Syarifah Dewi

Cyclooxygenase-2 (COX-2) is a key enzyme in prostanoid production and is best known as a mediator of the inflammatory response. Beyond this well-established role, COX-2 also contributes to tissue regeneration by promoting neovascularization and supporting stem cell recruitment, proliferation, and differentiation. Despite this, research on harnessing the COX-2 pathway as a therapeutic tool, rather than solely as a target for inhibition, remains limited, presenting a promising avenue for future studies. In this review, we summarize current insights from both in vitro and in vivo models into COX-2 signaling in tissue regeneration, focusing on molecular mechanisms through which its downstream mediators, especially prostaglandin (PGE2), regulate vascular formation, tissue growth, and stem cell function. We also briefly outline the dual nature of these processes, which can either facilitate repair or drive pathological outcomes, and discuss emerging strategies for achieving controlled therapeutic applications.

The intricate interplay between physical exercise, mitochondrial function, and lipid metabolism has garnered considerable attention, particularly in the context of energy balance and overall metabolic health. Studies comparing which exercise has the most beneficial effects on mitochondrial activity and lipid metabolism are still scarce. This study aimed to investigate the effects of anaerobic and aerobic exercise on mitochondrial activity and biogenesis, as well as lipid metabolism, in healthy young adults. Eighteen subjects (young male adults) were randomly divided into two groups: anaerobic exercise group (n=9) and aerobic exercise group (n=9) for 4 weeks. Blood samples were collected before and after training and the whole blood was separated into leucocyte cells and plasma. Lysate from leucocyte cells was used for the measurement of mitochondrial function, including succinate dehydrogenase (SDH) activity, peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α), and ATP levels. Blood plasma was used for the measurement of lipid metabolism, including HDL cholesterol, adiponectin, and free fatty acids levels. This study demonstrated that SDH activity increases significantly after aerobic exercise (122%) compared to before exercise, although it is not supported by the results of PGC-1a and ATP levels. This may be because these parameters are measured in the blood (leukocyte cells). Adiponectin levels increase significantly after anaerobic exercise (43.8%) while free fatty acid levels increase significantly after aerobic exercise (104%) compared to before exercise. The results of HDL cholesterol levels found a tendency to increase both after aerobic (12%) and anaerobic exercise (10%) compared to before exercise. We conclude that aerobic exercise gives the best impact on increasing mitochondrial activity systemically (significantly increasing SDH activity), supported by the significant increase in free fatty acid levels in the blood, which reflects that lipolysis is increased.

Proteostasis, the integrated network regulating protein synthesis, folding, trafficking, and degradation, is essential for cellular function and organismal health. Reduced oxygen availability disrupts proteostasis through increased reactive oxygen species (ROS) production, endoplasmic reticulum (ER) stress, impaired ATP-dependent protein folding, and altered chaperone expression. In cancer, tumor cells exploit chronic unfolded protein response (UPR) signaling to enhance survival, angiogenesis, and therapeutic resistance. Inhibition of IRE1α and PERK pathways has shown efficacy in preclinical models, though clinical translation faces challenges including off-target toxicity. In neurodegenerative diseases—Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis—chronic hypoxia accelerates protein aggregate accumulation through oxidative modifications and impaired autophagy-lysosome function. Therapeutic strategies targeting γ-secretase, BACE1, and protein clearance pathways have demonstrated limited clinical success despite mechanistic rationale. Understanding hypoxia-induced proteostasis failure may inform therapeutic development, though significant obstacles remain in translating preclinical findings to effective treatments for cancer and neurodegenerative diseases.

