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Cancer-associated cachexia (CAC) constitutes a metabolic dysfunction characterized by systemic inflammation and body weight loss. Muscle atrophy and adipose tissue lipolysis might explain weight loss in CAC. Specific functions of numerous hormones and cytokines derived from tumours can provoke cachexia. Extracellular vesicles (EVs) can be involved in intercellular communication. However, whether EVs participate in this process has not been investigated thoroughly. Using Lewis lung carcinoma (LLC) cell cultures, we tested whether LLC-derived EVs induced C2C12 myotube atrophy and 3T3-L1 adipocyte lipolysis. EVs derived from LLC cells and serum from patients with lung cancer, non-lung cancer controls, tumour-bearing mice, and non-tumour-bearing control mice were isolated and characterized biochemically and biophysically. LLC cell-derived EVs induced dose-dependent effects of atrophy in C2C12 myotubes and lipolysis in 3T3-L1 adipocytes. Mechanistically, EVs directly fused with target C2C12 myotubes and 3T3-L1 adipocytes, and transferred interleukin-6 (IL-6) activates the STAT3 signalling pathway in C2C12 myotubes and 3T3-L1 adipocytes. Neutralization of extracellular IL-6 prevented the atrophy and lipolysis effects of EVs. Inhibiting the STAT3 signalling pathway also prevented the atrophy and lipolysis effects of EVs. PKH67-labelled (PKH 67 is a lipid dye that can be used to label extracellular vesicles) LLC-EVs were readily internalized into myotubes and adipocytes. Our data showed that LLC cell-derived EVs induced myotube atrophy and adipocyte lipolysis via the extracellular IL-6-mediated STAT3 pathway in target cells. These findings represent a potentially novel basis for further research in this field towards identifying targets and developing strategies for maintaining weight in CAC., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Blood-brain barrier (BBB) damage and astrocyte activation are important cause of recurrent epilepsy. There is experimental evidence for increased angiotensin receptor type 1 (AT1) expression during BBB breakdown and brain injury, and that blocking the AT1 receptor (e.g., with losartan) can improve microcirculation, attenuate inflammation and oxidative stress, and exhibit neuroprotective effects. Thus, in the present study, we examined the effects of losartan on status epilepticus-induced astrocyte activation and BBB damage in the lithium-pilocarpine model of epilepsy in rats. We found that losartan treatment reduced astrocyte activation and BBB damage. However, under physiological condition, losartan have not effect on BBB permeability and astrocyte activation. Further, losartan exhibited a direct antiepileptic effect, which was mediated, at least in part by normalizing AQP4 expression after SE. As the changes of AQP4 expression were closely related to astrocyte activation and BBB permeability, the antiepileptic action of losartan likely relates to its effects on astrocyte activation and BBB permeability. Overall, these data suggest that losartan may be a useful antiepileptic agent in the clinic, either alone or in combination with other antiepileptic drugs., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Emerging evidence has highlighted the important role of abnormal lipid accumulation in cancer development and progression, but the mechanism for this phenomenon remains unclear. Here, it is demonstrated that phospholipase C-like 1/uncoupling protein 1 (PLCL1)/(UCP1)-mediated lipid browning promotes tumor cell "slimming" and represses tumor progression. By screening three independent lipid metabolism-related gene sets in clear cell renal cell carcinoma (ccRCC) and analyzing the TCGA database, it is found that PLCL1 predicted a poor prognosis and was downregulated in ccRCC. Restoration of PLCL1 expression in ccRCC cells significantly represses tumor progression and reduces abnormal lipid accumulation. Additionally, a phenomenon called tumor cell "slimming," in which tumor cell volume is reduced and lipid droplets are transformed into tiny pieces, is observed. Further studies show that PLCL1 promotes tumor cell "slimming" and represses tumor progression through UCP1-mediated lipid browning, which consumes lipids without producing ATP energy. Mechanistic investigations demonstrate that PLCL1 improves the protein stability of UCP1 by influencing the level of protein ubiquitination. Collectively, the data indicate that lipid browning mediated by PLCL1/UCP1 promotes tumor cell "slimming" and consumes abnormal lipid accumulation, which represses the progression of ccRCC. Tumor cell "slimming" offers a promising new concept and treatment modality against tumor development and progression., Competing Interests: The authors declare no conflict of interest.

