Search Results (30,343)

Treatment-resistant depression (TRD) is associated with immune dysregulation. Ketamine, a rapid-acting antidepressant, may exert effects via immunomodulation. The aim was to examine ketamine’s impact on immune markers in TRD, including T-cell subsets, cytokines, and in vitro T-cell responses. Eighteen TRD inpatients received 0.5 mg/kg iv ketamine. Blood was sampled at baseline, 4 h, and 24 h to analyze T-cell phenotypes (CD28, CD69, CD25, CD95, HLA-DR) and serum cytokines (IL-6, IL-8, IL-10, TNF-α, IL-1β, IL-12p70). In vitro, PBMCs from TRD patients and controls were exposed to low (185 ng/mL) and high (300 ng/mL) ketamine doses. Ketamine induced a transient increase in total T cells and CD4⁺CD25⁺ and CD4⁺CD28⁺ subsets at 4 h, followed by a reduction in CD4⁺ and an increase in CD8⁺ T cells at 24 h, decreasing the CD4⁺/CD8⁺ ratio. Activation markers (CD4⁺CD69⁺, CD4⁺HLA-DR⁺, CD8⁺CD25⁺, CD8⁺HLA-DR⁺) declined at 24 h. Serum IL-10 increased, IL-6 decreased, and IL-8 levels—initially elevated—showed a sustained reduction. In vitro, high-dose ketamine enhanced the proliferation of TRD CD4⁺ T cells and dose-dependent IL-8 and IL-6 secretion from activated cells. Ketamine induces rapid, transient immune changes in TRD, including reduced T-cell activation and cytokine modulation. A sustained IL-8 decrease suggests anti-inflammatory effects and potential as a treatment-response biomarker. Full article

The biological effects of nanoparticles are closely related to their intracellular content and location, both of which are influenced by various factors. This study investigates the effects of surface charge on the uptake, intracellular distribution, and exocytosis of CdSe/ZnS quantum dots (QDs) in Raw264.7 macrophages. Negatively charged 3-mercaptopropanoic acid functionalized QDs (QDs-MPA) show higher cellular uptake than positively charged 2-mercaptoethylamine functionalized QDs (QDs-MEA), and serum enhances the uptake of both types of QDs via protein corona-mediated receptor endocytosis. QDs-MEA primarily enter the cells through clathrin/caveolae-mediated pathways and predominantly accumulate in lysosomes, while QDs-MPA are mainly internalized through clathrin-mediated endocytosis and localize to both lysosomes and mitochondria. Exocytosis of QDs-MPA is faster and more efficient than that of QDs-MEA, though both exhibit limited excretion. In addition to endocytosis and exocytosis, cell division influences intracellular QD content over time. These results reveal the charge-dependent interactions between QDs and macrophages, providing a basis for designing biocompatible nanomaterials. Full article

Forests are considered one of the most valuable natural areas in metropolitan region landscapes. Considering the sensitivity and ecosystem services provided by trees, the definition of urban forest ecosystems is nowadays based on a comprehensive understanding of the entire urban ecosystem. The effective capturing of particulate matter is one of the ecosystem services provided by urban forests. These ecosystems function as efficient biological filters. Plants accumulate pollutants passively via their leaves. Therefore, another ecosystem service provided by city forests could be the use of tree organs as bioindicators of pollution. This paper aims to estimate differences in trace metal pollution between the wooded urban areas of Vienna and Krakow using leaves of evergreen and deciduous trees as biomonitors. An additional objective of the research was to assess the ability of the applied tree species to act as biomonitors. Plant samples of five species—Norway spruce, Scots pine, European larch, common white birch, and common beech—were collected within both areas, in seven locations: four in the “Wienerwald” Vienna forest (Austria) and three in the “Las Wolski” forest in Krakow (Poland). Concentrations of Cr, Cu, Cd, Pb, and Zn in plant material were determined. Biomonitoring studies with deciduous and coniferous tree leaves showed statistically higher heavy metal contamination in the “Las Wolski” forest compared to the “Wienerwald” forest. Based on the conducted analyses and the literature study, it can be concluded that among the analyzed tree species, only two: European beech and common white birch can be considered potential indicators in environmental studies. These species appear to be suitable bioindicators, as both are widespread in urban woodlands of Central Europe and have shown the highest accumulation levels of trace metals. Full article

