Targeting endoplasmic reticulum stress signaling in ovarian cancer therapy

The endoplasmic reticulum(ER),an organelle present in various eukaryotic cells,is responsible for intracellular protein synthesis,post-translational modification,and folding and transport,as well as the regulation of lipid and steroid metabolism and Ca2+homeostasis.Hypoxia,nutrient deficiency,and a low pH tumor microenvironment lead to the accumulation of misfolded or unfolded proteins in the ER,thus activating ER stress(ERS)and the unfolded protein response,and resulting in either restoration of cellular homeostasis or cell death.ERS plays a crucial role in cancer oncogenesis,progression,and response to therapies.This article reviews current studies relating ERS to ovarian cancer,the most lethal gynecologic malignancy among women globally,and discusses pharmacological agents and possible targets for therapeutic intervention.

A double-edged sword:ROS related therapies in the treatment of psoriasis

In the onset and progression of psoriasis,redox imbalance is a vital factor.It's widely accepted that too much reactive oxygen species(ROS)always make psoriasis worse.Recent research,however,has shown that the accumulation of ROS is not entirely detrimental,as it helps reduce psoriasis lesions by inhibiting epidermal proliferation and keratinocyte death.As a result,ROS appears to have two opposing effects on the treatment of psoriasis.In this review,the current ROS-related therapies for psoriasis,including basic and clinical research,are presented.Additionally,the design and therapeutic benefits of various drug delivery systems and therapeutic approaches are examined,and a potential balance between antioxidative stress and ROS accumulation is also trying to be investigated.

Ganoboninketal C from Ganoderma boninense improves the efficacy of CDDP-based chemotherapy through inhibiting translesion DNA synthesis

Translesion DNA synthesis(TLS)can bypass DNA lesions caused by chemotherapeutic drugs,which usually result in drug resistance.Given its key role in mutagenesis and cell survival after DNA damage,inhibition of the TLS pathway has emerged as a potential target for improving the efficacy of DNA-damaging agents such as cisplatin(CDDP),a widely used anticancer agent.Unfortunately,few suitable natural TLS inhibitors have been reported.Here,we found that a triterpenoid compound Ganoboninketal C(26-3)from Ganoderma boninense,a traditional Chinese medicine,can impair CDDP-induced TLS polymerase eta(Polη)focus formation,PCNA monoubiquitination as well as mutagenesis.Moreover,26-3 can significantly sensitize tumor cells to CDDP killing and reduce the proportion of cancer stem cells in AGS and promote apoptosis after CDDP exposure.Interestingly,26-3 can also sensitize tumor cells to Gefitinib therapy.Mechanistically,through RNA-seq analysis,we found that 26-3 could abrogate the CDDP-induced upregulation of Polηand PIDD(p53-induced protein with a death domain),2 known factors promoting TLS pathway.Furthermore,we found that activating transcription factor 3 is a potential novel TLS modulator.Taken together,we have identified a natural TLS inhibitor 26-3,which can be potentially used as an adjuvant to improve clinical efficacy.

The Missing Link： Japan as an Intermediary in the Transculturation of the Diary of A Madman

The Diary of A Madman （Kuangren r/j/）, Lu Xun＇s first well-known short stoW and the alleged first modem short stow in vernacular Chinese, is famous for its first-person narrative by an intellectual that is suffering from a persecution complex. As acknowledged by Lu Xun himself and argued by most scholars, this short stoW was influenced by Gogol＇s homonymic short stow, but has developed more profound melancholy and indignation. However, as my paper demonstrates, this perspective neglects the role of Japan as an intermediary in the transculturation of madness. First, Lu Xun＇s initial encounter with Gogol＇s Diary of A Madman was through his reading of Futabatei Shimei＇s translation in the Japanese magazine Ky6mi. Second, the framed narrative and contrasting styles of Lu Xun＇s short stow, which are not features of Gogol＇s, might also be due to the inspiration from the Japanese genbun itchi movement in the Meiji period. Third, and most importantly, cannibalism, a major theme in Lu Xun＇s Diary of A Madman, was arguably shaped by the heated discussion in Japan on national character and cannibalism. My paper will trace the double origin of the depiction of madness and cannibalism in Lu Xun＇s work and illustrate the importance of the role of Japan in the transculturation of the stow of a madman.

The mRNA–miRNA–lncRNA Regulatory Network and Factors Associated with Prognosis Prediction of Hepatocellular Carcinoma

The aim of this study was to identify novel prognostic mRNA and microRNA(miRNA)biomarkers for hepatocellular carcinoma(HCC)using methods in systems biology.Differentially expressed mRNAs,miRNAs,and long non-coding RNAs(lncRNAs)were compared between HCC tumor tissues and normal liver tissues in The Cancer Genome Atlas(TCGA)database.Subsequently,a prognosis-associated mRNA co-expression network,an mRNA–miRNA reg-ulatory network,and an mRNA–miRNA–lncRNA regulatory network were constructed to identify prognostic biomarkers for HCC through Cox survival analysis.Seven prognosis-associated mRNA co-expression modules were obtained by analyzing these differentially expressed mRNAs.An expression module including 120 mRNAs was significantly corre-lated with HCC patient survival.Combined with patient survival data,several mRNAs and miRNAs,including CHST4,SLC22A8,STC2,hsa-miR-326,and hsa-miR-21 were identified from the network to predict HCC patient prognosis.Clinical significance was investigated using tissue microarray analysis of samples from 258 patients with HCC.Functional annotation of hsa-miR-326 and hsa-miR-21-5p indicated specific associations with several cancer-related pathways.The present study provides a bioinformatics method for biomarker screening,leading to the identification of an integrated mRNA–miRNA–lncRNA regulatory network and their co-expression patterns in relation to predicting HCC patient survival.