Chronic polymicrobial infections of the lung are the foremost cause of morbidity and mortality in cystic fibrosis (CF) patients. The composition of the microbial flora of the airway alters considerably during infection, particularly during patient exacerbation. An understanding of which organisms are growing, their environment and their behaviour in the airway is of importance for designing antibiotic treatment regimes and for patient prognosis. To this end, we have analysed sputum samples taken from separate cohorts of CF and non-CF subjects for metabolites and in parallel, and we have examined both isolated DNA and RNA for the presence of 16S rRNA genes and transcripts by high-throughput sequencing of amplicon or cDNA libraries. This analysis revealed that although the population size of all dominant orders of bacteria as measured by DNA- and RNA- based methods are similar, greater discrepancies are seen with less prevalent organisms, some of which we associated with CF for the first time. Additionally, we identified a strong relationship between the abundance of specific anaerobes and fluctuations in several metabolites including lactate and putrescine during patient exacerbation. This study has hence identified organisms whose occurrence within the CF microbiome has been hitherto unreported and has revealed potential metabolic biomarkers for exacerbation.
Icariin has been mostly reported to enhance bone fracture healing and treat postmenopausal osteoporosis in ovariectomized animal model. As another novel animal model of osteoporosis, there is few publication about the effect of Icariin on osteoprotegerin-deficient mice. Therefore, the goal of this study is to find the effect on bone formation and underlying mechanisms of Icariin in osteoprotegerin (OPG) knockout (KO) mice. We found that Icariin significantly stimulated new bone formation after local injection over the surface of calvaria at the dose of 5 mg/kg per day. With this dose, Icariin was also capable of significantly reversing OPG-deficient-induced bone loss and bone strength reduction. Real-time PCR analysis showed that Icariin significantly upregulated the expression of BMP2, BMP4, RUNX2, OC, Wnt1, and Wnt3a in OPG KO mice. Icariin also significantly increased the expression of AXIN2, DKK1, TCF1, and LEF1, which are the direct target genes of β-catenin signaling. The in vitro studies showed that Icariin induced osteoblast differentiation through the activation of Wnt/β-catenin-BMP signaling by in vitro deletion of the β-catenin gene using β-cateninfx/fx mice. Together, our findings demonstrate that Icariin significantly reverses the phenotypes of OPG-deficient mice through the activation of Wnt/β-catenin-BMP signaling.
Macroautophagy is an important process for removing misfolded and aggregated protein in cells, the dysfunction of which has been directly linked to an increasing number of neurodegenerative disorders. However, the details of macroautophagy in prion diseases remain obscure. Here we demonstrated that in the terminal stages of scrapie strain 263K-infected hamsters and human genetic prion diseases, the microtubule-associated protein 1 light chain 3 (LC3) was converted from the cytosolic form to the autophagosome-bound membrane form. Macroautophagy substrate sequestosome 1 (SQSTM1) and polyubiquitinated proteins were downregulated in the brains of sick individuals, indicating enhanced macroautophagic protein degradation. The levels of mechanistic target of rapamycin (MTOR) and phosphorylated MTOR (p-MTOR) were significantly decreased, which implies that this enhancement of the macroautophagic response is likely through the MTOR pathway which is a negative regulator for the initiation of macroautophagy. Dynamic assays of the autophagic system in the brains of scrapie experimental hamsters after inoculation showed that alterations of the autophagic system appeared along with the deposits of PrPSc in the infected brains. Immunofluorescent assays revealed specific staining of autophagosomes in neurons that were not colocalized with deposits of PrPSc in the brains of scrapie infected hamsters, however, autophagosome did colocalize with PrPSc in a prion-infected cell line after treatment with bafilomycin A1. These results suggest that activation of macroautophagy in brains is a disease-correlative phenomenon in prion diseases.
transmissible spongiform encephalopathies; autophagy; neurodegenerative diseases
Close relationships between ticks and microbial communities are important for tick fitness and pathogen colonization and transmission. Haemaphysalis longicornis, distributed widely in China, can carry and transmit various pathogens and pose serious damages to public health and economics. However, little is known about the broader array of microbial communities and symbionts in H. longicornis under natural conditions. In the present study, we investigated the composition of bacterial communities associated with H. longicornis and evaluated the putative symbionts.
