Danggui Shaoyao San Alleviates Early Cognitive Impairment in Alzheimer's Disease Mice Through IRS1/GSK3ß/Wnt3a-ß-Catenin Pathway.

INTRODUCTION: Alzheimer's disease (AD) is a neurodegenerative disease characterized by Amyloid plaques and neurofibrillary tangles. We explored the potential mechanism by which Danggui Shaoyao San (DSS) modulates central glucose metabolism via the insulin receptor substrate 1 (IRS1)/glycogen synthase kinase-3ß (GSK3ß)/Wnt3a-ß-catenin pathway, thereby exerting protective effects on cognitive functions. METHODS: In vitro, HT22 cells were induced with streptozotocin (STZ) to investigate the impact of GSK3ß on pathway transduction. The active components in the DSS stock solution were validated using mass spectrometry. Subsequently, an AD model in C57BL/6J mice was established through STZ injection into both ventricles. The success of the model was validated behaviorally and pathologically. The Morris Water Maze (MWM) test, immunohistochemistry, Western blotting, quantitative reverse transcription-PCR, and 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) were employed to evaluate the influence of DSS on memory and pathological changes in AD. RESULTS: The DSS stock solution, rich in active components, ameliorated the memory deficits in AD mice in the MWM. In vitro, GSK3ß exhibited regulatory control over Wnt and ß-catenin, with GSK3ß inhibition mitigating ß-amyloid and tau redundancies at protein and gene levels, facilitating signal transduction. In vivo, DSS impacted key targets in the IRS1/GSK3ß/Wnt3a-ß-catenin pathway, mitigated senile plaques resulting from amyloid ß (Aß) deposition and neurofiber tangles induced by tau hyperphosphorylation, and alleviated the decline in central glucose metabolism observed in FDG-PET. CONCLUSIONS: Our findings suggest that DSS potentially confers cognitive protection by alleviating central hypoglycemia through the IRS1/GSK3ß/Wnt3a-ß-catenin pathway. This may serve as a promising therapeutic avenue for AD.

Cancer-Thylakoid Hybrid Membrane Camouflaged Thulium Oxide Nanoparticles with Oxygen Self-Supply Capability for Tumor-Homing Phototherapy.

Nanomaterials that generate reactive oxygen species (ROS) upon light irradiation have significant applications in various fields, including photodynamic therapy (PDT) that is widely recognized as a highly momentous strategy for the eradication of cancer cells. However, the ROS production rate of photosensitizers, as well as the tumor hypoxia environment, are two major challenges that restrict the widespread application of PDT. In this study, a cancer-thylakoid hybrid membrane-camouflaged thulium oxide nanoparticles (Tm2O3) for tumor-homing phototherapy through dual-stage-light-guided ROS generation and oxygen self-supply is developed. Tm2O3 as a type II photosensitizer are viable for NIR-stimulated ROS generation due to the unique energy levels, large absorption cross section, and long lifetime of the 3H4 state of Tm ions. The thylakoid membrane (TK) plays a catalase-like role in converting hydrogen peroxide into oxygen and also acts as a natural photosensitizer that can generate lethal ROS through electron transfer when exposed to light. In addition, fluorescence dye DiR is embedded in the hybrid membrane for in vivo tracing as well as photothermal therapy. Results show that tumors in Tm2O3@TK-M/DiR group are effectively ablated following dual-stage-light irradiation, highlighting the promising potential of rare-earth element-based type II photosensitizers in various applications.

Relationship Between Intestinal Flora and Bone and Joint Diseases and Regulation of Traditional Chinese Medicine： A Review / 中国实验方剂学杂志

Intestinal flora is the largest microbial community in human body， which consists of more than 1 000 species. Its structure and metabolites change dynamically with the age， diet and intestinal environment of the host. Study shows that the intestinal microbes play a pivotal role in regulating human physiological and pathological processes， and intestinal flora imbalance may be the key factors affecting the occurrence and development of bone and joint diseases， including osteoporosis， osteoarthritis， rheumatoid arthritis and gouty arthritis. At present， calcitonin， estrogen， nonsteroidal anti-inflammatory drugs， immunosuppressants， xanthine oxidase inhibitors and other western drugs are mostly used to treat the above diseases. However， long-term use of western drugs leads to poor compliance and obvious gastrointestinal adverse reactions among patients. Traditional Chinese medicine （TCM） predominates in the treatment of bone and joint diseases due to its low price， high efficacy and slight side effects， with the advantages of multi-targets， multi-mechanism and multi-levels. In recent years， many scholars have carried out experiments and clinical studies on the treatment of bone and joint diseases by TCMs on the basis of the liver and kidney theory such as "tonifying liver and kidney and strengthening muscles and bones". Gratifying results have been achieved. However， the mechanism of action has not been fully clarified. Intestinal flora becomes a hot spot in medical research， and a close relationship between intestinal flora and bone and joint diseases has been unveiled. Relevant literature in China and abroad showed that TCM has a significant effect on the treatment of bone and joint diseases by regulating intestinal flora. In this paper， the relationship between intestinal flora and bone and joint diseases was summarized and the intervention of TCM active ingredients and compounds on intestinal flora was reviewed to facilitate the prevention and treatment of bone and joint diseases by TCM.

Role of Cytokines in Osteoporosis and Intervention with Traditional Chinese Medicine： A Review / 中国实验方剂学杂志

Osteoporosis （OP） is one of the most common diseases in the aged population worldwide. Due to the rapid change in world population structure， the effective prevention and treatment of OP is increasingly becoming the health problem of global concern and also the hot spot of clinical research. OP can be affected by many factors such as heredity， endocrine dyscrasia， nutritional deficiency， and bad living habits. The breakdown of coupling of osteoclast-mediated bone resorption to osteoblast-mediated bone formation leads to stronger bone resorption than bone formation， which is currently recognized as the main pathogenesis of OP. The exploration of OP in modern medicine based on molecular immunology has revealed that related cytokines play an important role in the pathogenesis of OP，and regulating the osteoclast-mediated bone resorption and osteoblast-mediated bone formation is essential for controlling the occurrence and development of OP. Tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） are able to stimulate bone formation and inhibit osteoblast function， thus playing a key role in bone destruction. By contrast， such cytokines as vascular endothelial growth factor （VEGF）， transforming growth factor-β （TGF-β）， bone morphogenetic protein （BMP）， and osteoprotegerin （OPG） strengthen osteoblast differentiation and promote bone formation. At present， western medicine like calcitonin， estrogen， and bisphosphonate are mostly used for clinical treatment of OP， but a long-term use of these drugs will result in poor compliance and obvious gastrointestinal adverse reactions. Traditional Chinese medicine （TCM） occupies an important position in the treatment of OP due to its advantages of overall regulation， low price， and few side effects. In addition， with the deepening of research on network pharmacology and molecular biology， it has been found that TCM exerts the therapeutic effect against OP by interfering with the expression of various cytokines and adjusting bone homeostasis. This paper has elaborated the role of related cytokines in the pathogenesis of OP and reviewed the research results concerning the regulation of related cytokines by TCM， in order to provide reference for the prevention and treatment of OP with TCM.