Recent Progress in Phage Therapy to Modulate Multidrug-Resistant Acinetobacter baumannii, Including in Human and Poultry

Acinetobacter baumannii is a multidrug-resistant and invasive pathogen associated with the etiopathology of both an increasing number of nosocomial infections and is of relevance to poultry production systems. Multidrug-resistant Acinetobacter baumannii has been reported in connection to severe challenges to clinical treatment, mostly due to an increased rate of resistance to carbapenems. Amid the possible strategies aiming to reduce the insurgence of antimicrobial resistance, phage therapy has gained particular importance for the treatment of bacterial infections. This review summarizes the different phage-therapy approaches currently in use for multiple-drug resistant Acinetobacter baumannii, including single phage therapy, phage cocktails, phage–antibiotic combination therapy, phage-derived enzymes active on Acinetobacter baumannii and some novel technologies based on phage interventions. Although phage therapy represents a potential treatment solution for multidrug-resistant Acinetobacter baumannii, further research is needed to unravel some unanswered questions, especially in regard to its in vivo applications, before possible routine clinical use

Human Wharton's jelly mesenchymal stem cells show unique gene expression compared with bone marrow mesenchymal stem cells using single-cell RNA-sequencing

Human Wharton's jelly stem cells (hWJSCs) isolated from the human umbilical cord are a unique population of mesenchymal stem cells (MSCs) with significant clinical utility. Their broad differentiation potential, high rate of proliferation, ready availability from discarded cords, and prolonged maintenance of stemness properties in culture make them an attractive alternative source of MSCs with therapeutic value compared with human bone marrow MSCs (hBMMSCs). We aimed to characterize the differences in gene expression profiles between these two stem cell types using single-cell RNA sequencing (scRNA-Seq) to determine which pathways are involved in conferring hWJSCs with their unique properties. We identified 436 significantly differentially expressed genes between the two cell types, playing roles in processes, including immunomodulation, angiogenesis, wound healing, apoptosis, antitumor activity, and chemotaxis. Expression of immune molecules is particularly high in hWJSCs compared with hBMMSCs. These differences in gene expression may help to explain many of the advantages that hWJSCs have over hBMMSCs for clinical application. Although cell surface protein marker expression indicates that isolated hWJSCs and hBMMSCs are both homogenous populations, using scRNA-Seq we can clearly identify extreme variability in expression levels between individual cells within a certain cell type. If the cells are examined as bulk populations, it is not possible to appreciate that a single cell may be making a major unique contribution to the apparent overall expression level. We demonstrated how the fine tuning of expression within hWJSCs and hBMMSCs may be achieved by expression of molecules with opposing function between two cells. We hypothesize that a greater understanding of these differences in gene expression between the two cell types may aid in the development of new therapies using hWJSCs.This work was supported by the Singapore National University Health System (NUHS) Aspiration Fund (New Idea; R-174-000-155-720) research grant

A single-chip UHF RFID reader in 0.18 mu m CMOS process

A single-chip UHF RFID reader that integrates all building blocks-including an RF transceiver, IQ data converters, and a digital baseband-is implemented in a 0.18 mu m CMOS process. A high-linearity RX front-end and a low-phase-noise synthesizer are proposed to handle the large self-interferer, which is a key challenge in the reader RX design. Highly reconfigurable mixed-signal baseband architecture for channel-selection filtering is proposed to achieve power optimization for multi-protocol operation with different system dynamic ranges and data rates. The reader dissipates a maximum power of 276.4 mW when transmitting maximum output power of 10.4 dBm and receiving the tag's response of -70 dBm in the presence of -5 dBm self-interferer while occupying 18.3 mm(2)

Acute cardiovascular protective effects of corticosteroids are mediated by non-transcriptional activation of endothelial nitric oxide synthase.

Corticosteroids have been shown to exert beneficial effects in the treatment of acute myocardial infarction, but the precise mechanisms underlying their protective effects are unknown. Here we show that high-dose corticosteroids exert cardiovascular protection through a novel mechanism involving the rapid, non-transcriptional activation of endothelial nitric oxide synthase (eNOS). Binding of corticosteroids to the glucocorticoid receptor (GR) stimulated phosphatidylinositol 3-kinase and protein kinase Akt, leading to eNOS activation and nitric oxide dependent vasorelaxation. Acute administration of pharmacological concentrations of corticosteroids in mice led to decreased vascular inflammation and reduced myocardial infarct size following ischemia and reperfusion injury. These beneficial effects of corticosteroids were abolished by GR antagonists or eNOS inhibitors in wild-type mice and were completely absent in eNOS-deficient (Nos3(-/-)) mice. The rapid activation of eNOS by the non-nuclear actions of GR, therefore, represents an important cardiovascular protective effect of acute high-dose corticosteroid therapy