The eubacterial 16S rRNA gene clone libraries of H. longicornis were constructed and analyzed by restriction fragment length polymorphism (RFLP) and DNA sequencing. In addition, diagnostic PCR was performed to assess the prevalence, vertical transmission and infection sites of the symbionts in H. longicornis.
Vertically-transmitted symbionts, potential pathogens and allochthonous nonpathogenic bacteria were identified from the field-collected H. longicornis. Three types of symbionts (Coxiella-like, Arsenophonus-like and Rickettsia-like symbionts) were identified in a single host simultaneously. A series of analyses revealed the vertical transmission, prevalence, and infection sites of these symbionts. However, only Coxiella-like bacteria were transmitted stably in the laboratory-reared ticks. In addition, we identified a novel Coxiella-like agent with 95.31% sequence similarity to the taxon described previously.
The present study demonstrated that natural H. longicornis harboured a diverse array of microbial communities. Three types of symbionts were identified in a single host simultaneously. Moreover, high prevalence, vertical transmission and the infection sites supported an obligate symbiotic association between Coxiella symbiont and its host. The role of Coxiella symbiont in the host fitness and the interaction among microbial communities remained to be elucidated. Our investigation of microbial communities in the ticks revealed the complexity of ecological interactions between host and microbe and provided insight for the biological control of ticks.
Haemaphysalis longicornis; Microbial communities; Coxiella-like symbiont; Arsenophonus-like symbiont; Rickettsia-like symbiont
Neuritic dystrophy is one of the important pathological features associated with amyloid plaques in Alzheimer’s disease (AD) and age-dependent neuronal dysfunctions. We have previously reported that reticulon-3 (RTN3) immunoreactive dystrophic neurites (RIDNs) are abundantly present in the hippocampus of AD patients, in AD mouse models and in aged wild-type mice. Transgenic mice overexpressing the human RTN3 transgene spontaneously develop RIDNs in their hippocampi and the formation of RIDNs correlates with the appearance of RTN3 aggregation. To further elucidate whether the formation of RIDNs is reversible, we generated transgenic mice expressing wild-type human RTN3 under the control of a tetracycline-responsive promoter. Treatment with doxycycline for two months effectively turned off expression of the human RTN3 transgene, confirming the inducible nature of the system. However, the formation of hippocampal RIDNs was dependent on whether the transgene was turned off before or after the formation of RTN3 aggregates. When transgenic human RTN3 expression was turned off at young age, formation of RIDNs was largely eliminated compared to the vehicle-treated transgenic mice. More importantly, a fear conditioning study demonstrated that contextual associative learning and memory in inducible transgenic mice was improved if the density of RIDNs was lowered. Further mechanistic study suggested that a reduction in BDNF levels in transgenic mice might contribute to the reduced learning and memory in transgenic mice overexpressing RTN3. Hence, we conclude that age-dependent RIDNs cannot be effectively cleared once they have formed and we postulate that successful prevention of RIDN formation should be initiated prior to RTN3 aggregation.
RTN3; reticulon; Nogo; dystrophic neurites; RIDNs; amyloid peptide; BACE1; inducible expression; aggregation
The northern reef of Yongxing Island, the largest reef island of the Xisha Islands in the South China Sea, was in good condition with significant cover of scleractinian corals until 2002. Surveys in 2008 and 2010, however, found that coral coverage had declined rapidly and severely, implying that catastrophic coral mortality occurred during the past 8 years. A blackish mat was observed covering live and dead corals in both 2008 and 2010 that was identified as an encrusting sponge, Terpios hoshinota, by special surface morphology and spicule structure. In addition, spicule residues were found on the surface of long-dead corals, indicating a previous invasion of T. hosinota.T. hoshinota is referred to as the “black disease” because it rapidly overgrows and kills corals. Our evidence indicates that outbreaks of black disease are at least partially responsible for the massive coral mortality at the northern reef of Yongxing Island over the past 8 years, although human activities and heat-related coral bleaching cannot be discounted as minor causes for this coral decline.
