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Simple Summary: Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of hematological malignancies but is often associated with significant adverse events. As these events affect up to 80% of patients, they constitute a crucial problem to overcome. This review focuses on the monitoring process of CAR-T cell therapy including the monitoring of the persistence, activity, and phenotyping of the cells. The implementation of tools like flow cytometry and polymerase chain reaction provides insights into cellular responses, enabling the optimization of CAR-T cell therapy for more precise and personalized treatment and addressing the challenge of tumor relapse. Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment for relapsed/refractory B-cell lymphomas. Despite its success, this therapy is accompanied by a significant frequency of adverse events, including cytokine release syndrome (CRS), immune-effector-cell-associated neurotoxicity syndrome (ICANS), or cytopenias, reaching even up to 80% of patients following CAR-T cell therapy. CRS results from the uncontrolled overproduction of proinflammatory cytokines, which leads to symptoms such as fever, headache, hypoxia, or neurological complications. CAR-T cell detection is possible by the use of flow cytometry (FC) or quantitative polymerase chain reaction (qPCR) assays, the two primary techniques used for CAR-T evaluation in peripheral blood, bone marrow (BM), and cerebrospinal fluid (CSF). State-of-the-art imaging technologies play a crucial role in monitoring the distribution and persistence of CAR-T cells in clinical trials. Still, they can also be extended with the use of FC and digital PCR (dPCR). Monitoring the changes in cell populations during disease progression and treatment gives an important insight into how the response to CAR-T cell therapy develops on a cellular level. It can help improve the therapeutic design and optimize CAR-T cell therapy to make it more precise and personalized, which is crucial to overcoming the problem of tumor relapse. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor T-cell (CAR-T) therapy is a novel anticancer therapy using autologous or allogeneic T-cells. To date, six CAR-T therapies for specific B-cell acute lymphoblastic leukemia (B-ALL), non-Hodgkin lymphomas (NHL), and multiple myeloma (MM) have been approved by the Food and Drug Administration (FDA). Significant barriers to the effectiveness of CAR-T therapy include cytokine release syndrome (CRS), neurotoxicity in the case of Allogeneic Stem Cell Transplantation (Allo-SCT) graft-versus-host-disease (GVHD), antigen escape, modest antitumor activity, restricted trafficking, limited persistence, the immunosuppressive microenvironment, and senescence and exhaustion of CAR-Ts. Furthermore, cancer drug resistance remains a major problem in clinical practice. CAR-T therapy, in combination with checkpoint blockades and bispecific T-cell engagers (BiTEs) or other drugs, appears to be an appealing anticancer strategy. Many of these agents have shown impressive results, combining efficacy with tolerability. Biomarkers like extracellular vesicles (EVs), cell-free DNA (cfDNA), circulating tumor (ctDNA) and miRNAs may play an important role in toxicity, relapse assessment, and efficacy prediction, and can be implicated in clinical applications of CAR-T therapy and in establishing safe and efficacious personalized medicine. However, further research is required to fully comprehend the particular side effects of immunomodulation, to ascertain the best order and combination of this medication with conventional chemotherapy and targeted therapies, and to find reliable predictive biomarkers. [ABSTRACT FROM AUTHOR]

Simple Summary: Glioblastoma is one of the most dangerous tumors of the central nervous system, and still cannot be fully overcome. We still mainly rely on standard treatments combining chemotherapy, radiotherapy, and surgery in various combinations. However, advances in technology, particularly biotechnology, are allowing the introduction of new, more precise therapies. These are more personalized, targeting a specific stage of tumor development or a particular cell population. The treatment of glioma is one of the areas in which we see more and more personalized medicine. In this article, we have tried to describe the current state of knowledge regarding the use of modern therapies in treating glioblastoma and the primary concerns. Glioblastoma is the most common malignant primary brain tumor in the adult population, with an average survival of 12.1 to 14.6 months. The standard treatment, combining surgery, radiotherapy, and chemotherapy, is not as efficient as we would like. However, the current possibilities are no longer limited to the standard therapies due to rapid advancements in biotechnology. New methods enable a more precise approach by targeting individual cells and antigens to overcome cancer. For the treatment of glioblastoma, these are gamma knife therapy, proton beam therapy, tumor-treating fields, EGFR and VEGF inhibitors, multiple RTKs inhibitors, and PI3K pathway inhibitors. In addition, the increasing understanding of the role of the immune system in tumorigenesis and the ability to identify tumor-specific antigens helped to develop immunotherapies targeting GBM and immune cells, including CAR-T, CAR-NK cells, dendritic cells, and immune checkpoint inhibitors. Each of the described methods has its advantages and disadvantages and faces problems, such as the inefficient crossing of the blood–brain barrier, various neurological and systemic side effects, and the escape mechanism of the tumor. This work aims to present the current modern treatments of glioblastoma. [ABSTRACT FROM AUTHOR]

