Galectin-3's Complex Interactions in Pancreatic Ductal Adenocarcinoma: From Cellular Signaling to Therapeutic Potential.

Galectin-3 (Gal-3) plays a multifaceted role in the development, progression, and prognosis of pancreatic ductal adenocarcinoma (PDAC). This review offers a comprehensive examination of its expression in PDAC, its interaction with various immune cells, signaling pathways, effects on apoptosis, and therapeutic resistance. Additionally, the prognostic significance of serum levels of Gal-3 is discussed, providing insights into its potential utilization as a biomarker. Critical analysis is also extended to the inhibitors of Gal-3 and their potential therapeutic applications in PDAC, offering new avenues for targeted treatments. The intricate nature of Gal-3's role in PDAC reveals a complex landscape that demands a nuanced understanding for potential therapeutic interventions and monitoring.

Increased Pro Th1 And Th17 Transcriptional Activity In Patients With Severe COVID-19.

Background: COVID-19 is known to disrupt immune response and induce hyperinflammation that could potentially induce fatal outcome of the disease. Until now, it is known that interplay among cytokines is rather important for clinical presentation and outcome of COVID-19. The aim of this study was to determine transcriptional activity and functional phenotype of T cells and the relationship between pro- and anti-inflammatory cytokines and clinical parameters of COVID-19 severity. Methods: All recruited patients met criteria for COVID-19 are were divided in four groups according to disease severity. Serum levels of IL-12, IFN-γ, IL-17 and IL-23 were measured, and flow cytometry analysis of T cells from peripheral blood was performed. Results: Significant elevation of IL-12, IFN-γ, IL-17 and IL-23 in stage IV of the disease has been revealed. Further, strong intercorrelation between IL-12, IFN-γ, IL-17 and IL-23 was also found in stage IV of the disease, marking augmented Th1 and Th17 response. Analyses of T cells subsets indicate a noticeable phenotype change. CD4+, but not CD8+ T cells expressed increased transcriptional activity through increased expression of Tbet and RORγT, accompanied with increased percentage of IFN-γ and IL-17 producing T cells. Conclusion: Our results pose a novel hypothesis of the underlying mechanism behind deteriorating immune response in severe cases of COVID-19.

Anemia of inflammation in patients with colorectal cancer: Correlation with interleukin-1, interleukin-33 and galectin-1.

Background: Patients with colorectal cancer (CRC) have anemia often present as a consequence of chronic bleeding from tumor. The exact role of lL-33, Galectin-l and IL-l in the pathological genesis of anemia in colorectal cancer patients has not been elucidated yet. The main goal of this research was to analyze Gal-l, IL-l and lL-33 systemic values in anemic and non-anemic CRC patients. Methods: Concentrations of IL-33, Galectin-1 and IL-1 have been studied in blood samples of 55 CRC patients (27 without anemia and 28 with anemia). Results: CRC patients with anemia had more severe and local advanced disease compared to CRC non-anemic patients. Anemia positively correlated with higher nuclear grade, lymph and blood vessel invasion, as well as with higher TNM stage, detectable metastatic lesions in lung and liver and peritoneal carcinomatosis. Significantly higher IL-33, Gal-1 and IL-1 concentration have been found in sera of patients with CRC and detected anemia. CRC patients mostly had microcytic anemia, while ferritin values were in normal range. Analysis revealed positive mutual correlation between serum values of galectin-1, IL-1 and IL-33 in CRC patients. Level of hemoglobin negatively correlated with serum IL-33, Gal-1 and IL-1. We have analyzed the Receiver Operating Characteristic (ROC) curves of serum IL-33, Gal-1 and IL-1 showed that these cytokines can be treated as additional markers for anemia of inflammation in CRC patients. Conclusions: Predomination of Galectin-1, IL-1 and IL-33 in anemic CRC patients implicates on their potential role in anemia genesis and further development.

IL 33 Correlates With COVID-19 Severity, Radiographic and Clinical Finding.

