DEC1 is involved in circadian rhythm disruption-exacerbated pulmonary fibrosis.

BACKGROUND: The alveolar epithelial type II cell (AT2) and its senescence play a pivotal role in alveolar damage and pulmonary fibrosis. Cell circadian rhythm is strongly associated with cell senescence. Differentiated embryonic chondrocyte expressed gene 1 (DEC1) is a very important circadian clock gene. However, the role of DEC1 in AT2 senescence and pulmonary fibrosis was still unclear. RESULTS: In this study, a circadian disruption model of light intervention was used. It was found that circadian disruption exacerbated pulmonary fibrosis in mice. To understand the underlying mechanism, DEC1 levels were investigated. Results showed that DEC1 levels increased in lung tissues of IPF patients and in bleomycin-induced mouse fibrotic lungs. In vitro study revealed that bleomycin and TGF-ß1 increased the expressions of DEC1, collagen-I, and fibronectin in AT2 cells. Inhibition of DEC1 mitigated bleomycin-induced fibrotic changes in vitro and in vivo. After that, cell senescence was observed in bleomycin-treated AT2 cells and mouse models, but these were prevented by DEC1 inhibition. At last, p21 was confirmed having circadian rhythm followed DEC1 in normal conditions. But bleomycin disrupted the circadian rhythm and increased DEC1 which promoted p21 expression, increased p21 mediated AT2 senescence and pulmonary fibrosis. CONCLUSIONS: Taken together, circadian clock protein DEC1 mediated pulmonary fibrosis via p21 and cell senescence in alveolar epithelial type II cells.

LncRNA SNHG26 promotes gastric cancer progression and metastasis by inducing c-Myc protein translation and an energy metabolism positive feedback loop.

Metastasis is a bottleneck in cancer treatment. Studies have shown the pivotal roles of long noncoding RNAs (lncRNAs) in regulating cancer metastasis; however, our understanding of lncRNAs in gastric cancer (GC) remains limited. RNA-seq was performed on metastasis-inclined GC tissues to uncover metastasis-associated lncRNAs, revealing upregulated small nucleolar RNA host gene 26 (SNHG26) expression, which predicted poor GC patient prognosis. Functional experiments revealed that SNHG26 promoted cellular epithelial-mesenchymal transition and proliferation in vitro and in vivo. Mechanistically, SNHG26 was found to interact with nucleolin (NCL), thereby modulating c-Myc expression by increasing its translation, and in turn promoting energy metabolism via hexokinase 2 (HK2), which facilitates GC malignancy. The increase in energy metabolism supplies sufficient energy to promote c-Myc translation and expression, forming a positive feedback loop. In addition, metabolic and translation inhibitors can block this loop, thus inhibiting cell proliferation and mobility, indicating potential therapeutic prospects in GC.

The Impact of Nursing Interventions on the Treatment Outcomes of Renal Cell Carcinoma with Postoperative Interleukin-2 and Recombinant Human Interferon.

Objective: This study investigates the impact of nursing interventions on treatment outcomes and adverse reaction rates in renal cell carcinoma (RCC) patients treated postoperatively with Interleukin-2 and recombinant human Interferon. Methods: In a retrospective analysis of 90 RCC patients, 43 received standard care (control group), while 47 received additional nursing interventions (intervention group), including psychological care, vital signs monitoring, dietary care, adverse reaction management, and post-discharge care. Patients with concurrent major diseases or other malignancies were excluded. Key assessments included clinical symptom improvement, treatment efficacy, and postoperative adverse reactions. Results: Among the 90 participants, no significant demographic differences were found between the two groups. The intervention group showed significant improvements in fever resolution, leukocyte normalization, and shorter hospital stays. The overall treatment effectiveness was similar in both groups (90.7% in the intervention group vs 91.5% in the control group). However, the intervention group experienced significantly fewer postoperative adverse reactions, including fever, gastrointestinal symptoms, bone marrow suppression, and neurological abnormalities (6.3% vs 23.2%). Conclusion: The study suggests that nursing interventions can improve treatment outcomes by reducing postoperative adverse reactions in RCC patients receiving postoperative Interleukin-2 and recombinant human Interferon. The overall effectiveness of treatment and care was comparable between the groups. Further extensive studies are needed to confirm these findings and fully understand the impact of nursing interventions on RCC patient outcomes.

BMAL1/p53 mediating bronchial epithelial cell autophagy contributes to PM2.5-aggravated asthma.

