Au 25 nanoclusters as a self-therapeutic nanodrug significantly modulated macrophage polarization from M1 to M2 and could act as an inhibitor of thioredoxin reductase (TrxR), which induced ROS-mediated FLS apoptosis by breaking redox homeostasis.
Rheumatoid arthritis (RA) is a chronic inflammatory and systemic autoimmune disease with an unknown aetiology. Accumulative studies suggest that the pathogenesis of RA involves the excessive activation of synoviocytes and immune cells, increasing the secretion of inflammatory mediators and cytokines in synoviocytes, causing dysfunctional E-prostanoid (EP)-G-protein-cyclic adenosine monophosphate (cAMP) and mitogen-associated-protein kinase (MAPK) signalling in synoviocytes. Total glucosides of paeony (TGP) extracted from the roots of Paeonia lactiflora Pall, was approved by the China Food and Drug Administration as an anti-inflammatory and immuno-modulator drug in 1998. Paeoniflorin (Pae), a water-soluble monoterpene glucoside,is the main effective component of TGP. TGP and Pae produce anti-inflammatory and immuno-regulatory effects by suppressing immune cells and synoviocytes activation, decreasing inflammatory substance production and restoring abnormal signalling in synoviocytes. In this review, the regulation of the inflammatory-immune responses and the therapeutic mechanism between RA and TGP and Pae are discussed in detail. The aim of this review was to provide novel insights into the treatment of RA.
Abstract BACKGROUND Pancreatic ductal adenocarcinoma (PDAC) is recognized as the most lethal solid malignancies with very few therapeutic options. Until very recently, FDA approved the first molecularly targeted therapy with the PARP inhibitor Olaparib for pancreatic cancer patients with germline mutations on BRCA1/2, two types of homologous recombination (HR)/DNA damage repair (DDR) genes. In addition, the sensitivity of platinum-based chemotherapy and anti-PD-1 antibodies have been connected with DDR spectrum. However, the genetic landscape of PDAC is mainly based on data from Caucasian population. In this study, we sought to explore the germline mutation spectrum of DDRs in oriental PDAC for clinical practice. METHODS Germline DNA extracted from 256 Asian peri ampullary cancer patients (201 PDAC, 20 adenosquamous carcinoma, and 35 vater periampullary carcinoma) underwent whole exome sequencing. The mean depth of sequencing was 67 X. 229 DDR genes were focused for variant callings using the GATK and its pathogenicity according to the guidelines from ACMG. Pathogenic or likely pathogenic(P/LP) were further analyzed. RESULTS Pathogenic variants were identified in 26 of 256 patients (10.2%),and one patient had mutations in two genes. The 27 pathogenic mutations occurred in 16 different genes,including ERCC2 (n=4), OGG1 (n=4), PALB2 (n=3), FAN1 (n=3), RAD54L (n=2), WRN (n=1), POLH (n=1), MUTYH (n=1), MSH6 (n=1), MLH3 (n=1), LIG1 (n=1), ERCC6 (n=1), CHEK2 (n=1), BRCA2 (n=1), BRCA1 (n=1), and ATM (n=1). The detailed gene profiles were mainly involved in five pathways, Homologous recombination(HR), Fanconi anemia(FA), Mismatch repair(MMR), Base excision repair(BER)and Nucleotide excision repair(NER. Of note, two mutations MSH6 c.261-1G>A and BRCA2 c.3912_3916del, were first reported to be associated with cancer and classified as likely pathogenic owing to their frameshift variant or splice site and low frequencies of occurrence. To determine the difference of germline DDR mutation landscape between oriental and American populations, we compared our cohort with American cohorts from Yurgelun and TCGA. The BRCA1/2 germline mutations were found at low levels in our cohort (0.8%) compared to the American cohorts (2.4~2.7%), Furthermore, the whole DDR mutations exhibited highest proportion [10.5% (27/256) from our study, compared with 7.3% (21/289) from Yurgelun, and 5.4% (10/185) from TCGA, respectively]. CONCLUSION In conclusion,our results characterized the germline mutation landscape of DDRs in the largest oriental cohort of pancreatic cancer to date, and first discovered two novel germline mutations in pancreatic cancer. Most importantly, nearly 10% of PDAC patients in this study were found to harbor germline DDR mutations, which may benefit more patients with an effective therapeutic synergy for PARP and PD-1 inhibitors in clinical practice. Citation Format: Shiwei Guo, Lisha Jiang, Xiaohan Shi, Suizhi Gao, Bo Li, Ling Lin, Jun Yu, Gang Jin. Germline mutation landscape of DNA damage repair genes in Oriental pancreatic cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3540.
RNA modifications,especially methylation of the N6 position of adenosine(A)––m6A,represent an emerging research frontier in RNA biology.MeRIP-Seq,which combines m6A-specific methylated RNA immunoprecipitation with next-generation sequencing(NGS)technology,can catch the modifications in whole transcriptome.
Pain has been a prominent medical concern since ancient times. Despite significant advances in the diagnosis and treatment of pain in contemporary medicine, there is no a therapeutic cure for chronic pain. Chinese herbaceous peony, a traditional Chinese analgesic herb has been in clinical use for millennia, with widespread application and substantial efficacy. Paeoniflorin (PF), the main active ingredient of Chinese herbaceous peony, has antioxidant, anti-inflammatory, anticancer, analgesic, and antispasmodic properties, among others. The analgesic effect of PF, involving multiple critical targets and pain regulatory pathways, has been a hot spot for current research. This article reviews the literature related to the analgesic effect of PF in the past decade and discusses the molecular mechanism of the analgesic effect of PF, including the protective effects of nerve cells, inhibition of inflammatory reactions, antioxidant effects, reduction of excitability in nociceptor, inhibition of the nociceptive excitatory neuroreceptor system, activation of the nociceptive inhibitory neuroreceptor system and regulation of other receptors involved in nociceptive sensitization. Thus, providing a theoretical basis for pain prevention and treatment research. Furthermore, the prospect of PF-based drug development is presented to propose new ideas for clinical analgesic therapy.
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