Self-Assembled Nanomaterials for Enhanced Phototherapy of Cancer.

Following the wisdom of nature to assemble functional candidates into exquisite nanoarchitectures is emerging as a promising field of research and has been widely applied in biomedical sciences. Owing to their excellent properties of structural controllability, functional diversity, dynamic adjustability, and prominent biocompatibility, the self-assembled nanoarchitectures come to play a pivotal role in fighting against cancer. This review outlines the most up-to-date developments in constructing phototherapeutic nanomaterials for photodynamic and photothermal therapy (PDT and PTT) of tumors, with emphasis on design ideas, building blocks, and advantageous characteristics of self-assembly. The prominent activities of cancer therapy obtained by these photoinduced nanotheranostics are also explored in-depth, together with the connections between the specific nanostructures and unique features, providing a comprehensive understanding of the self-assembled nanomaterials in improving the outcomes of PDT and PTT. This review aims to highlight the significance of self-assembled nanomaterials in enhancing phototherapeutic efficacy and to promote its development in various research interests ranging from material science and nanoscience to biomedicine and clinical medicine.

Nitrate-NRT1.1B-SPX4 cascade integrates nitrogen and phosphorus signalling networks in plants.

To ensure high crop yields in a sustainable manner, a comprehensive understanding of the control of nutrient acquisition is required. In particular, the signalling networks controlling the coordinated utilization of the two most highly demanded mineral nutrients, nitrogen and phosphorus, are of utmost importance. Here, we reveal a mechanism by which nitrate activates both phosphate and nitrate utilization in rice (Oryza sativa L.). We show that the nitrate sensor NRT1.1B interacts with a phosphate signalling repressor SPX4. Nitrate perception strengthens the NRT1.1B-SPX4 interaction and promotes the ubiquitination and degradation of SPX4 by recruiting NRT1.1B interacting protein 1 (NBIP1), an E3 ubiquitin ligase. This in turn allows the key transcription factor of phosphate signalling, PHR2, to translocate to the nucleus and initiate the transcription of phosphorus utilization genes. Interestingly, the central transcription factor of nitrate signalling, NLP3, is also under the control of SPX4. Thus, nitrate-triggered degradation of SPX4 activates both phosphate- and nitrate-responsive genes, implementing the coordinated utilization of nitrogen and phosphorus.

Construction of a Glutathione-Responsive and Silica-Based Nanocomposite for Controlled Release of Chelator Dimercaptosuccinic Acid.

Dimercaptosuccinic acid (DMSA) is an oral heavy metal chelator. Although DMSA is the most acceptable chelator in the urinary excretion of toxic elements from children and adults, its defects in plasma binding and the membrane permeability limit its interaction with intracellular elements and affect its efficacy in chelation therapy. Herein, a novel nanocomposite composed of mesoporous silica nanoparticles (MSNs), disulfide bond, and DMSA was synthesized and characterized with a scanning/transmission electron microscope, IR and Raman spectra, and TGA analysis. The in vitro interactions with glutathione (GSH) and cellular uptake assays showed that it was able to be stable in extracellular environments such as in blood, be internalized by cells, and release DMSA inside via GSH-triggered disulfide cleavage reaction. The in vitro adsorption assays showed that MSNs-SH as its intracellular metabolite had strong adsorbability for models of Hg2+ or Pb2+. The hemolysis and cell viability assays showed that it was compatible with blood and cells even at a concentration of 1000 µg·mL-1. All above could not only enable it to be a GSH-responsive drug delivery system (DDS) for DMSA delivery but also to be a solution for its defects and efficacy. Thus, introduction of intelligent DDS might open a new avenue for DMSA-based chelation therapy.

Tea consumption and risk of cardiovascular outcomes and total mortality: a systematic review and meta-analysis of prospective observational studies.