BACKGROUND: Fine particulate matter (PM2.5) is associated with increased incidence and severity of asthma. PM2.5 exposure disrupts airway epithelial cells, which elicits and sustains PM2.5-induced airway inflammation and remodeling. However, the mechanisms underlying development and exacerbation of PM2.5-induced asthma were still poorly understood. The aryl hydrocarbon receptor nuclear translocator-like protein 1 (BMAL1) is a major circadian clock transcriptional activator that is also extensively expressed in peripheral tissues and plays a crucial role in organ and tissue metabolism. RESULTS: In this study, we found PM2.5 aggravated airway remodeling in mouse chronic asthma, and exacerbated asthma manifestation in mouse acute asthma. Next, low BMAL1 expression was found to be crucial for airway remodeling in PM2.5-challenged asthmatic mice. Subsequently, we confirmed that BMAL1 could bind and promote ubiquitination of p53, which can regulate p53 degradation and block its increase under normal conditions. However, PM2.5-induced BMAL1 inhibition resulted in up-regulation of p53 protein in bronchial epithelial cells, then increased-p53 promoted autophagy. Autophagy in bronchial epithelial cells mediated collagen-I synthesis as well as airway remodeling in asthma. CONCLUSIONS: Taken together, our results suggest that BMAL1/p53-mediated bronchial epithelial cell autophagy contributes to PM2.5-aggravated asthma. This study highlights the functional importance of BMAL1-dependent p53 regulation during asthma, and provides a novel mechanistic insight into the therapeutic mechanisms of BMAL1. Video Abstract.

Blockade of phosphotyrosine pathways suggesting SH2 superbinder as a novel therapy for pulmonary fibrosis.

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible fibrotic disease with high mortality. Currently, pirfenidone and nintedanib are the only approved drugs for IPF by the U.S. Food and Drug Administration (FDA), but their efficacy is limited. The activation of multiple phosphotyrosine (pY) mediated signaling pathways underlying the pathological mechanism of IPF has been explored. A Src homology-2 (SH2) superbinder, which contains mutations of three amino acids (AAs) of natural SH2 domain has been shown to be able to block phosphotyrosine (pY) pathway. Therefore, we aimed to introduce SH2 superbinder into the treatment of IPF. Methods: We analyzed the database of IPF patients and examined pY levels in lung tissues from IPF patients. In primary lung fibroblasts obtained from IPF patient as well as bleomycin (BLM) treated mice, the cell proliferation, migration and differentiation associated with pY were investigated and the anti-fibrotic effect of SH2 superbinder was also tested. In vivo, we further verified the safety and effectiveness of SH2 superbinder in multiple BLM mice models. We also compared the anti-fibrotic effect and side-effect of SH2 superbinder and nintedanib in vivo. Results: The data showed that the cytokines and growth factors pathways which directly correlated to pY levels were significantly enriched in IPF. High pY levels were found to induce abnormal proliferation, migration and differentiation of lung fibroblasts. SH2 superbinder blocked pY-mediated signaling pathways and suppress pulmonary fibrosis by targeting high pY levels in fibroblasts. SH2 superbinder had better therapeutic effect and less side-effect compare to nintedanib in vivo. Conclusions: SH2 superbinder had significant anti-fibrotic effects both in vitro and in vivo, which could be used as a promising therapy for IPF.

A New Predictive Model for the Prognosis of MDA5+ DM-ILD.

