Journal of physiology and biochemistry最新文献

Aerobic training (beneficial for type 1 diabetes mellitus (T1DM) patients) could result boring, leading to inactivity or suboptimal performance. Therefore, High-Intensity Interval Training (HIIT) could be an appealing alternative. The present study aimed to compare modulation of certain inflammatory cytokines in T1DM participants performing aerobic vs. HIIT routines. We recruited 26 T1DM male subjects: ages 18-40, T1DM ≥ 2 years, glycated hemoglobin < 8.5%, stable insulin regimen for 6 months, minimum 90 min weekly physical activity and completion of International Physical Activity Questionnaire (IPAQ). IPAQ:2 corresponds to moderate activity and IPAQ:3 to intense physical activity. Participants performed a single aerobic or HIIT session separated by at least 72 h. Blood plasma samples were collected 20 min before and after each session. Cytokines were measured using LUMINEX technique. After aerobic exercise, pro-inflammatory cytokines interleukin (IL)-1β, IL-6, IL-7, IL-8, IL-17 A, tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) showed no significant differences in participants (IPAQ:2 and 3). Only anti-inflammatory cytokine IL-2 increased significantly in IPAQ:3 participants. Compared to pre-exercise, post-exercise HIIT situation presented a similar pattern. The 4 participants (IPAQ:3) that voluntarily followed a 12-week HIIT routine, showed significant increases in IL-7, IL-8, and TNF- α, and the detection of the anti-inflammatory cytokine IL-22. Altogether, these results suggest that HIIT favors the presence of some pro-inflammatory cytokines. The anti-inflammatory action of certain cytokines, such as IL-22, should be considered for a possible compensatory action. Nevertheless, programs of interval exercises at moderate intensity could be at the moment a safe option for T1DM patients.

High-altitude hypoxia (HH) significantly affects mammalian physiological functions, especially sleep rhythms, anxiety-like behavior, and neuroinflammation. In this study, adult male Sprague-Dawley rats were randomly assigned to five groups: Control, HH, HH with low-dose dexmedetomidine (Dex), HH with high-dose Dex, and Control with Dex. Rats were exposed to a simulated 6000-meter altitude for 7 days. Behavioral tests, enzyme-linked immunosorbent assay (ELISA), reverse transcription quantitative PCR (RT-qPCR), and Western blotting were used to assess hormone levels, gene/protein expression, and inflammatory markers. HH exposure elevated hypothalamic serotonin (5-hydroxytryptamine, 5-HT) and reduced melatonin levels. The sleep rhythm-related gene Timeless was downregulated, while Homer1 was upregulated at both mRNA and protein levels. Knockdown of Timeless or overexpression of Homer1 resulted in a significant increase in hypothalamic 5-HT levels and a marked decrease in melatonin levels. HH induced enhanced anxiety-like behaviors and reduced spontaneous activity, accompanied by elevated levels of L-1β, IL-6, and TNF-α in both serum and hypothalamus. Inhibition of the TLR4-MyD88-NFκB pathway significantly alleviated both hormonal disturbances and anxiety-like behaviors in HH rats.Dex treatment, especially at high doses, suppressed inflammatory responses, normalized hormone levels, restored sleep gene expression, and improved behavioral outcomes. These results indicate that dex mitigates HH-induced sleep and inflammatory disturbances, highlighting its therapeutic potential for high-altitude neurological dysfunction.

Long non-coding RNAs (lncRNAs), defined as transcripts exceeding 200 nucleotides without protein-coding potential, have emerged as pivotal regulators in diverse physiological and pathological processes, particularly in tumorigenesis. Among them, NR2F1-AS1, a recently characterized lncRNA, has garnered growing attention due to its dysregulated expression across a spectrum of malignancies and its significant correlation with key clinicopathological parameters. Accumulating evidence from molecular and cellular studies reveals that NR2F1-AS1 plays multifaceted roles in cancer initiation and progression through the modulation of signaling pathways, regulation of gene expression, and interactions with microRNAs and protein complexes. Notably, its biological function appears to be context-dependent: acting as an oncogene in many cancer types, such as breast, lung, liver, and gastric cancer, while exhibiting potential tumor-suppressive activity in others, including colorectal cancer, cervical squamous cell carcinoma, and thymic epithelial tumors. This review comprehensively summarizes the aberrant expression patterns, prognostic significance, biological functions, and molecular mechanisms of NR2F1-AS1, while also highlighting its emerging potential as a context-specific diagnostic biomarker and therapeutic target in human cancers.

