Non-clinical, quality and environmental impact assessments of cell and gene therapy products: Report on the 5th Asia Partnership Conference of Regenerative Medicine - April 7, 2022.

The 5th Asia Partnership Conference of Regenerative Medicine (APACRM) was held online on April 7, 2022 to promote regulatory harmonization of regenerative medicine products throughout Asia. The recognition of domestic regulatory guidelines within each country and region and the underpinning rationales are important initial steps toward the harmonization of regulations. The 5th APACRM featured open dialog regarding non-clinical, quality and environmental impact assessment settings for cell and gene therapy products through presentations from the industry and panel discussions with regulatory agencies. The latest updates on regenerative medicine fields in each country and region were also introduced. This paper summarizes the proceedings of the 5th APACRM for public dissemination to foster future discussion.

Nonclinical and quality assessment of cell therapy products: Report on the 4th Asia Partnership Conference of Regenerative Medicine, April 15, 2021.

The 4th Asia Partnership Conference of Regenerative Medicine (APACRM) was held online on April 15, 2021, to promote regulatory harmonization of regenerative medicine products throughout Asia. Recognizing domestic regulatory guidelines within each country and region, and their underpinning rationales, is an important initial step toward a convergence of regulations. The 4th APACRM consisted of an open dialog with regulatory agencies regarding nonclinical and quality settings for cell therapy products (CTPs) through industry presentations and panel discussions with regulatory agencies. The latest updates on regenerative medicine fields in each country and region, and specific regulatory schematics in Japan, were also introduced. The objective of this paper is to summarize the proceedings of the 4th APACRM for public dissemination and to foster further discussion in the future.

Food texture affects glucose tolerance by altering pancreatic ß-cell function in mice consuming high-fructose corn syrup.

The incidence of metabolic diseases, such as type 2 diabetes, has increased steadily worldwide. Diet, beverages, and food texture can all markedly influence these metabolic disorders. However, the combined effects of food texture and beverages on energy metabolism remains unclear. In the present study, we examined the effect of food texture on energy metabolism in mice administered high-fructose corn syrup (HFCS). Mice were fed a soft or hard diet along with 4.2% HFCS or tap water. Body weight and total caloric intake were not affected by food texture irrespective of HFCS consumption. However, caloric intake from HFCS (i.e., drinking volume) and diet were higher and lower, respectively, in the hard food group than in the soft food group. The hard food group's preference for HFCS was absent in case of mice treated with the µ-opioid receptor antagonist naltrexone. Despite increased HFCS consumption, blood glucose levels were lower in the hard-diet group than in the soft-diet group. In HFCS-fed mice, insulin levels after glucose stimulation and insulin content in the pancreas were higher in the hard food group than the soft food group, whereas insulin tolerance did not differ between the groups. These food texture-induced differences in glucose tolerance were not observed in mice fed tap water. Thus, food texture appears to affect glucose tolerance by influencing pancreatic ß-cell function in HFCS-fed mice. These data shed light on the combined effects of eating habits and food texture on human health.

Fetal androgen signaling defects affect pancreatic ß-cell mass and function, leading to glucose intolerance in high-fat diet-fed male rats.

We previously demonstrated that androgen signaling expands pancreatic ß-cell mass in the sexual maturation period (Am J Physiol Endocrinol Metab 314: E274-E286, 2018). The aim of this study was to elucidate whether fetal androgen signaling plays important roles in ß-cell mass development and ß-cell function in adulthood, defects of which are associated with type 2 diabetes mellitus. In the pancreas of male fetuses, androgen receptor (AR) was strongly expressed in the cytoplasm and at the cell membrane of Nkx6.1-positive ß-cell precursor cells but was markedly reduced in insulin-positive ß-cells. Administration of the anti-androgen flutamide to pregnant dams during late gestation reduced ß-cell mass and Ki67-positive proliferating ß-cells at birth in a male-specific manner without affecting body weight. The decrease of ß-cell mass in flutamide-exposed male rats was not recovered when rats were fed a standard diet, whereas it was fully recovered when rats were fed a high-fat diet (HFD), at 6 and 12 wk of age. Flutamide exposure in utero led to the development of glucose intolerance in male rats due to a decrease in insulin secretion when fed HFD but not standard diet. Insulin sensitivity did not differ between the two groups irrespective of diet. These results indicated that the action of fetal androgen contributed to ß-cell mass expansion in a sex-specific manner at birth and to the development of glucose intolerance by decreasing the secretion of insulin in HFD-fed male rats. Our data demonstrated the involvement of fetal androgen signaling in hypothesized sex differences in the developmental origins of health and disease by affecting pancreatic ß-cell function.

