The aim of this study is to investigate the acute and chronic effects of aerobic training performed indoors and outdoors on irisin, adropin, and cholesterol levels in winter. Thirty-two healthy males participated in this study. Participants were divided into two groups: outdoor group (n = 16) and indoor group (n = 16). They then performed 40-min aerobic running exercises 4 days/week for 18 weeks. The outdoor group trained at −5°C–5°C environmental temperature, while the indoor group trained at 21°C–25°C. Blood samples were collected before and after the 18-week training period and immediately after the first training. The results showed that single aerobic exercise induced minimal increase in serum irisin concentrations in both groups. In addition, irisin levels did not change in the outdoor group but significantly decreased in the indoor group after the 18-week training period. Aerobic exercise had no acute or chronic effects on serum adropin levels in the indoor group. However, the aerobic training caused a decrease in adropin levels chronically, but there was no acute effect after single aerobic exercise in the outdoor group. Furthermore, there was no acute effect on high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, and total cholesterol after single aerobic exercise in both groups. However, after the 18-week training period, there was a significant increase in HDL-C levels in both groups. Moreover, the increase in HDL-C in the outdoor group was higher than in the indoor group. Thus, this study provides evidence for the beneficial chronic effects of aerobic exercise and cold on HDL-C levels as well as the beneficial acute effects on irisin concentrations.

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Osteoarthritis (OA) is a degenerative joint disorder and is the leading cause of disability of people, which negatively impact people's physical and mental health. Although OA causes great socioeconomic burden and individual suffering, no effective treatment options are provided so far. This is partially resulted from poor regenerative activity of articular cartilage and our incomplete understanding of the underlying mechanism of OA. Traditional drug therapies such as acetaminophen and opioids are effective in relieving pain but do not reverse cartilage damage and are often associated with adverse events. Therefore, it is necessary to find effective OA drugs. In recent years, novel regenerative therapies have received much attention because they can effectively promote tissue repair and regeneration. The fibroblast growth factor (FGF) signaling has been suggested to involve in cartilage homeostasis for decades. The current research shows that sprifermin/recombinant FGF18 significantly reduces the loss of cartilage thickness and volume without serious side effects, thus warrants a continued research for potential new medications of OA. This review mainly highlights the current research progress on FGFs and FGF receptors as a potential therapeutic target for OA.

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Neuropeptide FF (NPFF) is known as a morphine-modulating peptide and was first isolated in 1985. It has been characterized as an RF-amide peptide. The traditional role of NPFF is mediation of the pain response, and it displays both anti-opioid and pro-opioid actions through central nervous system. In the recent decade, additional evidence has revealed some untraditional features of NPFF, such as regulation of the neuroendocrine system, energy homeostasis, anti-inflammation, pain transmission, and peripheral modulation of adipose tissue macrophages. Neuropeptide FF receptor 2 (NPFFR2) is a physiological receptor of NPFF, and the actions of NPFF may occur through downstream NPFFR2 signaling. NPFF and NPFFR2 increase the neuronal activity in various areas of the hypothalamus to modulate the hypothalamic–pituitary–adrenal axis, the autonomic nervous system, food intake, and energy balance. These underlying cellular mechanisms have been explored in the past few years. Here, we review the impact of NPFF and related RF-amide peptides on hypothalamic function. The interaction of NPFF with NPFFR2 in the hypothalamus is emphasized, and NPFF-NPFFR2 system may represent an important therapeutic target in hypothalamic-related disorders in the future.

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The purpose of this study was to investigate the effect of alcohol exposure on liver and kidney antioxidant systems in taurine exhibition during different time periods. Mice were divided into groups: I – control; II – alcohol (2.5 g/kg b.w.); III – taurine (42.84 mg/kg b.w.); and IV – alcohol + taurine. Treatments were provided for 24 h, 14 days, and 56 days. In the liver and kidney of the alcohol group, antioxidant enzyme (superoxide dismutase, catalase, and glutathione peroxidase) activities, reduced glutathione (GSH), and malondialdehyde (MDA) levels were decreased, as compared to the control group in all time periods. Taurine was found to be effectively inhibiting oxidative action of alcohol and increasing all the tested parameters in the liver (after 24 h) and kidney (after 24 h and 14 days). Moreover, the positive effect of taurine administration on GSH and MDA levels persisted in the kidneys of mice exposed to alcohol for 56 days. In conclusion, alcohol administration led to a significant influence on antioxidant system in the liver and kidney, but simultaneous intake of taurine, along with ethanol, partly attenuated the antioxidant changes in these organs.

