Antimikrobno djelovanje derivata 3-hidroksi-2-metilen-3-fenilpropionske kiseline

Twenty Baylis-Hillman adducts were synthesized from different aromatic aldehydes and activated vinyl derivatives. The adducts, which are differently substituted 3-hydroxy-2-methylene-3-phenylpropionic acid derivatives, were screened for their antimicrobial activity in vitro by the serial dilution method. Many of these molecules displayed potent antibacterial and antifungal activities. The ease of synthesis from low-cost starting materials along with potent antimicrobial activity of these molecules provide the lead for further improvement of activity and reflect the possibility of therapeutic use.Iz različitih aromatskih aldehida i aktiviranih vinil derivata sintetizirano je dvadeset Baylis-Hillmanovih adukata, različito supstituiranih derivata 3-hidroksi-2-metilen-3-fenilpropionske kiseline. Ispitano je njihovo antimikrobno djelovanje in vitro metodom serijskih razrjeđenja. Većina ispitivanih spojeva pokazala je snažno antibakterijsko i antifungalno djelovanje. Jednostavni sintetski postupak iz jeftinih sirovina i snažno antimikrobno djelovanje pružaju vodeće spojeve za daljnju modifikaciju, koji mogu dovesti do ljekovitih tvari pogodnih za terapijsku primjenu

MicroRNA-Enriched Exosomes from Different Sources of Mesenchymal Stem Cells Can Differentially Modulate Functions of Immune Cells and Neurogenesis

Adult Mesenchymal stem cells-derived exosomes carry several biologically active molecules that play prominent roles in controlling disease manifestations. The content of these exosomes, their functions, and effect on the immune cells may differ depending on their tissue sources. Therefore, in this study, we purified the exosomes from three different sources and, using the RNA-Seq approach, highly abundant microRNAs were identified and compared between exosomes and parental cells. The effects of exosomes on different immune cells were studied in vitro by incubating exosomes with PBMC and neutrophils and assessing their functions. The expression levels of several miRNAs varied within the different MSCs and exosomes. Additionally, the expression profile of most of the miRNAs was not similar to that of their respective sources. Exosomes isolated from different sources had different abilities to induce the process of neurogenesis and angiogenesis. Moreover, these exosomes demonstrated their varying effect on PBMC proliferation, neutrophil survival, and NET formation, highlighting their versatility and broad interaction with immune cells. The knowledge gained from this study will improve our understanding of the miRNA landscape of exosomes from hMSCs and provide a resource for further improving our understanding of exosome cargo and their interaction with immune cells

Bone marrow‐derived extracellular vesicles modulate the abundance of infiltrating immune cells in the brain and exert an antiviral effect against the Japanese encephalitis virus

Abstract Mesenchymal stem cells (MSCs) have regenerative capacity and have reported a beneficial effect on the Japanese encephalitis virus (JEV) in an encephalitis model. However, the MSCs do not cross the blood–brain barrier and have other disadvantages limiting their therapeutic utility scope. Recently, there has been a shift in concept from a cell‐based to a cell‐free approach using MSCs‐derived extracellular vesicles (MSC‐EVs). The MSC‐EVs retain regenerative and immunomodulatory capacity as their parental cells. However, the role of MSC‐EVs in limiting JEV pathology remains elusive. In this study, we have used Bone marrow (BM)‐derived EV (BM‐EVs) and assessed their effect on JEV replication and pathogenesis in primary neuronal stem cells and a murine model. The in vitro and in vivo studies suggested that BM‐derived EVs delay JEV‐induced symptoms and death in mice, improve the length of survival, accelerate neurogenesis in primary neuronal stem cells, reduce JEV‐induced neuronal death, and attenuate viral replication. BM‐EVs treatment upregulated interferon‐stimulated genes. Flow cytometry analysis revealed a reduction in the frequency of macrophages. At the same time, CD4+ T cells and neutrophils were significantly augmented, accompanied by the alteration of cytokine expression with the administration of BM‐EVs, reinforcing the immunomodulatory role of EVs during JEV‐induced encephalitis. In conclusion, our study describes the beneficial role of BM‐EVs in limiting JEV pathology by attenuating virus replication, enhancing antiviral response, and neurogenesis in primary neuronal stem cells. However, BM‐EVs do not seem to protect BBB integrity and alter immune cell infiltration into the treated brain

Ethnic variations in pathways into early intervention services for psychosis

BackgroundEthnic variations have previously been identified in the duration of untreated psychosis (DUP) and pathways into psychiatric services. These have not been examined in the context of early intervention services, which may alter these trajectories.AimsTo explore ethnic differences in the nature and duration of pathways into early intervention services.MethodIn a naturalistic cohort study, data were collected for 1024 individuals with psychotic disorders accepted for case management by eight London early intervention services.ResultsDuration of untreated psychosis was prolonged in the White British group compared with most other ethnic groups. White British individuals were more likely to make contact with their general practitioner and less likely to be seen within emergency medical services. All Black patient groups were more likely than their White British counterparts to experience involvement of criminal justice agencies.ConclusionsVariations continue to exist in how and when individuals from different ethnic groups access early intervention services. These may account for disparities in DUP.</jats:sec