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This study was to evaluate the potential mechanism of action of Artemisia annua L. (A. annua) in the treatment of acute myocardial infarction (AMI) using network pharmacology, molecular docking and in vivo experiments. 22 active chemical compounds and 193 drug targets of A. annua were screened using the Traditional Chinese Medicine System Pharmacological (TCMSP) database. 3876 disease targets were also collected. Then 158 intersection targets between AMI and A. annua were obtained using R 4.2.0 software. String database was used to construct the protein-protein interaction (PPI) network and 6 core targets (MAPK1, TP53, HSP90AA1, RELA, AKT1, and MYC) were screened. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed using the R package. GO enrichment results were mainly related to cell responses to chemical stress and cell membrane microregions. KEGG pathways were mainly involved in lipids, atherosclerosis and fluid shear stress. In addition, molecular docking between A. annua active compounds and core targets showed high binding activity. As for in vivo validation, A. annua extract showed significant effects on improving post-infarction ventricular function, delaying ventricular remodeling, and reducing myocardial fibrosis and apoptosis. This study has revealed the potential components and molecular mechanisms of A. annua in the treatment of AMI. Our work also showed that A. annua has great effect on reducing myocardial fibrosis and scar area after infarction.
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Objective:To investigate the serum levels of myonectin, corticostatin and Delta like ligand 4 (DLL4) in patients with type 2 diabetes mellitus (T2DM) diabetes retinopathy (DR) and their clinical significance.Methods:A prospective selection of 341 T2DM patients admitted to Beijing Hospital of Traditional Chinese Medicine, Huairou Hospital from May 2020 to March 2022 was conducted. The patients underwent fundus examination and were divided into a non DR group ( n=85 cases) and a DR group ( n=256 cases) based on DR diagnostic criteria. The DR group was divided into non proliferative and proliferative types according to the staging criteria in China′s DR clinical diagnosis and treatment guidelines, with 142 cases and 114 cases, respectively; 190 healthy individuals who underwent physical examinations in our hospital during the same period were selected as the control group. Enzyme linked immunosorbent assay was used to detect the levels of serum sarconectin, corticostatin, and DLL4 in three groups, collect patient data, and detect biochemical indicators. Logistic regression analysis was used to analyze the influencing factors of DR, and Pearson correlation analysis was used to investigate the relationship between serum sarconectin, corticostatin, DLL4, glucose and lipid metabolism, and insulin resistance; Logistic regression analysis was used to analyze the influencing factors of DR, and Pearson correlation analysis was used to investigate the relationship between serum sarconectin, corticostatin, DLL4, glucose and lipid metabolism, and insulin resistance; The receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of serum sarconectin, corticostatin, and DLL4 in DR. Results:The levels of serum sarconectin and DLL4 in the DR group and non DR group were higher than those in the control group, while the levels of corticostatin were lower than those in the control group (all P<0.05); The levels of sarconectin and DLL4 in the DR group were higher than those in the non DR group, while the levels of corticostatin were lower than those in the non DR group (all P<0.05). The serum levels of sarconectin and DLL4 in proliferative DR patients were higher than those in non proliferative DR patients, while the levels of corticostatin were lower than those in non proliferative DR patients (all P<0.05). The duration of T2DM in the DR group was longer than that in the non DR group, with smoking and alcohol consumption, systolic blood pressure, fasting blood glucose, glycated hemoglobin, triglyceride and insulin resistance index (HOMA-IR) were higher than those in non DR group (all P<0.05). Logistic regression analysis showed that the course of T2DM, systolic blood pressure, smoking and alcohol consumption, glycated hemoglobin, triglycerides, myonectin, corticostatin and DLL4 were the influencing factors of DR (all P<0.05). Pearson correlation analysis results showed that serum sarconectin, DLL4, and fasting blood glucose, glycated hemoglobin, fasting insulin and HOMA-IR were positively correlated (all P<0.05), while cortisol was negatively correlated with fasting blood glucose, glycated hemoglobin and HOMA-IR (all P<0.05). The ROC analysis results showed that the area under the curve (AUC) for the diagnosis of DR was 0.691, 0.745, 0.749, and 0.861 for sarconectin, corticostatin, and DLL4 alone and in combination, respectively. The combined application had higher diagnostic value. Conclusions:Patients with T2DM complicated with DR have elevated levels of serum sarconectin and DLL4, while decreased levels of corticostatin, which are closely related to glucose and lipid metabolism and insulin resistance, and are influencing factors for the occurrence of DR. Combined detection of the three can improve the value of predicting DR.