Atherosclerosis is a chronic inflammatory disease driven by lipid accumulation in the arteries, leading to narrowing and thrombosis that causes mortality. Emerging evidence has confirmed that atherosclerosis affects younger people and is involved in the majority of deaths worldwide. EVs are associated with critical steps in atherosclerosis, cholesterol metabolism, immune response, endothelial dysfunction, vascular inflammation, and remodeling. Endothelial cell-derived EVs can interact with platelets and monocytes, thereby influencing endothelial dysfunction, atherosclerotic plaque destabilization, and the formation of thrombus. EVs are potential diagnostic and prognostic biomarkers in atherosclerosis (AS) and cardiovascular disease (CVD). Importantly, EVs derived from stem/progenitor cells are essential mediators of cardiogenesis and cardioprotection and may be used in regenerative medicine and tissue engineering. [ABSTRACT FROM AUTHOR]

Simple Summary: Chimeric antigen receptor T (CAR-T) therapy has revolutionized cancer immunotherapy by inducing a durable response in patients with acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL). The challenges for cancer immunotherapy concern complex resistance mechanisms; therefore, a very important therapeutic approach is to focus on the development of rational combinations of targeted therapies with non-overlapping toxicities. Recent progress in the development of potential therapeutics has significantly improved anticancer responses, while next-generation CAR-T-cells may overcome current limitations and decrease unwanted side effects in targeting hematological malignancies. CAR-T cell therapy has revolutionized the treatment of hematological malignancies with high remission rates in the case of ALL and NHL. This therapy has some limitations such as long manufacturing periods, persistent restricted cell sources and high costs. Moreover, combination regimens increase the risk of immune-related adverse events, so the identification new therapeutic targets is important to minimize the risk of toxicities and to guide more effective approaches. Cancer cells employ several mechanisms to evade immunosurveillance, which causes resistance to immunotherapy; therefore, a very important therapeutic approach is to focus on the development of rational combinations of targeted therapies with non-overlapping toxicities. Recent progress in the development of new inhibitory clusters of differentiation (CDs), signaling pathway molecules, checkpoint inhibitors, and immunosuppressive cell subsets and factors in the tumor microenvironment (TME) has significantly improved anticancer responses. Novel strategies regarding combination immunotherapies with CAR-T cells are the most promising approach to cure cancer. [ABSTRACT FROM AUTHOR]

Genetically engineered T and NK cells expressing a chimeric antigen receptor (CAR) are promising cytotoxic cells for the treatment of hematological malignancies and solid tumors. Despite the successful therapies using CAR-T cells, they have some disadvantages, such as cytokine release syndrome (CRS), neurotoxicity, or graft-versus-host-disease (GVHD). CAR-NK cells have lack or minimal cytokine release syndrome and neurotoxicity, but also multiple mechanisms of cytotoxic activity. NK cells are suitable for developing an "off the shelf" therapeutic product that causes little or no graft versus host disease (GvHD), but they are more sensitive to apoptosis and have low levels of gene expression compared to CAR-T cells. To avoid these adverse effects, further developments need to be considered to enhance the effectiveness of adoptive cellular immunotherapy. A promising approach to enhance the effectiveness of adoptive cellular immunotherapy is overcoming terminal differentiation or senescence and exhaustion of T cells. In this case, EVs derived from immune cells in combination therapy with drugs may be considered in the treatment of cancer patients, especially effector T and NK cells-derived exosomes with the cytotoxic activity of their original cells. [ABSTRACT FROM AUTHOR]

