Carotenoids in red fruit (Pandanus conoideus Lam.) have a potential role as an anti­pigmentation agent (Review).

Melasma is a persistent condition characterized by excessive melanin production in the skin. The management of melasma necessitates a protracted treatment duration, which is associated with diminished levels of patient satisfaction. One effective strategy for mitigating occurrence of melasma is consumption of nutricosmetics with depigmentation properties. The present review aimed to investigate the potential of red fruit as a depigmentation agent. Carotenoids serve a crucial role in human nutrition as a precursor to vitamin A. Carotenoids serve as scavengers of reactive oxygen species generated by ultraviolet radiation. Carotenoids promote skin health. Red fruit, a fruit originating from Papua (Indonesia) has anti-pigmentation properties associated with its ability to block melanogenesis through various protein pathways such as PKA, ERK, and AKT signaling pathways. The consumption of food rich in carotenoids, such as red fruit, has advantageous properties to reduce hyperpigmentation and skin brightening.

Understanding the Roles of Selenium on Thyroid Hormone-Induced Thermogenesis in Adipose Tissue.

Brown adipose tissue (BAT) and white adipose tissue (WAT) are known to regulate lipid metabolism. A lower amount of BAT compared to WAT, along with adipose tissue dysfunction, can result in obesity. Studies have shown that selenium supplementation protects against adipocyte dysfunction, decreases WAT triglycerides, and increases BAT triiodothyronine (T3). In this review, we discuss the relationship between selenium and lipid metabolism regulation through selenoprotein deiodinases and the role of deiodinases and thyroid hormones in the induction of adipose tissue thermogenesis. Upon 22 studies included in our review, we found that studies investigating the relationship between selenium and deiodinases demonstrated that selenium supplementation affects the iodothyronine deiodinase 2 (DIO2) protein and the expression of its associated gene, DIO2, proportionally. However, its effect on DIO1 is inconsistent while its effect on DIO3 activity is not detected. Studies have shown that the activity of deiodinases especially DIO2 protein and DIO2 gene expression is increased along with other browning markers upon white adipose tissue browning induction. Studies showed that thermogenesis is stimulated by the thyroid hormone T3 as its activity is correlated to the expression of other thermogenesis markers. A proposed mechanism of thermogenesis induction in selenium supplementation is by autophagy control. However, more studies are needed to establish the role of T3 and autophagy in adipose tissue thermogenesis, especially, since some studies have shown that thermogenesis can function even when T3 activity is lacking and studies related to autophagy in adipose tissue thermogenesis have contradictory results.

MitoTEMPOL modulates mitophagy and histopathology of Wistar rat liver after streptozotocin injection.

Objectives: This study aims to explore the effect of mitoTEMPOL on histopathology, lipid droplet, and mitophagy gene expression of Wistar rat's liver after injection of streptozotocin (STZ). Materials and Methods: Twenty male Wistar rats were divided into 4 groups: Control (n=5); 100 mg/kg BW/day mitoTEMPOL orally (n=5); 50 mg/kg BW STZ intraperitoneal injection (n=5); and mitoTEMPOL+STZ (n=5). STZ was given a single dose, while mitoTEMPOL was given for 5 weeks after 1 week of STZ injection. Histopathological appearance, lipid droplets, mitophagy, and autophagy gene expression were examined after the mitoTEMPOL treatment. Results: We found metabolic zone shifting that might be correlated with the liver activity of fatty acid oxidation in the STZ group, a decrease of lipid droplets in mitoTEMPOL and mitoTEMPOL + STZ compared with Control and STZ groups were found in this study. We also found significant changes in PINK1, Parkin, BNIP3, Mfn1, and LC3 gene expression, but no difference in Opa1, Fis1, Drp1, and p62 gene expression, suggesting a change of mitochondrial fusion rather than mitochondrial fission correlated with mitophagy. Conclusion: All this concluded that mitoTEMPOL could act as a modulator of mitophagy and metabolic function of the liver, thus amplifying its crucial role in preventing mitochondrial damage in the liver in the early onset of diabetes mellitus.

The Role of Exercise-Induced Reactive Oxygen Species (ROS) Hormesis in Aging: Friend or Foe.

