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Background. Pinellia ternata (PT), a medicinal plant, has had an extensive application in the treatment of asthma in China, whereas its underlying pharmacological mechanisms remain unclear. Methods. Firstly, a network pharmacology method was adopted to collect activated components of PT from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Targets of PT were assessed by exploiting the PharmMapper website; asthma-related targets were collected from the OMIM website, and target-target interaction networks were built. Secondly, critical nodes exhibiting high possibility were identified as the hub nodes in the network, which were employed to conduct Gene Ontology (GO) comment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis. Finally, the tissue expression profiles of key candidate genes were identified by the Gene Expression Omnibus (GEO) database, and the therapeutic effect of PT was verified by an animal experiment. Results. 57 achievable targets of PT on asthma were confirmed as hub nodes through using the network pharmacology method. As revealed from the KEGG enrichment analysis, the signaling pathways were notably enriched in pathways of the T-cell receptor signaling pathway, JAK-STAT signaling pathway, and cytokine-cytokine receptor interaction. The expression profiles of candidate genes including Mmp2, Nr3c1, il-10, il-4, il-13, il-17a, il-2, tlr4, tlr9, ccl2, csf2, and vefgα were identified. Moreover, according to transcriptome RNA sequencing data from lung tissues of allergic mice compared to normal mice, the mRNA level of Mmp2 and il-4 was upregulated ( P < 0.001 ). In animal experiments, PT could alleviate the allergic response of mice by inhibiting the activation of T-helper type 2 (TH2) cells and the expression of Mmp2 and il-4. Conclusions. Our study provides candidate genes that may be either used for future studies related to diagnosis/prognosis or as targets for asthma management. Besides, animal experiments showed that PT could treat asthma by regulating the expression of Mmp2 and il-4.

Radiation-induced lung injury (RILI) is a common complication of radiotherapy for thoracic tumor. Its incidence rate is as high as 20%. At present, there is no effective treatment in clinical practice. However, to study the mechanism of radiation-induced lung injury, we should first establish an appropriate animal model. In a series of scientific studies on RILI, mice are the animals most often chosen by researchers. However, there are few reports on which strain of mice is more suitable as a model of RILI. In this study, Kunming (KM) and C57BL/6 strains of mice were used as research objects to find the most suitable mice to replicate the RILI model. C57BL/6 mice and KM mice were exposed to irradiation at a dose of 20 Gy. The lung tissue of C57BL/6 mice exposed to radiation showed dilation and hyperemia of capillaries, infiltration of inflammatory cells, and thickening of alveolar septum, while the lung tissue of KM mice exposed to radiation was not as obvious as that of C57BL/6 mice. After irradiation, the expression of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the lung tissue of C57BL/6 mice was significantly increased, while the expression of IL-6 and TNF-α in KM mice was almost unchanged. These studies showed that C57BL/6 mice are more suitable for the model of radiation-induced lung injury because of sensitive inflammatory reaction and the pathological changes of lung tissue.

Background Endoplasmic reticulum (ER) stress is closely related with the pathological progression of rheumatoid arthritis (RA), and fibroblast-like synoviocytes (FLSs) are known as its resistance against ER stress-induced apoptosis. Studies on overcoming such resistance would provide a novel treatment strategy for RA in a clinical setting. Methods IL13Rα1 expression was assessed in the synovial tissue by RT-qPCR, immunohistology, and Western blot. Gain or loss of functional analysis was applied to evaluate the biological roles of IL13Rα1 in RA FLSs. Cell viability and apoptosis were assessed by MTS, Western blot, and flow cytometry. The therapeutic effects of IL13Rα1 on the severity of type II collagen-induced arthritis (CIA) in DBA-/1 mouse model were evaluated by scoring synovitis, hyperplasia, cartilage degradation, and bone destruction. Results IL13Rα1 expression was selectively downregulated when RA FLSs were stimulated by ER stress inducers. Functionally, IL13Rα1 overexpression could inhibit the viability, but induce the apoptosis of RA FLSs in the presence of ER stress inducers. Mechanistically, IL13Rα1 promotes cell apoptosis via transcriptionally activating trail expression. Besides, IL13Rα1 could interact and stabilize DR5 protein, thus forming a positive loop involving trail and DR5 to render RA FLSs more susceptible to apoptosis. Additionally, intraarticular injection of IL13Rα1 conferred therapeutic effects in CIA models and showed a limited degree of synovial proliferation and joint destruction. Conclusions Together, our data establishes a regulatory role for IL13Rα1 to combat the apoptotic resistance of RA FLSs against ER stress. The inhibitory effects of IL13Rα1 on arthritis progression suggest the therapeutic potential in RA.

