Persistent and impaired inflammation impedes tissue healing and is a characteristic of chronic wounds. A better understanding of the mechanisms controlling wound inflammation is needed. In this study, we show that in human wound-edge keratinocytes, the expressions of microRNA (miR)-17, miR-18a, miR-19a, miR-19b, and miR-20a, which all belong to the miR-17∼92 cluster, are upregulated during wound repair. However, their levels are lower in chronic ulcers than in acute wounds at the proliferative phase. Conditional knockout of miR-17∼92 in keratinocytes as well as injection of miR-19a/b and miR-20a antisense inhibitors into wound edges enhanced inflammation and delayed wound closure in mice. In contrast, conditional overexpression of the miR-17∼92 cluster or miR-19b alone in mice keratinocytes accelerated wound closure in vivo. Mechanistically, miR-19a/b and miR-20a decreased TLR3-mediated NF-κB activation by targeting SHCBP1 and SEMA7A, respectively, reducing the production of inflammatory chemokines and cytokines by keratinocytes. Thus, miR-19a/b and miR-20a being crucial regulators of wound inflammation, the lack thereof may contribute to sustained inflammation and impaired healing in chronic wounds. In line with this, we show that a combinatory treatment with miR-19b and miR-20a improved wound healing in a mouse model of type 2 diabetes.

Alzheimer’s disease, a devastating neurodegenerative disorder, is characterized by progressive cognitive decline, primarily due to amyloid-beta protein deposition and tau protein phosphorylation. Effectively reducing the cytotoxicity of amyloid-beta42 aggregates and tau oligomers may help slow the progression of Alzheimer’s disease. Conventional drugs, such as donepezil, can only alleviate symptoms and are not able to prevent the underlying pathological processes or cognitive decline. Currently, active and passive immunotherapies targeting amyloid-beta and tau have shown some efficacy in mice with asymptomatic Alzheimer’s disease and other transgenic animal models, attracting considerable attention. However, the clinical application of these immunotherapies demonstrated only limited efficacy before the discovery of lecanemab and donanemab. This review first discusses the advancements in the pathogenesis of Alzheimer’s disease and active and passive immunotherapies targeting amyloid-beta and tau proteins. Furthermore, it reviews the advantages and disadvantages of various immunotherapies and considers their future prospects. Although some antibodies have shown promise in patients with mild Alzheimer’s disease, substantial clinical data are still lacking to validate their effectiveness in individuals with moderate Alzheimer’s disease.

JOURNAL/nrgr/04.03/01300535-202210000-00042/figure1/v/2026-05-26T060850Z/r/image-tiff The amyloid-β (Aβ) oligomer, rather than the Aβ monomer, is considered to be the primary initiator of Alzheimer’s disease. It was hypothesized that p(Aβ3–10)10-MT, the recombinant Aβ3–10 gene vaccine of the Aβ oligomer has the potential to treat Alzheimer’s disease. In this study, we intramuscularly injected the p(Aβ3–10)10-MT vaccine into the left hindlimb of APP/PS1/tau triple-transgenic mice, which are a model for Alzheimer’s disease. Our results showed that the p(Aβ3–10)10-MT vaccine effectively reduced Aβ oligomer levels and plaque deposition in the cerebral cortex and hippocampus, decreased the levels tau protein variants, reduced synaptic loss, protected synaptic function, reduced neuron loss, and ameliorated memory impairment without causing any cerebral hemorrhaging. Therefore, this novel DNA vaccine, which is safe and highly effective in mouse models of Alzheimer’s disease, holds a lot of promise for the treatment of Alzheimer’s disease in humans.

Cadmium (Cd), a ubiquitous environmental pollutant, exhibits potential neurotoxic risk. While compelling evidence links Cd accumulation to the pathogenesis of Alzheimer's disease (AD), the global impact of blood Cd exposure on AD mortality remains underexplored. We conducted an extensive review of 102 studies from 30 countries and standardized blood Cd concentrations to estimate the geometric mean (GM) and geometric standard deviation (GSD) of Cd exposure. Estimated annual percentage change (EAPC) was calculated to assess the trend in AD mortality, with 1000 Monte Carlo simulations to estimate population attributable fractions (RAF). The augmented human development index (AHDI) was used to analyze correlations with Cd-related mortality. Bayesian hierarchical regression models revealed a 72% reduction in GM in Egypt, contrasted by a 142% increase in Australia. Germany and Brazil demonstrated significant GM reductions along with increased GSD, reflecting regional variability. Conversely, Japan and South Korea exhibited marked rises in the regional variability, while Egypt and France achieved significant reductions in Cd-related AD deaths for both males and females, reaching zero by 2020. The number of deaths related to Cd in Australia and Japan has increased. While countries like Norway, Germany, and Lithuania showed declining mortality trends, others (e.g., Poland and Italy), exhibited rising mortality despite AHDI improvements. This study represents the first comprehensive assessment of the global burden of AD attributable to blood Cd exposure, reveal significant regional disparities. It provides epidemiological references for policymakers to formulate Cd management strategies and guides researchers in selecting impactful study directions.

Skin aging is a highly complex process embracing chronological aging and photoaging. Continuous advancement in the study of skin aging facilitates the innovations of skin rejuvenation therapies. However, the mechanism underlying skin aging remains largely unexplored. Herein, differential expression gene (DEG) analysis identified a gradual down‐regulation of PIK3R1 in aged untreated skin, aged treated skin (treated with intense pulsed light), and young skin. Among 11 964 background genes, thousands of DEGs were identified in all aged/young and PIK3R1‐low/high groups. Coexpression modules were created using weight gene correlation network analysis, showing an enrichment in PI3K/AKT, Rap1, regulating pluripotency of stem cells (rPSC), etc. Furthermore, DEGs with strong relation to skin vitality and PIK3R1 were extracted for network analysis, wherein cross‐talking pathways of PIK3R1 including PI3K/AKT, Rap1, and rPSC were identified. The same cross‐talking pathways were also replicated in aged untreated and treated skin, as implemented by enrichment analyses of DEGs in aged untreated versus young or aged treated skin. According to the area under the curve of 100% and 88%, PIK3R1 possibly predicted skin aging and skin rejuvenation, respectively. RT‐PCR and western blot confirmed the decline of PIK3R1 expression in aged treated and young skin, compared with aged untreated skin. PIK3R1 knockdown led to increased p‐AKT (Ser473) and Bcl‐2, and decreased p‐FOXO1 (Ser256) and MMP‐1, which may be the cause of more resistance to ultraviolet A induced cell senescence, proliferation inhibition, apoptosis, and collagen synthesis decline in PIK3R1 knockdown HDFs. Our study preliminarily elucidates the comprehensive role of PIK3R1 in skin aging, providing a potential new target for skin rejuvenation.