fat-covered-islet-transplantation-using-epididymal-white-adipose

Fat-Covered Islet Transplantation Using Epididymal White Adipose Tissue

Islet transplantation is a cellular replacement therapy for severe diabetes mellitus. The intraperitoneal cavity is typically the transplant site for this ...

Fukuoka University

Fukuoka University Hospital

Solid-state chiral chemistry has attracted significant scientific interest because of its application in the chiral-selective production, chiral recognition, resolution, and detection of enantiomers of a chiral compound. Combining a novel diffuse reflectance circular dichroism (DRCD) technique with powder X-ray crystallographic analysis, we investigated the origin of chiral properties from the molecular and supramolecular chiralities and the possibility of separating independent CD signals from the superimposed CD signal resulting from different chiral origins. 

A new method for separating configurational and constitutional chiralities using diffuse reflectance circular dichroism (DRCD).

The water-soluble 4-sulfonatophenyl meso-substituted porphyrin (TPPS) dye exhibits a transformation to a chiral self-aggregate from the non-aggregated species (diprotonated H4TPPS(2-)) at low concentration (no more than 1 × 10(-5) M). Immobilization of supramolecular chiral porphyrin homoassociates was mediated by the electrostatic interaction between the anionic TPPS molecule and cationic surfactant monolayer at the air-water interface. With the immobilization, a reversible transformation from monomeric TPPS to J-aggregate (M↔J) could be changed into an irreversible (M→J), which is desirable for stabilization of aggregation structure for a long period. The novel finding was achieved using a fine-tuned specialized solid-state circular dichroism (CD) spectrophotometer and derived analytical procedure to obtain artifact-free CD signals. To our knowledge, this is the first report achieving the chiral control of a homoassociate induced by a chiral surfactant at the air-water interface, indicating that the handedness of the formed homoassociate could be determined. 

Spectroscopic characterization of supramolecular chiral porphyrin homoassociates at the air-water interface.

Alpha lipoic acid (ALA), an active substance in anti-aging products and dietary supplements, need to be masked with an edible polymer to obscure its unpleasant taste. However, the high viscosity of the ALA molecules prevents them from forming microcomposites with masking materials even in supercritical carbon dioxide (scCO2). Therefore, the purpose of this study was to investigate and develop a novel production method for microcomposite particles for ALA in hydrogenated colza oil (HCO). Microcomposite particles of ALA/HCO were prepared by using a novel gas-saturated solution (PGSS) process in which the solid-dispersion method is used along with stepwise temperature control (PGSS-STC). Its high viscosity prevents the formation of microcomposites in the conventional PGSS process even under strong agitation. Here, we disperse the solid particles of ALA and HCO in scCO2 at low temperatures and change the temperature stepwise in order to mix the melted ALA and HCO in scCO2. As a result, a homogeneous dispersion of the droplets of ALA in melted HCO saturated with CO2 is obtained at high temperatures. After the rapid expansion of the saturated solution through a nozzle, microcomposite particles of ALA/HCO several micrometers in diameter are obtained. 

Gas-saturated solution process to obtain microcomposite particles of alpha lipoic acid/hydrogenated colza oil in supercritical carbon dioxide.

The present study reports on the ultrasonic enhancement of the liquid carbon dioxide (CO2) extraction of luteolin and apigenin from the leaves of Perilla frutescens (L.) Britt., to which ethanol is added as a cosolvent. The purpose of this research is also to investigate the effects of the particle size, temperature, pressure, irradiation power, irradiation time, and ethanol content in the liquid CO2 solution on the extraction yield using single-factor experiments. We qualitatively and quantitatively analyzed the yields in the extract using HPLC (high-performance liquid chromatography). The liquid CO2 mixed with ethanol was used at temperatures of 5, 20 and 25 °C with extraction pressures from 8 to 14 MPa. The yields of luteolin and apigenin in the extraction were clearly enhanced by the ultrasound irradiation, but the selectivity of the extract was not changed. The yields of luteolin and apigenin in the extract were also significantly improved by adjusting the operating temperature, the irradiation time, and the ethanol content in the liquid CO2 solution, but no change in the selectivity of the extract was observed.

