Search Results (358)

Background: In patients with ST-segment elevation myocardial infarction (STEMI), apelin is upregulated and exerts cardioprotective effects against ischemia–reperfusion injury (IRI). The present study aimed to investigate serum apelin-36 levels in STEMI patients and their relationship with the no-reflow phenomenon. Methods: In this study, 161 patients presenting with STEMI within 12 h of symptom onset and undergoing primary percutaneous coronary intervention (pPCI) were enrolled. Biochemical parameters, including apelin-36, troponin T, creatine kinase (CK), the MB fraction of creatine kinase (CK-MB), total cholesterol, triglycerides, and other routine laboratory parameters, were measured. Two-dimensional echocardiography was performed in all patients. Thereafter, patients were divided into two groups according to their level of aaapelin-36. Results: Among the 161 consecutive STEMI patients, 115 (71.42%) had Apelin-36 levels ≤ 0.58 ng/mL (group 1), whereas 46 (28.57%) had Apelin-36 levels > 0.58 ng/mL (group 2). In total, 51 (31.67%) STEMI patients experienced no-reflow phenomenon after PCI: 29 (25.21%) of patients with apelin-36 ≤ 0.58 ng/mL and 22 (47.82%) of those with a value > 0.58 ng/mL (p < 0.001). In terms of Gensini score, the mean value in group 1 was 70.29 (±28.76), while in group 2, it was 81.95 (±23.82) (p = 0.004). Overall, a positive correlation between apelin-36 and Gensini score was observed in both groups using Kendall’s correlation analysis (group 1: p = 0.05; group 2: p < 0.0001). Binary logistic regression analysis identified apelin-36 and diabetes mellitus as significant predictors at the 5% level, with p-values of 0.045 and 0.036, respectively. Patients with apelin-36 levels ≤ 0.58 ng/mL had troponin T levels of 290.0 (8.5–9510.0), while those with a value > 0.58 ng/mL had troponin T levels of 132.15 (9.4–5190.0) (p < 0.012). The receiver operating characteristics (ROC) curve of apelin-36 was used to plot the true positive rate against the false positive rate at different cut-off points, with AUC = 0.77 (95% CI, 0.69–0.84), and the cut-off value for apelin-36 was 0.58 ng/mL, with p = 0.001. Conclusions: Significant associations were observed between apelin-36 and the no-reflow phenomenon in patients with STEMI. An apelin-36 cut-off value of 0.58 ng/mL, measured at admission, could be used to identify patients who were at increased risk of no-reflow phenomenon/reperfusion injury. Full article

Background: Interindividual differences in statin efficacy and tolerability are partly determined by genetic and metabolic factors. The SLCO1B1 c.521T>C polymorphism affects hepatic statin transport, while vitamin D deficiency may influence lipid metabolism and muscular tolerance. This study aimed to assess the impact of SLCO1B1 genotype and vitamin D status on lipid-lowering response and adverse events in postmenopausal women treated with atorvastatin or rosuvastatin. Methods: A total of 145 Croatian postmenopausal women were prospectively followed for 16 weeks. Participants received atorvastatin or rosuvastatin with dose titration to achieve low-density lipoprotein cholesterol (LDL-C) targets. Serum lipids, liver enzymes, and creatine kinase were monitored monthly. Serum levels of 25-hydroxyvitamin D were quantified by LC–MS/MS, while SLCO1B1 c.521T>C genotyping was performed using real-time PCR. Results: Rosuvastatin achieved a higher LDL-C target attainment rate compared with atorvastatin (81.1% vs. 67.6%, p = 0.02). The SLCO1B1 genotype was not associated with lipid response but was significantly associated with adverse effects. In multivariable regression analysis, patients with the T/C genotype had a significantly higher risk of developing adverse effects compared with those with the T/T genotype (OR 7.4, 95% Cl 2.1–26.7, p = 0.002). Vitamin D status showed no significant association with lipid outcomes or adverse events, although participants with severe deficiency exhibited a weaker LDL-C response. Conclusions: Rosuvastatin demonstrated superior lipid-lowering efficacy and tolerability compared with atorvastatin in postmenopausal women. The SLCO1B1 c.521T>C variant primarily affected safety rather than efficacy, while severe vitamin D deficiency might contribute to diminished statin response. Integrating pharmacogenetic and endocrine profiling could enhance individualized statin therapy and cardiovascular prevention in women. Full article

