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  • Open Access Icon
  • Research Article
  • 10.1515/bmc-2025-0054
Entropy and mechanistic concepts after intraovarian platelet-rich plasma: Experimental considerations for local tissue responses mediated by NF-κB and TNF-α
  • Jul 18, 2025
  • Biomolecular Concepts
  • Eric Scott Sills + 6 more

Abstract 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.

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  • Research Article
  • Cite Count Icon 18
  • 10.1515/bmc-2025-0055
The impact of exercise on mitochondrial biogenesis in skeletal muscle: A systematic review and meta-analysis of randomized trials.
  • May 30, 2025
  • Biomolecular concepts
  • Diana Marisol Abrego-Guandique + 5 more

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.

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  • Research Article
  • Cite Count Icon 4
  • 10.1515/bmc-2025-0053
Quest for space: Tenacity of DNA, Protein, and Lipid macromolecules in intracellular crowded environment.
  • Mar 1, 2025
  • Biomolecular concepts
  • Priyanka Phogat + 5 more

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.

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  • Research Article
  • Cite Count Icon 4
  • 10.1515/bmc-2022-0050
Anti-arthritic potential of crude sulfated polysaccharide from marine macroalgae Sargassum ilicifolium (Turner) C. Agardh: Regulation of cytokine cascade.
  • Jan 23, 2025
  • Biomolecular concepts
  • Lavanya Ramamoorthi + 7 more

Seaweeds have been utilized as food, fodder, fertilizer, and medicine since ancient times; nevertheless, they have received only a little attention. In the current work, we extracted the sulfated polysaccharide from a marine source and investigated its anti-arthritic potential in vivo. The isolated and freeze-dried polysaccharide was tested for acute oral toxicity based on OECD 423. This step was followed by investigations on clinical signs and gross pathological alterations seen. A complete Freund's adjuvant-induced arthritis was used to test the in vivo activity in female Sprague-Dawley rats, which were divided into five groups: (1) normal control, (2) arthritic control, (3) methotrexate treatment (0.1 mg/kg), (4) crude sulfated polysaccharide (CSP) (5 mg/kg), and (5) CSP (10 mg/kg). CSP was from the marine brown algae Sargassum ilicifolium from the Gulf of Mannar. The body weight, paw volume, and biochemical markers (alanine aminotransferase, aspartate aminotransferase, creatinine, urea, and C-reactive protein levels) were also measured for each group coupled with histopathological and immunohistochemistry studies. The acute toxicity investigation indicated that the lethal dose of 50% (LD50) of the polysaccharide was more than 2,000 mg/kg. In addition, animals from the methotrexate and CSP (5 mg/kg, p.o.) groups had a substantial reduction in paw volume compared to other treatment groups. Methotrexate and CSP treatment dramatically decreased the levels of the investigated marker enzymes. Histopathology revealed that low-dose CSP (5 mg/kg, p.o.) significantly reduced the severity of synovitis, panniculitis, liver necrosis, inflammatory cell infiltration, and cortical and paracortical necrotic foci in node, compared to the high dose (10 mg/kg, p.o.). Immunohistochemical studies revealed that CSP (5 mg/kg) significantly inhibited pro-inflammatory cytokines such as tumor necrosis factor-alpha, interleukin-2, and CD4 cells. Overall, it can be concluded that a low-dose CSP (5 mg/kg) is an efficient anti-arthritic agent that confers its effects via the cytokine pathway.

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  • Research Article
  • Cite Count Icon 2
  • 10.1515/bmc-2025-0056
Bio-based hydrogel patches made of Îş-carrageenan enriched with degalactosylated xyloglucan for wound dressing applications.
  • Jan 1, 2025
  • Biomolecular concepts
  • Emanuela Muscolino + 1 more

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. Îş-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.

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  • Research Article
  • 10.1515/bmc-2025-0052
Clinical spectrum of COVID-19 patients and decreased serum level of miR-146a as a sign of inflammation.
  • Jan 1, 2025
  • Biomolecular concepts
  • Lucy BaldeĂłn Rojas + 11 more

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. 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. 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. 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. 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.

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  • Research Article
  • Cite Count Icon 7
  • 10.1515/bmc-2022-0051
Exploring cardiovascular implications in systemic lupus erythematosus: A holistic analysis of complications, diagnostic criteria, and therapeutic modalities, encompassing pharmacological and adjuvant approaches
  • Nov 27, 2024
  • Biomolecular concepts
  • John Dawi + 9 more

Systemic lupus erythematosus (SLE) poses a diagnostic challenge due to its heterogeneity. This study examines the cardiac complications of SLE comprehensively, covering pericarditis, myocarditis, pleural effusion, valvular disease, atherosclerosis, and cardiac arrhythmias. Nearly one-third of SLE-related deaths are attributed to cardiovascular diseases, necessitating a deeper understanding of cardiac pathophysiology. The impact of SLE on the cardiovascular system manifests in various ways, including recurrent and resistant pericarditis, severe myocarditis, and pleural effusion. Valvular diseases, atherosclerosis, and cardiac arrhythmias are prevalent, with immune complex deposition playing a role in atherosclerosis. Diagnostic criteria involve clinical features, laboratory findings, and autoantibodies, emphasizing the need for early diagnosis and a multidisciplinary diagnostic approach. The review explores pharmacological and non-pharmacological modalities for managing cardiac manifestations in SLE. Recommendations include NSAIDs, colchicine, and proton pump inhibitors for acute pericarditis, while selective immunosuppressive therapy is emerging for myocarditis. Valvular diseases require individualized treatment approaches, and careful corticosteroid management is crucial to avoid increased cardiovascular events. Anti-malarial therapy, particularly hydroxychloroquine, shows promise in mitigating cardiovascular risk factors. Non-pharmacological modifications, such as diet, exercise, and smoke cessation, significantly contribute to cardiovascular health in SLE patients. Adjuvant therapies involving glutathione and glutathione peroxidase focus on redox balance, offering potential interventions. This integrated approach combines diagnostic insights with diverse treatment modalities, providing a holistic strategy for managing cardiac complications in SLE. Ongoing research is essential to refine these strategies and optimize individualized treatment plans for improved patient outcomes.

