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Triglyceride-Glucose Index as A Crucial Marker for Polycystic Ovary Syndrome Women with Insulin Resistance 甘油三酯-葡萄糖指数是多囊卵巢综合征妇女胰岛素抵抗的关键标志物
Pub Date : 2024-02-23 DOI: 10.18585/inabj.v16i1.2639
A. Hestiantoro, Jaya Saraswati, David Eka Prasetya, Ferry Sandra, R. Muharam, G. Pratama, A. Harzif
BACKGROUND: Insulin resistance (IR) is considered as the main driver of polycystic ovary syndrome (PCOS) pathogenesis. In PCOS condition, IR is frequently related to glucose, anthropometric profile, lipid profile, and hormone profile parameters. However, not all PCOS phenotype show IR. Therefore, this study was conducted to determine the association the parameters mentioned above in PCOS subjects with and without IR.METHODS: Fifty PCOS women with IR and 26 PCOS women without IR were recruited. All subjects underwent physical examination for measurement of weight, waist circumference (WC), and body mass index (BMI). Ferriman Gallwey Score (FGS) was used to evaluate hirsutism. Blood sample was taken from each subject for measurement of fasting glucose, postprandial glucose, fasting insulin, low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol, triglyceride (TG), sex hormone binding globulin (SHBG), thyroid-stimulating hormone (TSH), luteinizing hormone (LH), follicle stimulating hormone (FSH), and prolactin. Homeostatic model assessment for IR (HOMA-IR), TG-glucose index (TyGI), and free testosterone index (FTI) were then calculated.RESULTS: From all the parameters examined, only fasting insulin (p<0.001), HOMA-IR (p<0.001), SHBG (p=0.012), TG (p<0.001), and TyGI (p=0.008) that show significant differences between PCOS subjects with and without IR. After multivariate analysis, TyGI was found to have strong association with IR occurrence in PCOS subjects (p=0.005) with an odd ratio of 5.26 (1.65–16.74).CONCLUSION: TyGI appears to have a significant association with the IR occurrence in PCOS subjects. Hence, it can be suggested that TyGI could be an important marker for PCOS women with IR.KEYWORDS: insulin resistance, lipid metabolism, polycystic ovary syndrome, triglyceride-glucose index
背景:胰岛素抵抗(IR)被认为是多囊卵巢综合征(PCOS)发病机制的主要驱动因素。在多囊卵巢综合症患者中,IR 通常与血糖、人体测量曲线、血脂曲线和激素曲线参数有关。然而,并非所有的多囊卵巢综合征表型都表现出 IR。因此,本研究旨在确定有 IR 和无 IR 的 PCOS 受试者的上述参数之间的关联。所有受试者均接受了体检,测量了体重、腰围(WC)和体重指数(BMI)。Ferriman Gallwey Score(FGS)用于评估多毛症。从每位受试者身上抽取血液样本,用于测量空腹血糖、餐后血糖、空腹胰岛素、低密度脂蛋白、高密度脂蛋白、总胆固醇、甘油三酯、性激素结合球蛋白、促甲状腺激素、促黄体生成素、促卵泡激素和催乳素。结果:在所有检查参数中,只有空腹胰岛素(p<0.001)、HOMA-IR(p<0.001)、SHBG(p=0.012)、TG(p<0.001)和 TyGI(p=0.008)在有 IR 和无 IR 的多囊卵巢综合征受试者之间存在显著差异。结论:TyGI似乎与多囊卵巢综合征受试者的IR发生有显著关联。因此,可以认为TyGI是多囊卵巢综合征女性IR的重要标志物。 关键词:胰岛素抵抗 脂质代谢 多囊卵巢综合征 甘油三酯-葡萄糖指数
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引用次数: 0
Effects of SGLT2-inhibitor on The Expression of MicroRNA-21, Transforming Growth Factor-β1, and Matrix Metalloproteinase-2 in The Process of Cardiac Fibrosis in Hyperglycemic Model Rats SGLT2 抑制剂对高血糖模型大鼠心脏纤维化过程中 MicroRNA-21、转化生长因子-β1 和基质金属蛋白酶-2 表达的影响
Pub Date : 2024-02-23 DOI: 10.18585/inabj.v16i1.2776
Muhammad Ridwan, H. Dimiati, M. Syukri, Ronny Lesmana
BACKGROUND: Sodium glucose co-transporter-2 inhibitor (SGLT2-i), a new oral antidiabetic drug, has been recommended for its morbidity and mortality benefits in patients with heart failure. This study aimed to determine the effect of acute SGLT2-i therapy on the relative ratio expression of microRNA-21 (miR-21), transforming growth factor-β1 (TGF-β1), and matrix metalloproteinase-2 (MMP-2) in the process of cardiac fibrosis in the hyperglycemia Wistar rat models compared to biguanide (metformin) therapy.METHODS: We used Streptozotocin (STZ) to induce hyperglycemia in Wistar rats (n=31), randomly divided into four groups: negative control (NC, n=4), positive control (PC, n=10), hyperglycemia plus metformin (M, n=8), and hyperglycemia plus empagliflozin (E, n=9). After seven weeks, the rats were sacrificed and the heart tissue was taken for microRNA and messenger RNA (mRNA) extraction, followed by reverse transcription quantitative real time polymerase chain reaction (RT-qPCR) examination. The data was analyzed using One-way ANOVA.RESULTS: Results showed a decreasing trend in the gene expression relative ratio of miR-21 (1.0 vs. 1.9; p=0.079) and TGF-β1 (0.9 vs. 3.2; p=0.145), but a significant increase in MMP-2 gene expression (1.3 vs. 0.7; p=0.002) in the SGLT2-i (empagliflozin) vs. biguanide (metformin) groups.CONCLUSION: Empagliflozin administration may play a significant role in preventing the occurrence of cardiac fibrosis in hyperglycemia.KEYWORDS: sodium glucose co-transporter-2 inhibitor, microRNA-21, transforming growth factor-β1, matrix metalloproteinase-2, cardiac fibrosis