Purpose: The purpose of this study is to analyze clinical information and combine significant parameters to generate a predictive model and achieve a better prognosis prediction of dermatomyositis-associated interstitial lung disease with positive melanoma differentiation-associated gene 5 antibody (MDA5+ DM-ILD) and stratify patients according to prognostic risk factors appropriately. Methods: We retrospectively reviewed 63 patients MDA5+ DM-ILD who were treated in our hospital from January 2018 to January 2021. Our study incorporated most clinical characteristics in clinical practice to explore the associations and predictive functions of clinical characteristics and prognosis. Student's t-test, Mann-Whitney U-test, chi-squared test, Pearson correlation analysis, Cox regression analysis, R, receiver operating characteristic curves (ROC curves), and Kaplan-Meier survival curves were performed to identify independent predictors for the prognosis of MDA5+DM-ILD. Results: In all the 63 patients with MDA5+DM-ILD, 44 improved but 19 did not. Poor prognosis was found more frequently in patients who were older, clinically amyopathic variant of dermatomyositis (CADM), and/or with short duration, short interval of DM and ILD, long length of stay, fever, dyspnea, non-arthralgia, pulmonary infection, pleural effusion (PE), high total computed tomography scores (TCTs), ground-glass opacity (GGO), consolidation score, reticular score and fibrosis score, decreased forced vital capacity (FVC), forced expiratory volume in 1s (FEV1), albumin, A/G, glomerular filtration rate (GFR) and tumor necrosis factor α (TNFα), high titer of anti-MDA5, proteinuria, high levels of monocyte, lactate dehydrogenase (LDH), ferritin (FER), neuron specific enolase (NSE) and glucocorticoid, antibiotic, antiviral, and non-invasive positive pressure ventilation (NPPV). The multivariate Cox regression analysis demonstrated that duration, fever, PE, TCTs and aspartate transaminase (AST) were independent predictors of poor prognosis in patients with MDA5+DM-ILD. The nomogram model quantified the risk of 400-day death as: duration ≤ 4 months (5 points), fever (88 points), PE (21 points), TCTs ≥10 points (22 points), and AST ≥200 U/L (100 points) with high predictive accuracy and convenience. The ROC curves possessed good discriminative ability for combination of fever, PE, TCTs, and AST, as reflected by the area under curve (AUC) being.954, 95% CI 0.902-1.000, and sensitivity and specificity being 84.2 and 94.6%, respectively. Conclusion: We demonstrated that duration, fever, PE, TCTs, and AST could be integrated together to be independent predictors of poor prognosis in MDA5+ DM-ILD with highly predictive accuracy.

Effects of Ginsenoside Rb1 on Expressions of Phosphorylation Akt/Phosphorylation mTOR/Phosphorylation PTEN in Artificial Abnormal Hippocampal Microenvironment in Rats.

Artificial abnormal microenvironment caused by microperfusion of L-glutamate (Glu) and Ca2+ in the hippocampus results in neuron damage, which is closely related to cerebral ischemia. Ginsenoside Rb1, a compound from Panax notoginseng, was previously used to counter the artificial abnormal hippocampal environment in a microperfusion model. In addition, while the Akt/mTOR/PTEN signaling pathway has been shown to mediate neuronprotection in cerebral ischemia, whether this pathway is involved in the neuroprotection of ginsenoside Rb1 is unknown. Here SH-SY5Y cells exposed to OGD/R injury in treated with LY294002, ginsenoside Rb1, ginsenoside Rb1+ LY294002. Expressions of phosphorylation (P-)Akt/P-mTOR/P-PTEN (24 h after OGD/R) were detected by Western blotting. Effects were examined via the memory function of rats (by Morris water maze test), morphological changes in pyramidal cell (by histology), and mRNA expression (by qRT-PCR) and phosphorylation (P-) (by Western blotting and immunohistochemical staining) of Akt, P-mTOR, and P-PTEN in the hippocampus. The memory deficit of rats and pyramidal cellular necrosis and apoptosis in the CA1 region of hippocampus after microperfusion of Glu and Ca2+ were dose dependently alleviated by ginsenoside Rb1.Moreover,Western blot showed that ginsenoside Rb1 increased the expressions of P-Akt, P-mTOR and reduced P-PTEN in vivo and vitro. Thus, the potent neuroprotection of ginsenoside Rb1 in artificial abnormal microenvironment is, at least partially, related to the activation of P-AKT/P-mTOR signaling pathway and inhibition of P-PTEN protein.

CBX7 regulates stem cell-like properties of gastric cancer cells via p16 and AKT-NF-κB-miR-21 pathways.

