Search Results (753)

One of the promising research areas involving carborane derivatives is boron neutron capture therapy (BNCT). Due to the high boron atom content in carborane molecules, these compounds are considered potential candidates for BNCT-based cancer treatment. Despite ongoing studies on various biologically active carboranyl-containing compounds, the search continues for substances that meet the stringent requirements of effective BNCT agents. In this study, the synthesis of carboranyl-containing derivatives of β-arylaliphatic acids is described, along with the investigation of their reactivity with primary and secondary amines, as well as with metals and their hydroxides. The molecular structures of the synthesized compounds were confirmed using Fourier-transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, elemental analysis, and mass spectrometry (LC-MS). Cytotoxicity of the water-soluble compound potassium 3-(2-isopropyl-1,2-dicarba-closo-dodecaboran-1-yl)-3-phenylpropanoate was evaluated using several cell lines, including HdFn and MCF-7. Full article

High-frequency (h. f.) harmonic distortion (HD) of advanced SiGe heterojunction bipolar transistor (HBT)-based power cells (PwCs), featuring optimized metallization interconnections between individual HBTs, was investigated. Single tone input power (P_in) excitations at 1, 2, 5, and 10 GHz frequencies were employed. The output power (P_out) of the fundamental tone and its harmonics were analyzed in both the frequency and time domains. A rapid increase in the third harmonic of P_out was observed at input powers exceeding −8 dBm for a fundamental frequency of 10 GHz in two different PwC technologies. This increase in the third harmonic was analyzed in terms of nonlinear current waveforms, the nonlinearity of the HBT p-n junction diffusion capacitances, substrate current behavior versus P_in, and avalanche multiplication current. To assess the RF power performance of the PwCs, scalar and vectorial load-pull (LP) measurements were conducted and analyzed. Under matched conditions, the SiGe PwCs demonstrated good linearity, particularly at high frequencies. The key power performance of the PwCs was measured and simulated as follows: input power 1 dB compression point (P_{in_1dB}) of −3 dBm, transducer power gain (G_T) of 15 dB, and power added efficiency (PAE) of 50% at 30 GHz. All measured data were corroborated with simulations using the compact model HiCuM L2. Full article

Background/Objectives: Organ transplantation is a life-saving intervention for patients with terminal organ failure, but long-term success is hindered by graft rejection and dependence on lifelong immunosuppressants. These drugs pose risks such as opportunistic infections and malignancies. Chimeric antigen receptor (CAR) technology, originally developed for cancer immunotherapy, has been adapted to regulatory T cells (Tregs) to enhance their antigen-specific immunosuppressive function. This systematic review evaluates the preclinical development of CAR-Tregs in promoting graft tolerance and suppressing graft-versus-host disease (GvHD). Methods: A systematic review following PROSPERO guidelines (CRD420251073207) was conducted across PubMed, Scopus, and Web of Science for studies published from 2015 to 2024. After screening 105 articles, 17 studies involving CAR-Tregs in preclinical or in vivo transplant or GvHD models were included. Results: CAR-Tregs exhibited superior graft-protective properties compared to unmodified or polyclonal Tregs. HLA-A2-specific CAR-Tregs consistently improved graft survival, reduced inflammatory cytokines, and suppressed immune cell infiltration across skin, heart, and pancreatic islet transplant models. The inclusion of CD28 as a co-stimulatory domain enhanced Treg function and FOXP3 expression. However, challenges such as Treg exhaustion, tonic signaling, and reduced in vivo persistence were noted. Some studies reported synergistic effects when CAR-Tregs were combined with immunosuppressants like rapamycin or tacrolimus. Conclusions: CAR-Tregs offer a promising strategy for inducing targeted immunosuppression in allogeneic transplantation. While preclinical findings are encouraging, further work is needed to optimize CAR design, ensure in vivo stability, and establish clinical-scale manufacturing before translation to human trials. Full article