Background: Pinellia ternata (PT), a medicinal plant, has had an extensive application in the treatment of asthma in China, whereas its underlying pharmacological mechanisms remain unclear.Methods: Firstly, the therapeutic effect of PT was verified by an animal experiment. Secondly, a network pharmacology method was adopted to collect activated components of PT from Traditional Chinese Medicine Systems Pharmacology Database and Analysis (TCMSP); binding targets of PT were assessed by exploiting Pharmmapper website; asthma-related targets were collected, and Target-Target interaction networks were built. Subsequently, critical nodes exhibiting high-possibility were identified as the hub nodes in the network, which employed to conduct GeneOntology (GO) comment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis. Finally, the tissue expression profiles and single-cell RNA sequencing (scRNA-Seq) data of candidate genes were identified by Gene Expression Omnibus database (GEO) and PanglaoDB databases.Results: In animal experiments, PT could alleviate the allergic response of mice by inhibiting the activation of T-helper type 2 (TH2) cells and the secretion of IL-4 and IL-5. Subsequently, 57 achievable targets of PT on asthma were confirmed as hub nodes, included candidate genes matrix metalloproteinase-2 (MMP2) and nuclear receptor subfamily 3 group C member 1(NR3C1). Moreover, according to transcriptome RNA sequencing data from lung tissues of allergic mice compared to normal mice, mRNA level of MMP2 was up-regulated (P NR3C1 was no significant difference (P=0.0749). Finally, we compared their levels of expression and distributions to those present in the single-cell level. Conclusions: With network pharmacology, our study provides candidate genes that may be either used for future studies related to diagnosis/prognosis or as targets for asthma management. Besides, more attention should be paid to methods of identifying the origin of these genes and determining their expression at the single-cell level.

Background Cancer stem cells (CSCs) have been proposed to be responsible for tumor recurrence and chemo-resistance. Previous studies suggested that miR-153 played essential roles in lung cancer. However, the molecular mechanism of miR-153 in regulating the stemness of non-small cell lung cancer (NSCLC) remains poorly understood. In this study, we investigated the role of miR-153 in regulation of the stemness of NSCLC. Methods The stemness property of lung stem cancer cells was detected by sphere formation assay, immunofluorescence, and Western blot. Luciferase reporter assay was performed to investigate the direct binding of miR-153 to the 3′-UTR of JAG1 mRNA. Animal study was conducted to evaluate the effect of miR-153 on tumor growth in vivo. The clinical relevance of miR-153 in NSCLC was evaluated by Rt-PCR and Kaplan-Meier analysis. Results MiR-153 expression was decreased in lung cancer tissues. Reduced miR-153 expression was associated with lung metastasis and poor overall survival of lung cancer patients. Jagged1, one of the ligands of Notch1, is targeted by miR-153 and inversely correlates with miR-153 in human lung samples. More importantly, we found that miR-153 inhibited stem cell-like phenotype and tumor growth of lung adenocarcinoma through inactivating the Jagged1/Notch1 axis. Conclusion MiR-153 suppresses the stem cell-like phenotypes and tumor growth of lung adenocarcinoma by targeting Jagged1 and provides a potential therapeutic target in lung cancer therapy.

Additional file 4: Table S2 List of potential IL13Rα1 partners in RA FLSs identified by mass spectrometry.

Additional file 3: Table S1 Clinical characteristics of RA patients.

Lung cancer remains one of the leading causes of death worldwide, and lung cancers have often already metastasized when diagnosed. Numerous studies have noted the infiltration of immune cells in the lung cancer microenvironment, but these cells play a dualistic role, i.e. they suppress and/or promote tumor development and growth based on tumor progression and different cytokines in the microenvironment. These tumor-infiltrating immune cells create different microenvironments depending on their type and interaction. Chemokines act as a bridge in this process by recruiting immune cells to the tumor site and they regulate the phenotypes and functions of those cells. The current review summarizes current knowledge about the tumor-infiltrating immune cells in lung cancer as well as the mechanisms involved in suppression and promotion of tumor development and growth.