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  • Research Article
  • Cite Count Icon 11
  • 10.1515/bmc-2022-0049
Toxicity of bisphenol A and p-nitrophenol on tomato plants: Morpho-physiological, ionomic profile, and antioxidants/defense-related gene expression studies.
  • Jun 26, 2024
  • Biomolecular concepts
  • Mahmoud S Abdelmoneim + 4 more

Bisphenol A (BPA) and p-nitrophenol (PNP) are emerging contaminants of soils due to their wide presence in agricultural and industrial products. Thus, the present study aimed to integrate morpho-physiological, ionic homeostasis, and defense- and antioxidant-related genes in the response of tomato plants to BPA or PNP stress, an area of research that has been scarcely studied. In this work, increasing the levels of BPA and PNP in the soil intensified their drastic effects on the biomass and photosynthetic pigments of tomato plants. Moreover, BPA and PNP induced osmotic stress on tomato plants by reducing soluble sugars and soluble proteins relative to control. The soil contamination with BPA and PNP treatments caused a decline in the levels of macro- and micro-elements in the foliar tissues of tomatoes while simultaneously increasing the contents of non-essential micronutrients. The Fourier transform infrared analysis of the active components in tomato leaves revealed that BPA influenced the presence of certain functional groups, resulting in the absence of some functional groups, while on PNP treatment, there was a shift observed in certain functional groups compared to the control. At the molecular level, BPA and PNP induced an increase in the gene expression of polyphenol oxidase and peroxidase, with the exception of POD gene expression under BPA stress. The expression of the thaumatin-like protein gene increased at the highest level of PNP and a moderate level of BPA without any significant effect of both pollutants on the expression of the tubulin (TUB) gene. The comprehensive analysis of biochemical responses in tomato plants subjected to BPA and PNP stress illustrates valuable insights into the mechanisms underlying tolerance to these pollutants.

  • Open Access Icon
  • Research Article
  • Cite Count Icon 7
  • 10.1515/bmc-2022-0027
A comprehensive review of the interaction between COVID-19 spike proteins with mammalian small and major heat shock proteins.
  • Jun 14, 2024
  • Biomolecular concepts
  • Liberty T Navhaya + 4 more

Coronavirus disease 2019 (COVID-19) is a novel disease that had devastating effects on human lives and the country's economies worldwide. This disease shows similar parasitic traits, requiring the host's biomolecules for its survival and propagation. Spike glycoproteins severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 spike protein) located on the surface of the COVID-19 virus serve as a potential hotspot for antiviral drug development based on their structure. COVID-19 virus calls into action the chaperonin system that assists the attacker, hence favoring infection. To investigate the interaction that occurs between SARS-CoV-2 spike protein and human molecular chaperons (HSPA8 and sHSP27), a series of steps were carried out which included sequence attainment and analysis, followed by multiple sequence alignment, homology modeling, and protein-protein docking which we performed using Cluspro to predict the interactions between SARS-CoV-2 spike protein and human molecular chaperones of interest. Our findings depicted that SARS-CoV-2 spike protein consists of three distinct chains, chains A, B, and C, which interact forming hydrogen bonds, hydrophobic interactions, and electrostatic interactions with both human HSPA8 and HSP27 with -828.3 and -827.9 kcal/mol as binding energies for human HSPA8 and -1166.7 and -1165.9 kcal/mol for HSP27.

  • Open Access Icon
  • Research Article
  • Cite Count Icon 6
  • 10.1515/bmc-2022-0048
Biochemical dynamics during postharvest: Highlighting the interplay of stress during storage and maturation of fresh produce.
  • Apr 8, 2024
  • Biomolecular Concepts
  • Ernesto Alonso Lagarda-Clark + 2 more

The lifecycle of fresh produce involves a sequence of biochemical events during their ontology, and these events are particularly significant for climacteric fruits. A high demand during ripening is observed in these plant products, which is reflected in a high rate of respiration and ethylene production. Increased respiratory demand triggers the activation of secondary pathways such as alternate oxidase, which do not experience critical increases in energy consumption in non-climacteric fruit. In addition, biochemical events produced by external factors lead to compensatory responses in fresh produce to counteract the oxidative stress caused by the former. The dynamics of these responses are accompanied by signaling, where reactive oxygen species play a pivotal role in fresh product cell perception. This review aims to describe the protection mechanisms of fresh produce against environmental challenges and how controlled doses of abiotic stressors can be used to improve quality and prolong their shelf-life through the interaction of stress and defense mechanisms.