Search Results (92)

Dengue mortality has traditionally been associated with severe thrombocytopenia and hemorrhagic complications. However, during 2024, dengue virus serotype 3 (DENV-3) increased significantly in western Mexico, leading to the emergence of a distinct clinical pattern. We conducted a retrospective cohort study of hospitalized dengue patients at the General Hospital of Colima (January–August 2024). Clinical features, laboratory parameters, and outcomes were compared between survivors and non-survivors. Among 201 hospitalized patients, 6 (3.0%) died. All deceased patients presented with generalized seizures, polyserositis (pleural effusion and/or ascites), and required mechanical ventilation. Contrary to classical patterns, they did not have severe thrombocytopenia. Instead, they showed significantly higher white blood cell counts and notably increased levels of serum urea and BUN, suggesting early renal impairment. ROC analysis indicated that BUN (AUC 0.904) and urea (AUC 0.906) were good to excellent discriminators of mortality. During 2024, with an increase in DENV-3 circulation, mortality was associated with neurological and systemic complications, including seizures and polyserositis, as well as biochemical evidence of renal dysfunction—but not with severe thrombocytopenia. These findings challenge current paradigms and highlight the need for early recognition of atypical clinical patterns. Full article

Probiotics offer a non-pharmacological approach to support immune function, yet clinical evidence for strain-specific benefits remains limited. We conducted an 8-week, randomized, double-blind, placebo-controlled trial of Lacticaseibacillus rhamnosus LM1019 in 121 generally healthy adults. Both the active and placebo arms produced comparable within-group increases in natural killer (NK) cell cytotoxicity and modest, non-differential declines in circulating cytokines; safety and tolerability were excellent, with mild adverse events evenly distributed. In a post-hoc subgroup defined by age ≥ 40 years, baseline white blood cell count ≥ 5.0 × 10³/µL, and LDL cholesterol < 130 mg/dL, the probiotic arm demonstrated statistically significant enhancements in NK activity (p = 0.021–0.008 across all effector-to-target ratios), whereas no change was observed in the placebo group. These findings suggest that this intervention may selectively boost NK-mediated immunity in individuals with preserved baseline immune and lipid profiles. Future larger trials using phenotype-driven enrollment and controlled dietary intake are warranted to confirm and extend these results. Full article

Background and Objectives: Hemophagocytic lymphohistiocytosis (HLH) is a rare hyperinflammatory condition characterized by excessive activation of cytotoxic lymphocytes and macrophages, resulting in a cytokine storm, multiorgan damage, and high mortality. HLH is classified into primary (genetic) and secondary (acquired) forms, with diagnosis often challenging due to nonspecific symptoms. Macrophage activation syndrome (MAS) refers to the secondary HLH triggered by rheumatic diseases. In this study, we retrospectively analyzed the clinical and laboratory features of patients with secondary HLH to enhance understanding of this life-threatening condition and summarize emerging management strategies. Materials and Methods: This single-center retrospective study analyzed medical records of patients hospitalized with HLH at the University Hospital in Kraków, Poland, from 2013 to 2024, based on HLH-2009 criteria and HScore > 169 points. Diagnostic criteria included clinical, laboratory, and histological findings, e.g., hemophagocytosis in bone marrow, circulating cytopenia, and elevated ferritin levels. Results: A total of 21 patients met the criteria for HLH diagnosis, with a median age of 35 (range: 19–67) years, including 12 women (57.1%). The median HScore among the patients was 244 (range: 208–304) points. Fever was the most common presenting symptom, occurring in all cases. High ferritin, hypertriglyceridemia, and hypofibrinogenemia in peripheral blood were also prevalent. Bone marrow hemophagocytosis was confirmed in 66.7% of cases (n = 12/18 of available data). Regarding immunosuppressive therapy, glucocorticosteroids were the most frequently used (used in all cases). Four (19.0%) patients died during HLH (cases triggered by lymphoma [twice], Epstein–Barr virus infection, unknown reason). Compared to survivors, these patients had lower counts of white blood cells, neutrophils, and lymphocytes at diagnosis (p < 0.05 for all). Conclusions: Secondary HLH is a severe syndrome requiring rapid diagnosis and timely intervention to improve patient outcomes. Lower white blood cell, neutrophil, and lymphocyte counts present worse prognostic factors. Full article

