Chinese Medicine Phenomics (Chinmedphenomics): Personalized, Precise and Promising.

The systematicness of phenomics and Traditional Chinese Medicine (TCM) enable these two disciplines to interlink with each other. This article discussed the similarity in theory and application between TCM and phenomics and illustrates their respective advantages in diagnosis and treatment of diseases, forming a new discipline eventually. Chinese medicine phenomics (Chinmedphenomics) is built on classic TCM, combined with phenomics technology, and the development of which needs the mega cohort with TCM syndrome and the characteristics of precision medicine as well as multi-disciplinary cooperation, which is personalized, precise and promising, providing unique scientific insights into understanding human health.

Idiopathic mesenteric phlebosclerosis: clinical and CT imaging characteristics.

BACKGROUND: The aim of our study was to evaluate the clinical characteristics and computed tomography (CT) imaging findings of idiopathic mesenteric phlebosclerosis (IMP). METHODS: From January 2013 to May 2019, the clinical data of 10 patients diagnosed with IMP were analyzed retrospectively. Computed tomography angiography (CTA) and colonoscopy were performed in all 10 patients. All CT imaging findings were evaluated by three radiologists, including the form and distribution of calcification, the bowel's thickness, and the surrounding fat gap. The calcification score was calculated according to the extent of the involved mesenteric veins. The colonic wall thickness was defined as the average value of the thickest and thinnest regions of the intestinal wall. The correlation between the calcification scores and the colonic wall thickness was analyzed using Spearman's correlation analysis. RESULTS: All 10 patients were male with an average age of 59.6 years (range, 51-83 years). The average smoking index was 712 (range, 0-1,800). Among them, 7 patients had a history of long-term excessive daily intake of medicinal liquor or Chinese herbal medicine. Clinical symptoms of abdominal pain, diarrhea, bloating, and nausea were found. Colonoscopy showed dark purple discolorations of the edematous mucosa, engorged blood vessels, extensive erosion, ulceration, and multi-focal nodular surface in all patients. CT demonstrated colonic wall thickening, calcification along the mesenteric vein, and blurry surrounding fat gap in all 10 patients. Mesenteric venous calcification involved the terminal ileum, the ascending and transverse colon in all patients, and the descending colon and sigmoid colon's involvement in two patients. A total of 33 segments of the intestinal wall were involved. The median calcification score was 6 points, the mean thickness of the colonic wall was 10.73±3.22 mm, and there was no significant correlation (P=0.782) between calcification score and thickness of the colonic wall. CONCLUSIONS: The main features of IMP are mesenteric venous calcification, colonic wall thickness, and pericolic fat stranding, and there is no correlation between calcification score and colonic wall thickness. Therefore, CT imaging combined with colonoscopy can improve the diagnostic accuracy of IMP.

The Intercalation of CORM-2 with Pharmaceutical Clay Montmorillonite (MMT) Aids for Therapeutic Carbon Monoxide Release.

The pharmaceutical clay montmorillonite (MMT) is, for the first time, explored as a carbon monoxide-releasing material (CORMat). MMT consists of silicate double layered structure; its exfoliation feature intercalate the CORM-2 [RuCl(µ-Cl)(CO)3]2 inside the layers to suppress the toxicity of organometallic segment. The infrared spectroscopy (IR) confirmed the existence of ruthenium coordinated carbonyl ligand in MMT layers. The energy-dispersive X-ray spectroscopy (EDX) analysis showed that ruthenium element in this material was about 5%. The scanning electron microscopy (SEM) and transmission electron microscope (TEM) images showed that the layer-structure of MMT has been maintained after loading the ruthenium carbonyl segment. Moreover, the layers have been stretched out, which was confirmed by X-ray diffraction (XRD) analysis. Thermogravimetric (TG) curves with huge weight loss around 100-200 °C were attributed to the CO hot-release of ruthenium carbonyl as well as the loss of the adsorbed solvent molecules and the water molecules between the layers. The CO-liberating properties have been assessed through myoglobin assay. The horse myoglobin test showed that the material could be hydrolyzed to slowly release carbon monoxide in physiological environments. The half-life of CO release was much longer than that of CORM-3, and it has an excellent environmental tolerance and slow release effect.

