Traditional uses, phytochemistry, pharmacology, toxicology, and quality control of Rhododendron dauricum L. leaves: A comprehensive review.

ETHNOPHARMACOLOGICAL RELEVANCE: Rhododendron dauricum L. is a traditional herb mainly distributed in the northeast China, Mongolia, Korea Peninsula, and Russia Far East. The dried leaves of Rhododendron dauricum L. (LRD), generally known "Man Shan Hong" have been traditionally applied as folk medicines to treat fever, copious phlegm, asthma, acute and chronic bronchitis, sore throat, dysentery, diabetes mellitus, cancer, and hypertension. To date, no comprehensive review on R. dauricum leaves has been published. AIM OF THE STUDY: Recent progresses in traditional use, phytochemistry, pharmacology, toxicology, and quality control of R. dauricum leaves are systematically presented and critically evaluated in order to provide scientifical basis for its reasonable utilization and further study. MATERIALS AND METHODS: All information about R. dauricum leaves were retrieved from internet scientific databases including Sci-Finder, Web of Science, PubMed, CNKI, Google Scholar, Elsevier, Wiley, ACS publications, SpringerLink, and the Chinese Pharmacopoeia between 1970 and 2022. Plant names were validated by "The Plant List" (http://www.theplantlist.org/). RESULTS: So far, 114 structurally diverse compounds have been isolated and identified from LRD, mainly including flavonoids, diterpenoids, triterpenoids, meroterpenoids, phenols, and 54 volatile components were identified from the essential oils of LRD. Among these, flavonoids are considered as characteristic components and major bioactive phytochemicals. The crude extracts and compounds from LRD have been reported to possess broad pharmacological effects including antitussive and expectorant, anti-inflammatory, anti-HIV, antibacterial, and cytotoxic effects, etc. CONCLUSIONS: As a traditional herb medicine, LRD have been used popularly. On the one hand, traditional uses of LRD provide valuable directions for current research; on the other hand, modern phytochemical and pharmacological studies verify the traditional uses to make its reasonable utilization. However, several defects such as active components determination, in vivo and clinical pharmacological evaluation, toxicology assessment, and quality control of LRD need further study.

Extreme drought exacerbates plant nitrogen­phosphorus imbalance in nitrogen enriched grassland.

The nitrogen­phosphorus (N-P) imbalance induced by N enrichment has received increasing concerns, because N:P ratios play a critical role in driving many fundamental ecological processes. Given the simultaneous occurrence of different global change drivers, it is important to understand whether and how would such N-induced N-P imbalance would be mediated by other global change factors. We examined the interactive effects of N addition (10 g N m-2 yr-1) and extreme drought (-66 % rainfall during the growing season) on species- and community-level N:P ratios in both green and senesced leaves in a temperate grassland of northern China. Extreme drought did not alter soil available N:P ratio under ambient N conditions, but increased that under N enriched conditions. Further, extreme drought did not alter the community-level N:P in both green and senesced leaves under ambient N conditions but significantly enhanced that under N enriched conditions. The drought-induced species turnover made a significant positive contribution to the changes in the community-level N:P ratio under N enriched conditions, but not under ambient N conditions. Our results suggest that the N-induced ecosystem N-P imbalance would be exacerbated by extreme drought event, the frequency of which is predicted to increase across global drylands. Such N-P imbalance would have consequences on litter decomposition, nutrient cycling, and the structures of above- and below-ground food webs. Our findings highlighted the complexity in predicting ecosystem N-P imbalance given the interactions between different global change drivers.

Toxicities of amyloid-beta and tau protein are reciprocally enhanced in the Drosophila model.

