Search Results (128)

Stem cells, both normal somatic (SSC) and cancer stem cells (CSC) exist in minimally two states, i.e., quiescent and activated. Regulation of these two states, including their reliance on different metabolic processes, i.e., FAO and glycolysis in quiescent versus activated stem cells respectively, involves the analysis of a complex array of factors (nutrient and oxygen levels, adhesion molecules, cytokines, etc.) to initiate the epigenetic changes to either depart or enter quiescence. Quiescence is a critical feature of SSC that is required to maintain the genomic integrity of the stem cell pool, particularly in long lived complex organisms. Quiescence in CSC, whether they are derived from mutations arising in SSC, aberrant microenvironmental regulation, or via dedifferentiation of more committed progenitors, is a critical component of therapy resistance and disease latency and relapse. At the beginning of vertebrate evolution, approximately 450 million years ago, a gene duplication generated the two members of the Kat3 family, CREBBP (CBP) and EP300 (p300). Despite their very high degree of homology, these two Kat3 coactivators play critical and non-redundant roles at enhancers and super-enhancers via acetylation of H3K27, thereby controlling stem cell quiescence versus activation and the cells metabolic requirements. In this review/perspective, we discuss the unique regulatory roles of CBP and p300 and how specifically targeting the CBP/β-catenin interaction utilizing small molecule antagonists, can correct lineage infidelity and safely eliminate quiescent CSC. Full article

The pyrolysis carbon black (CBp) from waste tires contains zinc, iron, and other metal elements, which have high recycling value. This study proposes a simple method of recovering zinc and iron from waste tire-derived CBp to synthesize hydrotalcite-type adsorbents for the treatment of anodic dye wastewater. Firstly, zinc-aluminum hydrotalcite (LDH) and zinc-iron aluminum hydrotalcite (FeLDH) were obtained by leaching the zinc and iron ions from CBp with an acid solution. As compared with LDH, FeLDH shows increased laminate metal ion arrangement density and layer spacing. By calcining the LDH and FeLDH at 500 °C, zinc aluminum oxides (LDO) and zinc iron aluminum oxides (FeLDO) were then prepared and applied for the adsorption of dye methyl orange (MO). The results demonstrate that the maximum adsorption capacity of LDO and FeLDO are 304.9 and 609.8 mg g⁻¹ at pH of 4.0, respectively. The adsorption processes of both LDO and FeLDO are consistent with the Langmuir adsorption isotherm and the proposed second-order kinetic model. The adsorption regeneration performance and adsorption mechanism of LDO and FeLDO were also investigated in detail. Regeneration experiments show that after three cycles, the removal rate of MO by LDO remains above 80%, while that of FeLDO only remains around 64% in the first cycle after regeneration. This work would provide a new pathway to realize the high-value metal recycling of waste tire-derived CBp and solve the contamination of dye wastewater. Full article

Blood pressure (BP), interarm differences (IAD) in BP, and arterial stiffness (AS) are related to cardiovascular disease risk and are attenuated by exercise training. While active, tennis players (TP) experience bilateral differences in shear stress, and thus vascular function due to the unilateral nature of the sport. However, it is unknown if this translates into attenuated bilateral differences in peripheral blood pressure (pBP), estimated central blood pressure (cBP), and AS, which could provide insight into the local versus systemic effects of exercise training on BP in women. Purpose: to evaluate bilateral differences in pBP, cBP, and AS in Division III female college TP and healthy recreationally active (RA) age- and sex-matched controls. Methods: In a parallel design, TP (n = 10) and RA controls (n = 10) were assessed for anthropometrics, body composition, and bilateral BP measurements using oscillometric cuff technique. Results: TP and RA were well-matched for body weight, body fat percentage, and BMI (all, p > 0.69). Interaction of arm and group, and effects of arm, or group were insignificant for pSBP and pDBP (all, p > 0.137). IAD in pSBP tended lower in TP (p = 0.096, d = 0.8), but IAD in cSBP was lower (p = 0.040, d = 0.8). Augmentation pressure and index were different between arms (p = 0.02), but no interactions (group by arm) were observed (p > 0.05). Conclusions: In groups well-matched for age and body composition, TP tended to have lower BP and IAD in pSBP, but cSBP revealed ~50% lower IAD in TP. Thus, measurement site and exercise training matter when assessing arterial stiffness and interarm differences in BP. Full article

