Search

Background. Jinlian Xiaodu Decoction (JXD) was reported to have anti-inflammatory and lung protection effects. This study aimed to explore the role and mechanism of JXD on bleomycin (BLM)-induced pulmonary fibrosis (PF). Methods. The UHPLC-Q/TOF-MS system was applied to analyze JXD composition. The PF model was established by BLM intratracheal administration in Wistar rats. Subsequently, BLM-treated rats were intragastrically administered with dexamethasone (DXM, 1 g/kg/d) or JXD (3.5, 7 or 14 g/kg/d). Next, the lung coefficient was calculated; H&E, Masson, and TUNEL staining were used for lung morphological analysis and apoptosis assessment. Bronchoalveolar lavage fluid (BALF) biochemical analysis was conducted to count the inflammatory cell number. The expression of inflammatory factors mRNA in the lung tissue and BALF were measured by qRT-PCR. The content and activity of oxidative stress-related proteins were detected. The expression of PF-related, apoptosis-related, and TGF-β1 pathway-related protein were assessed by immunohistochemistry or Western blot. Results. Twenty-six compounds were identified from JXD in both negative and positive ion modes. In BLM-induced rats, JXD reduced the lung coefficient and alleviated PF injury. JXD decreased inflammatory cell count and TNF-α, IL-1β, IL-6, and MCP-1 content. Meanwhile, JXD blunted BLM-induced oxidative stress and a high level of HYP. Furthermore, TUNEL analysis found that JXD inhibited cell apoptosis and increased Bcl-2/Bax ratio in BLM-induced lung. Moreover, JXD relieved the role of BLM on α-SMA, TGF-β1, collagen I, fibronectin, E-cadherin protein expression, and the phosphorylation of Smad2/3 in PF rat. Conclusion. This study revealed the protective effect and possible element of JXD on BLM-caused PF. [ABSTRACT FROM AUTHOR]

Acupuncture can significantly ameliorate inflammatory pain in acute visceral hyperalgesia. Hyperalgesia is attenuated by inflammatory mediators that activate transient receptor potential vanilloid 1 (TRPV1), and TRPV1 is regulated by nerve growth factor (NGF)-induced phosphatidylinositol 3-kinase (PI3K)/Akt pathway. However, it is unknown whether NGF-induced PI3K/Akt pathway is associated with manual acupuncture (MA). In this study, the effect and mechanism of MA at Shangjuxu (ST37) and Quchi (LI11) were examined using an acetic acid-induced rat model with visceral hyperalgesia. We demonstrated that MA at ST37 significantly decreased abdominal withdrawal reflex (AWR) scores, proinflammatory cytokine expression (TNF-α, IL-1β, and IL-6), and TRPV1 protein and mRNA expression in rats with acute visceral hyperalgesia compared with the untreated controls, while MA at LI11 showed no effect. The effects of MA at ST37 were reversed after treatment with the PI3K agonist IGF-1 30 min before MA. In rats with visceral hyperalgesia, the upregulation of NGF, tropomyosin-receptor-kinase A (TrkA), PI3K, and phosphorylation-Akt (p-Akt) was decreased by MA at ST37, indicating that TRPV1 regulation via the NGF-induced PI3K/Akt pathway plays a vital role in the effects of MA-mediated amelioration of acute visceral hyperalgesia. [ABSTRACT FROM AUTHOR]

Gefitinib is a tyrosine kinase inhibitor of EGFR (epidermal growth factor receptor) and represents the first-line treatment for EGFR mutation patients with NSCLC (non-small-cell lung cancer) therapeutics. However, NSCLC patients are inclined to develop acquired gefitinib drug resistance through nowadays, unarticulated mechanisms of chemoresistance. Here, we investigated the role of TF (Trifolium flavonoids) on sensitizing gefitinib resistance in NSCLC cells and revealed its potential mechanism of action. We demonstrated that TF exerted significantly potential chemosensitivity in gefitinib resistant NSCLC cells. MTT assay and cytological methods were used to analyze cell viability and apoptosis in NSCLC cell line PC-9R. Both TF and gefitinib suppressed PC-9R cell growth in a dose-dependent manner. Subtoxic concentrations of TF did significantly augment gefitinib-induced apoptosis in PC-9R cell line. The TF promoted chemosensitivity was major mediated by the PARP and caspases activation. Meanwhile, the TF promoted chemosensitivity also decreased the expression of Bcl-2 and Mcl-1. Finally, TF significantly reduced the phosphorylation levels of STAT3 and ERK. Altogether, the results of the present study indicated the potential mechanisms of chemosensitivity of TF in gefitinib-induced apoptosis of NSCLC by downregulating ERK and STAT3 signaling pathways and Bcl2 and Mcl-1 expression and a promising application of TF in therapy of NSCLC with gefitinib resistant. [ABSTRACT FROM AUTHOR]