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Abnormal pulmonary arterial vascular smooth muscle cells (PASMCs) proliferation is critical pathological feature of pulmonary vascular remodeling that acts as driving force in the initiation and development of pulmonary arterial hypertension (PAH), ultimately leading to pulmonary hypertension. Aloperine is a main active alkaloid extracted from the traditional Chinese herbal Sophora alopecuroides and possesses outstanding antioxidation and anti-inflammatory effects. Our group found Aloperine has protective effects on monocroline-induced pulmonary hypertension in rats by inhibiting oxidative stress in previous researches. However, the anti-inflammation effects of Aloperine on PAH remain unclear. Therefore, to further explore whether the beneficial role of Aloperine on PAH was connected with its anti-inflammatory effects, we performed experiments in vitro. Aloperine significantly inhibited the proliferation and DNA synthesis of human pulmonary artery smooth muscle cells (HPASMCs) induced by platelet-derived growth factor-BB, blocked progression through G₀/G₁to S phase of the cell cycle and promoted total ratio of apoptosis. In summary, these results suggested that Aloperine negatively regulated nuclear factor-κB signaling pathway activity to exert protective effects on PAH and suppressed HPASMCs proliferation therefore has a potential value in the treatment of pulmonary hypertension by negatively modulating pulmonary vascular remodeling.

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Glucocorticoid-induced bone loss is the most common form of secondary osteoporosis. This toxic effect has not been efficiently managed, possibly due to the incomplete understanding of the extraordinarily diverse cellular responses induced by glucocorticoid treatment. Previous literatures revealed that high dose of exogenous glucocorticoid triggers apoptosis in osteocytes and osteoblasts. This cell death is associated with glucocorticoid-induced oxidative stress. In this study, we aimed to investigate the mechanisms of glucocorticoid-induced apoptosis in osteoblasts and examine the responses of osteoclasts to the synthetic glucocorticoid, dexamethasone. We demonstrated the biphasic effects of exogenous glucocorticoid on osteoblastic mitochondrial functions and elevated intracellular oxidative stress in a dose- and time-dependent manner. On comparison, similar treatment did not induce mitochondrial dysfunctions and oxidative stress in osteoclasts. The production of reactive oxygen/nitrogen species was decreased in osteoclasts. The differences are not due to varying efficiency of cellular antioxidant system. The opposite effects on nitrogen oxide synthase might provide an explanation, as the expression levels of nos2 gene are suppressed in the osteoclast but elevated in the osteoblast. We further revealed that glucocorticoids have a substantial impact on the osteoblastic mitochondria. Basal respiration rate and ATP production were increased upon 24 h incubation of glucocorticoids. The increase in proton leak and nonmitochondrial respiration suggests a potential source of glucocorticoid-induced oxidative stress. Long-term incubation of glucocorticoids accumulates these detrimental changes and results in cytochrome C release and mitochondrial breakdown, consequently leading to apoptosis in osteoblasts. The mitochondrial alterations might be other sources of glucocorticoid-induced oxidative stress in osteoblasts.

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Obese sarcopenia is a progressive loss of skeletal muscle mass and strength with increases in adipocytes. The aim of this study was to investigate the effects of combination of exercise training and resveratrol on the pathological pathway from obesity to sarcopenia, and potential therapy for skeletal muscle declines in physical function. Two animal models were experimented: (1) C57BL/6J male mice were fed either a high-fat diet (HFD) for 8 weeks to induce obesity and resveratrol (low-, middle-, and high-dose) for 4 weeks. (2) senescence-accelerated mouse prone 8 (SAMP8) mice with sarcopenia were used. Skeletal muscle function of SAMP8 mice expressed an age-associated decline. In SAMP8 mice, resveratrol (150 mg/Kg BW, daily) was administered by oral gavage two times a week for 1 month of the experimental period. Exercise training based on adaptations in the muscle is training twice a week for 4 weeks. SAMP8 mouse skeletal muscle in each group was analyzed by H and E staining, transferase dUTP nick end labeling, and Western blot analysis. Mitochondrial function expression, apoptosis and relative hypertrophy signaling in HFD-induced obesity mice and SAMP8 mice were determined by Western blot analysis. Results of the present study indicate that effect of resveratrol on skeletal muscles of HFD-induced obesity mice is linked to an increase in Bcl-2 and phosphatidylinositol 3 kinase/AKT expressions. On the other hand, resveratrol, and its combination with exercise training, attenuate the aging-related mitochondrial dysfunction involving Bad, caspase 3, and interleukin-6 expressions in SAMP8 mice. Combination of exercise training and resveratrol induced hypertrophy in skeletal muscles of sarcopenia SAMP8 mice. Therefore, we suggest combination of exercise training and resveratrol as a therapeutic potential in obese sarcopenia.