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italic>Ardisia crispa (Thunb.) A. DC. is a traditional Miao medicinal herb with significant therapeutic effects in the treatment of sore throat, tonsillitis, edema of nephritis and bruising and rheumatism, etc. Ardisia crispa var. amplifolia and Ardisia crispa var. dielsii are varieties of A. crispa. A. crispa var. amplifolia and A. crispa var. dielsii are controversial in terms of species evolutionary relationships and taxonomic identification. In this study, we sequenced the whole genome sequences of A. crispa var. amplifolia and A. crispa var. dielsii chloroplasts using Illumina platform, assembled, annotated and characterized them, compared the structural features and degree of variation among chloroplast genomes using bioinformatics methods, and also downloaded constructing phylogenetic trees to analyze the phylogenetic relationships of chloroplasts in Primulaceae and Myrsinaceae using whole genome sequence information. The results showed that the complete chloroplast genome sequences of A. crispa var. amplifolia and A. crispa var. dielsii were 156 749 bp and 156 748 bp in length, with 132 genes annotated, including 87 protein-coding genes; the codon preference of A/U was greater than that of G/C; The differences in the coding regions of rps15 and rpoB genes in the comparative genome analysis can be used as loci for molecular identification of the two species; the differences in the coding regions of ycf1, ycf2, rpoC1, ycf3, petD and rpl16 genes in the chloroplast genome compared with those of the same genus can be used as loci for identification of the genus. In the phylogenetic results, A. crispa var. amplifolia and A. crispa var. dielsii were clustered together with 100% support, indicating that they are closely related. In this research, we analyzed the chloroplast genome structure and phylogenetic relationships of A. crispa var. amplifolia and A. crispa var. dielsii, providing an important theoretical basis for their molecular identification, genetic variation, breeding and phylogenetic analysis.
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Objectives@#Sacral insufficiency fracture (SIF) is not an uncommon osteoporosis fracture among the elderly. Aside from traditional treatments, sacroplasty and teriparatide (TPTD) injection have been introduced. This report aims to compare the effects of sacroplasty and teriparatide on clinical outcomes of SIF. @*Methods@#Thirty-one elderly patients with SIF were enrolled in this retrospective observational study. Four male patients were excluded. Fourteen patients who received TPTD for 6 months were classified into the TPTD group (TT), and 13 who underwent sacroplasty were classified into the sacroplasty group (SS). All patients in both groups were instructed to take calcium and vitamin D supplements daily. Their symptoms and signs, visual analog score (VAS), Oswestry disability index (ODI), and radiographic studies were retrospectively reviewed. @*Results@#The TT group showed significantly lower VAS than SS group after 3 (P < 0.001) and 6 months of treatment (P < 0.001). The TT group also has significant lower ODI than SS group after 1 (P = 0.010), 3 (P = 0.005) and 6 months (P < 0.001) of treatment. Upon generalized estimating equations (GEE) analysis, the TT group showed significantly more reduction in both VAS and ODI compared to the SS group at 1 month (P = 0.022, P = 0.001), 3 months (P < 0.001, P < 0.001), and 6 months (P < 0.001, P < 0.001) post-treatment. @*Conclusions@#Postmenoposal woman with SIF who received TPTD healed better than those who underwent sacroplasty after 1 month treatment.
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The ancient herbal books, and literatures were reviewed, and the textual research and origin of Caryophylli flos were explored from the differences between Caryophylli flos and Caryophylli fructus, the alias of Caryophylli flos and Caryophylli fructus, the origin and introduction of Caryophylli flos, and its efficacy and indications. The results indicated that Caryophylli flos and Caryophylli fructus were different from each other in terms of synonyms, chemical components and pharmacological effects. Caryophylli flos was brought to China as a spice in the Wei, Jin, Southern and Northern Dynasties, and the efficacy of Caryophylli flos was almost same in ancient and modern time. Caryophylli flos is widely used in digestive and dental diseases, and Caryophylli flos is also one of the seven natural spices, which can be used for food preservation.