背景:钠葡萄糖共转运体-2抑制剂(SGLT2-i)是一种新型口服抗糖尿病药物,因其对心力衰竭患者的发病率和死亡率有益而被推荐使用。本研究旨在确定与双胍类药物(二甲双胍)治疗相比,急性 SGLT2-i 治疗对高血糖 Wistar 大鼠模型心脏纤维化过程中 microRNA-21 (miR-21)、转化生长因子-β1 (TGF-β1) 和基质金属蛋白酶-2 (MMP-2) 相对比表达的影响。方法:我们使用链脲佐菌素(STZ)诱导Wistar大鼠(31只)发生高血糖,随机分为四组:阴性对照组(NC,4只)、阳性对照组(PC,10只)、高血糖加二甲双胍组(M,8只)和高血糖加恩格列净组(E,9只)。七周后,大鼠被处死,取心脏组织进行微RNA和信使RNA(mRNA)提取,然后进行反转录定量实时聚合酶链反应(RT-qPCR)检测。结果:结果显示,SGLT2-i(empagliflozin)与二甲双胍(metformin)相比,miR-21(1.0 vs. 1.9; p=0.079)和TGF-β1(0.9 vs. 3.2; p=0.145)的基因表达相对比呈下降趋势,但MMP-2基因表达显著增加(1.3 vs. 0.7; p=0.002)。结论:服用 Empagliflozin 可在预防高血糖时心脏纤维化的发生方面发挥重要作用。 关键词:钠葡萄糖协同转运体-2 抑制剂;microRNA-21;转化生长因子-β1;基质金属蛋白酶-2;心脏纤维化
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引用次数: 0
The Increase in CD14+CD16+ Monocytes is Correlated with Cardiovascular Disease Risk Marker in Type 2 Diabetes 2 型糖尿病患者 CD14+CD16+ 单核细胞的增加与心血管疾病风险指标相关
Pub Date : 2024-02-23 DOI: 10.18585/inabj.v16i1.2798
Ujang Saeful Hikmat, A. R. Prijanti, Heri Wibowo, I. Sukmawati, D. Tahapary
BACKGROUND: Type 2 Diabetes (T2D) impairs the innate immune system including monocytes. Monocytes are divided into two subgroups depending on the expression of cluster of differentiation (CD)14 and CD16 receptors, namely CD14+CD16- and CD14+CD16+. CD14+CD16+ are proinflammatory monocytes and develop into M1 type macrophages, which contribute to foam cell production, a risk factor for cardiovascular disease (CVD). Therefore, it is important to determine the influence of T2D conditions on changes in monocyte subsets and whether these changes correlate with CVD risk markers.METHODS: Peripheral blood mononuclear cell (PBMC) was obtained from 10 T2D subjects and 10 healthy donors. Subsequently, PBMC was incubated for 24 hours with and without 10 mL lipopolysaccharide. Flow cytometry was used to evaluate CD14 and CD16 expression, while multiplex immunoassays were applied to measure interleukin (IL)-1b and IL-10 concentrations in supernatants.RESULTS: In T2D, the percentage of CD14+CD16+ monocytes increased (p=0.07), and an increase in CD14+CD16+ monocytes more than 6.8% was linked with CVD risk markers (r=10.146, p=0.002). Meanwhile, inflammatory mediators released by monocytes shown an increase in IL-1b (p=0.041) but not in IL-10 (p=0.082) in T2D subjects. Fasting blood glucose levels were also found to be substantially linked with an increase in CD14+CD16+ monocytes (r=0.530, p=0.016).CONCLUSION: T2D patients had a higher percentage of CD14+CD16+ monocytes and IL-1b levels than healthy donors. An increase in CD14+CD16+ monocytes above 6.8% associated with CVD risk markers in T2D patients.KEYWORDS: type 2 diabetes, monocytes, CD14, CD16, cardiovaskular disease risk marker
背景:2 型糖尿病(T2D)会损害包括单核细胞在内的先天性免疫系统。根据分化簇(CD)14 和 CD16 受体的表达,单核细胞可分为两个亚群,即 CD14+CD16- 和 CD14+CD16+。CD14+CD16+ 是促炎性单核细胞,会发展成 M1 型巨噬细胞,导致泡沫细胞的产生,而泡沫细胞是心血管疾病(CVD)的危险因素。因此,确定 T2D 条件对单核细胞亚群变化的影响以及这些变化是否与心血管疾病风险指标相关非常重要。随后,将外周血单核细胞与 10 mL 脂多糖或无脂多糖培养 24 小时。结果:在 T2D 患者中,CD14+CD16+单核细胞的百分比增加(p=0.07),CD14+CD16+单核细胞增加超过 6.8%与心血管疾病风险指标相关(r=10.146,p=0.002)。同时,在 T2D 受试者中,单核细胞释放的炎症介质显示 IL-1b 增加(p=0.041),但 IL-10 没有增加(p=0.082)。结论:与健康供体相比,T2D 患者的 CD14+CD16+ 单核细胞比例和 IL-1b 水平更高。关键词:2 型糖尿病;单核细胞;CD14;CD16;心血管疾病风险标志物
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引用次数: 0
Hypoglycemic Activity and Safety Assessment of Pediococcus acidilactici Strain DNH16 in Experimental Type 2 Diabetes Mellitus Rats Induced with Streptozotocin 在链脲佐菌素诱导的实验性 2 型糖尿病大鼠中评估 Pediococcus acidilactici 菌株 DNH16 的降糖活性和安全性
Pub Date : 2024-02-23 DOI: 10.18585/inabj.v16i1.2781
E. Fachrial, Juliana Lina, Harmileni Harmileni, Sari Anggraini, Widya Yanti Sihotang
BACKGROUND: Type 2 diabetes mellitus (T2DM) cases tend to rise throughout the year in all parts of the world. The α-glucosidase inhibitors are frequently used to both prevent and treat T2DM. This α-glucosidase inhibitor activity is seen in some probiotic species, and a certain strain of Pediococcus acidilactici exhibits promising characteristics as an α-glucosidase inhibitor. This study was conducted to assess the hypoglycemic activity and safety of P. acidilactici strain DNH16 (PADNH16) in experimental rats with T2DM induced by streptozotocin.METHODS: The experiment was conducted in vivo using Wistar rats. Acarbose was employed as a positive control, and Lactobacillus casei was used as a