Atrial fibrillation (AF) is a leading cause of stroke, heart failure, and cardiovascular morbidity, yet its pathophysiology remains incompletely understood. Among various molecular regulators, microRNAs (miRNAs) have emerged as promising biomarkers for AF detection and burden monitoring. However, the optimal sample type for miRNA analysis remains unclear, posing a challenge for biomarker standardization. This study aimed to assess whether miRNA expression profiles remain consistent across plasma and blood cells, with a focus on identifying miRNAs with a strong predictive potential for AF burden. This exploratory study recruited patients diagnosed with sick sinus syndrome who had undergone permanent pacemaker implantation. Participants were stratified into three groups based on AF status: no AF (n = 2), paroxysmal AF (PaAF; n = 2), and persistent AF (PerAF; n = 2) for white blood cell (WBC) samples, and pooled plasma samples from no AF (n = 3 pools) and PerAF (n = 3 pools). Using an miRNA microarray analysis, miR-1-3p was consistently downregulated in both WBC and plasma samples of patients with AF, showing significant decreases (fold-change in WBC: PaAF 0.22, PerAF 0.20; plasma PerAF 0.28) and highlighting its potential as a circulating biomarker for AF burden. Additional differentially expressed miRNAs, including miR-451a and miR-382-5p, exhibited sample-dependent variations, underscoring the importance of validating miRNA expression across multiple biological compartments. The study highlights the need for mechanistic investigations to determine whether miR-1-3p directly contributes to AF pathogenesis or serves as a downstream consequence of atrial remodeling. These findings reinforce the potential of miR-1-3p as a reliable circulating biomarker for AF, offering new avenues for non-invasive monitoring and risk stratification. Future research should explore the role of miR-1-3p in AF-related molecular pathways and its applicability as a therapeutic target. Full article

The immune system is a vital defense network within the body, where lymph and lymph nodes play pivotal roles. Lymph is a transparent fluid containing white blood cells, specifically lymphocytes, which circulate through the lymphatic system, rapidly multiplying to fight viruses and bacteria. Lymph nodes function as filters, capturing and eliminating infections and abnormal cells found in the lymphatic fluid prior to its reentry into the circulatory system. A thorough meta-analysis of research publications in the topic is conducted utilizing Bibliometrix to comprehensively assess the current literature. The paper is centered on understanding the intricate relationship between interferons, dendritic cells, and macrophages in the lymphatic system during hepatitis virus infection. A nonlinear model for the development of the virus is used, together with the initial conditions, for a much better understanding of a hepatitis-C infection. The associated Cauchy problem is numerically solved and graphs are depicted. The interpretation of the figures explains the dynamics of interferons, dendritic cells, and macrophages as well as their interaction with other factors. By adopting an interdisciplinary approach, this study offers fresh perspectives and uncovers new research areas to better comprehend and battle hepatitis virus infections. Full article

