Keeping mammalian gastrointestinal (GI) tract communities in balance is crucial for host health maintenance. However, our understanding of microbial communities in the GI tract is still very limited. In this study, samples taken from the GI tracts of C57BL/6 mice were subjected to 16S rRNA gene sequence-based analysis to examine the characteristic bacterial communities along the mouse GI tract, including those present in the stomach, duodenum, jejunum, ileum, cecum, colon and feces. Further analyses of the 283,234 valid sequences obtained from pyrosequencing revealed that the gastric, duodenal, large intestinal and fecal samples had higher phylogenetic diversity than the jejunum and ileum samples did. The microbial communities found in the small intestine and stomach were different from those seen in the large intestine and fecal samples. A greater proportion of Lactobacillaceae were found in the stomach and small intestine, while a larger proportion of anaerobes such as Bacteroidaceae, Prevotellaceae, Rikenellaceae, Lachnospiraceae, and Ruminococcaceae were found in the large intestine and feces. In addition, inter-mouse variations of microbiota were observed between the large intestinal and fecal samples, which were much smaller than those between the gastric and small intestinal samples. As far as we can ascertain, ours is the first study to systematically characterize bacterial communities from the GI tracts of C57BL/6 mice.
The molecular links between shock-response and adaptation remain poorly understood, particularly for extremophiles. This has hindered rational engineering of solvent tolerance and correlated traits (e.g., productivity) in extremophiles. To untangle such molecular links, here we established a model that tracked the microevolution from shock to adaptation in thermophilic bacteria.
Temporal dynamics of genomes and transcriptomes was tracked for Thermoanaerobacter sp. X514 which under increasing exogenous ethanol evolved from ethanol-sensitive wild-type (Strain X) to tolerance of 2%- (XI) and eventually 6%-ethanol (XII). Based on the reconstructed transcriptional network underlying stress tolerance, genetic engineering was employed to improve ethanol tolerance and production in Thermoanaerobacter.
The spontaneous genome mutation rate (μg) of Thermoanaerobacter sp. X514, calculated at 0.045, suggested a higher mutation rate in thermophile than previously thought. Transcriptomic comparison revealed that shock-response and adaptation were distinct in nature, whereas the transcriptomes of XII resembled those of the extendedly shocked X. To respond to ethanol shock, X employed fructose-specific phosphotransferase system (PTS), Arginine Deiminase (ADI) pathway, alcohol dehydrogenase (Adh) and a distinct mechanism of V-type ATPase. As an adaptation to exogenous ethanol, XI mobilized resistance-nodulation-cell division (RND) efflux system and Adh, whereas XII, which produced higher ethanol than XI, employed ECF-type ϭ24, an alcohol catabolism operon and phase-specific heat-shock proteins (Hsps), modulated hexose/pentose-transport operon structure and reinforced membrane rigidity. Exploiting these findings, we further showed that ethanol productivity and tolerance can be improved simultaneously by overexpressing adh or ϭ24 in X.
Our work revealed thermophilic-bacteria specific features of adaptive evolution and demonstrated a rational strategy to engineer co-evolving industrial traits. As improvements of shock-response, stress tolerance and productivity have been crucial aims in industrial applications employing thermophiles, our findings should be valuable not just to the production of ethanol but also to a wide variety of biofuels and biochemicals.
Shock; Adaptation; Ethanol; Microevolution; Thermophile
Spinal cord injury without radiographic abnormality (SCIWORA) is a rare condition seen in adults. Many interbody fusion cages have been developed for its treatment, but clinical studies of Fidji cervical cage are still scarce. A total number of five patients (four male and one female) were reviewed. The ages of the patients ranged from 40 to 60 years. All the patients underwent neurological and radiological examinations. Neurological and functional outcomes were assessed on the basis of Frankel's grade. Three of the patients were Frankel B, and the rest two were Frankel C. Magnetic resonance imaging was also performed for the evaluation of spinal cord and intervertebral disc injury. Anterior cervical discectomy and Fidji cervical cage fusion were performed for all. The fusion status was evaluated on the basis of X-rays. After surgical intervention, the clinical symptoms improved for all the patients. The disc interspaces in all the patients achieved solid union at final follow-up. Fidji cervical cage is very efficient in achieving cervical fusion in patients with SCIWORA. There are few complications associated with the use of this cage, and the functional and neurological outcomes are satisfactory.
