Case report: Dendritic cell-cytokine induced killer cell therapy in subjects with chronic lymphocytic leukemia and peritoneal cancer

This study aimed to characterize the safety and efficacy of DC-CIK therapy in two patients with previously treated chronic lymphocytic leukemia or peritoneal cancer, respectively. Participants had received conventional chemotherapy treatment for their specific cancers, and in addition, 1–2 treatments of DC-CIK therapy were administered to subjects over the course of 1 year. Subject A received an initial dosage of 3 intravenous infusions of DC-CIK therapy on three successive days and a repeat dosage 6 months later. Subject B received an initial dosage of 3 intravenous infusions of DC-CIK therapy on three successive days and received further chemotherapy after approximately 1 year. No treatment-related adverse events were reported, and both patients experienced favorable outcomes from the treatment, including enhanced treatment response, increased chemotherapy tolerance, and prolonged survival in comparison to typical 5-year survival rates

Neurochemical and neuropharmacological characterization of acetylcholinesterase inhibitors for Alzheimer's disease

Considering the cholinergic neuronal loss as one of the main pathological features of Alzheimer's disease (AD), it is of special importance to search for agents that could increase acetylcholine and provide neuroprotective effects against neuronal cell death especially apoptosis. Tacrine, E2020 and Huperzine A have thus far been widely used in clinical for AD as acetylcholinesterase (AChE) inhibitors. Bis(7)-tacrine is a novel dimeric analog of tacrine and exhibits superior AChE inhibition efficacy. In the present study, we investigated the effects of these AChE inhibitors on different insults induced neuronal cell death. In vitro study indicated that pretreatment with bis(7)-tacrine protect against glutamate induced neuronal cell injury and ischemia-induced astrocyte apoptosis in primary cultured cerebral cortical neurons and astrocytes, respectively. Pretreatment with tacrine markedly protect the NG108-15 cells against staurosporine-induced cell death. However, E2020 do not display obvious protective effects against staurosporine-induced NG 108-15 cell apoptosis. Further investigation indicates that Tacrine decreases and delay the Bax protein expression and increase the Bcl-2 protein expression. It did not affect the Caspace-3 protein expression. These may partially contribute to their neuroprotective effects. Further research will be continued for structural modification of the standard drugs to develop new agents with more significant neuroprotection and or better AChE inhibition. We also investigated the expression of cyclin-dependent kinase 5 (Cdk5) and its regulatory subunits, p35 and p39, in different developing stages of rat brain. The Cdk5 protein level increased from El2 to postnatal day 7 (P7) and remained at this level until 18M. The Cdk5 kinase activity and the levels of both p35 mRNA and protein were low at E12, became prominent at El8-P14 but then decreased in the adult and aged rat brains of 3M to 18M. In comparison, the expression pattern of p39 appeared to have an inverse relationship to that of Cdk5 and p35. In regional distribution studies, p35 protein levels and Cdk5 kinase activity were significantly higher in the cerebral cortex and hippocampus, but lower in the cerebellum and striatum. These results suggested that Cdk5, p35 and p39 might have region-specific and developmental stage-specific functions in rat brain

Human Umbilical Mesenchymal Stem Cells-Derived Microvesicles Attenuate Formation of Hypertrophic Scar through Multiple Mechanisms

Mesenchymal stem cells and the derived extracellular microvesicles are potential promising therapy for many disease conditions, including wound healing. Since current therapeutic approaches do not satisfactorily attenuate or ameliorate formation of hypertrophic scars, it is necessary to develop novel drugs to achieve better outcomes. In this study, we investigated the effects and the underlying mechanisms of human umbilical mesenchymal stem cells (HUMSCs)-derived microvesicles (HUMSCs-MVs) on hypertrophic scar formation using a rabbit ear model and a human foreskin fibroblasts (HFF) culture model. The results showed that HUMSCs-MVs reduced formation of hypertrophic scar tissues in the rabbit model based on appearance observation, and hematoxylin and eosin (H&E), Masson, and immunohistochemical stainings. HUMSCs-MVs inhibited invasion of HFF cells and decreased the levels of the α-SMA, N-WASP, and cortacin proteins. HUMSCs-MVs also inhibited cell proliferation of HFF cells. The MMP-1, MMP-3, and TIMP-3 mRNA levels were significantly increased, and the TIMP-4 mRNA level and the NF-kB p65/β-catenin protein levels were significantly decreased in HFF cells after HUMSCs-MVs treatment. The p-SMAD2/3 levels and the ratios of p-SMAD2/3/SMAD2/3 were significantly decreased in both the wound healing tissues and HFF cells after HUMSCs-MVs treatment. CD34 levels were significantly decreased in both wound healing scar tissues and HFF cells after HUMSCs-MVs treatment. The VEGF-A level was also significantly decreased in HFF cells after HUMSCs-MVs treatment. The magnitudes of changes in these markers by HUMSCs-MVs were mostly higher than those by dexamethasone. These results suggested that HUMSCs-MVs attenuated formation of hypertrophic scar during wound healing through inhibiting proliferation and invasion of fibrotic cells, inflammation and oxidative stress, Smad2/3 activation, and angiogenesis. HUMSCs-MVs is a potential promising drug to attenuate formation of hypertrophic scar during wound healing