Grain-size is one of the yield components, and the first 14 days after pollination (DAP) is a crucial stage for wheat grain-size formation. To understand the mechanism of grain-size formation at the whole gene expression level and to identify the candidate genes related to grain pattern formation, cDNA libraries from immature grains of 5 DAP and 14 DAP were constructed. According to transcriptome analysis, a total of 12,555 new genes and 9,358 differentially expressed genes (DEGs) were obtained. In DEGs, 2,876, 3,357 and 3,125 genes were located on A, B and D subgenome respectively. 9,937 (79.15%) new genes and 9,059 (96.80%) DEGs were successfully annotated. For DEGs, 4,453 were up-regulated and 4,905 were down-regulated at 14 DAP. The Gene Ontology (GO) database indicated that most of the grain-size-related genes were in the same cluster. The Kyoto Encyclopedia of Genes and Genomes (KEGG) database analysis showed that 130, 129 and 20 DEGs were respectively involved in starch and sucrose metabolism, plant hormone signal transduction and ubiquitin-mediated proteolysis. Expression levels of 8 randomly selected genes were confirmed by qRT-PCR, which was consistent with the transcriptome data. The present database will help us understand the molecular mechanisms underlying early grain development and provide the foundation for increasing grain-size and yield in wheat breeding programs., Competing Interests: The authors have declared that no competing interests exist.

Cancer-associated cachexia (CAC) is a disorder characterized by unintended weight loss due to skeletal muscle wasting and adipose tissue loss. Although muscle atrophy in this condition has been well studied, the mechanisms underlying adipose tissue loss, which include browning, have not been investigated in detail. In this respect, though recent studies have shown that exosomes from cancer cells can promote lipolysis, the link between exosomes from cancer cells and CAC has not been clearly established. In this study, we investigate if exosomes from Lewis lung carcinoma (LLC) cells can induce lipolysis in vitro (in 3T3-L1 adipocytes) and in vivo (in LLC tumor-bearing mice). We find that exosomes from LLC cells do induce lipolysis in 3T3-L1 adipocytes and that the white adipose tissues of mice with LLC tumors show clear signs of lipolysis. We also find that this lipolysis can be inhibited using the neutral sphingomyelinase inhibitor GW4869. Our results indicate that GW4869 not only inhibits exosome generation and release from LLC cells, but can also inhibit lipolysis induced by LLC-derived exosomes in 3T3-L1 adipocytes. Furthermore, we also demonstrate that LLC tumor-bearing mice treated with GW4869 did not develop CAC. In summary, our results suggest that inhibiting exosome generation and release can inhibit lipolysis and adipose tissue browning, and may be useful as a novel strategy for treating CAC., (Copyright © 2018. Published by Elsevier Inc.)

Soil acidification is one of major problems limiting crop growth and especially becoming increasingly serious in China owing to excessive use of nitrogen fertilizer. Only the STOP1 of Arabidopsis was identified clearly sensitive to proton rhizotoxicity and the molecular mechanism for proton toxicity tolerance of plants is still poorly understood. The main objective of this study was to investigate the transcriptomic change in plants under the low pH stress. The low pH as a single factor was employed to induce the response of the wheat seedling roots. Wheat cDNA microarray was used to identify differentially expressed genes (DEGs). A total of 1057 DEGs were identified, of which 761 genes were up-regulated and 296 were down-regulated. The greater percentage of up-regulated genes involved in developmental processes, immune system processes, multi-organism processes, positive regulation of biological processes and metabolic processes of the biological processes. The more proportion of down-regulation genes belong to the molecular function category including transporter activity, antioxidant activity and molecular transducer activity and to the extracellular region of the cellular components category. Moreover, most genes among 41 genes involved in ion binding, 17 WAKY transcription factor genes and 17 genes related to transport activity were up-regulated. KEGG analysis showed that the jasmonate signal transduction and flavonoid biosynthesis might play important roles in response to the low pH stress in wheat seedling roots. Based on the data, it is can be deduced that WRKY transcription factors might play a critical role in the transcriptional regulation, and the alkalifying of the rhizosphere might be the earliest response process to low pH stress in wheat seedling roots. These results provide a basis to reveal the molecular mechanism of proton toxicity tolerance in plants.

