Search Results (2,519)

The pathophysiological mechanism linking oxidative stress and cardiovascular disease (CVD) is not completely elucidated, especially in young individuals. This study aimed to examine redox status in an adolescent Montenegrin population in relation to cardiovascular risk score (CVRS). A cohort of 182 adolescents (76% girls) aged between 16 and 19 was examined. Total antioxidant status (TAS), superoxide dismutase (SOD), advanced oxidation protein products (AOPPs), malondialdehyde (MDA), and total oxidant status (TOS) were determined. Pro-oxy score, anti-oxy score, and oxy score were calculated as comprehensive parameters of overall redox homeostasis status. CVRS was calculated by summarizing several risk factors (i.e., sex, age, obesity, hypertension, dyslipidemia, impaired fasting glucose, and smoking). A significant positive correlation between CVRS and TOS (rho = 0.246, p = 0.001) and AOPP (rho = 0.231, p = 0.002) and MDA (rho = 0.339, p < 0.001), respectively, and a negative correlation with the TAS/TOS ratio (rho= −0.208, p = 0.005) was observed. An increase in pro-oxy scores as well as oxy scores with CVRS risk increase were observed. Anti-oxy scores did not differ between CVRS subgroups. There is a significant relationship between cardiovascular risk score and oxidative stress in the adolescent Montenegrin population. These findings support the possibility for improvement of age-specific CVD risk algorithms by adding redox homeostasis parameters in addition to conventional ones. Full article

Skeletal muscle atrophy is a critical health issue affecting the quality of life of elderly individuals and patients with chronic diseases. These conditions induce dysregulation of glucocorticoid (GC) secretion. GCs play a critical role in maintaining homeostasis in the stress response and glucose metabolism. However, prolonged exposure to GC is directly linked to muscle atrophy, which is characterized by a reduction in muscle size and weight, particularly affecting fast-twitch muscle fibers. The GC-activated glucocorticoid receptor (GR) decreases protein synthesis and facilitates protein breakdown. Numerous antagonists have been developed to mitigate GC-induced muscle atrophy, including 11β-HSD1 inhibitors and myostatin and activin receptor blockers. However, the clinical trial results have fallen short of the expected efficacy. Recently, several emerging pathways and targets have been identified. For instance, GC-induced sirtuin 6 isoform (SIRT6) expression suppresses AKT/mTORC1 signaling. Lysine-specific demethylase 1 (LSD1) cooperates with the GR for the transcription of atrogenes. The kynurenine pathway and indoleamine 2,3-dioxygenase 1 (IDO-1) also play crucial roles in protein synthesis and energy production in skeletal muscle. Therefore, a deeper understanding of the complexities of GR transactivation and transrepression will provide new strategies for the discovery of novel drugs to overcome the detrimental effects of GCs on muscle tissues. Full article

The rhythm of epileptiform activity occurs in various brain injuries (ischemia, stroke, concussion, mechanical damage, AD, PD). The epileptiform rhythm is accompanied by periodic Ca²⁺ pulses, which are necessary for the neurotransmitter release, the repair of damaged connections between neurons, and the growth of new projections. The duration and amplitude of these pulses depend on intracellular calcium-binding proteins. The effect of the synthetic fast calcium buffer BAPTA on the epileptiform activity of neurons induced by the GABA(A)-receptor inhibitor, bicuculline, was investigated in a 14-DIV rat hippocampal culture. In the epileptiform activity mode, neurons periodically synchronously generate action potential (AP) bursts in the form of paroxysmal depolarization shift (PDS) clusters and their corresponding high-amplitude Ca²⁺ pulses. Changes in the paroxysmal activity and Ca²⁺ pulses were recorded continuously for 10–11 min as BAPTA accumulated. It was shown that during BAPTA accumulation, transformation of neuronal patch activity occurs. Moreover, GABAergic and glutamatergic neurons respond differently to the presence of calcium buffer. Experiments were performed on two populations of neurons: a population of GABAergic neurons that responded selectively to ATPA, a calcium-permeable GluK1 kainate receptor agonist, and a population of glutamatergic neurons with a large amplitude of cluster depolarization (greater than −20 mV). These neurons made up the majority of neurons. In the population of GABAergic neurons, during BAPTA accumulation, the amplitude of PDS clusters decreases, which leads to a switch from the PDS mode to the classical burst mode with an increase in the electrical activity of the neuron. In glutamatergic neurons, the duration of PDS clusters decreased during BAPTA accumulation. However, the amplitude changed little. The data obtained showed that endogenous calcium-binding proteins play a significant role in switching the epileptiform rhythm to the recovery rhythm and perform a neuroprotective function by reducing the duration of impulses in excitatory neurons and the amplitude of impulses in inhibitory neurons. Full article