Coral mortality; Black disease; Terpios hoshinota; Human activities; Coral bleaching; Crown-of-thorns starfish; South China Sea
Microglial activations have been described in different subtypes of human prion diseases such as sporadic Creutzfeldt-Jakob disease (CJD), variant CJD, Kuru and Gerstmann-Sträussler-Scheinker disease (GSS). However, the situation of microglia in other genetic prion diseases such as fatal familial insomnia (FFI) and familial CJD remains less understood. The brain microglia was evaluated comparatively between the FFI, G114V and sCJD cases in the study.
Specific Western blots, immunohistochemical and immunofluorescent assays were used to detect the changes of microglia and ELISA tests were used for levels of inflammatory cytokines.
Western blots, immunohistochemical and immunofluorescent assays illustrated almost unchanged microglia in the temporal lobes of FFI and G114V gCJD, but obviously increased in those of sCJD. The Iba1-levels maintained comparable in six different brain regions of FFI and G114V cases, including thalamus, cingulate gyrus, frontal cortex, parietal cortex, occipital cortex and temporal cortex. ELISA tests for inflammatory cytokines revealed significantly up-regulated IL-1β, IL-6 and TNF-α in the brain homogenates from sCJD, but not in those from FFI and G114V gCJD.
Data here demonstrates silent brain microglia in FFI and G114V gCJD but obviously increased in sCJD, which reflects various pathogenesis of different human prion diseases subtypes.
Prions; Microglia; Creutzfeldt-Jakob disease; Fatal familial insomnia; G114V; Cytokines
Acute gastrointestinal illness (AGI) is an important public-health problem worldwide. Previous national studies of the incidence of AGI in China were performed decades ago, and detailed information was not available. This study therefore sought to determine the magnitude, distribution, and burden of self-reported AGI in China.
Twelve-month, retrospective face-to-face surveys were conducted in 20 sentinel sites from six provinces between July 2010 and July 2011.
In total, 39686 interviews were completed. The overall adjusted monthly prevalence of AGI was 4.2% (95% confidence interval, 4.0–4.4), corresponding to 0.56 episodes of AGI per person-year. Rates of AGI were highest in children aged < 5 years. Healthcare was sought by 56.1% of those reporting illness. Of the cases who visited a doctor, 32.7% submitted a stool sample. The use of antibiotics was reported by 49.7% of the cases who sought medical care and 54.0% took antidiarrhoeals. In the multivariable model, gender, age, education, household type, residence, season, province and travel were significant risk factors of being a case of AGI.
This first population-based study in China indicated that AGI represents a substantial burden of health. Further research into the specific pathogens is needed to better estimate the burden of AGI and foodborne disease in China.
Prion diseases are kinds of progressive, incurable neurodegenerative disorders. So far, survival time of the patients with these diseases in China is unclear.
Based upon the surveillance data from Chinese Creutzfeldt-Jakob disease (CJD) surveillance network from January 2008 to December 2011, a retrospective follow-up survey was performed. The survival times of Chinese patients with prion diseases and the possible influencing factors were analyzed.
Median survival time of 121 deceased patients was 7.1 months, while those for sporadic CJD (sCJD), familial CJD (fCJD) and fatal familial insomnia (FFI) cases were 6.1, 3.1 and 8.2 months, respectively. 74.0% of sCJD patients, 100% of fCJD cases and 91.7% FFI cases died within one year. The general socio-demographic factors, abnormalities in clinical examinations, clinical manifestations, and social factors did not significantly influence the survival times of Chinese prion patients.
Survival time of Chinese patients with prion diseases was comparable with that of many Western countries, but obviously shorter than that of Japan. Patients with acute onset and rapid progression had significantly short survival times.