The inhibitory action and the possible mechanism of anticancer compound Sanguinarine (SAN) on vascular endothelial growth factor (VEGF) in human mammary adenocarcinoma cells MCF-7 were evaluated in this study. We exposed MCF-7 to SAN for 24 h, then cell viability was assessed by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. Human VEGF was measured using a paired antibody quantitative ELISA kit, relative expression of VEGF mRNA was calculated using the real-time PCR studies, and the effect of SAN on the reactive oxygen species (ROS) level was detected by the flow cytometer. Treatment with SAN remarkably inhibited growth of MCF-7 cells and induced cell apoptosis. We found that VEGF release was stimulated by subtoxic concentrations of SAN and inhibited by high dose of SAN, SAN-evoked VEGF release was mimicked by low concentration of H2O2, and SAN-regulated VEGF inhibition was accompanied by increasing of ROS; these changes were abolished by antioxidant. High concentration of SAN inhibited VEGF mRNA expression in MCF-7 cultures, suggesting an effect at transcriptional level, and was also abolished by antioxidant. The present findings indicated that the regulation of VEGF expression and release from MCF-7 cells were possibly through reactive oxygen species evoked by SAN.
In the title compound, C21H17N2P, the dihedral angles between the 1,5-naphthyridine ring system (r.m.s. deviation = 0.005 Å) and the phenyl rings are 89.18 (8) and 77.39 (8)°. The phenyl rings are almost perpendicular, making a dihedral angle of 88.12 (8)°. The only possible intermolecular interaction is a very weak aromatic π–π stacking interaction [centroid–centroid separation = 3.898 (2) Å].
The aim of this study is to investigate the effects and possible mechanisms of sodium ferulate (SF) on anti-apoptosis in steroid-induced femoral head osteonecrosis in rabbits. Japanese white rabbits were randomly divided into three groups (control group, treatment group, and model group), each with 24 rabbits. The model and treatment groups were first injected with an intravenous dose of horse serum, 10 ml/kg, three weeks later with an intravenous dose of 7.5 ml/kg, and two weeks later with an intramuscular dose of methylprednisolone, 45 mg/kg, three times in order to establish rabbit models of osteonecrosis. Concurrently, the treatment group was injected with intravenous doses of SF 20 mg/kg for two weeks, once per day. Three time points, Weeks 2, 4, and 8, were selected after modeling was completed. Osteonecrosis was verified by histopathology with haematoxylin-eosin (HE) staining. The apoptosis rate of osteonecrosis was observed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The apoptosis expressions of caspase-3 and Bcl-2 were analyzed by immunohistochemistry and Western blot. The rabbit models of osteonecrosis were successfully established and observed by HE staining. SF was effective in intervening in apoptosis and decreasing the apoptosis rate in femoral head necrosis by the immunohistochemistry and TUNEL assay (P<0.01). Western blot analysis indicated that there were statistical significances in the protein levels of caspase-3 and Bcl-2 (P<0.01). SF has a protective effect by reducing the incidence of early steroid-induced femoral head necrosis in rabbits, effectively intervening in apoptosis through decreasing caspase-3 expression and up-regulating Bcl-2 expression.
Femoral head necrosis; Glucocorticoid; Sodium ferulate; Apoptosis; Rabbit
Over the past decade, liposomes became a focal point in developing drug delivery systems. New liposomes, with novel lipid molecules or conjugates, and new formulations opened possibilities for safely and efficiently treating many diseases including cancers. New types of liposomes can prolong circulation time or specifically deliver drugs to therapeutic targets. This article concentrates on current developments in liposome based drug delivery systems for treating diseases of the gastrointestinal tract. We will review different types and uses of liposomes in the development of therapeutics for gastrointestinal diseases including inflammatory bowel diseases and colorectal cancer.
liposome; colorectal cancer; inflammatory bowel disease; drug delivery
Pancreatic neuritis is a histopathological hallmark of pancreatic neuropathy and correlates to abdominal neuropathic pain sensation in pancreatic adenocarcinoma (PCa) and chronic pancreatitis (CP). However, inflammatory cell subtypes that compose pancreatic neuritis and their correlation to the neuropathic pain syndrome in PCa and CP are yet unknown.