comparative. For 24 days, post-prandial blood glucose levels were assessed every 3 days, followed by serum biochemical levels measurement of liver, kidney, and lipid profiles. The pancreas was histopathologically examined utilizing the Hematoxyline-Eosin staining procedure.RESULTS: Administration of PADNH16 to T2DM rats lowered post-prandial blood glucose levels and gave hypoglycemic benefits comparable to acarbose and commercial probiotics. PADNH16 dosing did not affect serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), urea, or creatinine levels, showing that PADNH16 was not hazardous to liver or kidney function. The lipid profile assessment revealed that the values, including high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides, were comparable to the control group. The pancreatic histopathology revealed that injection of PADNH16 caused no alterations to pancreatic β cells.CONCLUSION: P. acidilactici isolate DNH16 has a hypoglycemic effect on T2DM rats, but does not affect liver function enzymes, kidneys, lipid profiles and does not provide significant changes in pancreatic β cells.KEYWORDS: diabetes mellitus, inhibitor α-glucosidase, Pediococcus acidilactici strain DNH16
背景:世界各地的 2 型糖尿病(T2DM)病例呈逐年上升趋势。α-葡萄糖苷酶抑制剂常用于预防和治疗 T2DM。α-葡萄糖苷酶抑制剂的活性可见于一些益生菌物种,其中一株酸乳乳酸钠钙球菌(Pediococcus acidilactici)作为一种α-葡萄糖苷酶抑制剂表现出良好的特性。本研究旨在评估 P. acidilactici 菌株 DNH16(PADNH16)在链脲佐菌素诱导的 T2DM 实验大鼠中的降糖活性和安全性。阿卡波糖作为阳性对照,干酪乳杆菌作为阴性对照。在 24 天内,每 3 天评估一次餐后血糖水平,然后测量肝脏、肾脏和血脂的血清生化水平。结果:给 T2DM 大鼠服用 PADNH16 可降低餐后血糖水平,降糖效果与阿卡波糖和商业益生菌相当。服用 PADNH16 不会影响血清谷草转氨酶 (SGOT)、血清谷丙转氨酶 (SGPT)、尿素或肌酐水平,这表明 PADNH16 不会危害肝脏或肾脏功能。血脂组合评估显示,包括高密度脂蛋白(HDL)、低密度脂蛋白(LDL)和甘油三酯在内的血脂值与对照组相当。结论:P. acidilactici 分离物 DNH16 对 T2DM 大鼠有降血糖作用,但不会影响肝功能酶、肾脏和血脂,也不会使胰腺 β 细胞发生显著变化。
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引用次数: 0
Intrauterine Transmission of Hepatitis B Cannot Be Ruled Out by A Single Negative Hepatitis B e Antigen (HBeAg) Result among Hepatitis B Surface Antigen (HBsAg) - Positive Pregnant Women 乙型肝炎表面抗原 (HBsAg) 阳性孕妇的乙型肝炎 e 抗原 (HBeAg) 单项阴性结果不能排除宫内传播乙型肝炎的可能性
Pub Date : 2024-02-23 DOI: 10.18585/inabj.v16i1.2726
M. Chalid, T. Judistiani, Rizalinda Syahril, Rina Masadah, Dwi Bahagia Febriani, Ridha Wahyuni, T. Turyadi, M. N. Massi
BACKGROUND: The risk factors for intrauterine transmission of hepatitis B virus (HBV) in hepatitis B surface antigen (HBsAg)-positive pregnant women are poorly understood. Numerous factors are considered to be involved, including placental barrier, obstetric environment, high viral load, and positivity of hepatitis B e antigen (HBeAg). This study was conducted to investigate the role of placenta barrier, clinical, and viral factors in intrauterine transmission of HBV.METHODS: A cross-sectional study was conducted involving 1,353 pregnant women who underwent HBsAg screening. Eighty-four (6.2%) women were detected as HBsAg positive and were examined for HBsAg level, anti-HBs, anti-HBc, HBeAg/hepatitis B e antibody (anti-HBe) status, and HBV DNA presence in cord blood. Quantitative HBV DNA was analyzed using real-time polymerase chain reaction (PCR).RESULTS: Eighty-four of 1,353 subjects were HBsAg-positive. HBV DNA was positive in 28/84 (33.7%) maternal sera, 19/79 (24.05%) placental specimens, and 9/83 (10.84%) in cord blood. There were significant associations between HBV DNA in maternal serum (p=0.000) and placental tissue (p=0.000) with HBV DNA in the cord blood. No clinical factors were associated with HBV DNA transmission in cord blood. Sixty percent of viral load >5.3 log10 copies/mL were found in the cord blood, of which 43.8% HBeAg positive and 3.1% HBeAg negative.CONCLUSION: Reduced transmission via compartments established the placenta’s barrier function in mother-to-child transmission. A high maternal viral load and positive HBeAg were risk factors for intrauterine transmission, while negative HBeAg still has the possibility of transmission.KEYWORDS: mother-to-child transmission, hepatitis B virus, intrauterine
背景:人们对乙型肝炎表面抗原(HBsAg)阳性孕妇宫内传播乙型肝炎病毒(HBV)的风险因素知之甚少。许多因素被认为与此有关,包括胎盘屏障、产科环境、高病毒载量和乙型肝炎 e 抗原(HBeAg)阳性。本研究旨在探讨胎盘屏障、临床和病毒因素在 HBV 宫内传播中的作用。方法:本研究是一项横断面研究,涉及 1,353 名接受 HBsAg 筛查的孕妇。84名(6.2%)孕妇被检测出HBsAg阳性,并接受了HBsAg水平、抗-HBs、抗-HBc、HBeAg/乙型肝炎e抗体(抗-HBe)状态和脐带血中HBV DNA存在情况的检查。结果:1353 名受试者中有 84 人 HBsAg 阳性。28/84(33.7%)的母体血清、19/79(24.05%)的胎盘标本和 9/83(10.84%)的脐带血中 HBV DNA 呈阳性。母体血清中的 HBV DNA(P=0.000)和胎盘组织中的 HBV DNA(P=0.000)与脐带血中的 HBV DNA 有明显的相关性。没有临床因素与脐带血中的 HBV DNA 传播相关。脐带血中病毒载量大于 5.3 log10 copies/mL 的占 60%,其中 43.8% HBeAg 阳性,3.1% HBeAg 阴性。母体病毒载量高和 HBeAg 阳性是宫内传播的危险因素,而 HBeAg 阴性仍有传播的可能性。