Addressing the physiological effects of bioactive compounds in metabolic diseases (i.e., obesity, diabetes, liver steatosis) and establishing their mechanisms of action have been a major interest for the last decades. However, methodologies that can be applied to achieve this can vary greatly, leading to a limited type of information. Thus, the accuracy, robustness, reliability and potential (human) translation are highly reliant on the experimental design and selected methodological models. This review presents an update exploring the main features, advantages and disadvantages of most important pre-clinical models used at the present time to study the effects of bioactive compounds on metabolic diseases. Moreover, future challenges in developing new methods are also depicted. In vitro models (enzyme assays and standard two-dimensional cultures of adipocytes, skeletal muscle cells) are intrinsically well established and constitute the first choice and most widely used methods to study bioactive compounds in metabolic diseases. However, novel models such as three-dimensional cultures (spheroids, organoids) are also starting to emerge and complement traditional culture systems. Models of small organisms (C. elegans, D. melanogaster) and non-mammal vertebrates (D. rerio) represent a scientific advantage and a middle-step before traditional mammalian models (rats and mice). This article provides extensive information and a critical overview of a wide range of methods that represent present and future avenues towards a further understanding of metabolic diseases. Combining and developing new methods will be key for future progression on the effects of bioactive compounds on metabolic diseases, as well as to minimize the use of mammalian models due to ethical reasons.

Atherosclerosis is a complex cardiovascular disease characterised by the accumulation of lipids, inflammatory cells, and fibrous elements within arterial walls, leading to plaque formation and increased risk of cardiovascular events. Recent evidence highlights the pivotal roles of purinergic receptors in mediating the inflammatory and cellular processes associated with atherosclerosis. This review examines the roles of purinergic receptors in the pathophysiology of atherosclerosis, with a particular focus on the P1 subtype (A2A and A3 receptors), the P2X subtype (P2X4 and P2X7 receptors), and the P2Y subtype (P2Y2, P2Y11, and P2Y12 receptors). The A2A and A3 receptors are involved in modulating vascular inflammation, endothelial cell function, and vascular smooth muscle cell calcification. P2X4 has been implicated in the production of pro-inflammatory cytokines and the promotion of plaque inflammation, whereas P2X7 contributes to vascular inflammation, plaque progression, and rupture. The P2Y2 receptor plays critical roles in regulating vascular inflammation and calcification, smooth muscle cell migration, and plaque growth. Furthermore, the P2Y11 receptor has been shown to modulate endothelial cell inflammation, while P2Y12 is associated with lipid accumulation, foam cell formation, vascular smooth muscle cell migration, and plaque development. By synthesising current knowledge on the involvement of purinergic signalling in atherosclerosis, this review discusses potential therapeutic targets for intervention. Specifically, P2Y receptor antagonists present promising avenues for reducing inflammation and improving vascular function in atherosclerotic patients. However, despite the advancements in understanding purinergic receptor functions, challenges remain in translating this knowledge into clinical practice. Further research is essential to unravel the intricate signalling pathways of these receptors and to develop effective biomarker strategies and therapeutic interventions aimed at combatting atherosclerosis and its associated complications.

Long-term consumption of high-calorie diets can lead to metabolic disorders. In this study, we evaluated the effects of an eight-week standard (control), high-fat high-fructose (HFFD), alpha-ketoglutarate (AKG)-supplemented (1% in drinking water), and combined diet (HFFD + AKG) on hematological and oxidative stress parameters across tissues of male C57BL/6J mice. Both HFFD and AKG decreased erythrocyte count and altered leukocyte profile, increasing neutrophils and monocytes while decreasing lymphocytes. HFFD increased visceral fat mass and intensified oxidative stress in adipose tissue, as indicated by elevated lipid peroxide (LOOH) levels. LOOH levels in adipose tissue of AKG- and HFFD + AKG-fed mice matched control. HFFD or AKG lowered glutathione peroxidase and NAD(P)H-quinone oxidoreductase 1 (NQO1) activities in adipose tissue relative to control, unlike HFFD + AKG-fed counterparts. The heart showed an adaptive response to HFFD, with increased glutathione-S-transferase (GST), glucose-6-phosphate dehydrogenase, and NQO1 activities, and lower levels of oxidized glutathione (GSSG). AKG increased reduced glutathione (GSH) levels and elevated GPx and GST activities in the heart, whereas HFFD + AKG-fed mice had lower LOOH levels than HFFD-fed counterparts. Similarly, HFFD and AKG decreased GSSG and increased GSH in skeletal muscle. Both AKG- and HFFD + AKG-fed mice had lower carbonyl protein levels in muscle compared to control and HFFD-fed mice. Like adipose, muscle of HFFD- and AKG-fed mice had lower NQO1 activity compared to control, unlike HFFD + AKG group. These findings suggest AKG may mitigate HFFD-induced oxidative stress and modulate hematological parameters, with tissue- and diet-dependent effects, suggesting its role as an antioxidant under metabolic stress and a regulator of baseline redox homeostasis.

