To determine the active ingredients in German chamomile volatile oil and the mechanism of action in the treatment of eczema, this study used two parameters (ingredient content and oil–water partition ...coefficient) and established a new network pharmacology method based on the dose–effect weight coefficient. Through the new network pharmacology method, we found that German chamomile volatile oil regulated T-cell lymphatic subpopulations to inhibit the Th17 cell differentiation signaling pathway. This resulted in a reduction of interleukin 17 (IL-17), thereby inhibiting the activation of the nuclear factor kappa beta (NF-κB) and MAPK pathways, decreasing the secretion of the pro-inflammatory factors (tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6)), and reducing inflammation. In this study, a new dose–effect relationship synergistic network pharmacology method was established to provide a new method for the screening of effective ingredients and pathways of drugs, and to provide a basis for the follow-up studies of German chamomile volatile oil in the treatment of eczema.
This study aimed to introduce a new weight coefficient combined with network pharmacology to predict the potential active components, action targets, and signal pathways of lavender essential oil and ...to investigate the therapeutic effect of lavender essential oil on colitis through animal experiments. The component targets of lavender essential oil were mined from the Pubchem and SwissTargetPrediction databases, and the relative content of lavender essential oil was compared with OB (oral bioavailability) to establish a "quantity-effect" weight coefficient. Online databases such as GeneCards and String were used to construct a "lavender essential oil compound target disease target" network to extract the key targets of core compounds acting on diseases. The clusterProfiler package in R language programming of Rstudio software was used to analyze the enrichment of the related targets by Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes (KEGG), and the enriched pathways were reordered according to the "quantity-effect" weight coefficient of the targets they participated in. Following up on the findings, the pharmacodynamic test showed that, after injecting lavender essential oil into mice, the levels of inflammatory cytokines including EGFR, TNF-α, and IFN-γ in serum and colon tissue decreased, and lavender essential oil could mediate Th17 cell differentiation by reducing dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) colonic mucosal damage. The results indicated that lavender essential oil can alleviate DSS-induced colonic mucosal injury in ulcerative Colitis mice. Based on the network pharmacology of the "quantity-effect" weight coefficient, this study indicated that lavender essential oil can regulate the level of inflammatory factors, inhibit inflammatory reactions through a multicomponent and multitarget strategy, and ultimately alleviate the colonic mucosal injury of UC mice. Through the weight coefficient network pharmacology mining, it was concluded that the Th17 cell differentiation, PI3K-Akt signaling pathway, and Th1 and Th2 cell differentiation of lavender essential oil in the treatment of UC may be the key pathway for the treatment of the disease. Through the establishment of a weight coefficient combined with network pharmacology and the combination of dose and effect, it shows that network pharmacology may provide a better basis for the treatment of disease mechanism.
Specific biomarkers for early detection and outcome prediction of lung squamous cell carcinoma (LSCC) are still lacking. This study assessed the differentially expressed miRNAs as potential ...biomarkers for early stage LSCC.
Base on the results of multi-phase study, we found that miR-324-3p was significantly up-regulated, whereas mir-1285 was significantly down-regulated in plasma of stage I LSCC patients compared to healthy controls. ROC analysis showed that AUC of miR-324-3p and miR-1285 were 0.79 and 0.85, respectively. The combination of these two miRNAs could further improve the diagnostic accuracy (AUC = 0.89). The multivariate analysis revealed that plasma miR-324-3p level was an independent prognostic predictor for early stage LSCC.
395 patients and 195 healthy controls were enrolled in this study. We screened the differentially expressed plasma miRNAs using TaqMan Low Density Arrays (TLDA) followed by three-phase qRT-PCR validation. We also evaluated the association of candidate miRNAs with overall survival of early stage LSCC patients. Finally, the target genes of the candidate miRNAs were analyzed using public available databases and bioinformatics methods.
The current study suggests that plasma miR-324-3p and miR-1285 levels could serve as LSCC early detection markers while miR-324-3p may serve as a prognostic marker for LSCC patients.
Objective
To evaluate clinical factors influencing the postoperative pulmonary sarcomatoid carcinoma (PSCs) prognosis.
Methods
We retrospectively evaluated patients with PSCs treated from October ...2012 to October 2017. Kaplan–Meier survival curves were calculated using univariable analysis (log-rank test). Univariable/multivariable Cox regression analysis was also performed.
Results
Mixed PSCs were most common (64.10%). Pure PSCs occurred more often with large tumors compared with mixed PSCs. Patients with vs without pleural retraction, respectively, had significantly worse overall survival (OS; 16 vs 23 months) and disease-free survival (DFS; 11 vs 20 months), and patients with airway dissemination had significantly shorter OS (14 vs 21 months) and DFS (11 vs 20 months). Patients with PSC with an adenocarcinoma component had favorable OS. Airway dissemination, pleural retraction, metastatic mediastinal lymph node (LN) number, and pathological tumor-node-metastasis (pTNM) stage were risk factors for short OS. Neither adjuvant chemotherapy nor adjuvant radiotherapy provided a survival advantage. Airway dissemination was an independent prognostic factor (odds ratio, 1.87; 95% confidence interval, 1.04–3.36).
Conclusion
Pure PSCs were more likely with large tumors compared with mixed PSCs. Airway dissemination, pleural retraction, and metastatic mediastinal LN number were associated with OS. Airway dissemination was an independent prognostic factor.
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.
