Fatty acid activated PPARγ promotes tumorigenicity of prostate cancer cells by up regulating VEGF via PPAR responsive elements of the promoter.

In previous work, it is suggested that the excessive amount of fatty acids transported by FABP5 may facilitate the malignant progression of prostate cancer cells through a FABP5-PPARγ-VEGF signal transduction axis to increase angiogenesis. To further functionally characterise the FABP5-PPARγ-VEGF signal transduction pathway, we have, in this work, investigated the molecular mechanisms involved in its tumorigenicity promoting role in prostate cancer. Suppression of PPARγ in highly malignant prostate cancer cells produced a significant reduction (up to 53%) in their proliferation rate, invasiveness (up to 89%) and anchorage-independent growth (up to 94%) in vitro. Knockdown of PPARγ gene in PC3-M cells by siRNA significantly reduced the average size of tumours formed in nude mice by 99% and tumour incidence by 90%, and significantly prolonged the latent period by 3.5 fold. Results in this study combined with some previous results suggested that FABP5 promoted VEGF expression and angiogenesis through PPARγ which was activated by fatty acids transported by FABP5. Further investigations showed that PPARγ up-regulated VEGF expression through acting with the PPAR-responsive elements in the promoter region of VEGF gene in prostate cancer cells. Although androgen can modulate VEGF expression through Sp1/Sp3 binding site on VEGF promoter in androgen-dependent prostate cancer cells, this route, disappeared as the cells gradually lost their androgen dependency; was replaced by the FABP5-PPARγ-VEGF signalling pathway. These results suggested that the FABP5-PPARγ-VEGF signal transduction axis, rather than androgen modulated route, may be a more important novel therapeutic target for angiogenesis-suppression treatment of castration resistant prostate cancer

MicroRNA-137 Inhibits EFNB2 Expression Affected by a Genetic Variant and Is Expressed Aberrantly in Peripheral Blood of Schizophrenia Patients

MicroRNAs (miRNAs) are a class of endogenous and non-coding single-stranded RNAs of approximately 22 nucleotides, many of which are evolutionarily conserved. Genome-wide association studies have identified a robust statistical association between the MIR137 gene and schizophrenia in Europeans, which was replicated in the Han Chinese population in a case-control study. In the previous study, we provided evidence for a significant association between the EFNB2 gene and schizophrenia in Han Chinese subjects. In the current study, we utilized computational analysis, vector construction of point mutations, luciferase reporter assays and gene expression assays including RT-qPCR and western blotting methods to investigate miR-137 directly targeting EFNB2 gene and explore the reversal effect of a genetic variant of SNP rs550067317 in the putative seed-pair region of EFNB2 3′-UTR. We also found that miR-137 could be detected in the peripheral blood of a cohort of first-onset schizophrenia patients and healthy controls, and the area under curve was 0.795 (95% confidence interval 0.700–0.890), which is a middle diagnostic value for disease, suggesting that it might be valuable for diagnosing schizophrenia. In summary, this study would improve our understanding of the role of miR-137 in schizophrenia-associated signaling pathways and identify the genetic basis of rs550067317 for schizophrenia. Furthermore, we provided new evidence for the involvement of miR-137 in the etiology and diagnosis of schizophrenia, which might contribute to the discovery of new biomarkers and therapeutic targets for the disease

Associations between modifiable risk factors and frailty progression among individuals with pre-frailty

Background: In the context of the present global aging phenomenon, the senior population and pace of aging in China have emerged as prominent issues on the worldwide stage. Frailty, a complicated condition that is closely linked to the clinical syndrome of advancing age, poses a considerable health risk to older individuals. Frailty status was assessed by the frailty index (FI) ranging from 0 to 1, pre-frailty was defined as >0.10 to <0.25, and frailty was defined as ≥0.25. To look at the connection between modifiable risk factors and frailty progression among individuals in the pre-frailty population. Methods: Using pre-frailty patients as characterized by the 32-frailty index, the study focused on middle-aged and elderly persons from China and ultimately recruited 5,411 participants for analysis. The relationship between modifiable factors and changes in pre-frailty status throughout follow-up was investigated. Modifiable factors were body mass index (BMI), abdominal obesity, smoking status, alcohol use, and sleep status. We employed logistic regression to examine the relationships between modifiable risk factors and changes in pre-frailty status, as well as the associations between modifiable factors scores and the corresponding pre-frailty progression. Additionally, we generated the modifiable factors scores and examined how these related to modifications in the pre-frailty stage. Results: In this study, after a mean follow-up of 6 years, (OR = 0.59, 95%CI: 0.48–0.71) for BMI ≥ 25 kg/m2 and (OR = 0.74, 95%CI: 0.63–0.89) for concomitant abdominal obesity were significantly associated with lower reversal to a healthy state; (OR = 1.24, 95%CI:1.07–1.44) and (OR = 1.25, 95%CI: 1.10–1.42) for the group that negatively progressed further to frailty were significantly associated with increased frailty progression profile. Subsequently, investigation of modifiable factor scores and changes of pre-frailty status found that as scores increased further, frailty developed (OR = 1.12, 95%CI:1.05–1.18), with scores of 3 and 4 of (OR = 1.38, 95%CI: 1.08–1.77) and (OR = 1.52, 95%CI:1.09–2.14). Finally, we also performed a series of stratified analyses and found that rural unmarried men aged 45 to 60 years with less than a high school degree were more likely to develop a frailty state once they developed abdominal obesity. Conclusion: In pre-frailty individuals, maintaining more favorable controllable variables considerably enhances the chance of return to normal and, conversely, increase the risk of progressing to the frailty

Protein Corona Fingerprinting Predicts the Cellular Interaction of Gold and Silver Nanoparticles

Using quantitative models to predict the biological interactions of nanoparticles will accelerate the translation of nanotechnology. Here, we characterized the serum protein corona ‘fingerprint’ formed around a library of 105 surface-modified gold nanoparticles. Applying a bioinformatics-inspired approach, we developed a multivariate model that uses the protein corona fingerprint to predict cell association 50% more accurately than a model that uses parameters describing nanoparticle size, aggregation state, and surface charge. Our model implicates a set of hyaluronan-binding proteins as mediators of nanoparticle–cell interactions. This study establishes a framework for developing a comprehensive database of protein corona fingerprints and biological responses for multiple nanoparticle types. Such a database can be used to develop quantitative relationships that predict the biological responses to nanoparticles and will aid in uncovering the fundamental mechanisms of nano–bio interactions

Additional file 1 of Zn-Shik-PEG nanoparticles alleviate inflammation and multi-organ damage in sepsis

Supplementary Material

Protein Corona Fingerprinting Predicts the Cellular Interaction of Gold and Silver Nanoparticles

Using quantitative models to predict the biological interactions of nanoparticles will accelerate the translation of nanotechnology. Here, we characterized the serum protein corona ‘fingerprint’ formed around a library of 105 surface-modified gold nanoparticles. Applying a bioinformatics-inspired approach, we developed a multivariate model that uses the protein corona fingerprint to predict cell association 50% more accurately than a model that uses parameters describing nanoparticle size, aggregation state, and surface charge. Our model implicates a set of hyaluronan-binding proteins as mediators of nanoparticle–cell interactions. This study establishes a framework for developing a comprehensive database of protein corona fingerprints and biological responses for multiple nanoparticle types. Such a database can be used to develop quantitative relationships that predict the biological responses to nanoparticles and will aid in uncovering the fundamental mechanisms of nano–bio interactions