Transcriptomics and metabolomics reveal the role of CYP1A2 in psoralen/isopsoralen-induced metabolic activation and hepatotoxicity.

Psoralen and isopsoralen are the pharmacologically important but hepatotoxic components in Psoraleae Fructus. The purpose of this study was to reveal the underlying mechanism of psoralen/isopsoralen-induced hepatotoxicity. Initially, we applied integrated analyses of transcriptomic and metabolomic profiles in mice treated with psoralen and isopsoralen, highlighting the xenobiotic metabolism by cytochromes P450 as a potential pathway. Then, with verifications of expression levels by qRT-PCR and western blot, affinities by molecular docking, and metabolic contributions by recombinant human CYP450 and mouse liver microsomes, CYP1A2 was screened out as the key metabolic enzyme. Afterwards, CYP1A2 induction and inhibition models in HepG2 cells and mice were established to verify the role of CYP1A2, demonstrating that induction of CYP1A2 aggravated the hepatotoxicity, and conversely inhibition alleviated the hepatotoxic effects. Additionally, we detected glutathione adducts with reactive intermediates of psoralen and isopsoralen generated by CYP1A2 metabolism in biosystems of recombinant human CYP1A2 and mouse liver microsomes, CYP1A2-overexpressed HepG2 cells, mice livers and the chemical reaction system using UPLC-Q-TOF-MS/MS. Ultimately, the high-content screening presented the cellular oxidative stress and relevant hepatotoxicity due to glutathione depletion by reactive intermediates. In brief, our findings illustrated that CYP1A2-mediated metabolic activation is responsible for the psoralen/isopsoralen-induced hepatotoxicity.

First Report of Leaf Spot on Ipomoea nil Caused by Alternaria alternata in China.

Ipomoea nil (Linnaeus) Roth, belonging to the Convolvulaceae family, is an ornamental and medicinal plant in China, which has the function of diuretic and expectorant, and it is also a common weed in the field. In October 2021, a leaf spot disease was observed on I. nil in a field as weed in Jingzhou (N 30° 21', E 112° 19'), Hubei Province, China. Symptoms began as small brown blotches, then developed into oval or irregularly shaped brown necrotic lesions. In severe cases, the leaves were completely necrotic and detached. In the surveyed area, the incidence was between 30% - 40%. To isolate the pathogen, twenty-one leaf pieces (5×5 mm) were cut from the lesion edges of seven symptomatic leaves, disinfected with 70% ethanol and 2% sodium hypochlorite (NaOCl), rinsed with sterile water five times, then placed on three potato dextrose agar (PDA) modified with 50 µg/mL kanamycin, and incubated at 25 °C in dark for 5 days. The isolates were subcultured by transferring mycelium tips. Sixteen fungal strains were isolated from the tissues, and nine of them showed similar morphological characteristics. After cultured 7 days on PDA at 25 °C, the nine colonies were initially white, then turned greenish brown to black in the center and had abundant fine villous aerial mycelia up to 61.5 mm in average diameter. To examine its conidial morphology, the fungi were cultured for 7 days on potato carrot agar (PCA) at 22°C with a light/dark period of 8/16 h. On PCA, conidia were brown or olive-brown, obclavate to obpyriform, with a short beak, one to five transverse and zero to three longitudinal septa. They formed chains of 1 - 8 conidia, with branches. Conidia were 16 - 46 µm long and 8 - 14 µm wide (n=50). These morphological features were similar to those described in Alternaria spp. (Simmons 2007). A single isolate "Q2" was selected for molecular identification because it was the most aggressive in preliminary leaf pathogenicity assays. The internal transcribed spacer (ITS) region of rDNA and histone 3 (H3) gene were amplified and sequenced using primers ITS1/ITS4 (White et al. 1990) and H3-1a/H3-1b (Zheng et al. 2015). BLAST analysis revealed that the sequences (ITS, ON360984; H3, ON375577) were 100% identical to Alternaria alternata (ITS, MK396607; H3, MN840996), respectively. Maximum likelihood analysis based on combined two gene sequences was conducted with an evolutionary model of GTR+I+G under 1000 bootstrap replicates. Phylogenetic tree showed that Q2 and Alternaria alternata 21-5 and BLH-YB-11 located in one clade supported with 99% bootstrap values. The pathogen was identified as A. alternata. To fulfill Koch's postulate, 10 ml conidia (106 spores/ml) of Q2 was sprayed on five healthy seedlings, with sterile distilled water as a control. All leaves were rinsed three times with sterile water before inoculation. All seedlings were placed in sealed plastic bags with air valves, and grown in a greenhouse (25 ± 2 ˚C, RH 65%). The test was repeated twice. After 10 days, symptoms typical of brown blotches similar to those observed in the field were observed on leaves of inoculated plants, while control remained healthy. A. alternata was re-isolated from the inoculated symptomatic leaves with a frequency of 100% based on morphological and molecular characters, thus Koch's postulate was confirmed. To the best of our knowledge, this is the first report of A. alternata causing leaf spot on I. nil in China. Our findings extended the host range of the pathogen A. alternata on characteristic plants.