To record aberrations with a corneal topographic device on the anterior surface of the cornea at different time-points prior to wearing and following discontinued use of rigid gas permeable (RGP) contact lenses. The effect of wearing RGP on the anterior surface of the cornea was discussed to provide guidance for clinical refractive error correction.
The study objects were 24 eyes from 24 patients. All patients underwent identical examination procedures prior to lens use, as well as afterwards, including slit-lamp examination, non-contact tonometer measurement, computer optometry and corneal curvature measurement, subjective refraction test, and corneal topography analysis. The patients wore contact lenses everyday for 1 month and then discontinued. Corneal topographies were recorded at certain time points of 30 minutes, 1 day, 3, 7 and 14 days following use.
Total corneal aberration at each time point following discontinued use of RGP contact lenses was less than the time point prior to use. Detailed results were as follows: root mean square (RMS) (pre)=(1.438±0.328)µm, RMS (30 minutes)=(1.076±0.355)µm, RMS (1 day)=(1.362±0.402)µm, RMS (3 days)=(1.373±0.398)µm, RMS (7 days)=(1.387±0.415)µm, and RMS (14 days)=(1.430±0.423)µm. Results showed that at 30 minutes after discontinued use of RGP contact lenses, almost all 2nd- and 3rd-order aberrations change. Quadrafoil Z10 and spherical Z12 of the 4th-order were also changed. Alterations to Z5, Z6, and Z12 at 1 day after discontinued use were significant differences compared with the time period prior to RGP use: Z5 and Z6 decreased, and Z12 increased slightly. Z5 and Z6 remained decreased at 3 days after discontinued use, but Z9 and Z10 continued to increase and Z12 returned to levels prior to RGP use. At 14 days after discontinued use, all aberrations were not significantly different from the values prior to use.
The use RGP contact lenses greatly reduced total aberration of the anterior surface of the cornea. Changes to 2nd- and 3rd-order aberrations (including Z3, Z4, Z5, Z6, Z7, and Z8) were more significant. Following discontinued use of RGP contact lenses, the majority of lower order aberrations returned to original levels in a short period of time. During this process, a transient higher order aberration appeared, but all changes disappeared within 14 days after discontinued use of RGP contact lenses.
aberration; rigid gas permeable contact lens; cornea
To evaluate the frequency, distribution and clinical significance of the antibodies to the fetal and/or adult acetylcholine receptor (AChR) in patients with myasthenia gravis (MG).
AChR antibodies were detected by cell-based assay in the serum of ocular MG (OMG) (n = 90) and generalized MG (GMG) patients (n = 110). The fetal-type (2α: β: γ: δ) and adult-type (2α: β: ε: δ) AChR were used as antigens, and their relevance to disease presentation was assessed.
The overall frequencies of anti-adult and anti-fetal AChR antibodies were similar in all 200 patients examined, with 14 having serum specific to the AChR-γ subunit, and 22 to the AChR-ε subunit. The overall sensitivity when using the fetal and adult AChR antibodies was higher than that when using the fetal AChR antibody only (P = 0.015). Compared with OMG patients, the mean age at disease onset and the positive ratio of antibodies to both isoforms of the AChR were significantly higher in patients who subsequently progressed to GMG. Older patients and patients with both anti-fetal and anti-adult AChR antibodies had a greater risk for developing generalized disease [odds ratio (OR), 1.03; 95% confidence interval (CI), 1.01–1.06 and OR, 5.09; 95% CI, 2.23–11.62].