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Objective:To investigate the therapeutic value of modified multipoint drainage for biliary complications after liver transplantation.Methods:A total of 125 patients treated by endoscopic retrograde cholangiopancreatography (ERCP) for biliary complications after liver transplantation in Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from May 2018 to May 2020 were enrolled. Patients were divided into endoscopic retrograde biliary drainage (ERBD) group ( n=67, treated with multiple drainage of bile duct stent) and modified multipoint drainage group [ n=58, treated with ERBD combined with endoscopic nasobiliary drainage (ENBD)] by random number table. Modified multipoint drainage group were further randomly divided into two groups, modification group 1, 31 cases, where nasobiliary ducts were cut proximal to duodenal papilla after one week under endoscopy and modification group 2, 27 cases, where they were cut proximal to duodenal papilla after two weeks under endoscopy. The changes of serological indexes in 2 weeks after the operation in three groups were compared, and the incidence of short-term and long-term complications were analyzed. Results:The serological indexes were improved in patients at 1 d, 7 d and 14 d after ERCP, especially in modified multipoint drainage groups. Two weeks after the operation, the improvement of serological indexes in modification group 2 was better than that in modification group 1. Incidence of recent complications including cholangitis, hyperamylasinemia, and pancreatitis in the ERBD group were higher than those in modification group 1 [32.84% (22/67) VS 12.90% (4/31), 46.27% (31/67) VS 19.35% (6/31), 20.90% (14/67) VS 3.23% (1/31), all P<0.05] and modification group 2 [32.84% (22/67) VS 11.11% (3/27), 46.27% (31/67) VS 22.22% (6/27), 20.90% (14/67) VS 3.70% (1/27), all P<0.05]. ERBD group had a higher incidence of long-term complications including recurrent biliary infection and jaundice than modification group 1 [ 58.21% (39/67) VS 35.48% (11/31), P=0.036; 49.25% (33/67) VS 25.81% (8/31), P=0.027] and modification group 2 [58.21% (39/67) VS 11.11% (3/27), P<0.001; 49.25% (33/67) VS 25.93% (7/27), P=0.038]. The incidence of recurrent biliary infection in modification group 1 was higher than that in modification group 2 [35.48% (11/31) VS 11.11% (3/27), P=0.030]. Conclusion:Multiple drainage with indwelling nasal bile duct by ERCP can effectively reduce the short-term and long-term complications and improve the recovery of serological indexes for patients with biliary complications after liver transplantation. It is suggested that the nasobiliary duct should be retained for 2 weeks and then transformed into a built-in tube to continue drainage.
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ObjectiveTo study the protective effect of total flavonoids of lavender on skin photoaging induced by ultraviolet B (UVB) in mice and to explore its mechanism from the perspective of nuclear factor E2-related factor 2 (Nrf2) antioxidant pathway. MethodEighty-four female KM mice were randomly divided into seven groups, namely blank group, model group, solvent group, vitamin E (0.013 g·kg-1) group, as well as low-, middle-, and high-dose (0.25, 1.25, 2.50 g·kg-1) groups of total flavonoids of lavender. The naked skin on the back of mice was irradiated with UVB for inducing optical damage. Thirty minutes before irradiation, the skin was coated with the total flavonoids of lavender. After continuous irradiation for one week, the skin moisture and elasticity on the back of mice were evaluated, and the effects of total flavonoids of lavender on histopathological changes in mouse skin were investigated by hematoxylin-eosin (HE) and Van Gieson (VG) staining. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), total antioxidant capacity (T-AOC), nitric oxide synthase (NOS), and glutathione peroxidase (GSH-Px) after skin homogenization were detected by colorimetry, the inflammatory factors interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in skin tissue by enzyme-linked immunosorbent assay (ELISA), and the mRNA expression levels of Nrf2, Kelch-like epichlorohydrin-associated protein 1 (Keap1), BTB-CNC homology 1 (Bach1), heme oxygenase-1 (HO-1), quinone oxidoreductase 1 (NQO1), and glutamate-cysteine ligase catalytic subunit (GCLC) by real-time polymerase chain reaction (Real-time PCR). ResultCompared with the blank group, the model group exhibited significantly increased appearance score (P<0.01), reduced skin moisture and elasticity (P<0.01), pronounced pathological changes in the skin tissue like epidermal thickening, scabbing, small abscess, and severe injury, elevated MDA, NOS, IL-1, IL-6 and TNF-α (P<0.05, P<0.01), lowered SOD, T-AOC, Nrf2, Keap1, NQO1 and GCLC mRNA expression (P<0.05,P<0.01), and up-regulated Bach1 mRNA expression (P<0.01). Compared with the model group, the total flavonoids of lavender at the low, middle, and high doses all remarkably reduced the appearance score (P<0.01), enhanced the skin moisture and elasticity (P<0.01), diminished the MDA, NOS, IL-1, IL-6, and TNF-α (P<0.05, P<0.01), increased SOD, T-AOC, Nrf2, Keap1, NQO1, HO-1 and GCLC mRNA expression (P<0.05, P<0.01), and down-regulated the expression of Bach1 mRNA (P<0.01). ConclusionThe protective effect of the total flavonoids of lavender against skin photoaging in mice is significant, which may be related to its activation of Keap1/Nrf2/ARE signaling pathway, regulation of oxidative stress, and improvement of inflammatory response.
