Stimulation of lipopolysaccharide from Pseudomonas aeruginosa following H9N2 IAV infection exacerbates inflammatory responses of alveolar macrophages and decreases virus replication.

H9N2 IAV infection contributed to P. aeruginosa coinfection, causing severe hemorrhagic pneumonia in mink. In this study, the in vitro alveolar macrophage models were developed to investigate the innate immune responses to P. aeruginosa LPS stimulation following H9N2 IAV infection, using MH-S cells. The cytokine levels, apoptosis levels and the viral nucleic acid levels were detected and analyzed. As a result, the levels of IFN-α, IL-1ß, TNF-α, and IL-10 in MH-S cells with P. aeruginosa LPS stimulation following H9N2 IAV infection were significantly higher than those in MH-S cells with single H9N2 IAV infection and single LPS stimulation (P < 0.05), exacerbating inflammatory responses. LPS stimulation aggravated the apoptosis of MH-S cells with H9N2 IAV infection. Interestingly, LPS stimulation influences H9N2 IAV replication and indirectly reduced H9N2 IAV replications in in vitro AMs. It implied that LPS should play an important role in the pathogenesis of H9N2 IAV and P. aeruginosa coinfection.

Mechanism of Polygonati Rhizoma on Treating Osteoporosis Based on Network Pharmacology and Preliminary Verification / 中国实验方剂学杂志

ObjectiveTo explore the potential mechanism of Polygonati Rhizoma on the treatment of osteoporosis （OP） based on network pharmacology and molecular docking method and to verify the mechanism by experiments. MethodThe main active ingredients and corresponding targets of Polygonati Rhizoma were screened out from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） 2.3 by conditional searching. The treatment targets were obtained from the genes related to OP and DisGeNET 7.0. The potential target genes of Polygonati Rhizoma for treating OP were obtained by the crossing of the corresponding targets and the treatment targets. Cytoscape 3.7.1 was used to construct the “Polygonati Rhizoma-active ingredient-potential target” network. The protein-protein interaction （PPI） analysis was carried out by STRING 11.0， and the PPI network was constructed. Metascape 3.5 was used to conduct Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analyses of the key targets. The core ingredients and key targets of Polygonati Rhizoma were selected for molecular docking by AutoDock Vina 1.1.2. Finally， the effect of β-sitosterol on osteogenic differentiation of MC3T3-E1 cells in rats was observed. ResultTwelve active ingredients and 32 potential targets of Polygonati Rhizoma for OP treatment were screened out. Six active ingredients including baicalein and β-sitosterol and key targets including protein kinase 1 （Akt1）， tumor suppressor p53 （TP53）， vascular endothelial growth factorA （VEGFA）， proto-oncogene Jun （JUN）， matrix metalloproteinase-9 （MMP-9）， and proto-oncogene c-Fos （FOS） were obtained by Cytoscape 3.7.1 topological analysis. A total of 995 GO entries and 181 signaling pathways involving the response to reactive oxygen species and regulations of growth were obtained from GO and KEGG enrichment analyses. The results of molecular docking showed that the core active ingredients possessed good binding activities with the respective key targets. The results of cell experiments showed that β-sitosterol promoted the osteogenic differentiation at the concentration of 2.5 μmol·L-1 and 5 μmol·L-1. ConclusionPolygonati Rhizoma had the therapeutic effect on treating OP by regulating inflammation， oxidative stress， apoptosis， and metabolism. The β-sitosterol significantly promoted the osteogenic differentiation of MC3T3-E1 cells.

