Design and synthesis of novel anti-multidrug-resistant staphylococcus aureus derivatives of glycyrrhetinic acid by blocking arginine biosynthesis, metabolic and H2S biogenesis.

With the soaring number of multidrug-resistant bacteria, it is imperative to develop novel efficient antibacterial agents and discovery new antibacterial pathways. Herein, we designed and synthesized a series of structurally novel glycyrrhetinic acid (GA) derivatives against multidrug-resistant Staphylococcus aureus (MRSA). The in vitro antibacterial activity of these compounds was evaluated using the microbroth dilution method, agar plate coating experiments and real-time growth curves, respectively. Most of the target derivatives showed moderate antibacterial activity against Staphylococcus aureus (S. aureus) and MRSA (MIC = 3.125-25 µM), but inactivity against Escherichia coli (E. Coli) and Pseudomonas aeruginosa (P. aeruginosa) (MIC > 200 µM). Among them, compound 11 had the strongest antibacterial activity against MRSA, with an MIC value of 3.125 µM, which was 32 times and 64 times than the first-line antibiotics penicillin and norfloxacin, respectively. Additionally, transcriptomic (RNA-seq) and quantitative polymerase chain reaction (qPCR) analysis revealed that the antibacterial mechanism of compound 11 was through blocking the arginine biosynthesis and metabolic and the H2S biogenesis. Importantly, compound 11 was confirmed to have good biocompatibility through the in vitro hemolysis tests, cytotoxicity assays and the in vivo quail chicken chorioallantoic membrane (qCAM) experiments. Current study provided new potential antibacterial candidates from glycyrrhetinic acid derivatives for clinical treatment of MRSA infections.

[Association between polymorphisms of Pen2 gene and late onset Alzheimer's disease].

OBJECTIVE: To explore the association between single nucleotide polymorphisms (SNPs) in Pen2 gene and late onset Alzheimer's disease (LOAD) in North Chinese population. METHODS: The genotypes of ApoE and Pen2 gene were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing respectively in 480 LOAD patients and 480 healthy controls. The strength of association between polymorphisms and AD was estimated with odds ratios (OR). RESULTS: The genotype of IVS2 + 335T < A was obtained. There was an association between IVS2 + 335T < A and apolipoprotein E (ApoE) genotypes (P = 0.002). In the subjects with APOEε 4 allele, there were significant differences in the distribution of alleles (P = 0.003) and genotypes (P = 0.007) between AD and control groups. The ORs (95% confidence interval (CI)) of allele A and T/A + A/A genotypes were 4.720 (1.517 - 10.654) and 3.886 (1.381 - 10.932) respectively with allele T and genotype T/T as references. CONCLUSION: An association exists between IVS2 + 335T < A and the development of LOAD in ApoEε 4 carriers within the northern Chinese population. And allele A of Pen 2 gene may increase the risk for LOAD.

Management and outcomes of delirious patients with hyperactive symptoms in a secured behavioral unit jointly used by geriatricians and pyschogeriatricians.

To compare the clinical outcomes and length of stay (LOS) between delirious patients with hyperactive symptoms admitted directly and those admitted indirectly from Emergency Department into a secured, behavioral unit jointly used by geriatricians and pyschogeriatricians (the Unit). A retrospective study analyzing data from the medical records of 122 patients with an admission diagnosis of delirium with hyperactive symptoms and subsequently discharged from the Unit, including restraint, one-to-one nursing care, falls, absconding, duration of delirium, recovery from delirium, destination and LOS. Significantly fewer patients with direct admission (n=68) required physical restraint or chemical restraint compared with those transferred (n=54). Patients admitted directly showed a higher discharge rate back home, shorter LOS, shorter duration of delirium and a higher rate of recovery from delirium than transferred patients. Of the transferred patients, more received one-to-one nursing care before transfer than after transfer. Three (5.6%) absconded before transfer, but none absconded from the Unit. The falls rate reduced from 14.2 to 6.7 falls/1000 patient delirium days after transfer. Delirious patients with hyperactive symptoms admitted directly to the Unit fared better in clinical outcomes and LOS. They also required less restraint, less intensive nursing and were unlikely to abscond compared to those transferred.