Galectin-3 levels in children with cystic fibrosis.

Cystic fibrosis (CF) is a multisystemic disease in which airway obstruction, infection, and inflammation play a critical role in the pathogenesis and progression of CF lung disease. The carbohydrate-binding protein Galectin-3 is increased in several inflammatory and fibrotic diseases and has recently been forwarded as a biomarker in these diseases. We aimed to define the role of serum Galectin-3 in children with CF by comparison with healthy subjects. This is a cross-sectional, case-control study. 143 CF and 30 healthy subjects were enrolled in the study. Peripheral blood and sputum concentrations of Galectins-3, interleukin (IL)-17A, IL-8, and neutrophil elastase (NE) were determined with commercial ELISA kits. There was no significant difference between the groups in age and gender (p = 0.592, p = 0.613, respectively). Serum Galectin-3 and NE concentrations were higher in the patient group than in healthy controls (p = 0.002, p < 0.001, respectively). There were no significant differences between groups according to IL-17A and IL-8 concentrations. Serum Galectin-3 was correlated with age (r = 0.289, p < 0.001) and body mass index (BMI) (r = 0.493, p < 0.001) in children with CF. Sputum Galectin-3 levels are negatively correlated with percent predictive forced expiratory volume in 1 s (FEV1) (r = - 0.297, p = 0.029), FEV1 z-score, (r = - 0.316, p = 0.020), percent predictive forced vital capacity (FVC) (r = - 0.347, p = 0.010), and FVC z-score (r = - 0.373, p = 0.006).   Conclusion: The study shows that serum Galectin-3 levels increased in clinically stable CF patients, and serum Galectin-3 response may depend on age, gender, and BMI. The sputum Galectin-3 was found to be negatively correlated with patients' lung functions. What is known: • Galectin-3 is a key regulator of chronic inflammation in the lung, liver, kidney, and tumor microenvironment. What is new: • Children with cystic fibrosis (CF) have higher serum Galectin-3 concentrations than healthy children. • Serum Galectin-3 expression influenced by age, BMI, and gender in children with CF.

Exercise Prevents Glucocorticoid-Induced Myocardial 4-Hydroxynonenal Production.

PURPOSE: Long-term administration of glucocorticoids (GCs) increases myocardial oxidative stress. 4-Hydroxynonenal (4-HNE) protein adducts, a marker of oxidative damage, have been associated with several cardiovascular diseases, including atherosclerosis, cardiac hypertrophy, cardiomyopathy, and ischemia-reperfusion injury. Exercise training has been shown to have a protective effect on the heart by lowering the level of oxidative stress in cardiomyocytes. Therefore, we aimed to investigate the effect of long-term dexamethasone treatment and exercise training on myocardial 4-HNE levels. METHODS: Twenty-four female Wistar albino rats were assigned to sedentary control-saline treated (C, n = 8), sedentary-dexamethasone treated (D, n = 8), and exercise training-dexamethasone treated (DE, n = 8) groups. Daily dexamethasone was injected for 28 days at a 1 mg kg-1 dose, while C animals were injected with the same volume of saline subcutaneously. DE animals underwent an exercise training protocol of 60 min/day, 5 days a week, at 25 m/min-1 (0% grade) for 28 days. Left ventricular 4-HNE, Hsp72 levels, and pHsp25/Hsp25 ratio were determined by Western blot. RESULTS: The administration of dexamethasone led to a significant elevation in 4-HNE levels in the myocardium of adult rats (p < 0.05; D vs. C). The concurrent implementation of exercise training impeded this increase (p > 0.05; DE vs. C). Exercise training induced a threefold increase in myocardial Hsp72 expression (p < 0.001; DE vs. C and D) and attenuated the dexamethasone-induced increase in Hsp25 phosphorylation (p < 0.05; C vs. D) (p < 0.001; DE vs. D). CONCLUSION: Our results indicate that long-term administration of dexamethasone is associated with an increase in cardiac 4-HNE levels, which is hindered by the addition of exercise training.

