Effect of ß-alanine on the athletic performance and blood amino acid metabolism of speed-racing Yili horses.

The objective of this study was to examine the effects of supplemental ß-alanine feeding on the athletic performance of Yili horses involved in speed racing, focusing on alterations in plasma free amino acid patterns pre and post exercise. Additionally, the research aimed to evaluate the effects of carnosine on the plasma acid-base buffering capacity and antioxidant levels in these horses. Twelve Yili horse stallions, averaging 3 years in age and 346.50 ± 21.39 kg in weight, were chosen and randomly divided into two groups: a control group and a test group, each comprising six horses. The control group received a supplementation of 300 mg/kg BW/day of α-alanine, while the test group received 300 mg/kg BW/day of ß-alanine. This supplementation regimen was maintained for a 30-day supplementation trial period, under identical feeding and management conditions. Throughout the trial, the horses participated in the 1,000 Speed Race, and three distinct blood samples were gathered for assessing plasma free amino acids, blood gases, biochemical parameters, and antioxidant parameters. The outcomes indicated a considerable enhancement in the 1,000 m exercise performance of the speed racing Yili horses in the test group compared to the control group, showcasing a noteworthy improvement of 12.01%, with the test group completing the race 13.29 s faster. Notably, the α-alanine content in the plasma of the control group Yili horses remained higher than that of the test group, demonstrating a consistent increasing trend. By contrast, the plasma ß-alanine content was notably higher in the test group than in the control group. Over the course of the supplementation period, plasma ß-alanine exhibited an escalating and then stabilizing trend in the test group, whereas in the control group, although ß-alanine content also increased, the trend was less pronounced. The plasma levels of histidine and carnosine showed minimal variance between the two groups. Overall, the test group of Yili horses exhibited slightly higher plasma levels of histidine and carnosine compared to the control group. The addition of ß-alanine to their diet for a duration of 30 days notably affected the plasma levels of amino acids both pre- and post-exercise in speed-racing Yili horses. Furthermore, ß-alanine demonstrated an inhibitory effect on the catabolism of these horses' bodies during high-intensity exercise. Ten marker amino acids, including valine, leucine, ß-alanine, isoleucine, carnosine, 3-methyl-histidine, lysine, ethanolamine, argnine, and taurine, displayed statistically significant changes. ß-alanine notably increased the blood glucose levels of Yili horses and played a role in expediting the restoration of blood gas levels post-exercise. Moreover, in the test group of Yili horses, the levels of superoxide dismutase, glutathione peroxidase, and total antioxidant capacity significantly increased both before and after the race, while the content of malondialdehyde, an oxidation product, exhibited an extremely significant decrease immediately after the race. These outcomes suggest that the addition of ß-alanine significantly augmented antioxidant levels during high-intensity exercise in Yili horses. Consequently, it reduced post-exercise injuries and accelerated the recovery process after exercise.

Serological investigation and isolation of Salmonella abortus equi in horses in Xinjiang.

BACKGROUND: Salmonella enterica subspecies enterica serovar abortus equi (S. abortus equi) is one of the main pathogens that causes abortion in pregnant horses and donkeys, which was highly infectious and greatly restricts the healthy development of the horse industry. OBJECTIVES: In order to investigate the prevalence and biological characteristics of S. abortus equi in different regions and breeds of horses in Xinjiang. METHODS: This study conducted ELISA detection of S. abortus equi antibodies on serum samples of 971 horses collected from three large-scale horse farms and five free-range horse farms in Yili Prefecture and Bayingol Mongolian Autonomous Prefecture of Xinjiang from 2020 to 2023. On this basis, bacterial isolation, culture, identification, and drug sensitivity tests were conducted on 42 samples of aborted foal tissues and 23 mare vaginal swabs. RESULTS: The results showed that the positive rate of S. abortus equi antibody was as high as 20.91% in 971 horse serum samples. Among them, the positive rate in the Ili region (29.09%) was significantly higher than that in the Bayingole region (11.24%), and the positive rate in mares (22.45%) was higher than that in stallions (14.05%). In terms of horse breeds, the positive rates of self-propagating thoroughbred horses, half-bred horses, Ili horses and Yanqi horses were 43.22%, 28.81%, 14.72% and 11.24% respectively. In addition, S. abortus equi was more susceptible to juvenile and elderly horses, with positive rates of 70.00%and 41.86%, respectively, both of which were significantly higher than young (10.97%) and adult (19.79%) horses. Further, 9 strains of S. abortus equi were obtained through bacterial isolation, culture and identification, which were resistant to five antibiotics (Clarithromycin, Clindamycin, penicillin, Sulfamethoxazole and Rifampicin), and sensitive to 13 antimicrobial agents (Amoxicillin, Ciprofloxacin and Gentamicin, et al.). CONCLUSION: There was a high infection rate of S. abortus equi in Ili Prefecture and self-propagating thoroughbred horses, and juvenile or old mares were more susceptible, which will provide scientific basis for the prevention of S. abortus equi infection in different regions and breeds of horses in Xinjiang.

