Hepatoenteric Protective Effect of Melanin from Inonotus hispidus on Acute Alcoholic Liver Injury in Mice.

SCOPE: Alcoholic liver disease (ALD) is a common disease with a high incidence. Because traditional drugs have obvious side effects, it is desired to find more effective drugs. METHODS AND RESULTS: This study investigates the effects of melanin from Inonotus hispidus fruiting bodies (IHFM) on acute alcoholic injury mice and detects the protective mechanisms via the gut-microbiota-liver axis. The results show that IHFM alleviates mouse liver injury by enhancing alcohol metabolism capacity, reducing inflammation response level and strengthening antioxidant activities. IHFM also improves mouse liver injury by activating Nrf2 signaling pathway and inhibiting toll-like receptor4 (TLR4)/nuclear factor-κß (NF-κß) signaling pathway. Furthermore, 16S amplification sequencing shows that IHFM can significantly increase the relative abundance of Lactobacillus reuteri and Lactobacillus johnsonii. The relative abundance of L. reuteri positively correlates with an antioxidant index, while negatively correlates with inflammatory factors. CONCLUSION: IHFM can protect mice from acute alcoholic liver injury by upregulating the Nrf2 signaling pathway, downregulating the TLR4/NF-κß signaling pathway, and upregulating the relative abundance of L. reuteri and L. johnsonii, representing a step forward in the development of IHFM.

[Distribution Characteristics and Source Analysis of Atmospheric Mercury Speciation in Suzhou].

To explore the variation of mercury in the atmosphere in Suzhou, continuous monitoring of gaseous element mercury (GEM), gaseous oxidized mercury (GOM), and particulate bound mercury (PBM) was conducted from January 1 to December 31, 2018, in Suzhou. The weights trajectory analysis method (CWT) and concentration rose were used to analyze the atmospheric mercury sources and concentration variation. The results showed that during the monitoring period, the concentration ranges of GEM, GOM, and PBM in Suzhou were 0-53.3 ng·m-3, 0-256 pg·m-3, and 0-5208 pg·m-3, respectively. The corresponding annual average concentrations of the three mercury species were (2.57±2.09) ng·m-3, (5.27±15.7) pg·m-3, and (16.0±157) pg·m-3, respectively. GEM was the main component of atmospheric mercury in Suzhou. During the monitoring period, the average concentration of GEM in Suzhou was highest in winter, higher in spring than in autumn, and lowest in summer. According to the CWT, the mercury-containing air mass in spring and winter predominantly originated from inland; in summer, it mainly originated from the local area, the Yellow Sea, and the East China Sea, and in autumn from inland, the Yellow Sea, and the Bohai Sea. The wind and mercury rose charts showed that atmospheric mercury concentrations were higher from inland and lower from the ocean. During the monitoring period, the average concentrations of GEM and PBM in Suzhou were lower during the day than the night. The diurnal variation of GEM and PBM was significantly and strongly correlated with solar radiation, humidity, and air temperature. The average concentration of GOM showed multiple peaks and valleys in one day. Some peaks were caused by fuel oil combustion emissions, and some by O3 oxidation with GEM.

RPS24c Isoform Facilitates Tumor Angiogenesis Via Promoting the Stability of MVIH in Colorectal Cancer.