Low-density lipoprotein (LDL) chemically modified by reactive oxygen species (ROS), for example, leaking from red blood cells in the vascular compartment, more readily crosses the vascular endothelium than does nonoxidatively modified LDL to enter tissue fluid. Oxidatively modified LDL (oxLDL) may also be created in the tissue fluid by ROS leaking from cells by design, for example, by inflammatory white cells, or simply leaking from other cells as a consequence of oxygen metabolism. As well as oxLDL, glycatively modified LDL (glycLDL) is formed in the circulation. High-density lipoprotein (HDL) appears capable of decreasing the burden of lipid peroxides formed on LDL exposed to ROS or to glucose and its metabolites. The mechanism for this that has received the most attention is the antioxidant activity of HDL, which is due in large part to the presence of paraoxonase 1 (PON1). PON1 is intimately associated with its apolipoprotein A1 component and with HDL’s lipid domains into which lipid peroxides from LDL or cell membranes can be transferred. It is frequently overlooked that for PON1 to hydrolyze lipid substrates, it is essential that it remain by virtue of its hydrophobic amino acid sequences within a lipid micellar environment, for example, during its isolation from serum or genetically modified cells in tissue culture. Otherwise, it may retain its capacity to hydrolyze water-soluble substrates, such as phenyl acetate, whilst failing to hydrolyze more lipid-soluble molecules. OxLDL and probably glycLDL, once they have crossed the arterial endothelium by receptor-mediated transcytosis, are rapidly taken up by monocytes in a process that also involves scavenger receptors, leading to subendothelial foam cell formation. These are the precursors of atheroma, inducing more monocytes to cross the endothelium into the lesion and the proliferation and migration of myocytes present in the arterial wall into the developing lesion, where they transform into foam cells and fibroblasts. The atheroma progresses to have a central extracellular lake of cholesteryl ester following necrosis and apoptosis of foam cells with an overlying fibrous cap whilst continuing to grow concentrically around the arterial wall by a process involving oxLDL and glycLDL. Within the arterial wall, additional oxLDL is generated by ROS secreted by inflammatory cells and leakage from cells generally when couplet oxygen is reduced. PON1 is important for the mechanism by which HDL opposes atherogenesis, which may provide a better avenue of inquiry in the identification of vulnerable individuals and the provision of new therapies than have emerged from the emphasis placed on its role in RCT. Full article

Background: Thrombospondin-1 (TSP1) is a multimeric glycoprotein that is increasingly recognized as a mediator of metabolic, thrombotic, and inflammatory processes. Although TSP1 expression has been associated with adipose tissue dysfunction and insulin resistance, the precise relationship with obesity severity remains unclear. Endothelin-1 (ET1), another important regulator of vascular homeostasis, may also contribute to obesity-related cardiometabolic risk, with evidence suggesting sex-specific differences, including delayed onset in women. The study aimed to investigate circulating TSP1 and ET1 levels in a cohort of nondiabetic obese female adults, evaluate their associations with metabolic and inflammatory parameters, and determine whether these markers differ according to obesity severity and related disease risk. Methods: Fifty-five nondiabetic women with obesity and no history of cardiovascular events were enrolled at the Endocrinology Unit (“R. Dulbecco” Univ. Hospital, Catanzaro, Italy). Anthropometric and clinical data, together with hematological and coagulation parameters and metabolic indices (HOMA-IR, HbA1c, and lipid profile), were evaluated. TSP1 and ET1 concentrations were measured using automated enzyme immunoassays (ELISAs). The participants were stratified by BMI (30–34.9 vs. ≥35 kg/m²) into low-risk and moderate/high-risk obesity based on the WHO classification, and correlations between biomarkers and metabolic/inflammatory parameters were evaluated. Results: The median BMI was 33.7 kg/m², with 52% of participants having moderate/high-risk obesity (WHO Class II/III). A significant proportion (69.8%) showed insulin resistance (HOMA-IR > 2.5). TSP1 was positively correlated with white blood cell count (WBC, r = 0.354, p < 0.01), platelet count (PLT, r = 0.411, p < 0.01), and glycated hemoglobin (r = 0.391, p < 0.01), suggesting an association with both inflammation and glycemic control. ET1 was positively correlated with liver enzymes and triglycerides but negatively correlated with PLT and D-dimer. Women with moderate/high-risk obesity had significantly higher HOMA-IR, D-dimer, and inflammatory markers, in addition to a lower TSP1-to-PLT ratio. Conclusions: In this pilot study, TSP1 and ET1 levels tended to decrease with increasing obesity severity in women but were associated with distinct metabolic and inflammatory profiles. The results support the potential role of TSP1 as a biomarker for obesity-related cardiometabolic risk and highlight the complex interplay between TSP1, ET1, and obesity progression. Further studies may clarify whether targeting TSP1 can ameliorate chronic inflammation and insulin resistance in obesity and the potential sex-specific influences on these mechanisms. Full article