Abortion storm of Yili horses is associated with Equus caballus papillomavirus 2 variant infection.

Nine different species of Equus caballus papillomavirus (EcPV) and three bovine papillomaviruses (BPVs) have been reported to infect horses. However, there are few descriptions of such infections in China. In our pioneer study on Chinese horses, we identified EcPV-2 in the nasal swabs (4/230, 1.7%) of Yili horses, and the semen (3/18, 16.7%) of thoroughbred horses. This indicated that EcPV is indeed hosted by horses in China, and that EcPV-2 might be transmitted though breeding. Further detection of EcPVs in the lung tissues of aborted fetuses of Yili horses, which were originally negative for equid herpes viruses, demonstrated EcPV-2 positivity in 19 of 50 samples, thereby indicating that EcPV-2 may be a new pathogen responsible for causing abortion. Thereafter, sequence analyses of the L1 genes of 26 EcPV-2 in China were performed, indicating that EcPV-2, which primarily infects horses in China, shared 98.3-99.9% nt identity with the published sequences for EcPV-2. These observations indicated that EcPV-2 identified in the current study were highly similar variants of the previously identified strains of EcPV-2. Phylogenetic analysis based on L1 gene sequences from GenBank showed that the EcPV-2 found in Chinese horses was closely related to and clustered together with an already known EcPV-2a lineage. Our study provides the first evidence related to EcPV-2 infection in Chinese horses, which can serve as a causative agent for Yili horse abortions, and may thus lay the foundation for a systematic and detailed epidemiological study of this infection in Chinese horses.

Molecular identification and phylogenetic analysis of gastrointestinal nematodes in different populations of Kazakh sheep.

Gastrointestinal nematode (GIN) infection in sheep has been recognized globally as a major problem challenging animal health and production. The objective of this study is to use a molecular diagnosis of the prevalence for gastrointestinal nematode (GIN) dominant species of Kazakh sheep and its hybrid (Kazakh × Texel). The internal transcribed spacer 2 (ITS-2) sequences of ribosomal DNA (rDNA) were used as the target sequence. In the study, three dominant species of nematodes, namely Haemonchus contortus, Trichostrongylus spp., and Teladorsagia (Ostertagia) circumcincta from the Kazakh sheep and the F1 and F2 generations of Texel × Kazakh sheep hybrids were subjected to molecular identification and phylogenetic analysis. The fecal and single larva genomic DNA were extracted and amplified by PCR using specific primers to determine the infection rate of the three nematode species. In addition, the PCR products were sequenced and analyzed using bioinformatics methods to construct a phylogenetic tree. The results showed that all the three species had their ITS-2 specific amplified. According to the sequence homology analysis of PCR products, the results showed a high homology (above 98.5% homology) with H. contortus, Trichostrongylus spp., T. circumcincta ITS-2 sequences in GenBank. Phylogenetic analysis showed that the ITS-2 sequences of the three species were on the same branch as the ITS-2 sequences of the same species in NCBI. And on different branches from those of the ITS-2 sequences of different families, genera and species. Sequences carried out on three species from different samples showed a close relationship and little genetic difference in phylogenetic tree. The infection rates based on fecal DNA were 35.59, 25.55, and 11.24% for H. contortus, Trichostrongylus spp., and T. circumcincta, respectively. While the infection rates based on larva DNA, were 24.07, 18.89, and 13.26% for H. contortus, Trichostrongylus spp., and T. circumcincta, respectively. The seasonal prevalence of the three dominant species in spring was significantly higher than that in autumn and winter. And there was no significant difference between Kazakh, F1 and F2 sheep considering the infection rate of the studied three species of nematodes. This study provides valuable molecular approaches for epidemiological surveillance and for assisting in the control of Nematodirus infection in sheep.