Study on regulation of CYP450 enzyme system to reduce liver toxicity through compatibility of Aconiti Kusnezoffii Radix Cocta with Chebulae Fructus and Glycyrrhizae Radix et Rhizoma / 中国中药杂志

Aconiti Kusnezoffii Radix Cocta is one of the most commonly used medicinal materials in Mongolian medicine. Due to the strong toxicity of Aconiti Kusnezoffii Radix Cocta, Mongolian medicine often uses Chebulae Fructus, Glycyrrhizae Radix et Rhizoma to reduce the toxicity, so as to ensure the curative effect of Aconiti Kusnezoffii Radix Cocta while ensuring its clinical curative effect, but the mechanism is not clear. The aim of this study was to investigate the effects of Chebulae Fructus, Glycyrrhizae Radix et Rhizoma and Aconiti Kusnezoffii Radix Cocta on the mRNA transcription and protein translation of cytochrome P450(CYP450) in the liver of normal rats. Male SD rats were randomly divided into negative control(NC) group, phenobarbital(PB) group(0.08 g·kg~(-1)·d~(-1)), Chebulae Fructus group(0.254 2 g·kg~(-1)·d~(-1)), Glycyrrhizae Radix et Rhizoma group(0.254 2 g·kg~(-1)·d~(-1)), Aconiti Kusnezoffii Radix Cocta group(0.254 2 g·kg~(-1)·d~(-1))and compatibility group(0.254 2 g·kg~(-1)·d~(-1),taking Aconiti Kusnezoffii Radix Cocta as the standard). After continuous administration for 8 days, the activities of total bile acid(TBA), alkaline phosphatase(ALP), amino-transferase(ALT) and aspartate aminotransferase(AST)in serum were detected, the pathological changes of liver tissue were observed, and the mRNA and protein expression levels of CYP1 A2, CYP2 C11 and CYP3 A1 were observed. Compared with the NC group, the serum ALP, ALT and AST activities in the Aconiti Kusnezoffii Radix Cocta group were significantly increased, and the ALP, ALT and AST activities were decreased after compatibility. At the same time, compatibility could reduce the liver injury caused by Aconiti Kusnezoffii Radix Cocta. The results showed that Aconiti Kusnezoffii Radix Cocta could inhibit the expression of CYP1 A2, CYP2 C11 and CYP3 A1, and could up-regulate the expression of CYP1 A2, CYP2 C11 and CYP3 A1 when combined with Chebulae Fructus and Glycyrrhizae Radix et Rhizoma. The level of translation was consistent with that of transcription. The compatibility of Chebulae Fructus and Glycyrrhizae Radix et Rhizoma with Aconiti Kusnezoffii Radix Cocta could up-regulate the expression of CYP450 enzyme, reduce the accumulation time of aconitine in vivo, and play a role in reducing toxicity, and this effect may start from gene transcription.

Molecular characteristics of H9N2 influenza viruses isolated from farmed raccoon dogs and arctic foxes in China.

In this study, eight H9N2 IAVs were isolated from infected diseased, farmed raccoon dogs and arctic foxes. Eight genes shared 98.6%-100% identity among the isolates possessing a PSRSSR/GL motif at the HA cleavage site, which is same as the motif of G1 and Y280 lineages of H9N2 IAVs. The phylogenetic analysis showed that the HA genes of the eight isolates clustered with Y280-like viruses, whereas the NA genes belonged to F/98-like sublineage. Interestingly, the NS, NP, PB2 and PA genes of the isolates were closely related to H7N9 IAVs. This is the first evidence for isolation of H9N2 IAVs from raccoon dogs and arctic foxes. Raccoon dogs and arctic foxes potentially serve as an intermediate host for influenza viruses with pandemic potential toward other animals due to co-expression of both SA α-2,6-Gal and SA α-2,3-Gal receptors in a wide range of their tissues.

Similarity between mutation spectra in hypermutated genomes of rubella virus and in SARS-CoV-2 genomes accumulated during the COVID-19 pandemic

