Oral intake of rice overexpressing ubiquitin ligase inhibitory pentapeptide prevents atrophy in denervated skeletal muscle.

We previously reported that intramuscular injections of ubiquitin ligase CBLB inhibitory pentapeptide (Cblin; Asp-Gly-pTyr-Met-Pro) restored lost muscle mass caused by sciatic denervation. Here, we detected Cblin on the basolateral side of Caco-2 cells after being placed on the apical side, and found that cytochalasin D, a tight junction opener, enhanced Cblin transport. Orally administered Cblin was found in rat plasma, indicating that intact Cblin was absorbed in vitro and in vivo. Furthermore, transgenic Cblin peptide-enriched rice (CbR) prevented the denervation-induced loss of muscle mass and the upregulation of muscle atrophy-related ubiquitin ligases in mice. These findings indicated that CbR could serve as an alternative treatment for muscle atrophy.

Characteristics of Electrospray-Ionization Detection of Synthetic Di- to Penta-Oligopeptides by Amine Derivatizations.

Chemical derivatizations have been extensively developed for highly sensitive detection of bioactive small peptides; however, their advantages from the viewpoint of longer oligopeptides remain unverified. In this study, electrospray-ionization (ESI)-mass spectrometric (MS) detection of synthetic di- to pentapeptides consisting of glycine and sarcosine were characterized by four amine derivatization methods. It was concluded that the ESI-MS detection of di- to pentapeptides was characterized by the molecular surface area of derivatized peptide moieties with an optimal value of 250 - 300 Å2, regardless of hydrophobicity and derivatization methods.

Perception of lexical neutral tones in mandarin compounds: Electroencephalographic evidence from an oddball paradigm.

The present electroencephalographic (EEG) study was designed to investigate the perception of Mandarin neutral tone (T0) by adult Mandarin speakers. For this purpose, we examined the event-related brain potential (ERP) correlates of T0 processing in two-character Mandarin compounds. Eighteen native Mandarin speakers were tested using a modified oddball paradigm. Sixty strong-strong and 60 strong-weak (T0) disyllabic Mandarin compounds were selected from the Contemporary Chinese Dictionary. Participants performed one explicit task of stress discrimination (i.e., deciding whether the fourth word in sequences of 4 spoken words had the same stress pattern as the previous words or a different one) and one implicit task of passive listening. Behaviorally, accuracy showed that Mandarin listeners were able to correctly discriminate T0 from the canonical strong-strong stress pattern in 87.2% of cases. Neurophysiologically, larger N200 and P200 were observed for the infrequent strong-weak stress pattern compared to the canonical strong-strong one. Critically, a N325 was replicated in Mandarin, with a larger N325 for strong-weak than for strong-strong compounds. Consistently with a previous interpretation proposed by Böcker et al. (1999) for Dutch, we argue that the N325 might be a manifestation of the extraction of stress pattern in Mandarin also. Taken together, the present data on T0 perception in Mandarin are discussed in the context of the Prosody-Assisted-Processing (PAP) model (Isel et al., 2003), a cognitive model of spoken compound processing based on stress-timed languages, which postulates an early involvement of prosody in order to guide the morphological analysis at the lexical level.

Identification of characteristic compounds of moderate volatility in breast cancer cell lines.

In this study, we were challenging to identify characteristic compounds in breast cancer cell lines. GC analysis of extracts from the culture media of breast cancer cell lines (MCF-7, SK-BR-3, and YMB-1) using a solid-phase Porapak Q extraction revealed that two compounds of moderate volatility, 1-hexadecanol and 5-(Z)-dodecenoic acid, were detected with markedly higher amount than those in the medium of fibroblast cell line (KMST-6). Furthermore, LC-TOF/MS analysis of the extracts clarified that in addition to the above two fatty acids, the amounts of five unsaturated fatty acids [decenoic acid (C10:1), decadienoic acid (C10:2), 5-(Z)-dodecenoic acid (C12:1), 5-(Z)-tetradecenoic acid (C14:1), and tetradecadienoic acid (C14:2)] in MCF-7 medium were higher than those in medium of KMST-6. Interestingly, H2O2-oxidation of 5-(Z)-dodecenoic acid and 5-(Z)-tetradecenoic acid produced volatile aldehydes that were reported as specific volatiles in breath from various cancer patients, such as heptanal, octanal, nonanal, decanal, 2-(E)-nonenal, and 2-(E)-octenal. Thus, we concluded that these identified compounds over-produced in breast cancer cells in this study could serve as potential precursors producing reported cancer-specific volatiles.

Current knowledge of intestinal absorption of bioactive peptides.