Long-term Dexamethasone Treatment Increases Cardiac Galectin-3 Levels.

PURPOSE: Glucocorticoids, which are widely prescribed around the world, cause cardiac remodeling in long-term treatment by triggering insulin resistance and increasing blood pressure. However, its role in cardiac remodeling remains unclear. Galectin-3 (gal-3) is a member of a beta-galactoside-binding animal lectins, upregulated as a result of insulin resistance and in the pressure-overloaded myocardium and regulate cardiac remodeling. We hypothesized that gal-3 may be upregulated in the myocardium with prolonged use of glucocorticoids and associated with cardiac hypertrophy. METHODS: To examine the involvement of glucocorticoids in gal-3 levels in rat myocardium, sixteen female Wistar Albino rats were assigned to control (C; n = 8) and dexamethasone (Dex; n = 8) groups. Daily dexamethasone was injected subcutaneously for 28 days at a dose of 1 mg.kg-1. Control animals were injected with the same volume of saline. The body weight and heart weights were determined. Gal-3 levels in myocardium were determined by Western blot. RESULTS: Our data shows that dexamethasone administration resulted in significant increase in heart weight (p < 0.05) and HW/BW ratios (p < 0.001) and 28 days of dexamethasone administration with the dose of 1 mg.kg-1 caused a twofold increase in the gal-3 expression in the left ventricle (p < 0.001). CONCLUSION: The finding of the current study is the first to show that dexamethasone causes an increase in gal-3 levels in myocardium. Our study provides an important step in the development of possible therapeutics by determining that dexamethasone causes an increase in gal-3 levels in the myocardium and raises awareness about the follow-up of patients receiving long-term glucocorticoid therapy.

Requirements for successful mitochondrial transplantation.

Maintenance of mitochondrial oxidative phosphorylation capacity and other mitochondrial functions are essential for the prevention of mitochondrial dysfunction-related diseases such as neurodegenerative, cardiovascular, and liver diseases. To date, no well-known treatment modality has been developed to prevent or reduce mitochondrial dysfunction. However, a novel approach that transplants fully functional mitochondria directly into defective cells has recently caught the attention of scientists. In this review, we provide an overview of the cell/tissue source of the mitochondria to prompt cell regeneration or tissue repair in vitro and in vivo applications. The animal and human models entail that effective procedures should be used in the isolation and confirmation of mitochondrial membrane potential and function. We believe that these procedures for mitochondrial transplantation for tissue or cell culture will confirm intact, viable, and free from contamination isolated mitochondria from the appropriate sources.

Possible Adaptation of the Adrenal Gland Hsp72 Expression to Hypoxic Stress.

Akin, Senay, Metin Bastug, Ridvan Colak, Hakan Ficicilar, Betul Simten Saglam, Nazan S. Kosar, and Haydar Demirel. Possible adaptation of the adrenal gland Hsp72 expression to hypoxic stress. High Alt Med Biol. 22:293-299, 2021. Background: Adrenal glands play a central role in the general response to stress and controlling wholebody homeostasis. One of the most severe environmental stresses encountered by high-altitude climbers is hypoxia. Since the 72 kDa heat shock protein (Hsp72) has a critical role in cellular homeostasis, regulation of Hsp72 in adrenal glands seems to be crucial for maintaining cellular integrity of the gland and sustaining an adequate whole-body stress response in a hypoxic environment. Therefore, this study investigated if 15 days of hypoxia results in the induction of Hsp72 in adrenal glands. In addition, we examined whether heat treatment had any effect on adrenal Hsp72 expression to hypoxia, as cellular and systemic physiological cross-adaptation was suggested between heat stress and hypoxic stress. Materials and Methods: Male 4-month-old Wistar rats were randomly assigned to one of the four experimental groups (n = 8 each group): (1) control (C), (2) heat treatment (15H), (3) heat treatment and 15 days of normobaric hypoxia (15HHp), and (4) 15 days of normobaric hypoxia (15Hp). Three one-hour heat treatment sessions at 41°C were applied on the first two days before hypoxic exposure and on the day 7. Hypoxic exposure was consisting of normobaric hypoxia containing 9.7% O2. Results: Fifteen days of hypoxia did not increase the adrenal Hsp72 levels (p = 0.99). Furthermore, when hypoxia was added to the heat treatment, heat-related increases in adrenal Hsp72 levels disappeared. Adrenal weight to body weight ratio was not different among groups (p = 0.11). Plasma corticosterone levels were significantly lower in all experimental groups compared with control (p < 0.05), and addition of hypoxia resulted in further significant reduction of the plasma corticosterone levels (C > 15H>15HHp >15Hp; p < 0.05). Conclusions: These data demonstrate the adaptation of the adrenal gland to 15-day chronic normobaric hypoxic stress as well as possible cross-adaptation between heat and hypoxic stress in the adrenal gland.