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Stroke is the second leading cause of death and the leading cause of adult disability worldwide. Despite an impressive amount of neuroprotective agents that has been identified in experimental stroke, none of them proved efficient in clinical trials. There is a general consensus that an effective treatment requires the ability to interact with not one, but multiple pathophysiological cascades at different levels that induced by the insult – cocktail therapy. Luckily, recent progress in the field of epigenetics revealed that epigenetic modifications had influence on many known pathways involved in the complex course of ischemic disease development. The fact that epigenetic molecules, by altering transcriptional regulation, may simultaneously act on different levels of ischemic brain injury makes them promising candidates for clinical use. These modifications arise typically owing to deoxyribonucleic acid methylation and histone acetylation. The aim of this review is to give a comprehensive overview of current advances in stroke epigenetics, in particular, the physiological and pathological functions of the 11 classical histone deacetylases.

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Reports on the coexistence of diabetes mellitus and osteoarthritis in human subjects dated back to the 1960s. However, there is no account in literature on the co-manifestation of these disease conditions in experimental animals. In our previous study, we reported for the first time, the effects of pharmacological agents on glucoregulatory indices, lipid profile, and inflammatory markers in experimental diabetic-knee osteoarthritic rat. However, in the present study, the effects of salmon calcitonin (Sct), and/or omega-3 fatty acids (N-3) were further investigated on other biomarkers. Forty-nine rats of seven animals per group were used for this study. Diabetes was induced by the administration of streptozotocin (65 mg/kg) and nicotinamide (110 mg/kg). Thereafter, knee osteoarthritis was induced by the intra-articular injection of 4 mg of sodium monoiodoacetate in 40 μl of saline. Nine days after the inductions, treatments started, and they lasted for 4 weeks. N-3 was administered at 200 mg/kg/day, while Sct was administered at 2.5 and 5.0 IU/kg/day. The results of the study indicated that the induced diabetes-knee osteoarthritis caused significant alterations in all the observed biomarkers. Sct showed a dose-specific effect and an additive action with N-3 in reducing malondialdehyde and lactate dehydrogenase, and in elevating total bilirubin and total antioxidant capacity. However, it largely demonstrated a nondose-specific effect and nonadditive action with N-3 on superoxide dismutase, catalase, glutathione peroxidase, total alkaline phosphatase, c-telopeptide of type-I collagen, collagen type-2 alpha 1, and hematological indices. In conclusion, the combined administration of Sct and N-3 proffer better therapeutic effects than the single therapy; therefore, they could be used in the management of diabetic-osteoarthritic condition.

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Acute lung injury (ALI) is a common and severe respiratory disease with high morbidity and mortality. Although some progress has been made in the past years, the pathogenesis of ALI is still poorly understood and the therapeutic outcome has still not been significantly improved. It is well-recognized that magnesium sulfate (MgSO₄) possesses potent anti-inflammation capacity. The present study was designed to investigate the protective effects of MgSO₄ in lipopolysaccharides (LPSs)-induced ALI taken into account that excessive inflammatory response plays critical role in the development of ALI. In this study, Kunming mice were intravenously injected with LPS through tail vein to establish the ALI model and in parallel, A549 cells were used to establish cell model. The lung wet-to-dry weight ratio, malondialdehyde (MDA) levels in lung tissue, lung permeability index, hematoxylin and eosin staining, cytokines in the serum and bronchoalveolar lavage fluid (BALF), neutrophil counts in BALF, LPS-induced A549 cell apoptosis as well as apoptosis-inducing factor (AIF), and Poly(ADP-ribose) polymerase-1 (PARP-1) expression in both mice and A549 cells were detected. Our results demonstrated that MgSO₄ significantly attenuated the LPS-induced ALI, oxidative stress (decreased MDA levels), and lung inflammatory response. Moreover, MgSO₄ exerted protective effects by mitigating LPS-induced A549 cell apoptosis. Furthermore, MgSO₄ decreased the AIF and PARP-1 expression both in vivo and in vitro. Our results, taken together, demonstrated that MgSO₄ is a potential therapeutic agent for ALI taken into consideration that MgSO₄ is commonly used in clinical settings.

