Arginine metabolism regulates the pathogenesis of inflammatory bowel disease.

The pathogenesis of inflammatory bowel disease (IBD) is related to genetic susceptibility, enteric dysbiosis, and uncontrolled, chronic inflammatory responses that lead to colonic tissue damage and impaired intestinal absorption. As a consequence, patients with IBD are prone to nutrition deficits after each episode of disease resurgence. Nutritional supplementation, especially for protein components, is often implemented during the remission phase of IBD. Notably, ingested nutrients could affect the progression of IBD and the prognostic outcome of patients; therefore, they should be cautiously evaluated prior to being used for IBD intervention. Arginine (Arg) is a semi-essential amino acid required for protein synthesis and intimately associated with gut pathophysiology. To help optimize arginine-based nutritional intervention strategies, the present work summarizes that during the process of IBD, patients manifest colonic Arg deficiency and the turbulence of Arg metabolic pathways. The roles of Arg-nitric oxide (catalyzed by inducible nitric oxide synthase) and Arg-urea (catalyzed by arginases) pathways in IBD are debatable; the Arg-polyamine and Arg-creatine pathways are mainly protective. Overall, supplementation with Arg is a promising therapeutic strategy for IBD; however, the dosage of Arg may need to be carefully tailored for different individuals at different disease stages. Additionally, the combination of Arg supplementation with inhibitors of Arg metabolic pathways as well as other treatment options is worthy of further exploration.

Double-Site Binding and Anti-/Pro-oxidation of Luteolin on Bovine Serum Albumin Mediated by Copper(II) Coordination.

The interactions of luteolin (Lut) with bovine serum albumin (BSA) mediated by Cu(II) were investigated by spectroscopic, calorimetric, and molecular dynamic (MD) methods. Fluorescence studies showed that the binding of Lut to BSA was significantly enhanced by Cu(II) coordination with the number of binding sites and binding constant increasing from n = 1 and K a = 3.2 × 105 L·mol-1 for Lut to n = 2 and K a = 7.1 × 105 L·mol-1 for a 1:1 Cu(II)-luteolin complex, in agreement with the results from isothermal titration calorimetry (ITC). Site-specific experiments with warfarin and ibuprofen and MD confirmed that two binding sites of BSA were sequentially occupied by two Cu(II)-luteolin complexes. Cu(II) coordination increased the antioxidant activity of luteolin by 60% in the inhibition of carbonyl formation from the oxidation of amino groups in the side chain of BSA induced by the peroxyl radical ROO•; however, it counteracted the antioxidant effects of luteolin and played pro-oxidative roles in BSA aggregation induced by •OH.

Effect of vocal respiratory training on respiratory function and respiratory neural plasticity in patients with cervical spinal cord injury: a randomized controlled trial.

In previous studies, researchers have used singing to treat respiratory function in patients with spinal cord injury. However, few studies have examined the way in which vocal training affects respiratory neural plasticity in patients with spinal cord injury. Vocal respiratory training (VRT) is a type of vocal muscle-related treatment that is often a component of music therapy (MT) and focuses on strengthening respiratory muscles and improving lung function. In this randomized controlled study, we analyzed the therapeutic effects of VRT on respiratory dysfunction at 3 months after cervical spinal cord injury. Of an initial group of 37 patients, 26 completed the music therapy intervention, which comprised five 30-minute sessions per week for 12 weeks. The intervention group (n = 13) received VRT training delivered by professional certified music therapists. The control group (n = 13) received respiratory physical therapy delivered by professional physical therapists. Compared with the control group, we observed a substantial increase in respiratory function in the intervention group after the 12-week intervention. Further, the nerve fiber bundles in the respiratory center in the medulla exhibited a trend towards increased diversification, with an increased number, path length, thickness, and density of nerve fiber bundles. These findings provide strong evidence for the effect of music therapeutic VRT on neural plasticity. This study was approved by the Ethics Committee of China Rehabilitation Research Center (approval No. 2020-013-1) on April 1, 2020, and was registered with the Chinese Clinical Trial Registry (registration No. ChiCTR2000037871) on September 2, 2020.

Diffusion tensor imaging of the hippocampus reflects the severity of hippocampal injury induced by global cerebral ischemia/reperfusion injury.

