Depression's complex pathogenesis involves neurotransmission disorders, chronic inflammation, and immune dysregulation. Supporting the inflammatory theory, this study analyzed lymphocyte subpopulations and surface molecule expression in patients to investigate immunological mechanisms and provide evidence for this clinical perspective. The study involved twenty-seven patients with newly diagnosed depression and ten healthy volunteers. Level of T-lymphocyte subpopulations, B-lymphocytes and NK-cells, as well as the expression of activation markers (CD25, CD69), inflammatory markers (TLR-4), apoptosis markers (CD95, TRAIL-R1) and maturity markers (CD10, CD40, CD5). A reduced proportion of NK-cells was observed in patients. An increase in number of immature B-cells CD19 + CD10+ and CD19 + CD5+ cells was observed, accompanied by a decrease in CD40 expression. TLR-4 expression on CD4 + and CD19 + lymphocytes in patients was more than twice as high compared with the group of healthy volunteers. There was also an increase in the expression of the activation markers CD25 and CD69 on T-lymphocytes, and CD95 and TRAIL-R1 on T and B-lymphocytes. Some parameters correlated with severity of depressive symptoms. The results confirm that chronic inflammation influences depression through changes in lymphocytes. This suggests that immunomodulatory and anti-inflammatory treatments should be implemented as an important adjunct to standard clinical management of this condition.

For years, the understanding of Alzheimer's disease (AD) has been shaped by the amyloid hypothesis, which suggests that pathological markers like amyloid-β (Aβ) and phosphorylated tau are the primary drivers of the disease. This hypothesis has guided the development of major treatment strategies, including monoclonal antibodies targeting Aβ. However, most of these treatments have failed to produce clinically significant results, highlighting the urgent need for a new therapeutic approach. It is now evident that AD is a complex, multifactorial disease that develops over decades, ultimately leading to Aβ and tau accumulation. Therefore, addressing the underlying causes of these depositions is crucial. One well-supported yet underrecognized theory is the infection hypothesis, which links infections to AD pathology. Despite substantial scientific evidence, this perspective has faced significant resistance. In this review, we describe how chronic infections contribute to AD by triggering neuroinflammation and Aβ accumulation. We also explore the barriers to accepting the infection hypothesis and the steps necessary for its integration into drug development and early-stage treatment strategies. Persisting with an amyloid-centric approach will only exacerbate the societal burden. Embracing the infection hypothesis could transform AD research, diagnosis, and treatment, bringing new hope to millions.

Rheumatoid arthritis (RA), an autoimmune disease with complex pathogenesis, is characterized by an immune imbalance reflected, e.g., in the disturbed cytokines’ profile. Various viruses and bacteria can cause the upregulation of pro-inflammatory cytokines influencing RA development. In particular, oral cavity dysbiosis, observed in multiple chronic diseases including periodontitis, may be linked to RA. The cytokine profile (IL-1β, IP-10, IL-29, GM-CSF, IFN-α2, IFN-β, TGF-β1, MPC-1, TNF-α, IFN-γ, IL-6, IL-10, IL-17A, IL-12p70, IL-2, and IL-4) of RA patients’ saliva was evaluated using flow cytometry and benchmarked with their levels in saliva of healthy controls and patients with other rheumatic diseases. The levels of IL-1β, IP-10, IL-2, and IL-4 were significantly elevated in RA patients’ saliva compared to other studied groups. To define the potential role of the most suspicious microbial agents (Epstein–Barr Virus (EBV), Cytomegalovirus, Parvovirus B19, Porphyromonas gingivalis, and Segatella copri) for RA pathogenesis, the amounts of their DNA in the saliva of patients with RA were assessed in all the groups mentioned above. The EBV and P. gingivalis DNA levels measured by qRT-PCR were significantly higher in RA patients’ saliva than in other groups, indicating either the important role of these agents in RA pathogenesis or the higher susceptibility of RA patients for those infectious factors. The comprehension of the association of specific cytokine profiles in RA and the occurrence of specific viral and/or bacterial infections can be a key to a better understanding of RA pathogenesis. These results illustrate the complexity of the immunological profile of RA, show the high diagnostic potential of saliva, and provide insight into how various infections can contribute to RA development.