BACKGROUND: Colorectal cancer (CRC) is the second leading cause of death worldwide, and distant metastasis is responsible for the poor prognosis in patients with advanced-stage CRC. RPS24 (ribosomal protein S24) as a ribosomal protein, multiple transcript variant encoding different isoforms have been found for this gene. Our previous studies have demonstrated that RPS24 is overexpressed in CRC. However, the mechanisms underlying the role of RPS24 in tumor development have not been fully defined. METHODS: Expression of RPS24 isoforms and lncRNA MVIH in CRC tissues and cell lines were quantified by real-time PCR or western blotting assay. Endothelial tube formation assay was performed to determine the effect of RPS24 on tumor angiogenesis. The cell viability of HUVEC was determined by MTT assay, and the migration and invasion ability of HUVEC were detected by transwell assay. PGK1 secretion was tested with a specific ELISA kit. RESULTS: Here, we found that RPS24c isoform was a major contributor to tumor angiogenesis, a vital process in tumor growth and metastasis. Real-time PCR revealed that RPS24c isoform was highly expressed in CRC tissues, while other isoforms are present in both normal and CRC tissues with no statistical difference. Moreover the change of RPS24 protein level is mainly due to the fluctuation of RPS24c. Furthermore, we observed that silencing RPS24c could decrease angiogenesis by inhibiting tubule formation, HUVEC cell proliferation and migration. Additionally, we investigated the molecular mechanisms and demonstrated that RPS24c mRNA interacted with lncRNA MVIH, the binding-interaction enhanced the stability of each other, thereby activated angiogenesis by inhibiting the secretion of PGK1. CONCLUSION: RPS24c facilitates tumor angiogenesis via the RPS24c/MVIH/PGK1 pathway in CRC. RPS24c inhibition may be a novel option for anti-vascular treatment in CRC.

Design and performance analysis of a single-unit polarizing beam-splitting prism based on negative refraction in a uniaxial crystal.

A new type of single-unit polarizing beam-splitting prism is proposed based on negative refraction and total internal reflection in uniaxial crystals. The performance of the proposed design is studied theoretically and experimentally using a calcite prism. The results indicate that the single-unit negative refraction polarization-splitting prism can yield a maximum splitting angle of 19.5° (for an incident light wavelength of 633 nm), whereby the splitting angle is insensitive to changes in the incidence angle. The proposed structure exhibits good stability and reliability. The design is beneficial to application in special working environments involving intense vibration and increased radiation.

AIM-SNPtag: A computationally efficient approach for developing ancestry-informative SNP panels.

Inferring an individual's ancestry or group membership using a small set of highly informative genetic markers is very useful in forensic and medical genetics. However, given the huge amount of SNP data available from a diverse of populations, it is challenging to develop informative panels by exhaustively searching for all possible SNP combinations. In this study, we formulate it as an algorithm problem of selecting an optimal set of SNPs that maximizes the inference accuracy while minimizes the set size. Built on this conception, we develop a computational approach that is capable of constructing ancestry informative panels from multi-population genome-wide SNP data efficiently. We evaluated the performance of the method by comparing the panel size and membership inference accuracy of the constructed SNP panels to panels selected through empirical procedures in previous studies. For the membership inference of population groups including Asian, European, African, East Asian and Southeast Asian, a 36-SNP panel developed by our approach has an overall accuracy of 99.07%, and a 21-SNP subset of the panel has an overall accuracy of 95.36%. In comparison, an existing panel requires 74 SNPs to achieve an accuracy of 94.14% on the same set of population groups. We further apply the method to four subpopulations within Europe (Finnish, British, Spanish and Italian); a 175-SNP panel can discriminate individuals of those European subpopulations with an accuracy of 99.36%, of which a 68-SNP subset can achieve an accuracy of 95.07%. We expect our method to be a useful tool for constructing ancestry informative markers in forensic genetics.

Risk factors analysis for hyperuricemic nephropathy among CKD stages 3-4 patients: an epidemiological study of hyperuricemia in CKD stages 3-4 patients in Ningbo, China.

