Self-assembly of cholesterol end-capped polymer micelles for controlled drug delivery.

BACKGROUND: During the past few decades, drug delivery system (DDS) has attracted many interests because it could enhance the therapeutic effects of drugs and reduce their side effects. The advent of nanotechnology has promoted the development of nanosized DDSs, which could promote drug cellular uptake as well as prolong the half-life in blood circulation. Novel polymer micelles formed by self-assembly of amphiphilic polymers in aqueous solution have emerged as meaningful nanosystems for controlled drug release due to the reversible destabilization of hydrophobic domains under different conditions. RESULTS: The amphiphilic polymers presented here were composed of cholesterol groups end capped and poly (poly (ethylene glycol) methyl ether methacrylate) (poly (OEGMA)) as tailed segments by the synthesis of cholesterol-based initiator, followed by atom transfer radical polymerization (ATRP) with OEGMA monomer. FT-IR and NMR confirmed the successfully synthesis of products including initiator and polymers as well as the Mw of the polymers were from 33,233 to 89,088 g/mol and their corresponding PDI were from 1.25 to 1.55 by GPC. The average diameter of assembled polymer micelles was in hundreds nanometers demonstrated by DLS, AFM and SEM. The behavior of the amphiphilic polymers as micelles was investigated using pyrene probing to explore their critical micelle concentration (CMC) ranging from 2.53 × 10-4 to 4.33 × 10-4 mg/ml, decided by the balance between cholesterol and poly (OEGMA). Besides, the CMC of amphiphilic polymers, the quercetin (QC) feeding ratio and polarity of solvents determined the QC loading ratio maximized reaching 29.2% certified by UV spectrum, together with the corresponding size and stability changes by DLS and Zeta potential, and thermodynamic changes by TGA and DSC. More significantly, cholesterol end-capped polymer micelles were used as nanosized systems for controlled drug release, not only alleviated the cytotoxicity of QC from 8.6 to 49.9% live cells and also achieved the QC release in control under different conditions, such as the presence of cyclodextrin (CD) and change of pH in aqueous solution. CONCLUSIONS: The results observed in this study offered a strong foundation for the design of favorable polymer micelles as nanosized systems for controlled drug release, and the molecular weight adjustable amphiphilic polymer micelles held potential for use as controlled drug release system in practical application.

[A de novo GJA1 mutation identified by whole-exome sequencing in a patient with oculodentodigital dysplasia].

OBJECTIVE: To explore the genetic basis for a patient with oculodentodigital dysplasia. METHODS: Genomic DNA was extracted from peripheral blood samples from the patient and his parents. Whole-exome sequencing was carried out for the trio family. Suspected mutation was verified by Sanger sequencing. RESULTS: A de novo c.412G>A mutation of the GJA1 gene was identified in the patient, which was validated by Sanger sequencing. CONCLUSION: The c.412G>A mutation of the GJA1 gene probably underlies the disease in the patient.

[Diagnosis of right ventricular outflow tract and intraoperative lesion in patients with right coronary artery sinus rupture by transthoracic echocardiography].

OBJECTIVE: To investigate the role of thoracic echocardiography in diagnosis and differential diagnosis of the right ventricular outflow tract into the right aorta with right ventricular aneurysm rupture. 
 Methods: A total of 19 patients with sinus rupture caused by ventricular septal defect in the right ventricular outflow road were reviewed. These patients were diagnosed as aortic right coronary sinus by preoperative transthoracic echocardiography from February 2010 to September 2016 in Xiangya Second Hospital and Xiangya Medical College Affiliated Haikou Hospital. The clinical symptoms, echocardiography and intraoperative lesions were compared and analyzed among the patients.
 Results: The intraoperative lesions were consistent with the preoperative echocardiographic diagnosis in 16 patients. Among them, 11 cases could be heard the continuous sound of the machine with systolic murmur and no tremor in left sternal rib 2-3 auscultation. The color Doppler imaging of right ventricular systolic indicated the based continuous Doppler spectrum. The preoperative echocardiography and intraoperative lesions testified the ventricular septal defect size and the right ventricular outflow tract into the right aorta with right ventricular aneurysm rupture. Among them, 3 cases were complicated with other heart diseases. Other 3 cases were not accorded with the preoperative diagnosis. There were auscultation smell and noise but no tremor. The preoperative echocardiography and lesions indicated the right ruptured aneurysm of the sinus of big and long mouth, 1 case with aortic valve stenosis and regurgitation, congenital aortic valve two valve malformation, 1 case with aortic valve-severe reflux, 1 case with pulmonary infection, and 3 cases with no intraoperative lesions in the ventricular septal defect.
 Conclusion: Preoperative transthoracic echocardiography is the preferred preoperative, quick and noninvasive method for ruptured aneurysm. Each stage of observation procedure and method can observe the ruptured aneurysm of aortic sinus, the location, size and adjacent of ventricular septal defect. Meanwhile, the flow spectrum characteristics of the ventricular septal defect in the right outflow tract of the right sinus aneurysm can be found by Doppler ultrasound imaging.

Photo-crosslinkable methacrylated konjac glucomannan (KGMMA) hydrogels as a promising bioink for 3D bioprinting.

Three-dimensional (3D) bioink with favorable printability, strength, and biocompatibility challenged the 3D bioprinting technology in cartilage tissue engineering. Herein, we innovatively fabricated photo-crosslinkable methacrylated konjac glucomannan (KGMMA) as a novel biomaterial ink for 3D extrusion bioprinting in an attempt to construct precisely patterned tissues. Specifically, konjac glucomannan (KGM) was modified by methacrylic anhydride, which is a kind of photoreactive group, to form KGMMA. After UV crosslinking, the printed KGMMA hydrogel formed a covalent crosslinking network with high strength, desired shearing, and swelling and degradation characteristics. The properties of the KGMMA hydrogel could be modulated by changing the contents of MA. The shear-thinning property of the KGMMA biomaterial ink enables excellent printability, which can print different shapes including lattices, hexagons, and flowers. Furthermore, the bioinks support cell growth after being printed with chondrocytes for a culture. Therefore, the biodegradable, injectable, and photo-crosslinkable KGMMA biomaterial ink holds a great promise for cartilage tissue engineering.

Weak acidic stable carbazate modified cellulose membranes target for scavenging carbonylated proteins in hemodialysis.

Carbazate groups were grafted on the commercial cellulose membrane (CM) to specifically scavenge the carbonylated proteins for hemodialysis. It confirmed that carbazate groups were successfully covalently attached on the CMs by XPS and EDS, and the modified CMs still saved their original morphology and crystalline structures by SEM and XRD. Furthermore, the modified CMs presented favorable physicochemical stability at wide pH range from 2.5 to 7.4. It was also found that the carbazate modified CMs could selectively remove carbonylated proteins from acrolein treated bovine serum albumin (BSA) or ESRD patient's blood serum in PBS buffer. The modified CMs showed the potential to be utilized as the substitute of dialysis membranes in hemodialysis.