Interleukin-17D (IL-17D) belongs to the IL-17 family of cytokines. While the members of the IL-17 family have been implicated in inflammation and host defense, the function of IL-17D remains unclear. Here, we showed that the lack of IL-17D expression confers protection against Listeria infection. A deficiency in IL-17D also resulted in less weight loss with reduced pathogen burden during influenza A virus infection. During infection, the loss of IL-17D resulted in compromised CD8 T cell activity. CD8 T cell depletion in IL-17D-deficient mice restored the bacterial burden to a level similar to that found in WT mice. Similarly, IL-17D-deficient mice in a RAG-deficient background had no difference in bacterial and viral burden compared to WT mice. IL-17D controlled CD8 T cell activity in part by suppressing the function of dendritic cells. We found that IL-17D from the non-hematopoietic compartment regulates protective immunity during infection. Together, our data led to the identification of IL-17D as a critical cytokine during intracellular bacteria and virus infection that suppresses the activity of CD8 T cells by regulating dendritic cells.

Integrally directional solidification of an advanced Nb silicide based ultrahigh temperature alloy was conducted with the use of special ceramic crucibles. The melt temperature was 2000°C and the withdrawing rate was respectively 5, 10, 15, 30, 50, 80 and 100 µm/s. The directionally solidified microstructure was composed of primary ( Nb ,X)5 Si 3 rods and ( Nb , Ti ) ss + ( Nb ,X)5 Si 3 eutectic colonies (here X represents Ti and Hf elements) that distributed evenly and aligned erectly along the growth direction. The quenched solid/liquid (S/L) interfaces had the morphology of a series of protruded parallel eutectic cells along the growth direction. ( Nb , Ti ) ss and ( Nb ,X)5 Si 3 slices grew in a coupled manner in each eutectic cell, forming a typical lamellar eutectic morphology. Both the average diameter of eutectic cells and lamellar spacing in them decreased with the increase of withdrawing rates. The solidification path was that primary ( Nb ,X)5 Si 3 rods formed firstly and then the retained liquid around solidified into ( Nb , Ti ) ss + ( Nb ,X)5 Si 3 eutectic cells.

As a sensitive factor of endocrine system, thyroxine exerts regulatory activities on a variety of cell types in immune system including T lymphocytes. Cytokines secreted by T lymphocytes are widely involved in numerous mechanisms, which are crucial for homeostasis at various statuses. Here we investigated the effects of thyroxine on the cytokine production of T lymphocytes in vivo and in vitro, using BALB/c mice with thyroxine treatment. We examined the IFN-gamma, IL-2, IL-4 and IL-10 of T-cell type cytokines transcriptions and the proportions of IFN-gamma, IL-4 and IL-10-secreting CD4(+)/CD8(+) T cells. The results showed that the administration of high-level thyroxine induced weakly expression of T-cell type cytokine in transcriptional level together with impaired responsibility to mitogen (Con A) stimulation. Along with the severe suppression on T-cell type cytokine transcription, the proportions of IFN-gamma, IL-4 and IL-10-producing T lymphocytes were markedly attenuated and the productions of serum IFN-gamma and IL-10 were significantly decreased synchronously. The repressive effects of thyroxine on T-cell type cytokine were seen both in mRNA and protein level. The results suggested that T lymphocytes under normal condition appear to be sensitive to suppression of high-level thyroxine administration.

Steroid hormone serving as an immunosuppressor often induces immunotoxicity when administered in highest dosage or accumulated in long-term usage. The stage of high concentration of steroid hormone leading to a wide range of symptoms is associated to the yang-deficient state, which is the part of yin-yang imbalance involved in processes of many diseases in traditional Chinese medicine. Here we intend to investigate the profile of Th1/Th2-related cytokine transcriptions under yang-deficient conditions in a yang-deficient animal model by intramuscular injection of hydrocortisone (a kind of steroid hormone). The yang-deficient symptoms were estimated by detecting activity, appetite, body weight and so on. T cell proliferation and cytokine transcriptions were analyzed. The results showed that yang-deficient mice were established successfully since typical yang-deficient symptoms were observed in this model with decreased activities, appetite, body weight and temperature. More interestingly, the transcriptions of IFN-gamma, IL-2, IL-4 and IL-10 in this model were markedly suppressed and the proliferation of lymphocytes significantly decreased as well. The results suggested that yang-deficient symptoms were related to the steroid-induced reduction of cytokine transcription and impairment of lymphocyte proliferation. Therefore, novel strategies through regulating cytokine production might be considered as potent approach to patients with yang-deficiency symptoms.