Acute pancreatitis is characterized by autodigestion of pancreatic cells followed by acute inflammation leading to pathology and death. In experimental acute pancreatitis, pancreatic acinar cells and infiltrating macrophages express Galectin-3 but its role in pathology of this disease is unknown. Therefore, we studied its role using Galectin-3 deficient mice. Deletion of Galectin-3 prolonged the survival of mice, led to attenuation of histopathology, and decreased infiltration of mononuclear cells and neutrophils that express TLR-4, in particular, pro-inflammatory N1 neutrophils. Galectin-3 and TLR-4 are also colocalized on infiltrating cells. Lack of Galectin-3 reduced expression of pro-inflammatory TNF-α and IL-1β in F4/80 + CD11c-and CD11c + F4/80 − cells. Thus, deletion of Galectin-3 ameliorates acute pancreatitis by attenuating early influx of neutrophils and inflammatory mononuclear cells of innate immunity. These findings provide the basis to consider Galectin-3 as a therapeutic target in acute pancreatitis.Keywords: acute pancreatitis r Galectin-3 r N1 neutrophils r TLR4

Galectin-3 (Gal-3) has a role in multiple inflammatory pathways. Various, opposite roles of Gal-3 in liver diseases have been described but there are no data about the role of Gal-3 in development of hepatitis induced with cytomegalovirus infection. In this study we aimed to clarify the role of Gal-3 in murine cytomegalovirus (MCMV)-induced hepatitis by using Gal-3–deficient (Gal-3 KO) mice. Here we provide the evidence that Gal-3 has the protective role in MCMV-induced hepatitis. Enhanced hepatitis manifested by more inflammatory and necrotic foci and serum level of ALT, enhanced apoptosis and necroptosis of hepatocytes and enhanced viral replication were detected in MCMV-infected Gal-3 deficient mice. NK cells does not contribute to more severe liver damage in MCMV-infected Gal-3 KO mice. Enhanced expression of TNF-α in the hepatocytes of Gal-3 KO mice after MCMV infection, abrogated hepatocyte death, and attenuated inflammation in the livers of Gal-3 KO mice after TNF-α blockade suggest that TNF-α plays the role in enhanced disease in Gal-3 deficient animals. Treatment with recombinant Gal-3 reduces inflammation and especially necrosis of hepatocytes in the livers of MCMV-infected Gal-3 KO mice. Our data highlight the protective role of Gal-3 in MCMV-induced hepatitis by attenuation of TNF-α-mediated death of hepatocytes.

Low Reynolds number airflow in the pulmonary acinus and aerosol particle kinetics therein are significantly conditioned by the nature of the tidal motion of alveolar duct geometry. At least two components of the ductal structure are known to exhibit stress-strain hysteresis: smooth muscle within the alveolar entrance rings, and surfactant at the air-tissue interface. We hypothesize that the geometric hysteresis of alveolar duct is largely determined by the interaction of the amount of smooth muscle & connective tissue in ductal rings, septal tissue properties, and surface tension-surface area characteristics of surfactant. To test this hypothesis, we have extended the well-known structural model of the alveolar duct by Wilson and Bachofen (J. Appl. Physiol. 52(4): 1064–1070, 1982) by adding realistic elastic and hysteretic properties of 1) the alveolar entrance ring, 2) septal tissue, and 3) surfactant. With realistic values for tissue and surface properties, we conclude that: 1) there is a significant, and underappreciated, amount of geometric hysteresis in alveolar ductal architecture; and 2) the contribution of smooth muscle and surfactant to geometric hysteresis are of opposite senses, tending toward cancellation. Quantitatively, the geometric hysteresis found experimentally by Miki et al. (J. Appl. Physiol. 75(4): 1630–1636, 1993) is consistent with little or no smooth muscle tone in anesthetized rabbits in control conditions, and with substantial smooth muscle activation following methacholine challenge. The observed local hysteretic boundary motion of the acinar duct would result in irreversible acinar flow fields, which might be important mechanistic contributors to aerosol mixing and deposition deep in the lung.

