Search Results (145)

Carboxymethylcellulose (CMC) is a biocompatible and biodegradable polysaccharide suitable for biomedical applications. Herein, an epichlorohydrin (ECH)-crosslinked CMC hydrogel (CMCG) was developed as a carrier for sustained drug release. Ether-type crosslinking between the hydroxyl groups of CMC and ECH yielded a transparent, highly water-absorbent gel. Structural analyses employing Fourier-transform infrared and solid-state ¹³C nuclear magnetic resonance spectroscopies confirmed successful crosslinking, and the hydrogel exhibited pH-dependent swelling. Carboplatin (CBP), a platinum-based anticancer drug, was incorporated into CMCG to prepare CBP-CMCG. In phosphate-buffered saline (pH 7.4), approximately 70% of CBP was released within 12 h, followed by a plateau phase, indicating diffusion-controlled release. Cytocompatibility assays using WI-38 normal human fibroblasts demonstrated that CMCG was non-cytotoxic, whereas free CBP induced significant cell death. In colorectal cancer HT-29 cells, CBP-CMCG exhibited gradual cytotoxicity, resulting in >80% nonviable cells after 24 h, indicating a sustained antitumor effect compared with free CBP. These results demonstrate that the newly developed ECH-crosslinked CMC hydrogel is a safe and effective platform for controlled drug delivery, enabling sustained release and prolonged therapeutic activity of CBP. Full article

Background: The juvenile-pubertal period is a critical window for linear growth and bone mass accumulation. This study investigated the joint effects of folic acid (FA) and colostrum basic protein (CBP)-fortified milk powder on growth, bone health, and metabolic safety in juvenile mice. Methods: Three-week-old C57BL/6J mice (n = 120) were acclimatized for 1 week and then randomly assigned to three isocaloric diet groups for an 8-week intervention starting at 4 weeks of age: Control (AIN-93M), Milk (AIN-93M + FA/CBP-fortified milk powder), and Positive Control (AIN-93G). Body length and weight were measured twice weekly. Bone microarchitecture was assessed by micro-computed tomography, and bone remodeling was evaluated through histology and serum biomarkers. The GH–IGF-1 axis and related metabolic parameters were also assessed. Results: FA–CBP–fortified milk powder significantly accelerated linear growth at intervention week 2, with body length higher in the Milk group than in the Control group (p < 0.01). After 8 weeks, the Milk group showed improved trabecular bone mass and microarchitecture compared with Control, especially in males (p < 0.01). Bone remodeling was transiently elevated at intervention week 4, as indicated by higher serum osteocalcin and CTX-I, and by increased osteoclast and cartilage matrix formation versus Control (p < 0.05). The GH–IGF-1 axis was also temporarily activated at week 4, with elevated serum GH and IGF-1/IGFBP-3 ratio compared with Control (p < 0.05). These skeletal benefits occurred without excess weight gain or adverse metabolic effects compared with Control (all p > 0.05). Conclusions: FA-CBP-fortified milk significantly enhanced linear growth during puberty and improved bone mass and microstructure in early adulthood. These skeletal benefits are consistent with the transient activation of the GH–IGF-1 axis. Importantly, no adverse metabolic effects were detected from early intervention through adulthood, supporting its potential application in growth-promoting nutritional strategies. Full article

Bullous pemphigoid (BP), the most prevalent autoimmune blistering skin disorder, has been associated with dipeptidyl peptidase-4 inhibitor (DPP4i) treatment in type 2 diabetic patients. This study aimed to investigate the association of DPP4 gene variants, rs3788979 and rs12617656, with classic BP (cBP)- and DPP4i-associated BP predisposition. Fifty-six (56) unrelated patients with cBP, 32 DPP4i-associated BP patients, 60 healthy controls, and 49 diabetic patients receiving DPP4i were included. Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism assay (PCR-RFLP). Statistical analyses were conducted using SPSS software. For rs3788979, the CT+TT genotypes were significantly associated with increased risk of DPP4i-associated BP compared with cBP [(Odds Ratio (OR) = 2.80, 95% Confidence Interval (CI) = 1.07–7.35; p-value = 0.034] and healthy controls (OR = 0.30, 95% CI = 0.13–0.86; p-value = 0.020). The T allele was also enriched in DPP4i-associated BP (OR = 2.57, 95% CI = 1.09–6.07; p-value = 0.027). Additionally, the TC genotype of rs12617656 (OR = 2.29, 95% CI = 1.04–5.03, p-value = 0.039) showed significant association with cBP susceptibility. These findings highlight DPP4 variants as potential BP risk factors, supporting personalized risk assessment prior to initiating gliptin therapy. Large-scale studies are warranted to validate these associations. Full article