Network pharmacology-based identification of major component of Angelica sinensis and its action mechanism for the treatment of acute myocardial infarction.

Background: To decipher the mechanisms of Angelica sinensis for the treatment of acute myocardial infarction (AMI) using network pharmacology analysis. Methods: Databases were searched for the information on constituents, targets, and diseases. Cytoscape software was used to construct the constituent-target-disease network and screen the major targets, which were annotated with the DAVID (Database for Annotation, Visualization and Integrated Discovery) tool. The cardioprotective effects of Angelica sinensis polysaccharide (ASP), a major component of A. sinensis, were validated both in H9c2 cells subjected to simulated ischemia by oxygen and glucose deprivation and in rats with AMI by ligation of the left anterior coronary artery. Results: We identified 228 major targets against AMI injury for A. sinensis, which regulated multiple pathways and hit multiple targets involved in several biological processes. ASP significantly decreased endoplasmic reticulum (ER) stress-induced cell death both in vitro and in vivo In ischemia injury rats, ASP treatment reduced infarct size and preserved heart function. ASP enhanced activating transcription factor 6 (ATF6) activity, which improved ER-protein folding capacity. ASP activated the expression of p-AMP-activated protein kinase (p-AMPK) and peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α). Additionally, ASP attenuated levels of proinflammatory cytokines and maintained a balance in the oxidant/antioxidant levels after AMI. Conclusion:In silico analysis revealed the associations between A. sinensis and AMI through multiple targets and several key signaling pathways. Experimental data indicate that ASP protects the heart against ischemic injury by activating ATF6 to ameliorate the detrimental ER stress. ASP's effects could be mediated via the activation of AMPK-PGC1α pathway.

Regulation of Intestinal Epithelial Cells Properties and Functions by Amino Acids.

Intestinal epithelial cells (IECs) line the surface of intestinal epithelium, where they play important roles in the digestion of food, absorption of nutrients, and protection of the human body from microbial infections, and others. Dysfunction of IECs can cause diseases. The development, maintenance, and functions of IECs are strongly influenced by external nutrition, such as amino acids. Amino acids play important roles in regulating the properties and functions of IECs. In this article, we briefly reviewed the current understanding of the roles of amino acids in the regulation of IECs' properties and functions in physiological state, including in IECs homeostasis (differentiation, proliferation, and renewal), in intestinal epithelial barrier structure and functions, and in immune responses. We also summarized some important findings on the effects of amino acids supplementation (e.g., glutamine and arginine) in restoring IECs' and intestine functions in some diseased states. These findings will further our understanding of the important roles of amino acids in the homeostasis of IECs and could potentially help identify novel targets and reagents for the therapeutic interventions of diseases associated with dysfunctional IECs.

Personalized medicine in cystic fibrosis: genistein supplementation as a treatment option for patients with a rare S1045Y-CFTR mutation.

Cystic fibrosis (CF) is a life-shortening disease caused by the mutations that generate nonfunctional CF transmembrane conductance regulator (CFTR) protein. A rare serine-to-tyrosine (S1045Y) CFTR mutation was earlier reported to result in CF-associated fatality. We identified an African-American patient with the S1045Y mutation in CFTR, as well as a stop-codon mutation, who has a mild CF phenotype. The underlying mechanism of CF caused by S1045Y-CFTR has not been elucidated. In this study, we determined that S1045Y-CFTR exhibits twofold attenuated function compared with wild-type (WT)-CFTR. We report that serine-to-tyrosine mutation leads to increased tyrosine phosphorylation of S1045Y-CFTR, followed by recruitment and binding of E3-ubiquitin ligase c-cbl, resulting in enhanced ubiquitination and passage of S1045Y-CFTR in the endosome/lysosome degradative compartments. We demonstrate that inhibition of tyrosine phosphorylation partially rescues S1045Y-CFTR surface expression and function. Based on our findings, it could be suggested that consuming genistein (a tyrosine phosphorylation inhibitor) would likely ameliorate CF symptoms in individuals with S1045Y-CFTR, providing a unique personalized therapy for this rare CF mutation.