Objective: The increased level of interleukin (IL)-33 is considered as a predictor of severe coronavirus disease 2019 (COVID-19) infection, but its role at different stages of the disease is still unclear. Our goal was to analyze the correlation of IL-33 and other innate immunity cytokines with disease severity. Methods: In this study, 220 patients with COVID-19 were included and divided into two groups, mild/moderate and severe/critical. The value of the cytokines, clinical, biochemical, radiographic data was collected and their correlation with disease severity was analyzed. Results: Most patients in the severe/critical group were male (81.8%) and older (over 64.5 years). We found a statistically significant difference (p < 0.05) in these two groups between clinical features (dyspnea, dry cough, fatigue, and auscultatory findings); laboratory [(neutrophil count, lymphocyte count, monocyte count, hemoglobin, plasma glucose, urea, creatinine, total bilirubin (TBIL), direct bilirubin (DBIL), aspartate aminotransferase (AST), albumin (ALB), lactate dehydrogenase (LDH), creatinine kinase (CK), D-dimer, C-reactive protein (CRP), procalcitonin (PCT), Fe, and Ferritin)], arterial blood gases (oxygen saturation-Sa02, partial pressure of oxygen -p02), and chest X-rays (CXR) lung findings (p = 0.000). We found a significantly higher serum concentration (p < 0.05) of TNF-α, IL-1ß, IL-6, IL-12, IL-23, and IL-33 in patients with COVID-19 with severe disease. In the milder stage of COVID-19, a positive correlation was detected between IL-33 and IL-1ß, IL-12 and IL-23, while a stronger positive correlation between the serum values of IL-33 and TNF-α, IL-1ß, IL-6, and IL-12 and IL-23 was detected in patients with COVID-19 with severe disease. A weak negative correlation (p < 0.05) between pO2 and serum IL-1ß, IL-12, and IL-33 and between SaO2 and serum IL-33 was noted. The positive relation (p < 0.05) between the serum values of IL-33 and IL-12, IL-33 and IL-6, and IL-6 and IL-12 is proven. Conclusion: In a more progressive stage of COVID-19, increased IL-33 facilitates lung inflammation by inducing the production of various innate proinflammatory cytokines (IL-1ß, IL-6, TNF-α, IL-12, and IL-23) in several target cells leading to the most severe forms of the disease. IL-33 correlates with clinical parameters of COVID-19 and might represent a promising marker as well as a therapeutic target in COVID-19.

Increased Severity of Ulcerative Colitis in the Terminal Phase of the Metabolic Syndrome.

Ulcerative colitis is chronic immune-mediated disorder that affects primarily colonic mucosa. The metabolic syndrome has increasing global prevalence with a significant impact on biology of chronic diseases, such as ulcerative colitis. Today it is known that the metabolic syndrome attenuates severity of ulcerative colitis. Still, there is no evidence that different stages of metabolic syndrome alter the course of the ulcerative colitis. The aim of this study was to dissect out how progression of the metabolic syndrome impacted the biology of ulcerative colitis and severity of clinical presentation. Seventy-two patients (41 men and 31 women, 22-81 years old) were enrolled in this observational cross-sectional study. Concentrations of pro- and anti-inflammatory cytokines in serum and feces samples were measured and phenotype of colon infiltrating cells was analyzed. Patients in the terminal phase of the metabolic syndrome have clinically and pathohistologically more severe form of ulcerative colitis, which is followed by decreased concentrations of systemic galectin-1, increased values of systemic pro-inflammatory mediators and increased influx of lymphocytes in affected colon tissue. Our data suggest that reduced concentrations of galectin-1 and predomination of the pro-inflammatory mediators in patients with terminal stage of the metabolic syndrome enhance local chronic inflammatory response and subsequent tissue damage, and together point on important role of galectin-1 in immune response in ulcerative colitis patients with the metabolic syndrome.

Morphometric analysis of nonsclerosed Glomeruli size and connective tissue content during the aging process.

Number of sclerotic glomeruli increases during the aging process. Consequently, majority of remained nonsclerosed glomeruli become hypertrophic and some of them sclerotic, too. The aim of this study was to quantify the size and connective tissue content of nonsclerosed glomeruli and to evaluate the percentage of hypertrophic ones in examined human cases during the aging. Material was right kidney's tissue of 30 cadavers obtained during routine autopsies. Cadavers were without previously diagnosed kidney disease, diabetes, hypertension, or any other systemic disease. Tissue specimens were routinely prepared for histological and morphometric analysis. Images of the histological slices were analyzed and captured under 400x magnification with digital camera. Further they were morphometrically and statistically analyzed with ImageJ and NCSS-PASS software. Multiple and linear regression of obtained morphometric parameters showed significant increase of glomerular connective tissue area and percentage. Cluster analysis showed the presence of two types of glomeruli. Second type was characterized with significantly larger size, connective tissue content, and significantly lower cellularity, in relation to the first type. Such glomeruli might be considered as hypertrophic. First type of glomeruli was predominant in younger cases, while second type of glomeruli was predominant in cases older than 55 years.

Mirasol PRT system inactivation efficacy evaluated in platelet concentrates by bacteria-contamination model.

