Bone morphogenetic protein-7 attenuates pancreatic damage under diabetic conditions and prevents progression to diabetic nephropathy via inhibition of ferroptosis.

Background: Approximately 30% of diabetic patients develop diabetic nephropathy, a representative microvascular complication. Although the etiological mechanism has not yet been fully elucidated, renal tubular damage by hyperglycemia-induced expression of transforming growth factor-ß (TGF-ß) is known to be involved. Recently, a new type of cell death by iron metabolism called ferroptosis was reported to be involved in kidney damage in animal models of diabetic nephropathy, which could be induced by TGF-ß. Bone morphogenetic protein-7 (BMP7) is a well-known antagonist of TGF-ß inhibiting TGF-ß-induced fibrosis in many organs. Further, BMP7 has been reported to play a role in the regeneration of pancreatic beta cells in diabetic animal models. Methods: We used protein transduction domain (PTD)-fused BMP7 in micelles (mPTD-BMP7) for long-lasting in vivo effects and effective in vitro transduction and secretion. Results: mPTD-BMP7 successfully accelerated the regeneration of diabetic pancreas and impeded progression to diabetic nephropathy. With the administration of mPTD-BMP7, clinical parameters and representative markers of pancreatic damage were alleviated in a mouse model of streptozotocin-induced diabetes. It not only inhibited the downstream genes of TGF-ß but also attenuated ferroptosis in the kidney of the diabetic mouse and TGF-ß-stimulated rat kidney tubular cells. Conclusion: BMP7 impedes the progression of diabetic nephropathy by inhibiting the canonical TGF-ß pathway, attenuating ferroptosis, and helping regenerate diabetic pancreas.

Solubility and bioavailability enhancement of ciprofloxacin by induced oval-shaped mono-6-deoxy-6-aminoethylamino-ß-cyclodextrin.

Ciprofloxacin is a broad-spectrum fluoroquinolone antibiotic used to treat bacterial infections; however, its limited aqueous solubility inhibits its broader clinical uses. This study investigated the complexation effect of mono-6-deoxy-6-aminoethylamino-ß-cyclodextrin on the aqueous solubility and bioavailability of ciprofloxacin. During complexation, the oval-shaped cavity induced by mono-aminoethylamine substitution on the primary rim of ß-cyclodextrin, was considered to be a key factor according to NMR spectroscopy and molecular modeling studies. The ciprofloxacin with mono-6-deoxy-6-aminoethylamino-ß-cyclodextrin complex was characterized using FE-SEM, DSC, FT-IR, T1 relaxation, 2D NOESY, and DOSY NMR spectroscopy and molecular modeling studies. The solubility property of ciprofloxacin complexed with mono-6-deoxy-6-aminoethylamino-ß-cyclodextrin was enhanced by seven-fold compared to that of pure ciprofloxacin. Furthermore antibacterial activity of that complex against methicillin-resistant Staphylococcus aureus was enhanced and it clearly showed the growth inhibition. The mono-6-deoxy-6-aminoethylamino-ß-cyclodextrin has the potential to be utilized for other oblong guest molecules besides ciprofloxacin based on the novel induced elliptical cavity.

SERS-Based Flavonoid Detection Using Ethylenediamine-ß-Cyclodextrin as a Capturing Ligand.

Ethylenediamine-modified ß-cyclodextrin (Et-ß-CD) was immobilized on aggregated silver nanoparticle (NP)-embedded silica NPs (SiO2@Ag@Et-ß-CD NPs) for the effective detection of flavonoids. Silica NPs were used as the template for embedding silver NPs to create hot spots and enhance surface-enhanced Raman scattering (SERS) signals. Et-ß-CD was immobilized on Ag NPs to capture flavonoids via host-guest inclusion complex formation, as indicated by enhanced ultraviolet absorption spectra. The resulting SiO2@Ag@Et-ß-CD NPs were used as the SERS substrate for detecting flavonoids, such as hesperetin, naringenin, quercetin, and luteolin. In particular, luteolin was detected more strongly in the linear range 10-7 to 10-3 M than various organic molecules, namely ethylene glycol, ß-estradiol, isopropyl alcohol, naphthalene, and toluene. In addition, the SERS signal for luteolin captured by the SiO2@Ag@Et-ß-CD NPs remained even after repeated washing. These results indicated that the SiO2@Ag@Et-ß-CD NPs can be used as a rapid, sensitive, and selective sensor for flavonoids.