Exercise-induced fatigue involves oxidative stress and metabolic dysregulation. While the anti-aging protein α-Klotho regulates metabolism and oxidative stress, its role in exercise fatigue is unexplored. This study investigated whether α-Klotho supplementation mitigates cumulative exercise-induced fatigue and elucidated the underlying tissue-specific mechanisms. Male C57BL/6J mice were divided into three groups (n = 10 per group), the control group, fatigue treated with saline, or α-Klotho (0.2 mg/kg, i.p. daily) group. Fatigue was induced by a 6-day exhaustive swimming protocol (5% body weight load). Tissues were collected 24h post-final exercise. Assessments included daily exhaustion time, grip strength, serum creatine kinase (CK), urea nitrogen (BUN), oxidative stress markers (H₂O₂, MDA, SOD, GSH/GSSG), tissue glycogen, and pathway protein expression (Western blot). α-Klotho supplementation prevented exercise-induced weight loss and restored grip strength. While exhaustive exercise markedly increased serum CK and BUN levels, α-Klotho selectively normalized CK without effecting serum BUN. α-Klotho attenuated oxidative damage by reducing hydrogen peroxide levels while enhancing antioxidant capacity, accompanied by activation of the NRF2/HO-1 pathway and further upregulation of PGC-1α. Notably, α-Klotho induced striking hepatic glycogen supercompensation through activation of the AKT/GS signaling pathway and upregulation of GLUT4, whereas muscle glycogen levels remained unchanged. In conclusion, α-Klotho ameliorates cumulative exercise-induced fatigue through dual recovery-phase mechanisms: NRF2/HO-1-mediated antioxidant protection in skeletal muscle and AKT/GS-triggered hepatic glycogen supercompensation, thereby facilitating oxidative stress resolution and enhancing energy reserve restoration. Full article

Doxorubicin (DOX), a clinical broad-spectrum anthracycline chemotherapeutic agent, induces dose-dependent cardiotoxicity that progresses to heart failure (HF), thereby severely limiting its clinical application. Mitochondrial dysfunction and oxidative stress dysregulation are core pathological mechanisms underlying DOX-induced myocardial injury. This study aimed to investigate the protective effect and underlying mechanism of Cistanche deserticola polysaccharides (CDPs) against DOX-induced cardiotoxicity in C57BL/6J mice. Compared with the DOX model group, CDPs significantly increased left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS), and reduced the activities of serum creatine kinase (CK), creatine kinase-MB (CK-MB), and lactate dehydrogenase (LDH). Additionally, CDPs notably decreased the malondialdehyde (MDA) levels in serum and myocardial tissue, while significantly enhancing the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Moreover, CDPs ameliorated mitochondrial swelling and crista fracture, upregulated the expression of mitochondrial respiratory chain complex-related genes, and increased adenosine triphosphate (ATP) production. In conclusion, CDPs alleviate DOX-induced cardiotoxicity and protect cardiac function by inhibiting myocardial oxidative stress and improving mitochondrial function, which provides a potential therapeutic strategy for preventing DOX-related cardiotoxicity. Full article

Background/Objectives: Myotonic dystrophy type 1 (DM1) is a multisystem disorder that affects the central nervous system. Despite previous studies, blood-based biomarkers have not been sufficiently characterized. This study investigated plasma neurofilament light chain (NfL), phosphorylated tau (p-tau181), amyloid-β (Aβ42/40), and glial fibrillary acidic protein (GFAP) in a Japanese cohort with DM1 to assess their potential as biomarkers. Methods: Forty patients with genetically confirmed DM1 were enrolled in this study. Plasma NfL, p-tau181, Aβ42/40, and GFAP were quantified using single-molecule array technology. Clinical and genetic variables, including age, CTG repeat size, Mini-Mental State Examination (MMSE) score, modified Rankin Scale (mRS) score, and creatine kinase levels, were analyzed for correlations. Results: NfL and p-tau181 were significantly elevated in patients with DM1 compared with controls, with 95% exceeding the p-tau181 cut-off. NfL was moderately correlated with age, age at onset, and mRS, and no significant associations were observed between p-tau181 and other biomarkers, although a correlation was noted with serum creatine kinase. Conclusions: These findings support that NfL is a marker of disease severity in DM1 and identified plasma p-tau181 as a potential novel biomarker. While the mechanisms underlying the increased p-tau181 levels remain unclear, they may reflect DM1-related pathologies in the brain and possibly in skeletal muscle. Study limitations include a small sample size and lack of age-matched controls, highlighting the need for longitudinal validation. This study demonstrates the utility of NfL and suggests that p-tau181 is an emerging biomarker for DM1, supporting future work toward biomarker-guided monitoring and therapeutic evaluation. Full article

