Regulatory mechanism underlying liver X receptor effects on the tumor microenvironment, inflammation and tumorigenesis.

INTRODUCTION: Liver X receptors (LXRs) have emerged as novel targets for tumor treatment. LXRs within the tumor microenvironment show the capacity to impact tumorigenesis and tumor development by regulating the infiltration of immune cells and release of cytokines to moderate inflammation. AREAS COVERED: In this review, we present a systematic description of recent progress in understanding the impact of LXRs on the tumor microenvironment and tumorigenesis. We also summarize the antitumor effects mediated by LXRs via their regulation of cytokine expression. Additionally, we discuss the limitations of LXR research in tumor studies to date. EXPERT OPINION: Previous studies have demonstrated abnormal LXR expression in tumor tissues, and activation of LXRs has been shown to inhibit tumorigenesis and promote apoptosis in tumor cells. However, LXRs can also affect tumorigenesis by regulating immune cell functions within the tumor immune microenvironment. By summarizing the impact of LXRs on immune cells, we provide new insights into the multifaceted nature of LXRs as antitumor targets.

Shikonin triggers GSDME-mediated pyroptosis in tumours by regulating autophagy via the ROS-MAPK14/p38α axis.

BACKGROUND: Shikonin (SK), a botanical drug extracted from Lithospermum erythrorhizon, has been shown to inhibit tumour growth through apoptosis and necrosis. However, whether SK induces pyroptosis in cancer cells is still unknown. PURPOSE: This study aims to investigated the mechanisms of SK-induced pyroptosis in tumour cells and mice. METHODS: In vivo and in vitro methods were used in this study. Cell deaths were analysed by LDH and CCK-8 assay and western blotting. To investigated the signalling pathway of SK-induced pyroptosis, various genes expressions were supressed by shRNA or inhibitors. High-sensitivity mass spectrometry assay was used to identified potential factors that regulate GSDME-mediated pyroptosis. Finally, a mouse model was used to investigate the effect of SK administration on tumour growth in vivo. RESULTS: The activation of BAX/caspase-3 signalling was essential for GSDME-mediated pyroptosis by SK. Mechanistically, the intracellular reactive oxygen species (ROS) generation induced by SK treatment initiated GSDME-dependant pyroptosis. SK stimulation induced protective autophagy in a ROS-dependant manner, and repressed autophagy significantly enhanced SK-induced pyroptosis. Moreover, MAPK14/p38α, a ROS sensor, modulated SK-induced autophagy and ultimately affected GSDME-dependant pyroptosis. CONCLUSION: Here, for the first time we demonstrated that SK treatment induced GSDME-dependant pyroptosis in tumour cells. Our results demonstrated that SK initiates ROS signalling to drive pyroptosis in cancer cells.

Figures of the Psychotherapist in Contemporary Chinese Literature.

Since the 1980s, psychoanalysis and psychotherapy have attracted great interest in Chinese society, and in parallel, the psychotherapist as a character has emerged in Chinese literature. Through four novels by three Chinese authors, namely, Xu Xiaobin , Ke Yunlu , and Bi Shumin , this article studies the evolution of the image of the psychotherapist in contemporary Chinese literature, which reflects the reception of psychoanalysis as well as the development of psychotherapy in China. In Xu Xiaobin's novel, two psychology students attempt to cure a psychotic patient through "transference therapy" based on a complete misunderstanding of the notion; Ke Yunlu features a "life counselor" who, like typical good counselors in Chinese classical novels, simply gives advice without caring about the patients' needs and desires; and the two novels by Bi Shumin show a significant change in the writer's understanding of the profession and therapeutic methods, as well as the current, unregulated situation of psychotherapy in China.

Proteins in plasma as a potential biomarkers diagnostic for pelvic organ prolapse.