BACKGROUND/AIM: Bacterial contamination of blood components, primarily platelet concentrates (PCs), has been identified as one of the most frequent infectious complications in transfusion practice. PC units have a high risk for bacterial growth/multiplication due to their storage at ambient temperature (20 +/- 2 degrees C). Consequences of blood contamination could be effectively prevented or reduced by pathogen inactivation systems. The aim of this study was to determine the Mirasol pathogen reduction technology (PRT) system efficacy in PCs using an artificial bacteria-contamination model. METHODS: According to the ABO blood groups, PC units (n = 216) were pooled into 54 pools (PC-Ps). PC-Ps were divided into three equal groups, with 18 units in each, designed for an artificial bacteria-contamination. Briefly, PC-Ps were contaminated by Staphylococcus epidermidis, Staphylococcus aureus or Escherichia coli in concentrations 10(2) to 10(7) colony forming units (CFU) per unit. Afterward, PC-Ps were underwent to inactivation by Mirasol PRT system, using UV (lambda = 265-370 nm) activated riboflavin (RB). All PC-Ps were assayed by BacT/Alert Microbial Detection System for CFU quantification before and after the Mirasol treatment. Samples from non-inactivated PC-P units were tested after preparation and immediately following bacterial contamination. Samples from Mirasol treated units were quantified for CFUs one hour, 3 days and 5 days after inactivation. Results. A complete inactivation of all bacteria species was obtained at CFU concentrations of 10(2) and 10(3) per PC-P unit through storage/investigation period. The most effective inactivation (10(5) CFU per PC-P unit) was obtained in Escherichia coli setting. Contrary, inactivation of all the three tested bacteria species was unworkable in concentrations of > or = 10(6) CFU per PC-P unit. CONCLUSION: Efficient inactivation of investigated bacteria types with a significant CFU depletion in PC-P units was obtained--3 Log for all three tested species, and 5 Log for Escherichia coli. The safety of blood component therapy, primarily the clinical use of PCs can be improved using the Mirasol PRT system.

Stem cell harvesting protocol research in autologous transplantation setting: large volume vs. conventional cytapheresis.

BACKGROUND/AIM: The use of peripheral blood as a source of hematopoietic stem cells (SCs) is progressively increasing and has nearly supplanted bone marrow transplantation. Interpatient variability in the degree and kinetics of SC mobilization into peripheral blood is an expected event after conventional chemotherapy-based treatment, followed by sequential administration of recombinant granulocyte-colony-stimulating factor (rHu-CSF). In this study, specific factors associated with the application of two different SC-harvesting approaches, including the use of large volume leukapheresis (LVL) vs. repetitive conventional apheresis (RCA), were analyzed. The basic goal of the study was to evaluate the influence of apheresis protocol (collection timing, processed blood volume and cell yield) upon the clinical outcome of transplantation. METHODS: Results obtained by LVL (76 pts) and RCA (20 pts--control group) were compared. The SC mobilizing regimen used was cyclophosphamide (4-7 g/m2) or polychemotherapy and rHuG-CSF 10-16 microg/kg of body mess (bm) per day. Cell harvesting was performed using Caridian-BCT Spectra (Gambro, USA). The volume of processed blood in LVL setting was > or = 3.5-fold of the patient's circulating blood quantity (ranged from 12.7 to 37.8 l). All patients tolerated well the use of intensive treatment, without any side or adverse effects. Our original controlled-rate cryopreservation was carried out with 10% dimethyl sulfoxide (DMSO) using Planer R203/200R or Planer 560-16 equipments (Planer Products Ltd, UK). Total nucleated cell (NC) and mononuclear cell (MNC) counts were examined by flow cytometry (Advia-2120 Bayer, Germany; Technicon H-3 System, USA). The CD34+ cell surface antigen was investigated by the EPICS XL-MCL device (Coulter, Germany). RESULTS: Performing LVL-apheresis, high-level MNC and CD34+ cell yields (7.6 +/- 4.6 x 10(8)/kg bm and 11.8 +/- 6.5 x 10(6)/kg bm, respectively) were obtained. As a result, rapid hematopoietic reconstitution ("graft-healing")--on the 9.4th and 12.4th day for granulocytes and platelets, respectively was achieved. Using repetitive conventional apheresis (2-3 procedures), the total MNC count was high (8.2 +/- 7.0 x 10(8)/kg bm), but the total CD34+ yield was lower 10.8 +/- 9.9 due to inferior CD34+ vs. MNC ratio. CONCLUSION: The results obtained suggest that well-timed LVL-apheresis increased SC-yield in cell harvest, resulting in faster bone marrow repopulation and hematological reconstitution, as well as better overall clinical outcome of transplantation. These results necessitate additional examinations of CD34+ subsets ratio in cell harvest.