{"title":"Intrauterine Transmission of Hepatitis B Cannot Be Ruled Out by A Single Negative Hepatitis B e Antigen (HBeAg) Result among Hepatitis B Surface Antigen (HBsAg) - Positive Pregnant Women","authors":"M. Chalid, T. Judistiani, Rizalinda Syahril, Rina Masadah, Dwi Bahagia Febriani, Ridha Wahyuni, T. Turyadi, M. N. Massi","doi":"10.18585/inabj.v16i1.2726","DOIUrl":"https://doi.org/10.18585/inabj.v16i1.2726","url":null,"abstract":"BACKGROUND: The risk factors for intrauterine transmission of hepatitis B virus (HBV) in hepatitis B surface antigen (HBsAg)-positive pregnant women are poorly understood. Numerous factors are considered to be involved, including placental barrier, obstetric environment, high viral load, and positivity of hepatitis B e antigen (HBeAg). This study was conducted to investigate the role of placenta barrier, clinical, and viral factors in intrauterine transmission of HBV.METHODS: A cross-sectional study was conducted involving 1,353 pregnant women who underwent HBsAg screening. Eighty-four (6.2%) women were detected as HBsAg positive and were examined for HBsAg level, anti-HBs, anti-HBc, HBeAg/hepatitis B e antibody (anti-HBe) status, and HBV DNA presence in cord blood. Quantitative HBV DNA was analyzed using real-time polymerase chain reaction (PCR).RESULTS: Eighty-four of 1,353 subjects were HBsAg-positive. HBV DNA was positive in 28/84 (33.7%) maternal sera, 19/79 (24.05%) placental specimens, and 9/83 (10.84%) in cord blood. There were significant associations between HBV DNA in maternal serum (p=0.000) and placental tissue (p=0.000) with HBV DNA in the cord blood. No clinical factors were associated with HBV DNA transmission in cord blood. Sixty percent of viral load >5.3 log10 copies/mL were found in the cord blood, of which 43.8% HBeAg positive and 3.1% HBeAg negative.CONCLUSION: Reduced transmission via compartments established the placenta’s barrier function in mother-to-child transmission. A high maternal viral load and positive HBeAg were risk factors for intrauterine transmission, while negative HBeAg still has the possibility of transmission.KEYWORDS: mother-to-child transmission, hepatitis B virus, intrauterine","PeriodicalId":22516,"journal":{"name":"The Indonesian Biomedical Journal","volume":"29 19","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140435622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Diosmin Enhances the Anti-migration Activity of Curcumin Analog PGV-1 on Colorectal Cancer Cells 地奥司明能增强姜黄素类似物 PGV-1 对结直肠癌细胞的抗迁移活性
Pub Date : 2024-02-23 DOI: 10.18585/inabj.v16i1.2829
Muthi’ Ikawati, Rohmad Yudi Utomo, Novia Permata Hapsari, E. Meiyanto, Chio Oka
BACKGROUND: Diosmin enhances the cytotoxicity of Pentagamavunone-1 (PGV-1) in cancer cells. PGV-1 and diosmin are predicted to target several matrix metalloproteinases (MMPs) in metastatic cancer, including colorectal cancer, but the anti-migration potency of their combination has not established yet. This study evaluates the anti-migration effect of PGV-1 and diosmin combination in colorectal cancer.METHODS: The cytotoxicity assay using Cell Counting Kit 8 (CCK-8) method in WiDr colorectal cancer cells was carried out to determine the concentration for anti-migration experiments. The wound healing assay was used to observe the anti-migration activity by measuring the cell-free area. Gelatin zymography was employed to detect the MMP activity indicating by the clear band density. The interaction between PGV-1 or diosmin and MMP proteins was predicted by molecular dockings.RESULTS: PGV-1 was cytotoxic (IC50 17 mM), while diosmin up to 100 mM did not affect cell viability. Both 10 mM PGV-1 as well as 50 and 100 mM diosmin slowed down the closure of cell-free area. A 100 mM diosmin was significantly enhance the anti-migratory activity of 50 and 100 mM PGV-1. The activity of MMP-9 and MMP-2 was also lower in the presence of diosmin compared to than that of PGV-1 alone. PGV-1 or diosmin was also able to interact with MMP proteins with a lower energy compared to than that of the native ligands.CONCLUSION: Diosmin enhances the anti-migration activity of PGV-1 in WiDr cells, possibly by affecting MMPs’ activity. This study is an evidence that diosmin is a potential co-chemotherapy candidate for PGV-1, that can be utilized to overcome metastatis in colorectal cancer.KEYWORDS: cancer, citrus flavonoid, co-chemotherapy, diosmin, matrix metalloproteinases (MMPs), migration, Pentagamavunone-1, WiDr cancer cell