Background/Objectives: Patients with chronic bacterial prostatitis (CBP) often present symptoms of sexual dysfunction. We aimed to evaluate the impact of the infection location and etiology on sexual dysfunction in patients with CBP. Methods: Male patients with CBP diagnosed by microbiological tests underwent a complete clinical assessment and were administered questionnaires for prostatitis (NIH-CPSI), voiding (IPSS), and sexual function (IIEF-15, PEDT). Results: Out of 614 patients, erectile dysfunction (ED) was present in 49.8%, and premature ejaculation (PE) in 40.7%. At least one sexual disorder was present in 86.3% when other disorders of ejaculation, orgasm, and sexual desire were considered. Patients with Gram-negative infections in expressed prostatic secretion (EPS) or voided urine after prostatic massage (VB3) had higher odds of moderate to severe erectile dysfunction compared to patients with infection by atypical pathogens (OR 3.31, CI 1.43–7.63, p = 0.0039). Rates of orgasmic dysfunction were also higher in Gram-negative and Gram-positive with respect to atypicals (OR 3.2, CI 1.36–7.90, p = 0.006 and OR 3.78, CI 1.64–8.71, p = 0.001). Hemospermia was more frequent in patients with semen infection by Gram-positive than in patients with infection by atypical pathogens (OR 2.2984, CI 1.3239–3.9901, p = 0.002). Prostatic calcifications at transrectal ultrasound were less frequent in patients with semen infection by Gram-negative compared to Gram-positive (OR 0.471, CI 0.3029–0.7322, p = 0.000). The addition of an “S” (sexual) domain to the UPOINT classification achieves a more significant correlation between the number of positive domains in each patient and the NIH-CPSI score. Conclusions: Infections by Gram-negative are associated with more sexual morbidity in patients with CBP. The use of a questionnaire investigating all the main domains of sexual dysfunction could be very useful for the phenotyping of patients with chronic prostatitis. Full article

The heat transfer (HT) characteristics of cylindrical biomass particles (CBPs) in fluidized beds (FBs) are important for their drying, direct combustion, and thermochemical transformation. To provide a deeper insight into the complex mechanisms behind the HT behaviors involving CBPs, this study developed a cylindrical particle HT model within the framework of computational fluid dynamics coupled with the discrete element method (CFD-DEM) in which the CBPs were characterized by the super-ellipsoid model, which has the unique merit of striking a balance between computational accuracy and efficiency. The newly developed heat transfer model considers particle–particle (P-P), particle–wall (P-W), and fluid–particle (F-P). Its accuracy was verified by comparing the numerical results with the experimental infrared thermography measurements in terms of the temperature evolution of the cylindrical particles. The effects of the gas velocity, inlet temperature, and thermal conductivity of particles on the HT behaviors of the CBPs were investigated comprehensively. The results demonstrated the following: (1) Gas velocity can improve the uniformity of bed temperature distribution and shorten the fluctuation process of bed temperature uniformity. (2) A 26.8% increase in inlet temperature leads to a 13.4% increase in the proportion of particles with an orientation in the range of 60–90°. (3) The thermal conductivity of particles has no obvious influence on the bed temperature, convective HT rate, or orientation of particles. Full article

Abnormal epigenetic reprogramming of nuclear-transferred (NT) embryos leads to the limited efficiency of producing cloned animals. Trichostatin A (TSA), a histone deacetylase inhibitor, improves NT embryo development, but its role in histone acetylation in porcine embryos cloned with mesenchymal stem cells (MSCs) is not fully understood. This study aimed to compare the effects of TSA on embryo development, histone acetylation patterns, and key epigenetic-related genes between in vitro fertilization (IVF), NT-MSC, and 40 nM TSA-treated NT-MSC (T-NT-MSC). The results demonstrated an increase in the blastocyst rate from 13.7% to 32.5% in the T-NT-MSC, and the transcription levels of CDX2, NANOG, and IGF2R were significantly elevated in T-NT-MSC compared to NT-MSC. TSA treatment also led to increased fluorescence intensity of acH3K9 and acH3K18 during early embryo development but did not differ in acH4K12 levels. The expression of epigenetic-related genes (HDAC1, HDAC2, CBP, p300, DNMT3a, and DNMT1) in early pre-implantation embryos followed a pattern similar to IVF embryos. In conclusion, TSA treatment improves the in vitro development of porcine embryos cloned with MSCs by increasing histone acetylation, modifying chromatin structure, and enhancing the expression of key genes, resulting in profiles similar to those of IVF embryos. Full article