Ultrasonically enhanced extraction of luteolin and apigenin from the leaves of Perilla frutescens (L.) Britt. using liquid carbon dioxide and ethanol.

Early rejection is a critical issue to be overcome to achieve successful islet transplantation. NLRP3 inflammasome is a protein complex that mediates the maturation of pro-interleukin (IL)-1β and pro-IL-18 to IL-1β and IL-18, respectively, which induce cellular death. Here, we investigated the impact of NLRP3 inflammasome and the effect of its inhibition by MCC950 in a rodent model of islet transplantation. We assessed the therapeutic effects of MCC950, a specific inhibitor of NLRP3 inflammasome, on gene expression, islet survival ratio and viability, and islet transplantation in mice. NLRP3 inflammasome-related gene (Nlrp3 and Il1b) expression was upregulated in islets stimulated with proinflammatory cytokines and suppressed when incubated with MCC950. Survival ratio and viability of incubated islets were reduced by cytokine stimulation and improved by MCC950. Regarding islet transplantation, the number of apoptotic cells in transplanted islets was reduced by MCC950. Furthermore, the expression of IL-1β in transplanted islets, migration of macrophages around islets, and fluctuation of blood glucose levels were suppressed by MCC950. Our study revealed that NLRP3 inflammasome worsened the therapeutic outcomes of islet transplantation and that MCC950 administration improved glycaemic control in syngeneic mice that underwent islet transplantation by inhibiting inflammation, which suppressed islet death.

Inhibition of NLRP3 inflammasome by MCC950 improves the metabolic outcome of islet transplantation by suppressing IL-1β and islet cellular death.

White adipose tissue (WAT) is a candidate transplantation site for islets. However, the mechanism of islet engraftment in WAT has not been fully investigated. In this study, we attempted to clarify the therapeutic effect and mechanism of islet transplantation into visceral WAT.

Mechanism of Transplanted Islet Engraftment in Visceral White Adipose Tissue.

The clinical utility of stem cell therapy for peripheral artery disease has not been fully discussed, and one obstacle is limited donor supplies. In this study, we attempted to rescue mouse ischemic hind limb by xenotransplantation of neonatal porcine bone marrow-derived mesenchymal stem cells (npBM-MSCs).

Xenotransplantation of neonatal porcine bone marrow-derived mesenchymal stem cells improves murine hind limb ischemia through lymphangiogenesis and angiogenesis.

Article	Year
A new method for separating configurational and constitutional chiralities using diffuse reflectance circular dichroism (DRCD). Applied spectroscopy\| PubMed ID: 24067579	2013
Spectroscopic characterization of supramolecular chiral porphyrin homoassociates at the air-water interface. Applied spectroscopy\| PubMed ID: 25286231	2014
Gas-saturated solution process to obtain microcomposite particles of alpha lipoic acid/hydrogenated colza oil in supercritical carbon dioxide. Pharmaceutical development and technology\| PubMed ID: 26024240	2016
Ultrasonically enhanced extraction of luteolin and apigenin from the leaves of Perilla frutescens (L.) Britt. using liquid carbon dioxide and ethanol. Ultrasonics sonochemistry\| PubMed ID: 26584980	2016
Inhibition of NLRP3 inflammasome by MCC950 improves the metabolic outcome of islet transplantation by suppressing IL-1β and islet cellular death. Scientific reports\| PubMed ID: 33087823	2020
Mechanism of Transplanted Islet Engraftment in Visceral White Adipose Tissue. Transplantation\| PubMed ID: 33215898	2020
Xenotransplantation of neonatal porcine bone marrow-derived mesenchymal stem cells improves murine hind limb ischemia through lymphangiogenesis and angiogenesis. Xenotransplantation\| PubMed ID: 33960029	2021

Ryo Kawakami

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