Reactive oxygen species (ROS) are oxygen derivatives that arise intrinsically from the oxidative phosphorylation process and extrinsically as a response to xenobiotics and pollution. ROS is involved in various conditions such as exercise, aging, inflammation, and neurodegenerative diseases. In the aging process, increased cellular senescence and decreased endogenous antioxidants also occur. Meanwhile, physical activity, specifically exercise, can modulate ROS. The impact of exercise on ROS varies from harmful to beneficial and depends on the type of exercise as they induce different types of ROS. Long-term exercise regulates signaling pathways that enhance antioxidant defense systems and control ROS production. This review will discuss studies on how exercise can regulate ROS and which type of exercise has a role in delaying the aging process. This review also exposes the impact of nutraceutical antioxidant agents that likely enhance the benefit of exercise. The nutraceutical antioxidants agents that likely enhance the benefit of exercise are creatine, whey, and ascorbic acid. Exercise is rewarding for the aging population concerning increasing their quality of life. Special consideration to exercise needs to be given to the type of exercise, and the exercise must be done continuously.

Potential role of ß-carotene-modulated autophagy in puerperal breast inflammation (Review).

Puerperal breast inflammation is common in the first 6-8 weeks postpartum, and without proper management, may lead to a decrease in breastmilk production and early cessation of breastfeeding. Recent studies showed that carotenoids decrease the severity of puerperal breast inflammation. This article summarizes the significant findings on ß-carotene with a potential role as an autophagy modulator in puerperal breast inflammation. Puerperal milk stasis causes an increase in inflammatory cytokines and inflammatory cells, leading to reactive oxygen species (ROS) activation that causes oxidative damage to mammary glands and affects breast milk secretion. ß-carotene has an anti-inflammatory effect related to its ROS-scavenging activity and modulates autophagy, thus stimulating the removal of damaged cellular structures and supporting milk gland survival. ß-carotene modulates autophagy through phosphorylation of NF-κB, JNK, p38, Akt, and Nrf2, affects the ratio of Microtubule-associated protein 1A/1B-light chain 3 (LC3)-II/LC3-I, and has a role in the regulation of the JAK2/STAT3, PI2K/Akt/mTOR and AMPK pathways. Although the in vitro and in vivo studies showed promising results, further studies on humans are required to better conclude the potential role of ß-carotene in managing puerperal breast inflammation.

MitoTEMPOL Inhibits ROS-Induced Retinal Vascularization Pattern by Modulating Autophagy and Apoptosis in Rat-Injected Streptozotocin Model.

Diabetic retinopathy leads to retinal malfunction, blindness, and reduced quality of life in adult diabetes patients. The involvement of reactive oxygen species (ROS) regulation stimulated by high blood glucose levels opens the opportunity for ROS modulator agents such as MitoTEMPOL. This study aims to explore the effect of MitoTEMPOL on ROS balance that may be correlated with retinal vascularization pattern, autophagy, and apoptosis in a streptozotocin-induced rat model. Four groups of male Wistar rats (i.e., control, TEMPOL (100 mg/kg body weight [BW]), diabetic (streptozotocin, 50 mg/kg BW single dose), and diabetic + TEMPOL; n = 5 for each group) were used in the study. MitoTEMPOL was given for 5 weeks, followed by funduscopy, and gene and protein expression were explored from the rat's retina. Streptozotocin injection decreased bodyweight and increased food and water intake, as well as fasting blood glucose. The results showed that MitoTEMPOL reduced retinal vascularization pattern and decreased superoxide dismutase gene expression and protein carbonyl, caspase 3, and caspase 9 protein levels. A modulation of autophagy in diabetes that was reversed in the diabetic + TEMPOL group was found. In conclusion, MitoTEMPOL modulation on autophagy and apoptosis contributes to its role as a potent antioxidant to prevent diabetic retinopathy by inhibiting ROS-induced retinal vascularization patterns.

Potential Role of Exercise in Regulating YAP and TAZ During Cardiomyocytes Aging.

