Search Results (26,457)

Electrospun regenerated cellulose (RC) nanofiber membranes were prepared starting from cellulose acetate (CA) with different degrees of substitution. The process was optimized to obtain continuous and uniformly sized CA fibers. After electrospinning, the CA membranes were heat-treated to increase their tensile strength before deacetylation to obtain regenerated cellulose (RC). Affinity membranes were obtained by functionalization, exploiting the hydroxyl groups on the cellulose backbone. 1,4-Butanediol-diglycidyl ether was used to introduce epoxy groups onto the membrane, which was further bioconjugated with the anti-CD63 antibody targeting the tetraspanin CD63 on the extracellular vesicle membrane surface. The highest ligand density was obtained with an anti-CD63 antibody concentration of 6.4 µg/mL when bioconjugation was performed in carbonate buffer. The resulting affinity membrane was tested for the adsorption of extracellular vesicles (EVs) from human platelet lysate, yielding a very promising binding capacity above 10 mg/mL and demonstrating the suitability of this approach. Full article

The impact of various modification methods on enhancing the adsorption performance of coal gangue (CG) for hazardous heavy metals has not been thoroughly investigated. In this study, three CG samples were first modified by calcination, followed by acid washing, alkali washing, and hydrothermal treatment, to obtain modified CG samples. The adsorption performance was assessed based on the adsorption capacities for Cd²⁺ and Pb²⁺ (i.e., q_e,Cd and q_e,Pb), and the kinetics of the adsorption processes were analyzed using kinetic equations. XRD, SEM-EDX, FTIR, and N₂ adsorption–desorption isotherms were used to elucidate the adsorption mechanisms. Results indicated that q_e,Cd and q_e,Pb of raw CG samples were approximately 10 and 25 mg/g, respectively, with only slight changes observed after calcination, acid washing, and alkali washing. In contrast, hydrothermal treatment yielded NaP and NaA zeolites, which significantly enhanced q_e,Cd and q_e,Pb to values of 48.5‒72.7 and 214.9‒247.5 mg/g, respectively. The hydrothermally treated CG samples primarily adsorbed Cd²⁺ and Pb²⁺ through ion exchange with Na⁺ within the zeolite structure, facilitating the entry of these ions into the zeolite’s pore channels. The adsorption processes were effectively described by the pseudo-second-order kinetic model. By optimizing the conditions of hydrothermal modification, the adsorption performance of CG samples is anticipated to further improve due to the creation of additional adsorption sites. Full article

2-deoxy-D-glucose (2DG) is a glycolysis and protein N-glycosylation inhibitor with promising anti-tumor and immunomodulatory effects. However, 2DG can also suppress T cell function, including IFN-γ secretion. Few human T cell studies have studied low-dose 2DG, which can increase IFN-γ in a Jurkat clone. We therefore investigated 2DG’s effect on IFN-γ in activated human T cells from PBMCs, with 2DG treatment commenced either concurrently with activation or 48 h after activation. Concurrent 2DG treatment decreased IFN-γ secretion in a dose-dependent manner. However, 2DG treatment of pre-activated T cells had a hormetic effect on IFN-γ, with 0.15–0.6 mM 2DG (achievable in vivo) increasing and >2.4 mM 2DG reducing its secretion. In contrast, IL-2 levels declined monotonously with increasing 2DG concentration. Lower 2DG concentrations reduced PD-1 and increased CD69 expression regardless of treatment timing. The absence of increased T-bet or Eomes expression or IFNG transcription suggests another downstream mechanism. 2DG dose-dependently induced the unfolded protein response, suggesting a possible role in increased IFN-γ secretion, possibly by increasing the ER folding capacity for IFN-γ via increased chaperone expression. Overall, low-dose, short-term 2DG exposure could potentially improve the T cell anti-tumor response. Full article

Fewer than 1% of patients with celiac disease (CD) will develop refractory CD (RCD). As such, most gastroenterologists might never need to manage patients with RCD. However, all gastroenterologists must be familiarized with the basic concepts of RCD and non-responsive CD (NRCD), since it can present as a severe disease with high mortality, not only due to intestinal failure, but also due to progression to enteropathy-associated T cell lymphoma (EATL) and a higher susceptibility to life-threatening infections. The diagnostic workup and differential diagnosis with other causes of gastrointestinal symptoms and villous atrophy, as well as the differentiation between type I and II RCD, are complex, and may require specialized laboratories and reference hospitals. Immunosuppression is efficient in the milder RCDI; however, the treatment of RCDII falls short, with current options probably only providing transient clinical improvement and delaying EATL development. This review summarizes the current diagnostic and therapeutic approach for patients with RCD that all doctors that manage patients with CD should know. Full article