Background/Objectives: While ART effectively suppresses HIV viremia, many PLWH exhibit persistent immune dysfunction. This study aimed to assess immune recovery and immune exhaustion (PD-1/PD-L1 expression) in newly diagnosed versus long-term ART-treated individuals. Methods: We analyzed 79 PLWH: 52 newly diagnosed individuals (12-month follow-up) and 27 long-term-treated patients (Ukrainian refugees). Flow cytometry was used to evaluate CD4+ and CD8+ counts, the CD4+/CD8+ ratio, and PD-1/PD-L1 expression on CD3+, CD4+, and CD19+ lymphocytes. ART regimen and HIV subtype were included as covariates in linear regression models. Results: At 12 months, CD4+ counts were similar between groups (median 596.5 vs. 621 cells/μL, p = 0.22), but newly diagnosed patients had higher CD8+ counts (872 vs. 620 cells/μL, p = 0.028) and a lower CD4+/CD8+ ratio (0.57 vs. 1.05, p = 0.0027). Immune exhaustion markers were significantly elevated in newly diagnosed individuals: CD4+ PD-1+ T cells (24.4% vs. 3.85%, p = 0.0002) and CD3+ PD-1+ T cells (27.3% vs. 12.35%, p < 0.0001). Linear regression confirmed group membership independently predicted higher CD3+ (β = +21.92, p < 0.001), CD4+ (β = +28.87, p < 0.0001), and CD19+ (β = +8.73, p = 0.002) percentages. Lipid parameters and SCORE2 did not differ significantly. Conclusions: Despite virologic suppression and CD4+ recovery, immune exhaustion markers remain elevated in newly diagnosed PLWH, suggesting incomplete immune normalization. Traditional parameters (CD4+ count and CD4+/CD8+ ratio) may not fully capture immune status, warranting broader immunologic profiling in HIV care. Full article

Avian influenza A viruses (IAVs) pose a persistent threat to the poultry industry, causing substantial economic losses. Although traditional vaccines have helped reduce the disease burden, they typically rely on multivalent antigens, emphasize humoral immunity, and require intensive production. This study aimed to establish a genetically matched host–cell system to evaluate antigen-specific immune responses and identify conserved CD8+ T cell epitopes in avian influenza viruses. To this end, we developed an MHC class I genotype (B21)-matched host (Lohmann VALO SPF chicken) and cell vector (DF-1 cell line) model. DF-1 cells were engineered to express the hemagglutinin (HA) gene of clade 2.3.4.4b H5N1 either transiently or stably, and to stably express the matrix 1 (M1) and nucleoprotein (NP) genes of A/chicken/South Korea/SL20/2020 (H9N2, Y280-lineage). Following prime-boost immunization with HA-expressing DF-1 cells, only live cells induced strong hemagglutination inhibition (HI) and virus-neutralizing (VN) antibody titers in haplotype-matched chickens. Importantly, immunization with DF-1 cells transiently expressing NP induced stronger IFN-γ production than those expressing M1, demonstrating the platform’s potential for differentiating antigen-specific cellular responses. CD8+ T cell epitope mapping by mass spectrometry identified one distinct MHC class I-bound peptide from each of the HA-, M1-, and NP-expressing DF-1 cell lines. Notably, the identified HA epitope was conserved in 97.6% of H5-subtype IAVs, and the NP epitope in 98.5% of pan-subtype IAVs. These findings highlight the platform’s utility for antigen dissection and rational vaccine design. While limited by MHC compatibility, this approach enables identification of naturally presented epitopes and provides insight into conserved, functionally constrained viral targets. Full article