Understanding the components of the diet, food groups, and nutritional strategies that help prevent MASLD (Metabolic Dysfunction-Associated Steatotic Liver Disease) is essential for identifying dietary behaviors that can stop the progression of this condition, which currently affects over one-quarter of the global population. This review highlights the importance of including antioxidant nutrients in the diet, such as vitamins C and E, CoQ10, and polyphenolic compounds. It also emphasizes substances that support lipid metabolism, including choline, alpha-lipoic acid, and berberine. Among food groups, it is crucial to choose those that help prevent metabolic disturbances. Among carbohydrate-rich foods, vegetables, fruits, and high-fiber products are recommended. For protein sources, eggs, fish, and white meat are preferred. Among fat sources, plant oils and fatty fish are advised due to their content of omega-3 and omega-6 fatty acids. Various dietary strategies aimed at preventing MASLD should include elements of the Mediterranean diet or be personalized to provide anti-inflammatory compounds and substances that inhibit fat accumulation in liver cells. Other recommended dietary models include the DASH diet, the flexitarian diet, intermittent fasting, and diets that limit fructose and simple sugars. Additionally, supplementing the diet with spirulina or chlorella, berberine, probiotics, or omega-3 fatty acids, as well as drinking several cups of coffee per day, may be beneficial. Full article

β-hydroxybutyrate (BHB) is the most abundant ketone body produced during ketosis, a process initiated by glucose depletion and the β-oxidation of fatty acids in hepatocytes. Traditionally recognized as an alternative energy substrate during fasting, caloric restriction, and starvation, BHB has gained attention for its diverse signaling roles in various physiological processes. This review explores the emerging therapeutic potential of BHB in the context of sarcopenia, metabolic disorders, and neurodegenerative diseases. BHB influences gene expression, lipid metabolism, and inflammation through its inhibition of Class I Histone deacetylases (HDACs) and activation of G-protein-coupled receptors (GPCRs), specifically HCAR2 and FFAR3. These actions lead to enhanced mitochondrial function, reduced oxidative stress, and regulation of inflammatory pathways, with implication for muscle maintenance, neuroprotection, and metabolic regulation. Moreover, BHB’s ability to modulate adipose tissue lipolysis and immune responses highlight its broader potential in managing chronic metabolic conditions and aging. While these findings show BHB as a promising therapeutic agent, further research is required to determine optimal dosing strategies, long-term effects, and its translational potential in clinical settings. Understanding BHB’s mechanisms will facilitate its development as a novel therapeutic strategy for multiple organ systems affected by aging and disease. Full article