Inflammatory cells within pancreatic neuritis lesions of patients with PCa (n = 20) and CP (n = 20) were immunolabeled and colorimetrically quantified with the pan-leukocyte marker CD45, with CD68 (macrophages), CD8 (cytotoxic T-lymphocytes), CD4 (T-helper cells), CD20 (B-lymphocytes), NCL-PC (plasma cells), neutrophil elastase, PRG2 (eosinophils), anti-mast cell (MC) tryptase and correlated to pain sensation. Perineural mast cell subtypes were analyzed by double immunolabeling with MC chymase. Expression and neural immunoreactivity of protease-activated receptor type 1 (PAR-1) and type 2 (PAR-2) were analyzed in PCa and CP and correlated to pain status of the patients.
In PCa and CP, nerves were predominantly infiltrated by cytotoxic T-lymphocytes (PCa: 35% of all perineural inflammatory cells, CP: 33%), macrophages (PCa: 39%, CP: 33%) and MC (PCa: 21%, CP: 27%). In both entities, neuropathic pain sensation was associated with a specific increase of perineural MC (PCa without pain: 14% vs. PCa with pain: 31%; CP without pain: 19% vs. CP with pain: 34%), not affecting the frequency of other inflammatory cell subtypes. The vast majority of these MC contained MC chymase. PAR-1 and PAR-2 expression did not correlate to the pain sensation of PCa and CP patients.
Pancreatic neuritis in PC and CP is composed of cytotoxic T-lymphocytes, macrophages and MC. The specific enrichment of MC around intrapancreatic nerves in neuropathic pain due to PCa and CP suggests the presence of MC-induced visceral hypersensitivity in the pancreas. Therefore, pancreatic and enteric neuropathies seem to share a similar type of neuro-immune interaction in the generation of visceral pain.
In Caenorhabditis elegans, the six proteins that make up the REF-1 family have been identified as functional homologs of the Hairy/Enhancer of Split (HES) proteins. These transcription factors act in both Notch dependent and Notch-independent pathways to regulate embryonic events during development; however, their post-embryonic functions are not well defined. As a first step toward understanding how the REF-1 family works together to coordinate post-embryonic events, we used gene expression microarray analysis to identify transcriptional targets of HLH-29 in L4/young adult stage animals. Here we show that HLH-29 targets are genes needed for the regulation of growth and lifespan, including genes required for oxidative stress response and fatty acid metabolism, and the ferritin genes, ftn-1 and ftn-2. We show that HLH-29 regulates ftn-1 expression via promoter sequences upstream of the iron-dependent element that is recognized by the hypoxia inducible factor, HIF-1. Additionally, hlh-29 mutants are more resistant to peroxide stress than wild-type animals and ftn-1(RNAi) animals, even in the presence of excess iron. Finally we show that HLH-29 acts parallel to DAF-16 but upstream of the microphthalmia transcription factor ortholog, HLH-30, to regulate ftn-1 expression under normal growth conditions.
Pulsus paradoxus is an exaggeration of the normal inspiratory decrease in systolic blood pressure. Despite a century of attempts to explain this sign consensus is still lacking. To solve the controversy and reveal the exact mechanism, we reexamined the characteristic anatomic arrangement of the circulation system in the chest and designed these mechanical models based on related hydromechanic principles. Model 1 was designed to observe the primary influence of respiratory intrathoracic pressure change (RIPC) on systemic and pulmonary venous return systems (SVR and PVR) respectively. Model 2, as an equivalent mechanical model of septal swing, was to study the secondary influence of RIPC on the motion of the interventriclar septum (IVS), which might be the direct cause for pulsus paradoxus. Model 1 demonstrated that the simulated RIPC had different influence on the simulated SVR and PVR. It increased the volume of the simulated right ventricle (SRV) when the internal pressure was kept constant (8.16 cmH2O), while it had the opposite effect on PVR. Model 2 revealed the three major factors determining the respiratory displacement of IVS in normal and different pathophysiological conditions: the magnitude of RIPC, the pressure difference between the two ventricles and the intrapericardial pressure. Our models demonstrate that the different anatomical arrangement of the two venous return systems leads to a different effect of RIPC on right and left ventricles, and thus a pressure gradient across IVS that tends to shift IVS left- and rightwards. When the leftward displacement of IVS reaches a considerable amplitude in some pathologic condition such as cardiac tamponade, the pulsus paradoxus occurs.
MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression by targeting the mRNAs of hundreds of human genes. Variations in miRNA expression levels were shown to be associated with glioma. We have previously found miR-30a-5p overexpression in glioma cell lines and specimens. Bioinformatics analyses predict that several miRNAs, including miR-30a-5p, are involved in the post-transcriptional regulation of SEPT7. SEPT7 is a member of the septin family, which is a highly conserved subfamily of GTPases implicated in exocytosis, apoptosis, synaptogenesis, neurodegeneration and tumorigenesis. Our previous study has also demonstrated that SEPT7 expression is decreased in astrocytic gliomas with different grades and plays a tumor suppressor role. In the present study, we knocked down miR-30a-5p with antisense oligonucleotide (miR-30a-5p AS) in LN229 and SNB19 glioblastoma(GBM) cells, and found that cell growth and invasion were inhibited, while apoptosis was induced. miR-30a-5p AS treated cells showed upregulation of SEPT7 and downregulation of PCNA, cyclin D1, Bcl2, MMP2 and MMP9. In contrast, when miR-30a-5p mimics were transfected into LN229 and SNB19 GBM cells, cell growth and invasion were promoted and the expression of relevant proteins increased. Meanwhile, the effect of miR-30a-5p mimics on glioma cells can be reversed by transfection of SEPT7 construct. Additionaly, miR-30a-5p directly targeting SEPT7 was identified by the reporter gene assay. Our study demonstrates,for the first time, that miR-30a-5p is a bona fide negative regulator of SEPT7 and the oncogenic activity of miR-30a-5p in human gliomas is at least in part through the repression of SEPT7.
Rice is one of the most important model crop plants whose heterosis has been well-exploited in commercial hybrid seed production via a variety of types of male-sterile lines. Hybrid rice cultivation area is steadily expanding around the world, especially in Southern Asia. Characterization of genes and proteins related to male sterility aims to understand how and why the male sterility occurs, and which proteins are the key players for microspores abortion. Recently, a series of genes and proteins related to cytoplasmic male sterility (CMS), photoperiod-sensitive male sterility, self-incompatibility, and other types of microspores deterioration have been characterized through genetics or proteomics. Especially the latter, offers us a powerful and high throughput approach to discern the novel proteins involving in male-sterile pathways which may help us to breed artificial male-sterile system. This represents an alternative tool to meet the critical challenge of further development of hybrid rice. In this paper, we reviewed the recent developments in our understanding of male sterility in rice hybrid production across gene, protein, and integrated network levels, and also, present a perspective on the engineering of male-sterile lines for hybrid rice production.
gene; male sterility; molecular mechanism; protein; rice
Iterative image reconstruction algorithms for optoacoustic tomography (OAT), also known as photoacoustic tomography, have the ability to improve image quality over analytic algorithms due to their ability to incorporate accurate models of the imaging physics, instrument response, and measurement noise. However, to date, there have been few reported attempts to employ advanced iterative image reconstruction algorithms for improving image quality in three-dimensional (3D) OAT. In this work, we implement and investigate two iterative image reconstruction methods for use with a 3D OAT small animal imager: namely, a penalized least-squares (PLS) method employing a quadratic smoothness penalty and a PLS method employing a total variation norm penalty. The reconstruction algorithms employ accurate models of the ultrasonic transducer impulse responses. Experimental data sets are employed to compare the performances of the iterative reconstruction algorithms to that of a 3D filtered backprojection (FBP) algorithm. By use of quantitative measures of image quality, we demonstrate that the iterative reconstruction algorithms can mitigate image artifacts and preserve spatial resolution more effectively than FBP algorithms. These features suggest that the use of advanced image reconstruction algorithms can improve the effectiveness of 3D OAT while reducing the amount of data required for biomedical applications.