The Tai Chi Flap: A Novel Design for the Radial Forearm Flap.

OBJECTIVE: Tai Chi is an ancient philosophy used to explain the universe. The Tai Chi symbol is represented by Yin/Yang fishes. The authors describe a novel radial forearm flap (RFF) design for the reconstruction of circular defects based on the Tai Chi symbol. METHODS: Eleven consecutive patients with craniofacial skin or mucus defects underwent reconstruction with a Tai Chi RFF. Patient perioperative and follow-up information was collected. RESULTS: The diameter of the Tai Chi RFF was 5 to 6 cm. All flaps healed uneventfully without ischemic problems, and all donor site defects were closed primarily without skin grafts. Remarkably, 2 patients received a tattoo to mark the Tai Chi symbol and greatly appreciate the shape of the flap. CONCLUSIONS: The Tai Chi flap is an economically friendly flap design that can be used to prevent skin grafts while providing psychological comfort to patients.

Surface functionalized exosomes as targeted drug delivery vehicles for cerebral ischemia therapy.

The safe and effective delivery of drugs is a major obstacle in the treatment of ischemic stroke. Exosomes hold great promise as an endogenous drug delivery nanosystem for the treatment of cerebral ischemia given their unique properties, including low immunogenicity, innate stability, high delivery efficiency, and ability to cross the blood-brain barrier (BBB). However, exosome insufficient targeting capability limits their clinical applications. In this study, the c(RGDyK) peptide has been conjugated to the exosome surface by an easy, rapid, and bio-orthogonal chemistry. In the transient middle cerebral artery occlusion (MCAO) mice model, The engineered c(RGDyK)-conjugated exosomes (cRGD-Exo) target the lesion region of the ischemic brain after intravenous administration. Furthermore, curcumin has been loaded onto the cRGD-Exo, and administration of these exosomes has resulted in a strong suppression of the inflammatory response and cellular apoptosis in the lesion region. The results suggest a targeting delivery vehicle for ischemic brain based on exosomes and provide a strategy for the rapid and large-scale production of functionalized exosomes.

Antioxidant Properties of Phenolic Compounds in Renewable Parts of Crataegus pinnatifida inferred from Seasonal Variations.

In this study, the effect of seasonal variations on Crataegus pinnatifida, changes in antioxidant activity and active components in C. pinnatifida leaves, roots, twigs, and fruits from May to October were investigated. Through correlation analysis of climatic factors and 7 phenolic compounds yield, the phenolic compounds content was positively correlated with temperatures and daytime. The correlation coefficient of temperatures and daytime were 0.912 and 0.829, respectively. 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, 2,2'-azino-bis 3-ethylbenzothiazoline-6-sulphonic acid (ABTS) radical scavenging and reducing power tests were employed to evaluate the antioxidant activity of the C. pinnatifida. C. pinnatifida leaves exhibited significant advantages in terms of higher phenolic contents and excellent antioxidant activities. Principal component analysis (PCA) revealed that 2 main PC characterize the C. pinnatifida phenolic composition (82.1% of all variance). C. pinnatifida leaves in September possessed remarkable antioxidant activity. The results elucidate that C. pinnatifida leaves, as renewable parts, are suitable for application as antioxidant ingredients.

Overview of application and research of Echinops genus in Chinese medicine / 中国中药杂志

Asteraceae Echionopos (Echinops genus) is one of the world's plants commonly used in traditional Chinese medicine herbs. In this paper, a lot of literature on the basis of domestic and foreign, and modern research on the application of medicinal plants in different ethnic groups in our country Echionopos made a brief presentation and evaluation, and its in Chinese Han, Mongolian, Uygur, Kazak, Korean and other ethnic groups in the application of traditional medicine and related research conducted profiles. To further comprehensive and accurate use of the abundant plant resources and research, in order to find biologically active natural products, provide reference basis for the clinical application of new drugs developed and expanded drug source.

[Intracellular calcium ion concentration in the prostate smooth muscle cells of chronic abacterial prostatitis rat models and normal controls].