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The aim of this study was to investigate the acute and chronic effects, and their correlation, after combined aerobic and resistance exercises in blood pressure (BP) and its variability (BPV) in hypertensive postmenopausal women. Fourteen hypertensive postmenopausal women monitored BP at rest and during 24 h by ambulatory BP monitoring in a control day without exercise performance a pretraining (baseline), after an acute exercise session (acute), and after a chronic exercise training for 10 weeks (chronic). After exercise training, systolic BP (SBP, Δ = −150 mmHg.24 h), diastolic BP (DBP, Δ = −96 mmHg.24 h), and mean BP (MBP, Δ = −95 mmHg.24 h) area under the curve were smaller than baseline measurements (P < 0.05) with no difference between acute and baseline measurements. The SBP (ΔSD₂₄ = −2, ΔSD_dn = −1.7, and ΔARV₂₄ = −1.9 mmHg), DBP (ΔSD₂₄ = −0.9, ΔSD_dn = −0.8, and ΔARV₂₄ = −0.9 mmHg), and MBP (ΔSD₂₄ = −1.5, ΔSD_dn = −1.3, and ΔARV₂₄ = −1.2 mmHg) variability reduced in acute session in relation to baseline, with no chronic effects. There are moderate correlations between acute and chronic responses in wake SBP, sleep DBP, and SD₂₄. In conclusion, combined exercise reduces ambulatory BP chronically but not acutely. In contrast, BPV decreases after an acute session but not chronically. Awake SBP, sleep DBP, and SD₂₄ indices are promising candidates to predict individual cardiovascular responses to exercise.

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This study aimed to assess the effect of Vitamin C on blood pressure (BP), and subsequently on oxidative stress and nitric oxide (NO) release, following the low-intensity exercise in the patients. This study included 24 patients with type 2 diabetes mellitus (T2D) (age, 53 ± 7 years; hemoglobin A1c, 10.1% ± 0.9%) randomized into two 6-week daily arms based on the consumption of either placebo or 1000 mg Vitamin C. The crossover trial occurred after a 6-week washout. Before and after both supplementation arms, all patients performed cycling exercise at 33% of peak oxygen consumption for 20 min. BP was measured before, immediately, and 60 min after the exercise. Blood samples were drawn immediately before and after the exercise to determine plasma ascorbate, malondialdehyde (MDA), F₂-isoprostanes (F₂-IsoPs), and NO concentrations. Data showed significant lower BP in the Vitamin C arm when compared with the placebo arm (systolic BP [SBP] P < 0.001 at every time point, diastolic BP [DBP] P < 0.001 except at immediately after exercise, P < 0.05). Plasma ascorbate concentration (P < 0.05 at every time point) and plasma NO (at resting P < 0.001, immediately after exercise P < 0.05) were significantly increased in the Vitamin C arm than in the placebo arm. Plasma MDA (P < 0.05 at every time point) and F₂-IsoPs (P < 0.05 at every time point) concentrations were significantly lower in the Vitamin C arm than in the placebo arm. In addition, data showed significantly lower SBP (P < 0.001 at every time point), DBP (P < 0.001 except at immediately after exercise P < 0.05), plasma MDA (P < 0.001 at every time point), and F₂-IsoPs (P < 0.05 at every time point) at post-supplementation than at pre-supplementation. Besides, there were significantly higher plasma ascorbate (P < 0.05 at every time point) and NO (at rest P < 0.01, immediately after exercise P < 0.05) concentrations at post-supplementation than at pre-supplementation. This is in contrast to the placebo treatment arm which demonstrated no statistical difference in all outcomes throughout the experiment. This study suggests that 6-week Vitamin C supplementation decreased preexercise and postexercise BPs, possibly due to improved oxidative stress and NO release. However, exercise had no effect on any outcome measures.

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Chronic inflammation is a major risk factor for colitis-associated colorectal carcinoma (CRC). Macrophages play a key role in altering the tumor microenvironment by producing pro-inflammatory and anti-inflammatory cytokines. Our previous studies showed that glucose metabolism conferred death resistance for tumor progression and exerted anti-inflammatory effects in ischemic gut mucosa. However, the effect of glucose and cancer metabolites in modulating macrophage cytokine profiles remains poorly defined. We used an in vitro system to mimic intestinal microenvironment and to investigate the roles of glucose and cancer metabolites in the cross-talk between carcinoma cells and macrophages. Human monocyte-derived THP-1 macrophages were stimulated with bacterial lipopolysaccharide (LPS) in the presence of conditioned media (CM) collected from human CRC Caco-2 cells incubated in either glucose-free or glucose-containing media. Our results demonstrated that glucose modulated the macrophage cytokine production, including decreased LPS-induced pro-inflammatory cytokines (i.e., tumor necrosis factor [TNF]α and interleukin [IL]-6) and increased anti-inflammatory cytokine (i.e., IL-10), at resting state. Moreover, glucose-containing CM reduced the macrophage secretion of TNFα and IL-8 but elevated the IL-12 and IL-23 levels, showing an opposite pattern of distinct pro-inflammatory cytokines modulated by cancer glucose metabolites. In contrast, LPS-induced production of macrophage inflammatory protein-1 (a macrophage-derived chemoattractant for granulocytes) was not altered by glucose or CM, indicating that resident macrophages may play a more dominant role than infiltrating granulocytes for responding to cancer metabolites. In conclusion, glucose metabolites from CRC triggered distinct changes in the cytokine profiles in macrophages. The downregulation of death-inducing TNFα and upregulation of Th1/17-polarizing IL-12/IL-23 axis in macrophages caused by exposure to cancer-derived glucose metabolites may contribute to tumor progression.

