Neng Tine Kartinah

Cardiovascular diseases remain a leading cause of morbidity and mortality worldwide, underscoring the need to better understand cardiovascular physiology. A key aspect involves identifying regulatory molecules that govern metabolic shifts. Forkhead box protein O1 (FoxO1) has emerged as a potential regulator; however, its role and underlying mechanisms remain unclear. This study investigated FoxO1 in metabolic adaptation using Wistar rats divided into age groups (fetal, postnatal day 1, postnatal day 7, adult) and treatment groups (control, hypoxia, FoxO1 inhibitor, combination). Hypoxia (12–14% O₂) and FoxO1 inhibitor (AS1842856, 10 mg/kgBW/day) were administered accordingly. Parameters assessed included hypoxia inducible factor 1 α (HIF-1α), FoxO1 mRNA and protein, glucose transporter type 1 (GLUT1), glucose transporter type 4 (GLUT4), cluster of differentiation 36 (CD36), hexokinase, pyruvate dehydrogenase kinase isoform 4 (PDK4), phosphoenolpyruvate carboxykinase (PEPCK), lactic acid, malonyl-CoA, carnitine palmitoyltransferase 1 (CPT1), citrate synthase, cytochrome c, and adenosine triphosphate (ATP). ATP production increased with age, associated with higher FoxO1 expression and metabolic shifts. Hypoxia in fetal hearts reduced HIF-1α and FoxO1. FoxO1 inhibition elevated glycolytic and oxidative markers. In conclusion, FoxO1 regulates glycolysis and lipid metabolism, offering insights into cardiac adaptation to hypoxia and potential therapeutic strategies.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder associated with progressive aging-related alterations in multiple organs, including the skin. Nonetheless, the specific structural and molecular changes that cause skin aging in diabetes remain poorly understood in preclinical animal models. The present study aimed to establish a rat model of T2DM-induced skin aging and to investigate the relationship between matrix metalloproteinase-9 (MMP-9) expression and dermal extracellular matrix (ECM) remodeling in diabetic skin aging. A total of 12 male Sprague-Dawley rats, aged 8-9 weeks and weighing 180-250 g, were assigned to the control and T2DM groups. Rats in the T2DM group received an 8-week high-fat diet (45% fat calories) with 40% fructose, followed by low-dose streptozotocin (25 mg/kg, IP) injection to induce diabetes. Metabolic phenotype was validated using fasting blood glucose and a 2-hour post-glucose measurement. After 16 weeks, dorsal skin was collected for histological evaluation, including measurements of epidermal/dermal thickness, collagen area, and fibroblast counts, as well as molecular analysis. The MMP-9 was measured using a sandwich enzyme-linked immunosorbent assay. Diabetic rats developed sustained hyperglycemia and increased body weight, confirming a T2DM-like metabolic phenotype. Histological analysis demonstrated a significant increase in dermal thickness and a marked reduction in dermal collagen density in diabetic skin, whereas epidermal thickness and fibroblast counts were not significantly altered. The MMP-9 concentration in diabetic dermal homogenates was elevated compared with that in the control group. The current findings demonstrated that T2DM in rats was associated with early dermal extracellular matrix remodeling, characterized by increased MMP-9 levels, decreased collagen density, and dermal thickening, suggesting an association between chronic hyperglycemia and altered dermal matrix homeostasis.

Stunting, a common form of chronic undernutrition, is associated with impaired nutrient absorption and glucose transport. Hibiscus sabdariffa Linn. (roselle) contains bioactive flavonoids and anthocyanins that have the potential to regulate glucose transporter 1 (GLUT1). This study aimed to examine the effect of H. sabdariffa phytochemicals on GLUT1 regulation in the intestine, using the HT29 cell line as a model. An integrated approach combining in silico docking and in vitro validation was employed. Seven key phytochemicals were docked to GLUT1 using AutoDock Vina. Cytotoxicity was evaluated by MTT assay, and GLUT1 mRNA expression was analyzed by qPCR after treatment with sub-cytotoxic concentrations (≤ IC₅₀ = 17.2 µg/mL) for 24 and 48 hours. The results of the study revealed that among the isolated chemicals, Delphinidin-3-sambubioside and cyanidin-3-sambubioside showed the highest affinities (–10.3 and –9.8 kcal/mol, respectively). Treatment with H. sabdariffa resulted in a significant downregulation of GLUT1 expression to 0.68 ± 0.09-fold (p < 0.05) after 24 hours and 0.42 ± 0.07-fold (p < 0.01) after 48 hours. These findings indicate that H. sabdariffa phytochemicals have the potential to modulate intestinal glucose transport by suppressing GLUT1 expression. This research provides initial insights into the regulation of nutrient uptake through phytochemicals, which may be relevant to the mechanisms underlying stunting.

