level. The proliferation of keloid fibroblasts was significantly decreased and positively correlated with the HIF-1α protein. CONCLUSION: HIF-1α regulates Cygb expression and fibroblast proliferation in keloids.

Background Glioblastoma multiforme (GBM) is the most malignant primary brain tumour and there is no definite cure. It has been suggested that there are significant interactions among mesenchymal stem cells (MSCs), their released factors and tumour cells that ultimately determine GBM's growth pattern. This study aims to analyse the expression of molecules involved in GBM cell apoptotic pathways following treatment with the MSC secretome. Methods A conditioned medium of umbilical cord-derived MSCs (UCMSC-CM) was generated by culturing the cells on serum-free αMEM for 24 h. Following this, human GBM T98G cells were treated with UCMSC-CM for 24 h. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was then performed to measure the mRNA expression of survivin, caspase-9, TNF-related apoptosis-inducing ligand (TRAIL), DR4 and DcR1. Results mRNA expression of caspase-9 in CM-treated T98G cells increased 1.6-fold (P = 0.017), whereas mRNA expression of survivin increased 3.5-fold (P = 0.002). On the other hand, TRAIL protein expression was upregulated (1.2-fold), whereas mRNA expression was downregulated (0.4-fold), in CM-treated cells. Moreover, there was an increase in the mRNA expression of both DR4 (3.5-fold) and DcR1 (1,368.5-fold) in CM-treated cells. Conclusion The UCMSC-CM was able to regulate the expression of molecules involved in GBM cell apoptotic pathways. However, the expression of anti-apoptotic molecules was more upregulated than that of pro-apoptotic molecules.

Background It has been widely reported that breast cancer aggressiveness may be driven by breast cancer stem cells (BCSCs). BCSCs display stemness properties that include self-renewal, tumourigenicity and pluripotency. The regulation of gene expression may have important roles in BCSC stemness and aggressiveness. Thus, the aim of this study was to examine the stemness and aggressiveness gene expression profile of BCSCs compared to MCF-7 and MDA-MB-231 breast cancer cells. Methods Human ALDH1+ BCSCs were grown in serum-free Dulbecco's Modified Eagle Medium (DMEM)/F12, while MCF-7 and MDA-MB-231 were cultured in DMEM supplemented with 10% foetal bovine serum under standard conditions. Total RNA was extracted using the Tripure Isolation Reagent. The relative mRNA expressions of OCT4, ALDH1A1 and CD44 associated with stemness as well as TGF-β1, TβR1, ERα1 and MnSOD associated with aggressiveness in BCSCs and MCF-7 cells were determined using the quantitative real-time PCR (qRT-PCR). Results The mRNA expressions of OCT4 (5.19-fold ± 0.338; P = 0.001), ALDH1A1 (3.67-fold ± 0.523; P = 0.006), CD44 (2.65-fold ± 0.307; P = 0.006), TGF-β1 (22.89-fold ± 6.840; P = 0.015), TβR1 (3.74-fold ± 1.446; P = 0.045) and MnSOD (4.6-fold ± 1.096; P = 0.014) were higher in BCSCs than in MCF-7 but were almost similar to MDA-MB-231 cells. In contrast, the ERα1 expression of BCSCs (0.97-fold ± 0.080; P = 0.392) was similar to MCF-7 cells, indicating that BSCSs are oestrogen-dependent breast cancer cells. Conclusion The oestrogen-dependent BCSCs express stemness and aggressiveness genes at a higher level compared to oestrogen-dependent MCF-7 but are almost similar to oestrogen-independent MDA-MB-231 cells.

The advancement of molecular biology provides benefit in the field of medicine to develop genetherapy. The aim of gene therapy is to repair the genetic damage or to replace damaged gene with thenormal gene. Delivery of gene is carried out by transfection technique, a technique to transfer nucleic acidinto eukaryote cells either using viral vectors (known as transduction), and also using non viral methodsuch as chemical substance, lipid and physical method. Some of the viral vectors used in the transductionare retrovirus, adenovirus, Adeno-associated virus (AAV) and Herpes Simplex Virus (HSV). The success oftransfection is determined by various factors which can be assessed using several reporters such as GreenFluorescence Protein (GFP).