Background/Objectives: Plasma glutamine levels in skeletal muscle change in response to exercise intensity and duration, both in physiological and pathological states. Glutamine contributes to muscle differentiation and regeneration; however, the mechanisms underlying this process remain unclear. This study investigated the role of glutamine glutaminolysis in myogenic differentiation, with a focus on epigenetic regulation of myogenin gene expression. Methods: C2C12 myoblasts were differentiated into myotubes using media containing various concentrations of glutamine, glutamate, or dimethyl 2-oxoglutarate (DM-α-KG), a cell-permeable analog of α-ketoglutarate. Results: Glutamine, glutamate, and DM-α-KG promoted C2C12 myoblast differentiation in a concentration-dependent manner, whereas the glutaminase inhibitor CB-839 suppressed differentiation. 4 mM glutamine increased myogenin mRNA expression by about 5-fold. CB-839 also inhibited glutamine-induced expression of myogenin but did not influence the effects of glutamate or DM-α-KG. Furthermore, glutamine increased histone H3 lysine 27 acetylation (H3K27ac) by about two-fold, whereas CB-839 (200 nM) and A-485 (10 µM), a CBP/p300 histone acetyltransferase inhibitor, reduced H3K27ac levels by about half. These results indicate that glutamine not only serves as a structural amino acid for muscle formation but also enhances myogenin transcription through epigenetic mechanisms. Conclusions: This report demonstrates glutaminolysis-dependent histone H3 acetylation, which induces myogenin transcription in myoblasts. These results, connecting glutamine supplementation during resistance training, may make it an effective strategy to accelerate muscle regeneration. Full article

The CITED proteins function as transcriptional modulators that are essential for vertebrate development. These proteins interact with numerous partners, notably transcription factors and co-activators. The hallmark of the CITED family is their conserved carboxy-terminal domain, which interacts strongly with the CBP/p300 co-activators. The expression of CITED genes is detected early during embryogenesis within embryonic and foetal regions critical for cardiac morphogenesis, among other developmental processes. Notably, CITED2 loss of function is strongly associated with congenital heart malformations in mice and zebrafish embryos, as well as congenital heart disease (CHD) in humans, whereas other CITED family members are not critical for cardiogenesis. Emerging evidence implicates CITED2 and CITED4 in regulating heart physiological adaptations and protective responses to pathological stress. This review provides a detailed analysis of CITED proteins and their interactors, focusing on CITED-target genes relevant for cardiogenesis and heart disease. We also highlight recent findings indicating that CITED2 and CITED4 may be instrumental for the development of novel therapeutic strategies to mitigate CHD and preserve adult cardiac function. Full article

The aim of the study was to evaluate the prevalence of hock lesions and cow hygiene as a cross-sectional study in dairy cows housed in compost-bedded pack barns (CBPs) in southern Germany. The effects of season, compost variables, and housing conditions on cow hygiene and hock lesion prevalences were also investigated. Eight farms that housed their cows in CBPs were visited once in the cold season and once in the warm season between January and December 2023. All cows (cold season n = 592; warm season n = 613) were scored for hygiene and hock lesions at each visit. Compost samples were collected for laboratory analysis, and the quality of the compost-bedded pack and condition of the lying surface and concrete walkways were assessed. The udder was the cleanest body zone in both seasons; poor udder hygiene (too dirty score) occurred in 15.0% of cows in the cold season and 7.5% in the warm season (p ≤ 0.05). Only 1% of the cows had a hairless area on a hock in the cold season compared with 3.8% in the warm season; 0.2% of the cows also had swelling of the hock in the warm season (p ≤ 0.05). The compost variables that impacted cow hygiene most frequently were dry matter and compost temperature. Based on our results, CBPs reduce the prevalence of hock lesions. Cow hygiene was affected by various factors, and therefore good management of CBPs is required for good cow hygiene. Full article

