<abstract>
<title style='display:none'>Abstract</title>
Venous thromboembolism, encompassing acute pulmonary embolism (APE) and deep vein thrombosis (DVT), is a potentially fatal disease with complex pathophysiology. Traditionally, the Virchow triad provided a framework for understanding the pathogenic contributors to thrombus formation, which include endothelial dysfunction, alterations in blood flow and blood hypercoagulability. In the last years, it has become apparent that immunity plays a central role in thrombosis, interacting with classical prothrombotic mechanisms, oxidative stress and vascular factors. Thrombosis amplifies inflammation, and exaggerated inflammatory processes can trigger thrombosis mainly due to the activation of leukocytes, platelets, and endothelial cells. APE-related endothelium injury is a major trigger for immune system activation. Endothelium is also a key component mediating inflammatory reaction and it is relevant to maintain vascular permeability. Exaggerated right ventricular wall stress and overload, with coexisting systemic hypotension and hypoxemia, result in myocardial injury and necrosis. Hypoxia, tissue factor activation and cytokine storm are engaged in the thrombo-inflammatory processes. Thrombus development is characterized by inflammatory state vascular wall caused mainly by an early extravasation of leukocytes and intense selectins and cytokines production. Nevertheless, immunity of DVT is well described, little is known about potential chemokine and cellular differences between thrombus that develops in the vein and thrombus that detaches and lodges in the pulmonary circulation being a cause of APE. There is a paucity of data considering inflammatory state in the pulmonary artery wall during an acute episode of pulmonary embolism. The main aim of this review is to summarize the knowledge of immunity in acute phase of pulmonary embolism in experimental models.
</abstract>

Acute Pulmonary Embolism and Immunity in Animal Models

<abstract>
<title style='display:none'>Abstract</title>
Most gastric cancers (GC) are thought to be caused by <italic>Helicobacter pylori</italic> (<italic>H. pylori</italic>) infections. However, there is mounting evidence that GC patients with positive <italic>H. pylori</italic> status have improved prognoses. The <italic>H. pylori</italic>-induced cellular immune reaction may inhibit cancer. In this study, BALB/c mice were immunized using recombinant plasmids that encode the <italic>ureF</italic> gene of <italic>H. pylori</italic>. Purified functional splenic CD3+ T lymphocytes are used to study the anticancer effects <italic>in vitro</italic> and <italic>in vivo</italic>. The immunological state of GC patients with ongoing <italic>H. pylori</italic> infection is mimicked by the <italic>H. pylori</italic> DNA vaccines, which cause a change in the reaction from Th1 to Th2. Human GC cells grow more slowly when stimulated CD3+ T lymphocytes are used as adoptive infusions because they reduce GC xenograft development <italic>in vivo</italic>. The more excellent ratios of infiltrating CD8+/CD4+ T cells, the decreased invasion of regulatory FOXP3+ Treg lymphocytes, and the increased apoptosis brought on by Caspase9/Caspase-3 overexpression and Survivin downregulation may all contribute to the consequences. Our findings suggest that in people with advanced GC, <italic>H. pylori</italic> pIRES2-DsRed-Express-<italic>ureF</italic> DNA vaccines may have immunotherapeutic utility.
</abstract>

Potential Gastric Cancer Immunotherapy: Stimulating the Immune System with <italic>Helicobacter pylori</italic> pIRES2-DsRed-Express-<italic>ureF</italic> DNA Vaccines

<abstract>
<title style='display:none'>Abstract</title>
The immune system is regulated by a complex set of genetic, molecular, and cellular interactions. Rapid advances in the study of immunity and its network of interactions have been boosted by a spectrum of “omics” technologies that have generated huge amounts of data that have reached the status of big data (BD). With recent developments in artificial intelligence (AI), theoretical and clinical breakthroughs could emerge. Analyses of large data sets with AI tools will allow the formulation of new testable hypotheses open new research avenues and provide innovative strategies for regulating immunity and treating immunological diseases. This includes diagnosis and identification of rare diseases, prevention and treatment of autoimmune diseases, allergic disorders, infectious diseases, metabolomic disorders, cancer, and organ transplantation. However, ethical and regulatory challenges remain as to how these studies will be used to advance our understanding of basic immunology and how immunity might be regulated in health and disease. This will be particularly important for entities in which the complexity of interactions occurring at the same time and multiple cellular pathways have eluded conventional approaches to understanding and treatment. The analyses of BD by AI are likely to be complicated as both positive and negative outcomes of regulating immunity may have important ethical ramifications that need to be considered. We suggest there is an immediate need to develop guidelines as to how the analyses of immunological BD by AI tools should guide immune-based interventions to treat various diseases, prevent infections, and maintain health within an ethical framework.
</abstract>

Artificial Intelligence, Big Data, and Regulation of Immunity: Challenges and Opportunities

<abstract>
<title style='display:none'>Abstract</title>
Endometriosis is a debilitating gynecological disease defined as the presence of endometrium-like epithelium and/or stroma outside the uterine cavity. The most commonly affected sites are the pelvic peritoneum, ovaries, uterosacral ligaments, and the rectovaginal septum. The aberrant tissue responds to hormonal stimulation, undergoing cyclical growth and shedding similar to appropriately located endometrial tissue in the uterus. Common symptoms of endometriosis are painful periods and ovulation, severe pelvic cramping, heavy bleeding, pain during sex, urination and bowel pain, bleeding, and pain between periods. Numerous theories have been proposed to explain the pathogenesis of endometriosis. Sampson’s theory of retrograde menstruation is considered to be the most accepted. This theory assumes that endometriosis occurs due to the retrograde flow of endometrial cells through the fallopian tubes during menstruation. However, it has been shown that this process takes place in 90% of women, while endometriosis is diagnosed in only 10% of them. This means that there must be a mechanism that blocks the immune system from removing endometrial cells and interferes with its function, leading to implantation of the ectopic endometrium and the formation of lesions. In this review, we consider the contribution of components of the Major Histocompatibility Complex (MHC)-I-mediated antigen-processing pathway, such as the ERAP, TAP, LMP, LNPEP, and tapasin, to the susceptibility, onset, and severity of endometriosis. These elements can induce significant changes in MHC-I-bound peptidomes that may influence the response of immune cells to ectopic endometrial cells.
</abstract>