Peptides have been demonstrated as potentially beneficial compounds against several life-style related diseases such as hypertension, hypercholesterolemia, and atherosclerosis, among others. However, limited research has been carried out on peptide absorption, resulting in a lack of understanding and control of this process. Therefore, this review discusses the recent insights gathered on in vitro and in vivo absorption of peptides across intestinal membranes, into blood circulation. Briefly, some di-/tripeptides permeate through intestinal membranes in their intact forms via peptide transporter systems, while others are vulnerable to protease degradation. Oligopeptides (>tetrapeptides) show a lower transport ability than di-/tripeptides, possibly due to the presence of paracellular tight junctions. The hydrophobicity of peptides (log P) does not seem to influence absorption, while peptide length and degradation of peptides (and peptide sequences) by intestinal proteases may be determinant factors of the absorption process.

Effect of Aging on the Absorption of Small Peptides in Spontaneously Hypertensive Rats.

In the present study, we aimed to evaluate the effect of aging on the absorption of small peptides in spontaneously hypertensive rats (SHRs). Three kinds of dipeptides, glycyl-sarcosine (Gly-Sar), Trp-His, and captopril (a dipeptidomimetic drug), a Gly-Sar-Sar tripeptide, a Gly-Sar-Sar-Sar tetrapeptide, and a Gly-Sar-Sar-Sar-Sar pentapeptide were administered at doses of 10 mg/kg each to 8- and 40-week-old SHRs. The peptides were all detected in their intact forms in the blood. There was a significantly promoted absorption of di/tripeptides in aged SHRs compared with young SHRs. In contrast, the absorption of tetra/pentapeptides was not affected by aging. PepT1 expression in the mid-jejunum was significantly increased in 40-week-old SHRs compared with 8-week-old SHRs, whereas aging did not alter the expression of claudin-1, a tight junction related protein. Thus, the present results suggest that SHR aging may enhance the absorption of di/tripeptides through the enhanced PepT1 transport route, although oligopeptides may be absorbed in an age-independent manner.

Functional significance of the semantic P600: evidence from the event-related brain potential source localization.

Previous event-related potentials studies of sentence comprehension have usually associated syntactic repair/reanalysis processes with the P600 component. However, the functional significance of the P600 was recently questioned on the basis of the observation of P600 effects in response to the processing of semantically anomalous sentences. In the present study, we investigated the functional significance of the 'semantic P600' using a semantic violation paradigm with a focus-on-syntax instruction. Using a source localization analysis, we tested three alternative hypotheses on the function of the P600: (i) a syntactic function, (ii) an executive function, and (iii) a semantic/integrational function. We assumed that distinct neuronal generators should reflect each of these functions. Although the syntactic generators are expected to be mainly located in the left inferior frontal gyrus, the semantic generators should be observed in the left superior temporal gyrus as well as in the right anterior prefrontal cortex (semantic retrieval); moreover, the generator of executive function (conflict monitoring) should be found in the anterior cingulate cortex. Critically, we defined a dipole model using 17 dipoles, 14 of which were placed in the three regions of interest corresponding to our hypotheses, namely, syntactic, executive, and semantic regions. Our data showed that the P600 effect was significant in the anterior cingulate cortex and marginally significant in the right anterior prefrontal cortex. This finding suggests that the P600 might reflect more general mechanisms of conflict monitoring and semantic reinterpretation leading to a retrieval of world knowledge from long-term memory rather purely syntactic processes.

Structural Design of Oligopeptides for Intestinal Transport Model.

Glycyl-sarcosine (Gly-Sar) is a well-known model substrate for the intestinal uptake of dipeptides through peptide transporter 1 (PepT1). However, there are no other model peptides larger than tripeptides to evaluate their intestinal transport ability. In this study, we designed new oligopeptides based on the Gly-Sar structure in terms of protease resistance. Gly-Sar-Sar was found to be an appropriate transport model for tripeptides because it does not degrade during the transport across the rat intestinal membrane, while Gly-Gly-Sar was degraded to Gly-Sar during the 60 min transport. Caco-2 cell transport experiments revealed that the designed oligopeptides based on Gly-Sar-Sar showed a significantly (p < 0.05) lower transport ability by factors of 1/10-, 1/25-, and 1/40-fold for Gly-Sar-Sar, Gly-Sar-Sar-Sar, and Gly-Sar-Sar-Sar-Sar, respectively, compared to Gly-Sar (apparent permeability coefficient: 38.6 ± 11.4 cm/s). Cell experiments also showed that the designed tripeptide and Gly-Sar were transported across Caco-2 cell via PepT1, whereas the tetra- and pentapeptides were transported through the paracellular tight-junction pathway.

[Diagnosis and treatment of vocal process granuloma induced by gastroesophageal reflux: four cases report].

