[Effect of acupuncture on TGF-ß1/Smads pathway in mice with airway remodeling mic].

OBJECTIVE: To investigate the effect of acupuncture on TGF-ß1/Smads signaling pathway in the lung tissue of mice with airway remodeling. METHODS: Thirty specific pathogen-free mice were randomly divided into blank group, model group and acupuncture group (n=10). Mouse models of asthma were established in the model group and the acupuncture group, and the mice in the latter group received 7 acupuncture therapies (at bilateral Fei Shu, Da Zhui and Zu Sanli, 20 min each time) every other day, starting on the 10th day after the modeling. At 24 h after the last acupuncture, the mice were subjected to inhalation of 1% OVA for 3 days, and 24 h after the last challenge, the mice were given methacholine chloride (Mch) inhalation at different concentrations for measurement of lung resistance using a noninvasive stroke volume meter. HE staining was used to observe the pathological changes in the lung tissues, and TGF-ß1 levels in the the bronchoalveolar lavage fluid (BALF) and serum were detected using ELISA; Western blotting was used to detect the differential protein expressions in the airway smooth muscles between the two groups. The airway smooth muscle cells were isolated from the mice in the acupuncture group and treated with a TGF- ß1 inhibitor (LY2157299), and the relative expressions of type-Ⅰ and Smads proteins were detected using Western blotting. RESULTS: The mice in the model showed obvious tracheal fistula with airway pathologies including lumen narrowing, bronchial mucosa thickening, dissociation of the epithelial cells, and thickening of the alveolar septum and airway smooth muscles. These pathological changes were obviously milder in the acupuncture group. The asthmatic mice exhibited significantly increased lung resistance in positive correlation with Mch concentration. Serum TGF-ß1 level was significantly elevated in asthmatic mice (P < 0.05); TGF-ß1 levels in the serum and BALF were significantly lower in the acupuncture group than in the model group (P < 0.05). In the model group, the expressions of α-SMA, TGF-ß1 and Smads in the airway smooth muscles were significantly higher than those in the other two groups (both P < 0.05). In cultured airway smooth muscle cells, the expressions of type-Ⅰ and Smads were significantly higher in cells treated with LY2157299 than in the control cells (P>0.05). CONCLUSIONS: Acupuncture can inhibit airway remodeling by inhibiting the expression of airway TGF-ß1 and down-regulating the expression of Smads and α-SMA to reduce airway inflammatory response. Airway expressions of type-Ⅰ and Smads proteins remain high after inhibiting TGF-ß1. Acupuncture may control asthma progression through the TGF-ß1/Smads pathway.

Carboxymethyl chitosan nanoparticles loaded with bioactive peptide OH-CATH30 benefit nonscar wound healing.

BACKGROUND: Nonscar wound healing is a desirable treatment for cutaneous wounds worldwide. Peptide OH-CATH30 (OH30) from king cobra can selectively regulate the innate immunity and create an anti-inflammatory micro-environment which might benefit nonscar wound healing. PURPOSE: To overcome the enzymatic digestion and control release of OH30, OH30 encapsulated in carboxymethyl chitosan nanoparticles (CMCS-OH30 NP) were prepared and their effects on wound healing were evaluated. METHODS: CMCS-OH30 NP were prepared by mild ionic gelation method and properties of the prepared CMCS-OH30 NP were determined by dynamic light scattering. Encapsulation efficiency, stability and release profile of OH30 from prepared CMCS-OH30 NP were determined by HPLC. Cytotoxicity, cell migration and cellular uptake of CMCS-OH30 NP were determined by conventional methods. The effects of prepared CMCS-OH30 NP on the wound healing was investigated by full-thickness excision animal models. RESULTS: The release of encapsulated OH30 from prepared CMCS-OH30 NP was maintained for at least 24 h in a controlled manner. CMCSOH30 NP enhanced the cell migration but had no effects on the metabolism and proliferation of keratinocytes. In the full-thickness excision animal models, the CMCS-OH30 NP treatment significantly accelerated the wound healing compared with CMCS or OH30 administration alone. Histopathological examination suggested that CMCS-OH30 NP promoted wound healing by enhancing the granulation tissue formation through the re-epithelialized and neovascularized composition. CMCS-OH30 NP induced a steady anti-inflammatory cytokine IL10 expression but downregulated the expressions of several pro-inflammatory cytokines. CONCLUSION: The prepared biodegradable drug delivery system accelerates the healing and shows better prognosis because of the combined effects of OH30 released from the nanoparticles.

Plumbagin suppresses dendritic cell functions and alleviates experimental autoimmune encephalomyelitis.

Plumbagin (PL, 5-hydroxy-2-methyl-1,4-naphthoquinone) is a herbal compound derived from medicinal plants of the Droseraceae, Plumbaginaceae, Dioncophyllaceae, and Ancistrocladaceae families. Reports have shown that PL exerts immunomodulatory activity and may be a novel drug candidate for immune-related disease therapy. However, its effects on dendritic cells (DCs), the most potent antigen-presenting cells (APCs), remain unclear. In this study, we demonstrate that PL inhibits the differentiation, maturation, and function of human monocyte-derived DCs. PL can also restrict the expression of Th1- and Th17-polarizing cytokines in mDC. In addition, PL suppresses DCs both in vitro and in vivo, as demonstrated by its effects on the mouse DC line DC2.4 and mice with experimental autoimmune encephalomyelitis (EAE), respectively. Notably, PL ameliorated the clinical symptoms of EAE, including central nervous system (CNS) inflammation and demyelination. Our results demonstrate the immune suppressive and anti-inflammatory properties of PL via its effects on DCs and suggest that PL could be a potential treatment for DC-related autoimmune and inflammatory diseases.

Thermosensitive injectable hydrogel enhances the antitumor effect of embelin in mouse hepatocellular carcinoma.

Embelin, an active ingredient of traditional herbal medicine, is used to treat many diseases such as cancer. However, embelin is hydrophobic and insoluble in water, which makes it unsuitable for in vivo applications. In this study, we constructed an embelin-loaded thermosensitive injectable hydrogel system that we named Embelin/PECT(gel) based on the amphiphilic triblock copolymer of poly (ε-caprolactone-co-1,4,8-trioxa[4.6]spiro-9-undecanone)-poly (ethylene glycol)-poly (ε-caprolactone-co-1,4,8-trioxa[4.6]spiro-9-undecanone) (PECT). The cytotoxicity and the antitumor effects of Embelin/PECT(gel) on mouse hepatic cancers were investigated in vitro and in vivo. Results indicated that embelin was formulated in PECT hydrogel and could be continuously released from Embelin/PECT(gel) , showing a higher cytotoxicity for H22 cells in vitro compared with free embelin. The aqueous solution of Embelin/PECT(gel) transformed into gel at the injection site within seconds, which later eroded and degraded over time in vivo. A single local peritumoral injection of Embelin/PECT(gel) in liver at a low dosage of 0.5 mg per mouse exhibited a significant antitumor effect, which was comparable to the antitumor effect of the embelin solution treatment at a total dose of 6 mg per mouse in mouse hepatic cancer. Embelin/PECT(gel) , as a drug delivery system in liver, represents a novel therapeutic drug candidate for the clinical treatment of advanced hepatocellular carcinoma.