Proper joint function has a significant impact on people’s quality of life. Joints are the point of connection between two or more bones and consist of at least three elements: joint surfaces, the joint capsule, and the joint cavity. Joint diseases are a serious social problem. Risk factors for the development of these diseases include overweight and obesity, gender, and intestinal microbiome disorders. Another factor that is considered to influence joint diseases is trace elements. Under normal conditions, elements such as iron (Fe), copper (Cu), cobalt (Co), iodine (I), manganese (Mn), zinc (Zn), silver (Ag), cadmium (Cd), mercury (Hg), lead (Pb), nickel (Ni) selenium (Se), boron (B), and silicon (Si) are part of enzymes involved in reactions that determine the proper functioning of cells, regulate redox metabolism, and determine the maturation of cells that build joint components. However, when the normal concentration of the above-mentioned elements is disturbed and toxic elements are present, dangerous joint diseases can develop. In this article, we focus on the role of trace elements in joint function. We describe the molecular mechanisms that explain their interaction with chondrocytes, osteocytes, osteoblasts, osteoclasts, and synoviocytes, as well as their proliferation, apoptosis, and extracellular matrix synthesis. We also focus on the role of these trace elements in the pathogenesis of joint diseases: rheumatoid arthritis (RA), osteoarthritis (OA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), and systemic lupus erythematosus (SLE). We describe the roles of increased or decreased concentrations of individual elements in the pathogenesis and development of joint diseases and their impact on inflammation and disease progression, referring to molecular mechanisms. We also discuss their potential application in the treatment of joint diseases. Full article

Background/Objectives: Celiac disease (CD) is an autoimmune disorder characterized by small intestinal enteropathy triggered by gluten ingestion, often associated with gut dysbiosis. The most effective treatment is strict adherence to a gluten-free diet (GFD), which alleviates symptoms. This study uniquely integrates taxonomic, functional, and resistance profiling to evaluate the gut microbiota of women with CD on a GFD. Methods: To evaluate the long-term impact of a GFD, this study analyzed the gut microbiota of 10 women with CD on a GFD for over a year compared to 10 healthy controls with unrestricted diets. Taxonomic diversity (16S rRNA gene sequencing and the analysis of α and β-diversity), metabolic functionality (Biolog EcoPlates^®), and antibiotic resistance profiles (Cenoantibiogram) were assessed. Results: Metagenomic analysis revealed no significant differences in taxonomic diversity but highlighted variations in the abundance of specific bacterial genera. Women with CD showed increased proportions of Bacteroides, Streptococcus, and Clostridium, associated with inflammation, but also elevated levels of beneficial genera such as Roseburia, Oxalobacter, and Paraprevotella. Despite no significant differences in metabolic diversity, higher minimum inhibitory concentrations (MICs) in women in the healthy control group suggest that dietary substrates in unrestricted diets may promote the proliferation of fast-growing bacteria capable of rapidly developing and disseminating antibiotic resistance mechanisms. Conclusions: These findings indicate that prolonged adherence to a GFD in CD supports remission of gut dysbiosis, enhances microbiota functionality, and may reduce the risk of antibiotic resistance, emphasizing the importance of dietary management in CD. Full article

Background/Objectives: Chronic kidney disease of unknown etiology (CKDu) disproportionately affects young male agricultural workers who are otherwise healthy. There is a scarcity of biomarkers for early detection of this type of kidney disease. We hypothesized that small extracellular vesicles (sEVs) released into urine may provide novel biomarkers. Methods: We obtained two urine samples at the start and the end of a workday in the fields from a limited set of workers with and without kidney impairment. Isolated sEVs were characterized for size, surface marker expression, and purity and, subsequently, their lipid composition was determined by mass spectrometry. Results: The number of particles per ml of urine normalized to osmolality and the size variance were larger in workers with possible CKDu than in control workers. Surface markers CD9, CD63, and CD81 are characteristic of sEVs and a second set of surface markers suggested the kidney as the origin. Differential expression of CD25 and CD45 suggested early inflammation in CKDu workers. Of the twenty-one lipids differentially expressed, several were bioactive, suggesting that they may have essential functions. Remarkably, fourteen of the lipids showed intermediate expression values in sEVs from healthy individuals with acute creatinine increases after a day of work. Conclusions: We identified twenty-one possible lipid biomarkers in sEVs isolated from urine that may be able to distinguish agricultural workers with early onset of CKDu. Differentially expressed surface proteins in these sEVs suggested early-stage inflammation. This pilot study was limited in the number of workers evaluated, but the approach should be further evaluated in a larger population. Full article