Avian pathogenic Escherichia coli (APEC) is highly infective in poultry, causing significant economic losses to the poultry industry. As an extraintestinal pathogenic strain, adherence is a critical step in the infection. The functions of several adhesins, including type I, P, and Curli fimbriae, have been extensively studied. However, the roles of other adhesins, like Sfm, remain largely unexplored. Sfm is widely present in E. coli. Although the Sfm cluster is an ortholog of the fim gene cluster of Salmonella type I fimbriae, the biological function of Sfm in APEC has not yet been elucidated. To investigate whether Sfm in APEC CE129 plays a role in virulence, in this study, we constructed recombinant strains by expressing Sfm in the fimbriae-deficient strain SE5000. Additionally, a CE129 sfmA mutant strain was constructed. The resulting changes in adherence, biofilm formation, resistance to macrophage phagocytosis, and resistance to serum bactericidal ability were observed. The adherence ability of CE129ΔsfmA was reduced by 41%. HD-11 cells demonstrated a 30% increase in the phagocytosis of CE129ΔsfmA, and a 50% reduction in SE5000 (pBR322-sfm). The sfm deletion mutant showed a 23.9% reduction in the resistance to serum bactericidal ability, while SE5000 (pBR322-sfm) displayed a 32% increase. SE5000 (pBR322-sfm) exhibited a 34% increase in biofilm formation, and CE129ΔsfmA demonstrated a 21% decrease. Real-time PCR was employed to examine the impact of Sfm deletion on the transcription level of key virulence factors (fimA, fliC, papC, tsh, ompA, and iss). The results indicated that Sfm in CE129 is closely associated with bacterial adherence and survivability, contributing to biofilm formation and influencing the expression of key virulence factors. This study yields initial insight into the functional roles of Sfm in APEC and provides a foundation for the effective control of E. coli in the poultry industry. Full article

The incidence of Hashimoto’s disease (HD) increases with age and in people who have other autoimmune diseases. It is characterized by lymphocytic infiltration, fibrosis, and atrophy of the thyroid parenchyma with the simultaneous presence of thyroid peroxidase antibodies (ATPO) and/or thyroglobulin antibodies (ATG). Eicosanoids are formed via the cyclooxygenase (COX), lipoxygenase (LOX), and monooxygenase (CYP450) pathways with arachidonic acid (ARA), resulting in the production of epoxyeicosatrienoic acids (EETs) or hydroxyeicosatetraenoic acids (HETEs). These eicosanoids can act in an autocrine or paracrine manner on target cells. This study aimed to examine whether a gluten-free diet (GFD) can modulate the enzymatic pathways of the pro-inflammatory ARA cascade. The study material consisted of serum samples from Caucasian female patients with HD aged 18–55 years. Participants were enrolled in the study based on the presence of an ultrasound characteristic of HD, and elevated serum levels of anti-thyroid peroxidase antibodies and anti-thyroglobulin antibodies. Patients with confirmed celiac disease did not participate in the study. A total of 78 samples were analyzed, with 39 collected after 3 months of following a GFD. Eicosanoids (thromboxane B2, prostaglandin E2, leukotriene B4, and 16R-hydroxy-5Z,8Z,11Z,14Z-eicosatetraenoic acid (16-RS HETE)) were extracted using high-performance liquid chromatography. The contribution of leukotriene (LTB) was analyzed in the LOX pathway, prostaglandins (PGE2) and thromboxane (TXB2) were selected for the involvement of the COX pathway, and 16RS HETE was used for the CYP450 pathway. All parameters were analyzed before and after a 3-month dietary intervention that included a gluten-free diet. In the obtained results, only one mediator, leukotriene B4, was significant (p < 0.05). The mean level on the initial visit was 0.202 ± 0.11 (SD), while it was 0.421 ± 0.27 (SD) on the subsequent visit, indicating a significant increase in its level after implementing a GFD. Although there was a trend in the CYP 450 pathway of decreased 16-RS HETE, the presented correlations show that thromboxane B4 and 16RS-HETE were positively correlated with the body mass and body fat mass of the examined patients. There was a trend in the CYP 450 pathway of decreased 16-RS HETE after GFD. Thromboxane B4 and 16RS-HETE levels before GFD were positively correlated with the body mass and body fat mass of the examined patients. A gluten-free diet in HD does not suppress the synthetic pathways of LOX, COX, or cytochrome P450 (CYP450). The level of adipose tissue has a greater impact on the inflammatory processes in HD than a gluten-free diet. This study does not confirm the suppressive effect of a gluten-free diet on the pro-inflammatory arachidonic acid cascade in any of the three analyzed mediator synthesis LOX, COX, CYP450 pathways. Full article