Using both fetal- and adult-type AChRs as the antigens may be more sensitive than using either subtype. Patients with serum specific to both isoforms are at a greater risk of progressing to GMG. Patients with disease onset at an advanced age appear to have a higher frequency of GMG conversion.
myasthenia gravis; acetylcholine receptor antibodies; acetylcholine receptor subunit; cell-based assay; adult; fetal
Background. Osteoporosis is a major health problem for the elderly population. Chinese herb may be beneficial to osteoporosis due to its capability. Objectives. This study was designed to evaluate the effectiveness of Chinese medicine treatment on the patients with osteoporosis. Search Methods. Randomized controlled trials were retrieved from different 9 databases. Results. This meta analysis included 12 RCTs involving 1816 patients to compare Chinese herbs with placebo or standard anti-osteoporotic therapy in the treatment of bone loss. The pooled data showed that the percent change of increased BMD in the spine is higher with Chinese herb compared to placebo (lumber spine: WMD = 0.07, 95% CI: 0.01–0.04). In the femoral, Chinese herb showed significantly higher increments of BMD compared to placebo (femoral neck: WMD = 0.06, 95% CI: −0.02–0.13). Compared to the other standard anti-osteoporotic drugs, Chinese herbs also show advantage in BMD change (lumber spine: WMD = 0.03, 95% CI: −0.01–0.08; femoral: WMD = 0.01, 95% CI: −0.01–0.02). Conclusions. Our results demonstrated that Chinese herb significantly increased lumbar spine BMD as compared to the placebo or other standard anti-osteoporotic drugs.
The shotgun strategy applying tandem mass spectrometry has been widely used to identify the proteins that are differentially distributed among diseases for its high reliability and efficiency. To find out the potential difference of protein profiles in cerebrospinal fluids (CSF) between Creutzfeldt-Jakob disease (CJD) and non-CJD patients, especially in the fraction ranging from 1–10 KD, the CSF samples of 40 probable sporadic CJD (sCJD) patients, 32 non-CJD cases with dementia and 17 non-CJD cases without dementia were separately pooled and enriched by the magnetic beads based weak cation exchange chromatography (MB-WCX). After trypsin digestion, each enriched CSF was separated and identified by RP-HPLC-ESI-QTOF MS/MS. In total, 42, 53 and 47 signals of proteins were identified in the pooled CSF fraction less than 10 KD of probable sCJD, non-CJD with dementia and non-CJD without dementia, respectively. Compared with that of probable sCJD, the similarity of CSF protein profiles of non-CJD with dementia (76.2%) were higher than that of non-CJD without dementia (57.1%). Nine CSF proteins were found to be specially observed in probable sCJD group. Those data may help to select the potential biomarkers for diagnosis of CJD. Additionally, further studies of the small segments of cellular proteins in CSF of CJD patients may also provide scientific clues for understanding the neuropathogenesis of TSEs.
Creutzfeldt-Jakob disease; CSF; MB-HPLC-ESI-QTOF; 1–10 KD; comparative peptidome
Foot-and-mouth disease virus (FMDV) causes a highly contagious infection in cloven-hoofed animals. The format of FMD virus-like particles (VLP) as a non-replicating particulate vaccine candidate is a promising alternative to conventional inactivated FMDV vaccines. In this study, we explored a prokaryotic system to express and assemble the FMD VLP and validated the potential of VLP as an FMDV vaccine candidate. VLP composed entirely of FMDV (Asia1/Jiangsu/China/2005) capsid proteins (VP0, VP1 and VP3) were simultaneously produced as SUMO fusion proteins by an improved SUMO fusion protein system in E. coli. Proteolytic removal of the SUMO moiety from the fusion proteins resulted in the assembly of VLP with size and shape resembling the authentic FMDV. Immunization of guinea pigs, swine and cattle with FMD VLP by intramuscular inoculation stimulated the FMDV-specific antibody response, neutralizing antibody response, T-cell proliferation response and secretion of cytokine IFN-γ. In addition, immunization with one dose of the VLP resulted in complete protection of these animals from homologous FMDV challenge. The 50% protection dose (PD50) of FMD VLP in cattle is up to 6.34. These results suggest that FMD VLP expressed in E. coli are an effective vaccine in guinea pigs, swine and cattle and support further development of these VLP as a vaccine candidate for protection against FMDV.