At present, predicting the severity of brain injury caused by global cerebral ischemia/reperfusion injury (GCI/RI) is a clinical problem. After such an injury, clinical indicators that can directly reflect neurological dysfunction are lacking. The change in hippocampal microstructure is the key to memory formation and consolidation. Diffusion tensor imaging is a highly sensitive tool for visualizing injury to hippocampal microstructure. Although hippocampal microstructure, brain-derived neurotrophic factor (BDNF), and tropomyosin-related kinase B (TrkB) levels are closely related to nerve injury and the repair process after GCI/RI, whether these indicators can reflect the severity of such hippocampal injury remains unknown. To address this issue, we established rat models of GCI/RI using the four-vessel occlusion method. Diffusion tensor imaging parameters, BDNF, and TrkB levels were correlated with modified neurological severity scores. The results revealed that after GCI/RI, while neurological function was not related to BDNF and TrkB levels, it was related to hippocampal fractional anisotropy. These findings suggest that hippocampal fractional anisotropy can reflect the severity of hippocampal injury after global GCI/RI. The study was approved by the Institutional Animal Care and Use Committee of Capital Medical University, China (approval No. AEEI-2015-139) on November 9, 2015.

Compound sophorae decoction enhances intestinal barrier function of dextran sodium sulfate induced colitis via regulating notch signaling pathway in mice.

BACKGROUND: Compound sophorae decoction (CSD), a Chinese Herbal decoction, is frequently clinically prescribed for patients suffered from ulcerative colitis (UC) characterized by bloody diarrhea. Yet, the underlying mechanism about how this formulae works is remain elusive. METHODS: In the present study, the experimental colitis in C57BL/6 J mice was induced by oral administration of standard diets containing 3% dextran sodium sulfate (DSS), and CSD was given orally for treatment at the same time. The clinical symptoms including stool and body weight were recorded each day, and colon length and its histopathological changes were observed. Apoptosis of colonic epithelium was studied by detecting protein expression of cleaved caspase-3, and cell proliferation by Ki-67 immunohistochemistry. Tight junction complex like ZO-1 and occludin were also determined by transmission electron microscope and immunofluorescence. The concentration of FITC-dextran 4000 was measured to evaluate intestinal barrier permeability and possible signaling pathway was investigated. Mucin2 (MUC2) and notch pathway were tested through western blot. The M1/M2 ratio in spleen and mesenteric lymph nodes were detected by flow cytometry. And the mRNA levels of iNOS and Arg1 were examined by qRT-PCR. RESULTS: CSD could significantly alleviate the clinical manifestations and pathological damage. Body weight loss and DAI score of mice with colitis were improved and shortening of colon was inhibited. The administration of CSD was able to reduce apoptotic epithelial cells and facilitate epithelial cell regeneration. Increased intestinal permeability was reduced in DSS-induced colitis mice. In addition, CSD treatment obviously up-regulated the expression of ZO-1 and occludin and the secretion of MUC2, regulated notch signaling, and decreased the ratio of M1/M2. CONCLUSIONS: These data together suggest that CSD can effectively mitigate intestinal inflammation, promote phenotypic change in macrophage phenotype and enhance colonic mucosal barrier function by, at least in part, regulating notch signaling in mice affected by DSS-induced colitis.

Synthesis and evaluation of chalcone analogues containing a 4-oxoquinazolin-2-yl group as potential anti-tumor agents.

The chalcone motif can be found in many molecules that contribute to essential biological processes, and many chalcone-containing compounds exhibit potent anti-cancer activity. Here, we synthesized two series of chalcone analogues (3a-s and 6a-s) based on substituting the chalcone B-ring or A-ring with a 4-oxoquinazolin-2-yl group, and then evaluated them for cytotoxic activity in human colorectal HCT-116 and breast cancer MCF-7 cell lines. Compounds 3a-s (in which a 4-oxoquinazolin-2-yl group functioned as the B-ring) were markedly more cytotoxic than compounds 6a-s (in which 4-oxoquinazolin-2-yl group functioned as the A-ring), based on their IC50 values to inhibit proliferation. Compound 3f was found as the most potent among 38 analogues and the mechanism of its cytotoxicity was investigated. Flow cytometry indicated that HCT-116 cells treated with compound 3f resulted in a dose-dependent accumulation of cells in the sub-G1 phase, which is representative of apoptotic cells. Subsequent assays (including Annexin V-FITC/PI, AO-EB, MitoSOX™ Red and JC-1 staining) confirmed that 3f exposure induced apoptosis in HCT-116 cells. Immunoblotting analysis indicated that cellular exposure to 3f increased the cleavage of PARP1 and caspases 3, 7, and 9. Taken together, this novel chalcone analogue has a cytotoxic effect on cultured cancer cell-lines that is likely mediated by inducing apoptosis via the mitochondrial death pathway.