While recent evidence has uncovered that circular RNAs (circRNAs) are vital regulators of carcinogenesis, their role in papillary thyroid cancer (PTC) is not clearly understood. In this study, we reveal that lower levels of circRNA circ-ITCH are expressed in PTC tissues than in normal adjacent tissues. Gain-of-functional assays show that circ-ITCH overexpression suppresses PTC cell proliferation and invasion and promotes apoptosis in vitro. Overexpression of circ-ITCH also leads to impaired tumor growth in vivo. Bioinformatics analysis and luciferase reporter assays demonstrate that circ-ITCH sponges miR-22-3p to upregulate the expression of CBL, an E3 ligase of nuclear β-catenin. Elevated levels of CBL suppress activation of the Wnt/β-catenin pathway and consequently attenuates PTC progression. In summary, our study reveals a novel signaling pathway of circ-ITCH/miR-22-3p/CBL/β-catenin involved in PTC development and progression., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Numerous scaffold-level sequences for wheat are now being released and, in this context, we report on a strategy for improving the overall assembly to a level comparable to that of the human genome., Results: Using chromosome 7A of wheat as a model, sequence-finished megabase-scale sections of this chromosome were established by combining a new independent assembly using a bacterial artificial chromosome (BAC)-based physical map, BAC pool paired-end sequencing, chromosome-arm-specific mate-pair sequencing and Bionano optical mapping with the International Wheat Genome Sequencing Consortium RefSeq v1.0 sequence and its underlying raw data. The combined assembly results in 18 super-scaffolds across the chromosome. The value of finished genome regions is demonstrated for two approximately 2.5 Mb regions associated with yield and the grain quality phenotype of fructan carbohydrate grain levels. In addition, the 50 Mb centromere region analysis incorporates cytological data highlighting the importance of non-sequence data in the assembly of this complex genome region., Conclusions: Sufficient genome sequence information is shown to now be available for the wheat community to produce sequence-finished releases of each chromosome of the reference genome. The high-level completion identified that an array of seven fructosyl transferase genes underpins grain quality and that yield attributes are affected by five F-box-only-protein-ubiquitin ligase domain and four root-specific lipid transfer domain genes. The completed sequence also includes the centromere.

Background/aims: MIAT is a long noncoding RNA (lncRNA) involved in cell proliferation and the development of tumor. However, the exact effects and molecular mechanisms of MIAT in clear cell renal cell carcinoma (ccRCC) progression are still unknown., Methods: We screened the lncRNAs' profile of ccRCC in The Cancer Genome Atlas database, and then examined the expression levels of lncRNA MIAT in 45 paired ccRCC tissue specimens and in cell lines by q-RT-PCR. MTS, colony formation, EdU, and Transwell assays were performed to examine the effect of MIAT on proliferation and metastasis of ccRCC. Western blot and luciferase assays were performed to determine whether MIAT can regulate Loxl2 expression by competitively binding miR-29c in ccRCC., Results: MIAT was up-regulated in ccRCC tissues and cell lines. High MIAT expression correlated with worse clinicopathological features and shorter survival rate. Functional assays showed that knockdown of MIAT inhibited renal cancer cell proliferation and metastasis in vitro and in vivo. Luciferase and western blot assays further confirmed that miR-29c binds with MIAT. Additionally, the correlation of miR-29c with MIAT and Loxl2 was further verified in patients' samples., Conclusion: Our data indicated that MIAT might be an oncogenic lncRNA that promoted proliferation and metastasis of ccRCC, and could be a potential therapeutic target in human ccRCC., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

In the course of modeling the naturally occurring tumor immunity seen in patients with paraneoplastic cerebellar degeneration (PCD), we discovered an unexpectedly high threshold for breaking CD8+ cytotoxic T cell (CTL) tolerance to the PCD autoantigen, CDR2. While CDR2 expression was previously found to be strictly restricted to immune-privileged cells (cerebellum, testes, and tumors), unexpectedly we have found that T cells also express CDR2. This expression underlies inhibition of CTL activation; CTLs that respond to epithelial cells expressing CDR2 fail to respond to T cells expressing CDR2. This was a general phenomenon, as T cells presenting influenza (flu) antigen also fail to activate otherwise potent flu-specific CTLs either in vitro or in vivo. Moreover, transfer of flu peptide-pulsed T cells into flu-infected mice inhibits endogenous flu-specific CTLs. Our finding that T cells serve as a site of immune privilege, inhibiting effector CTL function, uncovers an autorepressive loop with general biologic and clinical relevance.

Diabetes mellitus (DM)-induced high blood sugar severely damages vascular endothelial cells (VECs), which are in direct contact with the blood. Diabetic complications cause difficulties in skin wound healing and VECs are important for this process. Previous studies demonstrated that high blood sugar delayed the repair of wounded VECs, but the underlying mechanism has remained elusive. To explore the effects of diabetic conditions on VEC damage, cells were incubated in a medium with high glucose and then subjected to RNA-sequencing based transcriptome analysis. The results revealed that numerous biological processes were altered by HG stress, including extracellular matrix-receptor interaction, NOD-like receptor signaling and the nuclear factor (NF)-κB pathway. HG treatment increased the levels of phosphorylated inhibitor of NF-κB (IκB-α), the key NF-κB signaling regulator as well as the transcripts of plasminogen activator inhibitor-1 and interleukin-8, two inflammatory response markers. Treatment with extracellular signal-regulated kinase (ERK)- and c-Jun N-terminal kinase (JNK)-specific inhibitors U0126 and sp600125, respectively, led to the activation of IκB-α; however, the inhibitor of IκBα phosphorylation Bay11-7082 did not affect ERK and JNK activity, suggesting that ERK/JNK signaling occurs upstream of NF-κB in VECs. The present study provided useful information regarding the effects of diabetes on VECs, which may provide approaches for therapies of diabetes-associated complications in the future.