Biofilm formation and dispersal in the black rot pathogen Xanthomonas campestris pathovar campestris (Xcc) is influenced by a number of factors. The extracellular mannanase ManA has been implicated in biofilm dispersal whereas biofilm formation requires a putative glycosyl transferase encoded by the xag gene cluster. Previously we demonstrated that the post-transcriptional regulator RsmA exerts a negative regulatory influence on biofilm formation in Xcc. Here we address the mechanisms by which RsmA exerts this action. We show that RsmA binds to the transcripts of three genes encoding GGDEF domain diguanylate cyclases to influence their expression. Accordingly, mutation of rsmA leads to an increase in cellular levels of cyclic di-GMP. This effect is associated with a down-regulation of transcription of manA, but an upregulation of xag gene transcription. Mutation of clp, which encodes a cyclic di-GMP-responsive transcriptional regulator of the CRP-FNR family, has similar divergent effects on the expression of manA and xag. Nevertheless Clp binding to manA and xag promoters is inhibited by cyclic di-GMP. The data support the contention that, in common with other CRP-FNR family members, Clp can act as both an activator and repressor of transcription of different genes to influence biofilm formation as a response to cyclic di-GMP.
To examine the relationship between angiogenesis and lymphangigenesis in recurrent pterygia.
Tissues from 34 excised recurrent pterygia (including 12 Grade 1, 10 Grade 2, and 12 Grade 3) were involved in the study and tissues from 7 nasal epibulbar conjunctivae segments were used as controls. Sections from each pterygium were immunostained with CD31 and LYVE-1 monoclonal antibodies to evaluate lymphatic microvessel density (LMVD) and blood microvessel density (BMVD), and the relationship between LMVD and BMVD in the pterygium was examined.
There was a large number of CD31(+)LYVE-1(−) blood vessels but only a few CD31(+)LYVE-1(+) lymphatic vessels in grades 1 and 2 pterygium. However, lymphatic vessels were dramatically increased in grade 3 pterygium. LMVD correlated closely with BMVD in all pterygia, including grades 1, 2 and 3 peterygium patients (all P values <0.01). Although both the density of blood and lymphatic vessels increased in recurrent pterygia, lymphatic vessels developed much faster than blood vessels, especially in grade 3 pterygia.
There is a significant but not parallel relationship between angiogenesis and lymphangiogenesis in recurrent pterygium. The outgrowth of blood and lymphatic vessels provide evidence that immunological mechanism may play a role in the development and recurrence of pterygium.
angiogenesis; lymphangiogenesis; recurrent pterygium
Progesterone supplementation after in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) can improve the rates of clinical pregnancy and live birth, but the optimal duration of treatment remains controversial. The objective of this meta-analysis was to investigate the effects of early progesterone cessation on pregnancy outcomes in women undergoing IVF/ICSI.
We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), the Chinese biomedicine (CBM) literature database, and the Wanfang database. The final search was performed in July 2012. All available randomised trials that compared the effects of early progesterone cessation with progesterone continuation during early pregnancy after IVF/ICSI were included. The main outcome measures were live birth rate, miscarriage rate and ongoing pregnancy rate. Fixed or random-effects models were chosen to calculate the risk ratio (RR).
Six eligible studies with a total of 1,201 randomised participants were included in the final analysis. No statistically significant differences were detected between patients who underwent early progesterone cessation and those who received progesterone continuation for luteal phase support in terms of live birth rate (RR: 0.95, 95% CI: 0.86–1.05), miscarriage rate (RR: 1.01, 95% CI: 0.74–1.38) or ongoing pregnancy rate (RR: 0.97, 95% CI: 0.90–1.05). These results did not change after a sensitivity analysis.
The currently available evidence suggests that progesterone supplementation beyond the first positive hCG test after IVF/ICSI might generally be unnecessary, although large-scale randomised controlled trials are needed to strengthen this conclusion.