OBJECTIVE: Uric acid (UA) is a risk marker of CKD and SUA level in CKD 3-4 patients closely correlates with hyperuricemic nephropathy (HN) morbidity. This study was designed to evaluate the risk factors for HN in CKD 3-4 patients. METHODS: The 461 CKD 3-4 patients were recruited and all patients were divided into three groups (24 h UUA normal, underexeret, and overproduct type groups) according to the 24 h UUA level after receiving low purine food for five days. Clinical and biochemical characteristics of CKD patients were collected for the logistic regression analysis. Correlation analysis of the mRNA relative expression level of hUAT and hURAT1 with serum UA (SUA) level also was evaluated. RESULTS: There were significant increases in characteristics including average age, waist-to-height ratio (WHR), SUA levels, HN ratio, TG/HDL ratio, body mass index (BMI), blood pressure (BP), uNgal/Cr. ratio, and uKim-1/Cr. ratio in overproduct type group in comparison with the other two groups. Logistic regression analysis showed SUA, CHO, uKim-1/Cr. ratio and uNgal/Cr. ratio were independent and multiple risk factors for HN. Moreover, hUAT and hURAT1 mRNA relative expression levels were significantly correlated with SUA level in the underexeret type CKD 3-4 patients. CONCLUSIONS: These results showed SUA and other characteristics contributed to HN morbidity in CKD 3-4 patients.

Identification of eight key miRNAs associated with renal cell carcinoma: A meta-analysis.

Renal cell carcinoma (RCC) is the most common renal carcinoma in the human kidney. To date, to the best of our knowledge, there are no biomarkers for the early monitoring and diagnosis of RCC patients. The present study aimed to develop deeper insight into the molecular mechanisms of microRNAs (miRNAs/miRs) in the regulation of RCC development and to reveal candidate miRNA biomarkers in human RCC. A meta-analysis was used to integrate the published and independent RCC miRNA expression profiling investigations that compared the miRNA expression profiles in RCC samples with control samples. The meta-signature miRNA target genes were then predicted in TargetScan. The predicted targets were further analyzed using Gene Ontology and pathway enrichment analysis with the Database for Annotation, Visualization and Integrated Discovery online tool, and then the transcription factors of meta-signature miRNA target genes were identified in Tfacts. A total of 7 publicly available and independent RCC miRNA expression profiling datasets were collected, and 2 upregulated (hsa-miR-155-5p and hsa-miR-210-5p) and 6 downregulated (hsa-miR-138-5p, hsa-miR-141-5p, hsa-miR-200c-5p, hsa-miR-362-5p, hsa-miR-363-5p and hsa-miR-429) meta-signature miRNAs in renal carcinoma were identified. The targeted gene enrichment analysis indicated that the meta-signature miRNAs may influence several pathways that participate in cancerogenesis, including the 'rap1 signaling pathway', 'renal cell carcinoma' and 'microRNAs in cancer'. Overall, the present meta-analysis identified 2 upregulated and 6 downregulated meta-signature miRNAs from 7 renal carcinoma datasets, the dysregulated miRNAs that may contribute to kidney carcinoma development. This research may reveal candidate miRNA biomarkers in human RCC.

Musashi 2 contributes to the stemness and chemoresistance of liver cancer stem cells via LIN28A activation.

Accumulating evidence suggests that cancer stem cells (CSCs), a small subset of cancer cells, are responsible for tumor initiation, progression, relapse and metastasis. Musashi 2 (MSI2), a RNA-binding protein, was proposed to be a potent oncogene playing key roles in myeloid leukemia and gastrointestinal malignancies. However, it remains elusive how MSI2 regulates stem cell features in HCC. Herein, we demonstrated that MSI2 was highly expressed in liver CSCs. Overexpression or knockdown of MSI2 altered CSC-related gene expression, self-renewal as well as resistance to chemotherapy in HCC cell lines. In mouse xenograft models, MSI2 could markedly enhance tumorigenicity. Mechanistically, overexpression of MSI2 resulted in the upregulation of Lin28A. Stemness and chemotherapeutic drug resistance induced by MSI2 overexpression were dramatically reduced by Lin28A knockdown. Moreover, MSI2 and LIN28A levels positively correlated with the clinical severity and prognosis in HCC patients. In conclusion, MSI2 might play a crucial role in sustaining stemness and chemoresistance of liver CSCs via LIN28A-dependent manner in HCC. Our findings revealed that MSI2 and Lin28A might be used as potential therapeutic targets for eradicating liver CSCs.

