Baicalin alleviates silica-induced lung inflammation and fibrosis by inhibiting TLR4/NF-?B pathway in rats.

Silicosis is an occupational lung disease caused by inhaling silica dust. The disease is characterized by early lung inflammation and late irreversible pulmonary fibrosis. Here we report the effect of Baicalin, a main flavonoid compound from the roots of Chinese herbal medicine Huang Qin on silicosis in a rat model. Results showed Baicalin (50 or 100 mg/kg/day) can mitigate the silica-induced lung inflammation and reduce the harm of alveolar structure and the blue region of collagen fibers in rat lung at 28 days after administration. At the same time, Baicalin also diminished the level of interleukin-1beta (IL-1beta, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta1 (TGF-beta1) in lung tissues. The protein expression of collagen I (Col-1), alpha-smooth muscle actin (alpha-SMA) and vimentin were down-regulated while E-cadherin (E-cad) was increased in Baicalin-treated rats. In addition, the Toll Like Receptor 4 (TLR4)/ nuclear factor kappaB (NF-kappaB) pathway was enabled at 28 days after silica infusion, and the treatment of Baicalin diminished the expression of TLR4 and NF-?B in the lungs of rat with silicosis. These results suggested that Baicalin inhibited the pulmonary inflammatory and fibrosis in a rat model of silicosis, which could be attributed to inhibition of the TLR4/NF-kappaB pathway.

Identification of Ecdysone Hormone Receptor Agonists as a Therapeutic Approach for Treating Filarial Infections.

BACKGROUND: A homologue of the ecdysone receptor has previously been identified in human filarial parasites. As the ecdysone receptor is not found in vertebrates, it and the regulatory pathways it controls represent attractive potential chemotherapeutic targets. METHODOLOGY/ PRINCIPAL FINDINGS: Administration of 20-hydroxyecdysone to gerbils infected with B. malayi infective larvae disrupted their development to adult stage parasites. A stable mammalian cell line was created incorporating the B. malayi ecdysone receptor ligand-binding domain, its heterodimer partner and a secreted luciferase reporter in HEK293 cells. This was employed to screen a series of ecdysone agonist, identifying seven agonists active at sub-micromolar concentrations. A B. malayi ecdysone receptor ligand-binding domain was developed and used to study the ligand-receptor interactions of these agonists. An excellent correlation between the virtual screening results and the screening assay was observed. Based on both of these approaches, steroidal ecdysone agonists and the diacylhydrazine family of compounds were identified as a fruitful source of potential receptor agonists. In further confirmation of the modeling and screening results, Ponasterone A and Muristerone A, two compounds predicted to be strong ecdysone agonists stimulated expulsion of microfilaria and immature stages from adult parasites. CONCLUSIONS: The studies validate the potential of the B. malayi ecdysone receptor as a drug target and provide a means to rapidly evaluate compounds for development of a new class of drugs against the human filarial parasites.

Surgical treatment of trigeminal neuralgia.

Patients who had uncontrolled pain with carbamazepine therapy and those who suffered adversely from its side effects were selected for this safe, simple and repeatable surgery. Pain-free periods were achieved for at least 2 years. Functional difficulty was not experienced in the affected numb areas. When it recurred, pain was less intense and was better controlled with a reduced dosage of carbamazepine. In four cases, after avulsion of the involved nerves, a suitable-sized titanium screw was inserted into the mental and infra-orbital foramina. Obturation of the foramen prevented nerve regeneration, which further prolonged the pain remission period.