Background/Objectives: Cyclophosphamide (CYC) is a commonly used alkylating agent for treating various cancers and autoimmune disorders. However, its use is often hampered by serious side effects, affecting multiple organs. This study aimed to explore whether tenofovir (TFV), a nucleotide reverse transcriptase inhibitor, could offer protective benefits against CYC-induced organ toxicity in rats. Methods: Two different TFV doses (25 and 50 mg/kg) were tested. The researchers evaluated the effects of TFV on kidney and heart function biomarkers, oxidative stress, autophagy, apoptosis, and inflammatory markers. Results: The results showed that pre-treatment with TFV significantly reduced the harmful effects of CYC, as evidenced by decreasing the activity of serum lactate dehydrogenase (LDH) and creatine kinase-myocardial band (CK-MB), and the levels of serum creatinine (Cr.), blood urea nitrogen (BUN), and malondialdehyde (MDA). TFV also boosted antioxidant defenses by increasing the expression of key proteins such as Nrf2/HO-1, AMPK, and SIRT1. Also, TFV regulated inflammatory and apoptotic pathways (revealed by reducing IL-1β level and increasing Bcl-2 level) and improved autophagy (showed by reducing LC3 expression). Conclusions: Overall, these findings suggested that TFV has strong protective effects against CYC-induced organ toxicity, likely through its anti-inflammatory, antioxidant, and anti-apoptotic mechanisms. This points to TFV as a potential therapeutic agent to help mitigate the organ damage caused by CYC. Full article

The study evaluated whether organic chromium supplementation in the diets of Jersey cows in the final third of lactation has positive effects on productive performance and milk quality, as well as markers of metabolism, hematology, immunological, and oxidative response. We used 22 cows in a 56-day study, divided into two groups: control (n = 11) and chromium treatment at 10 mg/kg of dry matter per day (n = 11). We evaluated these animals’ productive performance markers (milk production, feed intake, and lactation persistence), milk quality (composition and somatic cell counts), and blood biomarkers to assess animal health. Chromium concentration at the beginning of the experiment was within normal limits for the animal category (221 to 246 nM). The cows’ consumption of organic chromium increased its bioavailability in the body, with higher concentration in the serum (p = 0.01) and milk (p = 0.013) of Jersey cows compared to the control cows. Supplementing cows with chromium resulted in higher fat-corrected milk production (p = 0.05), longer lactation persistence (p = 0.05), and feed efficiency (p = 0.02) compared to the control group. There was a lower SCC (p = 0.01) on days 28, 42, and 56, as well as a higher percentage of fat in the milk of supplemented cows on days 28 and 42 compared to that of the control group (p = 0.01). As a treatment effect (p ≤ 0.05), we found cows supplemented with chromium had a higher concentration of insulin, immunoglobulin G, and creatine kinase activity dismutase compared to control animals. Considering the treatment × day interaction (p ≤ 0.05), we observed greater activity of the creatine kinase enzymes (days 14, 28, and 56), as well as lower cholinesterase activity (days 42 and 56) compared to those of the control. The concentration of globulins (p = 0.05) and immunoglobulin G (p = 0.01) on day 56 was higher in cows that consumed chromium. Higher superoxide dismutase activity on days 42 and 56 (p = 0.04) was observed in the blood of cows supplemented with organic chromium compared to that of the control. Therefore, we conclude that the addition of organic chromium was beneficial to maintaining lactation persistence and increasing fat-corrected milk production. Full article