Adaptation of cardiac muscle to regular exercise results in morphological and structural changes known as physiological cardiac hypertrophy, to which the Hippo signaling pathway might have contributed. Two major terminal effectors in the Hippo signaling pathway are Yes-associated protein (YAP) and its homolog transcriptional coactivator with PDZ-binding motif (TAZ). The latest studies have reported the role of YAP and TAZ in different life stages, such as in fetal, neonatal, and adult hearts. Their regulation might involve several mechanisms and effectors. One of the possible coregulators is exercise. Exercise plays a role in cardiomyocyte hypertrophic changes during different stages of life, including in aged hearts. YAP/TAZ signaling pathway has a role in physiological cardiac hypertrophy induced by exercise and is associated with cardiac remodelling. Thus, it can be believed that exercise has roles in activating the signaling pathway of YAP and TAZ in aged cardiomyocytes. However, the studies regarding the roles of YAP and TAZ during cardiomyocyte aging are limited. The primary purpose of this review is to explore the response of cardiovascular aging to exercise via signaling pathway of YAP and TAZ.

Type, Intensity, and Duration of Exercise as Regulator of Gut Microbiome Profile.

ABSTRACT: Gut microbiome profile is related to individual health. In metabolic syndrome, there is a change in the gut microbiome profile, indicated by an increase in the ratio of Firmicutes to Bacteroidetes. Many studies have been conducted to determine the effect of exercise on modifying the gut microbiome profile. The effectiveness of exercise is influenced by its type, intensity, and duration. Aerobic training decreases splanchnic blood flow and shortens intestinal transit time. High-intensity exercise improves mitochondrial function and increases the essential bacteria in lactate metabolism and urease production. Meanwhile, exercise duration affects the hypothalamic-pituitary-adrenal axis. All of these mechanisms are related to each other in producing the effect of exercise on the gut microbiome profile.

The Role of Autophagy Modulated by Exercise in Cancer Cachexia.

Cancer cachexia is a syndrome experienced by many patients with cancer. Exercise can act as an autophagy modulator, and thus holds the potential to be used to treat cancer cachexia. Autophagy imbalance plays an important role in cancer cachexia, and is correlated to skeletal and cardiac muscle atrophy and energy-wasting in the liver. The molecular mechanism of autophagy modulation in different types of exercise has not yet been clearly defined. This review aims to elaborate on the role of exercise in modulating autophagy in cancer cachexia. We evaluated nine studies in the literature and found a potential correlation between the type of exercise and autophagy modulation. Combined exercise or aerobic exercise alone seems more beneficial than resistance exercise alone in cancer cachexia. Looking ahead, determining the physiological role of autophagy modulated by exercise will support the development of a new medical approach for treating cancer cachexia. In addition, the harmonization of the exercise type, intensity, and duration might play a key role in optimizing the autophagy levels to preserve muscle function and regulate energy utilization in the liver.

Elaborating the Physiological Role of YAP as a Glucose Metabolism Regulator:A Systematic Review.

Yes-associated protein (YAP) is one of the Hippo pathway's two effectors, a pathway associated with organ size control. Research on YAP has focused on its oncogenic potential. However, in cancer cells, aside from inducing growth, YAP was also found to regulate glucose metabolism. The present review explores YAP's control of glucose metabolism and whether these findings are translatable to physiological conditions. According to current literature, YAP induces the transcriptional activity of most genes associated with glucose metabolism from enzymes to transport proteins. In glycolysis and gluconeogenesis, YAP upregulates all enzymes except for enolase and pyruvate kinase. Multiple research has also shown YAP's ability to regulate the expression of glucose transporter of the GLUT family. Additionally, glucose concentration, hypoxia, and hormones such as insulin and glucagon regulate YAP activity and depend on YAP to exert their biological activity. YAP is thus a central regulator of glucose metabolism, controlling both enzymes and proteins involved in glucose transport. YAP is also situated strategically in several pathways controlling glucose and was found to mediate their effects. If these results were consistent in physiological conditions and across glucose-associated metabolic disturbances, then YAP may become a prospective therapeutic target.

Different training intensities induced autophagy and histopathology appearances potentially associated with lipid metabolism in wistar rat liver.