Several soluble mediators are activated during myogenesis and progression, and severe neurodegeneration, with related biomarkers, characterizes high myopia-related retinal atrophy. Targets of oxidative stress, epigenetics and neurogenic inflammation have been reported in the prospecting of some bioindicators to mirror retinal insults occurring in high myopia. The aim of the present study was to assess the expression of a few selected biomarkers belonging to the neurotrophin (NGF and BDNF), oxidative (NO, KEAP1/NRF2), and epigenetic (DNMT3 and HD1) pathways. Sixty-five (65; 76.25 ± 9.40 years) specimens—aqueous, anterior capsule (AC), and lens epithelial cells (LEC)—were collected at the time of cataract surgery and used for ELISA (aqueous) and transcripts analysis (AC/LEC). Biosamples were grouped as emmetrope (23; 81.00 ± 6.70 years); myopia (24; 75.96 ± 7.30); and high (pathological) myopia (18; 70.56 ± 11.68 years), depending on axial length (AL) and refractive error (RE). Comparisons and correlations were carried out between myopic and high-myopic subgroups. NGF and BDNF were lowered in myopic samples; NGF and BDNF transcripts were differentially expressed in LEC, and their expression correlated positively with NGF and negatively with BDNF, with the expression of the αSMA phenotype. NGF and BDNF correlated negatively with NO and nitrites. Oxidative stress (iNOS/NOX1/NOX4 and KEAP1/NRF2) and epigenetic (DNMTα3/HD1) transcripts were upregulated in myopic LEC, compared with emmetropic ones. Herein, we prospect the contribution of NGF and BDNF in both neuroinflammation and neuroprotection occurring in this chronic disease. Full article

This study develops and characterizes GelMA–dopamine conjugates as novel tissue adhesives, offering an alternative to sutures. GelMA was synthesized at 5%, 10%, and 15% (w/v) with medium and high dopamine (DOPA) conjugation. Adhesives were evaluated for swelling, degradation, mechanical strength, and cytocompatibility using AlamarBlue assays and F-actin staining to assess cell viability and adhesion. Our findings indicate that DOPA conjugation significantly reduced the swelling ratio while increasing the biodegradation rate, resulting in enhanced release of free methacrylate groups over time. The mechanical properties and adhesion capabilities showed a complex relationship with DOPA substitution. Notably, the formulation containing 10% GelMA with high dopamine conjugation (HD) exhibited superior adhesion and mechanical strength. All formulations demonstrated shear-thinning behavior and recovery, making them suitable for injection and bioprinting applications. Although increased DOPA levels negatively affected crosslinking, the optimal formulation achieved a balance between adhesion and gel concentration. Rapid crosslinking was achieved within five minutes, enhancing the material’s suitability for clinical applications. In vitro cell-based assays confirmed the non-cytotoxic nature of the optimal adhesives, with metabolic activity showing significant increases over a 7-day period. These advancements support the development of improved tissue adhesives, potentially reducing reliance on sutures and enhancing wound healing outcomes. Full article

Objectives: Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by persistent inflammation. Reliable biomarkers for predicting disease reactivation are lacking. This study aimed to investigate serum cytokines and cytotoxic molecules in both the inactive (iSLE) and active (aSLE) phases to identify potential predictors of disease activity. Methods: Fifty-five SLE patients were classified as having iSLE (n = 36) or aSLE (n = 19) on the basis of clinical parameters and the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K). Serum levels of cytokines, cytotoxic molecules, and CD8⁺ cells were analyzed through flow cytometry and principal component analysis (PCA). Additionally, seventeen healthy donors (HDs) served as a control group. Results: Serum perforin (median: 2219 pg/mL; p = 0.0020) and granulysin (median: 1347 pg/mL; p = 0.010) levels were significantly higher in patients with aSLE than in patients with iSLE. In contrast, sFas levels were elevated in both SLE groups compared with those in the HD group. Moreover, increased perforin and granulysin levels were correlated with increased SLEDAI-2K scores, and the proportion of cytotoxic cells (CD8⁺granzyme-B⁺perforin⁺ cells) was correlated with disease activity. Conclusions: The increased levels of cytotoxic molecules and the high CD8⁺ cell proportions suggest that integrating these parameters with traditional biomarkers could enhance disease monitoring and management. Full article

