A novel radiomics signature based on T2-weighted imaging accurately predicts hepatic inflammation in individuals with biopsy-proven nonalcoholic fatty liver disease:a derivation and independent validation study

Background:Currently,there are no effective methods for assessing hepatic inflammation without resorting to histological examination of liver tissue obtained by biopsy.T2-weighted images(T2WI)are routinely obtained from liver magnetic resonance imaging(MRI)scan sequences.We aimed to establish a radiomics signature based on T2WI(T2-RS)for assessment of hepatic inflammation in people with nonalcoholic fatty liver disease(NAFLD).Methods:A total of 203 individuals with biopsy-confirmed NAFLD from two independent Chinese cohorts with liver MRI examination were enrolled in this study.The hepatic inflammatory activity score(IAS)was calculated by the unweighted sum of the histologic scores for lobular inflammation and ballooning.One thousand and thirty-two radiomics features were extracted from the localized region of interest(ROI)in the right liver lobe of T2WI and,subsequently,selected by minimum redundancy maximum relevance and least absolute shrinkage and selection operator(LASSO)methods.The T2-RS was calculated by adding the selected features weighted by their coefficients.Results:Eighteen radiomics features from Laplacian of Gaussian,wavelet,and original images were selected for establishing T2-RS.The T2-RS value differed significantly between groups with increasing grades of hepatic inflammation(P<0.01).The T2-RS yielded an area under the receiver operating characteristic(ROC)curve(AUROC)of 0.80[95%confidence interval(CI):0.71-0.89]for predicting hepatic inflammation in the training cohort with excellent calibration.The AUROCs of T2-RS in the internal cohort and external validation cohorts were 0.77(0.61-0.93)and 0.75(0.63-0.84),respectively.Conclusions:The T2-RS derived from radiomics analysis of T2WI shows promising utility for predicting hepatic inflammation in individuals with NAFLD.

Prevention and treatment of cancer targeting chronic inflammation:research progress,potential agents,clinical studies and mechanisms

Numerous experimental and clinical studies indicate that chronic inflammation is closely related to the initiation, progression,and spread of cancer, in which proinflammatory cytokines, such as interleukin(IL)-6, IL-1β, and tumor necrosis factor-α(TNF-α), and transcription factors, such as nuclear factor-κB(NF-κB), and signal transducer and activator of transcription 3(STAT3), play pivotal roles. Stimulated by proinflammatory cytokines, NF-κB and STAT3 can modulate the expression of target genes, most of which are oncogenic ones, and promote the survival, proliferation, invasion, and metastasis of cancer cells. Now it is generally accepted that inflammation-related molecules and pathways are useful targets for the prevention and treatment of cancer. In this review, we summarize the relationship between chronic inflammation and cancer and describe some potentially useful agents including aspirin, meformin, statins, and some natural products(green tea catechins, andrographolide,curcumin) for their cancer prevention and treatment activities targeting chronic inflammation. The results of typical clinical studies are included, and the influences of these agents on the proinflammatory cytokines and inflammation-related pathways are discussed. Data from the present review support that agents targeting chronic inflammation may have a broad application prospect for the prevention and treatment of cancer in the future.

Contribution of CXCL16 / CXCR6 pathway activated by inflammation to atherosclerosis in patients with end-stage renal disease

Objective To investigate the effects of CXC chemokine ligand 16(CXCL16)/CXC chemokine receptor 6(CXCR6)pathway on cholesterol accumulation of atherosclerosis in the radial artery of end-stage renal disease(ESRD)patients under inflammatory stress and further to investigate its potential mechanisms modulated by purinergic receptor P2X ligandgated ion channel

LRRK2 enhances Nod1/2-mediated inflammatory cytokine production by promoting Rip2 phosphorylation

The innate immune system is critical for clearing infection, and is tightly regulated to avert excessive tissue damage. Nod1/2-Rip2 signaling, which is essential for initiating the innate immune response to bacterial infection and ER stress, is subject to many regulatory mechanisms. In this study, we found that LRRK2, encoded by a gene implicated in Crohn＇s disease, leprosy and familial Parkinson＇s disease, modulates the strength of Nod1/2-Rip2 signaling by enhancing Rip2 phosphorylation. LRRK2 deficiency markedly reduces cytokine production in macrophages upon Nod2 activation by muramyl dipeptide （MDP）, Nod1 activation by D-gamma-Glu-meso-diaminopimelic acid （iE-DAP） or ER stress. Our biochemical study shows that the presence of LRRK2 is necessary for optimal phosphorylation of Rip2 upon NOd2 activation. Therefore, this study reveals that LRRK2 is a new positive regulator of Rip2 and promotes inflammatory cytokine induction through the Nod1/2-Rip2 pathway.

AMPK and cardiac remodelling

Cardiac remodelling is generally accepted as a critical process in the progression of heart failure. Myocyte hypertrophy,inflammatory responses and cardiac fibrosis are the main pathological changes associated with cardiac remodelling.AMP-activated protein kinase(AMPK) is known as an energy sensor and a regulator of cardiac metabolism under normal and ischaemic conditions. Additionally, AMPK has been shown to play roles in cardiac remodelling extending well beyond metabolic regulation. In this review, we discuss the currently defined roles of AMPK in cardiac remodelling and summarize the effects of AMPK on cardiac hypertrophy, inflammatory responses and fibrosis and the molecular mechanisms underlying these effects. In addition, we discuss some pharmacological activators of AMPK that are promising treatments for cardiac remodelling.