Association of non-alcoholic fatty liver disease with major adverse cardiovascular events: A systematic review and meta-analysis.

Increasing evidence connects non-alcoholic fatty liver disease (NAFLD) to cardiovascular disease (CVD). The aim of this study is to assess whether and to what extent the excess risk of CVD is conferred by NAFLD in a meta-analysis. We systematically searched PubMed, EmBase, Web of Science, and Cochrane Library for reports published between 1965 and July 3, 2015. Studies that reported data on association between NAFLD and adverse cardiovascular events or mortality were included. Thirty-four studies (164,494 participants, 21 cross-sectional studies, and 13 cohort studies) were included. NAFLD was not associated with overall mortality (HR = 1.14, 95% CI: 0.99-1.32) and CVD mortality (HR = 1.10, 95% CI: 0.86-1.41). However, NAFLD was associated with an increased risk of prevalent (OR = 1.81, 95% CI: 1.23-2.66) and incident (HR = 1.37, 95% CI: 1.10-1.72) CVD. For some specific CVDs, NAFLD was associated with an increased risk of prevalent (OR = 1.87, 95% CI: 1.47-2.37) and incident (HR = 2.31, 95% CI: 1.46-3.65) coronary artery disease (CAD), prevalent (OR = 1.24, 95% CI: 1.14-1.36) and incident (HR = 1.16, 95% CI: 1.06-1.27) hypertension, and prevalent (OR = 1.32, 95% CI: 1.07-1.62) atherosclerosis. In conclusion, the presence of NAFLD is associated with an increased risk of major adverse cardiovascular events, although it is not related to mortality from all causes or CVD.

Hookworm Anemia in a Peritoneal Dialysis Patient in China.

Hookworm infections as well as other intestinal nematodiases are endemic in China. In this case, a 70-year-old male showed symptoms of chest tightness, shortness of breath, and both lower extremities edema. The diagnostic result was chronic renal insufficiency, chronic kidney disease (5th stage), and renal anemia at first. Then, he received treatment with traditional drugs. However, this treatment did not help to alleviate the symptoms of the patient significantly. The results of gastroendoscopy showed hookworms in the duodenum, also confirmed by pathology examination. Anemia was markedly ameliorated after eliminating the parasites. The results mentioned above suggested that ancylostomiasis was the leading causes of anemia in this patient, and the etiology of anemia in uremic patients should be systematically considered. Especially when anemia could not be cured by regular treatments, rare diseases should be investigated.

ADRB2 signaling promotes HCC progression and sorafenib resistance by inhibiting autophagic degradation of HIF1α.

BACKGROUND & AIMS: Considerable evidence suggests that adrenergic signaling played an essential role in tumor progression. However, its role in hepatocellular carcinoma (HCC) and the underlying mechanisms remain unknown. METHODS: The effect of adrenaline in hepatocarcinogenesis was observed in a classical diethylnitrosamine-induced HCC mouse model. Effects of ADRB2 signaling inhibition in HCC cell lines were analyzed in proliferation, apoptosis, colony formation assays. Autophagy regulation by ADRB2 was assessed in immunoblotting, immunofluorescence and immunoprecipitation assays. In vivo tumorigenic properties and anticancer effects of sorafenib were examined in nude mice. Expression levels of ADRB2 and hypoxia-inducible factor-1α (HIF1α) in 150 human HCC samples were evaluated by immunohistochemistry. RESULTS: We uncovered that adrenaline promoted DEN-induced hepatocarcinogenesis, which was reversed by the ADRB2 antagonist ICI118,551. ADRB2 signaling also played an essential role in sustaining HCC cell proliferation and survival. Notably, ADRB2 signaling negatively regulated autophagy by disrupting Beclin1/VPS34/Atg14 complex in an Akt-dependent manner, leading to HIF1α stabilization, reprogramming of HCC cells glucose metabolism, and the acquisition of resistance to sorafenib. Conversely, inhibition of ADRB2 signaling by ICI118,551, or knockdown ADRB2 expression, led to enhanced autophagy, HIF1α destabilization, tumor growth suppression, and improved anti-tumor activity of sorafenib. Consistently, ADRB2 expression correlated positively with HIF1α in HCC specimens and was associated with HCC outcomes. CONCLUSIONS: Our results uncover an important role of ADRB2 signaling in regulating HCC progression. Given the efficacy of ADRB2 modulation on HCC inhibition and sorafenib resistance, adrenoceptor antagonist appears to be a putative novel treatment for HCC and chemoresistance. LAY SUMMARY: ADRB2 signaling played an essential role in sustaining hepatocellular carcinoma cell proliferation and survival. ADRB2 signaling negatively regulated autophagy, leading to hypoxia-inducible factor-1α stabilization, reprogramming of hepatocellular carcinoma cells glucose metabolism, and the acquisition of resistance to sorafenib. Adrenoceptor antagonist appears to be a putative novel treatment for hepatocellular carcinoma and chemoresistance.