Oxidative stress and chronic inflammation, both at the systemic and central level, are critical early events in atherosclerosis and Alzheimer’s disease (AD). Purpose. To investigate the oxidative stress, inflammatory, and Tau-phosphorylation lowering effects of pomegranate polyphenols (PP) (punicalagin, ellagic acid, peels, and arils extracts). Methods. We used flow cytometry to quantify protein expression of proinflammatory cytokines (IL-1β) and anti-inflammatory mediators (IL-10) in THP-1 macrophages, as well as M1/M2 cell-specific markers (CD86 and CD163) expression in human microglia HMC3 cells. IL-10 protein expression was also quantified in U373-MG human astrocytes. The effect of PP on human amyloid beta 1-42 (Aβ1-42)-induced oxidative stress was assessed in microglia by measuring ROS generation and lipid peroxidation, using respectively two ′,7′-dichlorofluorescein diacetate (DCFH-DA) and thiobarbituric acid reactive substances (TBARS) tests. Neuronal viability and cell apoptotic response to Aβ1-42 toxicity were assayed using the MTT (3-(4, 5-dimethyl thiazolyl-2)-2, 5-diphenyltetrazolium bromide) assay and the annexinV-FITC apoptosis detection kit; respectively. Finally, flow cytometry analysis was also performed to evaluate the ability of PP to modulate Aβ1-42-induced Tau-181 phosphorylation (pTau-181). Results. Our data indicate that PP was significantly (p<0.05) effective in countering Aβ1-42-induced inflammation through increasing the anti-inflammatory cytokines (IL-10) (in U373-MG astrocytes and THP1 macrophages) and decreasing proinflammatory markers (IL-1β) expression in THP1 macrophages. PP was also significantly (p<0.05) effective in inducing the phenotypic transition of THP-1 macrophages and microglial cells from M1 to M2 by decreasing CD86 and increasing CD163 surface receptor expression. Moreover, our treatments have a significant (p<0.05) beneficial impact on oxidative stress, illustrated in the reduction of TBARS and ROS generation. Our treatments have significant (p<0.05) cell viability improvement capacities and anti-apoptotic effects on human H4 neurons. Furthermore, our results suggest that Aβ1-42 significantly (p<0.05) increases pTau-181. This effect was significantly (p<0.05) attenuated by arils, peels, and punicalagin and drastically reduced by ellagic acid treatments. Conclusion. Our results are attributed to PP's anti-inflammatory, antioxidant, anti-apoptotic, and anti-Tau pathology potential. Future studies should aim to extend our knowledge of the potential role of PP on A1-42-induced neurodegeneration, mainly its association with the tauopathy involved in AD.

Background: The aim of this study was to assess the effectiveness of hand grip strength (HGS) test in identifying highly stressed individuals and to examine the effect of exercise and lifestyle on HGS and stress measures. Material and method: It is cross-sectional study. Students of the Medical University of Gda & nacute;sk, Poland were asked to fill out a questionnaire, undergo body composition analysis, perform HGS test and provide a saliva sample for cortisol measurement. Results: Self-rated stress (SRS) was significantly higher in pre-clinical years (PCY) compared to clinical years (CY). HGS was significantly lower in PCY males than CY males. Participants who performed some form of exercise had significantly higher HGS compared with those who did not exercise. A positive correlation between HGS and BMI was noted. Students with low HGS were found to have lower levels of salivary cortisol (SC). However, there was no significant difference in SC levels between PCY and CY students. Conclusions: HGS may be a reliable method of identifying stressed individuals and promoting healthy lifestyle behaviors. HGS testing is a safe, cheap and easy to perform method for a large number of participants while being time economical.