OBJECTIVE: To explore the mechanism, clinical characterization, diagnosis and therapeutic approach of vocal process granuloma(VPG) induced by gastroesophageal reflux. METHOD: We performed a retrospective review of 4 cases. RESULT: In 4 male cases, 3 cases had no obvious symptoms of stomach and esophagus and 1 case had symptoms of bloating and acid reflux. Additionally, 4 cases in which lesions were all located to the left side were diagnosed by trial therapy with proton pump inhibitors (PPIs) with good responding. 2 of 4 cases were relapsed after operations. Meanwhile 4 patients were treated by Rabeprazole for acid suppression therapy and 3 cases were cured and 1 invalid case was cured by Pantoprazole. All patients were followed up for 4-48 months with no recurrence. CONCLUSION: Gastroesophageal reflux is an important pathogenic factor to the VPG. The majority of patients with VPG do not have gastroesophageal reflux symptoms. Besides, most lesions located in the left are associated with sleeping position. The diagnosis is mainly based on the laryngoscope examination and trial of acid suppression therapy. Moreover, recurrence risk is high-with simple operation in VPG therefore the main treatment is a antireflux and it is also valid by replacing byother PPI treatment. The treatment must be long enough. Meanwhile, the comprehensive treatment should be noticed.

Endogenous hydrogen sulfide is associated with angiotensin II type 1 receptor in a rat model of carbon tetrachloride-induced hepatic fibrosis.

The present study aimed to investigate the effects of endogenous hydrogen sulfide (H2S) on the expression levels of angiotensin II type 1 receptor (AGTR1) in a rat model of carbon tetrachloride (CCl4)­induced hepatic fibrosis. A total of 56 Wistar rats were randomly divided into four groups: Normal control group, model group, sodium hydrosulfide (NaHS) group, and DL­propargylglycine (PAG) group. Hepatic fibrosis was induced by CCl4. The rats in the PAG group were intraperitoneally injected with PAG, an inhibitor of cystathionine­Î³­lyase (CSE). The rats in the NaHS group were intraperitoneally injected with NaHS. An equal volume of saline solution was intraperitoneally injected into both the control and model groups. All rats were sacrificed at week three or four following treatment. The serum levels of hyaluronidase (HA), laminin protein (LN), procollagen III (PcIII), and collagen IV (cIV) were detected using ELISA. The serum levels of alanine transaminase (ALT), aspartate transaminase (AST), and albumin (ALB) were detected using an automatic biochemical analyzer. The liver mRNA expression levels of CSE were detected by reverse transcription­quantitative polymerase chain reaction. The liver expression levels of AGTR1 and the plasma expression levels of H2S were detected using western blot analyses. The results indicated that the severity of hepatic fibrosis, the serum expression levels of HA, LN, PcIII, cIV, ALT, and AST, the liver expression levels of CSE and AGTR1, and the plasma expression levels of H2S were significantly higher in the PAG group, as compared with the model group (P<0.05). Conversely, the expression levels of ALB were significantly lower in the PAG group, as compared with the model group. In addition, the severity of hepatic fibrosis, the serum expression levels of HA, LN, PcIII, cIV, ALT, and AST, the liver expression levels of CSE and AGTR1, and the plasma expression levels of H2S were significantly lower in the NaHS group, as compared with the model group (P<0.05). These results suggest that endogenous H2S is associated with CCl4­induced hepatic fibrosis in rats, and may exhibit anti­fibrotic effects. Furthermore, H2S reduced the liver expression levels of AGTR1, which may be associated with the delayed progression of hepatic fibrosis.

Core disgust and moral disgust are related to distinct spatiotemporal patterns of neural processing: an event-related potential study.

Core disgust is thought to rely more on sensory and perceptual processes, whereas moral disgust is thought to rely more on social evaluation processes. However, little is known about the neurocognitive mechanisms underlying these two types of disgust. We recorded event-related potentials (ERPs) from participants while they performed a lexical decision task in which core- and moral-disgust words were intermixed with neutral words and pseudowords. Lexical judgment was faster for coredisgust words and slower for moral-disgust words, relative to the neutral words. Core-disgust words, relative to neutral words, elicited a larger early posterior negative (EPN), a larger N320, a smaller N400, and a larger late positive component (LPC), whereas moral disgust words elicited a smaller N320 and a larger N400 than neutral words. These results suggest that the N320 and N400 components are particularly sensitive to the neurocognitive processes that overlap in processing both core and moral disgust, whereas the EPN and LPC may reflect process that are particularly sensitive to core disgust.

Modulation of semantic integration as a function of syntactic expectations: event-related brain potential evidence.

This study investigated syntax-semantics interactions during spoken sentence comprehension. We showed that expectations of phrase-structure incongruencies, which were induced by the experimental instructions, although not actually present in the sentences, were able to block the process of semantic integration. Although this process is usually associated with an N400 event-related brain potential component, here we found a P600, that is, an event-related brain potential component that is thought to reflect syntactic revision. This finding lends support to neurophysiological models of sentence interpretation, which postulates that the lexical-semantic integration of a given word can take place only when syntactic analysis has been successfully completed.