BACKGROUND: Pelvic organ prolapse (POP) is the most common and widespread type of female pelvic floor dysfunction disease (PFD). At present, the diagnosis of POP is mainly based on a complicated systematic evaluation of the clinical phenotype, medical history, and relevant functional examinations. Rapid and simple tests that are based on biochemical biomarkers that surpass the sensitivity and specificity of the current methods for the diagnosis of POP will greatly facilitate the timely diagnosis and treatment of women with POP. METHODS: A protein array was used to screen plasma samples collected from healthy controls and women with POP. Enzyme-linked immunosorbent assays (ELISAs) were used to determine the levels of three novel and potentially useful analytes: heat shock protein 10 (HSP10), zinc finger CCCH domain-containing protein 8 (ZC3H8), and unc-45 myosin chaperone A (UNC45A). We then determined the diagnostic value of each of these analytes as potential diagnostic biomarkers for clinical application. RESULTS: The mean levels of HSP10, ZC3H8, and UNC45A, were lower in the plasma samples from 76 patients with POP than in 56 samples from healthy controls (P<0.05). Comparisons between patients with POP and healthy controls demonstrated the sensitivity and specificity of HSP10 (73.7% and 71.4%), ZC3H8 (71.1% and 62.5%), and UNC45A (70.7% and 62.5%). CONCLUSIONS: Analysis indicated that plasma levels of HSP10, ZC3H8, and UNC45A, are sensitive and specific biomarkers for the diagnosis of POP.

Long non-coding RNA DANCR promotes the progression of non-small-cell lung cancer by inhibiting p21 expression.

BACKGROUND: Long non-coding RNAs (lncRNAs) play important roles in human cancers. However, the functional roles of lncRNAs in non-small-cell lung cancer (NSCLC) and the underlying mechanisms are not well understood. METHODS: We examined the expression of lncRNA DANCR in NSCLC by qRT-PCR and explored its biological roles in NSCLC progression by cell and molecular biology studies. RESULTS: DANCR expression level was increased in human NSCLC. The knockdown of DANCR inhibited NSCLC cell proliferation by inducing cell apoptosis and cell cycle arrest. In addition, DANCR knockdown suppressed NSCLC cell migration and invasion via inhibition of epithelial-mesenchymal transition (EMT). On the contrary, DANCR overexpression had the opposite effects. DANCR knockdown inhibited EZH-2-mediated epigenetic silencing of p21 promoter and increased p21 expression. Moreover, DANCR knockdown inhibited NSCLC cell proliferation, migration, and invasion in a p21-dependent manner. CONCLUSION: DANCR plays oncogenic roles in NSCLC and may provide a novel biomarker for NSCLC diagnosis and prognosis.

Anti-Inflammatory Activities and Related Mechanism of Polysaccharides Isolated from Sargentodoxa cuneata.

Sargentodoxa cuneata decoction has been used to treat arthritis in China for hundreds of years. Herein, the polysaccharide fraction (PSC) purified from S. cuneata was evaluated for its in vitro and in vivo anti-inflammatory effects. PSC and its sub-fractions PSCA-1 and PSCB-1 significantly suppressed nitric oxide (NO) release in LPS-induced RAW264.7 cells by down regulating the inducible nitric oxide synthase (iNOS) level. Furthermore, PSC markedly inhibited carrageenan induced rat hind paw edema, decreased in hind paw, serum and liver malondialdehyde (MDA) levels and prostaglandin E2 (PGE2 ) levels. In addition, PSC increased superoxide dismutase (SOD) activity in serum and liver of the rats. These results revealed that the polysaccharide obtained from S. cuneata (PSC) possessed potent anti-inflammatory activity and may be one of the important bioactive constituents from the plant responsible for the anti-arthritis effect.

Tetrandrine suppresses ß­glucan­induced macrophage activation via inhibiting NF­κB, ERK and STAT3 signaling pathways.