BACKGROUND: Chromobox protein homolog 7 (CBX7), a member of the polycomb group (PcG) family of proteins, is involved in the regulation of cell proliferation and cancer progression. PcG family members, such as BMI, Mel-18, and EZH2, are integral constituents of the polycomb repressive complexes (PRCs) and have been known to regulate cancer stem cell (CSC) phenotype. However, the role of other PRCs' constituents such as CBX7 in the regulation of CSC phenotype remains largely elusive. This study was to investigate the role of CBX7 in regulating stem cell-like properties of gastric cancer and the underlying mechanisms. METHODS: Firstly, the role of CBX7 in regulating stem cell-like properties of gastric cancer was investigated using sphere formation, Western blot, and xenograft tumor assays. Next, RNA interference and ectopic CBX7 expression were employed to determine the impact of CBX7 on the expression of CSC marker proteins and CSC characteristics. The expression of CBX7, its downstream targets, and stem cell markers were analyzed in gastric stem cell spheres, common cancer cells, and gastric cancer tissues. Finally, the pathways by which CBX7 regulates stem cell-like properties of gastric cancer were explored. RESULTS: We found that CBX7, a constituent of the polycomb repressive complex 1 (PRC1), plays an important role in maintaining stem cell-like characteristics of gastric cancer cells via the activation of AKT pathway and the downregulation of p16. Spearman rank correlation analysis showed positive correlations among the expression of CBX7 and phospho-AKT (pAKT), stem cell markers OCT-4, and CD133 in gastric cancer tissues. In addition, CBX7 was found to upregulate microRNA-21 (miR-21) via the activation of AKT-NF-κB pathway, and miR-21 contributes to CBX7-mediated CSC characteristics. CONCLUSIONS: CBX7 positively regulates stem cell-like characteristics of gastric cancer cells by inhibiting p16 and activating AKT-NF-κB-miR-21 pathway.

Comparison of hepatocellular carcinoma conspicuity on hepatobiliary phase images with gadoxetate disodium vs. delayed phase images with extracellular cellular contrast agent.

OBJECTIVE: To compare the conspicuity of hepatocellular carcinoma (HCC) on hepatobiliary phase of gadoxetate disodium-enhanced vs. delayed phase of gadodiamide-enhanced MR images, relative to liver function. METHODS AND MATERIALS: We retrospectively identified 86 patients with newly diagnosed HCC between 2010 and 2013 and recorded the severity of liver disease by Child-Pugh class (CPC). 38 patients had gadodiamide-enhanced 5-min delayed and 48 had gadoxetate disodium-enhanced 20-min delayed hepatobiliary MR images. The conspicuity of 86 HCCs (mean size, 2.7 cm) was graded visually on a 3-point scale and quantified by liver-to-tumor contrast ratios (LTC). The relative liver parenchymal enhancement (RPE) was measured. For different CPCs, we compared the conspicuity of HCC and RPE between gadodiamide and gadoxetate. RESULTS: In patients with CPC A, the visual conspicuity and LTC of the 27 HCCs imaged with gadodiamide were significantly lower than those of the 38 HCCs with gadoxetate (P < 0.01, <0.01, respectively). RPE was lower in gadodiamide scans than gadoxetate scans (P < 0.01). Conversely, in patients with CPC B and C, HCCs appeared more frequently as definite hypointensity when imaged with gadodiamide (72.7%, 8/11) than gadoxetate (20%, 2/10, P = 0.03). LTC (mean 18.1 vs. 7.5, P = 0.04) and RPE (mean 75.5 vs. 45.4, P = 0.04) was significantly higher in the gadodiamide than gadoxetate scans. CONCLUSION: In patients with compromised liver function, hypointensity of HCC is more conspicuous in the gadodiamide delayed phase than the gadoxetate hepatobiliary phase. This likely reflects the high extracellular accumulation of gadodiamide and poor hepatocyte uptake of gadoxetate in patients with compromised liver function.

Appearance and Frequency of Gas Interface Artifacts Involving Small Bowel on Rapid-Voltage-Switching Dual-Energy CT Iodine-Density Images.

OBJECTIVE: The purpose of this study is to describe the appearance and frequency of gas interface artifacts in the jejunum that may mimic severe bowel disease on iodine-density images generated from rapid-voltage-switching dual-energy CT (DECT) scans. MATERIALS AND METHODS: Two readers retrospectively reviewed 108 consecutive abdominal rapid-voltage-switching DECT scans to record the presence of image artifacts in jejunal segments with different degrees of gaseous luminal filling, classified as full, partial, or absent. Readers viewed iodine-density images and corresponding 140-kVp and 65-keV virtual monochromatic images and classified the jejunal artifacts on iodine-density images as pseudostratified appearance of the bowel wall, pseudopneumatosis, pseudohyperenhancement, or pseudohypoenhancement. We correlated the presence of the artifacts with clinical features suggesting bowel disease. RESULTS: Image artifacts were found in 91 of 108 scans (84.3%), appeared in 148 of 265 jejunal segments (55.8%), and included each type except for pseudohypoenhancement. Artifacts occurred exclusively when gas was present in the bowel lumen and were seen in 59 of 59 (100%) fully gas-distended segments, 89 of 98 (90.8%) partially gas-distended segments, and none of 108 gas-absent segments (p < 0.0001). In fully and partially gas-distended jejunal segments (n = 157), 148 (94.3%) segments had two or more artifacts. None of the patients was found to have clinical bowel-related injury on follow-up of medical records. CONCLUSION: Pseudostratified appearance, pseudopneumatosis, and pseudohyperenhancement, but not pseudohypoenhancement, artifacts are common in gas-filled jejunal segments on iodine-density images generated from rapid-voltage-switching DECT scans and are not seen in the corresponding 140-kVp or 65-keV images. Knowledge of the appearance of such iodine-density image artifacts will avoid potential examination interpretation pitfalls.