背景:薯蓣皂苷增强了五加黄酮-1(PGV-1)对癌细胞的细胞毒性。据预测,PGV-1 和地奥司明能靶向包括结直肠癌在内的转移性癌症中的几种基质金属蛋白酶(MMPs),但它们的联合抗迁移效力尚未确定。本研究评估了 PGV-1 和 diosmin 组合在结直肠癌中的抗迁移作用。方法:使用细胞计数试剂盒 8(CCK-8)法对 WiDr 结直肠癌细胞进行细胞毒性检测,以确定抗迁移实验的浓度。伤口愈合试验通过测量无细胞面积来观察抗迁移活性。明胶酶谱法通过清晰的条带密度来检测 MMP 活性。结果:PGV-1 具有细胞毒性(IC50 17 mM),而浓度高达 100 mM 的 diosmin 不影响细胞活力。10 mM PGV-1 以及 50 mM 和 100 mM diosmin 都能减缓无细胞区域的闭合。100 mM diosmin 能显著增强 50 mM 和 100 mM PGV-1 的抗迁移活性。与单独使用 PGV-1 相比,有 diosmin 存在时 MMP-9 和 MMP-2 的活性也更低。结论:地奥司明增强了 PGV-1 在 WiDr 细胞中的抗迁移活性,可能是通过影响 MMPs 的活性。这项研究证明,薯蓣皂苷是 PGV-1 潜在的联合化疗候选药物,可用于克服结直肠癌的转移问题。关键字:癌症,柑橘类黄酮,联合化疗,薯蓣皂苷,基质金属蛋白酶(MMPs),迁移,五加黄酮-1,WiDr 癌细胞
{"title":"Diosmin Enhances the Anti-migration Activity of Curcumin Analog PGV-1 on Colorectal Cancer Cells","authors":"Muthi’ Ikawati, Rohmad Yudi Utomo, Novia Permata Hapsari, E. Meiyanto, Chio Oka","doi":"10.18585/inabj.v16i1.2829","DOIUrl":"https://doi.org/10.18585/inabj.v16i1.2829","url":null,"abstract":"BACKGROUND: Diosmin enhances the cytotoxicity of Pentagamavunone-1 (PGV-1) in cancer cells. PGV-1 and diosmin are predicted to target several matrix metalloproteinases (MMPs) in metastatic cancer, including colorectal cancer, but the anti-migration potency of their combination has not established yet. This study evaluates the anti-migration effect of PGV-1 and diosmin combination in colorectal cancer.METHODS: The cytotoxicity assay using Cell Counting Kit 8 (CCK-8) method in WiDr colorectal cancer cells was carried out to determine the concentration for anti-migration experiments. The wound healing assay was used to observe the anti-migration activity by measuring the cell-free area. Gelatin zymography was employed to detect the MMP activity indicating by the clear band density. The interaction between PGV-1 or diosmin and MMP proteins was predicted by molecular dockings.RESULTS: PGV-1 was cytotoxic (IC50 17 mM), while diosmin up to 100 mM did not affect cell viability. Both 10 mM PGV-1 as well as 50 and 100 mM diosmin slowed down the closure of cell-free area. A 100 mM diosmin was significantly enhance the anti-migratory activity of 50 and 100 mM PGV-1. The activity of MMP-9 and MMP-2 was also lower in the presence of diosmin compared to than that of PGV-1 alone. PGV-1 or diosmin was also able to interact with MMP proteins with a lower energy compared to than that of the native ligands.CONCLUSION: Diosmin enhances the anti-migration activity of PGV-1 in WiDr cells, possibly by affecting MMPs’ activity. This study is an evidence that diosmin is a potential co-chemotherapy candidate for PGV-1, that can be utilized to overcome metastatis in colorectal cancer.KEYWORDS: cancer, citrus flavonoid, co-chemotherapy, diosmin, matrix metalloproteinases (MMPs), migration, Pentagamavunone-1, WiDr cancer cell","PeriodicalId":22516,"journal":{"name":"The Indonesian Biomedical Journal","volume":"20 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140437300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Andrographis paniculata Leaves Extract Inhibit TNF-α and Caspase-3 Expression of Septic Rats’ Intestinal Tissues 穿心莲叶提取物抑制败血症大鼠肠组织中 TNF-α 和 Caspase-3 的表达
Pub Date : 2024-02-23 DOI: 10.18585/inabj.v16i1.2727
Ryco Giftyan Ardika, B. Budiono, Nyoman Suci Widiastiti, Nani Maharani, N. Susilaningsih, Ferry Sandra
BACKGROUND: Microcirculation and cellular disturbances caused by sepsis might trigger significant intestinal damage. Andrographis paniculata extract decreases inflammatory intestinal epithelial cells with its role as an antiparasitic and anti-inflammatory agent. However, A. paniculata extract’s effect on sepsis have not been commonly studied, especially in the intestinal tissues. Therefore, this study was conducted to determine A. paniculata leaves extract (APLE) effect in sepsis-induced intestinal tissues of rats by examining the expression of inflammatory cytokines involved in sepsis, namely tumor necrosis factor (TNF)-α and Caspase-3.METHODS: Rats were divided into five groups; two groups received no pretreatment and the other three groups received 200, 400, and 500 mg/kg BW/day APLE, respectively. Three pretreated groups and one group with no pretreatment were then injected with 1 mg/200 g BW lipopolysaccharides (LPS) intraperitoneally to create septic rat models. Three days after the LPS-induction, rats were euthanized and the expression of TNF-α and Caspase-3 were assessed based on the immunohistochemical staining of rats’ intestinal tissues.RESULTS: Compared with NaCl (sham), LPS significantly (p<0.001) induced TNF-α expression from 6.60±1.36 to 25.37±1.74. Pretreatment of 200, 400, and 500 mg/kg BW/day APLE could significantly (p<0.001) inhibit the LPS-induced TNF-α expression (18.82±1.36, 11.45±1.18, and 6.89±1.90, respectively). Similar with TNF-α, compared with NaCl (sham), LPS significantly (p<0.001) induced Caspase-3 expression from 6.92±1.66 to 23.59±2.25. Pretreatment of 200, 400, and 500 mg/kg BW/day APLE could significantly (p<0.001) inhibit the LPS-induced Caspase-3 expression (17.47±1.68, 12.99±1.51, and 5.59±1.51, respectively).CONCLUSION: The pretreatment of APLE could inhibit the LPS-induced TNF-α and Caspase-3 expression, therefore APLE could be suggested as a potential sepsis-preventing agent.KEYWORDS: Andrographis paniculata, sepsis, TNF-α, Caspase-3, lipopolysaccharide 
背景:败血症导致的微循环和细胞紊乱可能会引发严重的肠道损伤。穿心莲提取物具有抗寄生虫和抗炎作用,可减少炎性肠上皮细胞。然而,穿心莲提取物对败血症的影响尚未得到广泛研究,尤其是对肠道组织的影响。因此,本研究通过检测参与败血症的炎性细胞因子(即肿瘤坏死因子(TNF)-α和Caspase-3)的表达,来确定A. paniculata叶提取物(APLE)对败血症诱导的大鼠肠道组织的影响。然后向三组预处理组和一组未预处理组腹腔注射 1 毫克/200 克体重的脂多糖(LPS),建立败血症大鼠模型。结果:与氯化钠(假)相比,LPS能显著(p<0.001)诱导TNF-α的表达,从6.60±1.36升至25.37±1.74。预处理 200、400 和 500 毫克/千克体重/天的 APLE 可显著(p<0.001)抑制 LPS 诱导的 TNF-α 表达(分别为 18.82±1.36、11.45±1.18 和 6.89±1.90)。与 TNF-α 相似,与氯化钠(假)相比,LPS 显著(p<0.001)诱导 Caspase-3 的表达,从 6.92±1.66 升至 23.59±2.25。200、400和500毫克/千克体重/天的APLE预处理可明显(p<0.001)抑制LPS诱导的Caspase-3表达(分别为17.47±1.68、12.99±1.51和5.59±1.51)。结论:APLE预处理可抑制LPS诱导的TNF-α和Caspase-3的表达,因此APLE可作为一种潜在的败血症预防剂。 关键词:穿心莲 败血症 TNF-α Caspase-3 脂多糖
{"title":"Andrographis paniculata Leaves Extract Inhibit TNF-α and Caspase-3 Expression of Septic Rats’ Intestinal Tissues","authors":"Ryco Giftyan Ardika, B. Budiono, Nyoman Suci Widiastiti, Nani Maharani, N. Susilaningsih, Ferry Sandra","doi":"10.18585/inabj.v16i1.2727","DOIUrl":"https://doi.org/10.18585/inabj.v16i1.2727","url":null,"abstract":"BACKGROUND: Microcirculation and cellular disturbances caused by sepsis might trigger significant intestinal damage. Andrographis paniculata extract decreases inflammatory intestinal epithelial cells with its role as an antiparasitic and anti-inflammatory agent. However, A. paniculata extract’s effect on sepsis have not been commonly studied, especially in the intestinal tissues. Therefore, this study was conducted to determine A. paniculata leaves extract (APLE) effect in sepsis-induced intestinal tissues of rats by examining the expression of inflammatory cytokines involved in sepsis, namely tumor necrosis factor (TNF)-α and Caspase-3.METHODS: Rats were divided into five groups; two groups received no pretreatment and the other three groups received 200, 400, and 500 mg/kg BW/day APLE, respectively. Three pretreated groups and one group with no pretreatment were then injected with 1 mg/200 g BW lipopolysaccharides (LPS) intraperitoneally to create septic rat models. Three days after the LPS-induction, rats were euthanized and the expression of TNF-α and Caspase-3 were assessed based on the immunohistochemical staining of rats’ intestinal tissues.RESULTS: Compared with NaCl (sham), LPS significantly (p<0.001) induced TNF-α expression from 6.60±1.36 to 25.37±1.74. Pretreatment of 200, 400, and 500 mg/kg BW/day APLE could significantly (p<0.001) inhibit the LPS-induced TNF-α expression (18.82±1.36, 11.45±1.18, and 6.89±1.90, respectively). Similar with TNF-α, compared with NaCl (sham), LPS significantly (p<0.001) induced Caspase-3 expression from 6.92±1.66 to 23.59±2.25. Pretreatment of 200, 400, and 500 mg/kg BW/day APLE could significantly (p<0.001) inhibit the LPS-induced Caspase-3 expression (17.47±1.68, 12.99±1.51, and 5.59±1.51, respectively).CONCLUSION: The pretreatment of APLE could inhibit the LPS-induced TNF-α and Caspase-3 expression, therefore APLE could be suggested as a potential sepsis-preventing agent.KEYWORDS: Andrographis paniculata, sepsis, TNF-α, Caspase-3, lipopolysaccharide ","PeriodicalId":22516,"journal":{"name":"The Indonesian Biomedical Journal","volume":"28 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139957215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Obesity: A Multi Perspective of Physiology and Neurobiology Energy Regulation 肥胖症:生理学和神经生物学的多重视角 能量调节
Pub Date : 2024-02-23 DOI: 10.18585/inabj.v16i1.2840
A. Meiliana, Nurrani Mustika Dewi, A. Wijaya