Serum lipid levels and suicidality: a meta-analysis of 65 epidemiological studies.

BACKGROUND: We conducted a systematic review and meta-analysis to determine the association between serum lipid levels and suicidality, as evidence from previous studies has been inconsistent. METHODS: We identified relevant studies by searching Medline, Web of Science, EMBASE, and the Cochrane Database of Systematic Reviews (1980 to Dec. 5, 2014). Studies assessing the association between serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and/or triglycerides (TG) levels and suicidality were included. We used a random-effects model to take into account heterogeneity among studies. RESULTS: We included 65 studies with a total of 510 392 participants in our analysis. Compared with the nonsuicidal patients, suicidal patients had significantly lower serum TC (weighted mean difference [WMD] -22.35, 95% confidence interval [CI] -27.95 to -16.75), LDL-C (WMD -19.56, 95% CI -26.13 to -12.99) and TG (WMD -23.40, 95% CI -32.38 to -14.42) levels, while compared with the healthy controls, suicidal patients had significantly lower TC (WMD -24.75, 95% CI -27.71 to -21.78), HDL-C (WMD -1.75, 95% CI -3.01 to -0.48) and LDL-C (WMD -3.85, 95% CI -7.45 to -0.26) levels. Furthermore, compared with the highest serum TC level category, a lower serum TC level was associated with a 112% (95% CI 40%-220%) higher risk of suicidality, including a 123% (95% CI 24%-302%) higher risk of suicide attempt and an 85% (95 CI 7%-221%) higher risk of suicide completion. The cut-off values for low and high serum TC level were in compliance with the categories reported in the original studies. LIMITATIONS: A major limitation of our study is the potential heterogeneity in most of the analyses. In addition, the suicidal behaviour was examined using different scales or methods across studies, which may further explain heterogeneity among the studies. CONCLUSION: We identified an inverse association between serum lipid levels and suicidality. More mechanistic studies are needed to further explain this association.

Cryoablation Versus Radiofrequency Ablation for Hepatic Malignancies: A Systematic Review and Literature-Based Analysis.

The aim of this study is to summarize and quantify the current evidence on the therapeutic efficacy of cryoablation compared with radiofrequency ablation (RFA) in patients with hepatic malignancies in a meta-analysis.Data were collected by searching PubMed, Scopus, and Cochrane databases for reports published up to May 26, 2015. Studies that reported data on comparisons of therapeutic efficacy of cryoablation and RFA were included. The random effects model was used to estimate the pooled relative risks of events comparing cryoablation to RFA for therapy of hepatic malignancies.Seven articles met the inclusion criteria and were included in the meta-analysis. The meta-analysis showed that there was no statistically significant difference in mortality of at least 6 months (odds ratio [OR] = 1.00, 95% confidence interval [CI]: 0.68-1.49) and local tumor progression according to both patients (OR = 1.64, 95% CI: 0.57-4.74) and tumors (OR = 1.81, 95% CI: 0.74-4.38) between cryoablation group and RFA group. However, the risk of complications was significantly higher in the cryoablation group than that in the RFA group (OR = 2.93, 95% CI: 1.15-7.46). When considering the specific complications, only thrombocytopenia (OR = 51.13, 95% CI: 2.92-894.21) and renal impairment (OR = 4.19, 95% CI: 1.34-13.11) but not other complications were significantly higher in the cryoablation group.In conclusion, the 2 methods had almost equal mortality and nonsignificant difference in local tumor progression, with higher risk of complications in cryoablation. Further large-scale, well-designed randomized controlled trials are needed to identify the current findings and investigate the long-term effects of cryoablation compared with RFA for therapy of hepatic malignancies.