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Three-quarters of the lands in Taiwan are over 1000 m above sea level. Formosan wood mice (Apodemus semotus), also called Taiwanese field mice, are largely found at altitudes of 1400 ~ 3700 m and are the dominant rodents in these areas. Notably, Formosan wood mice show high levels of exploratory behaviors, not only in the wild but also in laboratory situations. Therefore, in this study, we examined the behavioral responses and central dopaminergic activities of male C57BL/6J mice and Formosan wood mice in the open field test. Dopamine and its major metabolite 3,4-dihydroxyphenylacetic acid were used as indices of dopaminergic activities. Formosan wood mice showed higher levels of exploration and locomotor activity than C57BL/6J mice in the open field test. Higher central dopaminergic activities in the nucleus accumbens, striatum, and medial prefrontal cortex were found in Formosan wood mice than in C57BL/6J mice in the open field test. Higher levels of locomotion and central dopaminergic activities in Formosan wood mice were consistent after two exposures to the open field test; however, dramatic decreases in levels of locomotion and central dopaminergic activities in C57BL/6J mice were found after two exposures to the open field test. The present study found that Formosan wood mice exhibited higher levels of locomotor activity and exploration and central dopaminergic activities than C57BL/6J mice after one or two exposures to the open field test.

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The objective of this study was to evaluate the association between adiposity parameters and fasting serum levels of appetite-regulating peptides: leptin, neuropeptide Y (NPY), desacyl ghrelin, peptide YY(1-36), obestatin, cocaine- and amphetamine-regulated transcript (CART), and agouti-related protein in 30 healthy, non-obese subjects. Thirty European Caucasian adult participants were included in the study (17 men and 13 women). Body composition (body fat and lean body mass) was determined using bioelectrical impedance analysis. Concentrations of peptides in serum were assessed using the enzyme-linked immunosorbent assay. Women had higher level of leptin (P < 0.001), with no other differences for analyzed peptides. We have found a significant correlation between serum concentrations of CART and NPY (P < 0.001). Fasting leptin level was associated with age (P = 0.002), waist circumference (P < 0.001), and lean body mass (P < 0.001). Levels of ghrelin were lower in participants with dyslipidemia (P = 0.009). Levels of obestatin (P = 0.008) and leptin (P = 0.02) were higher in participants with insulin resistance. Associations between body fat and appetite-regulating peptides are more complex than simple feedback loops. Leptin is probably the first signal in the pathway that regulates body fat content, as of all analyzed peptides leptin was the only one that was associated with body composition or anthropometric measurements.

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Pancreatic damage is the major causative agent in type 1 diabetes mellitus (DM). Several strategies have been suggested to regenerate pancreatic functions, such as stem cell transplantation and administration of active components isolating from natural herbals. This study aims to investigate if the synergistically protective effect on damaged pancreatic tissues can be observed in STZ-induced DM rats with autologous transplantation of adipose-derived stem cells (ADSC) coupling with oral administration of resveratrol. Pathological conditions can be recognized in DM rats with pancreatic damage, including reduction of islet size, suppression of survival markers, downregulation of AMPK/Sirt1 axis, and activation of apoptotic signaling. Autologous transplantation of ADSC slightly improves pancreatic functions, whereas autologous transplantation of ADSC coupling with oral administration of resveratrol significantly improves pancreatic functions in DM rats. We suggest that oral administration of resveratrol may enhance the therapeutic effect on DM patients receiving autologous transplantation of ADSC.