Background/Objectives: Senecio scandens Buch.-Ham. is a flavonoid-rich traditional medicinal plant with established immunomodulatory properties. However, the mechanisms underlying the immunoregulatory and intestinal protective effects of its flavonoid extract (Senecio scandens flavonoids—SSF) remain unclear. This study characterized SSF’s bioactive components and evaluated its efficacy against cyclophosphamide (CTX)-induced immunosuppression and intestinal injury. Methods: The constituents of SSF were identified using UHPLC/Q-Orbitrap/HRMS. Mice with CTX-induced immunosuppression were treated with SSF (80, 160, 320 mg/kg) for seven days. Immune parameters (organ indices, lymphocyte proliferation, cytokine, and immunoglobulin levels) and gut barrier integrity markers (ZO-1, Occludin, Claudin-1 protein expression; sIgA secretion; microbiota composition) were assessed. Network pharmacology combined with functional assays elucidated the underlying regulatory mechanisms. Results: Twenty flavonoids were identified in SSF, with six prototype compounds detectable in the blood. The SSF treatment significantly ameliorated CTX-induced weight loss and atrophy of the thymus and spleen. It enhanced splenic T- and B-lymphocyte proliferation by 43.6% and 29.7%, respectively; normalized the CD4⁺/CD8⁺ ratio (1.57-fold increase); and elevated levels of IL-2, IL-6, IL-10, TNF-α, IFN-γ, IgM, and IgG. Moreover, SSF reinforced the intestinal barrier by upregulating tight junction protein expression and sIgA levels while modulating the gut microbiota, enriching beneficial taxa (e.g., the Lachnospiraceae_NK4A136_group, Akkermansia) and suppressing pathogenic Alistipes. Mechanistically, SSF activated the TLR/MyD88/NF-κB pathway, with isoquercitrin identified as a pivotal bioactive constituent. Conclusions: SSF effectively mitigates CTX-induced immunosuppression and intestinal damage. These findings highlight SSF’s potential as a dual-functional natural agent for immunomodulation and intestinal protection. Subsequent research should validate isoquercitrin’s molecular targets and assess SSF’s clinical efficacy. Full article

Chronic kidney disease (CKD) has now reached epidemic proportions in many parts of the world, primarily due to the high incidence of diabetes and hypertension. By 2040, CKD is predicted to be the fifth-leading cause of years of life lost. Developing strategies to prevent CKD and to reduce its progression to kidney failure is thus of great public health significance. Hypertension is known to be both a cause and a consequence of kidney damage and an eminently modifiable risk factor. An increased risk of hypertension, especially among women, has been linked to chronic exposure to the ubiquitous food contaminant cadmium (Cd). The mechanism is unclear but is likely to involve its action on the proximal tubular cells (PTCs) of the kidney, where Cd accumulates. Here, it leads to chronic tubular injury and a sustained drop in the estimated glomerular filtration rate (eGFR), a common sequela of ischemic acute tubular necrosis and acute and chronic tubulointerstitial inflammation, all of which hinder glomerular filtration. The present review discusses exposure levels of Cd that have been associated with an increased risk of hypertension, albuminuria, and eGFR ≤ 60 mL/min/1.73 m² (low eGFR) in environmentally exposed people. It highlights the potential role of 20-hydroxyeicosatetraenoic acid (20-HETE), the second messenger produced in the kidneys, as the contributing factor to gender-differentiated effects of Cd-induced hypertension. Use of GFR loss and albumin excretion in toxicological risk calculation, and derivation of Cd exposure limits, instead of β₂-microglobulin (β₂M) excretion at a rate of 300 µg/g creatinine, are recommended. Full article