Fast and bioluminescent detection of antibiotic contaminants by on-demand transcription of RNA scaffold arrays.

Cell-free biosensors have inspired low-cost and field-applicable methods to detect antibiotic contaminants. However, the satisfactory sensitivity of current cell-free biosensors is mostly achieved by sacrificing the rapidity, which prolongs turnaround time by hours. Additionally, the software-based result interpretation provides an obstacle for delivering these biosensors to untrained individuals. Here, we present a bioluminescence-based cell-free biosensor, termed enhanced Bioluminescence sensing of Ligand-Unleashed RNA Expression (eBLUE). The eBLUE leveraged antibiotic-responsive transcription factors to regulate the transcription of RNA arrays that can serve as scaffolds for reassembling and activating multiple luciferase fragments. This process converted target recognition into an amplified bioluminescence response, enabling smartphone-based quantification of tetracycline and erythromycin directly in milk within 15 min. Moreover, the detection threshold of eBLUE can be easily tuned according to the maximum residue limits (MRLs) established by government agencies. Owing to this tunable nature, the eBLUE was further repurposed as an on-demand semi-quantification platform, allowing for fast (∼20 min) and software-free identification of safe and MRL-exceeding milk samples only by glancing over the smartphone photographs. Overall, the sensitivity, rapidity and user-friendliness of eBLUE demonstrate its potentials for practical applications, especially in resource-limited and household settings.

Correction: An epidemiological study of gastrointestinal nematode and Eimeria coccidia infections in different populations of Kazakh sheep.

[This corrects the article DOI: 10.1371/journal.pone.0251307.].

First detection of the occurrence and study of the genetic diversity of novel putative kirkoviruses in donkey in China.

The first representative of a seemingly novel virus family has been found during the metagenomic examination of a diseased and dead horse in the USA [Li et al. in J Gen Virol 96:2721-2733, 2015]. These authors have suggested the need for the establishment of a new family with the tentative name Kirkoviridae; however, the suggested name is not official yet. Soon after the discovery, similar, relatively large CRESS-DNA viruses have been detected in various animals in China and elsewhere. Besides the two main genes (rep and cap), characteristic for members of the family Circoviridae, the tentative kirkoviruses have considerably larger genomes of approximately 4000 nucleotides. Accordingly, these viruses possess three four additional ORFs coding for proteins of unknown function. This has been described previously. In the present manuscript, the authors report the sequence of kirkovirus-like viruses, detected by PCR in donkey excretes in China. From 73 samples, 8 were found positive. From three of these newly detected viruses, the full genomic sequence was determined, whereas from the other five only one gene, namely the replication-associated (Rep) protein was sequenced.

Outbreak of neuropathogenic equid herpesvirus 1 causing abortions in Yili horses of Zhaosu, North Xinjiang, China.

BACKGROUND: EHV-1 is one of the most serious viral pathogens that frequently cause abortion in horses around the world. However, so far, relatively little information is available on EHV-1 infections as they occur in China. In January 2021, during an abortion storm which occurred in Yili horses at the Chinese State Studs of Zhaosu (North Xinjiang, China), 43 out of 800 pregnant mares aborted. RESULTS: PCR detection revealed the presence of EHV-1 in all samples as the possible cause of all abortions, although EHV-4, EHV-2 and EHV-5 were also found to circulate in the aborted fetuses. Furthermore, the partial ORF33 sequences of the 43 EHV-1 shared 99.3-100% and 99.0-100% similarity in nucleotide and amino acid sequences respectively. These sequences not only indicated a highly conserved region but also allowed the strains to group into six clusters. In addition, based on the predicted ORF30 nucleotide sequence, it was found that all the strains carried a guanine at the 2254 nucleotide position (aspartic acid at position 752 of the viral DNA polymerase) and were, therefore, identified as neuropathogenic strains. CONCLUSION: This study is the first one that establishes EHV-1 as the cause of abortions in Yili horses, of China. Further characterization of the ORF30 sequences revealed that all the EHV-1 strains from the study carried the neuropathogenic genotype. Totally, neuropathogenic EHV-1 infection in China's horse population should be concerned although the virus only detected in Yili horse abortions.

