A Novel Mechanism of Macrophage Activation by the Natural Yolkin Polypeptide Complex from Egg Yolk

Ageing is accompanied by the inevitable changes in the function of the immune system. It provides increased susceptibility to chronic infections that have a negative impact on the quality of life of older people. Therefore, rejuvenating the aged immunity has become an important research and therapeutic goal. Yolkin, a polypeptide complex isolated from hen egg yolks, possesses immunoregulatory and neuroprotective activity. Considering that macrophages play a key role in pathogen recognition and antigen presentation, we evaluated the impact of yolkin on the phenotype and function of mouse bone marrow-derived macrophages of the BMDM cell line. We determined yolkin bioavailability and the surface co-expression of CD80/CD86 using flow cytometry and IL-6, IL-10, TGF-β and iNOS mRNA expression via real-time PCR. Additionally, the impact of yolkin on the regulation of cytokine expression by MAPK and PI3K/Akt kinases was determined. The stimulation of cells with yolkin induced significant changes in cell morphology and an increase in CD80/CD86 expression. Using pharmaceutical inhibitors of ERK, JNK and PI3K/Akt, we have shown that yolkin is able to activate these kinases to control cytokine mRNA expression. Our results suggest that yolkin is a good regulator of macrophage activity, priming mainly the M1 phenotype. Therefore, it is believed that yolkin possesses significant therapeutic potential and represents a promising possibility for the development of novel immunomodulatory medicine.     

Antitumor Activity against A549 Cancer Cells of Three Novel Complexes Supported by Coating with Silver Nanoparticles

A novel biologically active organic ligand L (N’-benzylidenepyrazine-2-carbohydrazonamide) and its three coordination compounds have been synthesized and structurally described. Their physicochemical and biological properties have been thoroughly studied. Cu(II), Zn(II), and Cd(II) complexes have been analyzed by F-AAS spectrometry and elemental analysis. The way of metal–ligand coordination was discussed based on FTIR spectroscopy and UV-VIS-NIR spectrophotometry. The thermal behavior of investigated compounds was studied in the temperature range 25–800 °C. All compounds are stable at room temperature. The complexes decompose in several stages. Magnetic studies revealed strong antiferromagnetic interaction. Their cytotoxic activity against A549 lung cancer cells have been studied with promising results. We have also investigated the biological effect of coating studied complexes with silver nanoparticles. The morphology of the surface was studied using SEM imaging.     

Protein-Mediated Transformations of Superparamagnetic Nanoparticles Evidenced by Single-Particle Inductively Coupled Plasma Tandem Mass Spectrometry: A Disaggregation Phenomenon

Progress toward translating superparamagnetic iron oxide nanoparticles (SPIONs) with specific diagnostic and therapeutic properties for clinical applications depends on developing and implementing appropriate methodologies that would allow in-depth characterizations of their behavior in a real biological environment. Herein, we report a versatile approach for studying interactions between SPIONs and proteins using single-particle inductively coupled plasma tandem mass spectrometry. By monitoring the changes in the size distribution upon exposure to human serum, the formation of stable protein corona is revealed, accompanied by particle disaggregation.     

Synthesis and In Vitro Activity of Novel Melphalan Analogs in Hematological Malignancy Cells

Despite the continuous developments in pharmacology and the high therapeutic effect of new treatment options for patients with hematological malignancies, these diseases remain a major health issue. Our study aimed to synthesize, analyze in silico, and determine the biological properties of new melphalan derivatives. We obtained three methyl esters of melphalan having in their structures amidine moieties substituted with thiomorpholine (EM–T–MEL), indoline (EM–I–MEL), or 4-(4-morpholinyl) piperidine (EM–MORPIP–MEL). These have not yet been described in the literature. The in vitro anticancer properties of the analogs were determined against THP1, HL60, and RPMI8226 cells. Melphalan derivatives were evaluated for cytotoxicity (resazurin viability assay), genotoxicity (alkaline comet assay), and their ability to induce apoptosis (Hoechst33342/propidium iodide double staining method; phosphatidylserine translocation; and caspase 3/7, 8, and 9 activity measurements). Changes in mitochondrial membrane potential were examined using the specific fluorescence probe JC–1 (5,5′,6,6′-tetrachloro-1,1′,3,3′–tetraethylbenzimidazol carbocyanine). The EM–T–MEL derivative had the highest biological activity, showing higher cytotoxic and genotoxic properties than the parent drug. Moreover, it showed a high ability to induce apoptosis in the tested cancer cells. This compound also had a beneficial effect in peripheral blood mononuclear cells (PBMC). In conclusion, we verified and confirmed the hypothesis that chemical modifications of the melphalan structure improved its anticancer properties. The conducted study allowed the selection of the compound with the highest biological activity and provided a basis for chemical structure-biological activity analyses.     

Gold Nanopeanuts as Prospective Support for Cisplatin in Glioblastoma Nano-Chemo-Radiotherapy

Herein, we propose newly designed and synthesized gold nanopeanuts (Au NPes) as supports for cisplatin (cPt) immobilization, dedicated to combined glioblastoma nano-chemo-radiotherapy. Au NPes offer a large active surface, which can be used for drugs immobilization. Transmission electron microscopy (TEM) revealed that the size of the synthesized Au NPes along the longitudinal axis is ~60 nm, while along the transverse axis ~20 nm. Raman, thermogravimetric analysis (TGA) and differential scanning calorimetry (DCS) measurements showed, that the created nanosystem is stable up to a temperature of 110 °C. MTT assay revealed, that the highest cell mortality was observed for cell lines subjected to nano-chemo-radiotherapy (20–55%). Hence, Au NPes with immobilized cPt (cPt@AuNPes) are a promising nanosystem to improve the therapeutic efficiency of combined nano-chemo-radiotherapy.     