COVID-19 remains a significant threat, particularly to vulnerable populations. The emergence of new variants necessitates the development of treatments and vaccines that induce both humoral and cellular immunity. This study aimed to identify potentially immunogenic SARS-CoV-2 peptides and to explore the intricate host–pathogen interactions involving peripheral immune responses, memory profiles, and various demographic, clinical, and lifestyle factors. Using in silico and experimental methods, we identified several CD8-restricted SARS-CoV-2 peptides that are either poorly studied or have previously unreported immunogenicity: fifteen from the Spike and three each from non-structural proteins Nsp1-2-3-16. A Spike peptide, LA-9, demonstrated a 57% response rate in ELISpot assays using PBMCs from 14 HLA-A*02:01 positive, vaccinated, and mild-COVID-19 recovered subjects, indicating its potential for diagnostics, research, and multi-epitope vaccine platforms. We also found that younger individuals, with fewer vaccine doses and longer intervals since infection, showed lower anti-Spike (ELISA) and anti-Wuhan neutralizing antibodies (pseudovirus assay), higher naïve T cells, and lower central memory, effector memory, and CD4hiCD8low T cells (flow cytometry) compared to older subjects. In our cohort, a higher prevalence of Vδ2-γδ and DN T cells, and fewer naïve CD8 T cells, seemed to correlate with strong cellular and lower anti-NP antibody responses and to associate with Omicron infection, absence of confusional state, and habitual sporting activity. Full article

Cadmium (Cd) is a non-essential trace element that poses significant toxic effects on fish. This review focuses on hematological and plasma biochemical parameters as key indicators of fish health under Cd exposure. Hematological parameters, such as red blood cell (RBC) count, hemoglobin (Hb) concentration, and hematocrit (Ht), were selected for their critical role in oxygen transport and their sensitivity to Cd-induced disruptions, which often result in anemia and impaired oxygen delivery to tissues. Mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) provide further insights into erythropoiesis and hemoglobin synthesis, both of which are essential for assessing Cd toxicity. Plasma biochemical parameters, including calcium, magnesium, glucose, cholesterol, total protein, and liver enzymes such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP), are crucial for understanding ionic balance, metabolic regulation, and organ function, especially in fish exposed to Cd. These biomarkers offer a comprehensive view of the physiological stress and organ damage caused by Cd toxicity. This review synthesizes literature findings on the toxic effects of Cd on these parameters. It also discusses potential mitigation strategies, including dietary supplementation with antioxidants and trace elements, to counteract the harmful effects of Cd exposure. Full article

Atherosclerosis is characterized by the deposition and accumulation of extracellular cholesterol and inflammatory cells in the arterial blood vessel walls, and 27-hydroxycholesterol (27OHChol) is the most abundant cholesterol metabolite. 27OHChol is an oxysterol that induces immune responses, including immune cell activation and chemokine secretion, although the underlying mechanisms are not fully understood. In this study, we investigated the roles of the mechanistic target of rapamycin (mTOR) in 27HChol-induced inflammation using rapamycin. Treating monocytic cells with rapamycin effectively reduced the expression of CCL2 and CD14, which was involved with the increased immune response by 27OHChol. Rapamycin also suppressed the phosphorylation of S6 and 4EBP1, which are downstream of mTORC1. Additionally, it also alleviates the increase in differentiation markers into macrophage. These results suggest that 27OHChol induces inflammation by activating the mTORC1 signaling pathway, and rapamycin may be useful for the treatment of atherosclerosis-related inflammation involving 27OHchol. Full article