Although the clinical outcome of acute myocardial infarction (AMI) in patients with type 2 diabetes mellitus (T2DM) is well established to be worse than for non-diabetic patients, the reasons for this remain unclear. We hypothesized that this may be related to impairment of bone marrow-derived endothelial progenitor cells (EPCs) mobilization.
We observed short term bone marrow EPCs mobilization and long term clinical outcomes in 62 AMI patients with or without T2DM and investigated EPCs levels as well as bone marrow pathway changes in a rat model of diabetes after AMI. Patients with T2DM exhibited a delay (peak time diabetics vs. non-diabetics: day 7 vs. day 5) and a decrease in EPCs mobilization (diabetics vs. non-diabetics: 285±56/106 mononuclear cells (MNCs) vs. 431±88/106 MNCs, p<0.05) within one month after AMI. Plasma levels of VEGF and SDF-1α as well as of hsCRP were higher in T2DM patients. Over a mean of 2.26 years follow-up, T2DM patients exhibited a pronounced decrease in LVEF as well as an increase in clinical events. Glucose (HR 2.01, 95% CI 1.42–2.85, p = 0.008), first day EPC (HR 0.974, 95% CI 0.952–0.997, p = 0.02) and seven day EPCs (HR 0.966, 95% CI 0.945–0.988, p = 0.003) were independent prognostic variables for cardiovascular mortality. In a diabetic rat model of AMI, decreased circulating EPCs was accompanied by lower expression of phospho-Akt, phospho-eNOS, HIF, MMP-9 and MMP-9 activity in the bone marrow as well as impaired cardiac function, angiogenesis and increased left ventricle remodeling.
Bone marrow EPCs mobilization is delayed and reduced in diabetes, with impaired HIF/p-Akt/p-eNOS/MMP-9 signaling. This is likely to contribute to the deterioration in cardiac function and worsened clinical outcome seen in patients with T2DM.
We sought to test whether c-Src tyrosine kinase mediates connexin 43 (Cx43) reduction and sudden cardiac death in a transgenic mouse model of cardiac-restricted overexpression of angiotensin-converting enzyme (ACE8/8).
Renin-angiotensin system (RAS) activation is associated with an increased risk of arrhythmia and sudden cardiac death; however, that mechanism is not well understood. The upregulation of c-Src by angiotensin II may result in the reduction of Cx43, which impairs gap junction function and provides a substrate for arrhythmia.
Wild-type and ACE8/8 mice with and without treatment with the c-Src inhibitor PP1 were studied. Telemetry monitoring, in vivo electrophysiology studies, Western blot analyses for total and phosphorylated c-Src and Cx43, immunohistochemistry staining for Cx43, and functional assessment of Cx43 with fluorescent dye diffusion were performed.
The majority of the arrhythmic deaths resulted from ventricular tachycardia denegerating to ventricular fibrillation (83%). Levels of total and phosphorylated c-Src were increased and Cx43 reduced in ACE8/8 mice. PP1 reduced total and phospho c-Src levels, increased the Cx43 level by 2.1-fold (P < 0.005), increased Cx43 at the gap junctions (immunostaining), improved gap junctional communication (dye spread), and reduced ventricular tachycardia inducibility and sudden cardiac death. The survival rate increased from 11% to 86% with four weeks of PP1 treatment (P < 0.005). Treatment with an inactive analog did not change survival or Cx43 levels.
RAS activation is associated with c-Src upregulation, Cx43 loss, reduced myocyte coupling, and arrhythmic sudden death, which can be prevented by c-Src inhibition. This suggests that an increase in c-Src activity may help mediate RAS-induced arrhythmias and that c-Src inhibitors might exert antiarrhythmic activity.
Angiotensin II; c-Src tyrosine kinase; connexin43; sudden cardiac death
To compare the characteristics between 22-channel water-perfusion manometry (WPM) and solid-state manometry (SSM) with 36 sensors of the pressure measurements, as well as patients’ discomfort indices in nose and pharynx, the preparation and operation time of the manometry.
