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The incorporation of hydrophobic drugs into liposomes improve their bioavailability and leads to increased stability and anticancer activity, along with decreased drug toxicity. Curcumin (Cur) is a natural polyphenol compound with a potent anticancer activity in pancreatic adenocarcinoma (PA). In the present study, different types of Cur-loaded liposomal formulations were prepared and characterized in terms of size, shape, zeta potential, optimal drug-to-lipid ratio and stability at 4°C, 37°C; and in human plasma in vitro. The best formulation in terms of these parameters was PEGylated, cholesterol-free formulation based upon hydrogenated soya PC (HSPC:DSPE-PEG2000:Cur, termed H5), which had a 0.05/10 molar ratio of drug-to-lipid, was found to be stable and had a 96% Cur incorporation efficiency. All Cur-loaded liposomal formulations had potent anticancer activity on the PA cancer cell lines AsPC-1 and BxPC-3, and were less toxic to a normal cell line (NHDF). Furthermore, apoptosis-induction induced by Cur in PA cells was associated with morphological changes including cell shrinkage, cytoplasmic blebbing, irregularity in shape and the externalization of cell membrane phosphatidylserine, which was preceded by an increase in intracellular reactive oxygen species (ROS) generation and caspase 3/7 activation. Because the liposomal formulations tested here, especially the H5 variant which exhibited slow release of the Cur in the human plasma test, the formulation may be stable enough to facilitate the accumulation of pharmacologically active amounts of Cur in target cancer tissue by EPR. Therefore, our formulations could serve as a promising therapeutic approach for pancreatic cancer and other cancers.

The nursing profession entails many stressful situations and challenges, such as heavy workload, shift work, emotional demands and professional conflicts. In the light of the results of the research conducted so far, flexible coping has occurred to be highly adaptive, as its association with adaptive struggle with the disease, fewer depressive symptoms and both greater mental well-being and better health have been proven. In connection with the above, the aim of this study was to determine the nature of the relationship between cognitive flexibility and flexibility in coping in nurses, taking into account the moderating role of age of the respondents, seniority and the sense of stress. The study sample consisted of 280 persons working as nurses (age range: 21-66). The number of women and men reflected their percentage distribution in this profession, as it is highly feminized. The following methods were used in the study: the (CFI) by Dennis and Vander Wal, the (PSS-10) by Cohen et al., the (FCSQ-14) by Basińska et al., and a self-developed survey. As the obtained research results show, cognitive flexibility in both the Control and Alternatives subscales was a predictor of flexible coping and their subscales. The analysis revealed that the model of the relationship between cognitive flexibility and flexibility in coping was moderated by age, seniority and the sense of stress. Coping skills and flexibility are positively correlated with the psychological adjustment of nurses. Int J Occup Med Environ Health. 2020;33(4):507-21.

Intensive crop production leads to the disruption of the symbiosis between plants and their associated microorganisms, resulting in suboptimal plant productivity and lower yield quality. Therefore, it is necessary to improve existing methods and explore modern, environmentally friendly approaches to crop production. One of these methods is biotization, which involves the inoculation of plants with appropriately selected symbiotic microorganisms which play a beneficial role in plant adaptation to the environment. In this study, we tested the possibility of using a multi-microorganismal inoculum composed of arbuscular mycorrhizal fungi (AMF) and AMF spore-associated bacteria for biotization of the red raspberry. Bacteria were isolated from the spores of AMF, and their plant growth-promoting properties were tested. AMF inocula were supplemented with selected bacterial strains to investigate their effect on the growth and vitality of the raspberry. The investigations were carried out in the laboratory and on a semi-industrial scale in a polytunnel where commercial production of seedlings is carried out. In the semi-industrial experiment, we tested the growth parameters of plants and physiological response of the plant to temporary water shortage. We isolated over fifty strains of bacteria associated with spores of AMF. Only part of them showed plant growth-promoting properties, and six of these (belonging to the Paenibacillus genus) were used for the inoculum. AMF inoculation and co-inoculation of AMF and bacteria isolated from AMF spores improved plant growth and vitality in both experimental setups. Plant dry weight was improved by 70%, and selected chlorophyll fluorescence parameters (the contribution of light to primary photochemistry and fraction of reaction centre chlorophyll per chlorophyll of the antennae) were increased. The inoculum improved carbon assimilation, photosynthetic rate, stomatal conductance and transpiration after temporary water shortage. Raspberry biotization with AMF and bacteria associated with spores has potential applications in horticulture where ecological methods based on plant microorganism interaction are in demand.