N6-methyladenosine demethylase FTO promotes growth and metastasis of gastric cancer via m6A modification of caveolin-1 and metabolic regulation of mitochondrial dynamics.

Gastric cancer (GC) is the fifth most common tumor and the third most deadly cancer worldwide. N6-methyladenosine (m6A) modification has been reported to play a regulatory role in human cancers. However, the exact role of m6A in GC remains largely unknown, and the dysregulation of m6A on mitochondrial metabolism has never been studied. In the present study, we demonstrated that FTO, a key demethylase for RNA m6A modification, was up-regulated in GC tissues, especially in tissues with liver metastasis. Functionally, FTO acted as a promoter for the proliferation and metastasis in GC. Moreover, FTO enhanced the degradation of caveolin-1 mRNA via its demethylation, which regulated the mitochondrial fission/fusion and metabolism. Collectively, our current findings provided some valuable insights into FTO-mediated m6A demethylation modification and could be used as a new strategy for more careful surveillance and aggressive therapeutic intervention.

An epidemiological study of gastrointestinal nematode and Eimeria coccidia infections in different populations of Kazakh sheep.

This is an epidemiological study on the gastrointestinal nematode (GIN) and Eimeria coccidia infections in Kazakh sheep and the F1 and F2 generations of Kazakh × Texel sheep crosses. A total of 7599 sheep fecal samples were collected from the Zhaosu County and Nilka County in Ili Kazakh Autonomous Prefecture in the four seasons-spring, summer, autumn, and winter of 2019. The parasite causing the infection was identified by the saturated saline floating method, and the infection intensity was calculated by the modified McMaster method. SPSS19.0 was used to evaluate the differences in the fecal egg count (FEC) of for GIN and the fecal oocyst count (FOC) value of for coccidia per sample. The results showed that there were nine types of sheep GIN infections and Eimeria coccidia in these two counties of Ililocations, with the dominant parasite species of Haemonchus contortus, Trichostrongylus spp., and Ostertagia spp as the predominant parasites in the sheep. Most of the GIN and coccidia infections in these two regions were mild and moderate. The mean log (FEC) of GIN infection in the Zhaosu area was significantly higher than that in the Nilka area, whereas the mean log (FOC) of coccidia infection in Zhaosu was significantly lower than that of Nilka. The mean log (FEC) of GIN infection in the four seasons was the highest in spring, followed by in summer, then in autumn, and the lowest in winter. The mean log (FOC) of coccidia infection was the highest in spring, followed by in autumn, and was the lowest in summer and winter. The mean log (FEC) of GIN infection and log (FOC) of coccidia infection of Kazakh sheep was significantly higher than the F1 generation, which was then significantly higher than the F2 generation of summer. A positive correlation was found between the EPG and OPG levels in the sheep. These results showed that the GIN and coccidia infection intensities of the F1 generation sheep of Kazakh ×Texel crosses were significantly lower than that of Kazakh sheep paving the way for marker-based resistance selection.

Identification of Key Genes With Differential Correlations in Lung Adenocarcinoma.

BACKGROUND: With the advent of large-scale molecular profiling, an increasing number of oncogenic drivers contributing to precise medicine and reshaping classification of lung adenocarcinoma (LUAD) have been identified. However, only a minority of patients archived improved outcome under current standard therapies because of the dynamic mutational spectrum, which required expanding susceptible gene libraries. Accumulating evidence has witnessed that understanding gene regulatory networks as well as their changing processes was helpful in identifying core genes which acted as master regulators during carcinogenesis. The present study aimed at identifying key genes with differential correlations between normal and tumor status. METHODS: Weighted gene co-expression network analysis (WGCNA) was employed to build a gene interaction network using the expression profile of LUAD from The Cancer Genome Atlas (TCGA). R package DiffCorr was implemented for the identification of differential correlations between tumor and adjacent normal tissues. STRING and Cytoscape were used for the construction and visualization of biological networks. RESULTS: A total of 176 modules were detected in the network, among which yellow and medium orchid modules showed the most significant associations with LUAD. Then genes in these two modules were further chosen to evaluate their differential correlations. Finally, dozens of novel genes with opposite correlations including ATP13A4-AS1, HIGD1B, DAP3, and ISG20L2 were identified. Further biological and survival analyses highlighted their potential values in the diagnosis and treatment of LUAD. Moreover, real-time qPCR confirmed the expression patterns of ATP13A4-AS1, HIGD1B, DAP3, and ISG20L2 in LUAD tissues and cell lines. CONCLUSION: Our study provided new insights into the gene regulatory mechanisms during transition from normal to tumor, pioneering a network-based algorithm in the application of tumor etiology.