Cardioprotection against ischemia is achieved using openers of mitochondrial ATP-sensitive K⁺ (mitoKATP) channels such as diazoxide (DZX), leading to pharmacological preconditioning (PPC). We previously reported that PPC decreases the abundance of ventricular Cav1.2 channels, but PPC’s effects on other channels remain largely unexplored. In this study, we hypothesized that DZX regulates the expression of hyperpolarization-activated cyclic nucleotide potassium channel 4 (HCN4) channels in sinoatrial node cells (SANCs), the specialized cardiomyocytes that generate the heartbeat. DZX increased the heart rate in intact adult rats. Patch-clamp experiments revealed an increase in the magnitude of ionic currents through HCN4 channels, which was abolished by the reactive oxygen species (ROS) scavenger N-acetylcysteine (NAC) and the selective mitoKATP channel inhibitor 5-hydroxydecanoate (5-HD). Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and Western blot assays showed that DZX increased HCN4 channel expression at the mRNA and protein levels. Immunofluorescence analyses revealed that PPC increased HCN4 fluorescence, which was abolished by NAC. DZX increased nuclear translocation of c-Fos and decreased protein abundance of RE1 silencing transcription factor (REST)/neuron-restrictive silencer factor (NRSF), suggesting the involvement of these factors. Our results suggest that PPC increases the heart rate by upregulating HCN4 channel expression through a mechanism involving c-Fos, REST, and ROS. Full article

Eryptosis is a programmed cellular death involving red blood cells (RBCs). It is a physiological mechanism that leads to the removal of defective erythrocytes, similarly to apoptosis. Its typical features are cell shrinkage, cell membrane blebbing, and membrane scrambling with the consequent exposure of the aminophospholipid phosphatidylserine on the outer surface of RBCs. Different mechanisms play a role in the pathogenesis of eryptosis, such as the increase in cytosolic calcium concentration, oxidative stress, inflammation, and uremic toxins. If erythrocyte synthesis does not compensate for the accelerated eryptosis, anemia may develop. Moreover, enhanced eryptosis contributes to the pathogenesis of different clinical diseases, such as diabetes, sepsis, metabolic syndrome, and uremia. In particular, in patients with chronic kidney disease (CKD), deficiencies of erythropoietin and iron may further reduce the lifespan of RBCs. In this review, we focused on eryptosis in CKD and end-stage renal disease on peritoneal dialysis (PD) and hemodialysis (HD). Full article

Gastrointestinal graft-versus-host disease (GvHD) is a frequent and severe complication after allogeneic stem cell transplantation (aSCTx). Although biopsy and histopathology remain the gold standard for diagnosis of GvHD, this approach can be limited by thrombocytopenia accompanying aSCTx and the diagnostic delay associated with routine histopathology. Here, we report on two patients in which dye-based contact microscopy using a latest generation endocytoscope with 520-fold magnification enabled in vivo diagnosis of GvHD. The first patient was a 23-year-old man with acute lymphoblastic leukemia presenting with non-bloody diarrhea 3 months after aSCTx. After topical staining with crystal violet and methylene blue, endocytoscopy in the rectum showed several apoptotic epithelial cells. Histopathology confirmed GvHD grade III according to the Lerner classification. The second patient was a 59-year-old female with diarrhea 3 months after aSCTx. Apart from pathognomic apoptotic bodies, EC additionally revealed crypt lumina enlargement and mononuclear cell infiltrates in the lamina propria with subsequent crypt distension. The duration of the procedure was less than 5 min in each patient. These findings illustrate that in vivo microscopy using endocytoscopy can enable instantaneous diagnosis of GvHD with the benefit of accelerating therapeutic decisions in patients with suspected severe GvHD. Full article

Salmonella infection poses a serious threat to the poultry industry, causing significant economic losses. Under global warming conditions, the underlying molecular mechanisms by which heat stress affects bacterial infections in poultry remain unclear. This study conducted a Salmonella Typhimurium infection under heat stress in Guang Ming broilers. A total of 100 chickens were randomly divided into three groups: control group (CTL), Salmonella Typhimurium (ST) infection group, and heat stress and Salmonella Typhimurium (HS + ST) co-stimulation group. By integrating inflammatory phenotypes, liver transcriptome profiles, and weighted gene co-expression network analysis (WGCNA), we systematically investigated the key regulatory factors through which heat stress affects host susceptibility to Salmonella. The results demonstrated that heat stress reduced body weight gain, exacerbated Salmonella Typhimurium-induced inflammatory responses, and increased mortality. Transcriptome results revealed that heat stress led to excessive inflammatory responses and antioxidant defense imbalances. Combined differential expression analysis and WGCNA identified three hub regulatory genes: PTGDS and WISP2 showed significant correlations with the heterophil/lymphocyte ratio, while SLC6A9 was significantly correlated with serum IL-8 levels. Validation in HD11 cell infection models confirmed the differential expression of these genes under heat stress and Salmonella Typhimurium co-stimulation, indicating their critical roles in host immune regulation. This study elucidates the intrinsic regulatory relationships through which heat stress promotes Salmonella pathogenicity and inflammatory responses, providing important insights for disease-resistant poultry breeding and prevention strategies. Full article