(1) Background: Epigallocatechin gallate (EGCG) has been recognized as a flavonoid showing antiviral activity against various types of DNA and RNA viruses. In this work, we tested if EGCG-modified silver nanoparticles (EGCG-AgNPs) can become novel microbicides with additional adjuvant properties to treat herpes infections. (2) Methods: The anti-HSV and cytotoxic activities of EGCG-AgNPs were tested in human HaCaT and VK-2-E6/E7 keratinocytes. HSV-1/2 titers and immune responses after treatment with EGCG-AgNPs were tested in murine models of intranasal HSV-1 infection and genital HSV-2 infection. (3) Results: EGCG-AgNPs inhibited attachment and entry of HSV-1 and HSV-2 in human HaCaT and VK-2-E6/E7 keratinocytes much better than EGCG at the same concentration. Infected mice treated intranasally (HSV-1) or intravaginally (HSV-2) with EGCG-AgNPs showed lower virus titers in comparison to treatment with EGCG alone. After EGCG-AgNPs treatment, mucosal tissues showed a significant infiltration in dendritic cells and monocytes in comparison to NaCl-treated group, followed by significantly better infiltration of CD8+ T cells, NK cells and increased expression of IFN-α, IFN-γ, CXCL9 and CXCL10. (4) Conclusions: Our findings show that EGCG-AgNPs can become an effective novel antiviral microbicide with adjuvant properties to be applied upon the mucosal tissues.

Many studies have shown an association between herpes simplex virus type 1 (HSV-1) infection and the development of neurodegeneration processes later in life, such as Alzheimer's disease. The Fas/FasL death pathway plays an important role in the complex regulation of the local inflammatory response and mounting of the specific antiviral response in HSV-1 infection. Here, we applied a mouse model of latent HSV-1 neuroinfection to Fas- and FasL-deficient mice (lpr and gld) to explore whether the lack of functional Fas/FasL pathway protects from inflammation-related neurodegeneration. The latently infected Fas- and FasL-deficient mice (lpr and gld) were not protected from virus replication despite the accumulation of virus-specific cytotoxic T cells. However, the lack of Fas/FasL pathway decreased neuroinflammation- and neurodegeneration-related markers, including cognitive impairment, amyloid-β protein, and tau hyperphosphorylation. The use of a glucocorticoid, dexamethasone, to decrease neuroinflammation in wild-type mice did not protect from cognitive impairment, despite the improved antiviral response. Our data indicate that excessive neuroinflammation via the Fas/FasL pathway during HSV-1 infection is associated with neurodegeneration. Furthermore, the administration of immunomodulatory agents to ameliorate the outcome of HSV-1 latent infection should be restricted to the peak of neuroinflammation.

Herpes simplex virus type 2 (HSV-2) is a sexually transmitted pathogen that causes a persistent infection in sensory ganglia. The infection manifests itself as genital herpes but in rare cases it can cause meningitis. In this study, we used a murine model of HSV-2 meningitis to show that Fas and FasL are induced within the CNS upon HSV-2 infection, both on resident microglia and astrocytes and on infiltrating monocytes and lymphocytes. Mice lacking Fas or FasL had a more severe disease development with significantly higher morbidity, mortality, and an overall higher CNS viral load. In parallel, these Fas/FasL-deficient mice showed a severely impaired infection-induced CNS inflammatory response with lower levels of infiltrating CD4+ T-cells, lower levels of Th1 cytokines and chemokines, and a shift in the balance between M1 and M2 microglia/monocytes. In vitro, we confirmed that Fas and FasL is required for the induction of leucocyte apoptosis, but also show that the Fas/FasL pathway is required for adequate cytokine and chemokine production by glial cells. In summary, our data show that the Fas/FasL cell death receptor pathway is an important defense mechanism in the spinal cord as it down-regulates HSV-2-induced inflammation while at the same time promoting adequate anti-viral immune responses against infection.