Histone methyltransferase SETD2 inhibits tumor growth via suppressing CXCL1-mediated activation of cell cycle in lung adenocarcinoma.

The histone H3 lysine 36 methyltransferase SET-domain-containing 2 (SETD2) has been reported to be frequently mutated or deleted in many types of human cancer. However, the role of SETD2 in lung adenocarcinoma (LUAD) has not been well documented. In the present study, we found that SETD2 was significantly down-regulated both in LUAD tissues and cell lines. Functionally, the increased expression of SETD2 significantly attenuated the proliferation of cancer cells by affecting the cell cycle, whereas SETD2 deficiency dramatically improved these proliferative abilities of cancer cells. Through conjoint analysis of RNA-seq and ChIP data, we identified a functional target gene of SETD2, CXCL1, and its expression was negatively correlated with that of SETD2. Moreover, SETD2 deletion stimulated cell cycle-related proteins to promote LUAD. Further mechanistic studies demonstrated that histone H3 lysine 36 trimethylation (H3K36me3) catalyzed by SETD2 interacted with the promoter of CXCL1 to regulate its transcription and downstream signaling pathways, contributing to tumorigenesis in vitro and in vivo. Our findings suggested that SETD2 inhibited tumor growth via suppressing CXCL1-mediated activation of cell cycle, indicating that the regulation of H3K36me3 level by targeting SETD2 and/or the administration of downstream CXCL1 might represent a potential therapeutic way for new treatment in LUAD.

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To explore the effects of different intercropping species on growth, nutrition absorption, and fruit quality of oriental melon, we examined plant height, stem diameter, root activity, contents of mineral elements (N, P, K, Ca and Mg), and fruit quality and yield of oriental melon under the oriental melon monoculture (MM), intercropping of fennel/oriental melon (FM), tillered-onion/oriental melon (TM), or wormwood/oriental melon (WM). Results showed that plant height of intercropping treatments was significantly higher than that of the monoculture over time. The stem diameter of the FM and TM treatments was significantly higher than that of the MM treatment, while there was no significant difference between the WM and MM treatments. At the stretch tendril stage, fruit setting stage, and fruit expanding stage, root activity of FM treatment was significantly higher than that of MM and TM treatments. The mine-ral elements contents of oriental melon plants in three intercropping treatments were higher than that in MM treatment in different degrees, with the mine-ral elements contents of FM treatment being higher than that of TM and WM treatments. The single fruit weights of FM and TM treatments did not differ from the MM treatment. The fruit quality indices of FM treatment were not lower than MM treatment, while some fruit quality indices (including the contents of glucose, fructose, and sucrose) of WM and TM treatments were lower than that under MM treatment. In summary, fennel was a suitable species for intercropping with the oriental melon.

Over-expression of Nectin-4 promotes progression of esophageal cancer and correlates with poor prognosis of the patients.

BACKGROUND: Nectin-4, also known as PVRL4 (poliovirus-receptor-like 4), is specifically expressed in the embryo and placenta. Recent studies have reported that the Nectin-4 is over-expressed in multiple human cancers, and such abnormal expression is associated with cancer progression and poor prognosis of the patients. In the present study, we aimed to characterize the expression pattern of Nectin-4 in human esophageal cancer (EC) tissues, and to investigate its clinical implications, prognostic value and regulatory effects on cellular functions of EC cells. METHODS: In the present study, we first examined Nectin-4 expression in human EC tissues by using immunohistochemistry (IHC) assay and analyzed the clinical associations. Then the cellular studies in vitro and the nude mice tumor model in vivo were used to examine the regulatory role of Nectin-4 in the progression of EC. RESULTS: Our results demonstrated that over-expression of Nectin-4 in human EC tissues was significantly associated with tumor size, depth of tumor invasion, and poor prognosis of the patients. The intervention of Nectin-4 expression in EC cell lines showed that the increased Nectin-4 expression could significantly promote the cell viability, migration, invasion and tumor formation. CONCLUSIONS: Our present data unveiled that Nectin-4 played an important role in tumor biology and could serve as a useful prognostic predictor of human EC.