[Chemical constituents and cytotoxicity assay research in small polar substances from Vitis thunbergii var. taiwaniana].

This article studied the chemical constituents from the aerial part of Vitis thunbergii var. taiwaniana. The 60% ethanol extract was eluted with 95% ethanol though HP-20 macroporous adsorption resin column. 12 compounds, including (1) betulinic acid, (2)2, 2, 2'-bis (4-hydroxyphenyl) propane bis (2, 3-epoxypropyl) ether, (3) eriodictyol, (4) trans-ε-viniferin, (5) (+)-cis-ε-viniferin, (6) kobophenol A, (7) ampelopsin A, (8) nepalensinol B, (9) cis-miyabenol C, (10) cis-vitisin B, (11) cis-gnetin H and (12) (+)-hopeaphenol, were separated by using normal phase silica gel, ODS, Sephdadex LH-20 column chromatographies and semi-preparative or preparative HPLC. Compounds 2, 5, 6, 8, 9, 10, 11 were separated from the genus Vitis for the first time and compounds 3, 7, 12 were separated from Vitis thunbergii var. taiwaniana for the first time. At a concentration of 50 µmol · L(-1), compound 6, 7 and 11 showed strong cytotoxicity against MCF-7 cell lines with the inhibition rate of 66.58%, 57.16%, 52.84%, respectively.

Association between T174M polymorphism in the angiotensinogen gene and risk of coronary artery disease: a meta-analysis.

BACKGROUND: Angiotensinogen (AGT) T174M gene polymorphism has been suggested to be linked to risk of coronary artery disease, however, results from studies of this association have been inconsistent. In this study, we assess the relationship between AGT T174M gene polymorphism and coronary artery disease. METHODS: We conducted a meta-analysis of 18 case-control studies with 8,147 coronary artery disease cases and 5,344 controls in Google scholar, PubMed, Cochrane Library and China National Knowledge Infrastructure (CNKI) databases to identify eligible studies published by July, 2012. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated from these studies. RESULTS: Overall, a significant association was found between angiotensinogen T174M polymorphism and coronary artery disease risk when all studies were pooled into the meta-analysis (TT vs. MM: OR = 0.53, 95% CI = 0.40-0.71; dominant model: OR = 1.16, 95% CI = 1.01-1.35; recessive model: OR = 0.54, 95% CI = 0.40-0.72). In a stratified analysis, the results indicate a significant association in Caucasians suffering from coronary stenosis (TT vs. MM: OR = 0.38, 95% CI = 0.23-0.63; recessive model: OR = 0.39, 95% CI = 0.23-0.64). No significant increased risk for coronary artery disease was found in Asians. CONCLUSIONS: The meta-analysis indicate a significant association of T174M polymorphism with coronary stenosis risk in Caucasians.

The effects of Rhizoma drynariae on interleukin-2 and T-lymphocyte levels in rats after severe head injury.

OBJECTIVE: To investigate the effects of Rhizoma drynariae on the levels of interleukin-2(IL-2) and T-lymphocyte subset in rats with severe head injury (SHI). METHODS: 72 Sprague Dawley (SD) rats were randomly divided into 3 groups: control group, model group, and R. drynariae group. The experimental group received intragastrical infusions of with aqueous R. drynariae extract four hours after SHI while the other groups were administered with equivalent volumes of physiological saline. Infusions were administered to the 3 groups once a day for 7 d. IL-2 and T-lymphocyte (CD3, CD4, CD8) levels were measured at 24, 72, and 168 h after initial infusion. RESULTS: The levels of IL-2 and CD4 T cells reduced obviously after 24 h in the model group (P<0.05), but recovered to the levels of the control group after 72 h, and remained elevated after 168 h. In the R. drynariae group, IL-2 and CD4 levels were did not decrease while the level of CD8 T cells was reduced significantly (P<0.05). CONCLUSIONS: R. drynariae can protect against immune dysfunction or improve immunity in rats with severe head injury (SHI).