Socio-economic position as an intervention against overweight and obesity in children: a systematic review and meta-analysis.

Studies that investigated the association between socio-economic position (SEP) and obesity in children suggest inconsistent results. The aim of this study is to summarize and quantify the current evidence on SEP and risks of overweight and obesity in children aged 0-15 years. Relevant studies published between 1990 to Sep 4, 2014 were searched in Medline, Web of Science, Embase, and the Cochrane Database of Systematic Reviews. Risk estimates from individual studies were pooled using random-effects models, according to lowest vs the highest SEP category. A total of 62 articles were included in the meta-analysis. The odds of both overweight risk and obesity risk were higher in the children with lowest SEP than in those with highest SEP (OR, 1.10, 95% CI: 1.03-1.17, and OR, 1.41, 95% CI: 1.29-1.55, respectively). Sub-group analyses showed that the inverse relationships between SEP and childhood overweight and obesity were only found in high-income countries and in more economic developed areas. In conclusion, our study suggests that children with lower SEP had higher risks of overweight and obesity, and the increased risks were independent of the income levels of countries.

Family history of autoimmune diseases is associated with an increased risk of autism in children: A systematic review and meta-analysis.

BACKGROUND: We conducted a systematic review and meta-analysis to summarize the current evidence on the relationship between family history of autoimmune diseases (ADs) and risk of autism in children, as current evidence suggests inconsistent results. METHODS: We identified relevant studies by searching PubMed, EmBase, and Web of Science databases up to Dec 2014. Risk estimates from individual studies were pooled using random-effects models. Sub-groups analyses were conducted by some study-level factors. Publication bias was assessed by funnel plots, Egger's regression test and Begg-Mazumdar test. RESULTS: A total of 11 articles were included in the meta-analysis, including 3 cohort studies, 6 case-control studies, and 2 cross-sectional studies. The meta-analysis showed that family history of all ADs combined was associated with a 28% (95% CI: 12-48%) higher risk of autism in children. For some specific ADs, evidence synthesis for risk of autism in children showed a statistically significant association with family history of hypothyroidism (OR=1.64, 95% CI: 1.07-2.50), type 1 diabetes (OR=1.49, 95% CI: 1.23-1.81), rheumatoid arthritis (OR=1.51, 95% CI: 1.19-1.91), and psoriasis (OR=1.59, 95% CI: 1.28-1.97). The results varied in some subgroups. CONCLUSION: An overall increased risk of autism in children with family history of ADs was identified. More mechanistic studies are needed to further explain the association between family history of ADs and increased risk of autism in children.

Omega-3 fatty acids intake and risks of dementia and Alzheimer's disease: a meta-analysis.