Potassium (K) fertilization is crucial for plant resistance to pathogens, but the underlying mechanisms remain unclear. Here, we investigate the molecular mechanism by which the addition of K promotes resistance in Nicotiana benthamiana to Phytophthora parasitica. We found that N. benthamiana with high K content (HK, 52.3 g/kg) produced more ethylene in response to P. parasitica infection, compared to N. benthamiana with low-K content (LK, 22.4 g/kg). An exogenous ethylene application effectively increased resistance in LK N. benthamiana to the level under HK status, demonstrating the involvement of ethylene in the HK-associated resistance in N. benthamiana. Further, transcriptome analysis showed that NbSAMS1, encoding ethylene biosynthesis, was induced to upregulate P. parasitica about five times higher in HK than in LK N. benthamiana. NbSAMS1 overexpression enhanced resistance in LK plants, whereas NbSAMS1 silencing reduced resistance in HK plants, confirming its importance in conferring resistance. Furthermore, we identified a calcium-binding protein, NbCBP1, which interacted with NbSAMS1, promoting its expression in HK N. benthamiana. Silencing NbCBP1 compromised resistance in HK N. benthamiana, whereas its overexpression improved resistance in LK N. benthamiana. Notably, NbCBP1 protected NbSAMS1 from degradation by the 26S proteasome, thereby sustaining ethylene accumulation in HK N. benthamiana in response to P. parasitica infection. Thus, our research elucidated some mechanisms of the NbCBP1-NbSAMS1 module associated with disease resistance in HK N. benthamiana. Full article

Several studies have suggested that probiotics could play a role in the management of patients with chronic bacterial prostatitis (CBP). In this randomized, placebo-controlled clinical study, we evaluated the efficacy and safety of consumption of probiotics containing human Lactobacillus casei DG^® as an add-on treatment in patients with clinical recurrences of CBP, through gut microbiota modification analysis. Enrolled patients with CBP were randomized to receive for 3 months probiotics containing human Lactobacillus casei DG^® or placebo following 1 month treatment with ciprofloxacin. During the enrollment and follow-ups, urological examinations analyzed symptoms and quality of life, while microbiological tests analyzed gut and seminal microbiota. During the study, the development of adverse drug reactions was evaluated through the Naranjo scale. Twenty-four patients with CBP were recruited and treated for 3 months with placebo (n. 12) or with Lactobacillus casei DG^® (n. 12). Lactobacillus casei DG^® induced a significantly (p < 0.01) faster recovery of symptoms than placebo (2 days vs. 8 days) and an increased time free from symptoms (86 days vs. 42 days) without the occurrence of adverse events. In the probiotic group, the appearance of Lactobacilli after 30 days (T1) was higher vs. the placebo group, and a significant reduction in Corynebacterium, Peptoniphilus, Pseudomonas, Veillonella, Staphylococcus, and Streptococcus was also observed. These preliminary data suggest that in patients with CBP, the use of Lactobacillus casei DG after an antimicrobial treatment improves the days free of symptoms and the quality of life, without the development of adverse drug reactions. Full article