Caveolin-1 (CAV1) has been identified to be up-regulated in many cancers, including clear cell renal cell carcinoma (ccRCC). However, its potential function is still unclear in ccRCC. In this study, we demonstrated that CAV1 was frequently overexpressed in renal cell carcinoma tissues and cells, and was significantly associated with various clinicopathological parameters. In addition, high CAV1 expression was associated with poor disease-free survival (DFS) rate and could serve as a useful diagnostic indicator in ccRCC patients with different clinicopathological stages. Functional experiments demonstrated that CAV1 knockdown inhibited cell migration and invasion, whereas overexpression of CAV1 promoted cell migration and invasion in ccRCC. Moreover, CAV1 expression was up-regulated in sunitinib-resistant renal cancer cell lines, and its overexpression promoted sunitinib resistance. In general, our results confirm that CAV1 plays an important role in the metastasis of kidney cancer and induces sunitinib resistance, so CAV1 function suppression may become a promising clinical treatment strategy during renal cell carcinoma metastasis and sunitinib resistance., (Copyright © 2017. Published by Elsevier Inc.)

Agropyron elongatum (Host.) Neviski (synonym, Thinopyrum ponticum Podp., 2n = 70) has been used extensively as a valuable source for wheat breeding. Numerous chromosome fragments containing valuable genes have been successfully translocated into wheat from A. elongatum. However, reports on the transfer of powdery mildew resistance from A. elongatum to wheat are rare. In this study, a novel wheat-A. elongatum translocation line, 11-20-1, developed and selected from the progenies of a sequential cross between wheat varieties (Lankaoaizaoba, Keyu 818 and BainongAK 58) and A. elongatum, was evaluated for disease resistance and characterized using molecular cytogenetic methods. Cytological observations indicated that 11-20-1 had 42 chromosomes and formed 21 bivalents at meiotic metaphase I. Genomic in situ hybridization analysis using whole genomic DNA from A. elongatum as a probe showed that the short arms of a pair of wheat chromosomes were replaced by a pair of A. elongatum chromosome arms. Fluorescence in situ hybridization, using wheat D chromosome specific sequence pAs1 as a probe, suggested that the replaced chromosome arms of 11-20-1 were 5DS. This was further confirmed by wheat SSR markers specific for 5DS. EST-SSR and EST-STS multiple loci markers confirmed that the introduced A. elongatum chromosome arms belonged to homoeologous group 5. Therefore, it was deduced that 11-20-1 was a wheat-A. elongatum T5DL∙5AgS translocation line. Both resistance observation and molecular marker analyses using two specific markers (BE443538 and CD452608) of A. elongatum in a F2 population from a cross between line 11-20-1 and a susceptible cultivar Yannong 19 verified that the A. elongatum chromosomes were responsible for the powdery mildew resistance. This work suggests that 11-20-1 likely contains a novel resistance gene against powdery mildew. We expect this line to be useful for the genetic improvement of wheat.

Research on human immunology has been hindered by the lack of optimal small animal models, given that the protective immune responses of human and non-human species show significant differences. However, due to ethical constraints[1] and the high cost of clinical trials, it is urgent to improve the current animal models that can mimic faithfully human physiology, particularly the human immune system (HIS). HIS mice had been generated recently by engrafting human hematopoietic stem cells (hHSCs) or human peripheral mononuclear cells (hPBMCs) into highly immuno-deficient mice such as NSG, NOG or NRG mice. However, a major experimental drawback for studies using these models is the rapid onset of Graft-versus-Host Disease (GvHD). In the present study, we overcome this limitation by generating new immuno-deficient mice named "HUMAMICE" (HLA-A2+/+/DR1+/+/H-2-β2m-/-/IAβ-/-/Rag2-/-/IL2rγ-/-/Perf-/- mice), which expressed human HLA molecules instead of mouse MHC molecules (H-2), and whose immuno-deficient status was reversed by transferring functional HLA-matched PBMCs thus producing mice with an immuno-competent status with a functional human immune system. We showed that in this HLA-matched context, the hPBMC-transfer led to high lymphocytes engraftment rates without GvHD over three months in this novel mouse model. Furthermore, to evaluate the utility of the hPBMC-HUMAMICE, we immunized them with commercial vaccine of Hepatitis B virus (HBsAg, Hepvac@) which resulted in robust and reproducible production of high levels of HBsAg-specific antibodies, implying that both transferred T and B lymphocytes were functional in HUMAMICE. These responses are comparable to those observed in human clinical trials with this identical vaccine. In conclusion, these findings indicated that the HLA-matched-hPBMC-HUMAMICE represents a promising model for dissecting human immune responses in various human diseases, including infectious diseases, cancers and tumors, and to facilitate the development of novel vaccines and cellular therapies.

