EXCLI Journal最新文献

Pacing in multi-day long-distance triathlons has been investigated mainly in male athletes. We analyze physiological aspects such as energy expenditure and heart rate changes as well as biomechanical aspects in swimming (e.g. strokes per lane) and running (e.g. stride frequency, stride length, vertical ratio, vertical movement, ground contact time) in the first and only female triathlete to finish 30 IRONMAN^®-distance triathlons in 30 days. The split times, lap times for swimming, cycling and running and variables were recorded with Fenix 7 Sapphire Solar with Normalized Power^® (NP^®), Intensity Factor^® (IF^®) and Training Stress Score^® (TSS^®), and were analyzed. The models' estimations for pacing were assessed with R2. Variance (ANOVA) and associative (Pearson and Spearmen) analysis were conducted at a level of significance of 5 %. Swimming pace remained stable throughout the race (linear p = 0.473), cycling pace demonstrated a significant slowdown (third-order polynomial p < 0.001), and running pace significantly improved (third-order polynomial p < 0.001). Energy expenditure slightly decreased in swimming (p = 0.099) and progressively increased for both cycling (p = 0.034) and running (p = 0.044). Moderate-intensity swimming time initially increased and later decreased, with an opposite trend for high-intensity swimming time. Cycling times at both moderate and high intensities slightly decreased. Running showed decreasing moderate-intensity time and increasing high-intensity time, consistent with improved pace. Transition times increased over the race period, with T1 increasing more prominently. Biomechanical parameters in swimming, including total stroke count and SWOLF index, showed increasing trends. Overall, significant differences were observed in running time at moderate intensity (p < 0.001, η² = 0.513), high intensity (p < 0.001, η² = 0.518) and average pace (p < 0.001, η² = 0.603). The athlete spent significantly more time at moderate intensity (p = 0.019 and p = 0.002) and significantly less time at high intensity (p = 0.011 and p = 0.005) running in the initial phase, compared to the middle and final stages of the race. All biomechanical variables decreased slightly in the opening phase of the race but then increased in the middle and final stages of the race. Overall, the results highlight that running was the discipline most affected by physiological and pacing adaptations throughout the race; while cycling and swimming parameters demonstrated weaker or no consistent associations.

Extracellular vesicles (EVs) and microRNAs, involved in intercellular communication, have emerged as potential biomarkers in liver diseases. This study aimed to evaluate EV characteristics and microRNA transport across the full spectrum of metabolic dysfunction-associated steatotic liver disease (MASLD). 168 patients with MASLD and 50 controls were recruited. Biochemical and clinical variables were evaluated. EVs were isolated from serum and characterized by nanoparticle tracking analysis, flow cytometry, and Western blotting. Using MiRWalk 3.0 and the TarPmiR algorithm, candidate EV-associated microRNAs related to MASLD were identified. The expression of miR-4758, miR-188, miR-1226, and miR-122, was evaluated in EVs and serum. EV size and concentration varied significantly across disease stages (p<0.001 and p<0.05, respectively), with early MASLD dominated by exosome, and later stages showing a shift toward microvesicles. In MASLD patients, interestingly, miR-122 was lower in EVs compared to serum (p<0.05). In steatosis, it was higher in serum than EVs (p<0.05), without significant differences in later stages. miR-122 in EVs increased in association with GGT and cholesterol, and decreased with elevated creatinine. Serum miR-122 was also elevated in patients with high cholesterol. In MASLD miR-4758 was higher in EVs than in serum (p<0.05), expressed in steatosis and cirrhosis (p<0.05), suggesting it is a good disease marker, and detected exclusively in serum in HCC (p<0.05). miR-4758-EVs increased with high glucose. MiR-188 and miR-1226 were exclusively expressed in serum (p<0.05), and miR-1226 was elevated in patients with high cholesterol. EV size was reduced in individuals with high triglycerides and albumin, suggesting interaction between EVs, biochemical parameters and disease stage. These findings suggest that microRNA expression and transport in EVs and serum vary across MASLD stages and associate with key biochemical parameters, supporting the clinical value of jointly assessing both compartments as potential biomarkers to distinguish early disease from advanced stages such as HCC. See also the graphical abstract(Fig. 1).