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The incidence of psoriasis which is characterized by dryness, scaling and itching of the skin has been on the rise. It can have a profound psychological impact on patients' quality of life. Accumulating research has been conducted on the mechanisms of psoriasis in western medicine, from the difference of pathological manifestations of terminal keratinocytes, the disorder of expression of related factors and cells, to the immune imbalance of T lymphocytes and their subsets, or the abnormal transcription dominated by genetic genes. As a result, a complex and huge mechanism network has formed and many hypotheses have emerged. In recent years, with the in-depth research on non-coding genes, it has been clarified that microRNA-modified multi-pathway effect interferes with the occurrence and development of psoriasis and affects the proliferation, apoptosis, and differentiation of keratinocytes. The research on microRNA involves both genetics and immunology, which can help improve the key links in the micro pathway of psoriasis. Thus, it is a key part in the pathogenesis of psoriasis and has also become the hotspot and difficulty of modern research on psoriasis. At the same time, we should give full play to the advantages of traditional Chinese medicine (TCM) in syndrome differentiation and treatment. To be specific, microRNA targets of compound Chinese medicine preparations with the functions of clearing heat, cooling blood, detoxifying and removing blood stasis or effective medicinal monomers such as paeonol, tripterygium glycosides, shikonin, curcumin, total glucosides of paeony and indirubin should be explored, and microRNA can be used as the basis for blood syndrome differentiation of psoriasis. Thereby, the syndrome differentiation theory of TCM and micro indicators of western medicine are integrated, to make full use of characteristics of TCM and guide the clinical syndrome differentiation and treatment. At present, the intervention on microRNA in TCM is rarely studied, and available studies mainly focus on several targets such as microRNA-155, microRNA-210, microRNA-21, microRNA-203, microRNA-320, microRNA-124, microRNA-330, microRNA-146a, and microRNA-15a-5p. This paper summarizes the research on compound Chinese medicine prescriptions and monomers in the treatment and syndrome differentiation of psoriasis through the intervention of microRNA, which is expected to provide a reference for the research on psoriasis in TCM and western medicine and the establishment of microRNA-based database.
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Magnoliae Officinalis Cortex, a common Chinese medicinal in clinic, should undergo "sweating" process in producing area according to Chinese Pharmacopoeia, which affects its genuineness and quality. In light of the concept and research mode of quality marker(Q-marker) for decoction pieces, the active components of Magnoliae Officinalis Cortex pieces which altered significantly before and after "sweating" were identified in this study. The main pharmacodynamic material basis was clarified by pharmacodynamic, pharmacokinetic and drug property research, followed by the prediction of Q-markers of Magnoliae Officinalis Cortex before and after "sweating", for better improving its quality standard.