Background: Considering the increasing worldwide prevalence of inflammatory bowel disease (IBD), the early diagnosis of this disease is extremely important. However, non-invasive diagnostic methods remain limited, while invasive techniques are the most commonly used in daily practice. Therefore, there is a serious need to find new non-invasive biomarkers of IBD. Methods: The serum profiles of occludin, claudin-2, and zonulin were assessed in IBD patients using the ELISA method. The levels of the analyzed biomarkers were measured before and after a year of anti-inflammatory treatment, which was a tumor necrosis factor α (TNF-α) inhibitor (adalimumab) in patients with ulcerative colitis (UC) and conventional therapy in patients with Crohn’s disease (CD). Results: In IBD patients, the serum level of occludin (p < 0.001) decreased compared to healthy individuals, while the level of claudin-2 (p < 0.001) increased. Additionally, zonulin (p < 0.01) concentration increased in CD patients compared to the control group. The highest diagnostic ability was presented by occludin measurements with the area under the curve (AUC) of 0.959 (95% CI 0.907–1) in UC and 0.948 (95% CI 0.879–1) in CD. Claudin-2 also demonstrated very good ability in diagnosing UC and CD with AUC values of 0.864 (95% CI 0.776–0.952) and 0.896 (95% CI 0.792–0.999), respectively. The ability of zonulin to diagnose CD was estimated as good with an AUC of 0.74 (95% CI 0.598–0.881). Moreover, a significant correlation was identified between C-reactive protein (CRP), claudin-2 (r = −0.37; p < 0.05), and zonulin (r = −0.44; p < 0.05) in UC patients. Treatment with adalimumab improved the level of occludin, claudin-2, and zonulin in UC patients, while anti-inflammatory conventional therapy decreased the concentration of zonulin in CD. Conclusions: Occludin and claudin-2 measurements present significant utility in diagnosing both UC and CD, while zonulin assessments may be useful in CD diagnosis. Additionally, claudin-2 and zonulin measurements may be helpful in evaluating the intensity of the inflammatory process. Anti-TNF-α treatment improved the value of occludin, claudin-2, and zonulin, indicating its beneficial effect on the integrity of tight junctions in UC. Full article

The metabolic reprogramming characteristic of cancer cells, including the Warburg effect, has long been recognized as a hallmark of malignancy. This commentary explores three recent investigations focusing on the role of wild-type IDH2 in cancer and immune cell function. The first publication identifies wild-type IDH2 as a crucial factor in the survival of triple-negative breast cancer (TNBC) cells, with its inhibition leading to disrupted energy metabolism, reduced tumor growth, and enhanced apoptosis. The second analysis examines the role of IDH2 in CD8+ T cells, revealing that its inhibition promotes the differentiation of memory T cells, thereby enhancing the efficacy of cell-based immunotherapies like CAR T cells. A third investigation supports these findings, demonstrating that IDH2 inhibition in CAR T cells reduces exhaustion, enhances memory T cell formation, and improves anti-tumor efficacy. Collectively, these reports highlight wild-type IDH2 as a promising therapeutic target, with potential applications as a two-edged sword in both cancer treatment and immunotherapy. The development of specific wild-type IDH2 inhibitors could offer new avenues for therapy, particularly in tumors reliant on IDH2 activity as well as in enhancing the effectiveness of CAR T cell therapies. Full article

As a great economic Solanum with ornamental value and good adaptability, Solanum aculeatissimum is considered an excellent candidate for the phytoremediation of Cadmium-contaminated soils. However, there are no studies on the involvement of S. aculeatissimum in the response and tolerance mechanisms of cadmium (Cd) stress. In the present study, S. aculeatissimum was used for the first time for physiological and transcriptomic systematic analysis under different concentrations of Cd stress. The results showed that S. aculeatissimum was indeed well tolerant to Cd and showed Cd enrichment capabilities. Under the Cd stress treatment of 50 mg/kg (Cd6), S. aculeatissimum could still grow normally. At the 90th day of Cd stress, the amount of Cd content in different parts of the plant at the same concentration was in the order of root > stem > leaf. With the extension of the stress time up to 163 d, the trend of Cd content in each part was not consistent, and the results in the root (77.74 mg/kg), stem (30.01 mg/kg), leaf (29.44 mg/kg), immature fruit (18.36 mg/kg), and mature fruit (21.13 mg/kg) of Cd peaked at Cd4, Cd5, Cd1, Cd4, and Cd4, respectively. The enrichment and transport coefficients of all treatments were greater than 1. The treatment groups with the largest and smallest enrichment coefficients were Cd4 and CK, respectively. The treatment groups with the largest and smallest transport coefficients were CK and Cd4, respectively. Malondialdehyde (MDA), peroxidase (POD), and catalase (CAT) in the antioxidant system after Cd stress treatment were significantly increased compared to the untreated group. Under cadmium stress, by using real-time quantitative PCR, four genes (SaHMA20, SaL-AO, SaPrxs4, and SaPCs) were screened for possible correlations to Cd tolerance and absorption enrichment in S. aculeatissimum. The key DEGs are mainly responsible for the metabolic pathways of heavy metal ATPases, plastocyanin protein phytocyanins (PCs), peroxidases (Prxs), and ascorbate oxidase (AAO); these differential genes are believed to play an important role in Cd tolerance and absorption enrichment in S. aculeatissimum. Full article