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The pathophysiology of coronary artery disease (CAD) includes low-grade chronic inflammation. At its turn, inflammation is known to promote myocardial structural remodeling and to increase vulnerability to atrial arrhythmias. Meanwhile, the impact of chronic inflammation on the electrophysiological properties of the atria remains unknown. We aimed to evaluate the impact of low-grade chronic inflammation on atrial electrophysiology in patients with stable CAD undergoing elective coronary artery bypass grafting (CABG). Circulating levels of several inflammatory, angiogenesis, and endothelial dysfunction markers were determined 1 day before CABG in 30 consecutive CAD patients. Right atrial appendage samples were collected during the CABG procedure; action potential recordings were performed in six study patients using the microelectrode technique. Interleukin (IL)-1b (r = 1.00, P = 0.01), IL-6 (r = 0.98, P < 0.01), vascular endothelial growth factor (VEGF) (r = 0.98, P < 0.01), and hemoglobin (r = 0.98, P < 0.01) levels significantly positively correlated with the duration of atrial depolarization. Consequently, IL-6, VEGF, and hemoglobin (r = −0.86, P = 0.03 for all) levels significantly negatively correlated with the velocity of atrial depolarization. There was no significant correlation between any of the studied markers levels and any of the other parameters of the action potential (all P > 0.05). The present study is the first to demonstrate that in patients with stable CAD, chronic inflammation and ischemia are associated with pro-arrhythmic atrial electrical remodeling. These changes may contribute to the increased propensity to postoperative atrial arrhythmias seen in some of the patients undergoing CABG.

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Cajanus cajan (L.) Millsp., also named pigeon pea, is widely grown in the tropics and the subtropics. C. cajan roots (CR) and ribs stewed in hot water have been used as a traditional medicine in various cultures to treat diabetes. The purpose of this study was to determine the functional components of hot water (WCR) and 50%, 95% ethanol extracts (EECR50 and EECR95) from CR, then evaluating their antioxidant and anti-inflammatory effects. The results indicated that EECR95 had higher polyphenol, especially the isoflavones (e.x. daidzein, genistein, and cajanol) than those of the other extracts, and it also exhibited the most potent anti-oxidative activities by in vitro antioxidant assay. In the lipopolysaccharide-stimulated RAW 264.7 cells, we found that EECR95 significantly decreased intracellular reactive oxygen species and significantly enhanced the activities of superoxide dismutase and catalase. Mechanism studies showed that EECR95 mainly activated nuclear factor (NF) erythroid 2-related factor 2/antioxidant protein heme oxygenase-1 and inhibited nuclear factor kappa B (NF-κB) signaling pathway, and thus exhibited antioxidant and anti-inflammatory effects. Overall, this study suggests that CR may have the potential to be developed as a biomedical material and that genistein, which has relatively high uptakes (3.44% for the pure compound and 1.73% for endogenous genistein of EECR95) at 24 h of incubation with RAW 264.7 cells, could be the main active component of CR.

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Alzheimer's disease is a major health problem all over the world. The role of beta-amyloid (Aβ) is at the center of investigations trying to discover the disease pathogenesis and to develop drugs for treatment or prevention on Alzheimer's disease. This review summarizes both physiological and pathological functions of Aβ and factors that may participate in the disease development. Known genetic factors are trisomy of chromosome 21, mutations of presenilin 1 and 2, and apolipoprotein E4. Lifetime stresses that increase the risk of development of Alzheimer's disease are described. Another important factor is the level of education, especially of linguistic ability. Lifestyle factors include mental and physical exercise, head injury, social contacts, and diet. All these factors might potentiate the effect of aging on the brain to increase the risk of development of pathological changes. The review summarizes pathological features of Alzheimer brain, Aβ plaques, neurofibrillary tangles composed of hyperphosphorylated tau, and brain atrophy. Consequences of Alzheimer's disease that are reviewed include cognitive deficit, loss of function, and neuropsychiatric symptoms. Because there is no effective treatment, many persons with Alzheimer's disease survive to severe and terminal stages which they may fear. Alzheimer's disease at this stage should be considered a terminal disease for which palliative care is indicated. Importance of advance directives, promoting previous wishes of the person who was developing dementia and who subsequently lost decision-making capacity, and limitations of these directives are discussed. Information in this review is based on author's knowledge and clinical experience that were updated by searches of PubMed.