Possible value of galectin-3 on follow-up of cardiac remodeling during glucocorticoid treatment.

Glucocorticoids are among the most prescribed drugs globally due to their potent anti-inflammatory and immunosuppressive properties. Although they have positive effects on the treatment of various disease states; long-term administration is associated with high blood pressure, insulin resistance, and susceptibility to type 2 diabetes. The heart attempts to cope with increased blood pressure and a decrease in glucose utilization by developing pathological cardiac remodeling. However, in this process, cardiac fibrosis formation and deterioration in heart structure and functions occur. Galectin-3, a member of the ß-galactoside binding lectins, is consistently associated with inflammation and fibrosis in the pathogenesis of various disease states including insulin resistance and heart failure. Galectin-3 expression is markedly increased in activated macrophages and a subset of activated fibroblasts and vascular cells. Also, failing and remodeling myocardium show increased Gal-3 expression and elevated Gal-3 levels are related to heart failure severity and prognosis. Furthermore, Gal-3-related pathways are recently suggested as therapeutic targets both pharmacologically and genetically to increase insulin sensitivity in vivo. The objective of this review is to provide a summary of our current understanding of the role of glucocorticoid-associated insulin resistance, which is important for some cardiac events, and the potential role of galectin in this pathophysiological process.

Acute long-distance trail running increases serum IL-6, IL-15, and Hsp72 levels.

Interleukin-6 (IL-6), IL-15, and heat shock protein 72 (Hsp72) are molecules that have significant metabolic effects on glucose and fat metabolism and a cell's stress response. The aim of this study is to determine serum levels of these molecules in runners after a long-distance trail run. Serum IL-15 levels after such endurance events have not been investigated yet. Blood samples were collected from 37 athletes (11 female, 26 male) before and after a 35-km trail run, with a total climb of 940 m. Serum was obtained from the samples, and IL-6, IL-15, and Hsp72 levels were measured from using the sandwich ELISA method. The athletes completed the race in 308.3 ± 37.4 min on average. After the race, the mean serum IL-6, IL-15, and Hsp72 concentrations increased 13.2-fold, 2.22-fold, and 1.6-fold, respectively (p < 0.001, p < 0.001, and p = 0.039, respectively). This is the first study to demonstrate the increase in serum IL-15 levels following an acute endurance exercise. In addition to IL-15, we report that IL-6 and soluble Hsp72 levels also increased significantly following a 35-km trail run. Since these molecules are involved in regulating glucose and fat metabolism, significant increases of IL-6, IL-15, and soluble Hsp72 may have health benefits that may be associated with long-distance trail runs, which are becoming more popular worldwide.

Meloxicam and diclofenac do not change VEGF and PDGF-ABserum levels of platelet-rich plasma.