Circular RNA hsa_circ_0004015 regulates the proliferation, invasion, and TKI drug resistance of non-small cell lung cancer by miR-1183/PDPK1 signaling pathway.

Circular RNAs (circRNAs) were recently reported to be involved in the pathogenesis of Non-small cell lung cancer (NSCLC), however, the molecular mechanisms of circRNAs in cell proliferation, invasion and TKI drug resistance remain largely undetermined. Here, we identified hsa_circ_0004015 was upregulated in NSCLC tissues, and was associated with the poor overall survival rate of NSCLC patients. Knockdown of hsa_circ_0004015 significantly decreased cell viability, proliferation, and invasion, whereas overexpression exhibited opposed effects in vivo and in vitro. Furthermore, hsa_circ_0004015 could enhance the resistance of HCC827 to gefitinib. In mechanism, hsa_circ_0004015 acted as a sponge for miR-1183, and PDPK1 was revealed to be target gene of miR-1183. Subsequently, functional assays illustrated that the oncogenic effects of hsa_circ_0004015 was attributed to the regulation of miR-1183/PDPK1 axis. In conclusion, circ_0016760/miR-1183/PDPK1 signaling pathway might play vital roles in the tumorigenesis of NSCLC.

A quantitative analysis of global environmental protection values based on the world values survey data from 1994 to 2014.

The four most recent sub-datasets of the World Value Survey (WVS) database (i.e., WVS3, WVS4, WVS5, and WVS6) contain a total of 25 non-numerical variables of environmental protection values and cover the period from 1994 to 2014. This study utilized these datasets to obtain the spatiotemporal distributions of the values and provided a preliminary analysis of the environmental protection values in different cultural districts. The work includes 4 parts. First, the information from the values included in the 25 variables is subjectively classified into action values and attitude values according to the meanings of the variable labels. Then, quantitative clustering is used to verify the results of the first step. These two steps consistently classify the 25 variables into "action" and "attitude" families. At the third step, all variables are processed as horizontal distributions in terms of the country using the arithmetic mean of the serial numbers chosen by the respondents because these numbers reflect the grade of the behavior or attitude toward environmental protection. A clustering procedure is also included in this step to reconfirm the classification results of the previous two steps. Finally, the two families are quantified using their common factors, which are the first leading modes of the empirical orthogonal function for each family. The multiyear averaged cultural district mean "action" and "attitude" indices are analyzed according to the World Culture Map. The results show that districts with different cultures have very different environmental protection values.

Solexa Profiling Identifies Differentially Expressed MiRNAs Between Sexually Immature and Mature Equine Testis

ABSTRACT MicroRNAs (miRNAs) are a class of short non-coding RNAs identified as potent regulators of gene expression. Previous studies have suggested that miRNAs are involved in mammalian spermatogenesis. Stallion fertility is an important trait for the horse breeding industry, but stallion fertility traits are largely ignored in the industry. In this study, we generated expression profiles of miRNAs in foal (immature) and stallion (mature) testes using Solexa sequencing. We identified 438 known and homologous equine miRNAs and 199 novel miRNAs which were distributed among all the chromosomes. The two developmental stages showed significant differences in miRNA expression patterns. Our result expands the horse miRNA database and provided additional information on the stallion fertility and possible spermatogenesis regulation through specific miRNAs.

Expression of CCR6 in esophageal squamous cell carcinoma and its effects on epithelial-to-mesenchymal transition.

