Theranostic nanoparticles ZIF-8@ICG for pH/NIR-responsive drug-release and NIR-guided chemo-phototherapy against non-small-cell lung cancer.

This study leverages nanotechnology by encapsulating indocyanine green (ICG) and paclitaxel (Tax) using zeolitic imidazolate frameworks-8 (ZIF-8) as a scaffold. This study aims to investigate the chemo-photothermal therapeutic potential of ZIF-8@ICG@Tax nanoparticles (NPs) in the treatment of non-small cell lung cancer (NSCLC). An "all-in-one" theranostic ZIF-8@ICG@Tax NPs was conducted by self-assembly based on electrostatic interaction. First, the photothermal effect, stability, pH responsiveness, drug release, and blood compatibility of ZIF-8@ICG@Tax were evaluated through in vitro testing. Furthermore, the hepatic and renal toxicity of ZIF-8@ICG@Tax were assessed through in vivo testing. Additionally, the anticancer effects of these nanoparticles were investigated both in vitro and in vivo. Uniform and stable chemo-photothermal ZIF-8@ICG@Tax NPs had been successfully synthesized and had outstanding drug releasing capacities. Moreover, ZIF-8@ICG@Tax NPs showed remarkable responsiveness dependent both on pH in the tumor microenvironment and NIR irradiation, allowing for targeted drug delivery and controlled drug release. NIR irradiation can enhance the tumor cell response to ZIF-8@ICG@Tax uptake, thereby promoting the anti-tumor growth in vitro and in vivo. ZIF-8@ICG@Tax and NIR irradiation have demonstrated remarkable synergistic anti-tumor growth properties compared to their individual components. This novel theranostic chemo-photothermal NPs hold great potential as a viable treatment option for NSCLC.

Association between inflammatory markers and non-alcoholic fatty liver disease in obese children.

Background: Given the high prevalence of non-alcoholic fatty liver disease (NAFLD) in obese children, non-invasive markers of disease to date are still limited and worth exploring. Objective: This study aimed to evaluate the association between inflammatory markers and NAFLD in obese children. Methods: We performed a case-control study in Hunan Children's Hospital from September 2020 to September 2021. Study participants were children with obesity diagnosed with NAFLD by abdominal ultrasound examination. Mean platelet volume (MPV), platelet distribution width (PDW), neutrophil, lymphocyte, monocyte, and platelet counts were extracted from medical records and inflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA). Multivariable logistic regression analysis was performed to evaluate the association between inflammatory markers and NAFLD. We also used receiver operating characteristic curve analysis to assess the discriminative ability of inflammatory cytokines for NAFLD. Results: Two hundred and sixty-seven obese children were enrolled, including 176 NAFLD patients and 91 simple obesity controls. Multivariable logistic model indicated that increased interleukin (IL)-1ß [odds ratio (OR) = 1.15, 95% confidence interval (CI): 1.04-1.27], IL-6 (OR = 1.28, 95% CI: 1.07-1.53), and IL-17 (OR = 1.04, 95% CI: 1.02-1.07) levels were significantly associated with NAFLD. In contrast, we observed non-significant associations for IL-8, IL-12, IL-21, IL-32, tumor necrosis factor-α (TNF-α), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), mean platelet volume (MPV), and platelet distribution width (PDW) with NAFLD. The area under the curves (AUCs) of IL-1ß, IL-6, and IL-17 to discriminate obese children with or without NAFLD were 0.94, 0.94, and 0.97, respectively. Conclusions: Our results indicated that IL-1ß, IL-6, and IL-17 levels were significantly associated with NAFLD. These inflammatory cytokines may serve as non-invasive markers to determine the development of NAFLD and potentially identify additional avenues for therapeutic intervention.

Association of Inflammatory Cytokines With Non-Alcoholic Fatty Liver Disease.