BACKGROUND: World Health Organization has reported four million people die every year due to obesity comorbidity, and the prevalence of obesity is keep increasing, especially after COVID-19. Obesity has been defined as a chronic disease involving adipose tissue dysfunction which leads to metabolic diseases and psychosocial consequences. The review article will highlight some recent researches regarding the new conceptual framework that integrates both metabolic drives, as well as to summarize the numerous discussions about the current understanding of hypothalamic control of food intake and energy homeostasis.CONTENT: Obesity apparently is not simply regulated only by food and exercise. Hypothalamus takes part in controlling energy intake and expenditure via appetite regulation. Hedonic control in cortical and subcortical brain areas process cognitive, reward, information, and executive function. Managing metabolic adaptation, browning the white adipose tissue, and preserving lean mass can be another strategy to safely manage obesity.SUMMARY: Obesity need to be managed in a multimodal strategy including neurophysiology and physiology approach, together with environment support. Thus, a weight regain can be prevented. Commitment from both scientific and regulation point of view can shed a light to eradicate obesity.KEYWORDS: adipocyte, appetite, nutrition, obesity, physical activity, reward, satiety
背景:据世界卫生组织报告,每年有四百万人死于肥胖症,而且肥胖症的发病率还在不断上升,尤其是在 COVID-19 之后。肥胖被定义为一种慢性疾病,涉及脂肪组织功能障碍,导致代谢性疾病和社会心理后果。这篇综述文章将重点介绍最近关于整合两种代谢驱动力的新概念框架的一些研究,并总结目前关于下丘脑控制食物摄入和能量平衡的众多讨论:肥胖显然不仅仅受食物和运动的调节。下丘脑通过食欲调节参与控制能量摄入和消耗。大脑皮质和皮质下区域的享乐控制处理认知、奖赏、信息和执行功能。总结:肥胖症需要多模式策略管理,包括神经生理学和生理学方法,以及环境支持。因此,可以防止体重反弹。关键字:脂肪细胞、食欲、营养、肥胖、体力活动、奖赏、饱腹感
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引用次数: 0
Expression of GABAA Receptor Subunits α1 and β2 in Healthy Human Dental Pulp 健康人牙髓中 GABAA 受体亚基 α1 和 β2 的表达
Pub Date : 2024-02-23 DOI: 10.18585/inabj.v16i1.2742
Diveyaa Sivakumar, Wan Nazatul Shima Shahidan, N. Ghani, Tang Liszen, Rosmaliza Ramli
BACKGROUND: Gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the mammalian central nervous system (CNS), has a well-established role in pain modulation. While numerous studies have delved into the expression of GABA and its receptors in dental pulp, the exact influence of these receptors on dental pain signaling has not been fully elucidated. This study aimed to investigate the gene and protein expression of the two most abundantly expressed GABA type A (GABAA) receptor subunits, GABAA receptor subunit α1 (GABRA1) and β2 (GABRB2), in healthy human dental pulp.METHODS: Six tooth samples were collected from healthy individuals referred for orthodontic treatment. Total RNA was isolated from the pulp tissues of three samples and reverse transcription-polymerase chain reaction (RT-PCR) was performed to assess gene expression of GABRA1 and GABRB2. The other three samples were examined using immunohistochemistry (IHC) for visualization of GABRA1 and GABRB2 proteins within the dental pulp.RESULTS: RT-PCR analysis reported the presence of both GABRA1 and GABRB2 in the dental pulp, and independent t-test analysis revealed that the expression of GABRA1 was significantly higher than GABRB2. The immunohistochemical staining provided compelling visual evidence of the expression of GABRA1 and GABRB2 proteins within the odontoblast layer of dental pulp, clearly indicating their presence in the cell bodies and odontoblastic processes extending into the dentin.CONCLUSION: The presence of α1 and β2 subunits of the GABAA receptor in healthy human dental pulp offers valuable insights for further research into the potential roles of GABAA receptors in dental pain signaling.KEYWORDS: γ-aminobutyric acid, GABAA receptors, GABRA1, GABRB2, dental pain, pain signaling
背景:γ-氨基丁酸(GABA)是哺乳动物中枢神经系统(CNS)中的主要抑制性神经递质,在疼痛调节中具有公认的作用。虽然已有大量研究深入探讨了 GABA 及其受体在牙髓中的表达,但这些受体对牙痛信号转导的确切影响尚未完全阐明。本研究旨在调查健康人牙髓中两种表达最丰富的 GABA A 型(GABAA)受体亚基(GABAA 受体亚基 α1 (GABRA1) 和 β2 (GABRB2))的基因和蛋白表达情况。从三个样本的牙髓组织中分离出总 RNA,并进行反转录聚合酶链反应(RT-PCR)以评估 GABRA1 和 GABRB2 的基因表达。结果:RT-PCR 分析表明牙髓中存在 GABRA1 和 GABRB2,独立 t 检验分析表明 GABRA1 的表达明显高于 GABRB2。免疫组化染色提供了令人信服的直观证据,证明牙髓的牙本质细胞层中存在 GABRA1 和 GABRB2 蛋白,清楚地表明它们存在于细胞体和延伸至牙本质的牙本质过程中。结论:健康人牙髓中存在 GABAA 受体的 α1 和 β2 亚基,这为进一步研究 GABAA 受体在牙痛信号传导中的潜在作用提供了宝贵的见解。
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引用次数: 0
Increased Levels of TNF-α, IL-6, and IL-10 are Associated with The Degree of Liver Fibrosis in Chronic Hepatitis B Patients with NUC Therapy TNF-α、IL-6 和 IL-10 水平的升高与接受 NUC 治疗的慢性乙型肝炎患者的肝纤维化程度有关
Pub Date : 2024-02-23 DOI: 10.18585/inabj.v16i1.2848
U. Maimunah, Ulfa Kholili, Rheza Rahmadika Putra, Dio Brimantyo, Hendy Wirantara