The Antigen-Processing Pathway via Major Histocompatibility Complex I as a New Perspective in the Diagnosis and Treatment of Endometriosis

<abstract>
<title style='display:none'>Abstract</title>
Impaired autophagy, due to the dysfunction of lysosomal organelles, contributes to maladaptive responses by pathways central to the immune system. Deciphering the immune–inflammatory ecosystem is essential, but remains a major challenge in terms of understanding the mechanisms responsible for autoimmune diseases. Accumulating evidence implicates a role that is played by a dysfunctional autophagy–lysosomal pathway (ALP) and an immune niche in psoriasis (Ps), one of the most common chronic skin diseases, characterized by the co-existence of autoimmune and autoinflammatory responses. The dysregulated autophagy associated with the defective lysosomal system is only one aspect of Ps pathogenesis. It probably cannot fully explain the pathomechanism involved in Ps, but it is likely important and should be seriously considered in Ps research. This review provides a recent update on discoveries in the field. Also, it sheds light on how the dysregulation of intracellular pathways, coming from modulated autophagy and endolysosomal trafficking, characteristic of key players of the disease, i.e., skin-resident cells, as well as circulating immune cells, may be responsible for immune impairment and the development of Ps.
</abstract>

Insights into Autophagic Machinery and Lysosomal Function in Cells Involved in the Psoriatic Immune-Mediated Inflammatory Cascade

<abstract>
<title style='display:none'>Abstract</title>
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis of sensitive cancer cells, including colorectal cancer (CRC). Due to its short biological half-life after intravenous administration and related clinical ineffectiveness, novel formulations of TRAIL need to be developed. Here we propose <italic>Lactococcus lactis</italic> bacteria as a vehicle for local delivery of human soluble TRAIL (hsTRAIL) in CRC. The use of common probiotics targeting guts as carriers for TRAIL could ensure its sustained release at the tumor site and extend the duration of its activity. We have already engineered hsTRAIL-secreting <italic>L.lactis</italic> bacteria and showed their effectiveness in elimination of human CRC cells in vitro and in vivo in a mouse subcutaneous model. Here, <italic>L.lactis</italic>(hsTRAIL+) were administered by gastric gavage to SCID mice with orthotopically developed HCT116 tumor in cecum, in monotherapy or in combination with metformin (MetF), already shown to enhance the hsTRAIL anti-tumor activity in subcutaneous CRC model. Oral administration of <italic>L.lactis</italic>(hsTRAIL+) resulted in significant progression of HCT116 tumors and shortening of the colon crypts. Secretion of hsTRAIL in the colon was accompanied by infiltration of the primary tumor with M2-macrophages, while MetF promoted transient colonization of the gut by <italic>L.lactis</italic>. Our study indicates that <italic>L.lactis</italic> bacteria after oral administration enable delivery of biologically active hsTRAIL to colon, however its potential therapeutic effect in CRC treatment is abolished by its pro-tumorigenic signalling, leading to the recruitment of M2-macrophages and tumor growth promotion.
</abstract>

Human Soluble TRAIL Secreted by Modified <italic>Lactococcus lactis</italic> Bacteria Promotes Tumor Growth in the Orthotopic Mouse Model of Colorectal Cancer

<abstract>
<title style='display:none'>Abstract</title>
The rapid development of nanotechnology has led to the use of silver nanoparticles (Ag-NPs) in various biomedical fields. However, the effect of Ag-NPs on human mesenchymal stem cells (hMSCs) is not fully understood. Moreover, too frequent an exposure to products containing nanosilver in sublethal amounts raises widespread concerns that it will lead to the development of silver-resistant microorganisms. Therefore, this study aimed to evaluate the mechanism of action of Ag-NPs on hMSCs by analyzing the cellular uptake of Ag-NPs by the cells and its effect on their viability and to assess antimicrobial activity of Ag-NPs against emerging bacterial strains, including multidrug-resistant pathogens. For metabolic activity and viability evaluation, hMSCs were incubated with different concentrations of Ag-NPs (14 μg/mL, 7 μg/mL, and 3.5 μg/mL) for 10 min., 1 h and 24 h and subsequently analyzed for their viability by live-dead staining and metabolic activity by the MTS assay. The effect of Ag-NPs on bacterial pathogens was studied by determining their minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). In conclusion, it was observed that exposure of hMSCs to Ag-NPs of size &lt;10 nm has no cytotoxic effect on the metabolic activity of the cells at the concentration of 3.5 μg/mL, with minimal cytotoxic effect being observed at the concentration of 14 μg/mL after 24 h of incubation. Our findings also confirmed that Ag-NPs at the concentration of 4 μg/mL are effective broad-spectrum bactericidal agents, regardless of the antibiotic-resistance mechanism present in bacteria.
</abstract>

<italic>In Vitro</italic> Effects of Silver Nanoparticles on Pathogenic Bacteria and on Metabolic Activity and Viability of Human Mesenchymal Stem Cells

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