Stem cells-derived exosomes alleviate neurodegeneration and Alzheimer's pathogenesis by ameliorating neuroinflamation, and regulating the associated molecular pathways.

Amyloid beta (Aß) aggregation and tau hyper phosphorylation (p-tau) are key molecular factors in Alzheimer's disease (AD). The abnormal formation and accumulation of Aß and p-tau lead to the formation of amyloid plaques and neurofibrillary tangles (NFTs) which ultimately leads to neuroinflammation and neurodegeneration. ß- and γ-secretases produce Aß peptides via the amyloidogenic pathway, and several kinases are involved in tau phosphorylation. Exosomes, a recently developed method of intercellular communication, derived from neuronal stem cells (NSC-exos), are intriguing therapeutic options for AD. Exosomes have ability to cross the BBB hence highly recommended for brain related diseases and disorders. In the current study, we examined how NSC-exos could protect human neuroblastoma cells SH-SY5Y (ATCC CRL-2266). NSC-exos were derived from Human neural stem cells (ATCC-BYS012) by ultracentrifugation and the therapeutic effects of the NSC-exos were then investigated in vitro. NSC-exos controlled the associated molecular processes to drastically lower Aß and p-tau. A dose dependent reduction in ß- and γ-secretase, acetylcholinesterase, GSK3ß, CDK5, and activated α-secretase activities was also seen. We further showed that BACE1, PSEN1, CDK5, and GSK-3ß mRNA expression was suppressed and downregulated, while ADAM10 mRNA was increased. NSC- Exos downregulate NF-B/ERK/JNK-related signaling pathways in activated glial cells HMC3 (ATCC-CRL-3304) and reduce inflammatory mediators such iNOS, IL-1ß, TNF-α, and IL-6, which are associated with neuronal inflammation. The NSC-exos therapy ameliorated the neurodegeneration of human neuroblastoma cells SH-SY5Y by enhancing viability. Overall, these findings support that exosomes produced from stem cells can be a neuro-protective therapy to alleviate AD pathology.

Bone mineral density assessment for research purpose using dual energy X-ray absorptiometry.

Dual energy X-ray absorptiometry (DXA) has become the most common method for measuring bone mineral density (BMD) of small animals in metabolic bone disease research, and errors should be minimized in all procedures involved in research studies in order to increase the accuracy of the study results. DXA is simpler and rapid compared to micro-computed tomography for quantitative analysis of change in trabecular bone of test subject. In human research, measuring BMD is widely used; postoperative evaluation on orthopedic surgery, evaluation of osteoporosis medication in menopause and many other areas of study. For the study, the inspector should be trained by the equipment manufacturer regarding the utilization and analysis of the equipment and regular phantom testing should be conducted to ensure the stability of the equipment, and precision tests should be conducted to analyze the positioning and data analysis. They should also be familiar with the clinical trials and conduct studies based on the approval of the Institutional Review Board. In the absolute BMD measurement of the human body, it is necessary to apply and compare the position and condition, rotation degree, region of interest, and area of the scan in the follow-up test. In the case of small animals, animal selection, measurement and equipment should be modeled to match the research. Therefore, we would like to provide information for researchers to minimize the errors, effective data management and accurate data presentation. This article reviews the process of DXA measurement for research purpose including plan for DXA examination, BMD measurement in a human body study and small animal studies.

Carboxylated pillar[5]arene-coated gold nanoparticles with chemical stability and enzyme-like activity.

A facile synthesis of gold nanoparticles (AuNPs) covered with a multidentate macrocycle, carboxylated pillar[5]arene (CP), via a one-pot hydrothermal process is reported. The resulting AuNPs are highly stable against salts and pH variations, while their traditional counterparts are not stable at the same conditions. For the stabilization, multiple carboxylate groups of CP might contribute to electrostatic or steric stabilization. In addition, we found that CP-coated AuNPs exhibit greater peroxidase-like activity than citrate-stabilized AuNPs in the presence of silver cations. The system presented herein would provide a new scheme to fabricate unique sensory systems in combination with enzymes, which can bind to the pocket of CP.

Glucose-Responsive Disassembly of Polymersomes of Sequence-Specific Boroxole-Containing Block Copolymers under Physiologically Relevant Conditions.

Polymers containing organoboronic acids have recently gained interest as sugar-responsive materials owing to the reversible binding of saccharides to boronic acids, which triggers a change in the physical and chemical properties of these polymers, such as their water solubility. In particular, the ability of these polymers to bind glucose has attracted considerable attention because of the promise of these materials for the development of sensors and drug delivery systems for glucose-related human diseases, such as diabetes. We report here a new class of sugar-responsive polymers that are based on a sequence-specific copolymer of styreneboroxole and N-functionalized maleimide. The reversible addition-fragmentation and chain transfer (RAFT) polymerization of this pair of monomers ensured that a glucose receptor alternates with a nonresponsive solubilizing group throughout the sugar-responsive polymer chain. Due to the presence of hydrophilic solubilizing groups beween the solubility-switching boroxole moieties in the membrane-forming block, the polymersomes of the block copolymers responded to a lower level of glucose in the medium, resulting in diassembly of the bilayer membrane under a physiologically relevant pH and glucose level.

[Usefulness of a chromogenic selective agar for the identification of Bacillus cereus isolated from blood cultures].

BACKGROUND: The incidence of Bacillus cereus bacteremia is increasing, but the identification of Bacillus species remains difficult. Brilliance Bacillus cereus agar (BBC agar; Oxoid, UK) is a new CHROMagar medium that allows selective isolation and identification of B. cereus; however, its clinical usefulness is seldom studied. We evaluated the usefulness of BBC agar to identify B. cereus isolates recovered from blood cultures. METHODS: We analyzed a total of 53 blood isolates that showed a Bacillus-like morphology on Gram staining. All isolates were identified by using both the API Coryne (bioMérieux, France) and API 50CH/B (bioMérieux) systems. They were subsequently subcultured on BBC agar, incubated for 24 hr, and then examined for characteristic blue-green colonies. The clinical characteristics of patients whose isolates were identified as B. cereus were assessed. RESULTS: Of the 53 isolates, 18 were identified as B. cereus by API 50CH/B. With the API 50CH/B system used as gold standard, the sensitivity and specificity for the identification of B. cereus were 100% (18/18) and 100% (35/35), respectively, using BBC agar, and 67% (12/18) and 100% (35/35), respectively, using the API Coryne system. Of the 18 patients with B. cereus bacteremia, 15 showed infectious signs, and 3 had more than 2 blood cultures positive for B. cereus on separate days. CONCLUSIONS: Our study shows, for the first time, that BBC agar, with its good agreement and ease of use, is a valuable alternative to the API 50CH/B system for the presumptive identification of B. cereus isolates from blood cultures.