Increased generation of reactive oxygen species (ROS) has been implicated in the pathogenesis of a variety of diseases such as cardiovascular diseases and cancer. NADPH oxidase (Nox), a multicomponent enzyme, has been identified as one of the key sources of ROS. Nox4, one of the seven members of Nox family (Nox1, Nox2, Nox3, Nox4, Nox5, Duox1 and Duox2), has been extensively investigated in recent years. Its unique structures result in the constitutive generation of hydrogen peroxide (H2O2) as the main product. As a key oxygen sensor, Nox4-derived H2O2 plays diverse roles in cell proliferation, migration and death. Increased expression of Nox4 in cancer has been observed, which participates in metastasis, angiogenesis and apoptosis. Expression of Nox4 in endothelial cells actively mediated endothelial activation, dysfunction and injury, which contributes to the development of atherosclerosis, hypertension, cardiac hypertrophy and among others. This article explores the experimental studies related to the gene, structure, physiological function and pathological significance of Nox4. As Nox4 might serve as a potential target for the therapy of cardiovascular diseases and cancer, the Nox4 inhibitor is also discussed in this article.

Curcuma, a valuable genus in the family Zingiberaceae, includes approximately 110 species. These plants are native to Southeast Asia and are extensively cultivated in India, China, Sri Lanka, Indonesia, Peru, Australia, and the West Indies. The plants have long been used in folk medicine to treat stomach ailments, stimulate digestion, and protect the digestive organs, including the intestines, stomach, and liver. In recent years, substantial progress has been achieved in investigations regarding the chemical and pharmacological properties, as well as in clinical trials of certain Curcuma species. This review comprehensively summarizes the current knowledge on the chemistry and briefly discusses the biological activities of Curcuma species. A total of 720 compounds, including 102 diphenylalkanoids, 19 phenylpropene derivatives, 529 terpenoids, 15 flavonoids, 7 steroids, 3 alkaloids, and 44 compounds of other types isolated or identified from 32 species, have been phytochemically investigated. The biological activities of plant extracts and pure compounds are classified into 15 groups in detail, with emphasis on anti-inflammatory and antitumor activities.

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ICAM-1 overexpression and subsequent adhesion of leukocytes to endothelial cells play critical roles in the early stage of atherosclerosis. Danshenol A (DA) is an abietane-type diterpenoid isolated from traditional Chinese herb Salvia miltiorrhiza Bunge. The mechanisms under its regulation of adhesion of molecular expression are explored. Here, the effect of DA on TNF-α-induced ICAM-1 expression was investigated in endothelial cells. TNF-α-induced ICAM-1 expression and subsequent adhesion of monocytes, as well as elevated reactive oxygen species (ROS) generation and NOX4 expression were all significantly reversed by DA, siNOX4 and NOX4 inhibitor GKT137831. Furthermore, TNF-α-induced ICAM-1 expression, which was increased via IKKβ/IκBα-mediated activation of NF-κB p65, was also inhibited by DA. Interestingly, NOX4 overexpression suppressed the ICAM-1 expression, and this finding may be ascribed to the activation of Nrf-2. Additionally, NF-κB inhibitor PDTC, siNOX4, or DA can decrease the TNF-α-induced ICAM-1 expression and suppress the adhesion of monocytes. In all, DA inhibited TNF-α-induced ICAM-1 expression and subsequent monocyte adhesion to endothelial cells through the NOX4-dependent IKKβ/NF-κB pathway. Besides, NOX4 played dual role in regulating ICAM-1 expression via diverse signal pathway. This novel bioactivity will make DA a good candidate to be further explored for therapeutic or preventive application for atherosclerosis.

Chromatin complexes control a vast number of epigenetic developmental processes. Filamentous fungi present an important clade of microbes with poor understanding of underlying epigenetic mechanisms. Here, we describe a chromatin binding complex in the fungus Aspergillus nidulans composing of a H3K4 histone demethylase KdmB, a cohesin acetyltransferase (EcoA), a histone deacetylase (RpdA) and a histone reader/E3 ligase protein (SntB). In vitro and in vivo evidence demonstrate that this KERS complex is assembled from the EcoA-KdmB and SntB-RpdA heterodimers. KdmB and SntB play opposing roles in regulating the cellular levels and stability of EcoA, as KdmB prevents SntB-mediated degradation of EcoA. The KERS complex is recruited to transcription initiation start sites at active core promoters exerting promoter-specific transcriptional effects. Interestingly, deletion of any one of the KERS subunits results in a common negative effect on morphogenesis and production of secondary metabolites, molecules important for niche securement in filamentous fungi. Consequently, the entire mycotoxin sterigmatocystin gene cluster is downregulated and asexual development is reduced in the four KERS mutants. The elucidation of the recruitment of epigenetic regulators to chromatin via the KERS complex provides the first mechanistic, chromatin-based understanding of how development is connected with small molecule synthesis in fungi.