In Alzheimer’s disease (AD), the most common cause of dementia, patients generally forget to take pills or skip medication due to side effects, affecting the treatment efficacy. In this study, we combined a poly(lactic-co-glycolic acid), (PLGA)-poly(ethylene glycol), and (PEG)-PLGA thermo-sensitive hydrogel with curcumin (PGC) to deliver an intramuscular injection that could continuously release curcumin and maintain it at a constant level in blood to prevent AD development or progression. We evaluated the drug release profile and cytotoxicity of PGC and its effects on AD pathology through in vitro and in vivo studies and on cognitive function through an aluminum-chloride-induced AD rat model. In the in vitro study, PGC exhibited a lack of cytotoxicity, excellent anti-inflammatory and antioxidant properties, and microglial modulation. In the Morris water maze test, the PGC injection-administered AD rats presented well-focused searching behavior with the shortest swimming path and longest retention times in the quadrant where the platform was initially located. Furthermore, PGC reduced amyloid-beta aggregation and deposition and significantly increased hippocampal activity. This study demonstrated that intramuscular PGC injection can effectively prevent AD development or progression in rats without inducing toxicity; therefore, this strategy could help overcome the present challenges in AD management in humans.

The human corneal endothelium has limited regeneration capacity. Several methods have been developed in an attempt to repair it. Descemet stripping automated endothelial keratoplasty (DSAEK) is commonly performed on patients with endothelial dysfunction. However, donor demand far exceeds donor supply. Here, we prepared fish-scale collagen membrane (FSCM) and seeded it with CECs in preparation for corneal endothelial transplantation. The fish scales were decellularized, decalcified, and curved. The FSCM was inspected by fluorescence microscopy, SEM, and TGA to validate decellularization, microstructure, and decalcification, respectively. The cytotoxicity of FSCM and the viability of the cells in contact with it were evaluated by LDH and WST-1, respectively. CEC tight junctions and ZO-1 structure were observed by SEM and confocal microscopy. FSCM seeded with CECs were implanted to rabbit anterior chambers to evaluate host tissue reactions to it. FSCM biocompatibility and durability were also assessed. The results showed that FSCM has excellent transparency, adequate water content, and good biocompatibility. The cultivated CECs mounted on the FSCM were similar to normal CECs in vivo. The FSCM plus CECs developed here have high potential efficacy for endothelial keratoplasty transplantation.

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Oxidative stress has been suggested as an important factor in the progress of sarcopenia. The current treatments for sarcopenia have the disadvantages of insufficient effect or daily administration. Therefore, an alternative for effective, safety and long-term treatment may be a solution for unmet needs. Bletilla striata polysaccharide has been reported to have anti­oxidative and anti-inflammatory properties. In this study, we used Bletilla striata polysaccharide (BSP) combined with hydroxyapatite, a carrier. We hypothesized that the resulting combination (BSP-HAP) is a good formula for the controlled release of BSP via intramuscular (IM) administration, so as to prevent the worsening of presarcopenia or even recover from the early stage of the illness. In this research, BSP-HAP was synthesized by a modified low temperature co-precipitation process that would be beneficial for BSP loading. By conducting DCFDA, WST-1 and the Live/Dead assay, BSP-HAP is shown to be a biocompatible material which may release BSP by cells through the endocytosis pathway. Animal studies revealed that the rats treated with BSP-HAP could effectively recover muscle endurance, grip strength or fat/lean mass ratio from lipopolysaccharide (LPS)-induced sarcopenia. This study shows BSP delivered by BSP-HAP system has potential for application in the treatment and prevention of sarcopenia in the future.

Oxidative stress and later-induced chronic inflammation have been reported to play an important role on the progression of sarcopenia. Current treatments for sarcopenia are mainly administered to patients whom sarcopenia already developed. However, there has been no promising results shown in therapy. Therefore, the development of therapeutic and preventive strategies against sarcopenia would be necessary. Curcumin is a traditional medicine that possesses anti-inflammatory and anti­oxidative properties. In the present study, hydroxyapatite was subjected to hydrophobic surface modifications for curcumin loading (Cur-SHAP). It was, subsequently, utilized for delivery to the patient’s body via intramuscular injection in order to achieve constant release for more than 2 weeks, preventing the progression of the sarcopenia or even leading to recovery from the early stage of the illness. According to the results of WST-1, LIVE/DEAD, DCFDA, and gene expression assays, Cur-SHAP exhibited good biocompatibility and showed great antioxidant/anti-inflammatory effects through the endocytic pathway. The results of the animal studies showed that the muscle endurance, grip strength, and fat/lean mass ratio were all improved in Cur-SHAP-treated rats from LPS-induced sarcopenia. In summary, we successfully synthesized hydrophobic surface modification hydroxyapatite for curcumin loading (Cur-SHAP) and drug delivery via the IM route. The LPS-induced sarcopenia rats were able to recover from disease after the Cur-SHAP treatment.

Urological chronic pelvic pain syndrome (UCPPS) manifests as pelvic pain with frequent urination and has a 10% prevalence rate without effective therapy. Nanoceria (cerium oxide nanoparticles [CNPs]) were synthesized in this study to achieve potential long‐term pain relief, using a commonly used UCPPS mouse model with cyclophosphamide‐induced cystitis. Transcriptome sequencing analysis revealed that serpin family B member 2 (SerpinB2) was the most upregulated marker in mouse bladder, and SerpinB2 was downregulated with CNP pretreatment. The transcriptome sequencing analysis results agreed with quantitative polymerase chain reaction and western blot analysis results for the expression of related mRNAs and proteins. Analysis of Gene Expression Omnibus (GEO) datasets revealed that SerpinB2 was a differentially upregulated gene in human UCPPS. In vitro SerpinB2 knockdown downregulated proinflammatory chemokine expression (chemokine receptor CXCR3 and C‐X‐C motif chemokine ligand 10) upon treatment with 4‐hydroperoxycyclophosphamide. In conclusion, CNP pretreatment may prevent the development of UCPPS, and reactive oxygen species (ROS) scavenging and SerpinB2 downregulation may modulate the immune response in UCPPS.

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The global population of individuals afflicted with diabetes mellitus has been increasing year by year, and this disease poses a serious threat to human health as well as the economies worldwide. Pancreatic or islet transplantations provide one of the most effective and long-term therapies available to treat diabetes, but the scarcity and quality of pancreatic islets limit their use in treatments. Here, we report the development of a one-step, monolayer culture, and chemical-based protocol that efficiently mediates the differentiation of human adipose-derived stem cells (hADSCs) into insulin-producing cells (IPCs). Our data indicate that hADSCs in monolayer culture that are allowed to differentiate into IPCs are superior to those in suspension cultures with respect to insulin secretion capacity (213-fold increase), cell viability (93.5 ± 3.27% vs. 41.67 ± 13.17%), and response to glucose stimulation. Moreover, the expression of genes associated with pancreatic lineage specification, such as PDX1, ISL1, and INS (encoding insulin), were expressed at significantly higher levels during our differentiation protocol (6-fold for PDX1 and ISL1, 11.5-fold for INS). Importantly, in vivo studies demonstrated that transplantation with IPCs significantly mitigated hyperglycemia in streptozotocin-induced diabetic rats. Our results indicate that this one-step, rapid protocol increases the efficiency of IPC generation and that the chemical-based approach for IPC induction may reduce safety concerns associated with the use of IPCs for clinical applications, thereby providing a safe and effective cell-based treatment for diabetes.