Extracellular vesicles are evaluated by nanoparticle tracking analysis (NTA), providing information on their hydrodynamic diameters, and by atomic force microscopy (AFM) to calculate their geometric diameters. The aim of this study is to explore the influence of Brownian movements in a sample drop and preparation time on imaging-based measurements and to determine the relationship between the geometric and hydrodynamic sizes of the extracellular vesicles measured by the AFM and the NTA, respectively. Exosomes derived from the human prostate cancer cell line PC3 were evaluated by NTA and AFM, and those results were compared with Monte Carlo simulations. The mean size, evaluated by AFM shortly after application on the mica substrate, is less than its real value. It obtains the correct value faster for a thinner sample drop. Fitting the log-normal distribution to the geometric and hydrodynamic diameters leads to the conclusion that the latter could arise from the former by linear scaling by a factor that could be used to characterize the analyzed extracellular vesicles. The size of the vesicles attached to the mica substrate depends on time. The effect of Brownian motion and stretch of the lipid bilayer should be considered in the context of exosome AFM studies. [ABSTRACT FROM AUTHOR]

Ethanol, as a small-molecule organic compound exhibiting both hydrophilic and lipophilic properties, quickly pass through the biological barriers. Over 95% of absorbed ethanol undergoes biotransformation, the remaining amount is excreted unchanged, mainly with urine and exhaled air. The main route of ethyl alcohol metabolism is its oxidation to acetaldehyde, which is converted into acetic acid with the participation of cytosolic NAD+ - dependent alcohol (ADH) and aldehyde (ALDH) dehydrogenases. Oxidative biotransformation pathways of ethanol also include reactions catalyzed by the microsomal ethanol oxidizing system (MEOS), peroxisomal catalase and aldehyde (AOX) and xanthine (XOR) oxidases. The resulting acetic acid can be activated to acetyl-CoA by the acetyl-CoA synthetase (ACS). It is also possible, to a much smaller extent, non-oxidative routes of ethanol biotransformation including its esterification with fatty acids by ethyl fatty acid synthase (FAEES), re-esterification of phospholipids, especially phosphatidylcholines, with phospholipase D (PLD), coupling with sulfuric acid by alcohol sulfotransferase (SULT) and with glucuronic acid using UDP-glucuronyl transferase (UGT, syn. UDPGT). The intestinal microbiome plays a significant role in the ethanol biotransformation and in the initiation and progression of liver diseases stimulated by ethanol and its metabolite - acetaldehyde, or by lipopolysaccharide and ROS. [ABSTRACT FROM AUTHOR]

Tumor-derived exosomes (TEX) are involved in cancer development, metastasis, and disease progression. They can modulate angiogenesis to elevate the malignant degree of tumor cells. TEX carry immunosuppressive factors affecting the antitumor activities of immune cells. Tumor cells as well as immune cells secrete immunologically active exosomes which affect intercellular communication, antigen presentation, activation of immune cells, and immune surveillance. Cell proliferation and immune response suppression create a favorable microenvironment for tumor. TEX can inhibit immune cell proliferation, induce apoptosis of activated CD8+ Teffs, suppress NK cell activity, interfere with monocyte differentiation, and promote Treg as well as MDSC expansion. Exosomes of microenvironment cells may also contribute to the development of drug resistance in cancer therapy. An important role of TEX in modulating the sensitivity of tumor cells to immunotherapy is a promising area of research to make the cancer therapy more successful. [ABSTRACT FROM AUTHOR]

Exosomes, the smallest vesicles (30–100 nm) among multivesicular bodies, are released by all body cells including tumor cells. The cargo they transfer plays an important role in intercellular communication. Tumor-derived exosomes (TEXs) maintain interactions between cancer cells and the microenvironment. Emerging evidence suggests that tumor cells release a large number of exosomes, which may not only influence proximal tumor cells and stromal cells in the local microenvironment but can also exert systemic effects as they are circulating in the blood. TEXs have been shown to boost tumor growth promote progression and metastatic spread via suppression or modification of the immune response towards cancer cells, regulation of tumor neo-angiogenesis, pre-metastatic niche formation, and therapy resistance. In addition, recent studies in patients with cancer suggest that TEXs could serve as tumor biomarker reflecting partially the genetic and molecular content of the parent cancer cell (i.e., as a so-called "liquid biopsy"). Furthermore, recent studies have demonstrated that exosomes may have immunotherapeutic applications, or can act as a drug delivery system for targeted therapies with drugs and biomolecules. [ABSTRACT FROM AUTHOR]