Background: General control nonderepressible 5 (Gcn5) is a lysine acetyltransferase (KAT) that is evolutionarily conserved across eukaryotes, with two homologs (Kat2a and Kat2b) identified in humans and one (Gcn5) in Drosophila. Gcn5 contains a P300/CBP-associated factor (PCAF) domain, a Gcn5-N-acetyltransferase (GNAT) domain, and a Bromodomain, allowing it to regulate gene expression through the acetylation of both histone and non-histone proteins. In Drosophila, Gcn5 is crucial for embryonic development, with maternal Gcn5 supporting early development. However, the functional mechanisms of Gcn5 after the depletion of maternal deposits remain unclear. Methods: Our study employed the Gal4/UAS-RNAi system to achieve whole-body or heart-specific Gcn5 knockdown in Drosophila and selected 96-hour-old surviving larvae for transcriptomic and metabolomic analyses. Results: Omics results revealed that Gcn5 knockdown significantly impacts various metabolic pathways, as well as lysosomes, non-homologous end-joining, Toll and Imd signaling pathways, and circadian rhythms, among others. Furthermore, defects in chitin synthesis may be associated with impaired pupation. Additionally, heart-specific Gcn5 knockdown affected cardiac physiology but appeared to have a potential protective effect against age-related cardiac decline. Conclusions: These findings deepen our understanding of Gcn5’s roles in Drosophila development and provide valuable insights for developing Gcn5-targeted therapies, particularly considering its involvement in various human diseases. Full article

Trueperella pyogenes is a significant opportunistic pathogen that causes substantial economic losses in animal agriculture due to its ability to infect various animal tissues and organs. Limited research has been conducted on the prevalence and biological characteristics of T. pyogenes isolated from sheep and goats. This study aimed to isolate T. pyogenes from clinical samples of sheep and goats in western China, examining genetic evolutionary relationships, antibiotic resistance, and virulence genes. Between 2021 and 2023, standard bacteriological methods were used to isolate and identify T. pyogenes from 316 samples (209 from goats and 107 from sheep) collected from 39 farms. Susceptibility to 14 antibiotics was tested using broth microdilution per CLSI guidelines, and PCR detected eight virulence genes. Whole-genome sequencing analyzed genetic relationships and gene carriage status in 39 isolates. The results indicated that 86 strains of T. pyogenes were isolated from 316 samples, yielding an isolation rate of 27.2% (goats n = 47, 22.5%; sheep n = 39, 36.4%). The virulence genes plo, cbpA, nanH, nanP, fimA, fimC, and fimE were present in 100%, 66.7%, 64.1%, 71.8%, 69.2%, 59.0%, and 82.1% of isolates, respectively, with none carrying the fimG gene. The dominant virulence genotype was plo/nanH/nanP/fimA/fimC/fimE. The isolates exhibited resistance to erythromycin (44.2%, 38/86), gentamicin (38.4%, 33/86), sulfamethoxazole/trimethoprim (37.2%, 32/86), tetracycline (32.6%, 28/86), and streptomycin (32.6%, 28/86), and low resistance to chloramphenicol (14.0%, 12/86), ciprofloxacin (7.0%, 6/86), penicillin (5.8%, 5/86), and clindamycin (4.7%, 4/86). All isolates were susceptible to cefotaxime, vancomycin, and linezolid. Among the 86 isolates, 37 (43.0%) displayed multidrug resistance (MDR) characteristics. The whole genome sequencing of 39 isolates identified eight types of resistance genes, including ant(2″)-Ia, ant(3″)-Ia, cmlA1, cmx, erm(X), lnu(A), sul1, and tet(W). Except for tet(W), erm(X), and sul1, the other resistance genes were reported for the first time in T. pyogenes isolated in China. The drug susceptibility test results and resistance gene detection for the isolated strains were consistent for tetracycline, erythromycin, gentamicin, and sulfisoxazole. Similar allelic profiles and genetic evolutionary relationships were found among isolates from different farms. This study highlights the antibiotic resistance status and virulence gene-carrying rate of Trueperella pyogenes, providing a basis for clinical medication. Full article