Abstract
Blast wave will be generated in concrete when hit by projectiles at a high velocity. Such blast wave will severely threaten structures. The impact acceleration on the structure surface is an ...instinctive indicator of the propagation of blast wave, since the acceleration is closely linked to the penetration and explosion state of the warhead. This paper conducted acceleration measurement and analysis on the penetration and explosion of penetration warheads on reinforced concrete target. In addition, test results, on-board testing results and numerical results have been compared to analyze the damage process and mechanism of the target, providing basis for warhead design, target design, simulating calculation and damage efficacy evaluation.
Objectives: Atopic dermatitis (AD) is a common skin disorder characterized by skin inflammation caused by an imbalance in the immune response. The efficacy of lavender essential oil in treating ...atopic dermatitis has been demonstrated; however, its specific mechanism of action and active components remain unknown. Therefore, this study investigated the therapeutic effects and possible mechanism of action of LEO on AD in a 2,4-dinitrochlorobenzene (DNCB)-induced dermatitis mice model. Methods: To determine the efficacy of LEO, serum levels of the cytokines IL-6 and TNF-α were tested in Kunming mice, and network pharmacology was used to predict the targets and mechanisms of LEO in AD treatment, after which network pharmacology was combined with metabolomics to construct complex response–enzyme–gene networks and investigate their potential associations. Based on the predicted mechanisms, skin tissues were further examined by immunohistochemistry and immunoblotting analysis, and the skin epidermis was stained with hematoxylin-eosin (HE) and toluidine blue (TB). Results: LEO significantly suppressed the basal levels of IL-6 and TNF-α in the DNCB-induced mice model and predicted that Th17 cell differentiation is a critical pathway for LEO-based network pharmacology in AD treatment. As for the cytokines associated with the Th17 cell differentiation pathway, further experiments verified that LEO significantly reduced the protein expression of interleukin-17A (IL-17A)、Phosphorylated JAK2 (p-JAK)、Phosphorylated STAT3 (p-STAT3), and Retinoic acid-related orphan receptor γt (RORγt) but increased the expression of Foxp3. Additionally, the results of combined network pharmacology and metabolomics analysis showed that LEO could improve two metabolic pathways, namely, linoleic acid metabolism and arachidonic acid metabolism, by regulating the Th17 cell differentiation pathway; identify two key metabolites (linoleic acid, arachidonic acid); and regulate two differential genes (PTGS1, HPGD). Conclusion: LEO may alleviate DNCB-induced skin inflammation by inhibiting the STAT3/RORγt pathway in Th17 cell differentiation, and reducing the expression of associated inflammatory cytokines and chemokines and improving the metabolism of linoleic and arachidonic acid in vivo.
Macroseismic intensity data play an important role in seismic hazard analysis and in developing reliable earthquake loss models. This paper adopts an ellipse model to predict the macroseismic ...intensity attenuation in both the long-axis and the short-axis directions based on 136 earthquakes recorded throughout western China during 1970–2012. The geometric spreading and energy release of seismic waves are considered in the models proposed in this study. The proposed relation describes the macroseismic intensity simply as a function of the surface wave magnitude, source-to-site distance, and focal depth. This study adopts the focal depth that is not often considered in the current intensity prediction equations in China and uses different functional forms in the long- and short-axis directions. Based on residual analysis and evaluation, a more suitable macroseismic intensity predictive equation was established for western China, and it was compared and discussed with macroseismic intensity prediction equations of other researchers.
Objective
Cytokine-induced killer (CIK) cells have the ability to kill tumor in vitro and in vivo. This study was designed to evaluate the clinical efficacy of CIK cell immunotherapy following ...regular chemotherapy in patients with non-small cell lung cancer (NSCLC) after surgery.
Methods
A paired study, with 87 stage I–IV NSCLC patients in each group, was performed. Patients received either chemotherapy (arm 2) or chemotherapy in combination with autologous CIK cell immunotherapy (arm 1). Progression-free survival (PFS) and overall survival (OS) were evaluated.
Results
Of the 87 paired patients, 50 had early-stage disease (stage I–IIIA) and 37 had advanced-stage disease (stage IIIB–IV). Among early-stage patients, the distribution of 3-year PFS rate and median PFS time showed no statistical difference between the two groups (
p
= 0.259 and 0.093, respectively); however, the 3-year OS rate and median OS time in arm 1 were significantly higher than those in arm 2 (82 vs. 66 %;
p
= 0.049 and 73 vs. 53 months;
p
= 0.006, respectively). Among the advanced-stage patients, the 3-year PFS and OS rates of arm 1 were significantly higher than those of arm 2 (6 vs. 3 %;
p
< 0.001 and 31 vs. 3 %;
p
< 0.001, respectively); the median PFS and OS times in arm 1 were also significantly longer than those in arm 2 (13 vs. 6 months;
p
= 0.001 and 24 vs. 10 months;
p
< 0.001, respectively). Multivariate analyses indicated that the frequency of CIK cell immunotherapy was significantly associated with prolonged PFS (HR = 0.91; 95 % CI 0.85–0.98;
p
= 0.012) and OS (HR = 0.83; 95 % CI, 0.74–0.93;
p
= 0.001) in the arm 1.
Conclusions
The data suggested that CIK cell immunotherapy could improve the efficacy of conventional chemotherapy in NSCLC patients, and increased frequency of CIK cell treatment could further enhance the beneficial effects. A multi-center randomized trial is being carried out in our hospital to further validate these findings.
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