Macrophages are important in inflammation through the production of various proinflammatory mediators. ß­glucan is a polymer of glucose, which is produced by numerous different organisms, including fungi, and acts as a trigger for the induction of inflammatory responses. Tetrandrine (TET), a bis­benzylisoquinoline alkaloid isolated from the Chinese herb Radix Stephania tetrandra, has been demonstrated to modulate inflammatory responses. In the present study, it was investigated whether TET affects the inflammatory reaction induced by ß­glucan in murine and human macrophages. It was demonstrated that ß­glucan induced the activation of nuclear factor (NF)­κB and markedly increased the levels of tumor necrosis factor­α (TNF­α) and interleukin 1 ß (IL­1ß) in macrophages. Treatment with TET resulted in downregulation of phosphorylated NF­κB p65 and reduction of the production of TNF­α and IL­1ß. In addition, the phosphorylation of ERK and STAT3 was decreased by TET in activated macrophages. Furthermore, it was demonstrated that the inhibitory effects of TET on ß­glucan­induced macrophage activation was not due to its cytotoxic action. Conclusively, these results indicate that TET can decrease the inflammatory responses mediated by ß­glucan in macrophages. Thus, TET may serve as an effective tool for the treatment of ß­glucan­associated inflammatory diseases.

[Association of apolipoprotein A5 gene -1131T/C polymorphism with lipid metabolism and insulin resistance in patients with type II diabetes mellitus].

The purpose of this study was to explore the frequency of apolipoprotein A5 (APOA5) -1131T/C polymorphism in Zhenjiang and its effects on lipid metabolism and insulin resistance in type II diabetes mellitus(DM) patients. The genotypes of APOA5 -1131T/C polymorphism were determined in 152 healthy individuals and 71 type II DM patients by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Serum levels of lipids, glucose and insulin in these subjects were also estimated by biochemical methods. The frequency of the APOA5-1131C allele in DM patients was significantly higher than that of the control group (0.430 vs 0.296, P = 0.006). When compared with the TT genotype, CC homozygotes had a significantly increased DM risk (OR=3.75, 95% CI: 1.57-8.92). In the DM group, the serum levels of triglyceride (TG) of C carriers (TC+CC) were significantly higher than those of non-C carriers (TT) (P 0.01), and serum levels of total cholesterol (TC) and low density lipoprotein cholesterol(LDL-c) in subjects with the CC genotype were also significantly higher than those with the TT genotype (P 0.05). However, there was no significance in profiles of insulin resistance in various genotypes in both groups. The APOA5 single nucleotide polymorphism was associ-ated with serum TG level in the population. The -1131C allele contributed to the increase of serum levels of TG, TC and LDL-c and but had no effect on profiles of insulin resistance in DM patients. The APOA5 -1131C allele may be associated with increased susceptibility to type II diabetes mellitus.

Association of APOA5 c.553G>T polymorphism with type 2 diabetes mellitus in a Chinese population.

BACKGROUND: Several independent population studies have reported that c.553G>T polymorphism of the apolipoprotein A5 gene (APOA5) is associated with hypertriglyceridaemia. The aim of this study is to investigate the association between this genetic variation and the risk of type 2 diabetes mellitus. METHODS: In this study, APOA5 c.553G>T polymorphisms in 152 healthy individuals and 71 type 2 diabetes mellitus patients were detected by PCR-restriction fragment length polymorphism and agarose electrophoresis methods, and serum levels of lipids were also estimated by biochemical methods. RESULTS: The frequency of T alleles in the diabetes and control groups was 0.085 and 0.049, respectively. Compared with controls, there was no significant difference in the distribution of genotype and allele frequencies of c.553G>T polymorphic sites in diabetic patients (p=0.27 and p=0.15, respectively). However, the frequency of GT and TT genotypes and the T allele in the subgroup with hypertriglyceridaemia was significantly higher than that in the subgroup with normal triglyceridaemia in both the control group (p=0.034 and p=0.014, respectively) and the diabetes group (p=0.037 and p=0.007, respectively). In the diabetes and control groups, triglyceride levels in (GT+TT) genotype individuals were significantly higher than in GG genotype individuals (p=0.001 and p=0.003, respectively), and levels of low-density lipoprotein cholesterol were also significantly higher (p=0.044 and p=0.022, respectively). CONCLUSIONS: APOA5 c.553G>T polymorphism is not significantly associated with susceptibility to type 2 diabetes mellitus, but is associated with plasma triglyceride and low-density lipoprotein cholesterol levels.