Melatonin-stimulated exosomes enhance the regenerative potential of chronic kidney disease-derived mesenchymal stem/stromal cells via cellular prion proteins

Chronic kidney disease (CKD) is caused by dysfunctional kidneys, which result in complications like cardiovascular diseases. Chronic kidney disease-induced pathophysiological conditions decrease efficacy of autologous mesenchymal stem/stromal cell (MSC)-based therapy by reducing MSC functionality. To enhance therapeutic potential in patients with CKD, we isolated exosomes derived from melatonin-treated healthy MSCs (MT exosomes) and assessed the biological functions of MT exosome–treated MSCs isolated from patients with CKD (CKD-MSCs). Treatment with melatonin increased the expression of cellular prion protein (PrP^C) in exosomes isolated from MSCs through the upregulation of miR-4516. Treatment with MT exosomes protected mitochondrial function, cellular senescence, and proliferative potential of CKD-MSCs. MT exosomes significantly increased the level of angiogenesis-associated proteins in CKD-MSCs. In a murine hindlimb ischemia model with CKD, MT exosome–treated CKD-MSCs improved functional recovery and vessel repair. These findings elucidate the regenerative potential of MT exosome–treated CKD-MSCs via the miR-4516-PrP^C signaling axis. This study suggests that the treatment of CKD-MSCs with MT exosomes might be a powerful strategy for developing autologous MSC-based therapeutics for patients with CKD. Furthermore, miR-4516 and PrP^C could be key molecules for enhancing the regenerative potential of MSCs in ischemic diseases.     

Endoscopic Decompression for Optic Neuropathy in McCune-Albright Syndrome

McCune-Albright syndrome (MAS) is characterized by a triad of poly/monostotic fibrous dysplasia, café-au-lait macules and hyperfunctioning endocrinopathies including human growth hormone excess. Acromegaly as a manifestation of endocrine hyperfunction with MAS is uncommon. Surgical excision may be challenging due to the associated severe fibrous dysplasia of the skull base. Through the endoscopic procedures, we treated a case of MAS presenting with compressive optic neuropathy due to fibrous dysplasia and acromegaly caused by growth hormone secreting pituitary adenoma. We reviewed the literature on GH excess in MAS to highlight its surgical and medical challenges.     

The clue of Interstitial Cell of Cajalopathy (ICCpathy) in human diabetic gastropathy: The ultrastructural and electrical clues of ICCpathy in human diabetic gastropathy

Recent studies of diabetic animal models suggest an important role of ICC in the pathogenesis of gastropathy. The aim of this study was to characterize the ultrastructural features of ICC and record the electrical properties in the stomach of patients with type 2 DM. Gastric specimens were obtained from 13 diabetic patients and 6 control subjects with gastric cancer that underwent gastrectomy. All specimens were taken from disease-free areas. The samples were processed for both electron microscopic and electrophysiologic examination. The characteristic ultrastructural changes of the ICC were observed in both the nucleus and cytoplasm in patients with type 2 DM. Wrinkling of the nuclear envelope and changes in the cytoplasm such as dilatation of the endoplasmic reticulum, an increase of autophagic vacuoles, were more frequently observed in the diabetic patients. Apoptosis characterized by nuclear karyorrhexis or pyknosis was observed only in the diabetic patients. Slow waves were recorded in the circular muscle of stomach. In diabetic patients, the mean resting membrane potential was higher and amplitude was lower than controls. These changes of electrical activities of slow waves were accompanied with ultrastructural changes of ICC, particularly the characteristic nuclear changes. In human diabetic patients, the characteristic ultrastructural changes of ICC such as preapoptosis, accompanied with electrical dysrhythmia of slow waves, were observed. These results show several evidence converging to support that degeneration of the ICC may be associated with the pathogenesis of diabetic gastropathy.     

Hyperthyroidism and the management of atrial fibrillation.

Atrial fibrillation is often induced in patients with hyperthyroidism and may trigger heart failure. Its prevalence and outcome were examined to obtain up-to-date information. Persistent atrial fibrillation was observed in approximately 1.7% of new hyperthyroid patients. It occurs more frequently in males (2.86%) than in females (1.36%), even though the number of male hyperthyroid patients is only one fifth of female patients. The rate increased with age, being 8% in the patients older than 70 years old. The initial treatment is to control the heart rate with routine pharmacologic therapy and to start antithyroid therapy as quickly as possible. Attempted cardioversion should be deferred until approximately the fourth month of maintaining a euthyroid state, because more than 56% of atrial fibrillation spontaneously reverts to sinus rhythm when the thyroid hormone levels start to decline. Elective cardioversion for those whose atrial fibrillation persists is highly effective and sinus rhythm maintenance rates were 56.7% and 47.6% at the 10th and the 14th year, respectively, even though the duration of atrial fibrillation prior to cardioversion was extremely long (35.0 +/- 29.0 months).     

Preferential occupancy of Eu3+ and energy transfer in Eu3+ doped Sr2V2O7, Sr9Gd(VO4)7 and Sr2V2O7/Sr9Gd(VO4)7 phosphors

The vanadate-based phosphors Sr₂V₂O₇:Eu³⁺ (SV:Eu³⁺), Sr₉Gd(VO₄)₇:Eu³⁺ (SGV:Eu³⁺) and Sr₉Gd(VO₄)₇/Sr₂V₂O₇:Eu³⁺ (SGV/SV:Eu³⁺) were obtained by solid-state reaction. The bond-energy method was used to investigate the site occupancy preference of Eu³⁺ based on the bond valence model. By comparing the change of bond energy when the Eu³⁺ ions are incorporated into the different Sr, V or Gd sites, we observed that Eu³⁺ doped in SV, SGV or SV/SGV would preferentially occupy the smaller energy variation sites, i.e., Sr4, Gd and Gd sites, respectively. The crystal structures of SGV and SV, the photoluminescence properties of SGV:Eu³⁺, SV, SGV/SV and SGV/SV:Eu, as well as their possible energy transfer mechanisms are proposed. Interesting tunable colours (including warm-white emission) of SGV/SV:Eu³⁺ can be obtained through changing the concentration of Eu³⁺ or changing the relative quantities of SGV to SV by increasing the calcination temperature. Its excitation bands consist of two types of O²⁻ → V⁵⁺ charge transfer (CT) bands with the peaks at about 325 and 350 nm respectively, as well as f–f transitions of Eu³⁺. The obtained warm-white emission consists of a broad photoluminescence band centred at about 530 nm, which originates from the O²⁻ → V⁵⁺ CT of SV, and a sharp characteristic spectrum (⁵D₀–⁷F₂) at about 615 and 621 nm.

The vanadate-based phosphors Sr₂V₂O₇:Eu³⁺ (SV:Eu³⁺), Sr₉Gd(VO₄)₇:Eu³⁺ (SGV:Eu³⁺) and Sr₉Gd(VO₄)₇/Sr₂V₂O₇:Eu³⁺ (SGV/SV:Eu³⁺) were obtained by solid-state reaction.