Genomes of tens of thousands of SARS-CoV2 isolates have been sequenced across the world and the total number of changes (predominantly single base substitutions) in these isolates exceeds ten thousand. We compared the mutational spectrum in the new SARS-CoV-2 mutation dataset with the previously published mutation spectrum in hypermutated genomes of rubella - another positive single stranded (ss) RNA virus. Each of the rubella isolates arose by accumulation of hundreds of mutations during propagation in a single subject, while SARS-CoV-2 mutation spectrum represents a collection events in multiple virus isolates from individuals across the world. We found a clear similarity between the spectra of single base substitutions in rubella and in SARS-CoV-2, with C to U as well as A to G and U to C being the most prominent in plus strand genomic RNA of each virus. Of those, U to C changes universally showed preference for loops versus stems in predicted RNA secondary structure. Similarly, to what was previously reported for rubella, C to U changes showed enrichment in the uCn motif, which suggested a subclass of APOBEC cytidine deaminase being a source of these substitutions. We also found enrichment of several other trinucleotide-centered mutation motifs only in SARS-CoV-2 - likely indicative of a mutation process characteristic to this virus. Altogether, the results of this analysis suggest that the mutation mechanisms that lead to hypermutation of the rubella vaccine virus in a rare pathological condition may also operate in the background of the SARS-CoV-2 viruses currently propagating in the human population.

Mechanism of detoxification of Chebulae Fructus against Aconiti kusnezoffii radix toxicity based on network pharmacology / 药学学报

The mechanism of detoxification of Chebulae Fructus against Aconiti kusnezoffii radix toxicity, which was known as Mongolian medical theory, was studied by establishing network of active components-targets-pathways of detoxification and enrichment analysis of targets and pathways based on network pharmacology. Firstly, the targets of active components collected from TCMSP and TCM Database@Taiwan were obtained through SwissTargetPrediction compared with disease targets from OMIM, TTD, DiGSeE. Then, the target enrichment analysis of GO functional annotations and KEGG pathways and protein function were analyzed by Metascape, furthermore, the action between main active ingredients and targets was assessed by SystemsDock Web Site. At last, the Cytoscape was used to construct the network of active components-targets-pathways. In conclusion, there were 15 components and 40 targets related to the cardiotoxicity caused by Aconiti kusnezoffii radix. Furthermore, Chebulae Fructus could regulate cardiac function to detoxify the toxicity by Aconiti kusnezoffii radix through the biological process of negative regulation of blood vessel diameter, regulation of ion transport circulatory system process, muscle contraction inorganic ion homeostasis and the pathways of neuroactive ligand-receptor interaction, calcium signaling pathway, adrenergic signaling in cardiomyocytes, etc.

Current advance in cerebral malaria / 中国中药杂志

Cerebral malaria (CM), a severe neurological syndrome caused by Plasmodium falciparum infection, is a serious life-threatening disease with a high mortality. Survivors' persistent brain injury is manifested as long-term neurocognitive disorders. The main neuropathological feature of CM is the sequestration of parasited red blood cells (pRBCs) in cerebral microvessels. Other neuropathological features of CM include petechial hemorrhage in the brain parenchyma, annular hemorrhage, extensive brain endothelial cell activation, and focal endothelial cell injury and necrosis. However, its pathogenesis is still not clear. Currently, some studies have suggested that the pathogenesis of cerebral malaria mainly include pRBC adhesion, inflammatory reaction cascade, vascular leakage damage and brain hypoxia. Studies have shown that the biomarkers currently used as diagnostic and prognostic markers for CM include C-X-C motif chemokine ligand 10 (CXCL10), CXC chemokine ligand 4 (CXCL4), angiopoietin (Ang). In this paper, we systematically summarize the basic and clinical research for cerebral malaria in recent years and the latest literatures for drug studies, and focused on the advance of studies on cerebral malaria and its immunologic mechanism in the recent three years in the aspects of cytokines, immune cells, regulatory factors and biomarkers, so as to provide references for relevant studies.

Protective effect of Shuyu Yiban decoction on atherosclerosis in rats induced by chronic unpredictable mild stress / 中国中药杂志

