In this study, we investigated the effects of calycosin on breast cancer cell progression and their underlying mechanisms. Calycosin dose- and time-dependently inhibited proliferation, migration, and invasion by T47D and MCF-7 breast cancer cells by downregulating basic leucine zipper ATF-like transcription factor (BATF) expression. Moreover, BATF promoted breast cancer cell migration and invasiveness by increasing TGFβ1 mRNA and protein levels. Bioinformatics analysis, dual luciferase reporter assays, and chromatin immunoprecipitation assays confirmed the presence of BATF-binding sites in the promoter sequence of TGFβ1 gene. Calycosin treatment inhibited epithelial-mesenchymal transition (EMT) of breast cancer cells by significantly increasing E-cadherin levels and decreasing N-cadherin, Vimentin, CD147, MMP-2, and MMP-9 levels through downregulation of BATF and TGFβ1. TGFβ1 knockdown reduced the migration and invasiveness of BATF-overexpressing breast cancer cells, whereas incubation with TGFβ1 enhanced the migration and invasiveness of calycosin-treated breast cancer cells. Our findings demonstrated that calycosin inhibited EMT and progression of breast cancer cells by suppressing BATF/TGFβ1 signaling. This suggests calycosin would be a promising therapeutic option for breast cancer patients.

Pyroptosis is a form of cell death mediated by inflammasomes and gasdermins, and the relevance of pyroptosis to neurodegenerative diseases is currently receiving increasing attention. Alzheimer’s disease (AD) is a chronic progressive neurodegenerative disease that is closely associated with neuroinflammation. Its main pathological features include β-amyloid (Aβ) deposition, Tau protein hyperphosphorylation and neuronal loss. Aβ, tau-induced microglia pyroptosis and polarization leading to neuroinflammation play an important role in the pathogenesis of AD. Studying the pathogenesis and treatment of AD based on cellular pyroptosis has become a new direction in AD research. In this paper, we review the research progress of pyroptosis and will focus on the pathogenic roles of pyroptosis in AD and the role of targeted inhibition of inflammasome-dependent pyroptosis in AD treatment. These results deepen our understanding of the pathogenesis of AD and provide ideas for the development of new drugs based on the regulation of pyroptosis in AD patients.

Background: Oocyte quality is critical for the mammalian reproduction due to its necessity on fertilization and early development. During aging, the declined oocytes showing with organelle dysfunction and oxidative stress lead to infertility. AMP-activated protein kinase (AMPK) is a serine/threonine protein kinase which is important for energy homeostasis for metabolism. Little is known about the potential relationship between AMPK with oocyte aging. Results: In present study we reported that AMPK was related with low quality of oocytes under post ovulatory aging and the potential mechanism. We showed the altered AMPK level during aging and inhibition of AMPK activity induced mouse oocyte maturation defect. Further analysis indicated that similar with its upstream regulator PKD1, AMPK could reduce ROS level to avoid oxidative stress in oocytes, and this might be due to its regulation on mitochondria function, since loss of AMPK activity induced abnormal distribution, reduced ATP production and mtDNA copy number of mitochondria. Besides, we also found that the ER and Golgi apparatus distribution was aberrant after AMPK inhibition, and enhanced lysosome function was also observed. Conclusions: Taken together, these data indicated that AMPK is important for the organelle function to reduce oxidative stress during oocyte meiotic maturation.

Deoxynivalenol (DON) is a secondary metabolite of Fusarium fungi and belonged to trichothecenes, and it widely presents in various food commodities. Previous studies have highlighted its potent toxicity, adversely affecting the growth, development, and reproductive in both humans and animals. However, the potential impact of DON on porcine oocyte organelles remains elusive. In present study, we delved into the toxic effects of DON on mitochondria, endoplasmic reticulum, Golgi during the porcine oocyte maturation. Our findings revealed that DON exposure significantly impeded granulosa cell diffusion and the expulsion of the first polar body. Additionally, mitochondrial fluorescence intensity and membrane potential underwent notable alterations under DON exposure. Notably, lysosomal fluorescence intensity decreased significantly, suggesting protein degradation and potential autophagy, which was further corroborated by the enhanced fluorescence intensity of LC3. Furthermore, endoplasmic reticulum fluorescence intensity declined, and DON exposure elevated endoplasmic reticulum stress levels, evident from the upregulated expression of GRP78. Concurrently, we observed disruption in the fusiform cortex distribution of the Golgi apparatus, characterized by reduced Golgi apparatus fluorescence intensity and GM130 expression. Collectively, our results indicate that DON exposure profoundly affects the fundamental functions of porcine oocyte organelles during meiosis and maturation.

Background: Delay in diagnosis and treatment worsens the disease and clinical outcomes, which further enhances the transmission of tuberculosis (TB) in the community. Therefore, this study aims to assess treatment delay and its associated factors among childhood pleural TB patients in China. Methods: Between January 2006 and December 2019, consecutive patients aged ≤15 years with definite or possible pleural TB were included for analysis. Treatment delay duration was defined as the time interval from the onset of symptoms to treatment initiation and was stratified into two categories: < 30 days, ≥30 days (median delay day is 30 days). The electronic medical records of children were reviewed to obtain demographic characteristics, clinical characteristics, laboratory examinations, and radiographic findings. Univariate and multivariate logistic regressions were used to explore the factors associated with treatment delay in patients. Results: A total of 154 children with pleural TB were included, with a mean age of 12.4 ± 3.3 years. The median treatment delay was 30 days (interquartile range, 10–60 days) and 51.3% (n = 79) of patients underwent a treatment delay. Multivariate analysis revealed that heart rate (≤92 beats/min, age-adjusted OR = 2.503, 95% CI: 1.215, 5.155) and coefficient of variation of red cell distribution width (RDW-CV, ≥12.9%, age-adjusted OR = 4.705, 95% CI: 2.048, 10.811) were significant risk factors for treatment delays in childhood pleural TB. Conclusion: Our findings suggested that a significant treatment delay occurs among children with pleural TB in China. Patients with a low heart rate or a high RDW-CV experienced delays in the initiation of anti-TB therapy. Therefore, well awareness of the associations between clinical characteristics and treatment delay may improve the management of children with pleural TB and enable us to develop preventive strategies to reduce the treatment delay.