Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and is the most common cause of dementia. The pathogenesis of AD still remains unclear, including two main hypotheses: amyloid cascade and tau hyperphosphorylation. The hallmark neuropathological changes of AD are extracellular deposits of amyloid-β (Aβ) plaques and intracellular neurofibrillary tangles (NFTs). Endocytosis plays an important role in a number of cellular processes including communication with the extracellular environment, nutrient uptake, and signaling by the cell surface receptors. Based on the results of genetic and biochemical studies, there is a link between neuronal endosomal function and AD pathology. Taking this into account, we can state that in the results of previous research, endolysosomal abnormality is an important cause of neuronal lesions in the brain. Endocytosis is a central pathway involved in the regulation of the degradation of amyloidogenic components. The results of the studies suggest that a correlation between alteration in the endocytosis process and associated protein expression progresses AD. In this article, we discuss the current knowledge about endosomal abnormalities in AD.

Background: Tumor initiation and subsequent progression are usually long-term processes, spread over time and conditioned by diverse aspects. Many cancers develop on the basis of chronic inflammation; however, despite dozens of years of research, little is known about the factors triggering neoplastic transformation under these conditions. Molecular characterization of both pathogenetic states, i.e., similarities and differences between chronic inflammation and cancer, is also poorly defined. The secretory activity of tumor cells may change the immunophenotype of immune cells and modify the extracellular microenvironment, which allows the bypass of host defense mechanisms and seems to have diagnostic and prognostic value. The phenomenon of immunosuppression is also present during chronic inflammation, and the development of cancer, due to its duration, predisposes patients to the promotion of chronic inflammation. The aim of our work was to discuss the above issues based on the latest scientific insights. A theoretical mechanism of cancer immunosuppression is also proposed. Conclusions: Development of solid tumors may occur both during acute and chronic phases of inflammation. Differences in the regulation of immune responses between precancerous states and the cancers resulting from them emphasize the importance of immunosuppressive factors in oncogenesis. Cancer cells may, through their secretory activity and extracellular transport mechanisms, enhance deterioration of the immune system which, in turn, may have prognostic implications.

A total of 94 patients with colorectal cancer (CRC) were included in this study. Lymphocytic infiltration of CD45⁺ cells in the normal colon was more pronounced than that in the paired tumor stroma (p = 0.0008). The mean immunoscore of CD45⁺TILs was decreased in CRC compared with the controls (p = 0.0010). The percentage of CD3⁺ cells was higher in stage II than in stage IV (p = 0.0218) and showed a negative correlation with the TNM classification (r = -0.2867, p = 0.0109). The number of stromal CD4⁺TILs was higher in stage I than in stage III (p = 0.0116) and IV (p = 0.0104), and there was a negative correlation between this number and the stage (r = -0.3708, p = 0.0008). There was a positive correlation between the Ki-67 and CD45⁺ (r = 0.2468, p = 0.0294), CD3⁺ (r = 0.3822, p = 0.0006), and CD4⁺ cells (r = 0.5465, p < 0.0001). The levels of cancer-associated fibroblast (CAF) markers such as α-SMA, thrombin and fibronectin were significantly higher in CRC than in normal colonic mucosa. The immunohistochemical expression of α-SMA was negatively correlated with TILs, while fibronectin showed positive coexpression. A higher number of cells expressing IL-2Rα, PD-L1, CD33 and CD14 were found in colorectal adenocarcinomas than in controls. The number of CD14⁺ cells was also dependent on the TNM stage (p = 0.0444) and tumor budding (p = 0.0324). These findings suggest a suppressive impact of CRC on the adaptive immune response and emphasize the importance of CAFs in regulating tumor immunity.

Major depressive disorder (MDD) is not a single disease, but a number of various ailments that form one entity. Psychomotor retardation, anhedonia, sleep disorders, an increased suicide risk, and anxiety are the main symptoms that often define the clinical diagnosis of depression. Interleukin-6 (IL-6), as one of the proinflammatory cytokines, seems to be overexpressed during certain mental disorders, including MDD. Overexpression of IL-6 in depression is thought to be a factor associated with bad prognosis and worse disease course. IL-6 may directly affect brain functioning and production of neurotransmitters; moreover, its concentration is correlated with certain clinical symptoms within the wide range of depressive symptomatology. Furthermore, there is a strong correlation between IL-6 synthesis and psychosomatic functioning of the patient. This article discusses potential sources and significance of IL-6 in the pathogenesis of depression.