Cardiopulmonary bypass (CPB) can lead to cardiac damage due to oxidative stress (OS) and inflammation in heart failure (HF). We tested the hypothesis that preoperative HF patients with reduced ejection fraction (HFrEF) subjected to CBP have higher levels of OS and NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) in heart and plasma and in those that develop postoperative AF (pAF) as a clinical outcome. HF was categorized for preoperative left ventricular EF: preserved (HFpEF > 50%, n = 27) and reduced EF (HFrEF ≤ 40%, n = 25). Samples of atrial tissue, pericardial fluid, and plasma were collected at surgery to assess NLRP3 expression; 3-nitrotyrosine (3-NT), thiobarbituric acid reaction (TBARS), and nuclear factor erythroid 2-related factor 2 (Nrf2) in atrial tissue; NLRP3, IL-1β, and IL-18 expression in pericardial fluid; and antioxidant capacity, 8-isoprostanes, and malondialdehyde (MDA) in plasma. Reactive oxygen species, 3-NT, and NLRP3 in atrial tissue were determined by immunohistochemistry in a subset of pAF patients. Plasma and atrial tissue 3-NT and MDA were higher in HFrEF compared with HFpEF. Lipid peroxidation products were higher in both plasma and atrial tissue in pAF (n = 29), compared to sinus rhythm (SR) (n = 23). In HFrEF patients, the values of tissue ROS, 3-NT, and NLRP3 were higher than in HFpEF patients. In addition, the expression levels of NLRP3, IL-1β, and IL-18 were higher in atrial tissue and pericardial fluid in HFrEF. Patients with preoperative HFrEF showed higher OS in plasma and the expression of NLRP3, ROS, and 3-NT in atrial tissue biopsies and pericardial fluid. This finding suggests a potential pharmacologic therapy for pAF and clinical complications due to CPB. Full article

Objective: The role of calcium in coagulation homeostasis is well established, although the relationship between calcium levels and postoperative bleeding in major cardiac surgery remains largely unexplored. Methods: This retrospective, single-center study investigated the correlations between ionized calcium levels measured at several timepoints: preoperatively (after induction of anesthesia), immediately after cardiopulmonary bypass (CPB) weaning, on the first postoperative day measured three times at 8 h intervals, preoperative vitamin D values, and several significant bleeding outcomes. These outcomes included the volume of blood in the drainage bag (measured in milliliters on days 1 and 2), the need for surgical or medical hemostasis, the requirement for blood transfusion (red blood cells, fresh frozen plasma, or platelets), and the occurrence of extracardiac hemorrhagic complications. A multivariable logistic regression analysis was performed, with a two-sided p-value of <0.00625 considered significant after applying Bonferroni correction. Results: The study included 83 patients with a mean age of 64.9 ± 8.5 years, with 49 (59%) being male. The most common procedures were aortic valve replacement (26 patients, 31%) and coronary artery bypass grafting (26 patients, 31%). The multivariable regression analysis demonstrated a trend toward an association between low levels of preoperative calcium and increased bleeding volume immediately after CBP and on the first day after the intervention (r = 0.30; p = 0.08 for day 1 and r = 0.24; p = 0.03 for day 2). Similar trends were observed for the association between low levels of preoperative calcium, use of medical hemostasis (r = 0.30; p = 0.009), and red blood cell transfusion (r = 0.24; p = 0.03). Additionally, we observed a trend towards a positive correlation between lower serum vitamin D levels and increased postoperative blood loss on both day 1 (r = 0.32; p = 0.07) and day 2 (r = 0.29; p = 0.04). The subgroup analysis of valve procedures vs. coronary procedures showed no statistically difference between preoperative ionized calcium levels, postoperative bleeding (289 27 vs. 283 mL, p = 0.87), the need for surgical hemostasis (p = 0.5), or blood transfusion requirement (p = 0.57). Conclusions: In our study, preoperative calcium levels were consistently associated with increased bleeding after major cardiac surgery. Post-CPB ionized calcium levels did not influence bleeding outcomes. The role of calcium in coagulation homeostasis during major cardiac surgery warrants further research, ideally with more robust data, as our study’s small sample limits robust evidence. Further larger studies will conclude on the importance of calcium levels in cardiac surgery related to hemostasis and bleeding outcomes. Lower preoperative ionized calcium and vitamin D levels showed exploratory associations with increased bleeding-related outcomes following major cardiac surgery. These findings are hypothesis-generating, and larger prospective studies are needed to confirm these potential relationships and clarify their clinical implications. Full article

Asthma is a chronic inflammatory airway disease influenced by both genetic and environmental factors. Recent insights have underscored the pivotal role of epigenetic regulation in the pathogenesis and heterogeneity of asthma. This review focuses on key epigenetically important regulators categorized as writers, erasers, and readers that govern DNA methylation, histone modifications, and RNA modifications. These proteins modulate gene expression without altering the underlying DNA sequence, thereby influencing immune responses, airway remodeling, and disease severity. We highlight the structural and functional dynamics of histone acetyltransferases (e.g., p300/CBP), histone deacetylases (e.g., SIRT family), DNA methyltransferases (DNMT1, DNMT3A), demethylases (TET1), and methyl-CpG-binding proteins (MBD2) in shaping chromatin accessibility and transcriptional activity. Additionally, the m6A RNA modification machinery including METTL3, METTL14, FTO, YTHDF1/2, IGF2BP2, and WTAP is explored for its emerging significance in regulating post-transcriptional gene expression during asthma progression. Structural characterizations of these proteins reveal conserved catalytic domains and interaction motifs, mirroring their respective families such as SIRTs, p300/CBP, DNMT1/3A, and YTHDF1/2 critical to their epigenetic functions, offering mechanistic insight into their roles in airway inflammation and immune modulation. By elucidating these pathways, this review provides a framework for the development of epigenetic biomarkers and targeted therapies. Future directions emphasize phenotype-specific epigenomic profiling and structure-guided drug design to enable precision medicine approaches in asthma management. Full article