Association of rs712 polymorphism in Kras gene 3'-luntranslated region and cancer risk: a meta-analysis.

PURPOSE: Mutation and polymorphism of Kras oncogene are considered as candidate risk factor and drug response predictor for cancer. However, the conclusions of accumulating reports related to the relationship of rs712 of Kras gene and risk of cancer remain nuclear. METHODS: We performed a meta-analysis including 6 eligible studies containing 1661 cases and 2139 controls to explore the role of rs712 in the risk of cancer development. RESULTS: Meta-analysis results showed that rs712 allele T (P(H)=0.08, odds ratio/OR=1.35, 95% confidence interval/ CI=1.17-1.55) and genotype TT (P(H)=0.174, OR=2.32, 95% CI=1.60-3.37), and allele T carrier genotype (GT/TT) (P(H)=0.14, OR=1.30, 95% CI=1.10-1.55) were strongly associated with cancer in Chinese population. No evidence of association was observed between rs712 and risk of cancer in overall population. CONCLUSION: The findings suggested that allele T, genotype TT and allele T carrier (GT/TT) of rs712 may increase susceptibility to cancer risk in Chinese population, and can be used as a genetic factor for evaluating risk of cancer.

UBTD1 induces cellular senescence through an UBTD1-Mdm2/p53 positive feedback loop.

The tumour suppressor p53 plays an important role in tumourigenesis. Besides inducing apoptosis, it regulates cellular senescence, which constitutes an important barrier to tumourigenesis. The mechanism of regulation of cellular senescence by p53 and its downstream pathway are poorly understood. Here, we report that the ubiquitin domain-containing 1 (UBTD1) gene, a new downstream target of p53, induces cellular senescence and acts as a novel tumour suppressor by a mechanism that depends on p53. Expression of UBTD1 increased upon cellular senescence induced by serial passageing of cultures, as well as by exposure to DNA-damageing drugs that induce premature senescence. Over-expression of UBTD1 induces senescence in human fibroblasts and cancer cells and attenuation of the transformed phenotype in cancer cells. UBTD1 is down-regulated in gastric and colorectal cancer tissues, and its lower expression correlates with a more aggressive phenotype and worse prognosis. Multivariate analysis revealed that UBTD1 expression was an independent prognostic factor for gastric cancer patients. Furthermore, UBTD1 increased the stability of p53 protein, by promoting the degradation of Mdm2 protein. Importantly, UBTD1 and p53 function mutually depend on each other in regulating cellular senescence and proliferation. Thus, our data suggest that, upon DNA damage, p53 induction by UBTD1 creates a positive feedback mechanism to further increase p53 expression. Our results establish UBTD1 as a regulator of cellular senescence that mediates p53 function, and provide insights into the mechanism of Mdm2 inhibition that impacts p53 dynamics during cellular senescence and tumourigenesis.

Association studies of ERCC1 polymorphisms with lung cancer susceptibility: a systematic review and meta-analysis.