Kezimuke granules (KZMK), derived from traditional Kazakh folk medicine, exhibit a variety of pharmacological properties. Long-term clinical studies have demonstrated their efficacy in clearing heat, detoxifying, promoting qi circulation, and alleviating gonorrhea. However, their specific pharmacological effects on urinary tract infections remain unclear. This study employed UHPLC-MS/MS technology to identify the blood components of KZMK and integrated network pharmacology with bioinformatics analysis for molecular docking validation. The anti-inflammatory activity of KZMK was further evaluated using a rat model of LPS-induced cystitis. A total of 17 components in KZMK were identified as capable of entering the bloodstream. Predictive analysis revealed that its primary targets include Caspase-1, NLRP3, STAT1, TLR4, and TNF, with the NLRP3 inflammasome signaling pathway emerging as the key mechanism. In vivo studies showed that KZMK effectively reduced the white blood cell (WBC) count and bladder index in urine sediments of rats with cystitis. Additionally, KZMK alleviated bladder congestion, edema, and histopathological changes in the animals. Treatment with KZMK led to decreased levels of IL-18 and IL-1β cytokines. KZMK significantly inhibited the expression of NLRP3, GSDMD, and Caspase-1 in LPS-induced cystitis, further confirming its anti-inflammatory effects. These findings indicate that KZMK provides protection against LPS-induced cystitis, primarily by inhibiting the activation of the NLRP3 inflammasome. Collectively, the results suggest that KZMK holds promise as a potential therapeutic option for urinary tract infections. Full article

Neutrophils, the most abundant circulating white blood cells, are essential for the initial immune response to infection and injury. Emerging research reveals a dualistic function of neutrophils in cancer, where they can promote or inhibit tumor progression. This dichotomy is influenced by the tumor microenvironment, with neutrophils capable of remodeling the extracellular matrix, promoting angiogenesis, or alternatively inducing cancer cell death and enhancing immune responses. An intriguing yet poorly understood aspect of neutrophil–cancer interactions is the phenomenon of neutrophil engulfment by cancer cells, which has been observed across various cancers. This process, potentially mediated by LC3-associated phagocytosis (LAP), raises questions about whether it serves as a mechanism for immune evasion or contributes to tumor cell death through pathways like ferroptosis. This review examines current knowledge on neutrophil development, their roles in cancer, and the mechanisms of LAP in neutrophil engulfment by tumor cells. We discuss how manipulating LAP impacts cancer progression and may represent a therapeutic strategy. We also explore neutrophils’ potential as delivery vehicles for cancer therapeutic agents. Understanding the complex functions of tumor-associated neutrophils (TANs) and the molecular mechanisms underlying LAP in cancer may open new avenues for effective therapeutic interventions and mitigate potential risks. Full article

Background: Osteoarthritis (OA) is a prevalent degenerative joint disease that causes disability and diminishes quality of life. The pathogenesis of OA remains poorly understood, creating an urgent need for biomarkers to aid research, diagnosis, and treatment. Methods: This study integrated transcriptome data from the GEO database with bioinformatics analyses to identify biomarkers associated with OA. The bioinformatics methods utilized include the Limma package, WGCNA, PPI network analysis, and machine learning algorithms. Genetic variants were used as instrumental variables to evaluate the potential causal impact of circulating white blood cell (WBC) counts on OA. Data sources encompassed the largest genome-wide analysis for OA and a comprehensive GWAS summary for circulating WBC counts. Four mendelian randomization (MR) methods were employed to investigate the genetic association, with a primary focus on findings from the inverse variance-weighted (IVW) method. Results: Total of 233 OA-related genes were identified, showing significant enrichment in pathways associated with WBC function. Key biomarkers, including CD4, CSF1R, and TYROBP, were upregulated in OA samples and exhibited strong diagnostic potential. MR analysis findings provided evidence of a genetic association between elevated neutrophil counts and a reduced risk of OA across sites (IVW: OR = 0.97, 95% CI 0.93–1.00, p = 0.047). Additionally, higher circulating WBC counts, particularly neutrophil counts, were associated with a suggestive decrease in hip OA (WBC IVW: OR = 0.94, 95% CI 0.89–0.99, p = 0.015; neutrophil IVW: OR = 0.93, 95% CI 0.88–0.99, p = 0.017). Conversely, reverse MR analysis found no evidence to support a genetic effect of OA on circulating WBC counts. Conclusion: Our findings suggest that elevated neutrophil counts may offer protective effects against OA, underscoring the interplay between the immune functions and OA pathogenesis. CD4, CSF1R, and TYROBP emerge as promising OA biomarkers, meriting further validation in prospective studies. Full article