Innowacje są niewątpliwie jedną z głównych sił napędowych wzrostu gospodarczego. Zdolność do kreowania i implementowania rozwiązań innowacyjnych jest aktualnie podstawowym miernikiem sprawności funkcjonowania przedsiębiorstwa na rynku. Celem artykułu było zidentyfikowanie kluczowych czynników wewnątrz organizacji w największym stopniu sprzyjających ich innowacyjności oraz elastyczności. Badaniem objęto 620 respondentów z różnych małych i mikroprzedsiębiorstw. W trakcie badań przeprowadzono następujące prace: deskresearch, indywidualny wywiad pogłębiony oraz badania ankietowe. Na podstawie uzyskanych wyników stwierdzono, że większość ankietowanych członków organizacji dostrzega ścisłą zależność pomiędzy innowacyjnością a kreatywnością. Badani menedżerowie doceniają wspólnotę norm, wartości oraz wzorców zachowań w organizacji jako istotny czynnik innowacyjności. Autorzy uważają, że przeprowadzone badania mogą urozmaicić i wzbogacić literaturę dotyczącą innowacji i adaptowania, wdrażania, a także stymulować współpracę organizacji w zakresie wdrażania innowacji.

Our study aimed to identify markers of enterococci's virulence potential by evaluating the properties of strains of different sites of isolation. Enterococcal strains were isolated as commensals from faeces and as invasive strains from the urine and blood of patients from the University Clinical Centre, Gda & nacute;sk, Poland. Changes in monocytes' susceptibility to the cytotoxic activity of isolates of different origins and their adherence to biofilm were evaluated using a flow cytometer. The bacterial protein profile was estimated by matrix assisted laser desorption ionization-time of flight mass spectrometer. The cytotoxicity of biofilm and monocytes' adherence to it were the most accurate factors in predicting the prevalence of the strain in the specific niche. Additionally, a bacterial protein with mass-to-charge ratio (m/z) 5000 was found to be responsible for the increased bacterial cytotoxicity, while monocytes' decreased adherence to biofilm was linked with the presence of proteins either with m/z 3330 or 2435. The results illustrate that monocytes' reaction when exposed to the bacterial biofilm can be used as an estimator of pathogens' virulence potential. The observed differences in monocytes' response are explainable by the bacterial proteins' profile. Additionally, the results indicate that the features of both bacteria and monocytes impact the outcome of the infection.

Background: Oxidative stress and chronic inflammation, at both the systemic and the central level, are critical early events in atherosclerosis and Alzheimer’s disease (AD). Purpose: To investigate the oxidative stress-, inflammation-, and Tau-phosphorylation-lowering effects of pomegranate polyphenols (PPs) (punicalagin, ellagic acid, peel, and aril extracts). Methods: We used flow cytometry to quantify the protein expression of proinflammatory cytokines (IL-1β) and anti-inflammatory mediators (IL-10) in THP-1 macrophages, as well as M1/M2 cell-specific marker (CD86 and CD163) expression in human microglia HMC3 cells. The IL-10 protein expression was also quantified in U373-MG human astrocytes. The effect of PPs on human amyloid beta 1-42 (Aβ1-42)-induced oxidative stress was assessed in the microglia by measuring ROS generation and lipid peroxidation, using 2′,7′-dichlorofluorescein diacetate (DCFH-DA) and thiobarbituric acid reactive substance (TBARS) tests, respectively. Neuronal viability and cell apoptotic response to Aβ1-42 toxicity were assayed using the MTT (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide) assay and the annexin-V-FITC apoptosis detection kit, respectively. Finally, flow cytometry analysis was also performed to evaluate the ability of PPs to modulate Aβ1-42-induced Tau-181 phosphorylation (pTau-181). Results: Our data indicate that PPs are significantly (p < 0.05) effective in countering Aβ1-42-induced inflammation through increasing the anti-inflammatory cytokines (IL-10) in U373-MG astrocytes and THP1 macrophages and decreasing proinflammatory marker (IL-1β) expression in THP1 macrophages. The PPs were also significantly (p < 0.05) effective in inducing the phenotypic transition of THP-1 macrophages and microglial cells from M1 to M2 by decreasing CD86 and increasing CD163 surface receptor expression. Moreover, our treatments have a significant (p < 0.05) beneficial impact on oxidative stress, illustrated in the reduction in TBARS and ROS generation. Our treatments have significant (p < 0.05) cell viability improvement capacities and anti-apoptotic effects on human H4 neurons. Furthermore, our results suggest that Aβ1-42 significantly (p < 0.05) increases pTau-181. This effect is significantly (p < 0.05) attenuated by arils, peels, and punicalagin and drastically reduced by the ellagic acid treatment. Conclusion: Overall, our results attribute to PPs anti-inflammatory, antioxidant, anti-apoptotic, and anti-Tau-pathology potential. Future studies should aim to extend our knowledge of the potential role of PPs in Aβ1-42-induced neurodegeneration, particularly concerning its association with the tauopathy involved in AD.

