BackgroundUric acid (UA) plays important roles in inducing renal inflammation, intra-renal vasoconstriction and renal damage. Endothelin-1 (ET-1) is a well-known profibrotic factor in the kidney and is associated with fibroblast expansion. We examined the role of hyperuricemia conditions in causing elevation of ET-1 expression and kidney injury.MethodsHyperuricemia was induced in mice using daily intraperitoneal injection of uric acid 125 mg/Kg body weight. An NaCl injection was used in control mice. Mice were euthanized on days-7 (UA7) and 14 (UA14). We also added allopurinol groups (UAL7 and UAL14) with supplementation of allopurinol 50 mg/Kg body weight orally. Uric acid and creatinine serum were measured from blood serum. Periodic Acid Schiff (PAS) and Sirius Red staining were done for glomerulosclerosis, tubular injury and fibrosis quantification. mRNA expression examination was performed for nephrin, podocin, preproEndothelin-1 (ppET-1), MCP-1 and ICAM-1. PDGFRβ immunostaining was done for quantification of fibroblast, while α-SMA immunostaining was done for localizing myofibroblast. Western blot analysis was conducted to quantify TGF-β1, α-SMA and Endothelin A Receptor (ETAR) protein expression.ResultsUric acid and creatinine levels were elevated after 7 and 14 days and followed by significant increase of glomerulosclerosis and tubular injury score in the uric acid group (p < 0.05 vs. control). Both UA7 and UA14 groups had higher fibrosis, tubular injury and glomerulosclerosis with significant increase of fibroblast cell number compared with control. RT-PCR revealed down-regulation of nephrin and podocin expression (p < 0.05 vs. control), and up-regulation of MCP-1, ET-1 and ICAM-1 expression (p < 0.05 vs. control). Western blot revealed higher expression of TGF-β1 and α-SMA protein expression. Determination of allopurinol attenuated kidney injury was based on reduction of fibroblast cell number, inflammation mediators and ppET-1 expression with reduction of TGF-β1 and α-SMA protein expression.ConclusionsUA induced glomerulosclerosis, tubular injury and renal fibrosis with reduction of podocyte function and inflammatory mediator elevation. ET-1 and fibroblast expansion might modulate hyperuricemia induced renal fibrosis.

BackgroundDiabetes Mellitus (DM) is one of the metabolic diseases which leads to fatty tissue injury, and consequently inducing lipotoxicity and cellular senescence. This condition contributes to endothelial dysfunction with chronic inflammation and organ damage. Heparanase which has a role in disrupting endothelial surface layer (glycocalyx) may promote endothelial Nitric oxide synthase (eNOS) reduction and inflammation. However, its relationship with DM and organ injury has not been fully elucidated yet. This study aimed to determine how heparanase from fatty tissue may contribute to endothelial dysfunction and inflammation in patients with hyperglycemia and in a hyperglycemia model in rats.MethodsThis population study with a cross-sectional design was conducted with 28 subjects without diagnosis and medication of DM. Fasting blood glucose levels, lipid profile, heparanase protein, MCP-1 protein and HbA1c were quantified. In vivo study was performed with a diabetic model in Wistar rats induced with streptozotocin 60 mg/kg body weight by single intraperitoneal injection. Rats were euthanized after 1 month (DM1 group, n = 6), 2 months (DM2 group, n = 6) and 4 months (DM4 group, n = 6). White Adipose Tissue (WAT) was harvested from visceral fat. Real Time and Reverse Transcriptase-PCR (RT-PCR) was done to quantify expressions of heparanase, MCP-1, eNOS, IL-6 and p-16 (senescence). Immunostaining was performed to localize MCP-1 and macrophage (CD68). Western blot tests were used to examine eNOS, MCP-1 and heparanase protein expression.ResultsThis study revealed associations between blood glucose levels with higher HbA1c, LDL, cholesterol, heparanase and MCP-1. The in vivo study also revealed lipid levels as the source of Heparanase and MCP-1 mRNA and protein expressions. This finding was associated with inflammation, cellular senescence and macrophage infiltration in fat tissue based on immunostaining and qRT-PCR analysis. RT-PCR revealed significantly lower expression of eNOS and higher expression of IL-6 in DM groups compared to the control group.ConclusionHeparanase upregulation in fat tissue was associated with endothelial injury and inflammation in hyperglycemia conditions.

BACKGROUND: In March 2020, nursing schools in Indonesia were forced to abruptly shift from face-to-face learning to fully online learning due to the COVID-19 pandemic. Before the pandemic, fully online learning was still not widely used in Indonesian nursing education. AIM: This study aimed to identify barriers in online learning among Indonesian nursing students during the COVID-19 pandemic. METHODS: This study used a cross-sectional design and involved 530 undergraduate nursing students from five universities in Indonesia participated in this study. The authors sent an online self-administered questionnaire to nursing students from October to December 2020. The questionnaire consisted of four sections to obtain the following data: (1) Sociodemographic characteristic, (2) information about online learning, (3) platform used for online learning, and (4) perceived barriers in online learning. Descriptive statistics were used to analyze data with frequency distribution, percentages, means, and standard deviations. RESULTS: Nursing students in Indonesia were confronted by various barriers during the implementation of abrupt online learning in the current pandemic situation. Most frequently barriers encountered by nursing students during online learning were high costs for online learning, poor internet connection, lack of motivation toward online learning, lack of skill in using the online learning platforms, and lack of training and assistance to use the platforms. CONCLUSION: High cost for online learning, poor internet connection, low learning motivation, lack of skill in using the online learning platforms, and lack of training and assistance to use the platforms were identified as the most frequent barriers encountered by nursing students.

Background Hypospadias, the most frequent congenital male external genitalia abnormality, is usually associated with curvature of the ventral penis, i.e. chordee. Abnormality of darto tissue has been suggested as the pathophysiology of chordees. Collagen is one of the most abundant fibrous proteins within the extracellular matrix. In this study, we determined the expression of collagen 1 (COL1A1) and COL6A1 in patients with hypospadias and associated them with the severity of penile curvature. Methods We included 60 children < 18 years old, consisting of 20 distal hypospadias, 20 proximal hypospadias patients, and 20 controls in our institution from 2017 – 2020. The expression of COL1A1 and COL6A1 in darto tissue was determined by reverse-transcriptase polymerase chain reaction (qPCR). The penile curvature severity was classified as mild (< 30 degrees), moderate (30–60 degrees), and severe (> 60 degrees). Results qPCR showed that COL1A1 and COL6A1 expression was significantly downregulated in the distal (0.88 (0.38–2.53) and 0.54 (0.16–4.35), respectively) and proximal 0.76 (0.33–2.57) and 0.57 (0.18–1.38), respectively) hypospadias groups compared to controls (1.85 (0.24–4.61) and 0.93 (0.17–4.06), respectively) with p-values of 0.024 and 0.018, respectively. Furthermore, there was a moderate correlation between COL1A1 and COL6A1 expression (r = 0.458, p < 0.0001). Interestingly, COL1A1 and COL6A1 were also significantly downregulated in the moderate and severe chordee groups compared to the mild chordee groups, with p-values of 0.003 and 0.037, respectively. Conclusions Aberrant COL1A1 and COL6A1 expression might affect abnormalities in darto tissue and penile curvature severity in hypospadias patients.

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