Cadmium (Cd²⁺) is a non-essential and highly toxic element to all organic life forms, including plants and humans. In response to Cd stress, plants have evolved multiple protective mechanisms, such as Cd²⁺ chelation, vesicle sequestration, the regulation of Cd²⁺ uptake, and enhanced antioxidant defenses. When Cd²⁺ accumulates in plants to a certain level, it triggers a burst of reactive oxygen species (ROS), leading to chlorosis, growth retardation, and potentially death. To counteract this, plants utilize a complex network of enzymatic and non-enzymatic antioxidant systems to manage ROS and protect cells from oxidative damage. This review systematically summarizes how various elements, including nitrogen, phosphorus, calcium, iron, and zinc, as well as phytohormones such as abscisic acid, auxin, brassinosteroids, and ethylene, and signaling molecules like nitric oxide, hydrogen peroxide, and hydrogen sulfide, regulate the antioxidant system under Cd stress. Furthermore, it explores the mechanisms by which exogenous regulators can enhance the antioxidant capacity and mitigate Cd toxicity. Full article

Introduction: Therapeutic drug monitoring (TDM) has proven to be a valuable strategy for optimizing biologic therapies, among which are anti-tumor necrosis factor (anti-TNF) treatments in inflammatory bowel disease (IBD). In particular, reactive TDM has been shown to manage treatment failures more cost-effectively than empirical dose adjustments for anti-TNF drugs. However, several challenges currently impede the widespread adoption of TDM in clinical practice, particularly addressing the delay between sample collection and result availability. To overcome this limitation, the use of point-of-care technology tests (POCTs) is a potential solution. Point-of-care technology tests are medical diagnostic tests performed at the site of patient care to provide immediate results, allowing for quicker decision-making and treatment. The current standard of care (SOC) for drug level measurement relies on the enzyme-linked immunosorbent assay (ELISA), a method that is time-consuming and requires specialized personnel. This study aims to evaluate a novel, user-friendly, and efficient POCT method (ProciseDx Inc.) and compare its performance with the SOC ELISA in assessing infliximab and adalimumab levels in blood samples from IBD patients. Methods: In this prospective, single-center study, we collected blood samples from IBD patients, both CD and UC, receiving infliximab (87 IBD patients; 50% UC and 50% CD) or adalimumab (60 patients; 14% UC and 48% CD) and we analyzed the blood’s drugs levels using both the ProciseDx Analyzer POC and the SOC ELISA. We examined the correlation between the two methods using statistical analyses, including the Deming regression test. Additionally, we assessed the ease of use, turnaround time, and overall practicality of the POCT in a clinical setting. Results: The ProciseDx test demonstrated a strong correlation with the SOC ELISA for measuring both infliximab and adalimumab levels. In particular, the overall correlation between the ProciseDx POCT and the ELISA assessments showed an r coefficient of 0.83 with an R squared value of 0.691 (95% CI 0.717–0.902) for IFX measurements, and an r coefficient of 0.85 with an R squared value of 0.739 (95% CI 0.720–0.930). Conclusions: the ProciseDx POC test offers significantly faster turnaround times and is more straightforward to use, making it a viable alternative for routine clinical monitoring. Despite its promising potential, further refinement and validation of the ProciseDx test are necessary to ensure its effectiveness across diverse patient populations and clinical settings. Future research should focus on optimizing the POC tests’ performance and evaluating its long-term impact on IBD management. Full article