The purpose of this article is to explore whether and based on what criteria local governments employ reduced tax rates on means of transportation to encourage hybrid and electric vehicles. The study also aims to determine if there has been a more rapid increase in the number of means of transportation powered entirely or partially by electricity in local government units that have implemented more substantial incentives. The study encompasses the ten largest cities in Poland and the years 2018–2020. To achieve the above research objectives, an analysis of the texts of the resolutions of the city councils was carried out in terms of the tax rates in effect during the selected period. On the basis of the relevant amounts provided in the resolutions, the amount of concessions resulting from the application of lower tax rates was calculated, and the criteria for the use of these concessions related to the level of emissivity were presented. To assess the potential correlation between the scale of tax preferences and the dynamics of growth in the number of hybrid and electric vehicles, a statistical tool in the form of Spearman’s rank correlation coefficient was used for a thorough data analysis. The results suggest that municipalities use their authority to introduce differentiated tax rates on means of transportation. However, those utilizing hybrid and electric vehicles are more likely to employ these powers on an equal basis, with owners of vehicles adhering to lower emission standards covered by EURO standards. In addition, there was no positive correlation between the amount of tax credits and the rate of growth in the number of reduced-emission vehicles. This work can foster a green mindset and societal nature-based new thinking.

The inflammaging concept was introduced in 2000 by Prof. Franceschi. This was an evolutionary or rather a revolutionary conceptualization of the immune changes in response to a lifelong stress. This conceptualization permitted to consider the lifelong proinflammatory process as an adaptation which could eventually lead to either beneficial or detrimental consequences. This dichotomy is influenced by both the genetics and the environment. Depending on which way prevails in an individual, the outcome may be healthy longevity or pathological aging burdened with aging-related diseases. The concept of inflammaging has also revealed the complex, systemic nature of aging. Thus, this conceptualization opens the way to consider age-related processes in their complexity, meaning that not only the process but also all counter-processes should be considered. It has also opened the way to add new concepts to the original one, leading to better understanding of the nature of inflammaging and of aging itself. Finally, it showed the way towards potential multimodal interventions involving a holistic approach to optimize the aging process towards a healthy longevity.

This study focuses on the econometric modelling of immigration processes in the United Kingdom (UK) using endogenous pull factors. The study aims to investigate the impact of economic, social, housing and labour indicators on immigration inflows to the UK. In the article a regression model is employed, covering the period from 2000 to 2021 to estimate the relationship between the endogenous pull factors in the UK and immigra-tion processes. The endogenous pull factors considered in this study include economic factors such as GDP per capita, the number of new businesses per year, budget spend-ing per student and the average salary per year; social factors such as population den-sity, level of urbanization, and crime rate; housing factors such as the number of new residential buildings built; labour factors the unemployment and the employment rates. The results of the study show that key factors like GDP per capita, unemployment rate, newly registered businesses, and government spending per student have a significant influence on immigration inflows. In contrast, it was found that crime rate, average salary and population indicators don't affect international migration to the UK as much. The findings of this article have important implications for policymakers and researchers interested in understanding the dynamics of immigration processes in the UK. By iden-tifying the key endogenous pull factors driving immigration and using them to create forecasts such as the one in this study, policymakers can develop more effective immi-gration policies and better allocate resources to support immigrants and their integration into UK society.