Non-invasive, continuous monitoring of carotid artery hemodynamics may provide valuable insights on cerebral blood perfusion (CBP). Near-infrared spectroscopy (NIRS) is a non-invasive modality that may be a good candidate for real-time carotid artery monitoring. We designed a wearable NIRS system to monitor the left and right radial and carotid arteries in 20 healthy subjects. The changes in total hemoglobin concentration (HbT) and tissue oxygen saturation (StO₂) in all 80 arteries were continuously monitored in response to changes in oxygen supply. Wilcoxon non-parametric equivalence testing was used to compare changes in the radial (reference) and carotid arteries. The system-derived HbT and StO₂ trends matched the expected physiological responses over time in the radial and carotid arteries. The mean peak-to-peak amplitude [uM] of HbT during sustained deep breathing was practically equivalent between the left radial (0.9 ± 0.8) and left carotid (1.6 ± 1.1) arteries (p = 0.01). The mean peak-to-peak amplitude [%] of StO₂ was practically equivalent between the left radial (0.3 ± 0.2) and left carotid (0.3 ± 0.2) arteries (p < 0.001) and the right radial (0.4 ± 0.5) and right carotid (0.5 ± 0.4) arteries (p = 0.001). These findings indicate that NIRS may be a good option for monitoring the carotid arteries to track changes in CBP. Full article

Ischemic brain and retinal injuries trigger complex molecular cascades involving neuroinflammation, oxidative stress, and neuronal death. Among these mechanisms, epigenetic regulation has emerged as a critical modulator of the injury response. Histone deacetylases (HDACs) and histone acetyltransferases (HATs) dynamically control gene expression by altering chromatin structure. HDACs often promote neuroinflammation and neuronal apoptosis through repression of neuroprotective and anti-inflammatory genes, while HATs generally enhance the transcription of genes involved in cell survival and repair. In ischemia, specific HDAC isoforms (e.g., HDAC1, HDAC2, HDAC3, and HDAC6) have been implicated in microglial activation, glial reactivity, and disruption of immune balance. Conversely, HATs such as CBP/p300 and Tip60 contribute to neuronal resilience and immune regulation. Understanding the dual and context-dependent roles of these epigenetic enzymes offers promising therapeutic avenues. Selective HDAC inhibitors or HAT activators may represent novel strategies to mitigate ischemic damage, support neuroprotection, and facilitate functional recovery. Full article

Background/Objectives: Persons with Parkinson’s disease (PD) are at elevated risk of falling due to deficits in postural control, lower limb strength, and sensory integration. While community-based boxing programs (CBPs) have shown promise in improving strength and balance, their feasibility and potential role in addressing fall risk remain unclear. This preliminary, prospective cohort study explored the feasibility of a CBP enhanced with individualized balance training tailored to somatosensory deficits and explored early indications of potential impact on fall risk and related outcomes. Methods: Twenty individuals with mild-to-moderate PD participated in a 12-week exercise program consisting of group-based boxing, functional circuit training, and one-on-one balance training based on the Modified Clinical Test of Sensory Interaction in Balance. Self-reported falls were collected at baseline and 3 months post-intervention. Secondary outcomes included standard measures of balance, gait, and functional mobility. Results: Participants demonstrated significant improvements in balance and functional mobility including the Timed Up and Go (F(2, 40.85) = 24.83, p < 0.001, η² = 0.580), Five Times Sit-to-Stand Test (F(2, 78.13) = 50.22, p < 0.001, η² = 0.736), and Berg Balance Scale (F(2, 193.39) = 12.72, p < 0.001, η² = 0.414), among others. 4 participants experienced a decrease in falls, 2 experienced an increase, and the remainder had no change. Conclusions: These preliminary findings suggest that integrating individualized balance training with a CBP is feasible and may positively influence functional mobility and balance in persons with PD. However, effects on fall reduction remain inconclusive. These results should be interpreted as exploratory and used to inform the design of future structured clinical trials. Full article