OBJECTIVE: To investigate the difference in intracellular calcium ion [Ca2+]i concentration in prostate smooth muscle cells (PSMCs) between SD rat models of chronic abacterial prostatitis (CAP) and normal controls, and to evaluate the role of [Ca2+]i concentration in CAP. METHODS: We established CAP models in SD rats using purified prostate protein and Freund's complete adjuvant, cultured in vitro and then purified the PSMCs of both the CAP models and normal controls. Continuous dynamic scanning was performed under the laser confocal scanning microscope after incubation of the cells with FLUO-3AM. RESULTS: The fluorescence intensities of [Ca2+]i in the PSMCs were 80.39 +/- 9.00 and 27.95 +/- 10.04 in the CAP models and normal controls, respectively, with statistically significant differences between the two groups (P < 0.01). CONCLUSION: The concentration of [Ca2+]i increased in the PSMCs of the CAP rat models, which might enhance the constriction of PSMCs and subsequently increase the sensibility to pain and cause lower abdominal pain.

Anesthetic efficacy of inferior alveolar nerve block plus buccal infiltration or periodontal ligament injections with articaine in patients with irreversible pulpitis in the mandibular first molar.

OBJECTIVE: We compared the anesthetic efficacy of inferior alveolar nerve block (IANB) plus buccal infiltration (BI) and IANB plus periodontal ligament (PDL) articaine injections in patients with irreversible pulpitis in the mandibular first molar. STUDY DESIGN: Fifty-seven volunteers, patients with irreversible pulpitis in the mandibular first molar admitted to the Department of Stomatology, Second Affiliated Hospital, Sun Yat-Sen University, randomly received conventional IANB, containing 1.7 mL 4% articaine/HCl with 1:100,000 epinephrine, plus either BI or PDL injections containing 0.4 mL articaine/HCl with 1:100,000 epinephrine. The patients recorded the pain of the injections and endodontic access on a Heft-Parker visual analog scale (VAS). RESULTS: According to the VAS scores, all patients experienced no or mild pain with BI and PDL injections after the application of IANB. Anesthetic success occurred in 81.48% for IANB plus BI (IANB/BI) compared with 83.33% for IANB plus PDL injection (IANB/PDL injection). None of the observed differences between the 2 groups was significant (P > .05). CONCLUSION: Both injection combinations resulted in high anesthetic success in patients with irreversible pulpitis in the mandibular first molar.

Comparison of the efficiencies of permanent maxillary tooth removal performed with single buccal infiltration versus routine buccal and palatal injection.

OBJECTIVE: The aim of the present study was to demonstrate whether articaine/HCl administered alone as a single buccal infiltration in maxillary tooth removal provided favorable palatal anesthesia as compared to buccal and palatal injection, for a surgical procedure. STUDY DESIGN: In total, 71 patients for removal of bilateral permanent maxillary teeth were enrolled in the present study. For the experimental side, 1.7 mL of 4% articaine/HCl was injected into the buccal vestibule of the tooth. After 5 minutes, tooth extraction was performed. On the control side a similar protocol was applied with the addition of a palatal injection. All patients completed a 100-mm Visual Analogue Scale (VAS), Verbal Response Scale (VRS) after both injection and then extraction, respectively. RESULTS: According to the VAS scores, the pain of injection between buccal infiltration without a separate palatal injection and routine administration with additional palatal injection was statistically significant (P < .05). However, the VAS scores for permanent maxillary tooth removal showed no significant difference between the 2 types of injection (P > .05). All patients described both extractions as "acceptable" and no patient requested an additional palatal injection to ensure comfortable extraction. CONCLUSIONS: The routine use of a palatal injection for the removal of permanent maxillary teeth may not be required when articaine/HCl is used as the local anesthetic.

Effect of Yangqixue Qufengshi Recipe on rheumatoid arthritis model mice under different genetic backgrounds.

OBJECTIVE: To study the effect of Yangqixue Qufengshi Recipe (YQXQFS) on rheumatoid arthritis (RA) model mice under different genetic backgrounds. METHODS: Collagen Induced Arthritis (CIA) were established on HLA-DR4 transgenic (TG) mice and non-transgenic (NTG) mice, which partly were raised with YQXQFS, and the onset day of CIA, the level of type II collagen (CII)-reactive antibodies and the pathological scores of CIA were assessed. RESULTS: Under HLA-DR4 TG background (compared with NTG mice), the earlier onset day of CIA (11.22 +/- 3.35 days vs 16.56 +/- 4.75 days, P < 0.05) and higher level of CII-reactive antibodies (0.2274 +/- 0.1390 microg/ml vs 0.1101 +/- 0.0560 microg/ml, P < 0.05) were observed, but the pathological scores of CIA remained unchanged. YQXQFS could not influence the onset day of CIA and the level of CII-reactive antibodies, but had a certain effect on the total pathological scores (6.56 +/- 3.43 scores vs 11.11 +/- 5.64 scores) and bone erosion (0.22 +/- 0.44 scores vs 1.67 +/- 1.50 scores) of CIA on NTG mice (P < 0.05), NTG YQXQFS group compared with NTG experimental group. CONCLUSION: YQXQFS had a certain effect on RA model, but had no significant effect on HLA-DR4 related CIA.