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Angiotensin-(1-7) (Ang-[1-7]) can modulate glucose metabolism and protect against muscular damage. The aim of this study was to investigate the influence of lifetime increase of circulating levels of Ang-(1-7) at exhaustive swimming exercise (ESE). Sprague-Dawley (SD) and transgenic rats TGR(A1-7)3292 (TR) which overproduce Ang-(1-7) (2.5-fold increase) were submitted to ESE. The data showed no differences in time to exhaustion (SD: 4.90 ± 1.37 h vs. TR: 5.15 ± 1.15 h), creatine kinase, and transforming growth factor beta (TGF-β). Lactate dehydrogenase (SD: 219.9 ± 12.04 U/L vs. TR: 143.9 ± 35.21 U/L) and α-actinin (SD: 336.7 ± 104.5 U/L vs. TR: 224.6 ± 82.45 U/L) values were significantly lower in TR. There was a significant decrease in the range of blood glucose levels (SD: −41.4 ± 28.32 mg/dl vs. TR: −13.08 ± 39.63 mg/dl) in SD rats. Muscle (SD: 0.06 ± 0.02 mg/g vs. TR: 0.13 ± 0.01 mg/g) and hepatic glycogen (SD: 0.66 ± 0.36 mg/g vs. TG: 2.24 ± 1.85 mg/g) in TR were higher. The TR presented attenuation of the increase in skeletal muscle damage biomarkers and of the changes in glucose metabolism after ESE.

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Complementary and alternative medicines (CAMs) are widely applied and accepted for therapeutic purposes because of their numerous benefits. Negative ion treatment belongs to one of the critical categories defined by the National Center for CAM, with such treatment capable of air purification and ameliorating emotional disorders (e.g., depression and seasonal affective disorder). Negative ions can be produced naturally and also by a material with activated energy. Exercise-induced muscle damage (EIMD) often occurs due to inadequate warm up, high-intensity exercise, overload, and inappropriate posture, especially for high-intensive competition. Few studies have investigated the effects of negative ion treatment on muscular injury in the sports science field. In the current study, we enrolled badminton athletes and induced muscle damage in them through eccentric exercise in the form of a high-intensity squat program. We evaluated the effects of negative ion patches of different intensities at three points (preexercise, postexercise, and recovery) by analyzing physiological indexes (tumor necrosis factor [TNF]-α, interleukin [IL]-6, IL-10, creatine kinase [CK], and lactate dehydrogenase [LDH] levels) and performing a functional assessment (a countermovement jump [CMJ] test). We found that a high-intensity negative ion patch could significantly reduce the levels of TNF-α, an injury-associated inflammatory cytokine, and related markers (CK and LDH). In addition, muscular overload-caused fatigue could be also ameliorated, as indicated by the functional CMJ test result, and related muscular characteristics (tone and stiffness) could be effectively improved. Thus, the negative ion treatment could effectively improve physiological adaption and muscular fatigue recovery after EIMD in the current study. The negative ion patch treatment can be further integrated into a taping system to synergistically fulfill exercise-induced damage protection and functional elevation. However, the effects of this treatment require further experimental validation.

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Preeclampsia (PE) is the leading cause of maternal and fetal morbidity and mortality. It complicates around 2%–10% pregnancies worldwide due to imbalance between proangiogenic and anti-angiogenic factors, leading to incomplete placentation, ischemia, and endothelial dysfunction. The study was aimed to analyze the mRNA expression of vascular endothelial growth factor (VEGF) and its receptors, i.e., VEGF receptor-1 (VEGFR-1), VEGF receptor-2 (VEGFR-2), and soluble Fms-like tyrosine kinase-1 (sFlt-1) from maternal peripheral blood mononuclear cells (PBMCs) of PE patients. This was a cross-sectional comparative study comprising 18 normotensive and 18 PE patients; the patients were further divided as early-onset preeclampsia (EOP) and late-onset preeclampsia (LOP). The expression level of VEGF, its receptors (VEGFR-1 and VEGFR-2), and sFlt-1 was investigated using real-time polymerase chain reaction. There was a significant change in the mRNA expression with a decrease in VEGF, VEGFR-1, and VEGFR-2 and an increase in sFlt-1 in PBMCs of PE and normal pregnancies (P < 0.001). sFlt-1 mRNA expression was increased by 2.95-fold in the PE group with an inverse correlation with expression of VEGFR-2 (Spearman's rho = 0.68). Based on these findings, we conclude that PE is associated with decrease in the mRNA expression of VEGF, VEGFR-1, and VEGFR-2 as compared to an increase in sFlt-1 in PBMCs.