Receptor for advanced glycation end-products (RAGE) and toll-like receptors (TLRs) are the key factors indicating a danger to the organism. They recognize the microbial origin pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs). The primary response induced by PAMPs or DAMPs is inflammation. Excessive stimulation of the innate immune system occurs in arterial wall with the participation of effector cells. Persistent adaptive responses can also cause tissue damage and disease. However, inflammation mediated by the molecules innate responses is an important way in which the adaptive immune system protects us from infection. The specific detection of PAMPs and DAMPs by host receptors drives a cascade of signaling that converges at nuclear factor-κB (NF-κB) and interferon regulatory factors (IRFs) and induces the secretion of proinflammatory cytokines, type I interferon (IFN), and chemokines, which promote direct killing of the pathogen. Therefore, signaling of these receptors’ pathways also appear to present new avenue for the modulation of inflammatory responses and to serve as potential novel therapeutic targets for antiatherosclerotic therapy. [ABSTRACT FROM AUTHOR]

Toll-like receptors belong to the pattern recognition receptor (PRR) group, which plays a major role in maintaining a balance between the host immune system and the microbial invasion. They are key factors in the early, innate defense mechanisms of the immune system, which are manifested by the activation of classical and alternative inflammatory pathways. Excessive activity of these receptors has been shown to cause homeostasis disorders, so that the response of cells with these receptors must be strictly regulated to prevent any harmful effects of their abnormal activation. Thus, cellular responses mediated through TLR receptors have to be strictly regulated in order to prevent potentially harmful effects of their abnormal activation. There is an increasing evidence to suggest, that the Toll-like receptors can initiate and accelerate a development of atherosclerosis. Activation of these receptors leads to enhanced proinflammatory cytokine synthesis, promotes accumulation of foam cells in the aorta and migration of vascular smooth muscle cells from tunica to intima media. The major challenge for development of the TLR blocking drugs is to reduce inflammation without affecting the innate immunity of a body. Although preclinical studies confirm that they are promising therapeutic targets and potential biomarkers in the pathogenesis of atherosclerosis, however it is necessary to fully define their functions. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) play a key role in the pathogenesis of atherosclerosis. The main mechanisms which are involved are low-density lipoprotein oxidative modification, inactivation of nitric oxide and modulation of redox-sensitive signaling pathways. ROS contribute to several aspects of atherosclerosis including endothelial cell dysfunction, monocyte/macrophage recruitment and activation, stimulation of inflammation, and inducing smooth muscle cell migration and proliferation. NADPH oxidase is the main source of ROS in the vasculature. This enzyme consists of a membrane-bound heterodimer of gp91phox and p22phox, cytosolic regulatory subunits p47phox, p67phox and p40phox, and small GTP-binding proteins rac1 and rac 2. Seven distinct isoforms of this enzyme have been identified, of which four (NOX1, 2, 4 and 5) may have cardiovascular function. In this paper, we review the current state of knowledge concerning the role of oxidative stress and NOX enzymes in pathogenesis of atherosclerosis. Moreover, we analyze the experimental studies that explore the relationship between the NOX family and atherosclerosis. [ABSTRACT FROM AUTHOR]

