Insufficient Radiofrequency Ablation Promotes Angiogenesis of Residual Hepatocellular Carcinoma Via HIF-1α/VEGFA

Background: The mechanism of rapid growth of the residual tumor after radiofrequency (RF) ablation is poorly understood. In this study, we investigated the effect of hyperthermia on HepG2 cells and generated a subline with enhanced viability and dys-regulated angiogenesis in vivo, which was used as a model to further determine the molecular mechanism of the rapid growth of residual HCC after RF ablation. Methodology/Principal Findings: Heat treatment was used to establish sublines of HepG2 cells. A subline (HepG2 k) with a relatively higher viability and significant heat tolerance was selected. The cellular protein levels of VEGFA, HIF-1α and p-Akt, VEGFA mRNA and secreted VEGFA were measured, and all of these were up-regulated in this subline compared to parental HepG2 cells. HIF-1α inhibitor YC-1 and VEGFA siRNA inhibited the high viability of the subline. The conditioned media from the subline exerted stronger pro-angiogenic effects. Bevacizumab, VEGFA siRNA and YC-1 inhibited proangiogenic effects of the conditioned media of HepG2 k cells and abolished the difference between parental HepG2 cells and HepG2 k cells. For in vivo studies, a nude mouse model was used, and the efficacy of bavacizumab was determined. HepG2 k tumor had stronger pro-angiogenic effects than parental HepG2 tumor. Bevacizumab could inhibit the tumor growth and angiogenesis, and also eliminate the difference in tumor growth and angiogenesis between parental HepG2 tumor and HepG2 k tumor in vivo. Conclusions/Significance: The angiogenesis induced by HIF1α/VEGFA produced by altered cells after hyperthermia treatment may play an important role in the rapid growth of residual HCC after RF ablation. Bevacizumab may be a good candidate drug for preventing and treating the process

High density lipoprotein promotes proliferation of adipose-derived stem cells via S1P1 receptor and Akt, ERK1/2 signal pathways

Introduction: Adipose-derived stem cells (ADSC) are non-hematopoietic mesenchymal stem cells that have shown great promise in their ability to differentiate into multiple cell lineages. Their ubiquitous nature and the ease of harvesting have attracted the attention of many researchers, and they pose as an ideal candidate for applications in regenerative medicine. Several reports have demonstrated that transplanting ADSC can promote repair of injured tissue and angiogenesis in animal models. Survival of these cells after transplant remains a key limiting factor for the success of ADSC transplantation. Circulating factors like High Density Lipoprotein (HDL) has been known to promote survival of other stems cells like bone marrow derived stem cells and endothelial progenitor cells, both by proliferation and by inhibiting cell apoptosis. The effect of HDL on transplanted adipose-derived stem cells in vivo is largely unknown. Methods: This study focused on exploring the effects of plasma HDL on ADSC and delineating the mechanisms involved in their proliferation after entering the bloodstream. Using the MTT and BrdU assays, we tested the effects of HDL on ADSC proliferation. We probed the downstream intracellular Akt and ERK1/2 signaling pathways and expression of cyclin proteins in ADSC using western blot. Results: Our study found that HDL promotes proliferation of ADSC, by binding to sphingosine-1-phosphate receptor-1(S1P1) on the cell membrane. This interaction led to activation of intracellular Akt and ERK1/2 signaling pathways, resulting in increased expression of cyclin D1 and cyclin E, and simultaneous reduction in expression of cyclin-dependent kinase inhibitors p21 and p27, therefore promoting cell cycle progression and cell proliferation. Conclusions: These studies raise the possibility that HDL may be a physiologic regulator of stem cells and increasing HDL concentrations may be valuable strategy to promote ADSC transplantation.'973' National ST Major Project [2011CB503900]; National Natural Science Foundation of China [81270321, 81170101, 81370235]; Natural Science Foundation of Beijing, China [7122106]SCI(E)[email protected]; [email protected]