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When irisin and adropin were discovered, it was popularly hoped that they would become therapies for metabolic disorders that threaten global health. However, contradictory results have been reported in the subsequent period. Irisin, induced by exercise or cold exposure, is believed to be a myokine that causes the browning of adipose tissue thus increasing energy expenditure. Adropin is thought to be beneficial for health by regulating blood flow, capillary density, and playing an active role in glucose and insulin homeostasis. However, there were no experimental studies investigating the simultaneous effect of exercise and cold exposure in humans. The purpose of this study was to investigate irisin and adropin responses in young healthy individuals performing aerobic exercise in different environmental temperatures. Twenty-seven young, healthy individuals participated in this study. Participants performed 40 min of aerobic running exercise in environmental temperatures of 0°C, 12°C, and 24°C. Venous blood samples were taken pre- and post-exercise. Irisin and adropin levels were analyzed using an enzyme-linked immunosorbent assay. The principal findings showed that while serum irisin concentrations significantly increased after aerobic exercise was performed at an environmental temperature of 0°C, there was no significant difference between pre- and post-exercise recordings for physical activity performed at 12°C and 24°C. Adropin concentrations, however, remained unchanged between pre- and post-exercise at 0°C, 12°C, and 24°C. Interestingly, the exercise at 0°C caused an increase in adropin (12.5%), but this amount was not enough to be a statistically significant result. The findings of this study suggest that aerobic exercise in a cold environment causes greater irisin release. However, the combined effect of exercise and cold exposure may not be enough to statistically increase adropin level.

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Coronavirus disease 2019 (COVID-19) had caused a worldwide pandemic with public health emergencies since 2020. For the symptomatic patients, high mortality rate was observed if without timely and optimized management. In this study, we aimed to investigate the predictive and prognostic roles of hematologic and biochemical parameters obtained in the emergency department (ED) for COVID-19 patients. We conducted a retrospective study in a dedicated COVID-19 medical center, recruiting a total of 228 COVID-19 patients with 86 severe and 142 non-severe cases. Both the hematologic and biochemical parameters obtained in the ED upon arrival were analyzed to evaluate the association of the biomarkers with disease severity and prognosis among COVID-19 patients. Among these parameters, neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), procalcitonin (PCT), lactate dehydrogenase (LDH), ferritin, and D-dimer were significantly higher in the severe group than the non-severe one, whereas the platelet count and lymphocyte-to-monocyte ratio were significantly lower. Receiver operating characteristic curve analysis revealed that the areas under curve of CRP, PCT, LDH, ferritin, D-dimer, and NLR for differentiating the severity of COVID-19 were 0.713, 0.755, 0.763, 0.741, 0.733, and 0.683, respectively, whereas the areas under curve of CRP, PCT, LDH, ferritin, D-dimer, and NLR for differentiating the mortality of COVID-19 were 0.678, 0.744, 0.680, 0.676, 0.755, and 0.572, respectively. Logistic regression analysis revealed that CRP, PCT, LDH, ferritin, D-dimer, and NLR were independent indicators for prediction of severe COVID-19, and LDH and ferritin were independent factors associated with the mortality in COVID-19. In conclusion, higher CRP, PCT, LDH, ferritin, D-dimer, and NLR were associated with severe COVID-19, whereas higher LDH and ferritin were associated with the mortality in COVID-19. These findings could help early risk stratification in the ED and contribute to optimized patient management.

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We explored the therapeutic potential of intragastric administration of traditional Chinese medicine Glycine tomentella Hayata (I-Tiao-Gung [ITG]) extract and its major component Daidzin on cyclophosphamide (CYP)-induced cystitis, oxidative stress, fibrosis, inflammation, and bladder hyperactivity in rats. Female Wistar rats were divided into control, CYP (200 mg/kg), CYP+ITG (1.17 g/kg/day), and CYP+Daidzin (12.5 mg/kg/day) groups. We measured the voiding function by the transcystometrogram and evaluated the pathology with the hematoxylin and eosin and Masson stain. We determined the bladder reactive oxygen species (ROS) amount by an ultrasensitive chemiluminescence analyzer, the expression of 3-nitrotyrosine (3-NT) and NADPH oxidase 4 (NOX4) by Western blot and the expression of multiple cytokine profiles, including matrix metalloproteinase (MMP)-8 and tissue inhibitor of metalloproteinase (TIMP)-1 through a cytokine array. ITG extract contains 1.07% of Daidzin through high-performance liquid chromatography. The effect of ITG extract and Daidzin in scavenging hydrogen peroxide activity was more efficient than distilled water. CYP-induced higher urination frequency, shorter intercontraction interval, and lower maximal voiding pressure in the bladders and these symptoms were significantly ameliorated in CYP+ITG and CYP+Daidzin groups. The amount of in vivo bladder ROS and the expression of 3-NT and NOX4 expressions were significantly increased in CYP group but were efficiently decreased in the CYP+ITG and CYP+Daidzin groups. CYP-induced fibrosis, hemorrhage, leukocyte infiltration, and edema in the bladders were significantly attenuated in the CYP+ITG and CYP+Daidzin groups. These results suggested that ITG extract and its active component Daidzin effectively improved CYP-induced oxidative stress, inflammation, and fibrosis through inhibiting the MMP-8, TIMP-1, and oxidative stress.

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