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Medicamentos Herbarios Chinos , MagnoliaRESUMEN
This study aims to explore underlying mechanism of Lonicerae Japonicae Flos(LJF) in protecting rats against acute alcoholic liver injury(ALI) based on mitogen-activated protein kinase(MAPK) pathway. First, the targets of LJF in preventing ALI were predicted by network pharmacology and the component-target-pathway network was constructed, so that the key targets of LJF components acting on MAPK pathway were screened. Second, male SD rats were randomized into the control(KB) group, model(MX) group, positive(YX) group, and LJF high-(GJ), medium-(ZJ), and low-(DJ) dose groups. Each administration group was given(ig) corresponding drugs for 7 days and KB group and MX group received(ig) equal volume of distilled water every day. Except for KB group, rats were given Chinese spirit(56%, 3 days) for ALI modeling. The levels of aspartate transaminase(AST), alanine transaminase(ALT), interleukin-6(IL6) and tumor necrosis factor-α(TNF-α) in serum and malondialdehyde(MDA), glutathione(GSH), superoxide dismutase(SOD) and glutathione peroxidase(GSH-Px) in liver tissue of rats in each group were detected. Furthermore, we employed quantitative real-time PCR(qRT-PCR) to probe the effects of LJF on the key targets of MAPK pathway in ALI rats. A total of 28 active components of LJF were screened from TCMSP database, and 317 intersected with ALI-related targets. According to Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis, the 317 targets involved 226 pathways, which were mainly liver disease, inflammation, immunity, apoptosis and other related pathways. According to the MAPK pathway-target-active component network, the key active components of LJF, such as chlorogenic acid, hederagenol, and hyperoside, acted on 25 key targets of MAPK pathway. The results of in vivo experiments showed decreased levels of AST, ALT, and MDA in DJ, ZJ, and GJ groups(P<0.01 or P<0.05), reduced levels of IL6 in DJ and GJ groups(P<0.01 or P<0.05), and improved levels of SOD and GSH in ZJ and GJ groups(P<0.01 or P<0.05). The results of qRT-PCR demonstrated that the expression levels of mitogen-activated protein kinase kinase 4(MAPK2 K4) and mitogen-activated protein kinase 3(MAPK3) were decreased in DJ, ZJ, and GJ groups(P<0.01). The network pharmacology and experimental verification showed that the active components in LJF can reduce the inflammatory factor level and enhance the activities of SOD and GSH-Px by inhibiting the expression of key targets of MAPK pathway, thus alleviating and preventing liver damage caused by alcohol.
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Animales , Masculino , Ratas , Ácido Clorogénico , Medicamentos Herbarios Chinos , Hígado , Hepatopatías , Ratas Sprague-DawleyRESUMEN
Schisandrae Chinensis Fructus in six growth stages was taken as materials to study the species and content changes of material basis, which were detected by UPLC, GC and MS chromatography, including lignans, nucleosides, aroma components and fatty acids. The results showed that the texture, color and taste of Schisandrae Chinensis Fructus in six growth stages were different. On the material basis, 12 lignans were detected by UPLC-MS, and the content of total lignans was higher in the samples from late August to early September, among which the highest content of schisandrin was 0.67%±0.01%, followed by schizandrol B, angeloylgomisin H and schisandrin B, and the total content increased with the maturity of Schisandrae Chinensis Fructus. Thirteen kinds of nucleosides were detected by UPLC. The total nucleoside content was the highest in late July samples, in which the contents of uridine and guanosine were higher and decreased after maturity. Aroma components and fatty acids were identified by GC-MS. A total of 53 aroma components were detected and the highest total content was appeared in late August samples, of which ylangene was higher and bergamotene was followed. A total of 24 kinds of fatty acids were detected. The fruits matured basically in August, and the content of fatty acids in the samples was the highest, among which linoleic acid content was top the list and oleic acid was the second. To sum up, the maturity of Schisandra chinensis fruit is related to the content and variety of various material bases, and the growth period has different influences on the quality of Schisandrae Chinensis Fructus. Therefore, the appropriate harvesting time should be determined according to the change law of target components. The results of this study can provide reference for the quality evaluation of Schisandrae Chinensis Fructus material basis.
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Cromatografía Liquida , Medicamentos Herbarios Chinos , Frutas/química , Lignanos/análisis , Schisandra , Espectrometría de Masas en TándemRESUMEN
Objective:To explore the effect of radiofrequency heating on the morphology of articular cartilage in the knee and the expression of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the synovium using a rabbit model of knee osteoarthritis (OA).Methods:Fifty-four male rabbits had OA induced in their right hind limbs using the modified Hulth method. They were then randomly divided into a model group, a cervus and cucumis polypeptide (CCP) group and a radiofrequency thermotherapy (RT) group, each of 18. The CCP group was injected with deer melon peptide intramuscularly every day, while the RT group was given daily radiofrequency hyperthermia treatment at 36.5-38.5 ℃. The model group was not provided with any special treatment. On the 6th, 12th and 18th day of the treatment, 6 rabbits in each group were sacrificed to resect the right femur′s medial condyle cartilage. The morphological characteristics of the cartilage were evaluated using modified Mankins scoring, while the contents of lL-1B and TNF-a in the synovial membrane were detected using enzyme-linked immuno-sorbent assays.Results:The average Mankins scores and the levels of IL-1β and TNF-α decreased significantly at each time point, and significant differences were observed among the three groups. In the RT group the average Mankins score as well as the IL-1β and TNF-α levels decreased significantly with time throughout the experiment.Conclusions:Radiofrequency hyperthermia is superior to the injection of deer melon polypeptide in knee osteoarthritis, at least in rabbits. The therapeutic mechanism may be related to the control of IL-1β and TNF- α levels in the synovial membrane.