Background/aims: We previously performed microRNA (miRNA) microarray to identify effective indicators of clear cell renal cell carcinoma (ccRCC) tissue samples and preoperative/postoperative plasma in which we identified miR-144-3p as an oncomiRNA. However, the molecular mechanism of miR-144-3p remains unclear. This study aims to explore the roles of miR-144-3p in the invasion, migration and Sunitinib-resistance in ccRCC and to elucidate the underlying mechanisms., Methods: Gain and loss of function approaches were used to investigate the cell proliferation, cycle distribution, clonogenicity, migration, invasion, chemosensitivity of miR-144-3p in vitro. The xenograft model was used to assess the effects of miR-144-3p overexpression on tumorigenesis. Bioinformatics analysis and dual-luciferase reporter assay were used to indentify AT-rich interactive domain 1A (ARID1A) as a direct target gene of miR-144-3p. Quantitative RT-PCR, Western blotting, and immunohistochemical (IHC) staining were used to explore ARID1A expression level of the mRNA and protein., Results: We found that miR-144-3p overexpression enhanced cell proliferation, clonogenicity, migration, invasion, and chemoresistance in ccRCC cells. Notably, the oncotumor activities of miR-144-3p were mediated by repressing the expression of ARID1A. The downregulation of ARIDIA could promote the function of miR-144-3p in cell proliferation, metastasis and chemoresistance. Consistently, ARID1A mRNA and protein levels were decreased in ccRCC and in nude mice, and they negatively correlated with miR-144-3p., Conclusion: Higher miR-144-3p may enhance malignancy and resistance to Sunitinib in ccRCC by targeting ARID1A, the observations may uncover novel strategies of ccRCC treatment., (© 2017 The Author(s). Published by S. Karger AG, Basel.)

The elastic anisotropy and thermodynamic properties of the recently synthesized Pnnm -CN have been investigated using first-principles calculations under high temperature and high pressure. The calculated equilibrium crystal parameters and normalized volume dependence of the resulting pressure agree with available experimental and theoretical results. Within the considered pressure range of 0-90 GPa, the dependences of the bulk modulus, Young's modulus, and shear modulus on the crystal orientation for Pnnm -CN have been systematically studied. The results show that the Pnnm -CN exhibits a well-pronounced elastic anisotropy. The incompressibility is largest along the c -axis. For tension or compression loading, the Pnnm -CN is stiffest along [001] and the most obedient along [100] direction. On the basis of the quasi-harmonic Debye model, we have explored the Debye temperature, heat capacity, thermal expansion coefficient, and Grüneisen parameters within the pressure range of 0-90 GPa and temperature range of 0-1600K.

Background: A large proportion of acute respiratory tract infections (ARTI) remain without etiologic diagnosis, reason why new pathogens are investigated continuously. Human bocavirus (HBoV) was discovered in 2005, as a new member of Parvoviridae family and proposed to cause ARTI., Aim: To know the prevalence of HBoV among pediatric populations hospitalized for ARTI in two provinces of Argentina: Santa Fe and Tucuman; and to describe epidemiological and clinical aspects associated to its detection., Materials and Methods: We studied nasopharyn-geal aspirates of patients younger than 5 years old that were hospitalized during 2013 due ARTI. HBoV DNA was assayed using PCR described by Allander et al. Traditional virnses were studied by immunofluorescence. Personal, clinical and epidemiological data were collected in a standardized form., Results: The HBoV was detected in 7% of the samples and was prevalent in spring and summer and in children younger of 2 years old. Other respiratory viruses were detected in 22% of HBoV positive samples., Discussion: We detected HBoV in these two provinces of Argentina. Further studies should be performed to determine if it's a recent infection or prolonged viral shedding.

Objective: To study the spatial and temporal characteristics of Oncomelania hupensis in Eryuan County, Yunnan Province from 2005 to 2012, so as to provide the scientific evidence for snail surveillance and control., Methods: Based on the geographic database of O. hupensis snail distribution from 2005 to 2012, the spatial and local autocorrelation analysis and "hot spots" analysis were applied to analyze the spatial and temporal characteristics of the snails., Results: Percent of frames with O. hupensis snails in Eryuan County decreased as a whole from 2005 to 2012. The spatial clustering of global autocorrelation (Moran's I ) was increasing from 2007 to 2012 and all Moran's I values showed statistically significance. The local spatial autocorrelation analysis indicated that the number of villages of High-High type of correlation model increased from 2 in 2005 to 7 in 2012, which mainly clustered in plateau canyon areas. The infected snails with High-High type mainly distributed in plateau basin region in 2007. Further "hot spot" analysis found that the living snails gathered in Xinzhuang, Liantie, Xipo and Taiping nearby areas., Conclusions: The snail distribution in Eryuan has global and local spatial autocorrelations. The number of villages of High-High type of correlation increased. These findings provide the basis for target control of O.hupensis in the future.

