Acute kidney injury (AKI) is a fatal medical episode caused by sudden kidney damage or failure, leading to the death of patients within a few hours or days. Previous studies demonstrated that exosomes derived from various mesenchymal stem/stromal cells (MSC-exosomes) have positive effects on renal injuries in multiple experimental animal models of kidney diseases including AKI. However, the mass production of exosomes is a challenge not only in preclinical studies with large animals but also for successful clinical applications. In this respect, tangential flow filtration (TFF) is suitable for good manufacturing practice (GMP)-compliant large-scale production of high-quality exosomes. Until now, no studies have been reported on the use of TFF, but rather ultracentrifugation has been almost exclusively used, to isolate exosomes for AKI therapeutic application in preclinical studies. Here, we demonstrated the reproducible large-scale production of exosomes derived from adipose tissue-derived MSC (ASC-exosomes) using TFF and the lifesaving effect of the ASC-exosomes in a lethal model of cisplatin-induced rat AKI. Our results suggest the possibility of large-scale stable production of ASC-exosomes without loss of function and their successful application in life-threatening diseases.

Gastroretentive (GR) systems are designed to prolong gastric residence time to allow sustained absorption and improve the oral bioavailability of drugs with a narrow absorption window in the upper part of the gastrointestinal tract. The present study aimed to develop a GR system for acyclovir using 3D printing technology and evaluate its in vivo pharmacokinetics after oral administration in Beagle dogs. The system consisted of a gastro-floating device, which can float in the gastric fluid, prepared by a fused deposition modeling 3D printer and conventional acyclovir sustained-release (SR) tablet. The acyclovir SR tablet was inserted to the floating device to allow sustained release of the drug in the stomach. The buoyancy and sustained-release property of the developed GR system were determined using an in vitro dissolution test, in vivo pharmacokinetic study, and abdominal X-ray imaging in Beagle dogs. The in vivo dissolution profiles of the GR system were also predicted based on the in vivo pharmacokinetic data using a population pharmacokinetic (POP-PK) model. In the dissolution test, the sustained-release characteristic of the GR system was identified with a time corresponding to 80% dissolution (T₈₀) of 2.52 h. Following oral administration of the GR system, the time to reach the maximum concentration (T_max) of acyclovir was significantly prolonged, whereas the maximum concentration (C_max) decreased and the area under the curve increased compared with those obtained after the administration of immediate-release and SR tablets, indicating prolonged absorption. By X-ray imaging, we showed that the developed GR system stayed in the stomach for more than 12 h. The POP-PK model successfully described the observed plasma concentration-time data and predicted the in vivo biphasic dissolution profiles of the GR system, which was significantly different from the in vitro dissolution. The developed GR system could be applied to various drugs and had great prospects in the design and development of novel controlled-release formulations.

Background: Monitoring of an animal's blood glucose concentration is critical for diagnostic and therapeutic decisions. Over the past few decades, portable blood glucose meters (PBGMs) have been used to monitor blood glucose concentrations in animals. Recently, new and improved PBGMs have been made available on the market. Objective: The purpose of this study was to evaluate four PBGMs for use in dogs and cats. Animals and methods: A total of 155 venous blood samples of dogs and 85 venous blood samples of cats were tested using four PBGMs. Control solutions from manufacturers were used to determine the precision of each meter. The coefficient of variation was calculated to determine precision during a set of replicates. Pearson's correlation analysis, Passing–Bablok regression, and Bland–Altman analysis were used to determine the accuracy of four PBGMs against the hexokinase reference method. Error grid analysis was used to evaluate clinical relevance. Results: All PBGMs, except CERA-PET®, were clinically acceptable for monitoring blood glucose concentrations; AlphaTrak® and VetMate® appeared to be the most accurate ones, demonstrating that to use PBGMs for glucose monitoring, it is important to understand the strengths or limitations of each meter. The difference in results between the PBGMs and the reference method increased at high glucose concentration ranges, which were also affected by the hematocrit. Conclusions: Although readings of the PBGMs and the reference method varied across glycemic ranges (low, normal, and high glucose concentrations), most PBGMs were clinically acceptable for monitoring blood glucose concentrations in dogs and cats.

Context: Salicornia europaea (Amaranthaceae) (SE) has been shown to reduce obesity, but it remains a problem as a food supplement because of its high salt content (25–35% NaCl). Objectives: This study investigated the anti-obesity effects and mechanism of action of desalted SE powder (DSP). Materials and methods: Sprague–Dawley rats (n = 50) were divided into a normal control group (NC), a high-fat diet (HFD)-induced obesity control group (HFD), and HFD groups co-administered DSP (250 and 500 mg/kg) or Garcinia cambogia (Clusiaceae) extract (GE, 200 mg/kg, standard control) orally each day for 12 weeks. Results: The body weight was significantly reduced by co-administration of DSP (596.51 ± 19.84 kg, 4.60% and 562.08 ± 9.74 kg, 10.10%, respectively) and GE (576.00 ± 11.29 kg, 7.88%) relative to the HFD group (625.25 ± 14.02 kg) and was accompanied by reduced abdominal fat mass, and serum lipid levels, with no effects on feed intake. To find the underlying mechanism of the anti-obesity effects, trans-ferulic acid (TFA) was identified as the main ingredient and investigated with regard to whether it attenuated adipogenesity in 3T3L-1 cells. DSP-derived TFA suppressed adipocyte differentiation and accumulation of intracellular lipids. TFA also down-regulated the adipogenesis-related gene expression of sterol regulatory element-binding protein 1, peroxisome proliferator-activated receptor γ, CCAAT/enhancer binding protein-α and fatty acid synthase. Conclusions: These findings suggest that DSP may be considered for use as a food supplement intent of controlling obesity through its antiobesity and antiadipogenic properties.

Fucoidan, a natural sulfated polysaccharide, displays various biological activities including antioxidant properties. We examined the neuroprotective effect of fucoidan against transient global cerebral ischemia (tGCI) in high-fat diet (HFD)-induced obese gerbils and its related mechanisms. Gerbils received HFD for 12 weeks and fucoidan (50 mg/kg) daily for the last 5 days during HFD exposure, and they were subjected to 5-min tGCI. Pyramidal cell death was observed only in the CA 1 area (CA1) of the hippocampus in non-obese gerbils 5 days after tGCI. However, in obese gerbils, pyramidal cell death in the CA1 and CA2/3 occurred at 2 days and 5 days, respectively, after tGCI. In the obese gerbils, oxidative stress indicators (dihydroethidium, 8-hydroxyguanine and 4-hydroxy-2-nonenal) were significantly enhanced and antioxidant enzymes (SOD1 and SOD2) were significantly reduced in pre- and post-ischemic phases compared to the non-obese gerbils. Fucoidan treatment attenuated acceleration and exacerbation of tGCI-induced neuronal death in the CA1–3, showing that oxidative stress was significantly reduced, and antioxidant enzymes were significantly increased in pre- and post-ischemic phases. These findings indicate that pretreated fucoidan can relieve the acceleration and exacerbation of ischemic brain injury in an obese state via the attenuation of obesity-induced severe oxidative damage.