[H2O2 oxidation of 1,4-dihydropyridines over Mg2+ ion exchanged clinoptilolite and solventless solid state acid decomposition of ester to 3,5-pyridinedicarboxylic acid].

The acid property of alkali and alkali earth cation exchanged clinoptiolites were observed by micro-calorimetry of NH(3) adsorption at 200 degrees C. The reaction rates on decomposition of tert-butyl acetate (TBA) over clinoptilolites was proportional to the acid strength. 1,4-Dihydropyridines were oxidized to corresponding Pyridines in high yields at room temperature by H(2)O(2) aqueous solution over Mg(2+) ion exchanged clinoptilolte (CZ-Mg) in acetone. Solventless acid ester decomposition of Di-tert-butyl 3,5-pyridinedicarboxylate to 3,5-Pyridinedicarboxylic acid was effected using CZ-Mg at 170 degrees C.

[Derivatives of phenylpentanone in cultured mycelium of Mycoleptodonoides aitchisonii and the syntheses of their compounds].

A new perfumed dihydro-gamma-pyrone, 2-phenyl-5,6-dihydro-4H-pyrane-4-one (12) and seven components of C6-C5 phenylpentanone derivatives have been isolated from the neutral essential oil parts in cultured mycelium of Mycoleptodonoides aitchisonii. These compounds were elucidated on the basis of spectral data and syntheses. The derivatives are odorant components. The perfumed components in cultured mycelium were maximized amount at 7 days.

Active expression of matrix metalloproteinase-13 mRNA in the granulation tissue of equine superficial digital flexor tendinitis.

The DNA microarray analysis for matrix metalloproteinase (MMP)-related mRNA expression in equine superficial digital flexor tendinitis indicated that mRNA level of MMP-13 was apparently up-regulated in the tendinitis as compared to normal tendon. In situ hybridization also revealed that fibroblastic cells proliferated in the granulation tissue generated in the tendinitis actively expressed MMP-13 mRNA. On the other hand, in normal tendon, a few fibroblastic cells and vascular components lied in the endotenon barely expressed its mRNA, but other cellular components in the tendon bundle were not positively hybridized. As mentioned above, MMP-13 but not other collagenases or gelatinases, may play an important role in tendon injuries in the racehorses.

Analysis of protein adsorption and binding at biosensor polymer interfaces using X-ray photon spectroscopy and scanning electrochemical microscopy.

We describe a method, based on X-ray photoelectron spectroscopy (XPS) measurements, to assess the extent of protein adsorption or binding on a variety of different muTAS and biosensor interfaces. Underpinning this method is the labeling of protein molecules with either iodine- or bromine-containing motifs by using protocols previously developed for radiotracer studies. Using this method, we have examined the adsorption and binding properties of a variety of modified electrodeposited polymer interfaces as well as other materials used in muTAS device fabrication. Using polymer interfaces modified with poly(propylene glycol) (PPG) chains, our results indicate that a chain of at least approximately 30 monomer units is required to inhibit nonspecific adsorption from concentrated protein solutions. The XPS methodology was also used to probe specific binding of avidins and enzyme conjugates thereof to biotinylated and mixed biotin/PPG-modified polymer interfaces. In one example, using competitive binding, it was established that the mode of binding of a peroxidase-streptavidin conjugate to a biotinylated modified polymer interface was primarily via the streptavidin moiety (as opposed to nonspecific binding via the enzyme conjugate). XPS evaluation of nonspecific and specific peroxidase-streptavidin immobilization on various functionalized polymers has guided the design and fabrication of functionalized interdigitated electrodes in a biosensing muTAS device. Subsequent characterization of this device using scanning electrochemical microscopy (SECM) corroborated the adsorption and binding previously inferred from XPS measurements on macroscale electrodes.