Loxoscelism is a condition produced by the bite of Loxosceles laeta. It can present as cutaneous loxoscelism with only vascular dermal manifestations or as viscerocutaneus loxoscelism with systemic compromise and a mortality rate of 1 to 3%. We report the case of an adult patient presenting viscerocutaneus loxoscelism, who was evolving with macrohematuria, edema, and progressive blisters, requiring treatment in the intensive care unit. He was treated according to the actual scientific evidence with antihistamines, corticosteroids, and dual antibiotic therapy covering Streptococcus spp., Staphylococcus spp., and anaerobes, particularly penicillin and tetracycline resistant C. perfringens. The use of dapsone and antiloxosceles-serum was avoided. The patient showed a favorable clinical evolution.

Chemotherapy drugs treatment causes neuropathic pain, hyperalgesia and allodynia are common components of neuropathic pain, so effectively therapeutic strategy is required. In this study, we evaluated the antinociceptive effects of matrine on vincristine-induced neuropathic pain in mice. Vincristine (100 μg/kg i.p.) was administered once per day for 7 days (day 0-6) in mice. Matrine (15, 30, 60 mg/kg, i.p.) was repeated administration in early phase (day 0-6) or late phase (day 7-13). Hyperalgesia and allodynia were evaluated by withdrawal response using von Frey filaments, plantar and cold-plate on 7, 14 and 21 day. Injection of vincristine produced mechanical hyperalgesia and cold allodynia. Matrine was found to produce a protective role in both von Frey filaments and cold-plate test. The analysis of the effect supports the hypothesis that matrine is useful in therapy of vincristine-induced neuropathic pain. In conclusion, this study demonstrates that administration of matrine is associated with antinociceptive effect on mechanical and cold stimuli in a mice model of vincristine-induced neuropathy pain.

Hippocampal neuronal loss plays an important role in epileptogenesis, and it is considered a trigger of repeated spontaneous recurrent seizures (SRS). The BDNF/TrkB signaling pathway regulates neuronal plasticity in the CNS, and promotes epileptogenesis. Previous studies have shown that Peroxisome proliferator-activated receptor gamma (PPARγ) agonists exert neuroprotective effects by inhibiting oxidative stress and inflammation in epilepsy. In the present study, the PPARγ agonist rosiglitazone inhibited increases in BDNF and TrkB after status epilepticus (SE), and also prevented hippocampal neuronal loss. More importantly, our study showed that rosiglitazone suppressed SRS. However, the effects of rosiglitazone were significantly reversed by cotreatment with K252a, an antagonist of TrkB. Additionally, rosiglitazone did not affect the development and severity of SE. Thus, our data provide evidence that rosiglitazone exerts neuroprotective and antiepileptic effects involve BDNF/TrkB signaling. Our study also offers new perspectives for the treatment of epilepsy., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

In this study, we investigated the neuroprotective effect of oxysophoridine on ischemia and ischemia-like insults. Protection by oxysophoridine was studied at the in vivo level using a model of middle cerebral artery occlusion in mice and at the in vitro level using primary rat hippocampal neuronal cultures exposed to oxygen-glucose deprivation, a model of ischemia-like injury. The behavioral test was performed by using the neurological scores. The infarction volume of brain was assessed in the brain slices stained with 2,3,5-triphenyl tetrazolium chloride. The neuron apoptosis was evaluated by Hoechst 33342 staining. The morphological change in the neurons was examined using a Transmission Electron Microscope (TEM or EM). To evaluate neuron apoptosis, caspase-3, -9, and - 8 activities were measured using assay kits with an ELISA reader. The Western blotting assay was used to evaluate the release of cytochrome c and expression of caspase-3, Bcl-2, and Bax proteins. The quantitative real-time PCR assay was used to evaluate the release of cytochrome c and the expression of caspase-3 mRNA. Oxysophoridine-treated groups (62.5, 125, 250 mg/kg) markedly reduced neurological deficit scores and infarct volumes. Treatment with oxysophoridine (5, 20, 80 µmol/L) significantly attenuated neuronal damage, with evidence of decreased cell apoptosis and decreased cell morphologic impairment. Furthermore, treatment with oxysophoridine could effectively downregulate the expression of cytochrome c and caspase-3 in both mRNA and protein levels, and Bax in the protein level, and induce an increase of Bcl-2 in the protein level. The caspase-3, -9, and -8 activities were also inhibited. These findings suggested that oxysophoridine may be a potential neuroprotective agent for cerebral ischemia injury., (Georg Thieme Verlag KG Stuttgart · New York.)