Cancer stem cells (CSCs) are a subpopulation of cancer cells responsible for tumor maintenance and relapse due to their ability to resist various anticancer effects. Owing to the resistance of CSCs to the effects of targeted therapy, an alternative strategy that targets post‑translational glycosylation may be an improved approach to treat cancer as it disrupts multiple coordinated signaling that maintains the stemness of CSCs. Glucosamine acts as an anticancer agent possibly by inhibiting N‑linked glycosylation. The aim of the present study was to investigate the effect of glucosamine on the stemness of breast CSCs, which is regulated by signal transducer and activator of transcription 3 (STAT3) signaling. Human aldehyde dehydrogenase‑positive (ALDH+) breast CSCs and MCF7 cells were treated with various concentrations (0.25, 1 or 4 mM) of glucosamine for 24 h. Subsequently, cell viability was determined by performing a trypan blue exclusion assay, pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer‑binding transcription factor 4 (OCT‑4), and Krüppel‑like factor 4 (KLF4)] expression was determined using the reverse transcription‑quantitative polymerase chain reaction, and STAT3 and phosphorylated STAT3 (pSTAT3) levels were determined by performing western blot analysis. Furthermore, the number of mammosphere‑forming units (MFUs) in ALDH+ breast CSCs and MCF7 cells was determined. It was determined that glucosamine treatment decreased the viability of ALDH+ breast CSCs. Glucosamine treatment also decreased the stemness of ALDH+ breast CSCs and MCF7 cells, as indicated by decreased ALDH1A1, OCT‑4 and KLF4 expression level, and a decreased number of MFUs. This effect of glucosamine may be associated with a decreased pSTAT3/STAT3 ratio, indicating that glucosamine inhibited STAT3 activation; therefore, the results of the present study indicated that glucosamine treatment may be an improved approach to target the stemness of CSCs.

Cancer stem cells (CSCs) are a subpopulation of cancer cells responsible for tumor maintenance and relapse due to their ability to resist various anticancer effects. Owing to the resistance of CSCs to the effects of targeted therapy, an alternative strategy that targets post-translational glycosylation may be an improved approach to treat cancer as it disrupts multiple coordinated signaling that maintains the stemness of CSCs. Glucosamine acts as an anticancer agent possibly by inhibiting N-linked glycosylation. The aim of the present study was to investigate the effect of glucosamine on the stemness of breast CSCs, which is regulated by signal transducer and activator of transcription 3 (STAT3) signaling. Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs and MCF7 cells were treated with various concentrations (0.25, 1 or 4 mM) of glucosamine for 24 h. Subsequently, cell viability was determined by performing a trypan blue exclusion assay, pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer-binding transcription factor 4 (OCT-4), and Krüppel-like factor 4 (KLF4)] expression was determined using the reverse transcription-quantitative polymerase chain reaction, and STAT3 and phosphorylated STAT3 (pSTAT3) levels were determined by performing western blot analysis. Furthermore, the number of mammosphere-forming units (MFUs) in ALDH+ breast CSCs and MCF7 cells was determined. It was determined that glucosamine treatment decreased the viability of ALDH+ breast CSCs. Glucosamine treatment also decreased the stemness of ALDH+ breast CSCs and MCF7 cells, as indicated by decreased ALDH1A1, OCT-4 and KLF4 expression level, and a decreased number of MFUs. This effect of glucosamine may be associated with a decreased pSTAT3/STAT3 ratio, indicating that glucosamine inhibited STAT3 activation; therefore, the results of the present study indicated that glucosamine treatment may be an improved approach to target the stemness of CSCs.

Liver diseases are one of the major health problems worldwide and often difficult to treat. Hypoxia condition is one of its pathogenesis. This study was aimed to prove the hepatoprotective effects of the combination of Acalypha indica (AI) and Centella asiatica (CA) against hypoxia. Seven groups of Spraque-Dawley rats are used as follows: negative control without hypoxic condition, six other groups were put in hypoxic chamber and treated with water, AI, CA, two groups of AI-CA combination, and vitamin C, respectively. After 7 d of treatment, Malondialdehyde (MDA) levels were measured in plasma and liver. One of the AI-CA combination groups showed significant protective effect against hypoxia in liver (p < 0.001) but not in plasma.

The carcinogenic effect of benzene is associated with metabolites produced in benzene metabolism such as phenol, catechol, quinones, muconic acid (tt-MA), and phenyl mercapturic acid (s-PMA). The role of CYP4502E1 enzyme in benzene metabolism is very important, which is determined by its genetic polymorphism. This cross-sectional study is aimed to obtain the distribution of frequency of s-PMA concentration in workers who had been low exposure of benzene based on CYP4502E1 genetic polymorphism. The study was conducted between September 2007 and April 2010. Data were collected by methods of interviews, physical examinations, laboratory examinations, and direct observation on the work place. The variables studied were CYP4502E1, benzene exposure at the work place, age, type of work, history of work, length of work, body mass index (BMI), antioxidants intake, behavior and management, and s-PMA concentration in the urine. The distribution of CYP4502E1 genetic polymorphism in workers is 87.8% wild type homozygote, 11.3% heterozygote and 0.9% mutant homozygote. There was no significant difference in the proportion of s-PMA concentration based on CYP4502E1 genetic polymorphism (p=0.595; ORraw=0.98; 95% CI=0.95-1.01). There were also no differences of age, type of work, length of work, BMI, antioxidants consumptions, behavior and management of subjects with s-PMA. Further study should be conducted on CYP4502E1 genetic polymorphism in various Indonesian races at different workplace with low-level benzene.