Background Mycophenolate mofetil ( MMF) has beneficial effects in cardiac transplant patients beyond the suppression of tissue rejection. Moreover, mycophenolic acid ( MPA), its active metabolite, has been associated with positive effects on atherosclerosis in animal models. The attachment of leukocytes to the vascular endothelium and the subsequent migration of these cells into the vessel wall are early events in inflammation and atherosclerosis. The aim of this study was to investigate the effects of MPA on tumour necrosis-α ( TNF-α)-induced, endothelial cell proinflammatory responses and the underlying mechanisms. Methods and Results Human aortic endothelial cells ( HAECs) were treated with different concentrations (primarily 50 μM) of MPA before treatment with TNF-α. The surface protein and m RNA expressions of intercellular adhesion molecule-1 ( ICAM-1) and vascular cell adhesion molecule-1 ( VCAM-1) were determined by flow cytometry and real-time RT-PCR, respectively. Adhesion of leukocytes to TNF-α-treated HAECs was evaluated by an adhesion assay. Activation of mitogen-activated protein kinase ( MAPK) and nuclear factor-κB ( NF-κ B) was evaluated by measuring the levels of their phosphorylation using flow cytometry. NF-κ B p65 translocation was detected by Western blotting. The production of reactive oxygen species ( ROS) was determined by reduction in fluorescent 2′,7′-dichlorofluorescein diacetate ( H2 DCFH-DA). MPA significantly inhibits TNF-α-induced ICAM-1, VCAM-1 surface protein and m RNA expression as well as adhesion of mononuclear leukocytes to HAEC. ICAM-1 and VCAM-1 expressions were also reduced by antioxidants such as pyrrolidine dithiocarbamate, diphenylene iodonium and apocynin. MPA inhibited TNF-α-stimulated ROS generation similarly to apocynin. TNF-α increased ICAM-1 and VCAM-1 expression via c-Jun NH2-terminal kinase ( JNK), extracellular signal-regulated kinase ( ERK1/2) and p38 MAPK. MPA and apocynin inhibited TNF-α-induced phosphorylation of all three MAP kinases. Furthermore, TNF-α-induced NF-κB activation was attenuated by SP600125 (JNK inhibitor), PD98059 ( ERK1/2 inhibitor, SB203580 (p38 MAPK inhibitor) and MPA. MPA also inhibited TNF-α-induced nuclear translocation of NF-κB p65. Conclusion These results suggest that, in addition to the prevention of rejection, MPA may be a promising approach for the treatment of inflammatory vascular disease. [ABSTRACT FROM AUTHOR]

Intracellular signalling cascades, in which MAPK (mitogen-activated protein kinases) intermediate, are responsible for a biological response of a cell to an external stimulus. MAP kinases, which include ERK1/2 (extracellular signalling-regulated kinase), JNK (c-Jun N-terminal kinase) and p 38 MAPK, regulate the activity of many proteins, enzymes and transcription factors and thus have a wide spectrum of biological effects. Many basic scientific studies have defined numerous details of their pathway organization and activation. There are also more and more studies suggesting that individual MAP kinases probably play an important role in the pathogenesis of atherosclerosis. They may mediate inflammatory processes, endothelial cell activation, monocyte/macrophage recruitment and activation, smooth muscle cell proliferation and T-lymphocyte differentiation, all of which represent crucial mechanisms involved in pathogenesis of atherosclerosis. The specific inhibition of an activity of the respective MAP kinases may prove a new therapeutic approach to attenuate atherosclerotic plaque formation in the future. In this paper, we review the current state of knowledge concerning MAP kinase-dependent cellular and molecular mechanisms underlying atherosclerosis. [ABSTRACT FROM AUTHOR]