Age-associated sarcopenia is characterized by progressive loss of skeletal muscle mass and function. Irisin, a myokine, has been shown to improve sarcopenia; however, the dosage-dependence of its effects and the underlying molecular mechanisms remain unclear. To investigate the effects of irisin on age-associated sarcopenia, 22-week-old mice were used. Recombinant irisin was administered via intraperitoneal injections at doses of 0.5, 1, and 2 mg/kg, three times per week, to evaluate potential dosage-dependent effects. Skeletal muscle function was assessed using hanging time, grip strength, and muscle mass measurements. Morphological changes in muscle tissue were examined through hematoxylin and eosin staining, and fibrosis was quantified using Masson staining. Serum irisin levels were measured via enzyme-linked immunosorbent assay, and protein expression was analyzed using Western blotting. Recombinant irisin treatment significantly increased serum irisin levels in aged mice and improved functional metrics, including hanging time, maximum speed, grip strength, and muscle mass, in a dosage-dependent manner. Histological analysis revealed improvements in muscle structure and a reduction in fibrosis following irisin treatment. Molecular analyses suggested that irisin may modulate iron homeostasis and restore key oxidative stress-related proteins such as GPX4 and SLC7A11. Further exploration revealed that irisin treatment restored sirtuin 1 (SIRT1) levels, leading to deacetylation of P53 and subsequent reduction in its expression. Irisin treatment ameliorates age-associated sarcopenia in a dosage-dependent manner, potentially involving iron overload and the SIRT1/P53 pathway. These findings provide insights into the therapeutic potential of irisin for age-related skeletal muscle atrophy.

Mediated by the bitter taste receptors (TAS2R), the perception of bitter taste does not only involve the oral cavity but various physiological systems throughout the gastrointestinal tract. The relationship between stimulation and modulation is crucial for understanding the broader implications of bitter taste signalling in health and disease. In this study, we investigated how the expression of intestinal rat Tas2r (rTas2r) is affected by natural extracts containing bitter ligands, examined their association with obesity, and their effects on GLP-1 secretion. For this, we performed subchronic stimulations with a mixture of polyphenols and individual molecules in rats. Moreover, we also examined how the individual bitter molecule (epicatechin) affects the secretory profile of intestinal enteroendocrine cells. Treating rats with procyanidins up-regulated rTas2r in all the segments of the gastrointestinal tract, with the most changes observed in the duodenum and ascending colon. Epicatechin, one of the main components of the previously used extract, had a much more specific effect, as we observed mostly changes in the jejunum, where rTas2137, -139, -143 and -144 were up-regulated. In Hutu-80 cells, epicatechin downregulated TAS2R14 after 24 hours, which limited GLP-1 secretion after acute peptone stimulation. Our results support a network effect in the role of the bitter taste receptors along the intestinal areas that must be considered to address the work with bitter agonists.

Ceramides are sphingolipids formed from fatty acids linked to sphingosine and an amide, which are involved in cellular pathways such as apoptosis, fibrosis, oxidative stress, and inflammation. Six distinct fatty acyl selective ceramide synthases (CerS) produce ceramides. This specific enzymatic modulation can either increase or reduce the production of specific ceramides, which can have either adverse or protective effects, suggesting that enzymatic modulation may serve as a tool for innovative therapy. Specifically, modulation of glucosylceramide synthase, sphingomyelinase, or ceramidase can reverse the generation of potentially apoptotic ceramides, similar to how inhibition of serine palmitoyltransferase or ceramide synthases may be significant in inflammatory conditions by decreasing the generation of inflammatory ceramides. In this context, the modulation of plasma ceramides may represent a protective factor for chronic non-communicable diseases (NCDs), such as cardiovascular diseases, type 2 diabetes, and chronic kidney disease. Previous studies indicate that dietary fat and protein intake influence plasma sphingolipid levels. Therefore, this review aims to discuss the effects of ceramide on patients with NCDs, providing an overview of the influence of nutrition on ceramide levels and outlining future perspectives.