Transdermal drug delivery via microneedles for musculoskeletal systems.

As the population is ageing and lifestyle is changing, the prevalence of musculoskeletal (MSK) disorders is gradually increasing with each passing year, posing a serious threat to the health and quality of the public, especially the elderly. However, currently prevalent treatments for MSK disorders, mainly administered orally and by injection, are not targeted to the specific lesion, resulting in low efficacy along with a series of local and systemic adverse effects. Microneedle (MN) patches loaded with micron-sized needle array, combining the advantages of oral administration and local injection, have become a potentially novel strategy for the administration and treatment of MSK diseases. In this review, we briefly introduce the basics of MNs and focus on the main characteristics of the MSK systems and various types of MN-based transdermal drug delivery (TDD) systems. We emphasize the progress and broad applications of MN-based transdermal drug delivery (TDD) for MSK systems, including osteoporosis, nutritional rickets and some other typical types of arthritis and muscular damage, and in closing summarize the future prospects and challenges of MNs application.

A Core-Shell Nanoreinforced Ion-Conductive Implantable Hydrogel Bioelectronic Patch with High Sensitivity and Bioactivity for Real-Time Synchronous Heart Monitoring and Repairing.

To achieve synchronous repair and real-time monitoring the infarcted myocardium based on an integrated ion-conductive hydrogel patch is challenging yet intriguing. Herein, a novel synthetic strategy is reported based on core-shell-structured curcumin-nanocomposite-reinforced ion-conductive hydrogel for synchronous heart electrophysiological signal monitoring and infarcted heart repair. The nanoreinforcement and multisite cross-linking of bioactive curcumin nanoparticles enable well elasticity with negligible hysteresis, implantability, ultrahigh mechanoelectrical sensitivity (37 ms), and reliable sensing capacity (over 3000 cycles) for the nanoreinforced hydrogel. Results of in vitro and in vivo experiments demonstrate that such solely physical microenvironment of electrophysiological and biomechanical characteristics combining with the role of bioactive curcumin exert the synchronous benefit of regulating inflammatory microenvironment, promoting angiogenesis, and reducing myocardial fibrosis for effective myocardial infarction (MI) repair. Especially, the hydrogel sensors offer the access for achieving accurate acquisition of cardiac signals, thus monitoring the whole MI healing process. This novel bioactive and electrophysiological-sensing ion-conductive hydrogel cardiac patch highlights a versatile strategy promising for synchronous integration of in vivo real-time monitoring the MI status and excellent MI repair performance.

Highly Stretchable and Biocompatible Wrinkled Nanoclay-Composite Hydrogel With Enhanced Sensing Capability for Precise Detection of Myocardial Infarction.

It is challenging to balance high biocompability with good mechanical-electrical sensing performance, especially when triggering inflammatory stress response after in vivo implantation. Herein, a bioinspired wrinkle-reinforced adaptive nanoclay-interlocked soft strain-sensor based on a highly stretchable and elastic ionic-conductive hydrogel is reported. This novel nanoclay-composite hydrogel exhibits excellent tensile properties and high sensing capacity with steady and reliable sensing performance due to the structural-mechanical-electrical integrity of the nanoclay crosslinked and nano-reinforced interpenetrating network. The incorporation of amphiphilic ions provides the hydrogel with significant protein resistance, reducing its non-specific adsorption to proteins upon implantation, improving its biosafety as an implanted device, and maintaining the authenticity of the sensing results. Based on the revealed sensing enhanced mechanism based on hierarchical ordered structures as a proof-of-concept application, this hydrogel sensor is demonstrated to be able to accurately localize the region where myocardial infarction occurs and may become a novel strategy for real-time monitoring of pathological changes in heart disease.

Effects of sphingolipid metabolism disorders on endothelial cells.

Many cardiovascular disorders, including atherosclerosis, hypertension, coronary heart disease, diabetes, etc., are characterized by endothelial cell dysfunction. Endothelial cell function is closely related to sphingolipid metabolism, and normal sphingolipid metabolism is critical for maintaining endothelial cell homeostasis. Sphingolipid metabolites or key enzymes in abnormal situation, including sphingosine, ceramide (Cer), sphingosine-1-phosphate (S1P), serine, sphingosine kinase (SPHK), ceramide kinase (Cerk), sphingosine-1-phosphate lyase (S1PL) etc., may have a protective or damaging effect on the function of endothelial cells. This review summarizes the effects of sphingolipid metabolites and key enzymes disordering in sphingolipid metabolism on endothelial cells, offering some insights into further research on the pathogenesis of cardiovascular diseases and corresponding therapeutic targets.

Salidroside suppresses inflammation in a D-galactose-induced rat model of Alzheimer's disease via SIRT1/NF-κB pathway.

Age-related inflammation is the predominant factor for neurodegenerative diseases like Alzheimer's disease (AD). In the present study, we examined memory performance and neuroinflammation in D-galactose (D-gal)-induced sub-acute aging model of rats. Our results demonstrated that chronic administration of D-gal (120 mg/kg) produced cognitive impairment as determined by Morris water maze (MWM) test and step-down passive avoidance test. D-gal also activated nuclear factor kappa B (NF-κB) p65/RelA by down-regulating the expression level of sirtuins 1 (SIRT1) in the hippocampus. Treatment with Salidroside (Sal, 20, 40 mg/kg) for 28 days ameliorated D-gal-induced memory deficits and inflammatory mediators including tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß). Moreover, D-gal-induced activation of NF-κB signaling pathway in the brain was also inhibited by Sal via up-regulating SIRT1. These results suggest that D-gal-triggered memory impairment and inflammatory response may be associated with SIRT1/NF-κB signaling pathway, whereas treatment with Sal could positively affect these changes in hippocampus.

P2X7 as a new target for chrysophanol to treat lipopolysaccharide-induced depression in mice.

P2X7 receptor is a ligand gated ion channel found peripheral macrophages and microglia in the nervous system. The current study investigated the relationship between the activated P2X7 and depression for the first time. Chrysophanol (Chr) was examined for its protective effects against depression targeting P2X7. Chr (20mg/kg, 40mg/kg) and fluoxetine (20mg/kg) were intragastrically treated once daily for 7 consecutive days. Lipopolysaccharide (LPS, 0.5mg/kg) was intraperitoneally injected to develop depression model 30min after drug administration on day 7. Behavioral tests were measured 24h after LPS injection. Interleukin (IL)-6, IL-1ß and tumor necrosis factor (TNF)-α levels in serum and hippocampus were measured by enzyme-linked immunosorbent assay (ELISA). The expressions of P2X7/NF-κB pathway-related proteins were assessed by western blot. The findings showed that Chr remarkably reduced the elevations of IL-6, IL-1ß and TNF-α caused by LPS stimulation. The expressions of P2X7, p-IKKα, p-IKKß, p-IκBα and p-NF-κBp65 were significantly decreased by Chr pretreatment. In addition, immobility time in tail suspension test (TST) and forced swimming test (FST) were reduced by Chr without affecting spontaneous locomotor activity in open filed test (OFT) and the preference for sucrose was also recovered in sucrose preference test (SPT) with Chr preconditioning. Thus, it is reasonable to speculate that Chr might exert antidepressant effect through inhibiting P2X7/NF-κB signaling pathway.