Recombination-activating genes (RAGs) play a crucial role in the V(D)J recombination process and the development of immune cells. The development of the immune system and its mechanisms in pigs exhibit greater similarity to those of humans compared to other animals, thus rendering pigs a valuable tool for biomedical research. In this study, we utilized CRISPR/Cas9 gene editing and somatic cell nuclear transfer technology to generate RAG2 knockout (KO) pigs. Furthermore, we evaluated the impact of RAG2 KO on the immune organs and immune cell development through morphological observations, blood analysis and flow cytometry technology. RAG2 KO cell lines were used as donors for cloning. The reconstructed embryos were transplanted into 4 surrogate sows, and after 116 days of gestation, 2 sows gave birth to 12 live piglets, all of which were confirmed to be RAG2 KO. The thymus and spleen sizes of RAG2 KO pigs were significantly smaller than those of wild-type (WT) pigs. Hematoxylin-eosin staining results revealed that the thymus and spleen tissue structures of RAG2 KO pigs were disorganized and lacked the characteristic structures, indicating that RAG2 KO leads to dysplasia of the thymus and spleen. Hematological analysis demonstrated that the total number of white blood cells and lymphocytes in the circulation of RAG2 KO pigs was significantly lower, while the number of eosinophils was higher. Flow cytometry results indicated that the proportions of mature T and B lymphocytes were significantly reduced compared to WT pigs. These findings successfully verified the immunodeficiency phenotype of RAG2 KO pigs. This study may provide experimental animals for the development of tumor models and humanized animals. Full article

In elderly patients undergoing cardiac surgery, extracorporeal circulation affects the incidence of post-operative delirium and cognitive impairment with an impact on quality of life and mortality. In this study, a new oxygenator system (RemoweLL 2) was tested against a conventional system to assess its efficacy in reducing the onset of postoperative delirium and cognitive dysfunction and the levels of serum inflammatory markers. A total of 154 patients (>65 y.o.) undergoing cardiopulmonary bypass (CPB) were enrolled and randomly assigned to oxygenator RemoweLL 2 (n = 81) or to gold standard device Inspire (n = 73) between September 2019 and March 2022. The aims of the study were to assess the incidence of delirium and the cognitive decline by neuropsychiatric tests and the MoCa test intra-hospital and at 6 months after CPB. Inflammation biomarkers in both groups were also evaluated. Before the CPB, the experimental groups were comparable for all variables. After CPB, the incidence of severe post-operative delirium showed a better trend (p = 0.093) in patients assigned to RemoweLL 2 (16.0%) versus Inspire (26.0%). Differences in enolase levels (p = 0.049), white blood cells (p = 0.006), and neutrophils (p = 0.003) in favor of RemoweLL 2 were also found. The use of novel and better construction technologies in CPB oxygenator devices results in measurable better neurocognitive and neurological outcomes in the elderly population undergoing CPB. Full article