The metabolic environment provided by the culture medium plays a critical role in shaping cellular function and mitochondrial activity in vitro. In this study, we investigated the effects of metabolic priming on the metabolism and morphology of Normal Human Dermal Fibroblasts (NHDFs) by manipulating glucose availability in the culture medium. Our strategy involved transitioning NHDFs from traditional high-glucose medium (HGm) to either a medium with physiological glucose levels (LGm) or a glucose-free, galactose-containing medium (OXm). Prior to cellular characterization, we confirmed the absence of glucose in the culture media and fetal bovine serum using ¹H nuclear magnetic resonance (NMR) spectroscopy. Given previous observations of elevated reactive species under glucose-free conditions, we explored the cellular adaptations associated with a metabolic shift from glycolysis to oxidative phosphorylation (OXPHOS). Cells cultured in OXm exhibited increased metabolic activity, elevated protein content, and substantial metabolic remodeling. Morphological analysis revealed enlargement of the cell body, cytoplasm, mitochondria, and nuclei, indicative of extensive structural adaptation. Notably, oxygen consumption rate (OCR) nearly doubled within 24 h of exposure to OXm, reflecting a rapid mitochondrial response to metabolic stress. The presence of the antioxidant N-acetyl cysteine (NAC) attenuated this increase, suggesting that redox signaling plays a key role in mitochondrial bioenergetic adaptation. These findings underscore the complex interplay between metabolic context, oxidative stress, and cellular morphology, and highlight the importance of appropriate normalization strategies in metabolic studies. See also the graphical abstract(Fig. 1).

Octamethylcyclotetrasiloxane (D4) is a highly volatile cyclic siloxane used to produce silicone polymers. D4 has been shown to attenuate the LH surge in rats, resulting in reduced litter sizes. However, it has been hypothesized that these biological effects observed only at high dose levels of D4 may be because of changes in membrane microviscosity (fluidity) leading to a non-specific mode of action. Here, we set out to determine if D4 increases membrane microviscosity and link this to membrane domain function alterations. The studies reported here support the hypothesis that D4 affects ovulation via a concentration-dependent, physical-chemical mode of action that is not specific for any particular component of the neuro-endocrine system and is, therefore, not endocrine disruption but a non-specific effect. Furthermore, D4 also increases the membrane fluidity of the hypothalamic cell membrane in vitro. It is expected that a similar response would occur in vivo. This alteration in membrane fluidity decreases the release of GnRH and kisspeptin. GnRH and kisspeptin are necessary for the pre-ovulatory LH surge from the pituitary. In the absence of a GnRH and kisspeptin release, there is no signal to the pituitary for the driver of the LH surge. D4 can change membrane fluidity in vitro and likely in vivo and associated behaviors of membrane proteins/lipoproteins of various kinds via non-specific mechanisms.

Neuroinflammation is a key characteristic associated with neurological disorders, particularly depression and anxiety. This study aims to evaluate the neuroprotective and antidepressant-like effects of pine needle (PN) extracts in an LPS-induced neuroinflammation mouse model. Following seven days of oral administration of PN, the tail suspension test demonstrated a significant reduction in immobility time in PN-treated mice compared to LPS controls, surpassing the effect of the standard antidepressant bupropion. To elucidate the underlying mechanisms, we conducted a whole-genome microarray analysis. This analysis highlighted pathways related to neuroprotection, synaptic plasticity, and pro-inflammatory cytokine regulation, with a notable enrichment in the Apelin signaling pathway. Quantitative PCR analysis revealed that PN treatment increased the levels of Apelin and its receptor while decreasing proinflammatory cytokines Tnfa and IL1b in the hippocampus. ELISA further demonstrated elevated levels of key neurotransmitters, including dopamine and noradrenaline, in the mouse hippocampus. Additionally, we performed GC/MS analysis to identify bioactive compounds in PN, revealing D-Pinitol and Shikimic acid as major constituents. Importantly, catechol exhibited significant neuroprotective effects, and similar protective effects were also noted in the mixed compositions. The MTT assay showed that PN and its compounds significantly improved cell metabolic activity against dexamethasone-induced cytotoxicity. In conclusion, our findings highlight the potential of PN as a natural therapeutic agent for depressive symptoms, promoting neuroprotection, enhancing neurotransmitter levels, and modulating inflammatory responses. See also the graphical abstract(Fig. 1).

Interferon-gamma (IFN-γ), as a pleiotropic cytokine, plays a pivotal role in antitumor immunity. Its remarkable immunostimulatory, antiproliferative, and pro-apoptotic effects make it a promising candidate for tumor immunotherapy. Here, we highlight the dual role of IFN-γ in the tumor microenvironment during tumor development and treatment. IFN-γ can enhance antigen presentation, boost cytotoxic T cell and natural killer cell activity, and inhibit angiogenesis, promoting tumor regression and correlating with favorable therapeutic outcomes. However, prolonged exposure may induce the upregulation of immune checkpoint molecules such as programmed death-ligand 1, trigger T cell exhaustion, and recruit regulatory T cells, phenomena associated with the development of treatment resistance in cancer therapy. This dual nature poses significant challenges for harnessing IFN-γ in tumor treatment, necessitating an in-depth understanding of its mechanisms within specific microenvironments. Although numerous studies have explored IFN-γ-based tumor therapies, their outcomes have been inconsistent. Thus, although IFN-γ-based therapeutic strategies hold considerable promise, their clinical translation requires precise modulation to fully exploit its antitumor effects while mitigating potential protumor risks. See also the graphical abstract(Fig. 1).