The coronavirus disease 2019 (COVID-19) pandemic has encouraged global vaccine research, yet vaccine effectiveness in the elderly remains a concern due to immunosenescence. The aim of this study was to compare the cytokine response elicited by an inactivated virus-based COVID-19 vaccine between elderly and young adults, focusing on key cytokines involved in cellular and humoral immunity: tumor necrosis factor-alpha (TNF-α), interleukin (IL)-2, IL-6, IL-10, and interferon-gamma (IFN-γ). A cross-sectional study was conducted in the Jakarta-Bogor region of Indonesia from January 2023 to December 2023. The study population was divided into two age cohorts: elderly (60-85 years) and younger adults (30-40 years). Blood samples were collected twice, after the first booster dose and four weeks after the second booster dose. Serum cytokine concentrations were measured using Luminex assays with microparticles conjugated to monoclonal antibodies against TNF-α, IL-2, IL-6, IL-10, and IFN-γ. Comparisons of the cytokine levels were conducted using Student's t-tests or Mann- Whitney U tests as appropriate. A total of 74 individuals were included, with 37 each in the elderly and young adult groups. The results showed significant differences in cytokine responses between the two age groups. After the first booster, the levels of IL-6 and IFN- γ were significantly higher in young adults compared to the elderly. After the second booster, the levels of IL-6 were still significantly higher in the young adult group compared to the elderly group (p = 0.001). Data indicated that after the second booster dose, the levels of TNF-α increased significantly in the young adult group only (p = 0.004), while the levels of IL-2 (p = 0.040) and IFN-γ (p = 0.006) increased in the elderly group only compared to after the first dose. IL-10 levels increased in both groups (both had p = 0.020). This study highlights that young adults had stronger pro-inflammatory responses, while the elderly relied more on IL-2 and IFN-γ for T-cell immunity, suggesting the need for vaccination strategies for the elderly to optimize immune responses.

The coronavirus disease 2019 (COVID-19) pandemic has encouraged global vaccine research, yet vaccine effectiveness in the elderly remains a concern due to immunosenescence. The aim of this study was to compare the cytokine response elicited by an inactivated virus-based COVID-19 vaccine between elderly and young adults, focusing on key cytokines involved in cellular and humoral immunity: tumor necrosis factor-alpha (TNF-α), interleukin (IL)-2, IL-6, IL-10, and interferon-gamma (IFN-γ). A cross-sectional study was conducted in the Jakarta-Bogor region of Indonesia from January 2023 to December 2023. The study population was divided into two age cohorts: elderly (60−85 years) and younger adults (30−40 years). Blood samples were collected twice, after the first booster dose and four weeks after the second booster dose. Serum cytokine concentrations were measured using Luminex assays with microparticles conjugated to monoclonal antibodies against TNF-α, IL-2, IL-6, IL-10, and IFN-γ. Comparisons of the cytokine levels were conducted using Student’s t-tests or Mann-Whitney U tests as appropriate. A total of 74 individuals were included, with 37 each in the elderly and young adult groups. The results showed significant differences in cytokine responses between the two age groups. After the first booster, the levels of IL-6 and IFN-γ were significantly higher in young adults compared to the elderly. After the second booster, the levels of IL-6 were still significantly higher in the young adult group compared to the elderly group (p=0.001). Data indicated that after the second booster dose, the levels of TNF-α increased significantly in the young adult group only (p=0.004), while the levels of IL-2 (p=0.040) and IFN-γ (p=0.006) increased in the elderly group only compared to after the first dose. IL-10 levels increased in both groups (both had p=0.020). This study highlights that young adults had stronger pro-inflammatory responses, while the elderly relied more on IL-2 and IFN-γ for T-cell immunity, suggesting the need for vaccination strategies for the elderly to optimize immune responses.

Telerehabilitation has the potential to help expand the reach of rehabilitation intervention. An online questionnaire-based Delphi method set out to develop a telerehabilitation guideline for patients in Indonesia with Long COVID. A Delphi panel comprised of 24 experts was selected from all relevant disciplines. Over two rounds of Delphi testing, panelists gave opinions and indicated their level of agreement with each recommendation. Key elements of consensus for a telerehabilitation guideline for patients with Long COVID includes: the benefit of telerehabilitation, types of rehabilitation intervention needed, methods of intervention, criteria for home-based self-exercise training, set-up of rehabilitation prescription, exercise monitoring, evaluation of rehabilitation intervention and duration of rehabilitation intervention. Further research is needed to determine the feasibility and effectiveness of this guideline.

Introduction In the wake of the unprecedented global COVID-19 pandemic, the development of effective vaccines is crucial. While multiple vaccines have been developed, evidence suggests that immune response may vary especially in older adults. Evaluation of COVID-19 immunogenicity in this vulnerable population needs to be explored. Methods Literature search was performed in databases including PubMed, ScienceDirect, and Scopus. The quality of studies was evaluated using the Cochrane Risk of Bias 2.0 and Newcastle Ottawa Scale for Cohort Studies. Results There are 10 studies included in this review. Two doses of the COVID-19 vaccine showed a significant increase in antibody titers (MD 221.48 AU/mL; 95% CI 109.16-333.80; p=0.0001). Subgroup analysis showed a dose-dependent relationship, with the highest amount of increase in MVC-COV19 at 25 mcg. The increase in anti-RBD IgG was also significant (MD 3.355 log 10 AU/mL; 95% CI 3.03-4.08; p=0.00001). S1 reactive T cells and anti-S1 IgG was not significantly increased after 2 doses of the vaccine. Conclusion Our study found that in general, the COVID-19 vaccine is effective in increasing several immune parameters. Measures to increase efficacy in this population such as a third dose or vaccine booster are needed to overcome age-related changes in immunity, thus enhancing the health of the elderly.