This chapter attempts to combine the theoretical, methodological, and practical dimensions of entrepreneurship. Specifically, it looks into three questions: (1) the theoretical perspective of entrepreneurship and the roles it plays, (2) what can be done to measure entrepreneurship in practice, and (3) whether Poland's economic climate has influenced the level of entrepreneurship in 2017-2020. Today, entrepreneurship is strongly correlated with innovation. In this chapter, we discuss the impact of the pandemic on the growth and development of entrepreneurship. The economic and social data for the European Union presented herein confirm the significance of the pandemic's impact. A review of the selected entrepreneurship indicators presented in this chapter revealed a decline in the Polish economy and a clear decline in its dynamics. In looking at the main reasons for this slowing down of economic activity, we find that there are a number of factors at play that affect not only entrepreneurs and their companies but also the state budget. Lastly, we discuss the low level of innovation among Polish enterprises, which is a result of the lack of reliable systemic solutions.

INTRODUCTION:Clinically, Alzheimer's disease (AD) is a syndrome with a spectrum of various cognitive disorders. There is a complete dissociation between the pathology and the clinical presentation. Therefore, we need a disruptive new approach to be able to prevent and treat AD.AREAS COVERED:In this review, the authors extensively discuss the evidence why the amyloid beta is not the pathological cause of AD which makes therefore the amyloid hypothesis not sustainable anymore. They review the experimental evidence underlying the role of microbes, especially that of viruses, as a trigger/cause for the production of amyloid beta leading to the establishment of a chronic neuroinflammation as the mediator manifesting decades later by AD as a clinical spectrum. In this context, the emergence and consequences of the infection/antimicrobial protection hypothesis are described. The epidemiological and clinical data supporting this hypothesis are also analyzed.EXPERT OPINION:For decades, we have known that viruses are involved in the pathogenesis of AD. This discovery was ignored and discarded for a long time. Now we should accept this fact, which is not a hypothesis anymore, and stimulate the research community to come up with new ideas, new treatments, and new concepts.

Background In the course of allogeneic hematopoietic cell transplantation (allo-HCT) the donor’s hematopoietic progenitor cells are exposed to immense proliferative stress to reconstitute in the recipient the functional hematopoiesis. Moreover, recipients who develop infections or chronic GvHD are subjected to further proliferative stress, especially in the lymphocyte subset. We hypothesized that allo-HCT may induce changes in proinflammatory cytokines profile and immunophenotype in the allo-HCT recipients, especially in patients with cGVHD history. We compared the cytokine profile (Il-6, Il-10, and TNF-) between long-term allo-HCT recipients and their respective donors and we analyzed cytokines profile and the immunophenotype of lymphocytes in long-term recipients grouped according to the infection and GvHD history. Results We have found no differences in the proinflammatory cytokines between allo-HCT recipients and their respective donors, as well as between recipients grouped according to infectious risk status. Immunophenotyping of recipients grouped according to GvHD status revealed an increased percentage of B-cell presenting PD-1 in recipients without a history of GvHD. Conclusions Lack of differences in proinflammatory cytokines concentrations between recipients and donors of allo-HCT would suggest that allo-HCT does not induce acceleration of the inflammageing-resembling phenomenon. No differences in the cytokine profile and immunophenotype between recipients grouped according to infectious risk status suggest that infectious risk is not reflected by the immunophenotype and cytokine profile. Furthermore, the lack of significant differences in immunophenotype of the recipients grouped according to the history of GvHD may suggest that in long-term survivors the immune system tends to stabilize with time.

Human ageing is by far one of the most complex biological phenomena which affects all cells and tissues, leading to gradual loss of function, decrement in proliferative activity, and impaired cellular response. One of the key mechanisms of cellular ageing is proliferative stress which results in telomeric attrition, DNA damage, and deposition of senescence-associated proteins. Allogeneic hematopoietic cells transplantation (allo-HCT) serves as a good model for cellular ageing. Here we review the ageing of the immune system and the impact of proliferative stress on both innate and adaptive immune response, reflected by immunosenescence and inflammageing phenomena, in the context of iatrogenic proliferative stress induced by allo-HCT.