Background: Inflammatory cytokines have been considered to be significant factors contributing to the development and progression of non-alcoholic fatty liver disease (NAFLD). However, the role of inflammatory cytokines in NAFLD remains inconclusive. Objective: This study aimed to evaluate the association between inflammatory cytokines and NAFLD. Methods: PubMed, Web of Science, the Cochrane Library, and EMBASE databases were searched until 31 December 2021 to identify eligible studies that reported the association of inflammatory cytokine with NAFLD and its subtypes. We pooled odds ratios (ORs) and hazard risk (HRs) with 95% confidence intervals (CIs) and conducted heterogeneity tests. Sensitivity analysis and analysis for publication bias were also carried out. Results: The search in the databases identified 51 relevant studies that investigated the association between 19 different inflammatory cytokines and NAFLD based on 36,074 patients and 47,052 controls. The results of the meta-analysis showed significant associations for C-reactive protein (CRP), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and intercellular adhesion molecule-1 (ICAM-1) with NAFLD (ORs of 1.41, 1.08, 1.50, 1.15 and 2.17, respectively). In contrast, we observed non-significant associations for interferon-γ (IFN-γ), insulin-like growth factor (IGF-II), interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-7 (IL-7), interleukin-8 (IL-8), interleukin-10 (IL-10), interleukin-12 (IL-12), monocyte chemoattractant protein-1(MCP-1), and transforming growth factor-ß (TGF-ß) with NAFLD. Our results also showed that CRP, IL-1ß, and TNF-α were significantly associated with non-alcoholic steatohepatitis (NASH) and hepatic fibrosis. Conclusions: Our results indicated that increased CRP, IL-1ß, IL-6, TNF-α, and ICAM-1 concentrations were significantly associated with increased risks of NAFLD. These inflammatory mediators may serve as biomarkers for NAFLD subjects and expect to provide new insights into the aetiology of NAFLD as well as early diagnosis and intervention.

Chemokines in hepatocellular carcinoma: a meta-analysis.

Accumulating evidence suggests that chemokines may play an important role in the formation and mediating of the immune microenvironment of hepatocellular carcinoma (HCC). The purpose of this meta-analysis was to explore the differences in blood or tissues chemokines concentrations between HCC patients and controls. Online databases, namely PubMed, Web of Science, Embase and Cochrane Library, were systematically searched for relevant articles published on or before 15 January 2020. Standardized mean differences (SMDs) with corresponding 95% confidence intervals of the chemokines concentrations were calculated as group differences between the HCC patients and the controls. Sixty-five studies met the inclusion criteria for the meta-analysis. Altogether they consisted of 26 different chemokines compared between 5828 HCC patients and 4909 controls; and 12 different chemokines receptors compared between 2053 patients and 2285 controls. The results of meta-analysis indicated that concentrations of CCL20, CXCL8 and CXCR4 in the HCC patients were significantly higher than those in the controls (SMD of 6.18, 1.81 and 1.04, respectively). Therefore, higher concentration levels of CCL20, CXCL8 and CXCR4 may indicate the occurrence of HCC Future research should explore the putative mechanisms underlying this linkage. Meanwhile, attempts can be made to replicate the existing findings in prospective cohort populations and explore the cause-and-effect relationships pertaining to this linkage in order to develop new diagnostic and therapeutic strategies for HCC.

Gut metabolites and inflammation factors in non-alcoholic fatty liver disease: A systematic review and meta-analysis.

The interaction of gut microbiota, related metabolites and inflammation factors with nonalcoholic fatty liver disease (NAFLD) remains unclearly defined. The aim of this systematic review and meta-analysis was to synthesize previous study findings to better understand this interaction. Relevant research articles published not later than September, 2019 were searched in the following databases: Web of Science, PubMed, Embase, and Cochrane Library. The search strategy and inclusion criteria for this study yielded a total of 47 studies, of which only 11 were eligible for meta-analysis. The narrative analysis of these articles found that there is interplay between the key gut microbiota, related metabolites and inflammation factors, which modulate the development and progression of NAFLD. In addition, the results of meta-analysis showed that probiotic supplementation significantly decreased tumor necrosis factor-α (TNF-α) in NAFLD patients (standardized mean difference (SMD) = -0.52, confidence interval (CI): -0.86 to -0.18, and p = 0.003) and C-reactive protein (CRP) (SMD = -0.62, CI: -0.80 to -0.43, and p < 0.001). However, whether therapies can target TNF-α and CRP in order treat NAFLD still needs further investigation. Therefore, these results suggest that the interaction of the key gut microbiota, related metabolites and inflammation factors with NAFLD may provide a novel therapeutic target for the clinical and pharmacological treatment of NAFLD.