12 volunteers were included in the study. Each of the volunteers underwent esophageal manometry by both 22-channel water-perfusion catheter (WPC) and solid-state catheter (SSC) with 36 sensors in random order, and separated by 30 min. The subjects gave a VAS score soon after each test. Non-parametric tests were used to analyze the differences and Bland-Altman plots were used to assess the consistency of the two systems.
During the wet swallows, there were significant differences between the two systems in three measurements of location of lower esophageal sphincter (LES) upper margin (Z = -2.11, P = 0.035), LES relax ratio (Z = -2.20, P = 0.028) and IRP4s (Z = -2.05, P = 0.041). During the jelly pocket swallows, LES relax ratio measurements of the two systems showed significant differences (Z = -2.805, P = 0.005). Further Bland–Altman plots analysis presented good agreement between the two systems measurements of location of LES upper margin, LES relax ratio and IRP4s. The discomfort indices of subjects’ nasal sensation were higher when inserting the solid-state catheter [5(3.75-5)] than water-perfusion one (2.5(2-4)) (Z = -2.471, P = 0.013), as well as the discomfort indices of pharyngeal sensation (7.5(4.75-9) vs. 4.5(3.75-6.5)), (Z = -2.354, P = 0.019). The preparation time for WPC was 40(39-41) minutes, which was much longer than that for SSC 32.5(31.75-33) minutes, (Z = -3.087, P = 0.002). And the nurses reported it’s much easier to insert WPC (Z = -3.126, P = 0.002).
In conclusion, most pressure measurements were consistent between WPM and SSM. Patients tolerated better with WPC, while for operators, the SSC presented more convenient.
22-channel water-perfusion manometry; Solid-state manometry (SSM) with 36 sensors; Pressure measurements; Patients’ tolerance; Operators’ convenience; Comparative study
The yak (Bos grunniens) is a long-haired bovine that lives at high altitudes and is an important source of milk, meat, fiber and fuel. The recent sequencing, assembly and annotation of its genome are expected to further our understanding of the means by which it has adapted to life at high altitudes and its ecologically important traits.
The Yak Genome Database (YGD) is an internet-based resource that provides access to genomic sequence data and predicted functional information concerning the genes and proteins of Bos grunniens. The curated data stored in the YGD includes genome sequences, predicted genes and associated annotations, non-coding RNA sequences, transposable elements, single nucleotide variants, and three-way whole-genome alignments between human, cattle and yak. YGD offers useful searching and data mining tools, including the ability to search for genes by name or using function keywords as well as GBrowse genome browsers and/or BLAST servers, which can be used to visualize genome regions and identify similar sequences. Sequence data from the YGD can also be downloaded to perform local searches.
A new yak genome database (YGD) has been developed to facilitate studies on high-altitude adaption and bovine genomics. The database will be continuously updated to incorporate new information such as transcriptome data and population resequencing data. The YGD can be accessed at http://me.lzu.edu.cn/yak.
Yak genome; Genome database; High-altitude adaption; Bovine genomics
The esophageal intraluminal baseline impedance may be used to evaluate the status of mucosa integrity. Esophageal acid exposure decreases the baseline impedance. We aimed to compare baseline impedance in patients with various reflux events and with different acid-related parameters, and investigate the relationships between epithelial histopathologic abnormalities and baseline impedance.
A total of 229 GERD patients and 34 controls underwent 24-h multichannel intraluminal impedance and pH monitoring (MII–pH monitoring), gastroendoscopy, and completed a GERD questionnaire (GerdQ). We quantified epithelial intercellular spaces (ICSs) and expression of tight junction (TJ) proteins by histologic techniques.
