A randomized, double-blind study of AMG 108 (a fully human monoclonal antibody to IL-1R1) in patients with osteoarthritis of the knee

INTRODUCTION: AMG 108 is a fully human, immunoglobulin subclass G2 (IgG2) monoclonal antibody that binds the human interleukin-1 (IL-1) receptor type 1, inhibiting the activity of IL-1a and IL-1b. In preclinical studies, IL-1 inhibition was shown to be beneficial in models of osteoarthritis (OA). The purpose of this two-part study was to evaluate the safety and pharmacokinetics (PK; Part A) and clinical effect (Part B) of AMG 108 in a double-blind, placebo-controlled, multiple-dose study in patients with OA of the knee. METHODS: In Part A, patients received placebo or AMG 108 subcutaneously (SC; 75 mg or 300 mg) or intravenously (IV; 100 mg or 300 mg) once every 4 weeks for 12 weeks; in Part B, patients received placebo or 300 mg AMG 108 SC, once every 4 weeks for 12 weeks. The clinical effect of AMG 108 was measured in Part B by using the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index pain score. RESULTS: In Part A, 68 patients were randomized, and 64 received investigational product. In Part B, 160 patients were randomized, and 159 received investigational product. AMG 108 was well tolerated. Most adverse events (AEs), infectious AEs, serious AEs and infections, as well as withdrawals from the study due to AEs occurred at similar rates in both active and placebo groups. One death was reported in an 80-year-old patient (Part A, 300 mg IV AMG 108; due to complications of lobar pneumonia). AMG 108 serum concentration-time profiles exhibited nonlinear PK. The AMG 108 group in Part B had statistically insignificant but numerically greater improvement in pain compared with the placebo group, as shown by the WOMAC pain scores (median change, -63.0 versus -37.0, respectively). CONCLUSIONS: The safety profile of AMG 108 SC and IV was comparable with placebo in patients with OA of the knee. Patients who received AMG 108 showed statistically insignificant but numerically greater improvements in pain; however, minimal, if any, clinical benefit was observed. TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov with the identifier NCT00110942.Stanley B Cohen, Susanna Proudman, Alan J Kivitz, Francis X Burch, John P Donohue, Deborah Burstein, Yu-Nien Sun, Christopher Banfield, Michael S Vincent, Liyun Ni, and Debra J Zac

CH₃NH₃PbI₃ Perovskite Nanorods Saturable Absorber for Stable Ultra-Fast Laser

In this paper, we propose a novel ultrafast laser with nanostructure CH3NH3PbI3 nanorods, yielding a higher modulation depth and lower optical loss. Our experiment is performed through nanopatterned CH3NH3PbI3 rods and an all-solid-state passive mode-locked laser system. The prepared nanoarray CH3NH3PbI3 perovskite exhibits a modulation depth of 8.1% under a saturation intensity of 9.53 MW/cm2. By applying the CH3NH3PbI3 nanoarray as a saturable absorber in the ultrafast 1064-nm laser system, a mode-locked pulse with a 30-ps pulse width and an 87.3-MHz repetition rate is achieved. A maximum output power of 542 mW was measured, under an absorption pump power of 5.4 W. With the new structured CH3NH3PbI3, our experiment verifies a new method in ultrafast lasers with low light loss, which potentially uncovers an avenue to develop ultrafast lasers

Development of SNP Markers for Original Analysis and Germplasm Identification in <i>Camellia sinensis</i>

Tea plants are widely grown all over the world because they are an important economic crop. The purity and authenticity of tea varieties are frequent problems in the conservation and promotion of germplasm resources in recent years, which has brought considerable inconvenience and uncertainty to the selection of parental lines for breeding and the research and cultivation of superior varieties. However, the development of core SNP markers can quickly and accurately identify the germplasm, which plays an important role in germplasm identification and the genetic relationship analysis of tea plants. In this study, based on 179,970 SNP loci from the whole genome of the tea plant, all of 142 cultivars were clearly divided into three groups: Assam type (CSA), Chinese type (CSS), and transitional type. Most CSA cultivars are from Yunnan Province, which confirms that Yunnan Province is the primary center of CSA origin and domestication. Most CSS cultivars are distributed in east China; therefore, we deduced that east China (mainly Zhejiang and Fujian provinces) is most likely the area of origin and domestication of CSS. Moreover, 45 core markers were screened using strict criteria to 179,970 SNP loci, and we analyzed 117 well-Known tea cultivars in China with 45 core SNP markers. The results were as follows: (1) In total, 117 tea cultivars were distinguished by eight markers, which were selected to construct the DNA fingerprint, and the remaining markers were used as standby markers for germplasm identification. (2) Ten pairs of parent and offspring relationships were confirmed or identified, and among them, seven pairs were well-established pedigree relationships; the other three pairs were newly identified. In this study, the east of China (mainly Zhejiang and Fujian provinces) is most likely the area of origin and domestication of CSS. The 45 core SNP markers were developed, which provide a scientific basis at the molecular level to identify the superior tea germplasm, undertake genetic relationship analysis, and benefit subsequent breeding work

Combination of berberine and evodiamine inhibits intestinal cholesterol absorption in high fat diet induced hyperlipidemic rats

Abstract Background Hyperlipidemia characterized of elevated serum lipid levels is a prevalent disease frequently resulting in cardiovascular disease (CVD). Berberine and evodiamine are herbal products of traditional Chinese herb Coptis chinensis and Evodia rutaecarpa, which are indicated to exert regulation of lipid metabolism. Therefore, the objective of this study was to investigate the lipid-lowering effect of berberine and evodiamine combination in hyperlipidemic rats. Method The rat model of hyperlipidemia was established by providing high-fat-diet (HFD) for 4 weeks. Berberine (BB), evodiamine (EV), and their combination (BB + EV) were orally administered to HFD induced rats for 4 weeks. Body weight, food utilization, histopathology of liver tissues, lipid profiles of serum and liver were measured. Gas chromatography (GC) analysis was applied to examine the level of plasma total cholesterol and ß- Sitosterol (BS) to estimate cholesterol absorption activity. Furthermore, intestinal NPC1L1, ACAT2, and ApoB48 protein expressions were evaluated by immunohistochemical assay. Result According to the results, decreased levels of serum cholesterol (TC), triglycerides (TG), low density lipoprotein-cholesterol (LDL-C), as well as hepatic TC were showed in hyperlipidemic rats treated by combination of berberine and evodiamine. GC analysis indicated that the elevated plasma BS was significantly ameliorated by BB, EV, and BB + EV. In addition, immunohistochemical analysis revealed that BB + EV treatment down-regulated the expressions of intestinal NPC1L1 and ACAT2, and ApoB48 in HFD induced rats. Conclusion Based on the above results, combination of berberine and evodiamine exerted a promising preventive effect on hyperlipidemia, partially through inhibiting intestinal absorption of cholesterol