Background/Objectives: Obesity increases reactive oxygen species (ROS), thereby triggering oxidative stress. Coriander seeds contain polyphenolic compounds that act as natural antioxidants to reduce oxidative stress. Coriander seed ethanolic extract has been proven to decrease malondialdehyde and increase catalase activity in the liver of high-fat-diet-fed rats. Thus, coriander seeds are thought to protect against obesity-induced oxidative liver damage; however, their molecular mechanism has not been revealed. Nuclear factor erythroid 2-related factor 2 (Nrf2) and Forkhead Box O3 (FOXO3) are transcription factors involved in cellular antioxidant regulation (e.g., superoxide dismutase/SOD, glutathione peroxidase/GPx expression, and reduced glutathione/GSH) that are negatively regulated by Kelch-like ECH-associated Protein 1 (Keap1) and 14-3-3 protein to maintain cellular homeostasis. This study aimed to analyze the regulation of antioxidant expression through in silico and in vivo experiments. Methods: The in silico study assessed the potential of coriander seed ethanolic extract to inhibit Keap1 and 14-3-3 using molecular docking. Then, the drug-likeness, pharmacokinetics, and toxicity of the top three compounds were analyzed. Meanwhile, the in vivo study investigated how the coriander seed ethanolic extract impacted the level of Nrf2, FOXO3, and their downstream effectors (T-SOD, MnSOD, GPx, and GSH). The in vivo study involved five groups of rats with obesity induced by a high-fat diet that were fed with 100 mg/kgBW coriander seed ethanolic extract for 12 weeks. Results: The in silico tests revealed that shionoside b had the highest potential to inhibit Keap1 (ΔG = −8.90 kcal/mol; Ki = 298.01 nM) and 14-3-3 protein (ΔG = −6.85 kcal/mol; Ki = 9.46 µM). The in vivo tests showed that the Nrf2, FOXO3, MnSOD, and GPx mRNA expression was significantly different between the groups (p < 0.05). Meanwhile, T-SOD, MnSOD, GPx, and GSH activity were not significantly different between the groups (p > 0.05). Nrf2 was significantly correlated with FOXO3 as well as the T-SOD, MnSOD, and GPx activity, and FOXO3 was significantly correlated with the T-SOD, MnSOD, GPx, and GSH activity. Conclusions: In obese rats, coriander seeds tend to increase Nrf2 and FOXO3 expression, which is positively correlated with their downstream enzymatic and nonenzymatic antioxidant activity. This is possibly due to the interaction between the coriander seed phytoconstituents and protein inhibitors (Keap1 and 14-3-3), which contribute to the stability and nuclear mobilization of Nrf2 and FOXO3.

Introduction: Exercise, despite its well-established benefits, can lead to several adverse effects, including muscle injuries and significant elevations in liver enzymes. Objective: This study investigated the effects of aerobic and anaerobic exercise on serum biomarkers of muscle injury (lactate, LDH, CK) and liver function (ALT, AST). Methodology: Eighteen healthy young male adults were randomized to a 4-week aerobic (n=9) or anaerobic (n=9) exercise program. Blood samples were collected pre- and post-intervention to measure the aforementioned biomarkers. Results: Both aerobic (p=0.028) and anaerobic (p=0.027) exercise significantly increased LDH activity. Lactate levels did not significantly change in either group. CK activity significantly decreased after aerobic exercise (p=0.003) but not after anaerobic exercise (p=0.231). No significant changes in ALT or AST activity were observed in either group. Discussion: The observed LDH increase aligns with existing literature, while the contrasting CK response (decrease after aerobic, no change after anaerobic exercise) highlights differing impacts on muscle integrity. Consistent with prior research, no significant changes in liver enzymes (ALT/AST) were observed, suggesting no exercise-induced liver stress. Conclusions: These findings reveal distinct effects of aerobic and anaerobic exercise on muscle biomarkers, with only aerobic exercise significantly decreasing CK levels, while both affected LDH. Importantly, no evidence of exercise-induced liver stress was observed based on ALT/AST levels.