Glutathione Modulation in PVYNTN Susceptible and Resistant Potato Plant Interactions

Glutathione is a metabolite that plays an important role in plant response to biotic stress through its ability to remove reactive oxygen species, thereby limiting the degree of potential oxidative damage. It can couple changes in the intracellular redox state to the development, especially the defense responses, of plants. Several studies have focused on measuring glutathione levels in virus infected plants, but have not provided complete information. Therefore, we analyzed, for the first time, the content of glutathione as well as its ultrastructural distribution related to susceptible and hypersensitive potato–Potato virus Y NTN (PVY^NTN) interaction, with an aim of providing new insight into interactive responses to PVY^NTN stress. Our findings reported that the inoculation of PVY^NTN caused a dynamic increase in the content of glutathione, not only in resistance but also in susceptible reaction, especially at the first steps of plant–virus interaction. Moreover, the increase in hypersensitive response was much more dynamic, and accompanied by a significant reduction in the content of PVY^NTN. By contrast, in susceptible potato Irys, the content of glutathione decreased between 7 and 21 days after virus inoculation, which led to a significant increase in PVY^NTN concentration. Additionally, our findings clearly indicated the steady induction of two selected potato glutathione S-transferase StGSTF1 and StGSTF2 genes after PVY^NTN inoculation, regardless of the interaction type. However, the relative expression level of StGSTF1 did not significantly differ between resistant and susceptible plants, whereas the relative expression levels of StGSTF2 differed between susceptible and resistant reactions. Therefore, we proposed that StGSTF2 can act as a marker of the type of response to PVY^NTN. Our observations indicated that glutathione is an important component of signaling as well as the regulatory network in the PVY^NTN–potato pathosystem. In resistance responses to PVY^NTN, this metabolite activates plant defenses by reducing potential damage to the host plant cell, causing a reduction in virus concentration, while it can also be involved in the development of PVY^NTN elicited symptoms, as well as limiting oxidative stress, leading to systemic infection in susceptible potato plants.     

Melatonin Protects Tobacco Suspension Cells against Pb-Induced Mitochondrial Dysfunction

Recent studies have shown that melatonin is an important molecule in plant physiology. It seems that the most important is that melatonin effectively eliminates oxidative stress (direct and indirect antioxidant) and switches on different defence strategies (preventive and interventive actions) during environmental stresses. In the presented report, exogenous melatonin potential to protect Nicotiana tabacum L. line Bright Yellow 2 (BY-2) exposed to lead against death was examined. Analyses of cell proliferation and viability, the level of intracellular calcium, changes in mitochondrial membrane potential (ΔΨm) as well as possible translocation of cytochrome c from mitochondria to cytosol and subsequent caspase-like proteolytic activity were conducted. Our results indicate that pretreatment BY-2 with melatonin protected tobacco cells against mitochondrial dysfunction and caspase-like activation caused by lead. The findings suggest the possible role of this indoleamine in the molecular mechanism of mitochondria, safeguarding against potential collapse and cytochrome c release. Thus, it seems that applied melatonin acted as an effective factor, promoting survival and increasing plant tolerance to lead.     

Apoptosis in Type 2 Diabetes: Can It Be Prevented? Hippo Pathway Prospects

Diabetes mellitus is a heterogeneous disease of complex etiology and pathogenesis. Hyperglycemia leads to many serious complications, but also directly initiates the process of β cell apoptosis. A potential strategy for the preservation of pancreatic β cells in diabetes may be to inhibit the implementation of pro-apoptotic pathways or to enhance the action of pancreatic protective factors. The Hippo signaling pathway is proposed and selected as a target to manipulate the activity of its core proteins in therapy-basic research. MST1 and LATS2, as major upstream signaling kinases of the Hippo pathway, are considered as target candidates for pharmacologically induced tissue regeneration and inhibition of apoptosis. Manipulating the activity of components of the Hippo pathway offers a wide range of possibilities, and thus is a potential tool in the treatment of diabetes and the regeneration of β cells. Therefore, it is important to fully understand the processes involved in apoptosis in diabetic states and completely characterize the role of this pathway in diabetes. Therapy consisting of slowing down or stopping the mechanisms of apoptosis may be an important direction of diabetes treatment in the future.     

Synthetic Retinoids as Potential Therapeutics in Prostate Cancer—An Update of the Last Decade of Research: A Review

Prostate cancer (PC) is the second most common tumor in males. The search for appropriate therapeutic options against advanced PC has been in process for several decades. Especially after cessation of the effectiveness of hormonal therapy (i.e., emergence of castration-resistant PC), PC management options have become scarce and the prognosis is poor. To overcome this stage of disease, an array of natural and synthetic substances underwent investigation. An interesting and promising class of compounds constitutes the derivatives of natural retinoids. Synthesized on the basis of the structure of retinoic acid, they present unique and remarkable properties that warrant their investigation as antitumor drugs. However, there is no up-to-date compilation that consecutively summarizes the current state of knowledge about synthetic retinoids with regard to PC. Therefore, in this review, we present the results of the experimental studies on synthetic retinoids conducted within the last decade. Our primary aim is to highlight the molecular targets of these compounds and to identify their potential promise in the treatment of PC.