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Network pharmacology and the mouse model of viral pneumonia caused by influenza virus FM_1 were employed to explore the main active components and the mechanism of Pulsatilla chinensis against the inflammatory injury of influenza virus-induced pneumonia. The components and targets of P. chinensis were searched from TCMSP, and the targets associated with influenza virus-induced pneumonia were searched from GeneCards. The common targets between P. chinensis and influenza virus-induced pneumonia were identified with Venn diagram established in Venny 2.1. The herb-component-disease-target(H-C-D-T) network was constructed by Cytoscape 3.7.2. The above data were imported into STRING for PPI network analysis. Gene Ontology(GO) enrichment and KEGG pathway enrichment were performed with DAVID. BALB/cAnN mice were infected with the influenza virus FM_1 by nasal drip to gene-rate the mouse model of pneumonia. Immunohistochemistry was adopted to the expression profiling of inflammatory cytokines in the lung tissues of mice in the blank group, model group, and P. chinensis group 1, 3, 5, and 7 days after infection. The pathological changes of lung and trachea of mice in blank group, model group, and P. chinensis group were observed with light microscope and scanning electron microscope at all the time points. The network pharmacological analysis indicated that 9 compounds of P. chinensis were screened out, with a total of 57 targets, 22 of which were overlapped with those of influenza virus-induced pneumonia. A total of 112 GO terms(P<0.05) were enriched, including 81 terms of biological processes, 11 terms of cell components, and 20 terms of molecular functions. A total of 53 KEGG signaling pathways(P<0.05) were enriched, including TNF signaling pathway, influenza A signaling pathway, NF-κB signaling pathway, MAPK signaling pathway and other signaling pathways related to influenza/inflammation. In the P. chinensis group, the expression of TNF-α and IL-1 in the lung tissue was down-regulated on the 3 rd day after infection, and that of IL-6 in the lung tissue was down-regulated on the 5 th day after infection. Light microscopy and scanning electron microscopy showed that P. chinensis significantly alleviated the pathological damage of lung and trachea compared with the model group. This study reflects the multi-components, multi-targets, and multi-pathways of P. chinensis against influenza virus-induced pneumonia. P. chinensis may reduce the production of proinflammatory cytokines and mediators and block the pro-inflammatory signaling pathways to alleviate viral pneumonia, which provides reference for future research.
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Animales , Ratones , Medicamentos Herbarios Chinos , Farmacología en Red , Orthomyxoviridae , Neumonía/genética , PulsatillaRESUMEN
To study the effect of Lonicera fulvotometosa(LFH) on expression of genes related to inflammatory pathways in the lung tissue of rats with acute lung injury(ALI) induced by lipopolysaccharide(LPS), explore the lung-protective effects and inflammatory mechanisms of L. fulvotometosa water extract, and provide experimental and theoretical basis for the clinical application of LFH. Forty SD rats were randomly divided into 4 groups: normal group, model group(LPS, 5 mg·kg~(-1)), LFH group(7.2 g·kg~(-1)) and dexa-methasone group(Dexa, 5 mg·kg~(-1)). The rats in LFH group received intragastric administration of water extract once a day for 5 days; rats in dexamethasone group received intraperitoneal injection for 2 hours before modeling. Except the normal group, the rats in other groups were injected intraperitoneally with LPS(5 mg·kg~(-1)) to induce ALI rats model. Serum, bronchoalveolar lavage fluid(BALF) and lung tissues were collected 6 hours after modeling. The lung tissues were taken for pathological observation; enzyme-linked immunosorbent assay(ELISA) was used to detect changes of inflammatory factors in serum and BALF; Real-time quantitative polymerase chain reaction(RT-qPCR) was applied to detect mRNA expression of tumor necrosis factor alpha inducible protein 3(TNFAIP3), interleukin(IL) 1 R1, interleukin(IL) 6 R and nuclear factor κB inhibitor α(NFKBIA) in the lung tissues. The degree of lung injury was lighter in LFH group than that in the LPS group. As compared with the LPS group, the levels of interleukin-1ß(IL-1ß), interleukin-6(IL-6), tumor necrosis factor-α(TNF-α) in serum and BALF, malondialdehyde(MDA) and myeloperoxidase(MPO) in lung tissues were significantly reduced in LFH group and Dexa group, while glutathione peroxidase(GSH-Px), superoxide dismutase(SOD) in lung tissues were significantly increased; the mRNA expression of TNFAIP3, IL1 R1, IL6 R and NFKBIA in the lung tissues of the LFH group was significantly lower than that of the LPS group. The water extract of LFH can significantly reduce the content of inflammatory factors in rats with ALI, and down-regulate the mRNA expression of TNFAIP3, IL1 R1, IL6 R and NFKBIA in the lung tissues, showing significant anti-inflammatory effect. Its mechanism may be related to the regulation of NF-κB signaling pathway, and the pulmonary inflammation response may be reduced by down-regulating the expression of downstream-related inflammatory factors.