Postmortem diagnosis of sudden cardiac death (SCD) may escape detection due to the absence of thrombi and slow development of structural and immunohistochemical changes. Therefore, this study explores the possibility of analyzing relevant clinical chemistry biomarkers in myocardial homogenates and serum. Following an initial pilot study, myocardial samples from 113 autopsy cases were homogenized with distilled water, T-PER or 2 M urea. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine kinase (CK-MB), lactate dehydrogenase (LDH), orosomucoid and total protein were analyzed with an IndikoPlus and a subset was also analyzed with a Roche Cobas 8000 c701 analyzer, which also provided results for cardiac Troponin T, myoglobin and NT-proBNP. Although the yields varied with different extraction buffers depending on the analyte, distilled water was often as effective as T-PER and 2 M urea extraction for most analytes. Biomarker levels were consistently higher in the myocardial homogenates than in serum. Proteomic profiling on a subset confirmed higher concentrations of the cardiac markers in the tissue samples than in serum. Finally, we investigated whether selected markers could support the diagnosis of acute cardiac disease by classifying cases as sudden cardiac death (SCD) or controls. There was no significant difference in serum concentrations of the selected biomarkers between SCD cases and controls, whereas a significant loss of several markers was observed in SCD myocardial samples as compared to controls. Hence, our results suggest that analysis of tissue homogenates is likely better for detecting early ischemia, and we show that an in-house benchtop multi-analyzer can provide rapid results to assist the pathologist’s decision-making during autopsy. Full article

Background/Objectives: Despite the growing popularity of fresh food for dogs, there is an extremely small amount of literature evaluating the potential health benefits of fresh food and reduced processing compared to traditionally processed shelf stable cans, extruded kibble, or other food formats. Additionally, aging dogs have been previously documented to have altered metabolism and nutritional needs compared to a healthy adult dog population, but these differences are not well defined. The objective of the study was to compare the effects of feeding a fresh, human-grade food versus a standard extruded kibble diet in a year-long longitudinal study on serum metabolomic profiles in senior dogs. Methods: Twenty-two healthy mixed-breed geriatric Alaskan sled dogs were age- and sex matched into two feeding groups. All dogs were fed the extruded diet (control) for a 4-month washout period prior to being transitioned into their respective treatment group. Group 1 continued to be fed the control diet, while Group 2 was transitioned to a fresh, human-grade food (treatment). Body weight and body condition were assessed monthly, and calorie intake was adjusted to maintain body weight. Individual serum samples were collected at day 0 and months 1, 3, 6, and 12. Metabolomic profiling of serum samples was performed by Metabolon, Inc. (Durham, NC, USA). Data was analyzed using two-way analysis of variance with repeated measures to determine treatment differences. Results: Dogs fed the treatment food had an increase in branched-chain amino acid metabolism, creatine, carnosine, anserine, fatty acid metabolism, long-chain n-3 fatty acids, lipolysis, and ketogenesis. The treatment group had decreased advanced glycation end products, fatty acid synthesis, and creatinine. Conclusions: This study is the first long-term feeding study evaluating serum metabolomics in dogs that demonstrates the dramatic and sustained impact that diet can have on canine metabolism. Full article

Background: Although Ti-Fu-Kang (TFK) decoction has been clinically used for fatigue management, the systematic understanding of its mechanisms, particularly against central fatigue, remains largely unknown. This study is the first to employ an integrative approach of network pharmacology and metabolomics to explore the mechanisms of TFK against central fatigue. Methods: The central fatigue rat model was established using the modified multiple platform method in conjunction with alternate-day fasting. Behavioral alterations were evaluated through six behavioral tests, while brain injury was assessed through HE and Nissl staining. Serum metabolic indicators were analyzed to identify fatigue-related metabolic disturbances. Western blot analysis was used to assess the protein phosphorylation level of PI3K and AKT1. Oxidative stress was assessed by measuring superoxide dismutase, malondialdehyde, and glutathione peroxidase activities. Network pharmacology and serum metabolomics investigated the molecular mechanisms and metabolic pathways. Results: TFK significantly ameliorated behavioral abnormalities and brain pathological damage in central fatigue model rats. Network pharmacology analysis and in vivo experiment revealed that TFK may mediate biological processes such as oxidative stress and neuron death via the PI3K-AKT signaling pathway. Moreover, analysis of serum fatigue-related metabolic indicators indicated that TFK significantly modulated metabolic disruptions by elevating the levels of glucose, liver glycogen, and muscle glycogen and reducing the levels of alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, creatine kinase, lactate, and lactate dehydrogenase in central fatigue rats. Serum metabolomics analysis revealed that TFK ameliorates central fatigue by modulating amino acid metabolism, specifically by altering the levels of leucine and L-tryptophan, which subsequently contributes to the restoration of 5-hydroxytryptamine and dopamine homeostasis. Conclusions: This study elucidates the potential therapeutic mechanism of TKF in alleviating central fatigue, providing a scientific and theoretical basis for broader application and development of TFK. Full article