Extracellular aggregation of amyloid-beta (Aß) and intracellular tau tangles are two major pathogenic hallmarks and critical factors of Alzheimer's disease. A linear interaction between Aß and tau protein has been characterized in several models. Aß induces tau hyperphosphorylation through a complex mechanism; however, the master regulators involved in this linear process are still unclear. In our study with Drosophila melanogaster, we found that Aß regulated tau hyperphosphorylation and toxicity by activating c-Jun N-terminal kinase. Importantly, Aß toxicity was dependent on tau hyperphosphorylation, and flies with hypophosphorylated tau were insulated against Aß-induced toxicity. Strikingly, tau accumulation reciprocally interfered with Aß degradation and correlated with the reduction in mRNA expression of genes encoding Aß-degrading enzymes, including dNep1, dNep3, dMmp2, dNep4, and dIDE. Our results indicate that Aß and tau protein work synergistically to further accelerate Alzheimer's disease progression and may be considered as a combined target for future development of Alzheimer's disease therapeutics.

Diterpenoids from the whole plants of Croton yunnanensis and their bioactivities.

Four new 19-nor-clerodane diterpenoids (1-4), one new 15,16-dinor-ent-pimarane diterpenoid (5) together with four known diterpenoids (6-9) were isolated from whole plants of Croton yunnanensis. The structures of these compounds were determined by extensive spectroscopic methods including 1D, 2D NMR, HR-ESI-MS, and by comparing their NMR data with those of previously reported compounds. The experimental and calculated electronic circular dichroism data were used to define their absolute configurations. The 1H and 13C NMR spectra of 6 were completely assigned for the first time. All isolated compounds (1-9) were evaluated for their cytotoxic activities against five human cancer cell lines (including SMMC-7721, HL-60, A-549, MCF-7, and SW-480), and anti-inflammatory activities in LPS-induced RAW264.7 macrophages. Crotonyunnan E (5) exhibited selective cytotoxicities against three tumor cell lines, SMMC-7721 (human hepatoma cells, IC50 4.47 ± 0.39 µM), HL-60 (human premyelocytic leukemia, IC50 14.38 ± 1.19 µM), and A-549 (human lung cancer cells, IC50 27.42 ± 0.48 µM), while none of the compounds showed obviously anti-inflammatory activities at 50 µM level.

Immediate Intracoronary Delivery of Human Umbilical Cord Mesenchymal Stem Cells Reduces Myocardial Injury by Regulating the Inflammatory Process Through Cell-Cell Contact with T Lymphocytes.

Inflammatory response regulation is a mechanism through which human umbilical cord mesenchymal stem cells (HUCMSCs) improve myocardial ischemia reperfusion injury (IRI); however, the timing of HUCMSC delivery to achieve maximum effectiveness is controversial. To investigate the effects of HUCMSC delivery on the acute inflammatory stage of IRI, we transplanted HUCMSCs or HUCMSCs with cyclosporin A (CsA) through the coronary artery simultaneously during ischemia reperfusion in pigs. Ferumoxytol-labeled HUCMSCs (HUCMSC), HUCMSCs with cyclosporin A (HUCMSC+CsA), and PBS (control) groups were investigated to evaluate the homing of transplanted cells and changes in infarct features, cardiac activity, and inflammatory response at three time points post-transplantation. Animals were sacrificed 2 weeks later for histological analysis of the hearts. We detected Prussian blue-dyed granules distributed around T lymphocyte clusters in the infarct area in the HUCMSC group. Infarct size and collagen deposition in the infarct area were lower in the HUCMSC group than in the control and HUCMSC+CsA groups. Cardiac function was mildly impaired in both the control and HUCMSC groups, whereas added CsA had a more severe impact. The levels of proinflammatory markers were lower in the HUCMSC group than in the control group at 24-h follow-up, and the difference was more significant after adding CsA. There were more CD3+ T lymphocytes and Foxp3+ Tregs in the HUCMSC group infarct area than in the other two groups. Proliferation rate of T lymphocytes was higher in the HUCMSC group than in the other two groups. Indirect co-culture experiments in vitro showed that MSCs promoted the generation of CD4+CD25+ Foxp3+Tregs through a paracrine mechanism. These results indicate that immediate intracoronary delivery of HUCMSCs after ischemia reperfusion can reduce acute myocardial IRI and promote myocardial repair, mainly through T lymphocyte interactions to regulate the intense inflammatory response during the acute inflammatory stage.