Simple Summary: Most prostate cancers are initially hormone-dependent but later gain a hormone-independent phenotype associated with changes in lipid metabolism, including enhanced absorption of extracellular fatty acids. The aim of our study was to assess the effect of ciprofloxacin conjugates with fatty acids on different type of prostate cancer (LNCaP and DU-145) and normal (RWPE-1) cells, as well as their influence on cell lipid metabolism by proteomic analysis. All tested conjugates exhibited cytotoxic potential, the most powerful for oleic, elaidic and docosahexaenoic acids. The hormone-independent DU145 line was more sensitive to derivatives than the hormone-dependent LNCaP line. These results are consistent with previously observed pronounced cytotoxic effect of conjugates on a hormone-insensitive PC3 line. Tested derivatives decreased intensity of proteins involved in prostate cancer lipid metabolism. Our findings confirm the involvement of lipid metabolism in prostate carcinogenesis indicating a target for fatty acids as drug carriers. Purpose: To assess cytotoxic effect of ciprofloxacin conjugates with fatty acids on prostate cancer cells (LNCaP and DU-145) with different hormone sensitivity, based on previous promising results from the PC3 cells. Methods: Cytotoxicity were estimated using MTT and LDH tests, whereas its mechanisms were estimated by apoptosis and IL-6 assays. The intensity of proteins involved in lipid metabolism was determined using ML-CS assay. Results: The hormone insensitive DU-145 cells were more vulnerable than the hormone sensitive LNCaP cells. The IC50 values for oleic (4), elaidic (5) and docosahexaenoic acid (8) conjugates were 20.2 µM, 17.8 µM and 16.5 µM, respectively, in DU-145 cells, whereas in LNCaP cells IC50 exceeded 20 µM. The strong conjugate cytotoxicity was confirmed in the LDH test, the highest (70.8%) for compound (5) and 64.2% for compound (8) in DU-145 cells. This effect was weaker for LNCaP cells (around 60%). The cytotoxic effect of unconjugated ciprofloxacin and fatty acids was weaker. The early apoptosis was predominant in LNCaP while in DU-145 cells both early and late apoptosis was induced. The tested conjugates decreased IL-6 release in both cancer cell lines by almost 50%. Proteomic analysis indicated influence of the ciprofloxacin conjugates on lipid metabolic proteins in prostatic cancer. Conclusion: Our findings suggested the cytotoxic potential of ciprofloxacin conjugates with reduction in proteins involved in prostate cancer progress. [ABSTRACT FROM AUTHOR]

A chronic inflammatory process characteristic of obstructive sleep apnea promotes vascular endothelial dysfunction and atherogenesis. This process can lead to destabilization and rupture of cardiovascular plaques, which clinically manifests as an acute coronary syndrome or stroke. The aim of this study was to investigate the inflammatory pathway leading to plaque destabilization in non-to-mild and moderate-to-severe groups of OSA patients. This prospective study involved enrollment of patients scheduled for endarterectomy. A sleep study was performed prior to surgery. Immunohistochemistry was performed on atherosclerotic plaques from carotid arteries obtained during standard open endarterectomy to determine levels of CD40, CD40L receptors, MCP-1, and MMP-9. The 46 patients included 14 controls, 13 with mild, 11 with moderate, and 8 with severe OSA. Increased expression of CD40, CD40L receptors, MCP-1, and MMP-9 were found to be proportionate with OSA severity. However, significant differences among groups were observed only for MCP-1 (p = 0.014). Increased expression of inflammatory markers (CD40, CD40L, MCP-1, MMP-9) is associated with increasing OSA severity. This suggests the CD40-CD4-L inflammatory pathway may contribute to plaque instability and rupture in OSA patients. [ABSTRACT FROM AUTHOR]

Twelve novel derivatives of N-(furan-2-ylmethyl)-1H-tetrazol-5-amine were synthesized. For obtained compound 8, its corresponding substrate single crystals were isolated and X-ray diffraction experiments were completed. In the initial stage of research, in silico structure-based pharmacological prediction was conducted. All compounds were screened for their antibacterial and antimycobacterial activities using standard and clinical strains. The cytotoxic activity was evaluated against a panel of human cancer cell lines, in contrast to normal (HaCaT) cell lines, by using the MTT method. All examined derivatives were found to be noncytotoxic against normal cell lines. Within the studied group, compound 6 showed the most promising results in antimicrobial studies. It inhibited four hospital S. epidermidis rods' growth, when applied at the amount of 4 µg/mL. However, the most susceptible to the presence of compound 6 was S. epidermidis T 5501 851/19 clinical strain, for which the MIC value was only 2 µg/mL. Finally, a pharmacophore model was established based on lead compounds from this and our previous work. [ABSTRACT FROM AUTHOR]