Background. Hyperglycemia is a major risk factor for endothelial dysfunction. Endothelial dysfunction is associated with the inability of endothelial cells to maintain homeostasis of the cardiovascular system. Regular exercise may be considered as an effective and low-cost nonpharmacological tool for improving vascular function, though there is no agreement on the best type of exercise. Objectives. To determine how high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) may prevent endothelial dysfunction under hyperglycemic conditions, and to compare these two interventions. Method. Twenty-four eight-week-old male Wistar rats were randomly assigned into four groups: healthy nonexercising control (C), hyperglycemic control (HG-C), hyperglycemic+HIIT (HG-IT), and hyperglycemic+MICT (HG-CT). Hyperglycemia was induced by a single injection of streptozotocin. Hyperglycemic animals were subjected to HIIT or MICT protocols six days a week for six weeks. Decapitation was performed the day after the exercise protocols were completed. The ascending aorta (until the abdominal artery) was examined. An enzyme-linked immunosorbent assay (ELISA) was used to measure the glucagon-likepeptide-1 (GLP-1), endothelial nitric oxide synthase (eNOS), and tumor necrosis factor-alpha (TNFα) levels. A colorimetric assay was used to measure superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels. Quantitative real-time polymerase chain reaction (PCR) was used to measure the expression of the receptor for advanced glycation end-products (RAGE) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Hematoxylin and eosin (H&E) staining was used to histologically analyze the aortas. Results. There was a significantly higher level of GLP-1 and lower expression of RAGE, NF-κB, and TNFα in the HG-IT and HG-CT group compared to the HG-C group. Microscopic examination of aortic tissue showed a better tissue arrangement in both treatment groups than in the HG-C group. Except for the MDA level, there were no significant differences in any of the measured parameters between the HG-IT and HG-CT groups. Conclusion. Under hyperglycemic conditions, both HIIT and MICT have a protective role against endothelial dysfunction.

Objective: This study aimed to test the hypothesis that Hibiscus sabdariffa Linn. Extract (HSE) would increase arcuate nucleus Lep-R, NPY, and white adipose tissue β3AR mRNA expression in DIO rats. This study also analyzed the potency of H. sabdariffa bioactive compounds as an activator of Lep-R and β3AR. Methods: Twenty-four male Sprague-Dawley rats were separated into four groups: Control (standard chow), DIO (HFD), DIO-Hib200 (HFD+HSE 200 mg/kg BW), and DIO-Hib400 (HFD+HSE400 mg/kg BW). HSE administration was administered orally for five weeks, once a day. Result: The administration of HSE significantly (P<0,05) increased the arcuate nucleus Lep-R expression, but not for the ARC NPY and WAT β3AR. The Lee index of DIO rats also significantly decrease (p<0,001 for a dose of 200 mg/kg BW and p<0,01 for a dose of 400 mg/kg BW) into the normal range (≤ 310). Among 39 bioactive compounds, 5-O-caffeoylshikimic acid has high free binding scores (-8,63) for Lep-R, and myricetin_3_arabinogalactoside has high free binding scores (-9,39) for β3AR. These binding predictions can activate Lep-R and β3AR. Conclusion: HSE increases leptin sensitivity and reduces obesity, and its bioactive compounds can activate the Lep-R and β3AR to regulate energy balance. HSE could be a potential therapeutic target for obesity.

The healthy Indonesia program with a family approach (PIS-PK) has not been implemented optimally. There are several obstacles and challenges in this program’s implementation, e.g., human resources. A community-based health information system (CBHIS) is a strategic approach to obtain data and information at the population level by directly involving cadres and the community. A project with the CBHIS approach was implemented in Kasemen Village, Serang, Banten Province, Indonesia to support the PIS-PK program. The study aimed to determine the population’s health status according to the healthy family index through the CBHIS approach. The data of healthy family indicators in the village were collected by cadres using a mHealth application. Overall, 1316 households consisting of 5312 residents were registered. The analysis results of the healthy family index showed that most families in the Kasemen subdistrict were pre-healthy (64.2%), almost one third were unhealthy (27.8%) and only a small proportion were healthy (8%). Assessing the healthy family index through the CBHIS approach can support decision-making at the community level, thereby determining the magnitude of family health problems and providing appropriate interventions to improve community health status. Well-trained cadres equipped with better electronic data collection tools may be an alternative to community-based data collection.