Background: Glioblastoma multiforme (GBM) is a primary malignant brain tumor which has poor prognosis. High incidence of oxidative stress-based therapy resistance could be related to the high antioxidant status of GBM cells. Our previous study has reported that manganese superoxide dismutase (MnSOD) antioxidant expression was significantly higher in high grade glioma than in low grade. The aim of this study was to analyze the impact of MnSOD suppression toward GBM cell survival.Methods: This study is an experimental study using human glioblastoma multiforme T98G cell line. Suppression of MnSOD expression was performed using in vitro transfection MnSOD-siRNA. The MnSOD expression was analyzed by measuring the mRNA using real time RT-PCR, protein using ELISA technique, and specific activity of enzyme using inhibition of xantine oxidase. Concentration of reactive oxygen species (ROS) intracellular was determined by measuring superoxide radical and hydrogen peroxide. Cell survival was analyzed by measuring viability, proliferation, and cell apoptosis.Results: In vitro transfection of MnSOD-siRNA suppressed the mRNA, protein, and specific activity of MnSOD. This treatment significantly increased the concentration of superoxide radical; however, it did not influence the concentration of hydrogen peroxide. Moreover, viability MnSOD-suppressing cell significantly decreased, accompanied by increase of cell apoptosis without affecting cell proliferation.Conclusion: The suppression of MnSOD expression leads to decrease glioblastoma multiforme cell survival, which was associated to the increase of cell apoptotic.

Transforming growth factor-beta (TGF-β) is a regulatory cytokine secreted by various types of cell such as stromal cell, immune cells and tumor cells. Signaling of TGF-β plays an important role in proliferation, differentiation and apoptosis regulation of various cell, including glial cell. Disruption in the signaling pathway of TGF-β is commonly seen in tumor cells and is believed to contribute to the initiation and progression of cancer cells. Changes in the chromosome accompanied by genetic mutation has been observed which causes TGF-β to act as an oncogene, a substance which promote normal cells to differentiate to cancer cells.Increased level expression of TGF-β molecules has been seen in more malignant gliomas which yields a lower prognosis for the patient compared to those with lower expression of TGF-β. Malignant gliomas are characterized by rapid proliferation, invasion of parenchyma and angiogenic capabilities, are most common type of primary brain tumors. Studies have now implemented specific targeted therapy which act as a treatment for glioma cases. This review will focus on the role of TGF-β in glioma and its application in the treatment of glioma.International Journal of Human and Health Sciences Vol. 04 No. 03 July’20 Page : 156-160

Oxidative stress contributed in aging process and several degenerative diseases. Selenium was an important trace element due to as a component of antioxidants enzymes (selenoproteins), including glutathione peroxidase for protection against free radical. Objective: We aimed to study the correlation between blood selenium level and plasma glutathione peroxidase activity in elderly. Materials and Methods: Cross sectional study was held in 5 elderly communities in south Jakarta. Body mass index, blood selenium level and plasma glutathione peroxidase activity were measured in 95 elderly aged between 60-86 years old. Nonparametric correlation was used for correlation analysis. Results and Discussion: The median of subject’s age was 69 years old (60-86) and for body mass index was 23.57 (13.59-36.05). The median of selenium level among subject was 0.19 (0.023-0.56). The mean of plasma glutathione peroxidase activity was 164.45 U/L ± 68.07. There was no correlation among variables. However, plasma glutathione peroxidase activity decreased with increasing age and body mass index although it was not significant. Conclusion: There was no correlation between blood selenium level and plasma glutathione peroxidase activity. Detection of plasma selenium level is needed to confirm this result. International Journal of Human and Health Sciences Vol. 04 No. 02 April’20 Page : 89-93

Cathepsin dan calpain adalah anggota sistein protease yang merupakan enzim proteolitik yaitu enzim yang mengkatalisis pemecahan protein melalui hidrolisis ikatan peptida. Hidrolisis ikatan peptida pada ribuan protein baik di dalam maupun di luar sel berfungsi untuk mengontrol dinamika turn-over protein. Cathepsin merupakan enzim keluarga papain yang terletak di lisosom. Enzim tersebut memiliki 11 anggota yang berperan dalam pencernaan, presentasi antigen serta remodeling matriks. Calpain adalah kelompok sistein protease sitoplasmik yang aktivitasnya tergantung kalsium. Calpain mempunyai implikasi dalam proteolisis sejumlah protein intraseluler yang berhubungan dengan peningkatan kalsium intraseluler. Aktivasi protease tersebut berhubungan dengan pengikatan membran yang diikuti autolisis. Protein regulator seperti protein kinase C, actin-binding protein dan integrin sitoplasmik mengalami pemotongan oleh calpain, maka calpain dianggap berperan dalam proses signaling seluler. Kata kunci: cathepsin, calpain, protease