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Lesión Pulmonar Aguda , Lonicera , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/genética , Animales , Antiinflamatorios/uso terapéutico , Líquido del Lavado Bronquioalveolar , Lipopolisacáridos/toxicidad , Pulmón , FN-kappa B/genética , Ratas , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
In this paper, the possible molecular mechanism of Forsythia suspensa for the anti-tumor effect was investigated through the network pharmacology and molecular docking. The main components of F. suspensa were obtained by literature mining and TCMSP database. Cancer-related genes were collected with use of GAD and OMIM databases. The interaction network of Compounds-Targets-Pathways was constructed through Cytoscpe software. The targets were analyzed by GO and KEGG means in DAVID database, and the KEGG signal pathways were visualized. Component-Target network analysis results were verified by PyRx molecular docking. The results showed that a total of 26 main components of F. suspensa may act on key targets such as AKT1, IL6, ESR1, EGFR, EGF and CCND1, and were involved in 20 signal pathways. Molecular docking analysis showed that hydrogen bonding, hydrophobic action and Pi-cation bonding maybe the main forms of interaction. In this study, we revealed the anti-tumor effect of F. suspensa through the network of Compounds-Targets-Pathways and molecular docking verification, providing reference and guidance for systematically elucidating the anti-tumor molecular mechanism of the main components of F. suspensa.
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Medicamentos Herbarios Chinos , Forsythia , Neoplasias , Medicamentos Herbarios Chinos/farmacología , Forsythia/genética , Humanos , Simulación del Acoplamiento Molecular , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Transducción de SeñalRESUMEN
Despite the excellent efficacy and low toxicity of photoresponse therapy, which has attracted considerable attention for use in non-small cell lung cancer (NSCLC) therapy, unsatisfactory cellular permeability, and instability, both in vitro and in vivo have limited further clinical applications of indole cyanine photosensitizers. Here, we explore the supramolecular self-assembly of a 'hyalurosome' that is mediated by calcium phosphate nanonuclei. Through hyaluronate-mediated CD44 targeting, the constructed hyalurosome specifically delivers ICG into NSCLC cells and then induces severe hyperthermia accompanied by the generation of singlet oxygen upon photoirradiation. In contrast to the action of the native form, indocyanine green encapsulated in a hyalurosome showed significantly increased cellular endocytosis and inhibited cell proliferation both in vitro and in vivo. Our study indicated that this hyalurosome is a promising candidate for the targeted delivery of photosensitizers, which may be useful in NSCLC therapy.
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Carcinoma de Pulmón de Células no Pequeñas/terapia , Ácido Hialurónico/química , Neoplasias Pulmonares/terapia , Fototerapia/métodos , Células A549 , Animales , Fosfatos de Calcio/química , Carcinoma de Pulmón de Células no Pequeñas/patología , Proliferación Celular/fisiología , Sistemas de Liberación de Medicamentos , Femenino , Humanos , Receptores de Hialuranos/metabolismo , Hipertermia Inducida/métodos , Verde de Indocianina/administración & dosificación , Neoplasias Pulmonares/patología , Ratones , Ratones Desnudos , Fármacos Fotosensibilizantes/administración & dosificación , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
italic>Inula japonica, Inula hupehensis and Inula linaariifolia are all medicinal plants of Inula L. in the Compositae family, and Inula hupehensis is endemic to China. In order to compare their genomic sequence differences and provide scientific basis for their germplasm conservation and development, we obtained and analyzed the complete chloroplast genomes of these three species. Total DNAs were extracted from fresh leaves and subjected to next-generation DNA sequencing. NOVOPlasty was used to assemble the chloroplast genomes from the sequence reads. CPGAVAS2 was used to annotate the genes and repeats in each genome. Lastly, phylogenomics analysis was conducted using RAxML. The results showed that the total length of the chloroplast genome of Inula japonica, Inula hupehensis and Inula linaariifolia is 150 754, 150 909, and 150 812 bp respectively, each consisting of a large single copy region, a small single copy region and a pair of inverted repeat regions. In addition, the G/C content of all three chloroplast genomes was approximately 37.7% and each encoded 111 unique genes, including 79 protein-coding, 28 tRNA and 4 rRNA genes. Meanwhile, 32, 33, 34 simple repeat sequences, 18, 22, 18 tandem repeat sequences and 33, 37, 38 scattered repeat sequences were identified in three species. Phylogenomic analysis showed that all three species of Inula L. and Pluchea indica were clustered together, with the relationship between Inuleae and Senecioneae closer, suggesting that Inuleae may have originated from the Senecioneae, not the Cardueae. The data in this study not only enriches the chloroplast genome database of Inula L., but also lays the foundation for the future studies of species identification, phylogenetic relationships, evolution history and genetic diversity of Inula species.