Lactoferrin is an iron-binding glycoprotein with multiple functions in the body. Its activity against a broad spectrum of both DNA and RNA viruses as well as the ability to modulate immune responses have made it of interest in the pharmaceutical and food industries. The mechanisms of its antiviral activity include direct binding to the viruses or its receptors or the upregulation of antiviral responses by the immune system. Recently, much effort has been devoted to the use of nanotechnology in the development of new antivirals. In this review, we focus on describing the antiviral mechanisms of lactoferrin and the possible use of nanotechnology to construct safe and effective new antiviral drugs.

(1) Background: Lactoferrin has been recognized as a potent inhibitor of human herpetic viruses, such as herpes simplex type 1 (HSV-1) and 2 (HSV-2). In this work, we tested if silver and gold nanoparticles modified with lactoferrin (LF-Ag/AuNPs) can become novel microbicides with additional adjuvant properties to treat genital herpes infection. (2) Methods: The antiviral and cytotoxic activities of LF-Ag/AuNPs were tested in human skin HaCaT and vaginal VK-2-E6/E7 keratinocytes. Viral titers and immune responses after treatment with LF-Ag/AuNPs were tested in murine vaginal HSV-2 infection. (3) Results: LF-Ag/AuNPs inhibited attachment and entry of HSV-2 in human keratinocytes much better than lactoferrin. Furthermore, pretreatment with LF-AgNPs led to protection from infection. Infected mice treated intravaginally with LF-Ag/AuNPs showed lower virus titers in the vaginal tissues and spinal cords in comparison to treatment with lactoferrin. Following treatment, vaginal tissues showed a significant increase in CD8+/granzyme B + T cells, NK cells and dendritic cells in comparison to NaCl-treated group. LF-Ag/AuNPs-treated animals also showed significantly better expression of IFN-γ, CXCL9, CXCL10, and IL-1β in the vaginal tissues. (4) Conclusions: Our findings show that LF-Ag/AuNPs could become effective novel antiviral microbicides with immune-stimulant properties to be applied upon the mucosal tissues.

Herpes simplex virus-1 (HSV-1) is a neurotropic virus that can infect the brain, and an uncontrolled infection can lead to severe encephalitis. NO can exert both antiviral as well as cytotoxic effects in the central nervous system (CNS) depending on its concentration and site of infection. In this study, we report that treatment of an intranasal murine HSV-1 infection with aminoguanidine (AMG) decreases both neuroinflammation and neurodegeneration markers, but its positive effect depends on the time of treatment. Specifically, early treatment with AMG impaired the activation of microglia/monocytes, leading to decreased virus-specific antiviral response and higher viral titers in the brain. However, AMG treatment during the peak of brain infection significantly improved antiviral response, reduced inflammation and improved general clinical score. We also found that treatment with AMG decreased beta amyloid levels during both primary and latent infections and protected from the accumulation of phosphorylated Tau protein during early infection. Our findings position inducible nitric oxide synthetase (iNOS) as a potential therapeutic target for mitigating virus-induced neuroinflammation and neurodegeneration.

Background The results of numerous studies indicate that the nurse profession is burdened with an increased risk of feeling stressed and experiencing professional burnout. Effective coping with stress can protect against professional burnout as well as impact on patient care. These effects may be influenced, e.g., by personality traits. By the study, the authors decided to check whether personality traits such as empathy, impulsiveness and venturesomeness would play a predictive role for flexibility in coping with stress. Material and Methods By the study, the authors analyzed the results obtained from 137 nurses. The following research tools were used: the Impulsiveness-Venturesomeness-Empathy Questionnaire by Eysenck and Eysenck, in the Polish adaptation by Aleksandra Jaworowska, and the Flexibility in Coping with Stress Questionnaire (FCSQ-14) by Małgorzata Basińska et al. Both tools were characterized by satisfactory statistical properties. By addition, the respondents completed a personal survey which allowed collecting basic personal data. Results Venturesomeness positively correlated with flexibility in coping with stress and all its dimensions (strategy repertoire, strategy variability and reflexivity) at the low level. Similar dependencies for empathy and impulsiveness were not shown. Similarly, in assessing the predictive role of selected personality traits for flexibility in coping with stress, only venturesomeness turned out to be an important predictor. Although the model turned out to be statistically significant, it allowed explaining the variability of flexibility only in 7%. Conclusions There was a low statistically significant relationship between the nurses’ venturesomeness and their flexibility in coping with stress. Empathy and impulsiveness did not play a predictive role for flexibility in coping with stress. Med Pr. 2020;71(4):451–9