Background: Physical conditioning is essential to meet the operational demands of military environments. However, high-intensity exercise provokes muscle microinjuries resulting in exercise-induced muscle damage. This condition is typically monitored using serum biomarkers such as creatine kinase (CK), myoglobin (MYO), and lactate dehydrogenase (LDH). Nevertheless, individual variability and genetic factors complicate the interpretation. In this context, the rs1815739 variant (ACTN3), the most common variant related to exercise phenotypes, hypothetically could interfere with the muscle physiological response. This study aimed to evaluate the kinetics of serum biomarkers during a high-intensity activity and their potential association with rs1815739 polymorphism. Materials and Methods: 32 male cadets were selected during the Army Paratrooper Course. Serum was obtained at six distinct moments while they performed regular course tests and recovery time. Borg scale was assessed in 2 moments (~11 and ~17). Results: Serum levels of CK, CK-MB, MYO, and LDH significantly increase after exercise, proportionally to Borg’s level, following the applicability of longitudinal studies to understand biomarker levels in response to exercise. R allele carriers (ACTN3) were only slightly associated with greater levels of MYO and CK, mainly in relative kinetic levels, and especially at moments of greater physical demand/recovery. Although the ACTN3 was slightly related to different biomarker levels in our investigation, the success or healthiness in military activities is multifactorial and does not depend only on interindividual variability or physical capacity. Conclusions: Monitoring biomarkers and multiple genomic regions can generate more efficient exercise-related phenotype interventions. Full article

The most common cause of morbidity and death worldwide is acute myocardial infarction (AMI), which is typified by severe and deadly arrhythmias resulting from cardiac ischemia and reperfusion (CIR). We chose to investigate the possible cardioprotective activity of epiisopiloturine (EPI), an imidazole alkaloid presents in the leaves of Pilocarpus microphyllus, in an animal model of CIR in rats. Control rats were treated with 0.9% saline solution and then subjected to CIR (SS + CIR); they were compared to rats pretreated with either 10 mg/kg (EPI10 + CIR group) or 15 mg/kg EPI (EPI15 + CIR) before CIR. ECG analysis was used to assess the incidence of ventricular arrhythmias (VAs), atrioventricular block (AVB), and lethality (LET) brought on by CIR in these rats. Serum creatine kinase-MB (CK-MB) was assessed using a colorimetric assay. In comparison to the SS + CIR group, animals treated with EPI15 + CIR had lower AVB incidence, which decreased from 85.7% to 21.4%, while LET incidence decreased from 71.4% to 21.4%. In both EPI10 + CIR and EPI15 + CIR groups, serum CK-MB was lower than in SS + CIR positive controls. These findings suggest that administration of EPI (15 mg/kg) before CIR could reduce the incidences of AVB and LET, as well as cardiac injury markers, which suggests that, likely due to its antioxidant effects, EPI may be a promising drug to reduce LET in patients with severe and fatal arrhythmia due to AMI. Full article