Obesity is a serious health problem that is often caused by consuming a high-fat diet (HFD) and exacerbated by a sedentary lifestyle. Non-alcoholic fatty liver disease (NAFLD), a condition where triacylglycerol (TAG) is accumulated in the liver as lipid droplets, could be found as a complication associated with obesity. The main objective of this study was to analyze the effect of coriander seed ethanolic extract (CE) treatment on liver TAG synthesis and lipid droplets in HFD-induced obese rats. A total of twenty-five Wistar rats were divided into the following five groups: control group, control-CE group, HFD-CE group, obese group, and obese-CE group. Obesity induction was conducted for the first 12 weeks followed by CE treatment for the second 12 weeks and then the rats were sacrificed, and the liver organ was collected. We measured the TAG level, the level of peroxisome proliferator-activated receptor gamma (PPAR-γ) protein, the relative mRNA expression of PLIN2 and DGAT2, also histology analysis of lipid droplets in the liver. The results of this study demonstrated that the TAG levels in the liver of the obese group were associated with the increase in DGAT2 and PLIN2 mRNA expression compared to the control group. The histology section also showed a large amount of lipid droplets in the obese group. The results also showed that the CE treatment, either in the HFD-CE or the obese-CE group, generated the reduction of liver TAG levels, mRNA expression of DGAT2 and PLIN2, and lipid droplets in the liver compared to the control group. In conclusion, the results showed that CE treatment in obese or HFD-induced rats could suppress lipid droplets in the liver by decreasing triacylglycerol synthesis.

As the altitude increases, the partial pressure of oxygen will decrease and cause hypobaric hypoxia conditions. During hypoxia, the anaerobic glycolysis will be activated, which is facilitated by the lactate dehydrogenase (LDH) enzyme. This study aimed to analyze the LDH-specific activity in rat muscle and liver tissue, as well as lactate and glucose levels in blood plasma after intermittent hypobaric hypoxia exposure. Twenty-five Wistar rats were divided into five groups: one control group and four hypobaric hypoxia (HH) exposure groups consisting of group 1 (1× HH), group 2 (2× HH), group 3 (3× HH), and group 4 (4× HH) with a range of 7 days between exposure. This study found that LDH-specific activity increased in muscle tissues in group 1, but then decreased in the intermittent group (groups 2–4). The change in LDH-specific activity in muscle tissues was similar to the change in lactate plasma levels. Interestingly, in liver tissues, there was a slight increase in the LDH-specific activity in group 1, and it started to increase significantly in group 2 and kept increasing in groups 3 and 4. The change in LDH-specific activity in liver tissues was similar to the change in glucose plasma level. We conclude that the LDH activity in muscle tissue contributes to lactate plasma levels, but the LDH activity in liver tissue contributes to maintaining glucose plasma after intermittent hypobaric hypoxia exposures. This finding could be implemented in individuals who experience intermittent hypoxia exposures or in various diseases with hypoxic conditions as their pathogenesis

In December 2022, the Indonesian Ministry of Health projected that rare diseases might affect 8–10% of the population, equating to approximately 27 million people. These diseases, often congenital, are linked to genetic inheritance or mutations, leading to structural or functional defects. Despite advancements in diagnostic and treatment methods, many rare diseases remain challenging for healthcare practitioners. RNA interference (RNAi) presents a promising therapeutic approach by enabling the selective inhibition of genes responsible for genetic disorders. RNAi employs small RNA molecules, such as small interfering RNA (siRNA) and microRNA (miRNA), to bind specific mRNA molecules and prevent their translation into proteins. Current research showed that RNAi-based therapies have the potential to treat various genetic diseases, including acute hepatic porphyria (AHP) and primary hyperoxaluria type 1 (PH1). However, the mechanisms of RNAi in hereditary disorders like AHP and PH1 require further documentation. RNAi offers several advantages, including gene-specific targeting, versatility in treating diverse genetic disorders, and scalability for mass production. Nonetheless, challenges remain, such as side effects, difficulties in targeting specific cells, and high development cost. Despite these obstacles, RNAi-based therapy holds significant potential for revolutionize the treatment of genetic disorders.

The proportion of elderly individuals is rising globally, and data have shown that as high as 8% of the elderly community suffer from malnutrition. Protein energy malnutrition has shown to elevate morbidity and mortality risk in the elderly; therefore, protein and energy supplement are needed for the elderly populations to create healthy conditions. This chapter describes about general structure of protein, protein turnover, amino acid metabolism including metabolism in the elderly, protein change in aging, supplementation of amino acid as well as vitamin and mineral for the elderly. The discussion in this section aims to provide a general description of protein, amino acids, changes in amino acid metabolism in the elderly, and the benefits of supplementing amino acids as well as vitamins and minerals for the elderly. Keywords Elderly Protein Metabolism Amino acid Supplementation Vitamin Mineral