Introduction: Patients undergoing hemodialysis (HD) often exhibit an impaired cellular immune response, which may contribute to an increased susceptibility to infections and other complications. Th1 cells, a subset of T-helper cells, play a crucial role in cellular immunity. However, the modulation of Th1 cells by HD treatment remains unclear. Objective: This study aims to investigate the levels of circulating T cells, especially Th1 cells, and the neutrophil-to-lymphocyte ratio (NLR) in HD patients. Methods: We recruited 26 HD patients and 10 healthy volunteers. Demographical data were collected, and peripheral blood samples were analyzed. Absolute blood cell counts were determined, and T-cell populations were identified using flow cytometry. Th1 cells were defined as IFN-γ-producing CD4⁺ T cells after in vitro activation, and NLR was calculated through the ratio between the neutrophil and lymphocyte counts measured in peripheral blood. Results: We have observed a significant decrease in Th1 subpopulation frequency in HD patients, as well as significant correlations between immunological and demographic parameters, among which are the NLR values and the absolute values of T-cell subsets. Conclusions: These results seem to clarify the role of Th1 cells in modulating the immune responses of hemodialysis-treated patients, potentially considering its frequency as an indicator for CKD development. Full article

Weaning stress can trigger diarrhea, cause intestinal damage, and disrupt the intestinal flora of piglets, ultimately resulting in retarded growth or even the death of the animals. Traditional Chinese medicine residues encompass numerous bioactive compounds and essential nutrients; however, their efficient utilization remains a challenge. Consequently, our study sought to explore the impact of traditional Chinese medicine residues, specifically Isatidis Root residue (IRR), on the growth performance, intestinal function, and occurrence of weaning diarrhea in newly weaned piglets. Forty healthy, castrated Duroc × Landrace × Yorkshire males, weaned at 21 days old and exhibiting similar body conditions, were randomly allocated into five groups, with eight piglets in each group. The results indicated that the dietary inclusion of IRR at concentrations ranging from 0.5% to 4.0% notably decreased the incidence of diarrhea in weaned piglets compared to the control group (p < 0.05). Serum LDL-C and globulin (GLB) contents were reduced in response to dietary IRR concentrations (0.5% to 4.0%), while serum albumin (ALB) and albumin/globulin (A/G) contents were enhanced (p < 0.05). Dietary 0.5%, 1.0%, and 2.0% IRR resulted in significant increases in villus height (VH) and villus height/crypt depth (V/C) ratios in the jejunum, V/C ratios in the ileum, and the number of villi goblet cells both in the jejunum and ileum. IRR also led to a significant decrease in the crypt depth (CD) of the jejunum and ileum (p < 0.05). Furthermore, the expression of IL-6 in the jejunum was significantly increased in IRR-fed piglets (0.5% to 4.0%) (p < 0.05). IRR demonstrated inhibitory effects on harmful bacteria in the gastrointestinal microbiome, including Campylobacter, Actinobacillus minor, and Ralstonia pickettii, indicating its broad-spectrum bacteriostatic properties. In conclusion, dietary IRR alleviated diarrhea in weaned piglets and improved gut function and microbial compositions. Full article

In this study, in order to obtain excellent mechanical properties in TiB₂/Al–Cu–Mn–Cd composite, an optimized heat treatment, i.e., short-time solution treatment at 535 °C for 1 h following long-time solution at 523 °C for 11 h, and aging treatment, i.e., aged at 170 °C for 12 h, is proposed. In addition, this study investigated the connection between microstructure evolution and mechanical properties during heat treatment. The results show that with adoption of the optimized solution treatment, the area fraction of second and eutectic Al₂Cu phases decreased from 5.08% in the as-cast state to less than 0.36% owing to improvement of dissolution efficiency in the high-temperature short-time solution. Comparing mechanical properties of the composite in the as-cast state and in the peak-aged state, average ultimate tensile strength and yield strength increased from 211.9 MPa to 523.0 MPa and from 115.8 MPa to 451.8 MPa, respectively. However, average elongation slightly decreased from 8.78% to 8.24%. Strength contribution of the peak-aged TiB₂/Al–Cu–Mn–Cd composite was mainly ascribed to Cd-rich, θ″ and θ′ precipitates. In the peak-aged state, number density and average diameter of the plate-like θ″ and θ′ precipitates reached 4.266 × 10²¹ m³ and 64.30 nm, respectively, and severe lattice distortions occurred around the Cd-rich precipitates, providing the strongest precipitation strengthening. These findings indicate that the two-stage solution treatment successfully solved the problem of the eutectic phase at the triangular grain boundary being difficult to dissolve in a TiB₂/Al-Cu-Mn-Cd composite, and excellent mechanical properties were acquired with the optimized aging treatment. Full article