Esophageal squamous cell carcinoma (ESCC) is the most common esophageal cancer associated with poor prognosis. We detected the expression of C-C motif chemokine receptor 6 (CCR6) and epithelial-to-mesenchymal transition (EMT) markers in esophageal tissues/cells, and evaluated the effects of CCR6 on ESCC cells proliferation, migration and invasion in response to C-C motif chemokine ligand 20 (CCL20) treatment. Our data showed CCR6 was highly expressed in ESCC cell lines (ECA-109 and TE-1), whereas kept in a low expression in normal cell lines HEEC (P < 0.001). CCL20 stimulus induced a significant decrease in the proliferation ability of ESCC (P < 0.05). The healing speed of CCL20 group was significantly higher than control in ECA-109 (P < 0.01), whereas significantly lower in αCCR6+CCL20 group than CCL20 group (P < 0.05).The number of cells permeabling through the polycarbonate membrane in CCL20 group was higher than control (P < 0.01). The cell number in αCCR6+CCL20 group was significantly reduced compared to CCL20 group in ECA-109 (P < 0.05). Moreover, after CCL20 stimulated in ECA-109, both mRNA and protein level of E-cadherin significantly decreased compared to control, while Vimentin was significantly higher. In αCCR6+CCL20 group, mRNA and protein level of E-cadherin significantly increased compared to CCL20 group, while Vimentin was much lower than CCL20 group. There was no significant difference in TE-1. In summary, high expression of CCR6 existed in the lymph node metastasis and TNM stage of ESCC. CCR6 play an important role in the regulation of tumor cell proliferation, invasion and migration. CCR6 may participate in regulating the occurrence of EMT in ESCC.

Apelin-13 exerts antidepressant-like and recognition memory improving activities in stressed rats.

Apelin is the endogenous ligand for the G-protein-coupled receptor (APJ). The localization of APJ in limbic structures suggests a potential role for apelin in emotional processes. However, the role of apelin in the regulation of stress-induced responses such as depression and memory impairment is largely unknown. In the present study, we evaluated the role of apelin-13 in the regulation of stress-induced depression and memory impairment in rats. We report that repeated intracerebroventricular injections of apelin-13 reversed behavioral despair (immobility) in the forced swim (FS) test, a model widely used for the selection of new antidepressant agents. Apelin-13 also reversed behavioral deficits (escape failure) in the learned helplessness test. The magnitude of the antiimmobility and anti-escape failure effects of apelin-13 was comparable to that of imipramine, a classic antidepressant used as a positive control. Rats exposed to FS stress showed memory performance impairment in the novel object recognition test, and this impairment was improved by apelin-13 treatment. Apelin-13 did not affect recognition memory performance in non-stressed rats. Furthermore, the pretreatment of LY294002 (PI3K inhibitors) or PD98059 (ERK1/2 inhibitor) blocked apelin-13-mediated activities in FS-stressed rats. These findings suggest that apelin-13 exerts antidepressant-like and recognition memory improving activities through activating PI3K and ERK1/2 signaling pathways in stressed rats.

Serum lemur tyrosine kinase-3: a novel biomarker for screening primary non-small cell lung cancer and predicting cancer progression.

PURPOSE: We aimed to determine the expression level of serum soluble lemur tyrosine kinase-3 (sLMTK3) in human non-small cell lung cancer (NSCLC), and to examine whether the s sLMTK3 level could be used as a biomarker to screen primary NSCLC and to predict lung cancer progression. METHODS: Serum levels of sLMTK3 in 67 patients with primary NSCLC, 28 patients with lung benign lesion, and 53 healthy volunteers were measured by sandwich ELISA. LMTK3 protein expression in NSCLC tissues and normal lung tissues was also detected by using immunohistochemical staining. Receiver operating characteristic (ROC) curve was selected to evaluate the sensitivity and the specificity of serum sLMTK3 level. RESULTS: The mean concentration of sLMTK3 in NSCLC group was significantly higher than in the lung benign lesion group (P < 0.001) and the healthy control group (P < 0.001). Higher sLMTK3 level was correlated with age (P = 0.013), tumor-node-metastasis (TNM) stage (P < 0.001), and lymph node metastasis (P < 0.001) of NSCLC. In contrast to the normal lung tissues, increased LMTK3 expression was found in the NSCLC tissues, and was mainly located on the cytoplasm and the nuclei of cancer cells. For separating NSCLC from control group, the corresponding areas under the ROC curve (AUC) were 0.947 for sLMTK3 and 0.804 for CEA. With cutoffs of 10.05 ng/ml for sLMTK3 and 5.0 ng/ml for CEA respectively, the sensitivity and the specificity of sLMTK3 and CEA were, 80.60% and 97.53%, 35.82% and 96.30%, respectively, indicating better diagnostic value of sLMTK3. CONCLUSIONS: The sLMTK3 level was significantly increased in human NSCLC, and could be used as a potential and valuable biomarker for screening primary NSCLC and for predicting the progression of patients with this malignancy.