RESUMEN
The aim of this study was to determine whether the anti-fibrotic effects of pirfenidone (Pirf) and nintedanib (Nint) associated with the regulation of the alveolar epithelial type 2 cell (AEC II)-mediated lung alveolar regeneration in single- and multiple-dosage animal models of bleomycin-induced pulmonary fibrosis. All procedures involving animal treatment were approved according to the Committee on the Ethics of Animal Experiments of the Institute of Materia Medica, Chinese Academy of Medical Sciences. We found that the Pirf and Nint treatment of mice decreased the lung weight index, inflammation level, and the content of hydroxyproline compared with nontreated fibrotic mice in the single dosage model. Also, Pirf and Nint increased the oxygen saturation level and improved the lung functions in fibrotic mice, indicating that both drugs have anti-fibrotic effects in this model. However, the anti-fibrotic effects of Pirf and Nint were not observed in the multiple-dosage model. Further studies showed that Pirf and Nint decreased the expression of β-catenin, Axin2, c-Myc, Cyclin D1, and inhibited the Wnt/β-catenin signaling pathway, suggesting that Pirf and Nint did not produce anti-fibrotic effects in the multiple-dosage model due to their inhibiting the Wnt/β-catenin pathway and suppressing the stemness of AEC II, namely, suppressing AEC II-mediated lung alveolar regeneration.
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This study was to determine the expression of the cell cycle inhibitor p21 in alveolar macrophages (AMs) and the role of p21 in activation of AMs in bleomycin (BLM) injury-induced lung fibrosis. The expression of CD206 in AMs was measured by immunofluorescence staining. Reverse transcription-polymerase chain reaction (RT-PCR) assay was used to detect the expression of macrophage activation markers. The coculture assay for macrophage and fibroblast was employed to explore the effect of macrophage on fibroblast activation. Immunofluorescence staining and western blotting assay were adopted to detect the expression of p21 in fibrotic tissues. AMs were treated with p21 knockdown or overexpression virus, RT-PCR and the co-culture system were used to explore the effect of p21 expression on macrophage activation. The Experimental Animal Welfare Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College approved all of the protocols for this research. Our results showed that the expression of CD206 and macrophage activation markers was increased in AMs from fibrotic mice, indicating that AMs from fibrotic mice were associated with a profibrotic phenotype. Moreover, the expression of p21 was upregulated in AMs after BLM treatment. Depletion of p21 suppressed macrophage activation, while overexpression of p21 promoted the profibrotic phenotype of AMs from healthy mice. In summary, BLM injury causes the progressive accumulation of p21 in AMs, which induces the production of a number of profibrotic factors promoting the development of pulmonary fibrosis.
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Intra-abdominal infections (IAIs) are common in the clinical practice,which include a variety of pathological conditions.Severe IAIs can lead to sepsis,secondary organ dysfunction,and threaten the lives of patients.Patients with IAIs are under a high metabolic reaction,and often have gastrointestinal dysfunction,manifesting as impaired intestinal mucosal barrier function,out of control in intestinal flora regulation,and continuous loss of nutrients.The body is in a malnutrition condition,and body resistance severely declines,which further aggravates disease progression.Intestinal micro-ecology is the largest and most complex ecosystem in the human body.In the case of coexistence of many bacteria,the synergy and antagonism between different strains maintain the balance of digestive tract microecology.Intestinal flora and nutritional status under IAIs have their particularity.Understanding the mechanism of intestinal flora abnormalities under IAIs,reasonable and effective nutritional support treatment and management is essential for improving the prognosis of patients with IAIs.