Plant-specific WUSCHEL (WUS)-related homeobox (WOX) family of transcription factors are involved in apical meristem maintenance, embryogenesis, lateral organ development, and hormone signaling. Among the members of this family, WOX1 is known to play essential roles in many species. However, the function of the peony ‘Feng Dan’ (Paeonia ostii L.) WOX1 (PoWOX1) remains unknown. The initial bioinformatic analysis revealed that PoWOX1 belongs to the modern clade of the WOX gene family and has a highly conserved homeodomain (HD), the WUS motif, the STF-box, and the MAEWEST/WOX4-box. Subsequent heterologous overexpression in Arabidopsis thaliana revealed that PoWOX1 promotes root growth, early shoot initiation, and flowering. The root vascular tissues, especially the arrangement and size of xylem cells, were different between the PoWOX1-overexpressing transgenics and the wild-type plants, and the pericycle cells adjacent to the xylem divided more easily in the transgenics than in the wild type. Furthermore, under in vitro conditions, the transgenic leaf explants exhibited more callus induction and differentiation than the wild-type leaf explants. Thus, the study’s findings provide novel insights into the role of PoWOX1 in promoting root development and callus tissue induction and differentiation, serving as a reference for developing an efficient regeneration system for the peony. Full article

Recent investigations into the neuroepigenome of the brain are providing unparalleled understanding into the impact of post-translational modifications (PTMs) of histones in regulating dynamic gene expression patterns required for adult brain cognitive function and plasticity. Histone acetylation is one of the most well-characterized PTMs shown to be required for neuronal function and cognition. Histone acetylation initiates neural circuitry plasticity via chromatin control, enabling neurons to respond to external environmental stimuli and adapt their transcriptional responses accordingly. While interplay between histone acetylation and deacetylation is critical for these functions, dysregulation during the aging process can lead to significant alterations in the neuroepigenetic landscape. These alterations contribute to impaired cognitive functions, neuronal cell death, and brain atrophy, all hallmarks of age-related neurodegenerative disease. Significantly, while age-related generation of DNA mutations remains irreversible, most neuroepigenetic PTMs are reversible. Thus, manipulation of the neural epigenome is proving to be an effective therapeutic strategy for neuroprotection in multiple types of age-related neurodegenerative disorders (NDs) that include Alzheimer’s disease (AD), Parkinson’s disease (PD), Amyotrophic lateral sclerosis (ALS) and Huntington’s disease (HD). Here, we highlight recent progress in research focusing on specific HAT-based neuroepigenetic mechanisms that underlie cognition and pathogenesis that is hallmarked in age-related NDs. We further discuss how these findings have potential to be translated into HAT-mediated cognitive-enhancing therapeutics to treat these debilitating disorders. Full article

Retinal dysfunction is emerging as a potential early marker of neurodegenerative diseases. Within the retina, the dopaminergic circuit, comprising dopaminergic amacrine cells, dopamine synthesis and turnover, and dopamine receptor signalling, is essential for visual processing, particularly colour contrast perception. Disruption of this circuit may underline early retinal alterations observed in Huntington’s disease (HD) and Alzheimer’s disease (AD). In this study, we systematically analysed retinal dopaminergic dysfunction in murine models of HD (genetic origin) and AD (sporadic), across different disease stages. We assessed dopamine levels, turnover, tyrosine hydroxylase expression, D1 and D2 receptor gene expression, and neurotransmitter balance. HD mice showed early and marked alterations: reduced dopamine content, decreased tyrosine hydroxylase, increased turnover, and downregulation of D1 receptor expression—all preceding motor symptoms and detectable brain pathology. In contrast, AD mice showed only mild changes at later stages; however, clinical evidence suggests that similar dysfunction may occur earlier in human AD. These findings position retinal dopaminergic disruption as a potential early biomarker in HD and possibly in AD. While the current study relies on invasive techniques in animal models, it lays the groundwork for non-invasive retinal assessments, such as electroretinography or optical coherence tomography, as promising tools for early diagnosis and disease monitoring in neurodegeneration. Full article