Open Access

YC-1 enhances the anti-tumor activity of sorafenib through inhibition of signal transducer and activator of transcription 3 (STAT3) in hepatocellular carcinom

Boron tin oxide for filterless intrinsic-narrowband solar-blind ultraviolet detectors with tunable photoresponse peak from 231 to 275 nm

Solar-blind ultraviolet (SBUV) detection has a great prospect in a wide range of applications, in which the synthesis of semiconductor materials with a suitable bandgap can be an important research focus. In this work, BSnO films with good selectivity for SBUV were grown by magnetron sputtering with the bandgap adjusted from 4.1 to 5.3 eV. Based on the BSnO films, filter-less narrowband SBUV detectors were fabricated first, exhibiting a narrow detection range and an ultra-high responsivity (113 A/W) required by the detection of extremely weak SBUV signals. In addition, graphene/BSnO/SiC heterojunction photovoltaic detectors were also fabricated, with a high photo-to-dark current ratio and an ultra-fast response exhibited under 0 V bias, confirming their ability to handle the detection of transient signals

Pleiotropic activities of succinate: The interplay between gut microbiota and cardiovascular diseases

Abstract Cardiovascular diseases (CVDs) continue to be a significant contributor to global mortality, imposing a substantial burden and emphasizing the urgent need for disease control to save lives and prevent disability. With advancements in technology and scientific research, novel mechanisms underlying CVDs have been uncovered, leading to the exploration of promising treatment targets aimed at reducing the global burden of the disease. One of the most intriguing findings is the relationship between CVDs and gut microbiota, challenging the traditional understanding of CVDs mechanisms and introducing the concept of the gut‐heart axis. The gut microbiota, through changes in microbial compositions and functions, plays a crucial role in influencing local and systemic effects on host physiology and disease development, with its metabolites acting as key regulators. In previous studies, we have emphasized the importance of specific metabolites such as betaine, putrescine, trimethylamine oxide, and N,N,N‐trimethyl‐5‐aminovaleric acid in the potential treatment of CVDs. Particularly noteworthy is the gut microbiota‐associated metabolite succinate, which has garnered significant attention due to its involvement in various pathophysiological pathways closely related to CVDs pathogenesis, including immunoinflammatory responses, oxidative stress, and energy metabolism. Furthermore, we have identified succinate as a potential biomarker, highlighting its therapeutic feasibility in managing aortic dissection and aneurysm. This review aims to comprehensively outline the characteristics of succinate, including its biosynthetic process, summarize the current evidence linking it to CVDs causation, and emphasize the host‐microbial crosstalk involved in modulating CVDs. The insights presented here offer a novel paradigm for future management and control of CVDs

Apoptosis of Platelets Inhibited By Herba Sarcandrae Extract through the Mitochondria Pathway

The purpose of the present study is to decode the underlying mechanism of Herba Sarcandrae that indicated antipurpuric effect and to unveil one of its primary components, flavonoids, which play an important role. An immune mediated bone marrow failure (BMF) model in mouse was established by infusion thymus suspension cells after radiation in vivo. Platelets isolated in vitro were prepared from normal mice and BMF mice, respectively. The expressions of PS, P-selectin, PAC-1, Bax, Bad, Bid, and caspase-9 were examined by flow cytometry, and alteration of morphology of platelets under different conditions was observed. Our results indicated that the number of platelets was increased by addition of total flavonoids, and some of apoptotic markers such as Bax, Bad, Bid, and Caspase-9 were downregulated. In addition, the phosphatidylserine (PS) exposure on platelets was inhibited by total flavonoids, and the expressions of PAC-1 and P-selectin were decreased. In conclusion, it is suggested that the total flavonoids of Herba Sarcandrae may inhibit the excessive platelet apoptosis through mitochondrial pathway. In addition, activation of platelets may be also involved in mediating apoptosis of platelets