BACKGROUND:There is increasing evidence that inflammation is an important determinant in COVID-19 pathogenesis. Several studies describe cytokines and microRNAs as important regulators of immune and inflammatory responses in other diseases, regarding them as valuable biomarkers. AIM:Identify a potential relationship between cytokines (interleukin [IL]-6, IL-8) and microRNAs (miR-146a-5p, miR-155-5p) and clinical characteristics of COVID-19 patients, focusing on disease severity and mortality risk. METHODS:Serum expression levels of miR-146a, miR-155, IL-6, IL-8, C-reactive protein, ferritin, and neutrophil-to-lymphocyte ratio, of 25 mild, 73 moderate, and 39 severe COVID-19 patients from Quito-Ecuador, were determined to correlate outcomes with clinical parameters. RESULTS:In all groups, overweight and obesity were the most prevalent comorbidities (75.91%). Serum levels of IL-6 were significantly elevated in patients with moderate and severe COVID-19 (analysis of variance [ANOVA] p ≤ 0.000). miR-146a was significantly decreased in moderate and severe COVID-19 patients when compared with mild cases (ANOVA p = 0.002). ROC curve analysis showed that selected cut-off values for miR-146a > 3.999 ΔCt for mild vs moderate condition (sensitivity 83.56%, specificity 48%) and miR-146a > 3.999 ΔCt for mild vs severe condition (sensitivity 84.62%, specificity 40%), and IL-6 ≥ 72.25 pg/mL (sensitivity 78.95%, specificity 60.61%) when combined with clinical pretest probability, can be used to predict aggravation and death in COVID-19 patients. Odds ratios (ORs) of miR-146a (OR = 4.322) and IL-6 (OR = 3.198) indicate an increased risk of worsening and death, respectively, when cut-off points were taken into consideration. CONCLUSION:This study shows that elevated inflammatory IL-6 and decreased serum levels of anti-inflammatory miR-146a-5p can be discriminatory markers of COVID-19 severity and mortality.
Hydrogels have become popular for biomedical applications, such as patches and scaffolds for tissue engineering, due to their high-water content, biocompatibility, and tunable physico-chemical and mechanical properties. For instance, chronic wounds remain one of the major global healthcare burdens and, therefore, demand sophisticated ways of managing dressings for fast wound healing to reduce pain, prevent infection, and accelerate healing. κ-Carrageenan (kC) is a polysaccharide extracted from red seaweeds and has been widely considered a promising wound dressing material owing to its biocompatibility and hemostatic properties. Degalactosylated xyloglucan (dXG), obtained through the partial enzymatic removal of galactose from xyloglucan, has demonstrated biocompatibility, anti-inflammatory activity, and excellent scaffolding potential for cells. Both polymers show temperature-induced sol-to-gel transition; however, none of the two form hydrogels that can be used as wound dressings; dXG is too soft, while kC is too brittle, lacking adhesiveness and interconnected porosity. To address these limitations, this study explores interpenetrating hydrogel networks composed of kC and dXG. The resulting kC/dXG hydrogels demonstrate improved mechanical integrity due to the structural contribution of kC, while dXG imparts enhanced swelling capacity and surface adhesiveness. Together, these features make the kC/dXG hydrogel films promising candidates for bioactive wound dressings, yielding hydrogels with good mechanical stability due to kC and enhanced biological properties attributed to dXG.
The negative slope of human ovulatory fidelity begins with a high follicular fund balance with gradual withdrawals over time. This depletion of reserve is a sentinel event foreshadowing severe reproductive loss and, eventually, systemic aging. Conversely, the youthful ovarian phenotype requires coordination among endothelial, granulosa, immune, perivascular, stromal, and perhaps germline stem cells. This diverse tissue matrix theoretically can be modified by platelet (PLT)-derived moieties, but this awaits experimental confirmation in adult ovaries. Indeed, while the cellular entropy states of menopause and low reserve could follow a final common pathway, cell kinetics are not always irreversible within this set. We propose an experimental design to track nuclear factor κB (NF-κB) oscillations, tumor necrosis factor-alpha (TNF-α), selected gene expression, apoptosis, and key immune/inflammatory actions as entropy drivers antagonizing reproductive fitness. Since NF-κB and TNF-α are discharged in activated PLT releasate (or react to its cargo proteins), our investigation audits response markers pre- vs post-injection of processed platelet-rich plasma (PRP), connecting discrete signals to transcriptional output, cell function, and ovarian cytoarchitecture. This may reveal intraovarian PRP operating as a local entropy rectifier, with organ field function shifting to support oocyte competence incidentally, where “menopause reversal” is merely a beneficial secondary effect.
The interaction between exercise and mitochondrial biogenesis in skeletal muscle is fundamental to human physiology, with important implications for health and athletic performance. While exercise is known to stimulate mitochondrial biogenesis, the effectiveness of varying-intensity exercise remains unclear. This systematic review and meta-analysis aimed to evaluate the impact of physical activity on mitochondrial biogenesis pathways in skeletal muscle and identify key biomolecular markers in healthy individuals. Among these, PGC-1α emerged as the most consistently reported marker. The meta-analysis showed a significant increase in PGC-1α expression following endurance exercise, with a pooled effect size of Hedge’s g = 1.17 (95% confidence interval: 0.14–2.19, I 2 = 84.5%), indicating a large effect with substantial heterogeneity. Subgroup analyses revealed that both interval and continuous endurance training produced large effects (Hedge’s g = 1.29 and 1.01, respectively), with no significant difference between modalities (p > 0.05). These findings confirm that exercise induces significant molecular and structural mitochondrial adaptations, with responses influenced by exercise type, intensity, and duration. This underscores exercise as a potent stimulus for mitochondrial biogenesis, supporting its role in promoting metabolic health and physical performance.
The biochemical processes in the cellular milieu involving biomacromolecular interaction usually occur in crowded and heterogeneous environments, impacting their structure, stability, and reactivity. The crowded environment in vivo is typically ignored for experimental investigations since the studies get complex due to intracellular biophysical interactions between nucleic acids, proteins, cellular membranes, and various cations/anions present in the cell. Thus, being a ubiquitous property of all cells, studying those biophysical aspects affecting biochemical processes under realistically crowded conditions is of prime importance. Crowders or crowding agents are usually exploited to mimic the in vivo conditions on interacting with such genomic species, revealing structural and functional changes resulting from excluded volume and soft interactions. In the last few years, studies including crowders of varied sizes have gained attention concerning the consequences of crowding agents on biomolecular structural transitions and stability. This review comprehensively summarizes macromolecular crowding, emphasizing the biophysical effects and contribution of soft interactions in the heterogeneous cellular environment.