Mean baseline values in reflux esophagitis (RE) (1752 ± 1018 Ω) and non-erosive reflux disease (NERD) (2640 ± 1143 Ω) were significantly lower than in controls (3360 ± 1258 Ω; p < 0.001 and p = 0.001, respectively). Among NERD subgroups, mean baselines in the acid reflux group (2510 ± 1239 Ω) and mixed acid/weakly acidic reflux group (2393 ± 1009 Ω) were much lower than in controls (3360 ± 1258 Ω; p = 0.020 and p < 0.001, respectively). The mean baseline in severe RE patients was significantly lower than in mild RE patients (LA-C/D vs. LA-A/B: 970 ± 505 Ω vs. 1921 ± 1024 Ω, p < 0.001). There was a significant negative correlation between baseline value and acid exposure time (AET) (r = −0.41, p < 0.001), and a weak but significant correlation (r = −0.20, p = 0.007) between baseline value and weakly AET. Negative correlations were observed between ICS and the baseline impedance (r = −0.637, p < 0.001) and claudin-1 and the baseline impedance (r = −0.648, p < 0.001).
Patients with dominant acid reflux events and with longer AET have low baseline impedance. Baseline values are correlated with esophageal mucosal histopathologic changes such as dilated ICS and TJ alteration.
Electronic supplementary material
The online version of this article (doi:10.1007/s00535-012-0689-6) contains supplementary material, which is available to authorized users.
Baseline impedance; Acid reflux; Intercellular spaces; Tight junction
Liriodendron chinense (L. chinense) is an endangered basal angiosperm plant in China because of its low reproductive efficiency. Recently, miRNAs have obtained great attention because they can play important roles. Through high throughput sequencing technique, large amount of miRNAs were identified from different plant species. But there were few studies about the miRNAs in the basal angiosperms especially in the sexual reproduction process.
Deep sequencing technology was applied to discover miRNAs in L. chinense flowers at different stages. After bioinformatic analysis, 496 putative conserved miRNAs representing 97 families and 2 novel miRNAs were found. Among them, one is previously regarded as gymnosperm specific. Their expressions were further validated by Real-time PCR for 13 selected miRNAs. Putative targeting genes were predicted and categorized with gene ontology (GO) analysis. About ten percents of the targets are involved in the reproduction process. Further expressional analysis showed that many of these miRNAs were highly related to the reproductive growth.
This is the first comprehensive identification of conserved and novel miRNAs in L. chinense. The data presented here might not only help to fill the gap of miRNA registered about basal angiosperm plants but also contribute to understanding the evolution of miRNAs. The differential expression of some of the miRNAs and the prediction of their target genes are also helpful in understanding the regulation of L. chinense sexual reproduction.
Vertebral artery dissection (VAD) is often associated with trauma or occurs spontaneously, inevitably causing some neurological deficits. Even though acute infection can be related to the development of spontaneous VAD (sVAD), VAD associated with viral meningitis has never been reported in the literature.
A 42-year-old man with fever, sore throat, and runny nose developed sudden onset of occipital headache, vertigo, transient confusion, diplopia, and ataxia. Brain stem encephalitis was diagnosed initially because the cerebrospinal fluid (CSF) study showed inflammatory changes. However, subsequent diffusion-weighted (DWI) magnetic resonance imaging of his brain demonstrated left lateral medullary infarction, and the digital subtraction angiography (DSA) confirmed VAD involving left V4 segment of the artery. Consequently, the patient was diagnosed as VAD accompanied by viral meningitis.
This case suggests that viral meningitis might lead to inflammatory injury of the vertebral arterial wall, even sVAD with multiple neurological symptoms.
Vertebral artery dissection; Cerebral ischemia; Viral meningitis; Infection
In traditional Chinese medicine (TCM), diagnosis of pathology and choice of treatment prescriptions are based on a method of differentiation of signs and symptoms known as syndrome differentiation or ZHENG. The cornerstone of TCM, ZHENG, relies on the gathering of clinical information through inspection, auscultation and olfaction, inquiry, and palpation. However, the biomolecular basis of the ZHENG remains unclear. In this study, we established mouse xenograft pancreatic cancer models with Shi-Re (Dampness-Heat), Pi-Xu (Spleen-Deficiency), or Xue-Yu (Blood-Stasis) ZHENG, which are regarded as the three major ZHENGs in pancreatic cancer. We found that tumors of the different ZHENG models exhibited significantly altered cancer-associated fibroblast (CAF) proliferative activity and tumor-associated macrophage (TAM) infiltration, which led to altered levels of CAF- and TAM-derived secreted cytokines such as SDF-1 and CCL5. The ZHENG model type also significantly influenced tumor growth, and administration of herbal medicine to the ZHENG model modified the tumor microenvironment. Therefore, this study partially unveiled the molecular basis of TCM ZHENG in pancreatic cancer.