Background/Objectives: Malignant hyperthermia (MH) is a pharmacogenetic hypermetabolic syndrome triggered by halogenated agents/succinylcholine. Most families present variants in the RYR1 and, rarely, in other genes (CACNA1S/STAC3/ASPH). However, each country or region presents differences in the type and frequency of MH variants. Objective: To present the genetic characteristics of Brazilian individuals with MH history. Methods: We reviewed clinical and laboratory data from all families referred for evaluation in the Brazilian MH unit due to a personal or family history of MH during anesthesia. Demographic and clinical data were collected, as well as serum creatine kinase (CK) levels, in vitro contracture test (IVCT) results, and the results of anatomopathological studies of skeletal muscle. Molecular analysis was performed using whole-exome sequencing (WES). Patients with and without variants were compared. Results: WES analysis was available for 61 patients (29 patients who survived an MH crisis and 32 relatives). Variants in the RYR1 were found in 38 patients (62.2%), and no variants were identified in 20 patients (32.7%). More than one variant in the RYR1 was found in six individuals. Variants in the CACNA1S were found in three patients (4.9%), all of them with concomitant variants in the RYR1. Three patients presented variants in the STAC3 (4.9%). Comparing the groups of patients with variants in the RYR1 with the one with no variants in this gene, it was observed that the first group showed higher levels of serum CK, a greater frequency of ptosis, strabismus, and cores, and a higher amplitude of contracture in the IVCT after caffeine or halothane. Conclusion: In this preliminary evaluation of Brazilian individuals with MH history, the frequency of RYR1 variants was similar to those of previous reports in other countries, but there was a higher frequency of STAC3 and CACNA1S variants. Full article

This study evaluated the effects of increasing phytase levels on serum biochemical parameters and renal and hepatic changes in Japanese quails (Coturnix japonica) under different temperature conditions. A total of 720 quails were distributed in a 5 × 3 factorial design with five phytase levels (0, 500, 1000, 1500, and 3000 FTU/kg) and three temperature ranges (24, 30, and 36 °C), totaling 15 treatments with six replicates of eight birds each. Data were collected in cycles 2 and 4. The parameters measured included eggshell thickness (ST), total egg production (TEP), liver weight (LW), gamma-glutamyl transferase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (FA), phosphorus (P), calcium (Ca), urea (URE), creatine kinase (CK), and uric acid (UA). PRO was higher at 30 °C compared to 24 °C and 36 °C. EC showed a significant interaction between phytase levels and temperature, with phytase improving EC, especially at 1500 FTU and 36 °C. PF was not affected in the second cycle but had a quadratic effect in the fourth cycle. Phytase supplementation improved shell thickness and regulated biochemical parameters, especially at high temperatures. Based on these results, a phytase level of 1500 FTU/kg is recommended to optimize performance and mitigate the negative effects of high temperatures on quail health. Full article

Objective: This study aimed to evaluate the effects of Cistanche deserticola Y.C. Ma (CD) supplementation on muscle strength and recovery in individuals with and without resistance training experience. Methods: A randomized, double-blind, placebo-controlled trial was conducted with 48 male participants, including 24 resistance-trained and 24 untrained individuals. Participants were stratified by training status and randomly assigned to either the CD or placebo (PLAC) group. All subjects completed a standardized resistance training program three times per week for eight weeks. The CD group received 5 g of CD extract twice daily, while the PLAC group consumed a matched placebo. Assessments included one-repetition maximum (1RM) for bench press and squat, maximal voluntary isometric contraction (MVIC), and repetitions to failure (RTF). Blood biomarkers including serum testosterone, cortisol, C-reactive protein (CRP), and creatine kinase (CK) were also measured. Results: No significant differences in dietary energy intake or macro-nutrient composition were observed based on two 5-day dietary records collected before baseline testing and at the end of the intervention. Among untrained individuals, the CD group showed significantly greater improvements in 1RM bench press and squat compared with the PLAC group (p < 0.05), with MVIC and RTF also significantly increased (p < 0.01). Serum cortisol levels were reduced (p < 0.05), and significant improvements were observed in testosterone, CRP, and CK (p < 0.01). In trained individuals, CD supplementation led to significant increases in 1RM squat and MVIC (p < 0.05), along with improvements in testosterone and cortisol levels (p < 0.05) and marked reductions in CRP and CK (p < 0.01). Conclusions: Daily supplementation with 5 g of CD extract for eight consecutive weeks significantly enhanced muscle strength and endurance in males with different training backgrounds and facilitated post-exercise recovery by modulating hormonal responses and reducing stress levels and inflammation. These findings provide experimental evidence supporting the application of CD in sports nutrition. Full article