QTL Mapping for Root Traits and Their Effects on Nutrient Uptake and Yield Performance in Common Wheat (<i>Triticum aestivum</i> L.)

Wheat is one of the most important crops in the world. Mapping QTLs for root traits is essential for the selection of wheat roots desirable for the efficient acquisition of nutrients. Here, a QTL analysis for wheat root traits was performed using 142 recombinant inbred lines derived from two wheat varieties Xiaoyan 54 and Jing 411 in a soil column culture trial. The genetic map used in this study contained 470 SSR markers and covered 3438.4 cM of wheat genome. A total of 25 QTLs for root and shoot traits were detected, located at 16 marker intervals of 13 chromosomes. The percentage of phenotypic variation explained by individual QTLs varied from 6.1% to 22.0%. The QTLs regulating RDW and root distribution on chromosomes 1A, 3A, 4A, and 5B are important for root growth in both the top- and subsoils. For qRDW-1A, qRDW-3A, and qRDW-5B, the nearest markers to the QTLs were much closer than that of qRDW-4A, with the genetic distances ranging from 0.01 to 1.18 cM. Combining these three QTLs not only increased RDW and nutrient uptake, but also increased GW, SDW, and BDW under low nitrogen conditions in the field trial. Therefore, these QTLs are valuable for marker-assisted selection of wheat root traits

Towards High-Performance Load-Balance Multicast Switch via Erasure Codes

Recent studies on switching fabrics mainly focus on the switching schedule algorithms, which aim at improving the throughput (a key performance metric). However, the delay (another key performance metric) of switching fabrics cannot be well guaranteed. A good switching fabric should be endowed with the properties of high throughput, delay guarantee, low component complexity and high-speed multicast, which are difficult for conventional switching fabrics to achieve. This has fueled great interest in designing a new switching fabric that can support large-scale extension and high-speed multicast. Motivated by this, we reuse the self-routing Boolean concentrator network and embed a model of multicast packet copy separation in front to construct a load-balanced multicast switching fabric (LB-MSF) with delay guarantee. The first phase of LB-MSF is responsible for balancing the incoming traffic into uniform cells while the second phase is in charge of self-routing the cells to their final destinations. In order to improve the throughput, LB-MSF is combined with the merits of erasure codes against packet loss. Experiments and analyses verify that the proposed fabric is able to achieve high-speed multicast switching and suitable for building super large-scale switching fabric in Next Generation Network(NGN) with all the advantages mentioned above. Furthermore, a prototype of the proposed switch is developed on FPGA, and presents excellent performance.National Natural Science Foundation of China [NSFC61179028]; Shenzhen Basic Research Program [JCYJ20140509093817684]SCI(E)[email protected]; [email protected]

Integrated Profiles of Transcriptome and mRNA m6A Modification Reveal the Intestinal Cytotoxicity of Aflatoxin B1 on HCT116 Cells

Aflatoxin B1 (AFB1) is widely prevalent in foods and animal feeds and is one of the most toxic and carcinogenic aflatoxin subtypes. Existing studies have proved that the intestine is targeted by AFB1, and adverse organic effects have been observed. This study aimed to investigate the relationship between AFB1-induced intestinal toxicity and N6-methyladenosine (m6A) RNA methylation, which involves the post-transcriptional regulation of mRNA expression. The transcriptome-wide m6A methylome and transcriptome profiles in human intestinal cells treated with AFB1 are presented. Methylated RNA immunoprecipitation sequencing and mRNA sequencing were carried out to determine the distinctions in m6A methylation and different genes expressed in AFB1-induced intestinal toxicity. The results showed that there were 2289 overlapping genes of the differentially expressed mRNAs and differentially m6A-methylation-modified mRNAs. After enrichment of the signaling pathways and biological processes, these genes participated in the terms of the cell cycle, endoplasmic reticulum, tight junction, and mitophagy. In conclusion, the study demonstrated that AFB1-induced HCT116 injury was related to the disruptions to the levels of m6A methylation modifications of target genes and the abnormal expression of m6A regulators