MOTS-c is a mitochondrial peptide that plays a crucial role in regulating energy metabolism, gene expression, and immune processes. However, current research primarily focuses on mammals like humans and mice, with no reports on avian MOTS-c. This study aimed to identify and characterize MOTS-c coding sequences across major poultry species through bioinformatics analysis and experimental validation. The alignment results showed high sequence similarity in the MOTS-c coding regions between avian and mammalian species. However, a single nucleotide deletion was identified in avian sequences at the position corresponding to the fourth amino acid residue of mammalian homologs, resulting in divergent downstream amino acid sequences. Despite this deletion, several residues were conserved across species. Phylogenetic analysis of mRNA sequences grouped pigeons with mammals, while protein sequence analysis revealed that poultry and mammals form separate branches, highlighting the divergence between avian and mammalian MOTS-c sequences. Tissue expression profiling demonstrated widespread distribution of chicken MOTS-c across multiple tissues, with the highest expression levels in the heart. Fasting significantly reduced heart MOTS-c expression, suggesting potential metabolic regulatory functions. Functional analysis of MOTS-c in primary hepatocytes revealed significant enrichment of the ribosome, oxidative phosphorylation, and key signaling pathways (PI3K-AKT and JAK-STAT) following 24 hours of treatment. Western blot validation confirmed MOTS-c-mediated activation of the AKT signaling pathway. This study represents the first comprehensive characterization of avian MOTS-c, providing critical insights into its evolutionary conservation and its potential functional roles in gene expression and cellular metabolism. Our findings establish a foundation for further investigation into the functions of mitochondrial-encoded peptides in avian species. Full article

The XPO1 (exportin 1) gene encodes exportin 1 protein responsible for transporting proteins and RNA from the nucleus to the cytoplasm. It has been used as a biomarker for lymphoma detection. XPO1^E571K mutation has been frequently observed and identified as a good prognostic indicator for lymphoma patients. The detection of a target molecule released by lymphoma cells into blood circulation (cell-free circulating tumor DNA, cfDNA) is a better method than tissue biopsy. However, cfDNA concentration in blood circulation is very low in cancer patients. Therefore, a precise and sensitive method is needed. In this study, cfDNA was extracted, and then the XPO1 gene was detected and amplified using conventional PCR. Sanger sequencing was employed to verify the DNA sequences. FAST-COLD-PCR was developed to detect XPO1^E571K gene mutation using a CFX96 Touch Real-Time PCR System. The optimal critical temperature (Tc) was 73.3 °C, allowing selective amplification of XPO1^E571K mutant DNA while wild-type XPO1 could not be amplified. XPO1^E571K gene mutation can be detected by this method with high specificity and sensitivity in lymphoma patients. This approach facilitates rapid and straightforward detection in a timely manner after the diagnosis. Accordingly, the optimized FAST-COLD-PCR conditions can be used as a prototype for XPO1^E571K mutant detection in lymphoma patients. Full article

Background: TGF-β is an immunosuppressive cytokine. Its signaling pathway plays a role in anti-inflammatory responses. Coronary artery disease (CAD) is a clinical consequence of atherosclerosis, which manifests as chronic inflammation and involves platelet mediators, including TGF-β. The aim of this study is to validate the diagnostic utility of TGF-β levels in relation to classical and molecular risk factors for CAD. Methods: The study group included 25 women and 75 men, all aged up to 55 and 50 years, respectively, who had been diagnosed with early-onset CAD. Fasting blood samples were taken to measure plasma levels of TGF-β, sCD36, PCSK9, TNF, VEGF, IL-6, and E-selectin using the ELISA method. Furthermore, a full lipid profile, apolipoproteins (Lp(a), ApoA1, and ApoB), C-reactive protein (hsCRP), and blood morphology were analyzed at the Central Hospital Laboratory. A physical examination was also performed. Results: Positive associations were observed between TGF-β concentration and TNF, platelet count, PTC, and triglyceride levels. TNF and platelet concentration were significant independent predictors of increased plasma TGF-β levels. None of the clinical parameters showed statistically significant associations with plasma TGF-β concentration. Conclusions: Our research has demonstrated that TGF-β levels, including circulating TNF, triglycerides, and platelets, are linked to specific biochemical risk factors in early-onset CAD cases. Full article

