Autophagy Modulation in Therapeutic Strategy of Breast Cancer Drug Resistance.

Breast cancer (BC) is a prevalent malignancy globally. Autophagy plays a pivotal role in all stages of this disease, including development, metastasis, and onset. Therefore, it is envisaged that targeting cell autophagy through appropriate tactics would evolve into a novel breast cancer prevention and therapy strategy. A multitude of chemotherapeutic medications can stimulate autophagy in tumor cells. It has led to divergent opinions on the function of autophagy in cancer treatment, as both stimulating and blocking autophagy can improve the effectiveness of anticancer medications. Consequently, the decision of whether to stimulate or inhibit autophagy during breast cancer treatment has become crucial. Understanding the distinctive mechanisms of autophagy in BC and its significance in medication therapy might facilitate the creation of targeted treatment plans based on the roles particular to autophagy. This review summarizes recent studies on the autophagy mechanism in breast cancer and provides insights into autophagy-based BC therapeutic techniques, giving fresh avenues for future BC treatment.

LINC00839 in Human Disorders: Insights into its Regulatory Roles and Clinical Impact, with a Special Focus on Cancer.

LINC00839 has captured significant attention within a spectrum of human disorders, including acute lung injury, osteoarthritis, and childhood obesity. Notably, aberrant expression patterns of LINC00839 have been observed across diverse cancer tissues and cell lines. LINC00839 emerges as an oncogenic factor in tumorigenesis and exerts a positive influence on tumor-associated behaviors. Its therapeutic potential for various cancers is underscored by its modulatory impact on pivotal signaling pathways, such as PI3K/AKT, OXPHOS, and Wnt/ß-catenin. Additionally, LINC00839's role in reducing sensitivity to drug and radiotherapy interventions presents opportunities for targeted intervention. Furthermore, elevated LINC00839 expression indicates advanced clinicopathological features and foretells unfavorable prognoses, as validated by publications and comprehensive analyses of tumor types using TCGA datasets. This review elucidates the multiple regulatory mechanisms and functional implications of LINC00839 in various diseases, especially malignancies, emphasizing its potential as a predictive biomarker and therapeutic target across multiple disease domains in humans.

Selective Targeting of Class I HDAC Reduces Microglial Inflammation in the Entorhinal Cortex of Young APP/PS1 Mice.

BG45 is a class Ⅰ histone deacetylase inhibitor (HDACI) with selectivity for HDAC3. Our previous study demonstrated that BG45 can upregulate the expression of synaptic proteins and reduce the loss of neurons in the hippocampus of APPswe/PS1dE9 (APP/PS1) transgenic mice (Tg). The entorhinal cortex is a pivotal region that, along with the hippocampus, plays a critical role in memory in the Alzheimer's disease (AD) pathology process. In this study, we focused on the inflammatory changes in the entorhinal cortex of APP/PS1 mice and further explored the therapeutic effects of BG45 on the pathologies. The APP/PS1 mice were randomly divided into the transgenic group without BG45 (Tg group) and the BG45-treated groups. The BG45-treated groups were treated with BG45 at 2 months (2 m group), at 6 months (6 m group), or twice at 2 and 6 months (2 and 6 m group). The wild-type mice group (Wt group) served as the control. All mice were killed within 24 h after the last injection at 6 months. The results showed that amyloid-ß (Aß) deposition and IBA1-positive microglia and GFAP-positive astrocytes in the entorhinal cortex of the APP/PS1 mice progressively increased over time from 3 to 8 months of age. When the APP/PS1 mice were treated with BG45, the level of H3K9K14/H3 acetylation was improved and the expression of histonedeacetylase1, histonedeacetylase2, and histonedeacetylase3 was inhibited, especially in the 2 and 6 m group. BG45 alleviated Aß deposition and reduced the phosphorylation level of tau protein. The number of IBA1-positive microglia and GFAP-positive astrocytes decreased with BG45 treatment, and the effect was more significant in the 2 and 6 m group. Meanwhile, the expression of synaptic proteins synaptophysin, postsynaptic density protein 95, and spinophilin was upregulated and the degeneration of neurons was alleviated. Moreover, BG45 reduced the gene expression of inflammatory cytokines interleukin-1ß and tumor necrosis factor-α. Closely related to the CREB/BDNF/NF-kB pathway, the expression of p-CREB/CREB, BDNF, and TrkB was increased in all BG45 administered groups compared with the Tg group. However, the levels of p-NF-kB/NF-kB in the BG45 treatment groups were reduced. Therefore, we deduced that BG45 is a potential drug for AD by alleviating inflammation and regulating the CREB/BDNF/NF-kB pathway, and the early, repeated administration of BG45 can play a more effective role.