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Clinical characteristics significantly influence mortality in STEMI; a significantly higher mortality is among women, patients in their 80's and 90's, anterior MI localization and prior coronary disease. RT significantly lowers mortality in STEMI compared to the use of classical therapeutic approach and therefore STEMI patients with a higher mortality determined by their prehospital charactheristics, i.e. higher risk, are those who have higher benefit of RT, which should be taken into consideration when making decision about the therapy of choice.

Acute pancreatitis (AP) is an abrupt, variable inflammatory condition of the pancreas, potentially escalating to severe systemic inflammation, rampant pancreatic necrosis, and multi-organ failure. Its complex pathogenesis involves an intricate immune response, with different T cell subsets (Th1, Th2, Th9, Th17, Th22, TFH, Treg, and CD8+ T cells) and B cells playing pivotal roles. Early T cell activation initiates the AP development, triggering cytokines associated with the Th1 response, which stimulate macrophages and neutrophils. Other T cell phenotypes contribute to AP’s pathogenesis, and the balance between pro-inflammatory and anti-inflammatory cytokines influences its progression. Regulatory T and B cells are crucial for moderating the inflammatory response and promoting immune tolerance. B cells further contribute through antibody production, antigen presentation, and cytokine secretion. Understanding these immune cells’ roles in AP could aid in developing new immunotherapies to enhance patient outcomes. However, further research is required to define these cells’ precise roles in AP and their potential as therapeutic targets.

Acute pancreatitis (AP) is a common, potentially lethal, acute inflammatory process with a highly variable clinical course. The aim of this study was to analyse early changes in the serum concentrations of pro- and anti-inflammatory cytokines in the peripheral blood of patients with the interstitial form of acute pancreatitis (IAP) and necrotic acute pancreatitis (NAP), especially in those patients who had lethal outcomes.The prospective study enrolled 52 patients who were divided into IAP (65.38% of patients) and NAP (34.62% of patients) groups. The serum levels of interleukins (IL) 6, 8 and 10, together with tumour necrosis factor (TNF)-alpha were measured on the 1st and 3rd day of hospitalisation. Significantly higher values of IL-6, IL-8 and IL-10 were found on day 1 and 3 in NAP than in IAP. IL-6 was significantly higher on both days of measurement, whereas IL-10 on the first day and IL-8 on the third day were significantly higher in the group of patients who did not survive in comparison with patients who had the interstitial form of AP.In conclusion, the data from this study showed that immune suppression and excessive immune stimulation in the first three days after admission could indicate the development of NAP and a potentially lethal outcome.

Galectin-3 (Gal-3), a beta-galactoside-binding lectin, plays a pivotal role in various cellular processes, including immune responses, inflammation, and cancer progression. This comprehensive review aims to elucidate the multifaceted functions of Gal-3, starting with its crucial involvement in viral entry through facilitating viral attachment and catalyzing internalization. Furthermore, Gal-3 assumes significant roles in modulating immune responses, encompassing the activation and recruitment of immune cells, regulation of immune signaling pathways, and orchestration of cellular processes such as apoptosis and autophagy. The impact of Gal-3 extends to the viral life cycle, encompassing critical phases such as replication, assembly, and release. Notably, Gal-3 also contributes to viral pathogenesis, demonstrating involvement in tissue damage, inflammation, and viral persistence and latency elements. A detailed examination of specific viral diseases, including SARS-CoV-2, HIV, and influenza A, underscores the intricate role of Gal-3 in modulating immune responses and facilitating viral adherence and entry. Moreover, the potential of Gal-3 as a biomarker for disease severity, particularly in COVID-19, is considered. Gaining further insight into the mechanisms and roles of Gal-3 in these infections could pave the way for the development of innovative treatment and prevention options for a wide range of viral diseases.