A new homozygous humanized transgenic mouse strain, HLA-A2.1(+/+)HLA-DP4(+/+) hCD4(+/+)mCD4(-/-)IAβ(-/-)β2m(-/-) (HLA-A2/DP4), was obtained by crossing the previously characterized HLA-A2(+/+)β2m(-/-) (A2) mouse and our previously created HLA-DP4(+/+) hCD4(+/+)mCD4(-/-)IAβ(-/-) (DP4) mouse. We confirmed that the transgenes (HLA-A2, HLA-DP4, hCD4) inherited from the parental A2 and DP4 mice are functional in the HLA-A2/DP4 mice. After immunizing HLA-A2/DP4 mice with a hepatitis B DNA vaccine, hepatitis B virus-specific antibodies, HLA-A2-restricted and HLA-DP4-restricted responses were observed to be similar to those in naturally infected humans. Therefore, the present study demonstrated that HLA-A2/DP4 transgenic mice can faithfully mimic human cellular responses. Furthermore, we reported four new HLA-DP4-restricted epitopes derived from HBsAg that were identified in both vaccinated HLA-A2/DP4 mice and HLA-DP4-positive human individuals. The HLA-A2/DP4 mouse model is a promising preclinical animal model carrying alleles present to more than a quarter of the human population. This model should facilitate the identification of novel HLA-A2- and HLA-DP4-restricted epitopes and vaccine development as well as the characterization of HLA-DP4-restricted responses against infection in humans.

Three starches from the wheat varieties AK58, ZM18 and YZ4110 were separated into large (A) and small (B) granules, which were characterized structurally and evaluated for their functional properties. SEM results showed that the size of A-granules from ZM18 and YZ4110 were about the same, but the sizes of A-granules and B-granules from AK58 were larger than those of ZM18 and YZ4110. FTIR spectra showed that all the samples exhibited a similar pattern, with seven main modes with maximum absorbance peaks near 3,500, 3,000, 1,600, 1,400, 1,000, 800, 500 cm-1. The B-granules of ZM18 and YZ4110 had less amylose content, although the difference among the total amylose contents of the three unfractionated starches was not significant. X-ray diffraction (XRD) patterns showed predominantly A-type crystallinity for all the starches. The A-granules showed sharper XRD patterns than the other starches. DSC analysis showed that the A-granules had broader ranges of gelatinization temperatures than the B-granules from the same wheat variety. The gelatinization enthalpy (ΔH) of A-granules was higher than that of B-granules. AK58 exhibited the smallest enthalpy, while ZM18 showed the largest enthalpy. In pasting tests, the A-granule starch of AK58 had higher peak, final and setback viscosity, lower breakdown and pasting temperature, and the B-granule starch and unfractionated starch of AK58 had lower peak, breakdown, final and setback viscosity and higher pasting temperature than ZM18 and YZ4110.

Gliomas, with a poor clinical course, account for 30% to 40% of all intracranial tumors. Immunotherapy with monoclonal antibodies has emerged as a promising area of investigation and recently it has been shown that antibodies utilize complementarity-determining regions (CDRs) of their variable domains to bind to antigens with high affinity and specificity. Here, we designed an antibody mimetic fused with diphtheria toxin to target the U87 MG glioma cell line. VHCDR1 and VLCDR3, together with 5 amino acid residues on both side of the CDRs, through a cognate framework region (VHFR2) yielded a mimetic of BT32/A6 (United States Patent number: 5639863). We fused the mimetic with the first 388 amino acid residues of diphtheria toxin and E. coli strain BL21 (ED3) was used to express the soluble immunotoxin DT-MG. The immunotoxin DT-MG alone did not kill Raji up to the maximal concentration tested (10-6M) in vitro. By contrast, concentrations ≥ 10-9M, of the fused DT-MG killed more than 95% of U-87 MG cells. It is suggested that the mimetic maintained the synergic interactions and high-affinity associated with the parent antibody. This construct holds promise for targeting specific cancer epitopes and may be useful when incorporated into diagnostic and therapeutic regimens.

