Traumatic brain injury (TBI) is known to cause perturbations in the energy metabolism of the brain, but current tests of metabolic activity are only indirect markers of energy use or are highly invasive. Here we show that hyperpolarized 13C magnetic resonance spectroscopic imaging (MRSI) can be used as a direct, non-invasive method for studying the effects of TBI on energy metabolism. Measurements were performed on rats with moderate TBI induced by controlled cortical impact on one cerebral hemisphere. Following injection of hyperpolarized [1-13C]pyruvate, the resulting 13C-bicarbonate signal was found to be 24 ± 6% lower in the injured hemisphere compared with the non-injured hemisphere, while the hyperpolarized bicarbonate-to-lactate ratio was 33 ± 8% lower in the injured hemisphere. In a control group, no significant difference in signal was found between sides of the brain. The results suggest an impairment in mitochondrial pyruvate metabolism, resulting in a decrease in aerobic respiration at the location of injury following TBI.
With the rapid growth of renewable energy resources, energy trading has been shifting from the centralized manner to distributed manner. Blockchain, as a distributed public ledger technology, has been widely adopted in the design of new energy trading schemes. However, there are many challenging issues in blockchain-based energy trading, e.g., low efficiency, high transaction cost, and security and privacy issues. To tackle these challenges, many solutions have been proposed. In this survey, the blockchain-based energy trading in the electrical power system is thoroughly investigated. Firstly, the challenges in blockchain-based energy trading are identified and summarized. Then, the existing energy trading schemes are studied and classified into three categories based on their main focuses: energy transaction, consensus mechanism, and system optimization. Blockchain-based energy trading has been a popular research topic, new blockchain architectures, models and products are continually emerging to overcome the limitations of existing solutions, forming a virtuous circle. The internal combination of different blockchain types and the combination of blockchain with other technologies improve the blockchain-based energy trading system to better satisfy the practical requirements of modern power systems. However, there are still some problems to be solved, for example, the lack of regulatory system, environmental challenges and so on. In the future, we will strive for a better optimized structure and establish a comprehensive security assessment model for blockchain-based energy trading system.
The main objective of this study is to explore the impact of cyclic RGD peptides and 99mTc chelates on biological properties of 99mTc radiotracers. Cyclic RGD peptide conjugates, HYNIC-K(NIC)-RGD2 (HYNIC = 6-hydrazinonicotinyl; RGD2 = E[c(RGDfK)]2 and NIC = nicotinyl) HYNIC-K(NIC)-3G-RGD2 (3G-RGD2 = Gly-Gly-Gly-E[Gly-Gly-Gly-c(RGDfK)]2), and HYNIC-K(NIC)-3P-RGD2 (3P-RGD2 = PEG4-E[PEG4-c(RGDfK)]2), were prepared. Macrocyclic 99mTc complexes [99mTc(HYNIC-K(NIC)-RGD2)(tricine)] (1), [99mTc(HYNIC-K(NIC)-3G-RGD2)(tricine)] (2) and [99mTc(HYNIC-K(NIC)-3P-RGD2)(tricine)] (3) were evaluated for their biodistribution and tumor-targeting capability in athymic nude mice bearing MDA-MB-435 human breast tumor xenografts. It was found that 1, 2 and 3 could be prepared with high specific activity (~111GBq/3mol). All three 99mTc radiotracers have two major isomers, which show almost identical uptake in tumors and normal organs. Replacing the bulky and highly charged [99mTc(HYNIC)(tricine)(TPPTS)] (TPPTS = trisodium triphenylphosphine-3,3′,3″-trisulfonate) with a smaller [99mTc(HYNIC-K(NIC))(tricine)] resulted in less uptake in the kidneys and lungs for 3. Surprisingly, all three 99mTc radiotracers shared a similar tumor uptake (1: 5.73 ± 0.40 %ID/g; 2: 5.24 ± 1.09 %ID/g; and 3: 4.94 ± 1.71 %ID/g) at 60 min p.i. The metabolic stability of 99mTc radiotracers depends on cyclic RGD peptides (3P-RGD2 > 3G-RGD2 ~ RGD2) and 99mTc chelates ([99mTc(HYNIC)(tricine)(TPPTS)] > [99mTc(HYNIC-K(NIC))(tricine)]). Immunohistochemical studies revealed a linear relationship between the αvβ3 expression levels and tumor uptake or tumor/muscle ratios of 3, suggesting that 3 is useful for monitoring the tumor αvβ3 expression. Complex 3 is a very attractive radiotracer for detection of integrin αvβ3 –positive tumors.