Studies that investigated the association between tea consumption and the risk of major cardiovascular events have reported inconsistent results. We conducted a meta-analysis of prospective observational studies in order to summarize the evidence regarding the association between tea consumption and major cardiovascular outcomes or total mortality. In July 2014, we performed electronic searches in PubMed, EmBase, and the Cochrane Library, followed by manual searches of reference lists from the resulting articles to identify other relevant studies. Prospective observational studies that reported effect estimates, with 95% confidence intervals (CIs), for coronary heart disease (CHD), stroke, cardiac death, stroke death, or total mortality for more than two dosages of tea consumption were included. A random-effects meta-analysis was performed to determine the risk of major cardiovascular outcomes associated with an increase in tea consumption by 3 cups per day. Of the 736 citations identified from database searches, we included 22 prospective studies from 24 articles reporting data on 856,206 individuals, and including 8,459 cases of CHD, 10,572 of stroke, 5,798 cardiac deaths, 2,350 stroke deaths, and 13,722 total deaths. Overall, an increase in tea consumption by 3 cups per day was associated with a reduced risk of CHD (relative risk [RR], 0.73; 95% CI: 0.53-0.99; P = 0.045), cardiac death (RR, 0.74; 95% CI: 0.63-0.86; P < 0.001), stroke (RR, 0.82; 95% CI: 0.73-0.92; P = 0.001), total mortality (RR, 0.76; 95% CI: 0.63-0.91; P = 0.003), cerebral infarction (RR, 0.84; 95% CI: 0.72-0.98; P = 0.023), and intracerebral hemorrhage (RR, 0.79; 95% CI: 0.72-0.87; P < 0.001), but had little or no effect on stroke mortality (RR, 0.93; 95% CI: 0.83-1.05; P = 0.260). The findings from this meta-analysis indicate that increased tea consumption is associated with a reduced risk of CHD, cardiac death, stroke, cerebral infarction, and intracerebral hemorrhage, as well as total mortality.

Association between B vitamins supplementation and risk of cardiovascular outcomes: a cumulative meta-analysis of randomized controlled trials.

BACKGROUND: Observational studies suggest that B vitamin supplementation reduces cardiovascular risk in adults, but this association remains controversial. This study aimed to summarize the evidence from randomized controlled trials (RCTs) investigating B vitamin supplementation for the primary or secondary prevention of major adverse cardiovascular outcomes and to perform a cumulative meta-analysis to determine the evidence base. METHODOLOGY AND PRINCIPAL FINDINGS: In April 2013, we searched PubMed, Embase, and the Cochrane Library to identify relevant RCTs. We included RCTs investigating the effect of B vitamin supplementation on cardiovascular outcome. Relative risk (RR) was used to measure the effect using a random-effect model. Statistical heterogeneity scores were assessed using the Q statistic. We included data on 57,952 individuals from 24 RCTs: 12 primary prevention trials and 12 secondary prevention trials. In 23 of these trials, 10,917 major adverse cardiovascular events (MACE) occurred; in 20 trials, 7,203 deaths occurred; in 15 trials, 3,422 cardiac deaths occurred; in 19 trials, 3,623 myocardial infarctions (MI) occurred; and in 18 trials, 2,465 strokes occurred. B vitamin supplementation had little or no effect on the incidence of MACE (RR, 0.98; 95% confidence interval [CI]: 0.93-1.03; P = 0.37), total mortality (RR, 1.01; 95% CI: 0.97-1.05; P = 0.77), cardiac death (RR, 0.96; 95% CI: 0.90-1.02; P = 0.21), MI (RR, 0.99; 95% CI: 0.93-1.06; P = 0.82), or stroke (RR, 0.94; 95% CI: 0.85-1.03; P = 0.18). CONCLUSION/SIGNIFICANCE: B vitamin supplementation, when used for primary or secondary prevention, is not associated with a reduction in MACE, total mortality, cardiac death, MI, or stroke.

Polyunsaturated fatty acid intake and risk of lung cancer: a meta-analysis of prospective studies.