Simple Summary: Precise and personalized radiology and nuclear medicine are in need of a new, biological contrast media and radionuclide. This inventive strategy is progressing due to the developing of contrast agents and radionuclides based on exosomes. The compatibility of exosomes with existing imaging modalities can accelerate incorporating these methods into clinical practice. Besides, a new generation of contrast media and radionuclides based on exosomes provides an opportunity to develop novel approaches in cancer diagnosis. Moreover, exosome-based diagnostic and therapeutic applications can open a new field in radiological departments called theranostics, combining simultaneous cancer diagnosis and therapy. An appropriate combination of biomarkers and imaging technologies will become standard practice in the future. Because the incidence of and mortality from cancers is rising, the further study of new approaches for the early detection and precise characterization of tumors is essential. Extracellular vesicles (EVs), including exosomes, prove to have great potential when it comes to diagnosis and targeted therapy. Due to their natural ability to pass through biological barriers, depending on their origin, EVs can accumulate at defined sites, including tumors, preferentially. This manuscript discusses the difficulties and simplicities of processing cell-derived materials, packaging diverse groups of agents in EVs, and activating the biological complex. Developing exosome-based diagnostic techniques to detect disease precisely and early as well as treat disease marks a new era of personalized radiology and nuclear medicine. As circulating drug delivery vehicles for novel therapeutic modalities, EVs offer a new platform for cancer theranostic. [ABSTRACT FROM AUTHOR]

Angiogenesis is the process through which new blood vessels are formed from pre-existing ones. Exosomes are involved in angiogenesis in cancer progression by transporting numerous pro-angiogenic biomolecules like vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMPs), and microRNAs. Exosomes promote angiogenesis by suppressing expression of factor-inhibiting hypoxia-inducible factor 1 (HIF-1). Uptake of tumor-derived exosomes (TEX) by normal endothelial cells activates angiogenic signaling pathways in endothelial cells and stimulates new vessel formation. TEX-driven cross-talk of mesenchymal stem cells (MSCs) with immune cells blocks their anti-tumor activity. Effective inhibition of tumor angiogenesis may arrest tumor progression. Bevacizumab, a VEGF-specific antibody, was the first antiangiogenic agent to enter the clinic. The most important clinical problem associated with cancer therapy using VEGF- or VEFGR-targeting agents is drug resistance. Combined strategies based on angiogenesis inhibitors and immunotherapy effectively enhances therapies in various cancers, but effective treatment requires further research. [ABSTRACT FROM AUTHOR]

Seven novel derivatives of bis(2-aminoethyl)amine were synthesized. For compounds 1 and 7 single crystals were isolated and X-ray diffraction experiments were done. Lipophilicity and drug likeness were calculated in the initial stage of research. All compounds were screened for their in vitro cytotoxic activity against a panel of human cancer cell lines, which is contrary to normal (HaCaT) cell lines, by using the MTT method. Studies were followed by lactate dehydrogenase assay, apoptotic activity, and interleukin-6 assay. Within the studied group, compound 6 showed the most promising results in all biological studies. The strongest influence in A549 cells was denoted for derivative 4, which inhibited interleukin release almost tenfold, as compared to the control. [ABSTRACT FROM AUTHOR]

Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases responsible for tissue remodeling and degradation of extracellular matrix (ECM) proteins. MMPs may modulate various cellular and signaling pathways in atherosclerosis responsible for progression and rupture of atherosclerotic plaques. The effect of MMPs polymorphisms and the expression of MMPs in both the atherosclerotic plaque and plasma was shown. They are independent predictors of atherosclerotic plaque instability in stable coronary heart disease (CHD) patients. Increased levels of MMPs in patients with advanced cardiovascular disease (CAD) and acute coronary syndrome (ACS) was associated with future risk of cardiovascular events. These data confirm that MMPs may be biomarkers in plaque instability as they target in potential drug therapies for atherosclerosis. They provide important prognostic information, independent of traditional risk factors, and may turn out to be useful in improving risk stratification. [ABSTRACT FROM AUTHOR]

