Cordycepin Modulates Microglial M2 Polarization Coupled with Mitochondrial Metabolic Reprogramming by Targeting HKII and PDK2.

The microenvironment mediated by the microglia (MG) M1/M2 phenotypic switch plays a decisive role in the neuronal fate and cognitive function of Alzheimer's disease (AD). However, the impact of metabolic reprogramming on microglial polarization and its underlying mechanism remains elusive. This study reveals that cordycepin improved cognitive function and memory in APP/PS1 mice, as well as attenuated neuronal damage by triggering MG-M2 polarization and metabolic reprogramming characterized by increased OXPHOS and glycolysis, rather than directly protecting neurons. Simultaneously, cordycepin partially alleviates mitochondrial damage in microglia induced by inhibitors of OXPHOS and glycolysis, further promoting MG-M2 transformation and increasing neuronal survival. Through confirmation of cordycepin distribution in the microglial mitochondria via mitochondrial isolation followed by HPLC-MS/MS techniques, HKII and PDK2 are further identified as potential targets of cordycepin. By investigating the effects of HKII and PDK2 inhibitors, the mechanism through which cordycepin targeted HKII to elevate ECAR levels in the glycolysis pathway while targeting PDK2 to enhance OCR levels in PDH-mediated OXPHOS pathway, thereby inducing MG-M2 polarization, promoting neuronal survival and exerting an anti-AD role is elucidated.

Early signs of neurodegenerative diseases: Possible mechanisms and targets for Golgi stress.

The Golgi apparatus plays a crucial role in mediating the modification, transport, and sorting of intracellular proteins and lipids. The morphological changes occurring in the Golgi apparatus are exceptionally important for maintaining its function. When exposed to external pressure or environmental stimulation, the Golgi apparatus undergoes adaptive changes in both structure and function, which are known as Golgi stress. Although certain signal pathway responses or post-translational modifications have been observed following Golgi stress, further research is needed to comprehensively summarize and understand the related mechanisms. Currently, there is evidence linking Golgi stress to neurodegenerative diseases; however, the role of Golgi stress in the progression of neurodegenerative diseases such as Alzheimer's disease remains largely unexplored. This review focuses on the structural and functional alterations of the Golgi apparatus during stress, elucidating potential mechanisms underlying the involvement of Golgi stress in regulating immunity, autophagy, and metabolic processes. Additionally, it highlights the pivotal role of Golgi stress as an early signaling event implicated in the pathogenesis and progression of neurodegenerative diseases. Furthermore, this study summarizes prospective targets that can be therapeutically exploited to mitigate neurodegenerative diseases by targeting Golgi stress. These findings provide a theoretical foundation for identifying novel breakthroughs in preventing and treating neurodegenerative diseases.

Photothermal hydrogels for infection control and tissue regeneration.

In this review, we report investigating photothermal hydrogels, innovative biomedical materials designed for infection control and tissue regeneration. These hydrogels exhibit responsiveness to near-infrared (NIR) stimulation, altering their structure and properties, which is pivotal for medical applications. Photothermal hydrogels have emerged as a significant advancement in medical materials, harnessing photothermal agents (PTAs) to respond to NIR light. This responsiveness is crucial for controlling infections and promoting tissue healing. We discuss three construction methods for preparing photothermal hydrogels, emphasizing their design and synthesis, which incorporate PTAs to achieve the desired photothermal effects. The application of these hydrogels demonstrates enhanced infection control and tissue regeneration, supported by their unique photothermal properties. Although research progress in photothermal hydrogels is promising, challenges remain. We address these issues and explore future directions to enhance their therapeutic potential.

Association of Circulating Apolipoprotein AI Levels in Patients With Alzheimer's Disease: A Systematic Review and Meta-Analysis.

With the development of medicine, our research on Alzheimer's disease (AD) has been further deepened, but the mechanism of its occurrence and development has not been fully revealed, and there is currently no effective treatment method. Several studies have shown that apolipoprotein AI (ApoA-I) can affect the occurrence and development of Alzheimer's disease by binding to amyloid ß (Aß). However, the association between circulating levels of ApoA-I and AD remains controversial. We conducted a meta-analysis of 18 studies published between 1992 and 2017 to determine whether the ApoA-I levels in the blood and cerebrospinal fluid (CSF) are abnormal in AD. Literatures were searched in PubMed, EMBASE and Web of Science databases without language limitations. A pooled subject sample including 1,077 AD patients and 1,271 healthy controls (HCs) was available to assess circulating ApoA-I levels; 747 AD patients and 680 HCs were included for ApoA-I levels in serum; 246 AD patients and 456 HCs were included for ApoA-I levels in plasma; 201 AD patients and 447 HCs were included for ApoA-I levels in CSF. It was found that serum and plasma levels of ApoA-I were significantly reduced in AD patients compared with HCs {[standardized mean difference (SMD) = -1.16; 95% confidence interval (CI) (-1.72, -0.59); P = 0.000] and [SMD = -1.13; 95% CI (-2.05, -0.21); P = 0.016]}. Patients with AD showed a tendency toward higher CSF ApoA-I levels compared with HCs, although this difference was non-significant [SMD = 0.20; 95% CI (-0.16, 0.56); P = 0.273]. In addition, when we analyzed the ApoA-I levels of serum and plasma together, the circulating ApoA-I levels in AD patients was significantly lower [SMD = -1.15; 95% CI (-1.63, -0.66); P = 0.000]. These results indicate that ApoA-I deficiency may be a risk factor of AD, and ApoA-I has the potential to serve as a biomarker for AD and provide experimental evidence for diagnosis of AD. Systematic Review Registration: PROSPERO, identifier: 325961.