Clinically, unique markers in fetal membrane cells may contribute to the search for biomarkers for preterm prelabor rupture of the fetal membranes (pPROM) in maternal blood. pPROM is associated with overwhelming inflammation and premature cellular senescence causing “biological microfractures” of the fetal membranes. We hypothesize that these pathological processes are associated with the shedding of fetal membrane cells into the maternal circulation. The aim of this study was to identify markers expressed exclusively in fetal membrane cells to facilitate their isolation, characterization, and determination of biomarker potential in maternal blood. We have (1), by their transcriptomic profile, identified markers that are upregulated in amnion and chorion tissue compared to maternal white blood cells, and (2), by immunohistochemistry, confirmed the localization of the differentially expressed proteins in fetal membranes, placenta, and the placental bed of the uterus. RNA sequencing revealed 31 transcripts in the amnion and 42 transcripts in the chorion that were upregulated. Among these, 22 proteins were evaluated by immunohistochemistry. All but two transcripts were expressed both on mRNA and protein level in at least one fetal membrane cell type. Among these remaining 20 proteins, 9 proteins were not significantly expressed in the villous and extravillous trophoblasts of the placenta. Full article

The isolation of circulating tumor cells (CTCs) from peripheral blood with high efficiency remains a challenge hindering the utilization of CTC enrichment methods in clinical practice. Here, we propose a microfluidic channel design for the size-based hydrodynamic enrichment of CTCs from blood in an epitope-independent and high-throughput manner. The microfluidic channel comprises a spiral-shaped part followed by a widening part, incorporating successive streamlined pillars, that improves the enrichment efficiency. The design was tested against two benchmark designs, a spiral microfluidic channel and a spiral microfluidic channel followed by a widening channel without the hydrofoils, by processing 5 mL of healthy blood samples spiked with 100 MCF-7 cells. The results proved that the design with hydrofoil-shaped pillars perform significantly better in terms of recovery (recovery rate of 67.9% compared to 23.6% in spiral and 56.7% in spiral with widening section), at a cost of slightly lower white blood cell (WBC) depletion (depletion rate of 94.2% compared to 98.6% in spiral and 94.2% in spiral with widening section), at 1500 µL/min flow rate. For analytical validation, the design was further tested with A549, SKOV-3, and BT-474 cell lines, yielding recovery rates of 62.3 ± 8.4%, 71.0 ± 6.5%, and 82.9 ± 9.9%, respectively. The results are consistent with the size and deformability variation in the respective cell lines, where the increasing size and decreasing deformability affect the recovery rate in a positive manner. The analysis before and after the microfluidic chip process showed that the process does not affect cell viability. Full article

Ovarian cancer has a high case fatality rate, but patients who have no visible residual disease after surgery have a relatively good prognosis. The presence of any cancer cells left in the peritoneal cavity after treatment may precipitate a cancer recurrence. In many cases, these cells are occult and are not visible to the surgeon. Analysis of circulating tumour DNA in the blood (ctDNA) may offer a sensitive method to predict the presence of occult (non-visible) residual disease after surgery and may help predict disease recurrence. We assessed 48 women diagnosed with serous ovarian cancer (47 high-grade and 1 low-grade) for visible residual disease and for ctDNA. Plasma, formalin-fixed paraffin-embedded (FFPE) tumour tissue and white blood cells were used to extract circulating free DNA (cfDNA), tumour DNA and germline DNA, respectively. We sequenced DNA samples for 59 breast and ovarian cancer driver genes. The plasma sample was collected after surgery and before initiating chemotherapy. We compared survival in women with no residual disease, with and without a positive plasma ctDNA test. We found tumour-specific variants (TSVs) in cancer cells from 47 patients, and these variants were sought in ctDNA in their post-surgery plasma. Fifteen (31.9%) of the 47 patients had visible residual disease; of these, all 15 had detectable ctDNA. Thirty-one patients (65.9%) had no visible residual disease; of these, 24 (77.4%) patients had detectable ctDNA. Of the patients with no visible residual disease, those patients with detectable ctDNA had higher mortality (20 of 27 died) than those without detectable ctDNA (3 of 7 died) (HR 2.32; 95% CI: 0.67–8.05), although this difference was not statistically significant (p = 0.18). ctDNA in post-surgical serum samples may predict the presence of microscopic residual disease and may be a predictor of recurrence among women with ovarian cancer. Larger studies are necessary to validate these findings. Full article