Background: A 2009 global influenza pandemic caused by a novel swine-origin H1N1 influenza A virus has posted an increasing threat of a potential pandemic by the highly pathogenic avian influenza (HPAI) H5N1 virus, driving us to develop an influenza vaccine which confers cross-protection against both H5N1 and H1N1 viruses. Previously, we have shown that a tetra-branched multiple antigenic peptide (MAP) vaccine based on the extracellular domain of M2 protein (M2e) from H5N1 virus (H5N1-M2e-MAP) induced strong immune responses and cross-protection against different clades of HPAI H5N1 viruses. In this report, we investigated whether such M2e-MAP presenting the H5N1-M2e consensus sequence can afford heterosubtypic protection from lethal challenge with the pandemic 2009 H1N1 virus., Results: Our results demonstrated that H5N1-M2e-MAP plus Freund's or aluminum adjuvant induced strong cross-reactive IgG antibody responses against M2e of the pandemic H1N1 virus which contains one amino acid variation with M2e of H5N1 at position 13. These cross-reactive antibodies may maintain for 6 months and bounced back quickly to the previous high level after the 2nd boost administered 2 weeks before virus challenge. H5N1-M2e-MAP could afford heterosubtypic protection against lethal challenge with pandemic H1N1 virus, showing significant decrease of viral replications and obvious alleviation of histopathological damages in the challenged mouse lungs. 100% and 80% of the H5N1-M2e-MAP-vaccinated mice with Freund's and aluminum adjuvant, respectively, survived the lethal challenge with pandemic H1N1 virus., Conclusions: Our results suggest that H5N1-M2e-MAP has a great potential to prevent the threat from re-emergence of pandemic H1N1 influenza and possible novel influenza pandemic due to the reassortment of HPAI H5N1 virus with the 2009 swine-origin H1N1 influenza virus.

Because of unique economic, cultural, and social factors, the personal experiences of HIV/AIDS patients in the rural areas of western China are not well understood. The aim of this study was to explore HIV/AIDS patients' thoughts and personal experiences in the environment and conditions of rural western China. Sixteen HIV/AIDS patients from remote western areas of China were interviewed by using an established qualitative method, during April to June 2008. The interviews were transcribed, and the findings were extracted after the interview content was read, classified, and analyzed repeatedly. We uncovered five general categories of personal experiences: worsening of family economic status, profound influence of traditional village culture, the family as the dynamic of surviving, an enhanced sense of familial responsibility, and dramatic psychological changes. The results of this study can provide useful information to assist health care professionals in China in their efforts to improve the general condition of these HIV/AIDS patients.

A laboratory experiment was conducted to study effects of urea fertilizer on the chemical composition of soil solutions over time, and to determine Al toxicity as a function of rates of urea application. The experiment revealed that addition of urea fertilizer to soils caused drastic changes in soil pH during the hydrolysis and nitrification stages of urea transformation in the experiment. These pH changes, depending on the N rate of urea application and time courses, had variable effects on soil exchangeable Al, extracted with artificial solutions containing 1 mol l(-1) KCl. The Al mobilization rate could be resolved into two phases: A declining phase for Al was attributed to the urea-induced hydrolysis while a second rising phase was dependent with the nitrification of added N fertilizer. The decreases in exchangeable Al reached the greatest in 4-7 days after fertilization, consistent with soil pH increase. Decreased Al availability had been observed as a consequence of increasing urea addition and soil pH when using Root elongation of maize seedlings as the estimators. Results from the present study demonstrate that urea fertilizer to the surface of soils may lead to a temporary immobilization of Al and, therefore, alleviated Al toxicity to plant seedlings.

Acetochlor and methamidophos are two important agrochemicals which are widely applied to agricultural production in northeast China. The investigation on the earthworm Eisenia fetida as an important type of soil animals exposed to single and binary-combined contamination of acetochlor and methamidophos was thus carried out. The single toxic effect test showed that the two agrochemicals had their toxicity to the earthworms living in phaiozem. Acetochlor had a stronger acute toxic effect on the earthworms than methamidophos. The mortality of the earthworms exposed to individual acetochlor and methamidophos changed with an increase in the exposure time and the exposed concentrations. The LD50 value of acetochlor and methamidophos toxic to the earthworms was 115.6-275.3 and 29.5-228.6 mg/kg, respectively. The weight of the earthworms was a more sensitive index compared to the mortality in indicating toxic effects of acetochlor and methamidophos in phaiozem. When considering both the mortality and the body-weight change, the combined pollution of acetochlor and methamidophos in phaiozem resulted in their synergic toxic effects on the earthworms.

Spike differentiation processes and freezing damage of three wheat varieties were studied by sowing in different stages. The results showed that under the condition of weather changing warm, the time of entering each stage of spike differentiation of wheat of strong spring variety was earlier than that of wheat of spring variety and semi-winter variety. Sowing times had more effects on durative time of the elongation stage, single-prism stage and two-prism stage of the spike differentiation. Under sowing early, the stronger the springness of wheat was, the quicker it developed, the higher spike differentiation phases it reached before winter, and the more serious freezing damage it suffered in wintering. According to this, the semi-winter varieties of wheat should be adopted first and arranged in pairs with spring varieties in wheat production, and the sowing times should not be too early as the weather becoming warm.