BACKGROUND: Excision repair cross-complimentary group 1 (ERCC1) is an essential component of the nucleotide excision repair system that is responsible for repairing damaged DNA. Functional genetic variations in the ERCC1 gene may alter DNA repair capacity and modulate cancer risk. The putative roles of ERCC1 gene polymorphisms in lung cancer susceptibility have been widely investigated. However, the results remain controversial. OBJECTIVES: An updated meta-analysis was conducted to explore whether lung cancer risk could be attributed to the following ERCC1 polymorphisms: rs11615 (T>C), rs3212986 (C>A), rs3212961 (A>C), rs3212948 (G>C), rs2298881 (C>A). METHODS: Several major databases (MEDLINE, EMBASE and Scopus) and the Chinese Biomedical database were searched for eligible studies. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to measure the strength of associations. RESULTS: Sixteen studies with 10,106 cases and 13,238 controls were included in this meta-analysis. Pooled ORs from 11 eligible studies (8,215 cases vs. 11,402 controls) suggested a significant association of ERCC1 rs11615 with increased risk for lung cancer (homozygous: CC versus TT, OR = 1.24, 95% CI: 1.04-1.48, P = 0.02). However, such an association was disproportionately driven by a single study. Removal of that study led to null association. Moreover, initial analyses suggested that ERCC1 rs11615 exerts a more profound effect on the susceptibility of non-smokers to lung cancer than that of smokers. Moreover, no statistically significant association was found between remaining ERCC1 polymorphisms of interest and lung cancer risk, except for rs3212948 variation (heterozygous: CG vs.GG, OR = 0.78, 95% CI: 0.67-0.90, P = 0.001; dominant: CG/CC vs.GG, OR = 0.79, 95% CI: 0.69-0.91, P = 0.001). CONCLUSION: Overall, this meta-analysis suggests that ERCC1 rs3212948 G>C, but not others, is a lung cancer risk-associated polymorphism. Carefully designed studies with large sample size involving different ethnicity, smoking status, and cancer types are needed to validate these findings.

Combining automatic tube current modulation with adaptive statistical iterative reconstruction for low-dose chest CT screening.

OBJECTIVE: To reduce radiation dose while maintaining image quality in low-dose chest computed tomography (CT) by combining adaptive statistical iterative reconstruction (ASIR) and automatic tube current modulation (ATCM). METHODS: Patients undergoing cancer screening (n = 200) were subjected to 64-slice multidetector chest CT scanning with ASIR and ATCM. Patients were divided into groups 1, 2, 3, and 4 (n = 50 each), with a noise index (NI) of 15, 20, 30, and 40, respectively. Each image set was reconstructed with 4 ASIR levels (0% ASIR, 30% ASIR, 50% ASIR, and 80% ASIR) in each group. Two radiologists assessed subjective image noise, image artifacts, and visibility of the anatomical structures. Objective image noise and signal-to-noise ratio (SNR) were measured, and effective dose (ED) was recorded. RESULTS: Increased NI was associated with increased subjective and objective image noise results (P<0.001), and SNR decreased with increasing NI (P<0.001). These values improved with increased ASIR levels (P<0.001). Images from all 4 groups were clinically diagnosable. Images with NI = 30 and 50% ASIR had average subjective image noise scores and nearly average anatomical structure visibility scores, with a mean objective image noise of 23.42 HU. The EDs for groups 1, 2, 3 and 4 were 2.79 ± 1.17, 1.69 ± 0.59, 0.74 ± 0.29, and 0.37 ± 0.22 mSv, respectively. Compared to group 1 (NI = 15), the ED reductions were 39.43%, 73.48%, and 86.74% for groups 2, 3, and 4, respectively. CONCLUSIONS: Using NI = 30 with 50% ASIR in the chest CT protocol, we obtained average or above-average image quality but a reduced ED.

Non-association of IL-16 rs4778889 T/C polymorphism with cancer risk in Asians: a meta-analysis.

The IL-16 rs4778889 T/C polymorphism is associated with cancer risk. However, the results are conflicting. We performed this meta-analysis to derive a more precise estimation of the relationship. A comprehensive literature search was performed using PubMed, Embase and Web of Science databases. Odds ratio (OR) and 95% confidence interval (CI) were used to assess the strength of association. A total of 6 studies including 1,603 cases and 2,342 controls were identified. With all studies involved, results showed no statistically significant association between IL-16 rs4778889 T/C polymorphism and cancer risk (CC vs. CT+TT: OR=0.74, 95%CI: 0.55-1.02, Ph=0.15; CC+CT vs. TT: OR=0.89, 95%CI: 0.72-1.10, Ph =0.03; CC vs. TT: OR=0.73, 95%CI: 0.53- 1.00, Ph =0.08; CT vs. TT: OR=0.91, 95%CI: 0.79-1.05, Ph =0.08; C vs. T: OR=0.89, 95%CI: 0.74-1.07, Ph =0.02). In addition, the results were not changed when studies were stratified by cancer type. However, to verify our findings, it is essential to perform more well-designed studies with larger sample sizes in the future.

