MST4: A Potential Oncogene and Therapeutic Target in Breast Cancer

The mammalian STE 20-like protein kinase 4 (MST4) gene is highly expressed in several cancer types, but little is known about the role of MST4 in breast cancer, and the function of MST4 during epithelial-mesenchymal transition (EMT) has not been fully elucidated. Here we report that overexpression of MST4 in breast cancer results in enhanced cell growth, migration, and invasion, whereas inhibition of MST4 expression significantly attenuates these properties. Further study shows that MST4 promotes EMT by activating Akt and its downstream signaling molecules such as E-cadherin/N-cadherin, Snail, and Slug. MST4 also activates AKT and its downstream pro-survival pathway. Furthermore, by analyzing breast cancer patient tissue microarray and silicon datasets, we found that MST4 expression is much higher in breast tumor tissue compared to normal tissue, and significantly correlates with cancer stage, lymph node metastasis and a poor overall survival rate (p 0.05). Taken together, our findings demonstrate the oncogenic potential of MST4 in breast cancer, highlighting its role in cancer cell proliferation, migration/invasion, survival, and EMT, suggesting a possibility that MST4 may serve as a novel therapeutic target for breast cancer

Plant-mediated biosynthesis of nanoparticles as an emerging tool against mosquitoes of medical and veterinary importance: a review

Mosquitoes (Diptera: Culicidae) are a key threat for millions of people worldwide, since they act as vectors for devastating parasites and pathogens. Mosquito young instars are usually targeted with organophosphates, insect growth regulators and microbial control agents. Indoors residual spraying and insecticide-treated bed nets are also employed. However, these chemicals have strong negative effects on human health and the environment. Newer and safer tools have been recently implemented to enhance control of mosquitoes. In this review, I focus on characterization, effectiveness, and non-target effects of mosquitocidal nanoparticles synthesized using botanical products (mosquitocidal nanoparticles, MNP). The majority of plant-fabricated MNP are silver ones. The synthesis of MNP is usually confirmed by UV-visualization spectroscopy, followed by scanning electron microscopy or transmission electron microscopy, energy-dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, and X-ray diffraction studies. Interestingly, plant-synthesized metal nanoparticles have been reported as effective ovicides, larvicides, pupicides, adulticides, and oviposition deterrents against different mosquito species of medical and veterinary importance. Few parts per million of different MNP are highly toxic against the malaria vector Anopheles stephensi, the dengue vector Aedes aegypti, and the filariasis mosquito Culex quiquefasciatus. However, despite the growing number of evidences about the effectiveness of MNP, moderate efforts have been carried out to shed light on their possible non-target effects against mosquito’s natural enemies and other aquatic organisms. In the final section, particular attention was dedicated to this issue. A number of hot areas that need further research and cooperation among parasitologists and entomologists are highlighted

Histone deacetylase 3 controls lung alveolar macrophage development and homeostasis

Alveolar macrophages (AMs) derived from embryonic precursors seed the lung before birth and self-maintain locally throughout adulthood, but are regenerated by bone marrow (BM) under stress conditions. However, the regulation of AM development and maintenance remains poorly understood. Here, we show that histone deacetylase 3 (HDAC3) is a key epigenetic factor required for AM embryonic development, postnatal homeostasis, maturation, and regeneration from BM. Loss of HDAC3 in early embryonic development affects AM development starting at E14.5, while loss of HDAC3 after birth affects AM homeostasis and maturation. Single-cell RNA sequencing analyses reveal four distinct AM sub-clusters and a dysregulated cluster-specific pathway in the HDAC3-deficient AMs. Moreover, HDAC3-deficient AMs exhibit severe mitochondrial oxidative dysfunction and deteriorative cell death. Mechanistically, HDAC3 directly binds to Pparg enhancers, and HDAC3 deficiency impairs Pparg expression and its signaling pathway. Our findings identify HDAC3 as a key epigenetic regulator of lung AM development and homeostasis