Background. Osteonecrosis of the femoral head (ONFH) is a challenge for surgeons and is still without effective treatment method. This study is aimed at evaluating the combined pharmacotherapy with alendronate and desferoxamine for preventing glucocorticoid-induced osteonecrosis of the femoral head (GIOFH) and evaluating the efficacy of the combined medicine in regulating the bone resorption and bone regeneration. Materials and Methods. Thirty-six rats were randomly assigned to three groups: group A received alendronate and desferoxamine (n = 12), group B received alendronate only (n = 12), and group C acted as the control group received placebo (n = 12). All rats induced the GIOFH using methylprednisolone combined with lipopolysaccharide. Eight weeks later, all rats were killed and their tissues were subjected to radiographic and histological analyses. Results. According to the results, alendronate administration improved the trabecular thickness and separation in micro-CT analysis but had no significant evidence in increasing the bone area and decreasing the ratio of osteocyte lacunae in histological analysis when compared with the control group. Meanwhile, the alendronate group had more OCs, but less OCN and VEGF levels along with decreased p-AKT, HIF-1α, RANKL, and NFATc1 expressions than the control group. For comparison, alendronate combined with DFO further improved the bone volume, trabecular number, trabecular separation, and trabecular thickness with lower ratio of osteocyte lacunae and OC number, higher expression of OCN and VEGF and upregulated signal factors of HIF-1α and β-catenin, and decreased RANKL and NFATc1. Conclusion. Combined pharmacotherapy with alendronate and desferoxamine provide significant effects in regulating the bone resorption and bone regeneration for preventing GIOFN. [ABSTRACT FROM AUTHOR]

Objective. To evaluate the effects of human bone marrow mesenchymal stem cells (hBMSCs) and osteoblasts (hFOB1.19) on PC3 prostate cancer cells. Methods. To simulate the in vivo interaction between the bone/bone marrow microenvironments and prostate cancer cells, we established cocultures of PC3 cells with hBMSC or hFOB1.19 cells and evaluated their effects on the proliferation, cell cycle distribution, cell migration, and invasion of PC3 cells. Quantitative reverse transcription polymerase chain reaction was used to detect CD59 mRNA expression in PC3 cells. The expression of receptor activator of nuclear factor- (NF-) κB (RANK), RANK ligand (RANKL), osteoprotegerin (OPG), CD59, NF-κB (p50 subunit), and cyclin D1 in PC3 cells was analyzed by immunofluorescence and western blotting. Results. hBMSCs and hFOB1.19 cells enhanced the proliferation, migration, and invasion of PC3 cells; increased the proportion of PC3 cells in the S and G2/M phases of the cell cycle; and upregulated RANK, RANKL, OPG, CD59, cyclin D1, and NF-κB (p50 subunit) expression by PC3 cells. The RANKL inhibitor, scutellarin, inhibited these effects in PC3-hFOB1.19 cocultures. Conclusion. hBMSCs and hFOB1.19 cells modulate the phenotype of PC3 prostate cancer cells and the expression of CD59 by activating the RANK/RANKL/OPG signaling pathway. [ABSTRACT FROM AUTHOR]

The non-small-cell lung cancer (NSCLC) is the most common lung cancer which seriously threatens the human health. Xu Li's experiential prescription (XLEP) can treat the NSCLC. However, whether XLEP can regulate the autophagy in the EGFR-positive NSCLC still remains unknown. We found that the cellular activity of drug-resistant cells and sensitive cells were all decreased in the TCM group and TCM + Gef group. The expression of autophagy-associated proteins (mTOR and Beclin1-Vps34) in drug-resistant cells was decreased in the TCM group, while the expression of autophagy-associated proteins in sensitive cells was all decreased in the TCM + Gef group. The ratio of M1/M2 macrophages was increased when IL-4-induced RAW264.7 was treated with TCM. TCM treatment promoted the expression of CCL2 and CCL3 while it downregulated the CCL22 level among A549, H1975, and PC9 cells. The expression of TNF-α and IL-6 was increased, and the expression of IL-10 and TGF-β was decreased in IL-4-induced RAW264.7 cells treated with TCM. And, TCM treatment also decreased the expression of Fizz1 and TGM2. In conclusion, this study indicated that XLEP could suppress the proliferation of EGFR-TKI-resistant cancer cells and increase the ratio of M1/M2 macrophages by inhibiting autophagy to treat the drug-resistant EGFR-positive NSCLC. [ABSTRACT FROM AUTHOR]

ELK3, an ETS domain-containing transcription factor, participates in various physiological and pathological processes including cell proliferation, migration, angiogenesis, and malignant progression. However, the role of ELK3 in prostate cancer cells and its mechanism are not fully understood. The contribution of ELK3 to prostate cancer progression was investigated in the present study. We showed that silencing of ELK3 by siRNA in prostate cancer cell DU145 induced S-M phase arrest, promoted apoptosis, inhibited cell proliferation and migration in vitro, and suppressed xenograft growth in mice in vivo. In accordance with its ability to arrest cells in S-M phase, the expression of cyclin A and cyclin B was downregulated. In addition, the expression of p53 was upregulated following ELK3 knockdown, while that of antiapoptotic Bcl-2 was decreased. The migration inhibition may partly due to upregulation of SERPINE1 (a serine protease inhibitor) followed ELK3 knockdown. Consistently, downregulation of SERPINE1 resulted in a modest elimination of migration inhibition resulted from ELK3 knockdown. Furthermore, we found that the AKT signaling was activated in ELK3 knockdown cells, and treatment these cells with AKT inhibitor attenuated SERPINE1 expression induced by ELK3 silencing, suggesting that activation of AKT pathway may be one of the reasons for upregulation of SERPINE1 after ELK3 knockdown. In conclusion, modulation of ELK3 expression may control the progression of prostate cancer partly by regulating cell growth, apoptosis, and migration. [ABSTRACT FROM AUTHOR]