Candesartan inhibits LPS-induced expression increase of toll-like receptor 4 and downstream inflammatory factors likely via angiotensin II type 1 receptor independent pathway in human renal tubular epithelial cells.

The present study was to determine whether candesartan, an angiotensin II type 1 receptor blocker (ARB), exerts anti-inflammatory effects through inhibiting the toll-like receptor 4 (TLR4) pathway in human renal tubular epithelial cells (HKCs). The experiments were carried on cultured HKCs. By means of flow cytometry, Western blot, RT-PCR and ELISA techniques, the TLR4 protein, angiotensin II type 1 receptor (AT1R) and phosphorylated nuclear factor-kappa B (NF-κB) p65 protein level, mRNA levels of macrophage chemoattractant protein-1 (MCP-1) and regulated upon expression normal T cell expressed and secreted (RANTES), as well as MCP-1 and RANTES protein concentrations in conditioned media were measured. The results showed that lipopolysaccharide (LPS) upregulated the TLR4 protein level in cultured HKCs. Application of LPS increased NF-κB activation and induced release of its downstream inflammatory factors including MCP-1 and RANTES. Candesartan reversed LPS-induced upregulation of TLR4 expression, inhibited NF-κB activation, and reduced MCP-1 and RANTES release. However, knockdown on AT1R by siRNA did not change those previous effects of candesartan. These results suggest that candesartan-induced anti-inflammatory effect may be through a novel pathway, independent of AT1R.

Prevalence and distribution of metabolic syndrome in a southern Chinese population. Relation to exercise, smoking, and educational level.

OBJECTIVE: To investigate the prevalence and distribution of metabolic syndrome (MetS) and the impact of exercise, smoking, and educational level on the risk of MetS in a southern Chinese population. METHODS: A cross-sectional study was conducted in Zhuhai City, China from June to August 2012. Data on exercise, smoking, and educational level, anthropometric parameters, blood pressure, lipid, and glucose levels were collected. The prevalence of MetS (as defined by the International Diabetes Federation) was determined. Data necessary to evaluate MetS, the socio-economic characteristics, and lifestyle were obtained for 4645 subjects aged 18-75 years old. RESULTS: A total of 19.8% of the participants had MetS. The adjusted odds of having MetS were lower among males (adjusted odds: 0.75; 95% confidence interval [CI]: 0.57-1.01) compared with females. Those participants who currently smoked had a higher risk of developing MetS compared with non-smokers (adjusted odds: 1.61; 95% CI: 1.13-2.50). Those who had no physical exercise had a higher risk of developing MetS compared with those who physically exercised more than 60 minutes/day (adjusted odds: 1.51; 95% CI: 1.12-2.23;). Compared with those with no education, every category of attained educational level had a lower risk of developing MetS (p<0.001). CONCLUSION: The findings in this study revealed that current smokers had a greater risk of developing MetS compared with non-smokers. Increased physical activity and higher levels of education attained served as protective factors for the population.

Computed tomography perfusion in evaluating the therapeutic effect of transarterial chemoembolization for hepatocellular carcinoma.

AIM: To prospectively assess the changes in parameters of computed tomography (CT) perfusion pre- and post-transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC) in different treatment response groups, and to correlate the changes with various responses of HCC to TACE. METHODS: Thirty-nine HCC patients underwent CT perfusion examinations pre-(1 d before TACE) and post-treatment (4 wk after TACE). The response evaluation criteria for solid tumors (RECIST) were referred to when treatment responses were distributed. Wilcoxon-signed ranks test was used to compare the differences in CT perfusion parameters pre- and post-TACE for different response groups. RESULTS: Only one case had treatment response to CR and the CT perfusion maps of post-treatment lesion displayed complete absence of signals. In the PR treatment response group, hepatic artery perfusion (HAP), hepatic arterial fracture (HAF) and hepatic blood volume (HBV) of viable tumors post-TACE were reduced compared with pre-TACE (P = 0.001, 0.030 and 0.001, respectively). In the SD group, all CT perfusion parameters were not significantly different pre- and post-TACE. In the PD group, HAP, HAF, portal vein perfusion (PVP) and hepatic blood flow (HBF) of viable tumors post-TACE were significantly increased compared with pre-TACE (P = 0.005, 0.012, 0.035 and 0.005, respectively). CONCLUSION: Changes in CT perfusion parameters of viable tumors are correlated with different responses of HCC to TACE. Therefore, CT perfusion imaging is a feasible technique for monitoring response of HCC to TACE.