BACKGROUND: Liver fibrosis in chronic hepatitis B (CHB) involves the host immune responses mainly T-lymphocyte regulatory cells and cytokines production. Tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 have been reported to play a crucial role in the development of liver fibrosis. However, their association with liver fibrosis in treated CHB patients remains unclear. Therefore, this study was conducted to investigate the association between TNF-α, IL-6, and IL-10 with the degree of liver fibrosis in treated CHB patients.METHODS: This was a cross-sectional prospective study including 101 treated chronic hepatitis B subjects. TNF-α, IL-6, and IL-10 serum levels were measured with quantitative sandwich enzyme-linked immunosorbent assay (ELISA) kit. Transient elastography result was classified according to METAVIR score. Data was analyzed by the Spearman correlation test with a p<0.05 was considered statistically significant.RESULTS: From 101 subjects, there were significant differences were seen in TNF-α, IL-6, and IL-10 between patients with mild, significant and advance fibrosis. TNF-α (r=0.292; p<0.05), IL-6 (r=0.221; p<0.05), and IL-10 (r=0.208; p<0.05) were significantly correlated with the degree of fibrosis. After multivariate analysis, TNF-α was the only one cytokine parameter which significantly correlated with the degree of fibrosis.CONCLUSION: Levels of TNF-α, IL-6 and IL-10 are associated with the degree of liver fibrosis. These parameters may potentially be used to evaluate the development of liver fibrosis in treated CHB patients.KEYWORDS: chronic hepatitis B, liver fibrosis, cytokines, transient elastography
背景:慢性乙型肝炎(CHB)的肝纤维化涉及宿主免疫反应,主要是 T 淋巴细胞调节细胞和细胞因子的产生。据报道,肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6 和 IL-10 在肝纤维化的发展中起着至关重要的作用。然而,它们与接受治疗的慢性乙型肝炎患者肝纤维化的关系仍不清楚。因此,本研究调查了TNF-α、IL-6和IL-10与接受治疗的慢性乙型肝炎患者肝纤维化程度的关系。采用定量夹心酶联免疫吸附试验(ELISA)试剂盒测定 TNF-α、IL-6 和 IL-10 血清水平。瞬态弹性成像结果根据 METAVIR 评分进行分类。结果:101 名受试者的 TNF-α、IL-6 和 IL-10 在轻度、重度和晚期纤维化患者之间存在显著差异。TNF-α(r=0.292;p<0.05)、IL-6(r=0.221;p<0.05)和IL-10(r=0.208;p<0.05)与纤维化程度显著相关。结论:TNF-α、IL-6 和 IL-10 的水平与肝纤维化程度相关。结论:TNF-α、IL-6 和 IL-10 的水平与肝纤维化程度相关,这些参数可用于评估接受治疗的慢性乙型肝炎患者肝纤维化的发展情况。
{"title":"Increased Levels of TNF-α, IL-6, and IL-10 are Associated with The Degree of Liver Fibrosis in Chronic Hepatitis B Patients with NUC Therapy","authors":"U. Maimunah, Ulfa Kholili, Rheza Rahmadika Putra, Dio Brimantyo, Hendy Wirantara","doi":"10.18585/inabj.v16i1.2848","DOIUrl":"https://doi.org/10.18585/inabj.v16i1.2848","url":null,"abstract":"BACKGROUND: Liver fibrosis in chronic hepatitis B (CHB) involves the host immune responses mainly T-lymphocyte regulatory cells and cytokines production. Tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 have been reported to play a crucial role in the development of liver fibrosis. However, their association with liver fibrosis in treated CHB patients remains unclear. Therefore, this study was conducted to investigate the association between TNF-α, IL-6, and IL-10 with the degree of liver fibrosis in treated CHB patients.METHODS: This was a cross-sectional prospective study including 101 treated chronic hepatitis B subjects. TNF-α, IL-6, and IL-10 serum levels were measured with quantitative sandwich enzyme-linked immunosorbent assay (ELISA) kit. Transient elastography result was classified according to METAVIR score. Data was analyzed by the Spearman correlation test with a p<0.05 was considered statistically significant.RESULTS: From 101 subjects, there were significant differences were seen in TNF-α, IL-6, and IL-10 between patients with mild, significant and advance fibrosis. TNF-α (r=0.292; p<0.05), IL-6 (r=0.221; p<0.05), and IL-10 (r=0.208; p<0.05) were significantly correlated with the degree of fibrosis. After multivariate analysis, TNF-α was the only one cytokine parameter which significantly correlated with the degree of fibrosis.CONCLUSION: Levels of TNF-α, IL-6 and IL-10 are associated with the degree of liver fibrosis. These parameters may potentially be used to evaluate the development of liver fibrosis in treated CHB patients.KEYWORDS: chronic hepatitis B, liver fibrosis, cytokines, transient elastography","PeriodicalId":22516,"journal":{"name":"The Indonesian Biomedical Journal","volume":"20 17","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140436487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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The Indonesian Biomedical Journal
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