INTRODUCTION: Aerobic training has a beneficial effect on enhancing liver functions. Autophagy might potentially play a role in preventing excessive lipid accumulation, regulating oxidative stress, and inflammation in the liver. OBJECTIVE: To investigate the potential linking role of autophagy-related gene expressions and protein levels with histopathology changes in Wistar rat livers after treadmill training under different intensities. METHODS: 20 rats were divided into 4 groups (control, low intensity, moderate intensity, and high intensity). 8 weeks of treadmill training was conducted with a frequency of 5 days per week, for a duration of 30 min per day. Liver histopathology was studied using hematoxylin-eosin, and oil red O staining. RNA and protein from the liver tissues were extracted to examine the autophagy-related gene (LC3, p62) and protein levels (Beclin, ATG5, LC3, p62). The gene expressions of CPT1a, CD36, FATP 2,3,5, GLUT2, and FGF21 were also studied. RESULTS: Different intensities of training might potentially modulate autophagy-related gene expressions in rat livers. LC3 and p62 mRNA expressions in moderate and high intensities decreased compared to control. Beclin, ATG5, and LC3 protein level increased compared to control, while p62 protein level decreased compared to control. Whereas for the other genes, we found an increase in CPT1a, but we did not observed any changes in the expression of the other genes. Interestingly, autophagy-related gene expressions might be correlated with the changes of sinusoidal dilatation, cloudy swelling, inflammation, and lipid droplets of the liver tissues. CONCLUSION: Moderate and high intensities of training induce autophagy activity, combined with a shift in metabolic zonation in liver that might be potentially correlated with lipophagy. Our results showed the potential interplay role between autophagy and liver histopathology appearances as a part of the adaptation process to training.

Tranexamic Acid Cream Protects Ultraviolet B-induced Photoaging in Balb/c Mice Skin by Increasing Mitochondrial Markers: Changes Lead to Improvement of Histological Appearance.

Tranexamic acid (TSA) is widely used as an antiaging treatment for reducing melasma and wrinkles. There are various mechanisms for wrinkle formation, and one of them is due to damage of the mitochondria. Research on mitochondria in the skin is very limited, so we are interested to see the changes that occur after application of TSA cream. We explored the effect of TSA on mitochondrial protein levels (PGC1α, Tom20, COX IV), which had affected to skin histological structure. Thirty male, 6-week-old, Balb/C mice were divided into five groups (negative control, positive control, TSA 3%, TSA 4% and TSA 5%). After 10 days of acclimatization, four groups of mice were exposed to UVB light, of which three groups were given TSA cream for 10 weeks. The skin tissue was excised for protein and histological studies. H&E staining was performed for evaluating histological changes in epidermal thickness and dermal elastosis. TSA treatment on the mice skin increased mitochondrial marker levels and epidermal thickness while decreasing dermal elastosis for all the treatment groups. Topical application of TSA significantly increased mitochondrial biogenesis which may cause alteration in epidermal thickness and reduced dermal elastosis in the histology of mice skin.

Adaptation of aerobic training essentially involved autophagy, mitochondrial marker and muscle fibre genetic modulation in rat cardiac muscles.

Information about the role of moderate acute treadmill training in modulating autophagy and mitochondrial markers that might be correlated with alteration of muscle fibre gene expression in rat cardiac muscles is very limited. In this present study, the researchers divided twenty male Wistar rats into four groups: sedentary control, 3, 6 and 15 days and subjected them to treadmill training with moderate intensity (20 m/min), 30 min each day. RNA was extracted from cardiac muscles and stored in temperature of -80°C. Specific primers were utilized for semi-quantitative PCR. Treadmill training decreased autophagy-related gene expression (LC3, p62) and upper stream signalling of autophagy (PIK3CA, Akt and mTOR) in 3 and 6 d, but stimulated gene expression of mitochondrial markers (PGC1α, Cox1, Cox2 and Cox4) in 15 days. αMHC gene expression increased while ßMHC gene expression decreased in 15 days. In line with this, autophagy-related genes increased in 3 and 6 days and returned to baseline in 15 days. The increment in mitochondrial gene expression might be correlated with shifting gene expression of αMHC and ßMHC in 15 days. Taken together, acute adaptation in cardiac muscles is stimulated by genetic modulation of autophagy, mitochondrial marker and muscle fibre that may explain physiological cardiac adaptation after training. This study can be used as a reference for optimizing performance in period of cardiac muscle adaptation stimulated by treadmill training.

