[Treatment of chronic prostatitis with Xiongji Formula based on the concept of "brain-heart-kidney-essence chamber" axis of medication].

Chronic prostatitis is a process of kidney deficiency and blood stasis mixed with various pathological factors involving the essence chamber, which is manifested as kidney deficiency and blood stasis. Based on the concept of the "brain-heart-kidney-essence chamber" axis of medication, Xiongji Formula is applied to the treatment of chronic prostatitis, due to its "simultaneous holistic and local action" and effects of tonifying the kidney yang and assisting the systemic yang, acting on the brain, heart and kidney as a whole, and meanwhile activating blood circulation, eliminating blood stasis and restoring the function of the essence chamber. This paper discusses the etiology and pathogenesis of chronic prostatitis with kidney deficiency and blood stasis in Chinese medicine, expounds the significance of "brain-heart-kidney-essence chamber" axis of medication, and explores the specific value and clinical application of Xiongji Formula.

Kaempferol protects gut-vascular barrier from high glucose-induced disorder via NF-κB pathway.

Kaempferol is a natural edible flavonoid reported to treat high-fat diet-induced intestinal inflammation; however, the underlying molecular mechanisms remain unclear. This research aims to investigate the protective effect of kaempferol on the gut-vascular barrier (GVB) induced by high glucose and elucidate the underlying mechanism. Evans blue albumin efflux assay was used to test endothelial cell permeability. The results showed that kaempferol (50 µM) significantly reversed the high glucose-induced monolayer barrier permeability of rat intestinal microvascular endothelial cells (RIMVECs), while kaempferol significantly alleviated the high glucose-induced rarefication of the tight junction protein Claudin-5. Moreover, kaempferol also reduced high glucose-induced angiogenesis and cell migration via inhibiting the VEGFR2/p38 pathway. Kaempferol also protected against high glucose-induced overproduction of intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 by inhibiting NF-κB p65 nuclear translocation. In addition, kaempferol had similar effects to the NF-κB inhibitor SN50 in reducing high glucose-induced ICAM-1 expression and endothelial barrier permeabilization. Our findings in part reveal the pathological mechanism of hyperglycemia-related gastrointestinal diseases and underlie the molecular mechanism of kaempferol in inhibiting bowel inflammation from a novel perspective.

Exploring New Mechanism of Depression from the Effects of Virus on Nerve Cells.

Depression is a common neuropsychiatric disorder with long-term recurrent depressed mood, pain and despair, pessimism and anxiety, and even suicidal tendencies as the main symptoms. Depression usually induces or aggravates the development of other related diseases, such as sleep disorders and endocrine disorders. In today's society, the incidence of depression is increasing worldwide, and its pathogenesis is complex and generally believed to be related to genetic, psychological, environmental, and biological factors. Current studies have shown the key role of glial cells in the development of depression, and it is noteworthy that some recent evidence suggests that the development of depression may be closely related to viral infections, such as SARS-CoV-2, BoDV-1, ZIKV, HIV, and HHV6, which infect the organism and cause some degree of glial cells, such as astrocytes, oligodendrocytes, and microglia. This can affect the transmission of related proteins, neurotransmitters, and cytokines, which in turn leads to neuroinflammation and depression. Based on the close relationship between viruses and depression, this paper provides an in-depth analysis of the new mechanism of virus-induced depression, which is expected to provide a new perspective on the mechanism of depression and a new idea for the diagnosis of depression in the future.

Computational identification of mutually exclusive transcriptional drivers dysregulating metastatic microRNAs in prostate cancer.

Androgen-ablation therapies, which are the standard treatment for metastatic prostate cancer, invariably lead to acquired resistance. Hence, a systematic identification of additional drivers may provide useful insights into the development of effective therapies. Numerous microRNAs that are critical for metastasis are dysregulated in metastatic prostate cancer, but the underlying molecular mechanism is poorly understood. We perform an integrative analysis of transcription factor (TF) and microRNA expression profiles and computationally identify three master TFs, AR, HOXC6 and NKX2-2, which induce the aberrant metastatic microRNA expression in a mutually exclusive fashion. Experimental validations confirm that the three TFs co-dysregulate a large number of metastasis-associated microRNAs. Moreover, their overexpression substantially enhances cell motility and is consistently associated with a poor clinical outcome. Finally, the mutually exclusive overexpression between AR, HOXC6 and NKX2-2 is preserved across various tissues and cancers, suggesting that mutual exclusivity may represent an intrinsic characteristic of driver TFs during tumorigenesis.

Synergistic action of master transcription factors controls epithelial-to-mesenchymal transition.

Epithelial-to-mesenchymal transition (EMT) is a complex multistep process in which phenotype switches are mediated by a network of transcription factors (TFs). Systematic characterization of all dynamic TFs controlling EMT state transitions, especially for the intermediate partial-EMT state, represents a highly relevant yet largely unexplored task. Here, we performed a computational analysis that integrated time-course EMT transcriptomic data with public cistromic data and identified three synergistic master TFs (ETS2, HNF4A and JUNB) that regulate the transition through the partial-EMT state. Overexpression of these regulators predicted a poor clinical outcome, and their elimination readily abolished TGF-ß-induced EMT. Importantly, these factors utilized a clique motif, physically interact and their cumulative binding generally characterized EMT-associated genes. Furthermore, analyses of H3K27ac ChIP-seq data revealed that ETS2, HNF4A and JUNB are associated with super-enhancers and the administration of BRD4 inhibitor readily abolished TGF-ß-induced EMT. These findings have implications for systematic discovery of master EMT regulators and super-enhancers as novel targets for controlling metastasis.