Effects of rapamycin against paraquat-induced pulmonary fibrosis in mice.

BACKGROUND AND AIMS: Ingestion of paraquat (PQ), a widely used herbicide, can cause severe toxicity in humans, leading to a poor survival rate and prognosis. One of the main causes of death by PQ is PQ-induced pulmonary fibrosis, for which there are no effective therapies. The aim of this study was to evaluate the effects of rapamycin (RAPA) on inhibiting PQ-induced pulmonary fibrosis in mice and to explore its possible mechanisms. METHODS: Male C57BL/6J mice were exposed to either saline (control group) or PQ (10 mg/kg body weight, intraperitoneally; test group). The test group was divided into four subgroups: a PQ group (PQ-exposed, non-treated), a PQ+RAPA group (PQ-exposed, treated with RAPA at 1 mg/kg intragastrically), a PQ+MP group (PQ-exposed, treated with methylprednisolone (MP) at 30 mg/kg intraperitoneally), and a PQ+MP+RAPA group (PQ-exposed, treated with MP at 30 mg/kg intraperitoneally and with RAPA at 1 mg/kg intragastrically). The survival rate and body weight of all the mice were recorded every day. Three mice in each group were sacrificed at 14 d and the rest at 28 d after intoxication. Lung tissues were excised and stained with hematoxylin-eosin (H&E) and Masson's trichrome stain for histopathological analysis. The hydroxyproline (HYP) content in lung tissues was detected using an enzyme-linked immunosorbent assay (ELISA) kit. The expression of transforming growth factor-ß1 (TGF-ß1) and α-smooth muscle actin (α-SMA) in lung tissues was detected by immunohistochemical staining and Western blotting. RESULTS: A mice model of PQ-induced pulmonary fibrosis was established. Histological examination of lung tissues showed that RAPA treatment moderated the pathological changes of pulmonary fibrosis, including alveolar collapse and interstitial collagen deposition. HYP content in lung tissues increased soon after PQ intoxication but had decreased significantly by the 28th day after RAPA treatment. Immunohistochemical staining and Western blotting showed that RAPA treatment significantly down-regulated the enhanced levels of TGF-ß1 and α-SMA in lung tissues caused by PQ exposure. However, RAPA treatment alone could not significantly ameliorate the lower survival rate and weight loss of treated mice. MP treatment enhanced the survival rate, but had no significant effects on attenuating PQ-induced pulmonary fibrosis or reducing the expression of TGF-ß1 and α-SMA. CONCLUSIONS: This study demonstrates that RAPA treatment effectively suppresses PQ-induced alveolar collapse and collagen deposition in lung tissues through reducing the expression of TGF-ß1 and α-SMA. Thus, RAPA has potential value in the treatment of PQ-induced pulmonary fibrosis.

[On connotation of Jin's three-needle technique].

Jin's three-needle technique is named after Professor JIN Rui. The connotation of Jin's three-needle technique is summarized by his followers through long-term teaching and clinical practice. His principle and method of point combination are based on syndrome differentiation of acupuncture. And his unique needling technique and treating principle of mental tranquilization also play an important role in his clinical practice.

ß,ß-Dimethylacrylshikonin induces mitochondria dependent apoptosis through ERK pathway in human gastric cancer SGC-7901 cells.

ß,ß-Dimethylacrylshikonin, one of the active components in the root extracts of Lithospermum erythrorhizon, posses antitumor activity. In this study, we discussed the molecular mechanisms of ß,ß-dimethylacrylshikonin in the apoptosis of SGC-7901 cells. ß,ß-Dimethylacrylshikonin reduced the cell viability of SGC-7901 cells in a dose- and time-dependent manner and induced cell apoptosis. ß,ß-Dimethylacrylshikonin treatment in SGC-7901 cells down-regulated the expression of XIAP, cIAP-2, and Bcl-2 and up-regulated the expression of Bak and Bax and caused the loss of mitochondrial membrane potential and release of cytochrome c. Additionally, ß,ß-dimethylacrylshikonin treatment led to activation of caspases-9, 8 and 3, and cleavage of poly (ADP-ribose) polymerase (PARP), which was abolished by pretreatment with the pan-caspase inhibitor Z-VAD-FMK. ß,ß-Dimethylacrylshikonin induced phosphorylation of extracellular signal-regulated kinase (ERK) in SGC-7901 cells. U0126, a specific MEK inhibitor, blocked the ERK activation by ß,ß-dimethylacrylshikonin and abrogated ß,ß-dimethylacrylshikonin -induced apoptosis. Our results demonstrated that ß,ß-dimethylacrylshikonin inhibited growth of gastric cancer SGC-7901 cells by inducing ERK signaling pathway, and provided a clue for preclinical and clinical evaluation of ß,ß-dimethylacrylshikonin for gastric cancer therapy.

[Involvement of LMO4 in tumorigenesis associated epithelial-mesenchymal transition].

LMO4 is a novel member of the LIM-only (LMO) subfamily of LIM domain-containing transcription factors, so named because they are composed almost entirely of two tandem LIM domains. This subgroup of LIM proteins has 4 members: LMO-1, LMO-2, LMO-3 and LMO-4. They all play important roles in the normal mammalian development, functioning as an important regulator of cell proliferation. LMO4 is highly expressed in the epithelial compartments at locations of active epithelial-mesenchymal interactions, and can interact with some signaling pathways involved in epithelial-mesenchymal signaling. Thus the disregulation of LMO4 expression may be involved in tumorigenesis. In this paper, we will at first expound LMO4 in detail, based on which the possible mechanisms for its interaction with TGF-ß signaling and the roles of this cross-talk between them in the vital process of cell will be introduced. All of those will add to our understanding of tumorigenesis and contribute to the search of new targets for the treatment of cancer.

[Fibroblasts-colorectal cancer cells interaction induces the expression of IGFBP7].

OBJECTIVE: To investigate the impact of intracellular interaction between fibroblasts and colorectal cancer cells on the expression of insulin growth factor binding protein7 (IGFBP7). METHODS: Colorectal cancer cells SW480 were cultured with or without fibroblasts HELF cells in RPMI 1640 medium for 0 h, 48 h, 7 2 h and 96 h, respectively. By RT-PCR and immunohistochemical staining methods,the expression of IGFBP7 was detected in mono-and co-cultured cells. RESULT: When SW480 cells were co-cultured with HELF cells, IGFBP7 expression in SW480 cells was significantly upregulated. Furthermore, IGFBP7 was induced in HELF cells both at mRNA and protein levels, which did not express when cells were mono-cultured. CONCLUSION: Fibroblasts-colorectal cancer cells interaction induces the expression of IGFBP7, which indicates tumor-stroma interactions may play an important role in colorectal cancer development.