Δ⁹-Tetrahydrocannabiphorol (Δ⁹-THCP, THCP) a psychoactive cannabinoid recently found in Cannabis sativa L., is widely used as a legal marijuana substitute. THCP is encountered in sprayed Cannabis, edibles, and vape liquids. The distributors of such products claim that the THCP in use originates from a natural source. The legal status of this substance varies from country to country. THCP and similar cannabinoids with a dibenzoyprane structure have been banned in Switzerland since October 2023. A vape liquid, which contains 90% THCP and 10% terpenes according to the distributor, was analyzed by gas chromatography coupled with mass spectrometry (GC-MS). Besides CBP, CBDP, Δ⁹-THCP and Δ⁸-THCP and some terpenes, other compounds were found which probably result from a synthetic procedure. This sample contained 5-heptylresorcinol, the heptyl homologue of olivetol, a common precursor for the synthesis of tetrahydrocannabinol (THC). Bisalkylated compounds (m/z 476) were found as a result of the reaction of one equivalent of 5-heptylresorcinol with two equivalents of (+)-p-mentha-1,8-dien-4-ol or another precursor. Similar bisalkylated compounds are known as undesired side products of the synthesis of THC. The sample contained unidentified isomers of Δ⁹-THCP, presumably abnormal cannabinoids (abn-Δ⁹-THCP; abn-Δ⁸-THCP) and iso-cannabinoids (iso-THCP). Chiral derivatization with Mosher acid chlorides revealed that the Δ⁹-THCP in the sample was enantiopure. Full article

CBP and p300 are versatile transcriptional co-activators that play essential roles in regulating a wide range of signaling pathways, including Wnt/β-catenin, p53, and HIF-1α. These co-activators influence various cellular processes such as proliferation, differentiation, apoptosis, and response to hypoxia, making them pivotal in normal physiology and disease progression. The Wnt/β-catenin signaling pathway, in particular, is crucial for cellular proliferation, differentiation, tissue homeostasis, and embryogenesis. Aberrant activation of this pathway is often associated with several types of cancer, such as colorectal tumor, prostate cancer, pancreatic and hepatocellular carcinomas. In recent years, significant efforts have been directed toward identifying and developing small molecules as novel anticancer agents capable of specifically inhibiting the interaction between β-catenin and the transcriptional co-activators CBP and p300, which are required for Wnt target gene expression and are consequently involved in the regulation of tumor cell proliferation, migration, and invasion. This review summarizes the most significant and original research articles published from 2010 to date, found by means of a PubMed search, highlighting recent advancements in developing both specific and non-specific inhibitors of CBP/β-catenin and p300/β-catenin interactions. For a more comprehensive view, we have also explored the therapeutic potential of CBP/p300 bromodomain and histone acetyltransferase inhibitors in disrupting the transcriptional activation of genes involved in various signaling pathways related to cancer progression. By focusing on these therapeutic strategies, this review aims to offer a detailed overview of recent approaches in cancer treatment that selectively target CBP and p300, with particular emphasis on their roles in Wnt/β-catenin-driven oncogenesis. Full article

An amylolytic industrial yeast strain named 1974-GA-temA, developed previously by our research team by coexpressing the α-amylase and glucoamylase genes, combines enzyme production, sweet potato residue (SPR) hydrolysis, and glucose fermentation into ethanol in a one-step process. This consolidated bioprocessing (CBP) method has great application potential in the commercial production of bioethanol from SPR, but important fermentation parameters should be optimized to further increase the ethanol concentration and yield. In this study, the effects of the initial fermentation pH, solid-to-liquid ratio, inoculation volume, addition of exogenous enzyme, and supplementation with metal ions were systemically investigated. Single-factor experiments revealed that the optimal pH was 4.0. In the solid-to-liquid ratio test, an increase in the solid-to-liquid ratio corresponded with a gradual increase in the ethanol concentration, peaking at 1:5. However, the ethanol yield gradually decreased, with the optimal solid-to-liquid ratio identified as 1:5. The ethanol concentration and yield reached 9.73 g/L and 5.84%, respectively. Additionally, an increase in the inoculum size resulted in increased ethanol concentration and yield, with the optimal inoculum level determined to be 10%. An ethanol concentration of 7.87 g/L was attained under these specified conditions, equating to an ethanol yield of 4.72%. Further analysis was conducted to assess the effects of exogenous cellulase, hemicellulase, and pectinase, both individually and in combination, on ethanol concentration and yield. The results indicated that pectinase had a particularly significant effect. The highest ethanol concentration was observed when all three enzymes were administered concurrently, yielding 27.27 g/L ethanol. Then, the role of metal ions in SPR fermentation was evaluated. The metal ions did not significantly affect the process, with the exception of copper ions. The addition of copper ions at a specific concentration of 0.2 g/100 g SPR increased the ethanol concentration. However, concentrations exceeding 0.2 g/100 g SPR inhibited yeast cell growth. Finally, orthogonal optimization was employed to determine the optimal combination of factors: pH, 4.0; solid-to-liquid ratio, 1:6; inoculation volume, 10%; cellulase and pectinase addition; and the absence of Cu²⁺ addition. Under these conditions, strain 1974-GA-temA produced 34.83 ± 0.62 g/L ethanol after 8 days of fermentation, corresponding to a 20.90% ± 0.37% ethanol yield. This value markedly exceeds the outcomes of all the conducted orthogonal experiments. The fermentation optimization experiments in this study are expected to increase ethanol production during the CBP fermentation of SPR. Full article