BACKGROUND: Studies have reported inconsistent results for the existence of an association between polyunsaturated fatty acid (PUFA) intake and risk of lung cancer. The purpose of this study is to summarize the evidence regarding this relationship using a dose response meta-analytic approach. METHODOLOGY AND PRINCIPAL FINDINGS: We searched the PubMed, EmBase, and Cochrane Library electronic databases for related articles published through July 2013. Only prospective studies that reported effect estimates with 95% confidence intervals (CIs) of lung cancer incidence for greater than 2 categories of PUFA intake were included. We did random-effects meta-analyses of study-specific incremental estimates to determine the risk of lung cancer associated with a 5 g per day increase in PUFA intake. Overall, we included 8 prospective cohort studies reporting data on 1,268,442 individuals. High PUFA intake had little or no effect on lung cancer risk (risk ratio [RR], 0.91; 95% CI, 0.78-1.06; P = 0.230). Furthermore, the dose-response meta-analysis also suggested that a 5 g per day increase in PUFA has no significant effect on the risk of lung cancer (RR, 0.98; 95%CI: 0.96-1.01; P = 0.142). Finally, the findings of dose response curve suggested that PUFA intake of up to 15 g/d seemed to increase the risk of lung cancer. Furthermore, PUFA intake greater than 15 g/d was associated with a small beneficial effect and borderline statistical significance. Subgroup analyses for 5 g per day increment in PUFA indicated that the protective effect of PUFA was more evident in women (RR, 0.94; 95% CI, 0.87-1.01; P = 0.095) than in men (RR, 1.00; 95% CI, 0.98-1.02; P = 0.784). CONCLUSION/SIGNIFICANCE: Our study indicated that PUFA intake had little or no effect on lung cancer risk. PUFA intake might play an important role in lung cancer prevention in women.

Tea consumption and the risk of five major cancers: a dose-response meta-analysis of prospective studies.

BACKGROUND: We conducted a dose-response meta-analysis of prospective studies to summarize evidence of the association between tea consumption and the risk of breast, colorectal, liver, prostate, and stomach cancer. METHODS: We searched PubMed and two other databases. Prospective studies that reported risk ratios (RRs) with 95% confidence intervals (CIs) of cancer risk for ≥3 categories of tea consumption were included. We estimated an overall RR with 95% CI for an increase of three cups/day of tea consumption, and, usingrestricted cubic splines, we examined a nonlinear association between tea consumption and cancer risk. RESULTS: Forty-one prospective studies, with a total of 3,027,702 participants and 49,103 cancer cases, were included. From the pooled overall RRs, no inverse association between tea consumption and risk of five major cancers was observed. However, subgroup analysis showed that increase in consumption of three cups of black tea per day was a significant risk factor for breast cancer (RR, 1.18; 95% CI, 1.05-1.32). CONCLUSION: Ourresults did not show a protective role of tea in five major cancers. Additional large prospective cohort studies are needed to make a convincing case for associations.

Risk of treatment-related mortality with sorafenib in patients with cancer.

BACKGROUND: Fatal adverse events (FAEs) have been reported with sorafenib, a vascular endothelial growth factor receptor kinase inhibitor (VEGFR TKI). We here performed an up-to-date and detailed meta-analysis to determine the overall risk of FAEs associated with sorafenib. METHODS: Databases, including PubMed, Embase and Web of Science, and abstracts presented at the American Society of Clinical Oncology annual meetings were searched to identify relevant studies. Eligible studies included randomized controlled trials evaluating sorafenib effects in patients with all malignancies. Summary incidence rates, relative risks (RRs), and 95% confidence intervals (CIs) were calculated for FAEs. In addition, subgroup analyses were performed according to tumor type and therapy regimen. RESULTS: 13 trials recruiting 5,546 patients were included in our analysis. The overall incidence of FAEs with sorafenib was 1.99% (95%CI, 0.98-4.02%). Patients treated with sorafenib had a significantly increased risk of FAEs compared with patients treated with control medication, with an RR of 1.77 (95%CI 1.25-2.52, P=0.001). Risk varied with tumour type, but appeared independent of therapy regimen. A significantly increased risk of FAEs was observed in patients with lung cancer (RR 2.26; 95% CI 1.03-4.99; P= 0.043) and renal cancer (RR 1.84; 95% CI 1.15-2.94; P= 0.011). The most common causes of FAEs were hemorrhage (8.6%) and thrombus or embolism (4.9%). CONCLUSIONS: It is important for health care practitioners to be aware of the risks of FAEs associated with sorafenib, especially in patients with renal and lung cancer.