Shuyu Yiban decoction(SYYB) has significant effect in treating the patients with coronary heart disease combined with chronic psychological stress. In this study, in order to observe the effects of SYYB on early formation of atherosclerosis(As) and inflammation response induced by chronic psychological stress, high-fat diet+intraperitoneal injections of Vitamin D3 were given to establish As early lesion models, and based on these models, chronic unpredictable mild stress(CUMS) was used to observe whether the chronic psychological stress could increase coronary atherosclerotic lesions investigate the intervention effect of SYYB(6.6, 13.2, 26.4 mg•kg⁻¹). The tail suspension test and novelty-feeding test were adopted to detectadrenocortico-tropic hormone(ACTH), cortisol(Cor) andnoradrenaline(NE) in serum and weigh thymus and adrenal gland, in order to assess the effects of SYYB on CUMS model rats. The pathological changes of vascular tissues in aortic arch were observed by using hematoxylin and eosin(HE) staining, and then the levels of triglycerides(TG), total cholesterol(TC) and high density lipoprotein(HDL-C) in serum were determined to assess effects of SYYB on As lesions. The effects of SYYB on the inflammatory response in As rats were assessed by detecting high-sensitivity C-reactive protein(hsCRP), interleukin-1β(IL-1β) and interleukin-6(IL-6) in serum. The results showed that as compared with the blank control group, TC and TG levels in As group were increased while HDL-C was markedly decreased; furthermore, the aortic wall was thickened in HE staining. Meanwhile, foam cells were formed, and the behavioral assessment and serum stress hormone test showed that there was a chronic stress response, indicating successful establishment of As+CUMS models in this study. The experiment demonstrated that SYYB could lower the levels of serum TC and TG, reduce foam cells, calcification and inflammatory cells infiltration. Moreover, SYYB could obviously lower levels of ACTH, Cor and NE and the As related inflammatory indicatorhs-CRP, IL-1β and IL-6 in serum.These results indicated that SYYB had protective effect on chronic psychological stress induced in As rats, and the mechanism was associated with balancing the neuroendocrine-immune network system and regulating inflammation response.

Resources and application of She's nationality wild medicinal plants / 中国中药杂志

To make a thorough investigation of the common She's nationality wild medicinal plants resources in our country, including the species, the distribution, the folk application and the endemic medicinal plant species, Field surveyed was conducted with 25 She people mainly lived area (county, district or city) throughout the country, the folk prescription and treatment cases provided by She's medical personnel, the drug usage and dosage, the commonly used traditional She's medicine and drug samples were collected. And the distribution, growing environment of these plants were investigated, their characteristics, photographs, GPS data and track were record , and the fresh wax leaf or plants specimens were collected. In total 1 600 varieties of folk medicine of She's nationality, 450 disease names and 1 016 prescriptions were collected. 520 kinds of these medicinal plants were commonly used, growing mainly distributed in the southeastern China, about 200 meters above sea level to 1 500 meters. There are 5 First-Grade State protection wild plants (medicinal), 15 second-Grade State protection wild plants (medicinal), and 11 She characteristic medicinal plants in our study, they belong to 144 families, 312 genera 494 species, 2 subspecies, 17 varieties, 3 forms and 1 cultivated varieties of She's nationality. Folk medicine usage is different from the traditional Chinese medicine and ethnic medicine. This survey finds out the common She's nationality wild medicinal plants resources in China, including the species, the distribution, the folk application and commonly used drugs, and found the rare and endangered medicinal plants and the She's nationality endemic medicinal plants, which provides a basis for further development and use the traditional She's medicine resources.

Removal of hepatocellular carcinoma extending into the right atrium with extracorporeal circulation.

Hepatocellular carcinoma with tumor thrombus extending into the right atrium is rare and has an extremely poor prognosis. Surgery was once regarded as a contraindication, then as a palliative method to prevent emergencies such as pulmonary embolism or heart failure. With advances of imaging techniques, hepatectomy and widespread use of extracorporeal circulation, conventional viewpoint has gradually changed. For patients with adequate hepatic function reserve and no distant metastases, surgery is recommended. During the past four years, we experienced two such patients, for both of whom we simultaneously resected the hepatic tumor and tumor thrombus in the right atrium under cardiopulmonary circulation and total hepatic blood exclusion. Both of the patients survived the surgery. During the follow-up, one patient died 6 months later due to multiple lung metastases and tumor progression. The other patient experienced recurrence 4 months after surgery and underwent adjuvant treatment modalities including chemotherapy, radiofrequency ablation and transcatheter arterial chemoembolization. Thirty-eight months later, the patient died of multiple metastasis and hepatic failure.