The Signaling Pathways and Targets of Natural Compounds from Traditional Chinese Medicine in Treating Ischemic Stroke.

Ischemic stroke (IS) is a common neurological disorder associated with high disability rates and mortality rates. At present, recombinant tissue plasminogen activator (r-tPA) is the only US(FDA)-approved drug for IS. However, due to the narrow therapeutic window and risk of intracerebral hemorrhage, r-tPA is currently used in less than 5% of stroke patients. Natural compounds have been widely used in the treatment of IS in China and have a wide range of therapeutic effects on IS by regulating multiple targets and signaling pathways. The keywords "ischemia stroke, traditional Chinese Medicine, Chinese herbal medicine, natural compounds" were used to search the relevant literature in PubMed and other databases over the past five years. The results showed that JAK/STAT, NF-κB, MAPK, Notch, Nrf2, and PI3K/Akt are the key pathways, and SIRT1, MMP9, TLR4, HIF-α are the key targets for the natural compounds from traditional Chinese medicine in treating IS. This study aims to update and summarize the signaling pathways and targets of natural compounds in the treatment of IS, and provide a base of information for the future development of effective treatments for IS.

Mineral crude drug mirabilite (Mangxiao) inhibits the occurrence of colorectal cancer by regulating the Lactobacillus-bile acid-intestinal farnesoid X receptor axis based on multiomics integration analysis.

Mineral crude drug has revolutionized the treatment landscape in precision oncology niche that leads to the improvement in therapeutic efficiency on various tumor subtypes. Mangxiao (MX), a mineral crude drug in traditional Chinese medicine, has been used for treating gastrointestinal diseases for thousands of years. However, the action mechanisms are still ambiguous. Here, we attempt to explore inhibitory roles and associated pharmacological mechanisms of MX upon colorectal cancer (CRC) in APCMin/+ male mice by integrating metabolomics, 16S rDNA sequencing analyses, and metagenomic-based microbiota analysis. We found that MX can significantly inhibit the occurrence of CRC through the regulation of the dysregulated gut microbe metabolism. Furthermore, the correlation analysis of metabolomes and 16S rDNA revealed that MX could restore the disorders of gut microbes by specifically enriching the abundance of Lactobacilli to improve bile acid metabolism, which further activated the farnesoid X receptor (FXR) in CRC mice, then the improvement of gut dysbiosis could inhibit the development of CRC. Collectively, our effort confirmed MX has the capacity to intervene the development of CRC and further discovered that it targets Lactobacillus-bile acid-intestinal FXR axis, which can be regarded as a candidate medicine for future drug discovery and development against CRC.

Chinmedomics: a potent tool for the evaluation of traditional Chinese medicine efficacy and identification of its active components.

As an important part of medical science, Traditional Chinese Medicine (TCM) attracts much public attention due to its multi-target and multi-pathway characteristics in treating diseases. However, the limitations of traditional research methods pose a dilemma for the evaluation of clinical efficacy, the discovery of active ingredients and the elucidation of the mechanism of action. Therefore, innovative approaches that are in line with the characteristics of TCM theory and clinical practice are urgently needed. Chinmendomics, a newly emerging strategy for evaluating the efficacy of TCM, is proposed. This strategy combines systems biology, serum pharmacochemistry of TCM and bioinformatics to evaluate the efficacy of TCM with a holistic view by accurately identifying syndrome biomarkers and monitoring their complex metabolic processes intervened by TCM, and finding the agents associated with the metabolic course of pharmacodynamic biomarkers by constructing a bioinformatics-based correlation network model to further reveal the interaction between agents and pharmacodynamic targets. In this article, we review the recent progress of Chinmedomics to promote its application in the modernisation and internationalisation of TCM.

Multi-Omics Approaches in Colorectal Cancer Screening and Diagnosis, Recent Updates and Future Perspectives.

Colorectal cancer (CRC) is common Cancer as well as the third leading cause of mortality around the world; its exact molecular mechanism remains elusive. Although CRC risk is significantly correlated with genetic factors, the pathophysiology of CRC is also influenced by external and internal exposures and their interactions with genetic factors. The field of CRC research has recently benefited from significant advances through Omics technologies for screening biomarkers, including genes, transcripts, proteins, metabolites, microbiome, and lipidome unbiasedly. A promising application of omics technologies could enable new biomarkers to be found for the screening and diagnosis of CRC. Single-omics technologies cannot fully understand the molecular mechanisms of CRC. Therefore, this review article aims to summarize the multi-omics studies of Colorectal cancer, including genomics, transcriptomics, proteomics, microbiomics, metabolomics, and lipidomics that may shed new light on the discovery of novel biomarkers. It can contribute to identifying and validating new CRC biomarkers and better understanding colorectal carcinogenesis. Discovering biomarkers through multi-omics technologies could be difficult but valuable for disease genotyping and phenotyping. That can provide a better knowledge of CRC prognosis, diagnosis, and treatments.