The potential of adult human adipose tissue stem cells (hASCs) to differentiate into hepatocytes has generated much excitement over the possible use of hASCs in therapeutic applications. An understanding of the molecular mechanisms that underlie the plasticity of hASCs toward hepatocytes will help to make this possibility a reality. Herein, we show that a homogenous population of hASCs characterized by a high level of CD73, CD90, and CD105 express the pluripotent transcription factors OCT4, SOX2, NANOG, and SALL4 under proliferation conditions. A high level of activin A allows for hASCs acquiring the fate of definitive endoderm (DE) cells and expressing the specific transcription factors HEX, FOXA2, SOX17, and GATA4 synchronously. Using a reproducible three-stage method by mimicking liver embryogenesis, hASCs were directed to differentiate into functional hepatocytes. In the first stage, hASCs were induced to become DE cells by 2 days cultured in serum-free medium and 3 days of activin A treatment. Next, the presence of fibroblast growth factor (FGF) 4 and bone morphogenetic protein (BMP) 2 in the medium for 5 days induced efficient hepatic differentiation from DE cells. After 10 days of further maturated by the sequential exposure to hepatocyte growth factor (HGF), oncostatin M (OSM), and dexamethasone (DEX), the hASC-derived hepatocytes expressed mature hepatocytes marker and exhibited functional characterization, including albumin secretion, glycogen storage, urea production, activity of drug transporters, and cytochrome P450 activity. These findings will be useful for the implementation of hASC-derived hepatocytes in therapeutic purposes, metabolic analyses, drug toxicity screening, and studies of hepatocyte function.
Precise and full-scale preoperative evaluation, complete tumor resection, and multidisciplinary cooperation are crucial for successful treatment.
IntroductionAdult stem cell-derived hepatocytes transplantation holds considerable promise for future clinical individualized therapy of liver failure or dysfunction. However, the low engraftment of the available hepatocytes in the liver disease microenvironment has been a major obstacle.MethodsAcellular human amniotic membrane was developed as a three-dimensional scaffold and combined with hepatocyte-like cells derived from human adipose stem cells to engineer a hepatic tissue graft that would allow hepatocyte engraftment in the liver effectively.ResultsThe hepatic tissue grafts maintained hepatocyte-specific gene expression and functionality in vitro. When transplanted into the surgical incision in livers for engraftment, the engineered hepatic grafts significantly decreased the degree of liver injury caused by a carbon tetrachloride treatment and generated cords that were similar to the ductal plates in the liver between the acellular human amniotic membrane and the liver of receipts at day 3 post-transplantation. The hepatic tissue grafts maintained the expression of human hepatocyte-specific markers albumin, hepatocyte nuclear factor 4α, and cytochrome P450 2B6 in the liver of receipts, and acquired human-specific drug metabolism ability at eight weeks post-transplantation.ConclusionsThe acellular human amniotic membrane has the ability to maintain the functional phenotype of the hepatocyte-like cells derived from human adipose stem cells. Functional acellular human amniotic membrane-hepatocytes grafts integrated with the liver decreases the acute liver injury of mice. These engineered tissue constructs may support stem cell-based individualized therapy for liver disease and for bioartificial liver establishment.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-015-0208-9) contains supplementary material, which is available to authorized users.
Epidemiological studies have found that diabetes and cognitive dysfunction are closely related. Quercetin has been certified with the effect on improving diabetes mellitus (DM) and cognitive impairment. However, the effect and related mechanism of quercetin on diabetic encephalopathy (DE) are still ambiguous. In this study, we used the db/db mice (diabetic model) to discover whether quercetin could improve DE through the Sirtuin1/NLRP3 (NOD‐, LRR‐ and pyrin domain‐containing 3) pathway. Behavioural results (Morris water maze and new object recognition tests) showed that quercetin (70 mg/kg) improved the learning and memory. Furthermore, quercetin alleviated insulin resistance and the level of fasting blood glucose. Besides, Western blot analysis also showed that quercetin increased the protein expressions of nerve‐ and synapse‐related protein, including postsynapticdensity 93 (PSD93), postsynapticdensity 95 (PSD95), brain‐derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the brain of db/db mice. Quercetin also increased the protein expression of SIRT1 and decreased the expression of NLRP3 inflammation‐related proteins, including NLRP3, the adaptor protein ASC and cleaved Caspase‐1, the pro‐inflammatory cytokines IL‐1β and IL‐18. In conclusion, the present results indicate that the SIRT1/NLRP3 pathway may be a crucial mechanism for the neuroprotective effect of quercetin against DE.
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