Background: Polycystic Ovary Syndrome (PCOS) is a prevalent endocrine disorder characterized by excess body weight, hyperandrogenism, hyperglycemia, and insulin resistance often resulting in hirsutism and infertility. Dietary strategies have been shown to ameliorate metabolic disturbances, hormonal imbalances, and inflammation associated with PCOS. Recent evidence indicates that intermittent fasting (IF) could effectively enhance health outcomes and regulate circadian rhythm; however, its impact on PCOS remain unclear. Objective: Therefore, this systematic review and meta-analysis aims to examine the effect of IF on women diagnosed with PCOS. Methods: Comprehensive research was conducted across three major databases including PubMed, Scopus, and Web of Science without date restrictions. Meta-analysis was performed using Cochrane Review Manager Version 5.4 software. Results: Five studies fulfilled the inclusion criteria. IF significantly reduced body weight (MD = −4.25 kg, 95% CI: −7.71, −0.79; p = 0.02), BMI (MD = −2.05 kg/m², 95% CI: −3.26, −0.85; p = 0.0008), fasting blood glucose (FBG; MD = −2.86 mg/dL, 95% CI: −4.83, −0.89; p = 0.004), fasting blood insulin (FBI; MD = −3.17 μU/mL, 95% CI: −5.18, −1.16; p = 0.002), insulin resistance (HOMA-IR; MD = −0.94, 95% CI: −1.39, −0.50; p < 0.0001), triglycerides (TG; MD = −40.71 mg/dL, 95% CI: −61.53, −19.90; p = 0.0001), dehydroepiandrosterone sulfate (DHEA-S; MD = −33.21 μg/dL, 95% CI: −57.29, −9.13; p = 0.007), free androgen index (FAI; MD = −1.61%, 95% CI: −2.76, −0.45; p = 0.006), and C-reactive protein (CRP; MD = −2.00 mg/L, 95% CI: −3.15, −0.85; p = 0.006), while increasing sex hormone-binding globulin (SHBG; SMD = 0.50, 95% CI: 0.22, 0.77; p = 0.004). No significant changes were observed in waist-to-hip ratio (WHR), total cholesterol (TC), LDL, HDL, total testosterone (TT), or anti-Mullerian hormone (AMH). Conclusions: IF represents a promising strategy for improving weight and metabolic, hormonal, and inflammatory profiles in women with PCOS. However, the existing evidence remains preliminary, necessitating further robust studies to substantiate these findings. Full article

Background: Malnutrition and cancer-related fatigue (CRF) are prevalent in cancer patients, significantly impacting prognosis and quality of life. Oral nutritional supplements (ONSs) enriched with protein and ω-3 fatty acids may improve nutritional status and mitigate CRF. This study evaluates the effects of a high-protein, fish oil-enriched ONS (FOHP-ONS) on nutritional intake, body composition, fatigue, and quality of life in malnourished cancer patients. Methods: Cancer patients with malnutrition or inadequate food intake received 8 weeks of FOHP-ONS (2 cans/day, providing 4.2 g/day of ω-3 fatty acids). Dietary intake, body weight, handgrip strength, serum biochemical markers, nutritional status (PG-SGA), fatigue (BFI-T), and quality of life (EORTC QLQ-C30) were assessed at baseline, week 4, and week 8. Results: Of the 33 enrolled patients, 30 completed the study. Energy and protein intake significantly increased (p < 0.05), and body BMI and handgrip strength showed significant improvements (p < 0.05), while muscle mass did not change significantly. Nutritional status, assessed by PG-SGA, improved, with the proportion of severely malnourished patients (Stage C) decreasing from 46.7% to 13.3%, and moderately malnourished patients (Stage B) improving to well-nourished status (Stage A) from 10.0% to 30.0% (p < 0.001). Serum albumin levels increased significantly (p < 0.05), while fasting blood glucose significantly decreased (p < 0.05). Additionally, triglyceride levels significantly decreased (p < 0.05), while total cholesterol and LDL-C showed a downward trend. Cancer-related fatigue scores improved across all domains (p < 0.05), and quality of life significantly increased, particularly in physical and role functioning (p < 0.05). Conclusions: FOHP-ONS supplementation improved nutritional intake, body composition, and muscle strength while alleviating CRF and enhancing quality of life in malnourished cancer patients. These findings support its potential role in nutritional intervention for malnourished cancer patients. Full article