BACKGROUND: We systematically reviewed the association of omega-3 fatty acids intake with the incidence of dementia and Alzheimer's disease (AD) in this meta-analysis of prospective cohort studies, as evidence from previous studies suggests inconsistent results. METHODS: We identified relevant studies by searching PubMed, EmBase, and Web of Science databases up to June 2013. Prospective cohort studies reporting on associations of dietary intake of long-chain omega-3 fatty acids or fish with the incidence of dementia and AD were eligible. RESULTS: Comparing the highest to lowest category of long-chain omega-3 fatty acids intake and fish intake, the pooled relative risks (RRs) for dementia were 0.97 (95% CI 0.85-1.10) and 0.84 (95% CI 0.71-1.01), respectively. Evidence synthesis for AD risk did not show a statistically significant association with long-chain omega-3 fatty acids intake (RR=0.89, 95% CI 0.74-1.08). However, a higher intake of fish was associated with a 36% (95% CI 8-56%) lower risk of AD. Dose-response meta-analysis showed that an increment of 100g per week of fish intake was associated with an 11% lower risk of AD (RR=0.89, 95% CI 0.79-0.99). There was limited evidence of heterogeneity across studies or within subgroups. CONCLUSION: A higher intake of fish was associated with a lower risk of AD. However, there was no statistical evidence for similar inverse association between long-chain omega-3 fatty acids intake and risk of dementia or AD, nor was there inverse association between fish intake and risk of dementia.

Epigenetically silenced long noncoding-SRHC promotes proliferation of hepatocellular carcinoma.

PURPOSE: To investigate the expression of SRHC and the role of SRHC in the pathogenesis of hepatocellular carcinoma (HCC). METHODS: We analyzed HCC samples and matched non-tumor liver tissues (controls) collected from 81 patients who underwent hepatectomy in Shanghai, China. The expression levels of SRHC were determined by quantitative reverse-transcription polymerase chain reaction. Statistical analyses were used to associate the levels of SRHC with tumor features and patient outcomes. RESULTS: We found that a lower SRHC expression level was significantly more frequent in tissues with a high serum a-fetoprotein level (positive, >20 µg/L, P = 0.004) and a low degree of differentiated tumors (poorly differentiated, P = 0.017). Furthermore, we found that the promoter region of SRHC contains a CpG-rich island and that SRHC is down-regulated in tumors by DNA methylation. CONCLUSION: Here, we identified a new long noncoding RNA designated as SRHC that is capable of inhibiting cancer proliferation and is down-regulated in tumors at least partly by DNA methylation.

Platelets promote tumour metastasis via interaction between TLR4 and tumour cell-released high-mobility group box1 protein.

Increasing evidence suggests that TLR4 expression by tumour cells promotes tumour progression, but it is unclear whether TLR4 is involved in metastasis. Here we show that TLR4 deficiency significantly diminishes experimental lung metastasis without affecting primary tumour growth. Bone marrow transplantation experiment and application of antiplatelet agents in mice demonstrate that TLR4 on platelets plays an important role in metastasis. TLR4 is critical for platelet-tumour cell interaction in vitro. Furthermore, high-mobility group box1 (HMGB1) neutralization attenuates platelet-tumour cell interaction in vitro and metastasis in vivo in a TLR4-dependent manner, indicating that tumour cell-released HMGB1 is the key factor that interacts with TLR4 on platelets and mediates platelet-tumour cell interaction, which promotes metastasis. These findings demonstrate a mechanism by which platelets promote tumour cell metastasis and suggest TLR4, and its endogenous ligand HMGB1 as targets for antimetastatic therapies.

Effects of spironolactone on dialysis patients with refractory hypertension: a randomized controlled study.

The purpose of this study was to evaluate the effects of spironolactone on dialysis patients with refractory hypertension and possible adverse effects. This was a 12-week prospective, randomized, double-blind trial of 82 patients randomly assigned to 12-week treatment with 25 mg/d spironolactone or placebo as add-on therapy. Visits were scheduled at the start of treatment and after 12 weeks. Measurements of 24-hour ambulatory blood pressure (BP) monitoring and morning BP were performed. After 12 weeks, spironolactone significantly improved refractory hypertension. Average placebo-corrected morning BP was reduced by 16.7/7.6 mm Hg. Mean 24-hour ambulatory BP was reduced by 10.9/5.8 mm Hg. In contrast, serum aldosterone levels in the spironolactone group slightly increased and serum potassium levels insignificantly increased. This study has demonstrated that spironolactone (50 mg) safely and effectively reduces BP in patients with refractory hypertension undergoing dialysis.