Prediction of the mechanism of Dachengqi Decoction treating colorectal cancer based on the analysis method of " into serum components -action target-key pathway".

ETHNOPHARMACOLOGICAL RELEVANCE: Colorectal cancer (CRC) is a common digestive tract malignant tumor that its morbidity and mortality seriously affect human health. At present, Dachengqi Decoction (DCQ), a traditional Chinese medicine formula, has been clinically used as an adjuvant therapy for CRC. However, pharmacodynamic substance basis and therapeutic mechanism are still unclear. AIM OF THE STUDY: The main constituents absorbed in the blood and possible active targets after DCQ administration were explored based on the analysis method of "into serum components, action target and key pathway", which may provide reference for the study of the pharmacodynamic material basis and action mechanism of Dachengqi Decoction in the treatment of CRC. MATERIAL AND METHODS: Based on the serum pharmacochemistry of traditional Chinese medicine (TCM), the prescription prototype ingredients of DCQ in mice serum samples were identified by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry technology (UPLC-Q-TOF-MSE). Taking the prototype ingredients absorbed into serum as the research object, the possible targets and key pathways of DCQ in vivo were demonstrated by network pharmacology. Finally, using molecular docking verified the binding activity of prototype components and potential action targets. RESULTS: A total of 46 prototype components of DCQ were identified in mice serum, most of which were derived from flavonoids and anthraquinones in Citrus aurantium L. and Rheum palmatum L. Network pharmacology prediction results indicated that the drug prototype components entering the serum may mainly regulate targets including mitogen-activated protein kinase (MAPK), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), etc. and main pathways such as (phosphatidylinositol 3-kinase/protein kinase B) PI3K-AKT signaling pathway, advanced glycation end products-receptor for AGE (AGE-RAGE) signaling pathway and IL-17 signaling pathway, etc. Molecular docking showed that the prototype active components had strong binding activity to VEGF, Harvey rat sarcoma viral oncogene homolog (HRAS) and MAPK1. CONCLUSIONS: This study elucidated that most of the direct acting substances of DCQ in vivo were flavonoids and anthraquinones, which may play a role in regulating cell reproduction and apoptosis and inhibiting inflammation, providing a reference for the research of pharmacodynamic material basis and mechanism of DCQ in the treatment of CRC.

Caspr4 interaction with LNX2 modulates the proliferation and neuronal differentiation of mouse neural progenitor cells.

Contactin-associated protein 4 (Caspr4), also known as contactin-associated protein-like protein (CNTNAP4), is expressed in various regions of the brain. Recent reports suggest that CNTNAP4 is a susceptibility gene of autism spectrum disorders (ASDs). However, the molecular function of Caspr4 in the brain has yet to be identified. In this study, we show an essential role of Caspr4 in neural progenitor cells (NPCs). Caspr4 is expressed in NPCs in the subventricular zone (SVZ), a neurogenic region in the developing cortex. Knocking down of Caspr4 enhances the proliferation of NPCs derived from the SVZ of embryonic day 14 mouse. Neuronal differentiation is increased by overexpression of Caspr4, but decreased by knocking down of Caspr4 in cultured mouse NPCs. Transfection of the intracellular domain of Caspr4 (C4ICD) rescues the abnormal decreased neuronal differentiation of Caspr4-knocking down NPCs. Ligand of Numb protein X2 (LNX2), a binding partner of Numb, interacts with Caspr4 in a PDZ domain-dependent manner and plays a similar role to Caspr4 in NPCs. Moreover, transfection of LNX2 rescues the decreased neuronal differentiation in Caspr4-knocking down NPCs. In contrast, transfection of C4ICD fails to do so in LNX2-knocking down NPCs. These results indicate that Caspr4 inhibits neuronal differentiation in a LNX-dependent manner. Therefore, this study reveals a novel role of Caspr4 through LNX2 in NPCs, which may link to the pathogenesis of ASDs.