[Three-dimensional model analysis of obstructive sleep apnea hyponea syndrome patients with long-term treatment of oral appliances].

PURPOSE: The aim of the study was to investigate the dental changes of patients with obstructive sleep apnea hypopnea syndrome (OSAHS) with long-term treatment of oral appliances, via the method of three-dimensional model analysis. METHODS: Using Geomagic Studio 2014 software, we transferred the dental models, which were from 18 OSAHS patients before and after treatment of oral appliances, into three-dimensional models for digital analysis. Datasets obtained from pre- and after treatment were compared for accuracy via paired t test using SPSS 22.0 software package. RESULTS: Eighteen patients using oral appliances for 6.57±1.98 years, showed significant differences in some dentition values between pre-treatment and after-treatment. The total dentition changes indicated intrusion of upper premolars, buccalization of upper posterior teeth and mesialization of lower posterior teeth. Statistical analysis demonstrated decrease in upper dental arch length, increase in upper posterior arch width and decrease in upper arch depth and dramatic reduction of overjet in anterior teeth. In the same time, other values evaluated showed no significant change before and after treatment of oral appliances. CONCLUSIONS: Long-term wearing oral appliances results in changes in several variables of dental occlusion, which should not be ignored for dentists conducting this treatment plan. However, the side effect of dental occlusion changes is little on a whole, leading to high security in this aspect.

Controllable preparation of monodisperse alginate microcapsules with oil cores.

Here we report a novel strategy for controllable preparation monodisperse alginate microcapsules with oil cores, where the thickness of the alginate shells, as well as the number and diversity of the oil cores can be tailored precisely. Monodisperse oil-in-water-in-oil (O/W/O) emulsions are generated in a microfluidic device as templates, which contain alginate molecules and a water-soluble calcium complex in the middle aqueous phase. Alginate microcapsules are produced by gelling O/W/O emulsions in oil solution with acetic acid, where the pH decreasing will trigger the calcium ions being released from calcium complex and cross-linking with alginate molecules. Increasing the alginate molecule concentration in emulsion templates affects little on the thickness of the microcapsules but improves their stability in DI water. The strength of alginate microcapsules can be reinforced by post cross-linking in calcium chloride, polyetherimide, or chitosan solution. Typical payloads, such as thyme essential oil, lavender essential oil and W/O emulsions are encapsulated in alginate microcapsules successfully. Furthermore, tailoring the thickness of the alginate shells, as well as the number and the diversity of the oil cores precisely by manipulation the emulsion templates with microfluidics is also demonstrated. The proposed method shows excellent controllability in designing alginate microcapsules with oil cores.

Metabolic activity of Bacillus coagulans R11 and the health benefits of and potential pathogen inhibition by this species in the intestines of laying hens under lead exposure.

Probiotics are widely used in agricultural breeding for care and maintenance of animal health, especially Bacillus coagulans, a new and popular species that could replace Lactobacillus. However, lead contamination in feed might influence the beneficial function. In the present study, Bacillus coagulans R11 was used as a model bacterium to investigate the effect of lead on changes in metabolites and genes, which could influence the beneficial function on laying hen. At the laboratory scale, transcriptomics and metabolomics were used to screen the main metabolites and related genes under lead exposure. The results showed that 4-acetamidobutanoic acid, dodecanoic acid, L-3-phenyllactic acid, apigenin and daidzein, which are antioxidants and antibacterial agents, were the main metabolites, even in the 100 ppm lead exposure group (the levels of these metabolites were 1.17-, 1.10-, 4.80-, 1.43- and 1.67-fold higher in the 100 ppm group than in pure culture medium). Twenty-three genes associated with the syntheses of the above 5 main metabolites were identified. Further animal experiments showed that B. coagulans R11 feeding of laying hens under lead exposure could prevent oxidative damage by increasing T-AOC and T-SOD activity and reducing the MDA concentration in serum and reducing the abundances of potential pathogens (Escherichia coli, Pseudomonas aeruginosa and Salmonella). Further analysis also showed that the inhibition of pathogen growth was due to the regulation of gene expression, as observed by transcriptomics, and these genes were associated with the abovementioned 5 main metabolites. However, the laying rate decreased by 10.53% compared with that of the control group when the lead exposure concentration was 100 mg/kg. The present study suggested that Bacillus coagulans R11 could help prevent oxidative damage and inhibit pathogen growth in laying hens to maintain a healthy intestinal environment for daily breeding, but under high-lead conditions, Bacillus coagulans R11 feeding could decrease the laying rate.