The antitumor activity of tumor-homing peptide-modified thermosensitive liposomes containing doxorubicin on MCF-7/ADR: in vitro and in vivo.

Clotted plasma proteins are present on the walls of tumor vessels and in tumor stroma. Tumor-homing peptide Cys-Arg-Glu-Lys-Ala (CREKA) could recognize the clotted plasma proteins in tumor vessels. Thermosensitive liposomes could immediately release the encapsulated drug in the vasculature of the heated tumor. In this study, we designed a novel form of targeted thermosensitive liposomes, CREKA-modified lysolipid-containing thermosensitive liposomes (LTSLs), containing doxorubicin (DOX) (DOX-LTSL-CREKA), to investigate the hypothesis that DOX-LTSL-CREKA might target the clotted plasma proteins in tumor vessels as well as tumor stroma and then exhibit burst release of the encapsulated DOX at the heated tumor site. We also hypothesized that the high local drug concentration produced by these thermosensitive liposomes after local hyperthermia treatment will be useful for treatment of multidrug resistance. The multidrug-resistant human breast adenocarcinoma (MCF-7/ADR) cell line was chosen as a tumor cell model, and the targeting and immediate release characteristics of DOX-LTSL-CREKA were investigated in vitro and in vivo. Furthermore, the antitumor activity of DOX-LTSL-CREKA was evaluated in MCF-7/ADR tumor-bearing nude mice in vivo. The targeting effect of the CREKA-modified thermosensitive liposomes on the clotted plasma proteins was confirmed in our in vivo imaging and immunohistochemistry experiments. The burst release of this delivery system was observed in our in vitro temperature-triggered DOX release and flow cytometry analysis and also by confocal microscopy experiments. The antitumor activity of the DOX-LTSL-CREKA was confirmed in tumor-bearing nude mice in vivo. Our findings suggest that the combination of targeting the clotted plasma proteins in the tumor vessel wall as well as tumor stroma by using CREKA peptide and temperature-triggered drug release from liposomes by using thermosensitive liposomes offers an attractive strategy for chemotherapeutic drug delivery to tumors.

Functional regulation of cystic fibrosis transmembrane conductance regulator-containing macromolecular complexes: a small-molecule inhibitor approach.

CFTR (cystic fibrosis transmembrane conductance regulator) has been shown to form multiple protein macromolecular complexes with its interacting partners at discrete subcellular microdomains to modulate trafficking, transport and signalling in cells. Targeting protein-protein interactions within these macromolecular complexes would affect the expression or function of the CFTR channel. We specifically targeted the PDZ domain-based LPA2 (type 2 lysophosphatidic acid receptor)-NHERF2 (Na+/H+ exchanger regulatory factor-2) interaction within the CFTR-NHERF2-LPA2-containing macromolecular complexes in airway epithelia and tested its regulatory role on CFTR channel function. We identified a cell-permeable small-molecule compound that preferentially inhibits the LPA2-NHERF2 interaction. We show that this compound can disrupt the LPA2-NHERF2 interaction in cells and thus compromises the integrity of macromolecular complexes. Functionally, it elevates cAMP levels in proximity to CFTR and upregulates its channel activity. The results of the present study demonstrate that CFTR Cl- channel function can be finely tuned by modulating PDZ domain-based protein-protein interactions within the CFTR-containing macromolecular complexes. The present study might help to identify novel therapeutic targets to treat diseases associated with dysfunctional CFTR Cl- channels.

[Comparative study between montmorillonite and Smecta on anti-dysentery effect].

OBJECTIVE: To compare the efficiency of montmorillonite (Mengtuoshi) and Smecta. METHODS: The effects on the dysentery mice induced by MgSO4, rhubarb powder and castor oil, were observed by given respectively 15.6%, 31.2% Mengtuoshi and 31.2% Smecta. And the effects on the over-contracted rabbit intestines were also observed. RESULTS: Both Mengtuoshi and Smecta could relieve the over pushing speeding of stomach and intestine, and reduce the times of dysentery. CONCLUSION: The anti-dysentery effect of Mengtuoshi was similar to Smecta from France and may be used as good anti-dysentery drug.