Insulin resistance is one of the important underlying abnormalities of type 2 diabetes. The effect of thiazolidinedione on liver functions has been controversial in different studies. In this study, we evaluated the effect of rosiglitazone on liver enzymes in subjects with type 2 diabetes with and without abnormal liver function.
Materials and Methods:
Seventy-three patients with type 2 diabetes taking rosiglitazone 4 mg daily were enrolled in this 3-month study. Forty-two of them had normal liver function (NLF), and 31 had abnormal liver function (ABLF). Blood biochemistries were collected monthly during the treatment period.
At baseline, other than age and liver enzymes, there were no differences in body mass index, fasting plasma glucose, hemoglobin A1c (HbA1c), and lipid profiles between the NLF and ABLF groups. At the end of the treatment, HbA1c was lowered in both groups, but only significantly in the ABLF group (P = 0.027). More importantly, serum concentrations of both aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the ABLF group decreased significantly (AST: 57.8 ± 26.5 to 47.5 ± 20.2 U/L, P = 0.006; ALT 66.6 ± 35.0 to 51.9 ± 23.5 UL, P = 0.004), while in the NLF group, a similar change was not found.
After 3-month rosiglitazone treatment in subjects with type 2 diabetes with mildly elevated liver enzymes, significant improvement in AST and ALT were observed. Our study provides some hints that rosiglitazone might not be contraindicated in subjects with diabetes with abnormal liver function as previously thought, but further well-designed studies are necessary to clarify this issue.
Rosiglitazone; type 2 diabetes; liver function
Mesothelin, a differentiation antigen present in a series of malignancies such as mesothelioma, ovarian, lung and pancreatic cancer, has been studied as a marker for diagnosis and a target for immunotherapy. We, however, were interested in evaluating the effects of direct targeting of Mesothelin on the viability of cancer cells as the first step towards developing a novel therapeutic strategy. We report here that gene specific silencing for Mesothelin by distinct methods (siRNA and microRNA) decreased viability of cancer cells from different origins such as mesothelioma (H2373), ovarian cancer (Skov3 and Ovcar-5) and pancreatic cancer (Miapaca2 and Panc-1). Additionally, the invasiveness of cancer cells was also significantly decreased upon such treatment. We then investigated pro-oncogenic signaling characteristics of cells upon mesothelin-silencing which revealed a significant decrease in phospho-ERK1 and PI3K/AKT activity. The molecular mechanism of reduced invasiveness was connected to the reduced expression of β-Catenin, an important marker of EMT (epithelial-mesenchymal transition). Ero1, a protein involved in clearing unfolded proteins and a member of the ER-Stress (endoplasmic reticulum-stress) pathway was also markedly reduced. Furthermore, Mesothelin silencing caused a significant increase in fraction of cancer cells in S-phase. In next step, treatment of ovarian cancer cells (OVca429) with a lentivirus expressing anti-mesothelin microRNA resulted in significant loss of viability, invasiveness, and morphological alterations. Therefore, we propose the inhibition of Mesothelin as a potential novel strategy for targeting human malignancies.
The title compound, [Co(C7H5O2)2(C12H16N3O2)2(H2O)2], was obtained from a conventional solvent evaporation method. The complex molecule is centrosymmetric, so pairs of equivalent ligands lie trans to each other in a slightly distorted octahedral CoN2O4 geometry. The CoII ion is coordinated by the pyridine N atoms from NITpPy ligands [NITpPy is 4,4,5,5-tetramethyl-2-(pyridin-4-yl)imidazoline-1-oxyl 3-oxide), water O atoms and two monodentate benzoate O atoms. The complex molecules are connected by O—H⋯O hydrogen bonds between water molecules and benzoate ligands, forming chains parallel to . π–π stacking interactions between the benzoate ligands with centroid–centroid distances of 3.752 (2) Å connect the chains into layers parallel to (10-1).