Recalcitrant compounds resulting from anthropogenic activity are a significant environmental challenge, necessitating the development of advanced oxidation processes (AOPs) for effective remediation. This study explores the synthesis of cuprous oxide nanoparticles on cellulose-based paper (Cu₂O@CBP) using Eucalyptus globulus leaf extracts, leveraging green synthesis techniques. The scanning electron microscopy (SEM) analysis found the average particle size 64.90 ± 16.76 nm, X-ray diffraction (XRD) and Raman spectroscopy confirm the Cu₂O structure in nanoparticles; Fourier-transform infrared spectroscopy (FTIR) suggests the reducing role of phenolic compounds; and ultraviolet–visible diffuse reflectance spectroscopy (UV-Vis DRS) allowed us to determine the band gap (2.73 eV), the energies of the valence band (2.19 eV), and the conduction band (−0.54 eV) of Cu₂O@CBP. The synthesized Cu₂O catalysts demonstrated efficient degradation of methylene blue (MB) used as a model as recalcitrant compounds under LED-driven visible light photocatalysis and heterogeneous Fenton-like reactions with hydrogen peroxide (H₂O₂) using the degradation percentage and the first-order apparent degradation rate constant (k_app). The degradation efficiency of MB was pH-dependent, with neutral pH favoring photocatalysis (k_app = 0.00718 min⁻¹) due to enhanced hydroxyl (·OH) and superoxide radical (O₂·⁻) production, while acidic pH conditions improved Fenton-like reaction efficiency (k_app = 0.00812 min⁻¹) via ·OH. The reusability of the photocatalysts was also evaluated, showing a decline in performance for Fenton-like reactions at acidic pH about 22.76% after five cycles, while for photocatalysis at neutral pH decline about 11.44% after five cycles. This research provides valuable insights into the catalytic mechanisms and supports the potential of eco-friendly Cu₂O nanoparticles for sustainable wastewater treatment applications. Full article

T cell activation is critical for an effective immune response against pathogens. However, dysregulation contributes to the pathogenesis of autoimmune diseases, including Juvenile Idiopathic Arthritis (JIA). The molecular mechanisms underlying T cell activation are still incompletely understood. T cell activation promotes the acetylation of histone 3 at Lysine 27 (H3K27ac) at enhancer and promoter regions of proinflammatory cytokines, thereby increasing the expression of these genes which is essential for T cell function. Co-activators E1A binding protein P300 (P300) and CREB binding protein (CBP), collectively known as P300/CBP, are essential to facilitate H3K27 acetylation. Presently, the role of P300/CBP in human CD4+ T cells activation remains incompletely understood. To assess the function of P300/CBP in T cell activation and autoimmune disease, we utilized iCBP112, a selective inhibitor of P300/CBP, in T cells obtained from healthy controls and JIA patients. Treatment with iCBP112 suppressed T cell activation and cytokine signaling pathways, leading to reduced expression of many proinflammatory cytokines, including IL-2, IFN-γ, IL-4, and IL-17A. Moreover, P300/CBP inhibition in T cells derived from the inflamed synovium of JIA patients resulted in decreased expression of similar pathways and preferentially suppressed the expression of disease-associated genes. This study underscores the regulatory role of P300/CBP in regulating gene expression during T cell activation while offering potential insights into the pathogenesis of autoimmune diseases. Our findings indicate that P300/CBP inhibition could potentially be leveraged for the treatment of autoimmune diseases such as JIA in the future. Full article