Background: Inflammatory bowel diseases (IBD), such as Crohn’s disease (CD) and ulcerative colitis (UC), may impair bone metabolism, particularly in children. The RANKL/OPG axis, as a key regulator of bone turnover, may contribute to these disturbances. However, data in the pediatric population remain limited. Methods: A single-center, prospective observational study included 100 children aged 4–18 years, with a comparable number of girls and boys. Among them, 72 had IBD (27 CD, 45 UC) and 28 were healthy controls. Anthropometric, biochemical, and densitometric assessments were performed, including serum levels of RANKL and OPG, and markers of inflammation and bone turnover. Results: Children with CD had significantly lower height and weight percentiles compared to UC and controls. Serum RANKL and the RANKL/OPG ratio were significantly elevated in IBD patients, particularly in CD (p < 0.01). Total body BMD Z-scores were lower in IBD compared to controls (p = 0.03). Low BMD was found in 14.7% of UC and 26.3% of CD patients. In both groups, over 30% had values in the “gray zone” (−1.0 to −2.0). A positive correlation was observed between height and weight and bone density (p < 0.01). Higher OPG was associated with lower body weight (p < 0.001), while increased RANKL correlated with osteocalcin (p = 0.03). Patients receiving biological therapy had significantly lower BMD. Conclusions: Pediatric IBD is associated with significant alterations in the RANKL/OPG axis and reduced bone density. These findings support early screening and suggest RANKL/OPG as a potential biomarker of skeletal health. Full article

Introduction: Despite clinical evidence for efficacy, there has been minimal uptake of transcranial direct current stimulation (tDCS) for musculoskeletal conditions. Thus, our objective was to explore the perceptions and experiences of people living with lower-limb musculoskeletal injury as well as healthy physically active populations and relate this to the usage of tDCS and key aspects of tDCS design that would improve the capacity for implementation. Methods: We conducted a qualitative descriptive study of 16 participants (44% women) using semi-structured focus groups to identify the descriptions and experiences of people living with lower-limb musculoskeletal injury and healthy physically active populations. A thematic template was used to create a coding structure. Codes were then grouped, and key themes were derived from the data. Results: Four primary themes were identified from focus groups. These were (i) the impact of musculoskeletal injuries on health and quality of life, (ii) performance and injury recovery as facilitators to using tDCS, (iii) barriers and facilitators to tCDS application and (iv) design and aesthetic factors for a tDCS device. Discussion: Our qualitative descriptive study identified four themes relevant to the successful implementation of tDCS into rehabilitative and performance practice. To increase the likelihood of successful tDCS implementation, these barriers should be addressed and facilitators promoted. This should include innovative approaches to device application and structure that allow for a stylish, user-friendly design. Full article

The increasing demand for rapid, sensitive, and eco-friendly methods for the detection of trace heavy metals in environmental samples, attributed to their serious threats to health and the environment, has spurred considerable interest in the development of sustainable sensor materials. Toxic metal ions, namely, lead (Pb²⁺), cadmium (Cd²⁺), mercury (Hg²⁺), arsenic (As³⁺), and chromium, are potential hazards due to their non-biodegradable nature with high toxicity, even at trace levels. Acute health complications, including neurological, renal, and developmental disorders, arise upon exposure to such metal ions. To monitor and mitigate these toxic exposures, sensitive detection techniques are essential. Pre-existing conventional detection methods, such as atomic absorption spectroscopy (AAS) and inductively coupled plasma-mass spectrometry (ICP-MS), involve expensive instrumentation, skilled operators, and complex sample preparation. Electrochemical sensing, which is simple, portable, and eco-friendly, is foreseen as a potential alternative to the above conventional methods. Carbon-based nanomaterials play a crucial role in electrochemical sensors due to their high conductivity, stability, and the presence of surface functional groups. Biochar (BC), a carbon-rich product, has emerged as a promising electrode material for electrochemical sensing due to its high surface area, sustainability, tunable porosity, surface rich in functional groups, eco-friendliness, and negligible environmental footprint. Nevertheless, broad-spectrum studies on the use of biochar in electrochemical sensors remain narrow. This review focuses on the recent advancements in the development of biochar-based electrochemical sensors for the detection of toxic heavy metals such as Pb²⁺, Cd²⁺, and Hg²⁺ and the simultaneous detection of multiple ions, with special emphasis on BC synthesis routes, surface modification methodologies, electrode fabrication techniques, and electroanalytical performance. Finally, current challenges and future perspectives for integrating BC into next-generation sensor platforms are outlined. Full article

