Therapeutic effects of Saikosapoin D on bleomycininduced pulmonary fibrosis in mice via regulation of IL- 33/ST2 pathway

Purpose: To investigate the therapeutic effects of saikosapoin D (SSD) on bleomycin (BLM)-induced pulmonary fibrosis (PF) in mice and its probable mechanisms.Methods: PF mice were prepared by intraperitoneal (i.p.) injection of BLM (5 mg/kg). Twenty-four hours later, 72 mice in SSD group were administered SSD (1.8 mg/kg, ip). After 3, 7, 14 and 28 days of injection, the mice were sacrificed. Blood samples and lung tissues were collected from 6 mice in each group. The lung tissues were subjected to histological examination. In addition, expressions of MyD88, TRAF6, IL-33 and ST2 in lung tissue were determined by western blotting assay. Serum levels of hydroxyproline (HYP), interleukin (IL)-4, IL-13 and interferon (IFN)-γ were measured by enzyme-linked immunosorbent assay (ELISA).Results: Pathological results showed that SSD treatment alleviated alveolitis and lung fibrosis (p < 0.05) in lung tissues of PF mice at 14 and 28 days post-BLM injection. HYP and IL-13 levels of mice in SSD group were significantly lower than that in BLM group at days 14 and 28 post-BLM injection (p < 0.05). Levels of IL-4 and IFN-γ were significantly lower when compared with values in BLM group on day 28 (p < 0.05). Western blotting results revealed that expressions of MyD88, TRAF6, IL-33 and ST2 proteins were significantly decreased by SSD treatment (p < 0.05).Conclusion: SSD exerts therapeutic effects on BLM-induced experimental PF in mice via regulation ofIL-33/ST2 pathway.Keywords: Saikosapoin D, Idiopathic pulmonary fibrosis, Myeloid differentiation factor, Hydroxyproline, Interleukin, Interferon, IL-33/ST2 pathwa

Bloch surface plasmon enhanced blue emission from InGaN/GaN light-emitting diode structures with Al-coated GaN nanorods

InGaN/GaN light-emitting diode structures with Al-coated GaN nanorods were fabricated by using soft ultraviolet nanoimprint lithography. The intensity of light emission was found to be greatly enhanced due to the strong near-fields confined at the interface of Al/GaN and extended to the multiple quantum wells (MQWs) active region. The dynamics of carrier recombination and plasmon-enhanced Raman scattering were also investigated, providing a progressive view on the effective energy transfer between MQWs and surface plasmons.This work was supported by Special Funds for Major State Basic Research Project (Nos. 2011CB301900 and 2012CB619304), the Hi-tech Research Project (No. 2014AA032605), National Nature Science Foundation of China (Nos. 11104130, 61274003, 60990311, 61176063, and 61422401), the Program for New Century Excellent Talents in University (No. NCET-11-0229), Nature Science Foundation of Jiangsu Province (Nos. BK2011556, BK2011010, BK2010385, BY2013077, and BE2011132), Funds of Key Laboratory (No. 9140C140102120C14), Scientific Innovation Research of College Graduate in Jiangsu Province (CXZZ12_0052), PAPD, the Fundamental Research Funds for the Central Universities, the Research Funds from NJUYangzhou Institute of Opto-electronics, and the Australian Research Council Discovery Early Career Researcher Award (DE130101700)

N-Phenylpyridine-2-carb­amide

In the title compound, C12H10N2O, the dihedral angle between the pyridine ring system and the phenyl ring is 1.8 (1)°. There is an intra­molecular N—H⋯N hydrogen bond between the pyridine N atom and the amide NH function

Clinicopathological characteristics, molecular landscape, and biomarker landscape for predicting the efficacy of PD-1/PD-L1 inhibitors in Chinese population with mismatch repair deficient urothelial carcinoma: a real-world study

Urothelial carcinoma (UC) with deficient mismatch repair (dMMR) is a specific subtype of UC characterized by the loss of mismatch repair (MMR) proteins and its association with Lynch syndrome (LS). However, comprehensive real-world data on the incidence, clinicopathological characteristics, molecular landscape, and biomarker landscape for predicting the efficacy of PD-1/PD-L1 inhibitors in the Chinese patients with dMMR UC remains unknown. We analyzed 374 patients with bladder urothelial carcinoma (BUC) and 232 patients with upper tract urothelial carcinoma (UTUC) using tissue microarrays, immunohistochemistry, and targeted next-generation sequencing. Results showed the incidence of dMMR UC was higher in the upper urinary tract than in the bladder. Genomic analysis identified frequent mutations in KMT2D and KMT2C genes and LS was confirmed in 53.8% of dMMR UC cases. dMMR UC cases displayed microsatellite instability-high (MSI-H) (PCR method) in 91.7% and tumor mutational burden-high (TMB-H) in 40% of cases. The density of intratumoral CD8+ T cells correlated with better overall survival in dMMR UC patients. Positive PD-L1 expression was found in 20% cases, but some patients positively responded to immunotherapy despite negative PD-L1 expression. Our findings provide valuable insights into the characteristics of dMMR UC in the Chinese population and highlights the relevance of genetic testing and immunotherapy biomarkers for treatment decisions

Genomic Analyses Reveal Mutational Signatures and Frequently Altered Genes in Esophageal Squamous Cell Carcinoma

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers worldwide and the fourth most lethal cancer in China. However, although genomic studies have identified some mutations associated with ESCC, we know little of the mutational processes responsible. To identify genome-wide mutational signatures, we performed either whole-genome sequencing (WGS) or whole-exome sequencing (WES) on 104 ESCC individuals and combined our data with those of 88 previously reported samples. An APOBEC-mediated mutational signature in 47% of 192 tumors suggests that APOBEC-catalyzed deamination provides a source of DNA damage in ESCC. Moreover, PIK3CA hotspot mutations (c.1624G>A [p.Glu542Lys] and c.1633G>A [p.Glu545Lys]) were enriched in APOBEC-signature tumors, and no smoking-associated signature was observed in ESCC. In the samples analyzed by WGS, we identified focal (<100 kb) amplifications of CBX4 and CBX8. In our combined cohort, we identified frequent inactivating mutations in AJUBA, ZNF750, and PTCH1 and the chromatin-remodeling genes CREBBP and BAP1, in addition to known mutations. Functional analyses suggest roles for several genes (CBX4, CBX8, AJUBA, and ZNF750) in ESCC. Notably, high activity of hedgehog signaling and the PI3K pathway in approximately 60% of 104 ESCC tumors indicates that therapies targeting these pathways might be particularly promising strategies for ESCC. Collectively, our data provide comprehensive insights into the mutational signatures of ESCC and identify markers for early diagnosis and potential therapeutic targets