Doubly responsive polymersomes towards monosaccharides and temperature under physiologically relevant conditions

Organoboronic acid-containing polymers and block copolymers have recently attracted attention because of their ability to recognize important natural diol compounds such as saccharides and nucleotides under physiologically relevant conditions at neutral pH. In particular, polymers and block copolymers that are responsive toward multiple stimuli can be utilized to create smart delivery vehicles for use in applications in a complex environment. Here we report the monosaccharide-responsive polymers and block copolymers comprising styreneboroxole and oligo(ethylene glycol)-functionalized styrenes (OEG-STs) as repeating units. We have shown that homopolymers and copolymers of OEG-STs are thermally responsive by demonstrating that they possess the characteristic of tunable lower critical solution temperature (LCST) in water. When copolymerized with OEG-STs, styreneboroxole units function as a switch to change the solubility of the resulting polymers in aqueous solution by recognizing mono-saccharides via the formation of boronate ester. By introducing the minimum number of monosaccharide-responsive styreneboroxole units onto the thermally responsive OEG-ST backbone, we demonstrated the monosaccharide-responsive behavior of the resulting copolymers and their amphiphilic block copolymers in aqueous solution at physiologically relevant pH and temperature. A strategy based on doubly responsive block copolymers reported here could be utilized as new delivery vehicles for cargo molecules such as insulin, due to their ability to function in an in vivo environmentopen

Acute Viral Myopericarditis Presenting as a Transient Effusive-Constrictive Pericarditis Caused by Coinfection with Coxsackieviruses A4 and B3

Acute myopericarditis is usually caused by viral infections, and the most common cause of viral myopericarditis is coxsackieviruses. Diagnosis of myopericarditis is made based on clinical manifestations of myocardial (such as myocardial dysfunction and elevated serum cardiac enzyme levels) and pericardial (such as inflammatory pericardial effusion) involvement. Although endomyocardial biopsy is the gold standard for the confirmation of viral infection, serologic tests can be helpful. Conservative management is the mainstay of treatment in acute myopericarditis. We report here a case of a 24-year-old man with acute myopericarditis who presented with transient effusive-constrictive pericarditis. Echocardiography showed transient pericardial effusion with constrictive physiology and global regional wall motion abnormalities of the left ventricle. The patient also had an elevated serum troponin I level. A computed tomogram of the chest showed pericardial and pleural effusion, which resolved after 2 weeks of supportive treatment. Serologic testing revealed coxsackievirus A4 and B3 coinfection. The patient received conservative medical treatment, including nonsteroidal anti-inflammatory drugs, and he recovered completely with no complications

Improved Surgical Technique for Heterotopic Aortic Transplantation in Mice

Transplant arteriosclerosis is the main limitation for long-term survival of solid organ transplant recipients. Animal models would provide invaluable tools to investigate the cellular and molecular mechanisms underlying the pathogenesis of transplant arteriosclerosis, as well as for studies with novel drugs and other reagents for the prevention of the disease. We have therefore developed a modified technique for aortic transplantation in mice. The central suture ligation of the recipient abdominal aorta allowed a simpler end-to-side anastomosis of a segment of the donor thoracic aorta into the infrarenal portion of the recipient abdominal aorta. Using this technique, the overall survival rate was 94%. We also observed typical aspects of chronic rejection of the aortic allografts not observed with isografts. Our new technique is relatively easy to perform and has a low incidence of thrombosis, thus being useful for studying various aspects of transplant arteriosclerosis

Capric Acid Inhibits NO Production and STAT3 Activation during LPS-Induced Osteoclastogenesis

Capric acid is a second medium-chain fatty acid, and recent studies have shown that fatty acids are associated with bone density and reduce bone turnover. In this study, we investigated the effects of capric acid on lipopolysaccharide (LPS)-induced osteoclastogenesis in RAW264.7 cells. After treatment with capric acid (1 mM), the number of tartrate resistant acid phosphatase (TRAP)-positive cells decreased significantly. Capric acid reduced LPS-induced TRAP expression, an osteoclast differentiation marker, without inhibiting cell viability. LPS strongly upregulated inducible nitric oxide synthase (iNOS) mRNA levels and nitric oxide (NO) production, whereas capric acid inhibited them. Furthermore, capric acid also inhibited monocyte chemoattractant protein-1 (MCP-1) mRNA expression. Subsequently, we investigated various intracellular signaling proteins, including nuclear factor-κB (NF-κB), c-Jun-N-terminal kinase (JNK), extracellular signal regulated kinase 1/2 (ERK1/2), and signal transducer and activator of transcription 1 (STAT1) and STAT3 associated with osteoclastogenesis. Capric acid had no effects on LPS-induced activation of the NF-κB, JNK, ERK1/2, and STAT1 pathways. However, capric acid inhibited LPS-induced phosphorylation of Ser727 in STAT3. Additionally, stattic (a STAT3 inhibitor) inhibited LPS-induced iNOS and MCP-1 gene expression. In conclusion, we demonstrated that capric acid inhibited LPS-induced osteoclastogenesis by suppressing NO production via the STAT3 pathway. These results suggest that capric acid has important therapeutic implications for treating bone diseases associated with excessive osteoclastogenesis