BACKGROUND/AIM: Platelet-rich plasma (PRP) application has gained widespread interest for musculoskeletal injuries. Nonsteroidal antiinflammatory drugs are frequently used in sports medicine before and/or after PRP application. Our study seeks to determine whether serum levels of platelet-derived growth factor-AB (PDGF-AB) and vascular endothelial growth factor (VEGF) levels of PRP would be affected by nonsteroidal antiinflammatory drugs. MATERIALS AND METHODS: Two different final concentrations of diclofenac (0.5 µg mL-1 and 2.5 µg mL-1), meloxicam (0.8 µg mL-1 and 2.0 µg mL-1), and acetylsalicylic acid (final concentration 450 µm) were obtained in separate tubes with PRPs prepared from 20 healthy male volunteers. Medicine-free PRP was the control group. Growth factors were measured using ELISA. RESULTS: PDGF-AB and VEGF serum levels did not change with diclofenac, meloxicam, or acetylsalicylic acid addition. PDGF-AB and VEGF serum levels correlated with each other. CONCLUSION: Diclofenac, meloxicam, and acetylsalicylic acid did not affect PDGF-AB and VEGF serum levels.

Short-term treadmill exercise in a cold environment does not induce adrenal Hsp72 and Hsp25 expression.

Heat shock proteins (Hsps) have a critical role in maintaining cellular homeostasis and in protecting cells from a range of acute and chronic stressful conditions. Treadmill running exercise results in increased Hsp72 and Hsp25 levels in various tissues and heat production during exercise has been shown to be the main factor for the increased levels of Hsp72 in myocardium. Since the adrenal gland plays a vital role in general response to stress, regulation of Hsps in adrenal glands following stressful events seems to be critical for controlling the whole-body stress response appropriately. This study tested the hypothesis of whether elevation of temperature is solely responsible for exercise-induced adrenal Hsp72 and Hsp25 expression. Female Sprague-Dawley rats (3 months old) were randomly assigned to either a sedentary control group or one of two treadmill-running groups: a cold exercise group run in a cold room at 4 °C (CE), and a warm exercise group run at 25 °C temperature (WE). Animals were run 60 min a day at 30 m min-1 speed for 4 consecutive days following adaptation to treadmill exercise. Exercise resulted in a significant elevation of body temperature only in the WE group (p < 0.05). Adrenal Hsp72 and Hsp25 levels were significantly higher in the WE group compare to the other groups (p < 0.05). These data demonstrated that exercise-related elevations of body temperature could be the only factor for the inductions of adrenal Hsp72 and Hsp25 expression.

Elevation of body temperature is an essential factor for exercise-increased extracellular heat shock protein 72 level in rat plasma.

This study examined whether the exercise-increased extracellular heat shock protein 72 (eHsp72) levels in rats was associated with body temperature elevation during exercise. In all, 26 female Sprague-Dawley rats (3 mo old) were assigned randomly to control (CON; n = 8), exercise under warm temperature (WEx; n = 9), or exercise under cold temperature (CEx; n = 9). The WEx and CEx were trained at 25 degrees C or 4 degrees C, respectively, for nine days using a treadmill. Before and immediately after the final exercise bout, the colonic temperatures were measured as an index of body temperature. The animals were subsequently anesthetized, and blood samples were collected and centrifuged. Plasma samples were obtained to assess their eHsp72 levels. Only the colonic temperature in WEx was increased significantly (P < 0.05) by exercise. The eHsp72 level in WEx was significantly higher (P < 0.05) than that of either the CON or CEx. However, no significant difference was found between CON and CEx. Regression analyses revealed that the eHsp72 level increased as a function of the body temperature. In another experiment, the eHsp72 level of animals with body temperature that was passively elevated through similar kinetics to those of the exercise was studied. Results of this experiment showed that mere body temperature elevation was insufficient to induce eHsp72 responses. Collectively, our results suggest that body temperature elevation during exercise is important for induction of exercise-increased eHsp72. In addition, the possible role of body temperature elevation is displayed when the exercise stressor is combined with it.