Background: Intermittent fasting (IF) can improve inflammatory status, but its effects may be dependent on the mode of fasting. Objectives: We performed a systematic review with pairwise and network meta-analyses to investigate the effects of different modes of IF on inflammatory markers in adults. Methods: Three database searches were conducted, including PubMed, Scopus, and Web of Science, from inception to June 2024. The searches used two keyword groups: “intermittent fasting” and “inflammatory markers”. Randomized and non-randomized trials investigating any IF mode on inflammatory markers, including interleukin (IL)-6, tumor necrosis factor (TNF)α, C-reactive protein (CRP), leptin, and adiponectin, were included. Standardized mean differences (SMDs) were calculated using random effects models for both analyses. Results: A total of 21 studies (839 participants) were included. Compared with controls, IF reduced TNF-α [SMD: −0.31, p = 0.009], CRP [SMD: −0.19, p = 0.04], and leptin [SMD: −0.57, p = 0.005] but did not significantly affect IL-6 or adiponectin. Among the IF modes, time-restricted feeding (TRF) showed the largest reduction in TNF-α [−0.39, p = 0.001]. TRF had the highest probability ranking for changes in IL-6, TNF-α, leptin, and adiponectin; however, the effects on IL-6 and adiponectin were not statistically significant. The 5:2 diet ranked highest for CRP. Conclusions: IF may be an effective dietary therapy for improving some inflammatory markers, with effects potentially influenced by the mode of IF. TRF had the highest rankings across multiple markers, though the findings were not uniformly significant. Additional longer-term trials are needed to fully elucidate the anti-inflammatory potential of IF. Full article

Bovine serum albumin (BSA), the most commonly used protein in preimplantation embryo culture media, performs a variety of physiological functions. However, its involvement in long-term effects remains largely unclear. To investigate its physiological importance in culture media, we examined the developmental and metabolic consequences of BSA deprivation during preimplantation stages in mice. Embryos cultured in BSA-free media during specific time windows exhibited impaired blastocyst formation, with continuous deprivation from the two-pronuclei (2PN) stage significantly reducing trophectoderm (TE) and inner cell mass (ICM) cell numbers (p < 0.05), indicating compromised viability. Short-term BSA deprivation similarly disrupted lineage allocation, underscoring the sensitivity of early embryos to nutrient availability during cell fate determination. Although birth rates remained unaffected, suggesting compensatory mechanisms, longitudinal analysis revealed sex-specific metabolic dysfunction. Male offspring developed progressive glucose intolerance by 16 weeks, exhibiting elevated fasting glucose levels (p < 0.05) and impaired glucose clearance, whereas females showed no significant alterations in glucose metabolism. This study demonstrates that protein restriction during the preimplantation period not only disrupts early embryonic development but also programs long-term metabolic dysfunction, underscoring the importance of optimizing culture conditions in assisted reproductive technologies to minimize future health risks. Full article

Efficient and rapid detection of bacterial pathogens is crucial for food safety and effective disease control. While conventional methods such as PCR and ELISA are accurate, they are time-consuming, costly, and often require specialized infrastructure. Recently, electrochemical biosensors integrating graphene nanomaterials with bacteriophages—termed graphages—have emerged as promising platforms for pathogen detection, offering fast, specific, and highly responsive detection. This review critically examines all electrochemical biosensors reported to date that utilize graphene–phage hybrids. Key aspects addressed include the types of graphene nanomaterials and bacteriophages used, immobilization strategies, electrochemical transduction mechanisms, and sensor metrics—such as detection limits, linear ranges, and ability to perform in real matrices. Particular attention is given to the role of phage orientation, surface functionalization, and the use of receptor binding proteins. Finally, current limitations and opportunities for future research are outlined, including prospects for genetic engineering and sensor miniaturization. This review serves as a comprehensive reference for researchers developing phage-based biosensors, especially those interested in integrating carbon nanomaterials for improved electroanalytical performance. Full article