Cardiac hypertrophy is stimulated by altered training intensity and correlates with autophagy modulation in male Wistar rats.

BACKGROUND: The mechanism for cardiac hypertrophy process that would be a benefit for improvement of cardiovascular endurance needed to be investigated throughly. Specific intensity of training may play a role for homeostasis process in cardiac during training. In the present study, we examine the effect of different intensity of treadmill training on cardiac hypertrophy process and autophagy related gene expression in male wistar rats. METHODS: Three different intensities of treadmill training were conducted on 15 male wistar rats (Low Intensity: 10 m/minute, Moderate Intensity: 20 m/minute, and High Intensity: 30 m/minute) compared to 5 sedentary rats as control. Training duration was 30 min per day, frequency was 5 days per week, during 8 weeks period. Heart weight and heart weight/body weight ratio were measured after the experiments. Left ventricle myocardium was taken for microscopic analysis with HE staining. mRNA was extracted from left ventricle myocardium for examining αMHC and autophagy related gene expression (PIK3CA, mTOR, LC3, p62) using semi quantitative PCR. RESULTS: We observed that altered training intensity might stimulate cardiac hypertrophy process. MI and HI training increased heart weight and heart weight/body weight ratio. This finding is supported by microscopic result in which cardiac hypertrophy was found in MI and HI, with focal fibrosis in HI, and increased αMHC gene expression in MI (p < 0.05) and HI (p = 0.076). We also observed decreased PIK3CA (LI 0.8 fold, MI 0.9 fold), mTOR (LI 0.9 fold, MI 0.9 fold), LC3 (LI 0.9 fold, MI 0.8 fold, HI 0.8 fold), and p62 (LI 0.8 fold, MI 0.9 fold) compared to control. Interestingly, we found increased mTOR (HI 1.1 fold) and p62 (HI 1.1 fold) compared to control. CONCLUSION: Training with different intensity creates different cardiac hypertrophy process based on heart weight and heart weight/body weight ratio, microscopic examination and autophagy related gene expression.

Alteration of Autophagy Gene Expression by Different Intensity of Exercise in Gastrocnemius and Soleus Muscles of Wistar Rats.

Exercise-induced skeletal muscle adaptation requires degradation of cellular components carried out by autophagy. However, the alteration of autophagy by different intensity of exercise in skeletal muscle is still unknown. In the present study, we investigate whether low, moderate, and high-intensity exercises have different impacts on autophagy gene expression in gastrocnemius and soleus muscles of wistar rats. This work is limited because only rats are used, and does not cover human tissues. Twenty male wistar rats were assigned to four groups: sedentary control, low-intensity (LI, 10 m/minute), moderate-intensity (MI, 20 m/minute), and high-intensity (HI, 30 m/minute) exercises. Training was conducted 30 minutes/day with a 5 times/week interval for 8 weeks. RNA and protein were extracted from gastrocnemius and soleus muscles then stored in -80°C. Specific primers and antibodies for autophagy genes and protein levels were utilized for semi-quantitative PCR and Western Blot. Exercises decrease expression of autophagy gene LC3 (LI and MI 0.7 fold, HI 0.8 fold, p < 0.05) in gastrocnemius muscles and soleus muscle (LI, MI, and HI 0.8 fold, p < 0.05) compared to control. On the other side, we observed p62 gene expression decreased in gastrocnemius (0.8 fold, p < 0.05) and soleus (0.9 fold, p < 0.05) muscles with MI, but increased in soleus (1.1 fold, p < 0.05) muscles with HI. This result is consistent with the change of protein level, suggesting that autophagy might be modulated by different type of exercise. This study suggests that intensity of exercise and different type of muscle fibers effect autophagy gene expression in skeletal muscle of wistar rats. MI exercise increases autophagy gene expression in gastrocnemius and soleus muscles, but HI exercise decreases autophagy gene expression in soleus muscles of wistar rats. Soleus muscles are more responsive to exercise compared to gastrocnemius muscles.