Background: Diabetes mellitus (DM) is among the most common risk factors for cardiovascular disease in the world with prevalence of more than 500 million population in 2021. Cardiac fibrosis with its complex process has been hypothesized as one of the mechanisms explaining development of heart failure in diabetic patients. Recently, the biomolecular mechanism of cardiac fibrosis in the hyperglycemia setting has been focusing around transforming growth factor β-1 (TGFβ-1) as a major factor. However, there is interplay role of several factors including microRNAs (miRNAs) which acts as a potential regulator of cardiac fibrosis connected with TGFβ-1. In this review, we explored interplay role of several factors including microRNAs which acts as a potential regulator of cardiac fibrosis connected with TGFβ-1 in diabetes mellitus. This narrative review included articles from the PubMed and Science Direct databases published in the last 10 years (2012–2022). Main text: In diabetic patients, excessive activation of myofibroblasts occurs and triggers pro-collagen to convert into mature collagen to fill the cardiac interstitial space resulting in a pathological process of extracellular matrix remodeling. The balance between matrix metalloproteinase (MMP) and its inhibitor (tissue inhibitor of metalloproteinase, TIMP) is crucial in degradation of the extracellular matrix. Diabetes-related cardiac fibrosis is modulated by increasing level of TGF-β1 mediated by cellular components, including cardiomyocyte and non-cardiomyocyte cells involving fibroblasts, vascular pericytes smooth muscle cells, endothelial cells, mast cells, macrophages, and dendritic cells. Several miRNAs such as miR-21, miR-9, miR-29, miR-30d, miR-144, miR-34a, miR-150, miR-320, and miR-378 are upregulated in diabetic cardiomyopathy. TGF-β1, together with inflammatory cytokines, oxidative stress, combined sma and the mothers against decapentaplegic (smad) protein, mitogen-activated protein kinase (MAPK), and microRNAs, is interconnectedly involved in extracellular matrix production and fibrotic response. In this review, we explored interplay role of several factors including microRNAs which acts as a potential regulator of cardiac fibrosis connected with TGFβ-1 in diabetes mellitus. Conclusions: Long-term hyperglycemia activates cardiac fibroblast via complex processes involving TGF-β1, miRNA, inflammatory chemokines, oxidative stress, smad, or MAPK pathways. There is increasing evidence of miRNA’s roles lately in modulating cardiac fibrosis.

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

Stunting remains a major public health threat among children under five years of age in developing countries, including Indonesia. Studies have shown that water, sanitation, and hygiene (WASH) interventions are essential for reducing the prevalence of the disease. This study aimed to identify WASH-related risk factors associated with stunting among under-fives. This hospital-based cross-sectional study included 133 randomly sampled children who attended outpatient clinics or were admitted for treatment at Rumah Sakit Umum Daerah (Regional Public Hospital-RSUD) dr. Zainoel Abidin Banda Aceh between April and May 2024. Data were collected using structured questionnaires and anthropometric measurements. The bivariate chi-square test and multivariate logistic regression analysis were used to analyze the data. Statistical significance was set at P < 0.05, with a 95% confidence interval (CI). The results showed that the prevalence of stunting was 35.3% among children under fives attended RSUD dr. Zainoel Abidin Banda Aceh. Bivariate analysis showed that stunting was associated with the main source of drinking water {p=0.04, OR 2.29 (95% CI = 1.07 – 4.89). Multivariate regression analyses revealed the WASH-related risk factor for stunting, which was the child’s fecal disposal {p= 0.03, OR= 0.26 (95% CI 0.08 – 0.85)}. In conclusion, child’s fecal disposal is a WASH-related risk factor for stunting among children who attended RSUD dr. Zainoel Abidin Banda Aceh. This risk factor can be modified through health policies that consider WASH interventions to manage stunting prevalence.

Preterm infants, born before the 37-week gestation period, have limited storage for nutrients at birth and are vulnerable to poor feeding, severe nutritional deficits and growth retardation. The immature gastrointestinal system leads preterm infants to experience a delay in initiating enteral nutrition. Inappropriate feeding can cause acute and long-term morbidity, prolonged hospitalization and increased treatment cost. Generally, preterm infants that are born after 32 weeks of gestation without severe comorbidities do not have dysphagia and should start oral feeding soon after birth. Preterm infants should have well-developed sucking-swallowing-breathing coordination by 32–34 weeks of gestational age. However, some infants take days or weeks to master the skill. The oral feeding development involves forkhead box protein 2 (FOXP2)-expressing neurons that are found in the deep layers of the cortex, basal ganglia, parts of the thalamus and Purkinje cells of the cerebellum. In mammals, these areas belong to the brain network circuits working for motor coordination in learning and acquiring sensorimotor skills. This review aimed to describe the role of FOXP2 in oral-motor skills in preterm infants, including oral feeding, sucking-swallowing-breathing coordination and language development. The oral-motor skills development could be an early predictor for language delay in premature infants, representing a vulnerable group susceptible to such delays.

Complex revascularization strategies, particularly complete revascularization, are controversial in coronary artery disease (CAD), and data supporting routine revascularization in stable CAD is lacking. The importance of percutaneous coronary intervention (PCI) in CAD and N-terminal pro-brain natriuretic peptide (NT-proBNP), which has been studied as a predictor of major advanced cardiovascular events (MACE) in CAD patients, still requires further research. The aim of this study was to determine the association between NT-proBNP levels and the number of stents with MACE incidence in CAD cases. A prospective cohort study was conducted in both types of CAD (acute coronary syndrome (ACS) and chronic coronary syndrome (CCS)). The NT-proBNP levels were measured pre- and post-PCI using fluorescence immunoassay, while MACE was assessed three months post-PCI. The Student t-test was used to compare the levels of NT-proBNP between pre- and post-PCI and between those who had MACE and did not; both in patients treated with single or multiple stenting groups. A total of 32 CAD patients were recruited, consisting of 20 ACS cases and 12 CCS cases. NT-proBNP levels post-PCI increased significantly in both ACS and CCS patients compared to pre-PCI either among those treated with single and multiple stentings. MACE occurred in 4 (12.5%) out of a total of 32 patients, all of which occurred in ACS patients treated with multiple stentings. Those who had MACE had higher post-PCI NT-proBNP levels compared to those who did not have MACE (23,703.50 vs 11,600.17 pg/mL, p=0.013). This study highlights the association between elevated NT-proBNP levels and multiple stenting with the presence of MACE in CAD patients, particularly in ACS cases.