The tumor microenvironment (TME) is a complex system composed of multiple cells, such as non-cancerous fibroblasts, adipocytes, immune and vascular cells, as well as signal molecules and mediators. Tumor cells recruit and reprogram other cells to produce factors that maintain tumor growth. Communication between cancerous and surrounding cells is a two-way process and engages a diverse range of mechanisms that, in consequence, can lead to rapid proliferation, metastasis, and drug resistance, or can serve as a tumors-suppressor, e.g., through tumor–immune cell interaction. Cross-talk within the cancer microenvironment can be direct by cell-to-cell contact via adhesion molecules, electrical coupling, and passage through gap junctions, or indirect through classical paracrine signaling by cytokines, growth factors, and extracellular vesicles. Therapeutic approaches for modulation of cell-cell communication may be a promising strategy to combat tumors. In particular, integrative approaches targeting tumor communication in combination with conventional chemotherapy seem reasonable. Currently, special attention is paid to suppressing the formation of open-ended channels as well as blocking exosome production or ablating their cargos. However, many aspects of cell-to-cell communication have yet to be clarified, and, in particular, more work is needed in regard to mechanisms of bidirectional signal transfer. Finally, it seems that some interactions in TEM can be not only cancer-specific, but also patient-specific, and their recognition would help to predict patient response to therapy. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is the second most common cause of cancer-related mortality among men in the developed world. Conventional anti-PCa therapies are not effective for patients with advanced and/or metastatic disease. In most cases, cancer therapies fail due to an incomplete depletion of tumor cells, resulting in tumor relapse. Exosomes are involved in tumor progression, promoting the angiogenesis and migration of tumor cells during metastasis. These structures contribute to the dissemination of pathogenic agents through interaction with recipient cells. Exosomes may deliver molecules that are able to induce the transdifferentiation process, known as "epithelial to mesenchymal transition". The composition of exosomes and the associated possibilities of interacting with cells make exosomes multifaceted regulators of cancer development. Extracellular vesicles have biophysical properties, such as stability, biocompatibility, permeability, low toxicity and low immunogenicity, which are key for the successful development of an innovative drug delivery system. They have an enhanced circulation stability and bio-barrier permeation ability, and they can therefore be used as effective chemotherapeutic carriers to improve the regulation of target tissues and organs. Exosomes have the capacity to deliver different types of cargo and to target specific cells. Chemotherapeutics, natural products and RNA have been encapsulated for the treatment of prostate cancers. [ABSTRACT FROM AUTHOR]

Enhanced DNA damage and disturbances in DNA repair mechanisms are reported to be involved in the pathogenesis of chronic diseases like obesity, atherosclerosis, metabolic syndrome, diabetes, and cancer. The aim of the present study was to evaluate whether anthropometric factors and dietary habits are related to endogenous DNA damage. One hundred and fourteen premenopausal, apparently healthy women were included in the study: 88 obese individuals and 26 controls. The comet assay was used to measure basal DNA damage. Biochemical measurements included lipids, apolipoproteinAI, fasting insulin, glucose, and C-reactive protein high sensitivity (CRP-hs). Dietary intakes were assessed by 3-day food records. The mean level of DNA damage was almost two times higher in obese than in non-obese women (p < 0.001). Regression modeling showed that body mass index (BMI), daily intakes of energy, and vitamin C are key predictors of variance in basal DNA damage. Our data demonstrate the impact of obesity-associated inflammation on DNA damage and indicate that regardless of obesity, the level of DNA damage can be reduced by adequate intakes of vitamins C and E. It suggests that particular attention should be paid to the content of antioxidants in the diet of obese people and further studies are needed to modify dietary guidelines to prevent DNA damage in obese individuals. [ABSTRACT FROM AUTHOR]

Thirty new derivatives of palmitic acid were efficiently synthesized. All obtained compounds can be divided into three groups of derivatives: Thiosemicarbazides (compounds 1–10), 1,2,4-triazoles (compounds 1a–10a) and 1,3,4-thiadiazoles (compounds 1b–10b) moieties. 1H-NMR, 13C-NMR and MS methods were used to confirm the structure of derivatives. All obtained compounds were tested in vitro against a number of microorganisms, including Gram-positive cocci, Gram-negative rods and Candida albicans. Compounds 4, 5, 6, 8 showed significant inhibition against C. albicans. The range of MIC values was 50–1.56 μg/mL. The halogen atom, especially at the 3rd position of the phenyl group was significantly important for antifungal activity. The biological activity against Candida albicans and selected molecular descriptors were used as a basis for QSAR models, that have been determined by means of multiple linear regression. The models have been validated by means of the Leave-One-Out Cross Validation. The obtained QSAR models were characterized by high determination coefficients and good prediction power. [ABSTRACT FROM AUTHOR]