This study investigates the self-assembly and host–guest complexation behaviour of novel resveratrol-based lipophenols (LipoResv)—resveratrol-4′-linoleate (Resv-4′-LA) and resveratrol-4′-docosahexaenoate (Resv-4′-DHA)—with hydroxypropyl-β-cyclodextrins (HP-β-CDs). These amphiphilic molecules display surfactant-like properties, forming micellar aggregates in aqueous media. Fluorescence spectroscopy was used to determine the critical micelle concentration (CMC), revealing that LipoResv exhibit significantly lower CMC values than their free fatty acids, indicating higher hydrophobicity. The formation of inclusion complexes with HP-β-CDs was evaluated based on changes in CMC values and further confirmed by dynamic light scattering (DLS) and molecular modelling analyses. Resv-4′-LA formed 1:1 complexes (Kc = 720 M⁻¹), while Resv-4′-DHA demonstrated a 1:2 stoichiometry with lower affinity constants (K₁ = 17 M⁻¹, K₂ = 0.18 M⁻¹). Environmental parameters (pH, temperature, and ionic strength) significantly modulated CMC and binding constants. Computational docking and molecular dynamics simulations supported the experimental findings by revealing the key structural determinants of the host–guest affinity and micelle stabilization. Ligand efficiency (LE) analysis further aligned with the experimental data, favouring the unmodified fatty acids. These results highlight the versatile encapsulation capacity of HP-β-CDs for bioactive amphiphile molecules and support their potential applications in drug delivery and functional food systems. Full article

Histotripsy is a novel, noninvasive, non-thermal technology invented in 2004 for the precise destruction of biologic tissue. It offers a powerful alternative to more conventional thermal or surgical interventions. Using short-pulse, low-duty cycle ultrasonic waves, histotripsy creates cavitation bubble clouds that selectively and precisely destroy targeted tissue in a predefined volume while sparing critical structures like bile ducts, ureters, and blood vessels. Such precision is of value when treating tumors near vital structures. The FDA has cleared histotripsy for the treatment of all liver tumors. Major medical centers are currently spearheading clinical trials, and some institutions have already integrated the technology into patient care. Histotripsy is now being studied for a host of other cancers, including primary kidney and pancreatic tumors. Preclinical murine and porcine models have already revealed promising outcomes. One of histotripsy’s primary advantages is its non-thermal mechanical actuation. This feature allows it to circumvent the limitations of heat-based techniques, including the heat sink effect and unpredictable treatment margins near sensitive tissues. In addition to its non-invasive ablative capacities, it is being preliminarily explored for its potential to induce immunomodulation and promote abscopal inhibition of distant, untreated tumors through CD8+ T cell responses. Thus, it may provide a multilayered therapeutic effect in the treatment of cancer. Histotripsy has the potential to improve precision and outcomes across a multitude of specialties, from oncology to cardiovascular medicine. Continued trials are crucial to further expand its applications and validate its long-term efficacy. Due to the speed of recent developments, the goal of this review is to provide a comprehensive and updated overview of histotripsy. It will explore its physics-based mechanisms, differentiating it from similar technologies, discuss its clinical applications, and examine its advantages, limitations, and future. Full article