Background: Ginger contains gingerols, shagaols, paradols, gingerdiones, and terpenes, which have been shown to display anti-inflammatory properties and inhibit pain receptors. For this reason, ginger has been marketed as a natural analgesic. This study examined whether a specialized ginger extract obtained through supercritical CO₂ extraction and subsequent fermentation affects pain perception, functional capacity, and markers of inflammation. Methods: Thirty men and women (56.0 ± 9.0 years, 164.4 ± 14 cm, 86.5 ± 20.9 kg, 31.0 ± 7.5 kg/m²) with a history of mild to severe joint and muscle pain as well as inflammation participated in a placebo-controlled, randomized, parallel-arm study. Participants donated fasting blood, completed questionnaires, rated pain in the thighs to standardized pressure, and then completed squats/deep knee bends, while holding 30% of body mass, for 3 sets of 10 repetitions on days 0, 30, and 56 of supplementation. Participants repeated tests after 2 days of recovery following each testing session. Participants were matched by demographics and randomized to ingest 125 mg/d of a placebo or ginger (standardized to contain 10% total gingerols and no more than 3% total shogaols) for 58 days. Data were analyzed by a general linear model (GLM) analysis of variance with repeated measures, mean changes from the baseline with 95% confidence intervals, and chi-squared analysis. Results: There was evidence that ginger supplementation attenuated perceptions of muscle pain in the vastus medialis; improved ratings of pain, stiffness, and functional capacity; and affected several inflammatory markers (e.g., IL-6, INF-ϒ, TNF-α, and C-Reactive Protein concentrations), particularly following two days of recovery from resistance exercise. There was also evidence that ginger supplementation increased eosinophils and was associated with less frequent but not significantly different use of over-the-counter analgesics. Conclusions: Ginger supplementation (125 mg/d, providing 12.5 mg/d of gingerols) appears to have some favorable effects on perceptions of pain, functional capacity, and inflammatory markers in men and women experiencing mild to moderate muscle and joint pain. Registered clinical trial #ISRCTN74292348. Full article

p-Cresyl sulfate (PCS), a gut-derived uremic toxin with proinflammatory and cytotoxic effects, has been implicated in cardiovascular injuries among patients with chronic kidney disease (CKD). Aortic stiffness (AS), assessed by carotid–femoral pulse wave velocity (cfPWV), is a recognized predictor of cardiovascular risk. This study investigated the association between serum PCS levels and AS in patients with nondialysis-dependent CKD. In total, 165 patients with nondialysis-dependent CKD were enrolled. Clinical data and fasting blood samples were collected. Arterial stiffness (AS) was assessed bilaterally by measuring carotid–femoral pulse wave velocity (cfPWV) on both the left and right sides. A value above 10 m/s was considered indicative of increased stiffness. Serum PCS levels were quantified using high-performance liquid chromatography–mass spectrometry. Fifty patients (30.3%) had AS. The AS group was significantly older and had higher diabetes prevalence, systolic blood pressure, fasting glucose, urinary protein-creatinine ratio, and PCS levels than the control group. In the multivariate analysis, both PCS (odds ratio [OR]: 1.097; 95% confidence interval [CI]: 1.024–1.175; p = 0.008) and age (OR: 1.057; 95% CI: 1.025–1.090; p < 0.001) were independently associated with AS. In conclusion, elevated serum PCS and older age were independently associated with AS. Thus, PCS is a potential early marker of vascular damage in CKD. Full article