Pathogenesis and phylogenetic analyses of canine distemper virus strain ZJ7 isolate from domestic dogs in China.

A new isolate of canine distemper virus (CDV), named ZJ7, was isolated from lung tissues of a dog suspected with CDV infection using MDCK cells. The ZJ7 isolate induced cytopathogenic effects of syncytia in MDCK cell after six passages. In order to evaluate pathogenesis of ZJ7 strain, three CDV sero-negative dogs were intranasally inoculated with its virus suspension. All infected dogs developed clinical signs of severe bloody diarrhea, conjunctivitis, ocular discharge, nasal discharge and coughing, fever and weight loss at 21 dpi, whereas the mock group infected with DMEM were normal. The results demonstrated that CDV-ZJ7 strain isolated by MDCK cell was virulent, and the nucleotide and amino acid sequences of strain ZJ7 had no change after isolation by MDCK cell when compared with the original virus from the fresh tissues. Molecular and phylogenetic analyses for the nucleocapsid (N), phosphoprotein (P) and receptor binding haemagglutinin (H) gene of the ZJ7 isolate clearly showed it is joins to the Asia 1 group cluster of CDV strains, the predominant genotype in China.

Diagnosis and surgical treatment of congenital dextrocardia.

OBJECTIVE: To understand the pathological features of congenital dextrocardia and explore its diagnosis and surgical treatment. METHOD: The clinical data from 32 cases of congenital dextrocardia were collected to understand the major cardiac anomalies and evaluate the diagnostic approaches of this disease. Analysis of the effect of surgical treatment was also conducted in 16 among the 32 cases. RESULTS: Complex anomalies such as transposition of great artery (TGA), single ventricle (SV), common trunk (CMT) formation for the arteries were found in 8 out of 13 mirror-image dextrocardia cases, most of the dextroversion (DV) accompanied by physiological correction of the TGA (C-TGA, 11/17) which often involved ventricle septal defect (VSD) and pulmonary stenosis (PS, 8/11). Another 2 cases diagnosed as isolated dextrocardia (IDC) also suffered TGA combined with complete atrioventricular canal (CAVC) defect. Definite diagnoses of dextrocardia (DC) were derived from X-ray examination, including thoracic-abdominal plain X-ray film, hilar computed tomography, high kV chest plain film or ultrafast CT, echocardiogram and angiography. Fontan operation was performed in 8 cases and anatomical correction in 7 with surgical exploration in 1 case. Thirteen patients survived, among whom 8 had complex cardiac defect and 5 of them received modified Fontan operation or total cavopulmonary connection (TCPC). CONCLUSIONS: Complex cardiac anomalies are not rare in mirror-image dextrocardia, and dextroversion and isolated dextrocardia were usually related to C-TGA+VSD+PS and TGA+CAVC respectively. X-ray examinations are of great significance in the diagnoses and classification of dextrocardia, and echocardiogram and ultrafast CT constitute the major modalities for clarifying intracardial defect and surgical indications. Fontan operations, including modified Fontan and total cavopulmonary connection, might be hopeful surgical treatment for complex congenital heart disease when indications are carefully evaluated.