This study investigated the relationships between inspiratory performance (IP) and glenohumeral rotation in Division 1 Collegiate baseball players (D1CBP). Thirty D1CBP were recruited. The Test of Incremental Respiratory Endurance (TIRE) provides maximal inspiratory pressure (MIP), sustained maximal inspiratory pressure (SMIP), and inspiratory duration (ID). Right and left glenohumeral internal and external rotation (RGHIR, RGHER, LGHIR, and LGHER, respectively) were measured with the shoulder in 90 degrees(d) of abduction. Significant differences between position groups were observed. IP of the entire group was significantly correlated to height, weight, and negatively correlated to right total rotational motion (RTRM) (r = −0.41; p < 0.05). The IP of all pitchers was significantly negatively correlated to both RTRM and LTRM (r = −0.56 to −0.61; p < 0.05). IP of right-handed pitchers was significantly correlated negatively to RGHER (r = −0.83 to −0.93; p < 0.05). IP of left-handed pitchers was significantly correlated negatively to LGHER (r = −0.82; p = 0.04). GH motions are significantly related to the IP of D1CBP. This association may be explained by the involvement of overstretched internal rotators, which act as accessory inspiratory muscles. Full article

Some additives currently used to enhance drilling mud’s rheological qualities have a substantial economic impact on society. Carboxymethyl cellulose (CMC) and calcium carbonate (CaCO₃) are currently imported. Food crops have influences on food security; hence, this research explored the potential of utilizing cow bone powder (CBP), a bio-waste product and a renewable resource, as an environmentally friendly fluid-loss additive for drilling applications, in comparison with CaCO₃. Both samples (CBP and CaCO₃) were evaluated to determine the most efficient powder sizes (coarse, medium, and fine powder), concentrations (5–15 g), and aging conditions (before or after aging) that would offer improved rheological and fluid-loss control. The results obtained showed that CBP had a significant impact on mud rheology when compared to CaCO₃. Decreasing the particle size (coarse to fine particles) and increasing the concentration from 5 to 15 g positively impacted mud rheology. Among all the conditions analyzed, fine-particle CBP with a 15 g concentration produced the best characteristics, including in the apparent viscosity (37 cP), plastic viscosity (29 cP), and yield point (25.5 lb/100 ft²), and a gel strength of 16 lb/100 ft² (10 s) and 28 lb/100 ft² (10 min). The filtration control ability of CaCO₃ was observed to be better than that of the coarse and medium CBP particle sizes; however, fine-particle-size CBP demonstrated a 6.1% and 34.6% fluid-loss reduction at 10 g and 15 g concentrations when compared to respective amounts of CaCO₃. The thermal behavior of the Mud Samples demonstrated that it positively impacted rheology before aging. In contrast, after aging, it exhibited a negative effect where samples grew more viscous and exceeded the API standard range for mud properties. Therefore, CBP’s excellent rheological and fluid-loss control ability makes it a potential, sustainable, and economically viable alternative to conventional materials. This superior performance enhances the thinning properties of drilling muds in stationary and circulating conditions. Full article

Traumatic injuries to the peripheral (PNS) and central nervous systems (CNS) trigger distinct regenerative responses, with the PNS displaying limited regenerative capacity and the CNS remaining largely refractory. Recent research highlights the role of epigenetic modifications, particularly histone acetylation, in modulating the gene expression programs that drive axonal regeneration. This review synthesizes current findings on post-translational histone modifications, focusing on histone acetyltransferases (HATs), histone deacetylases (HDACs), and epigenetic readers, in addition to their impact on neuronal and non-neuronal cells following injury. While HATs like p300/CBP and PCAF promote the expression of regeneration-associated genes, HDAC inhibition has been shown to facilitate neurite outgrowth, neuroprotection, and functional recovery in both PNS and CNS models. However, HDAC3, HDAC5, and HDAC6 demonstrate context- and cell-type-specific roles in both promoting and limiting regenerative processes. The review also highlights cell-specific findings that have been scarcely covered in the previous literature. Thus, the immunomodulatory roles of epigenetic regulators in microglia and macrophages, their involvement in remyelination via Schwann cells and oligodendrocytes, and their impact on astrocyte function are within the scope of this review. Closely considering cell-context specificity is critical, as some targets can exert opposite effects depending on the cell type involved. This represents a major challenge for current pharmacological therapies, which often lack precision. This complexity underscores the need to develop strategies that allow for cell-specific delivery or target regulators with converging beneficial effects across cell types. Such approaches may enhance regenerative outcomes after CNS or PNS injury. Full article