Progesterone; Luteal phase support; IVF/ICSI; Pregnancy outcome; Meta-analysis
Although the aggregation of PrPSc is thought to be crucial for the neuropathology of prion diseases, there is evidence in cultured cells and transgenic mice that neuronal death can be triggered by the accumulation of cytosolic PrPs, leading to the hypothesis that the accumulation of PrPs in the cytosol of neurons may be a primary neurotoxic culprit. Hsp70, a molecular chaperone involved in protein folding/refolding and degradation in the cytoplasm, has a protective effect in some models of neurodegenerative diseases, e.g., Alzheimer’s and Parkinson’s diseases, but its role in prion diseases remains unclear.
To study the role of Hsp70 in prion diseases, we used immunoprecipitation to first identify a molecular interaction between Hsp70 and PrPs. Using immunofluorescence, we found that Hsp70 colocalized with cytosolic PrPs in HEK293 cells transiently transfected with plasmids for Cyto-PrP and PG14-PrP but not with wild-type PG5-PrP or endoplasmic reticulum (ER)-retained PrPs (3AV-PrP and ER-PrP). Using western blot analysis and apoptosis assays of cultured cells, we found that the overexpression of Hsp70 by transfection or the activation of Hsp70 by geldanamycin selectively mediated the degradation of cytosolic PrPs and restored cytosolic PrP-induced cytotoxicity. Moreover, we found that Hsp70 levels were up-regulated in cells expressing Cyto-PrP and in hamster brains infected with the scrapie agent 263K.
These data imply that Hsp70 has central role in the metabolism of cytosolic PrPs
Hsp70; Cytosolic PrP; Apoptosis; Prion disease; Geldanamycin
We previously reported that immune activation in the spinal dorsal horn contributes to pain induced by chronic pancreatitis (CP). Targeting immune response in the CNS may provide effective treatments for CP-induced pain. Recent findings demonstrate that resolvin D1 (RvD1) can potently dampen inflammatory pain. We hypothesized that intrathecal injection of RvD1 may inhibit pain of CP.
Rat CP model was built through intrapancreatic infusion of trinitrobenzene sulfonic acid (TNBS). All the rats were divided into three groups: TNBS, sham, and naïve controls and were further divided for intrathecal RvD1 administration. Pain behavior of rats was tested with von Frey filaments. Anxiety-like behavior and free locomotor and exploration of rats were evaluated by open field test and elevated plus maze. Pancreatic histology was evaluated with hematoxylin and eosin staining. Phosphorylation of NMDA receptor and expression of inflammatory cytokines were examined with Western blot, real-time RT-PCR and ELISA.
Behavioral study indicated that compared to the vehicle control, RvD1 (100 ng/kg) significantly decreased TNBS-induced mechanical allodynia at 2 h after administration (response frequencies: 49.2 ± 3.7% vs 71.3 ± 6.1%), and this effect was dose-dependent. Neither CP nor RvD1 treatment could affect anxiety-like behavior. CP or RvD1 treatment could not affect free locomotor and exploration of rats. Western blot analysis showed that compared with that of naïve group, phosphorylated NR1 (pNR1) and pNR2B in TNBS rats were significantly increased in the spinal cord (pNR1: 3.87±0.31 folds of naïve control, pNR2B: 4.17 ± 0.24 folds of naïve control). Compared to vehicle control, 10 ng/kg of RvD1 could significantly block expressions of pNR1 (2.21 ± 0.26 folds of naïve) and pNR2B (3.31 ± 0.34 folds of naïve). Real-time RT-PCR and ELISA data showed that RvD1 (10 ng/kg) but not vehicle could significantly block expressions of TNF-alpha, IL-1beta and IL-6. In addition, RvD1 did not influence pain behavior, NMDA receptor phosphorylation or cytokines production in sham-operated rats.
These data highly suggest that RvD1 could be a novel and effective treatment for CP-induced chronic pain.
Chronic pancreatitis; Pain; Spinal dorsal horn; Resolvin D1; NMDA Receptor
The pathogenic agent is hypothesized to be PrPSc in prion diseases. However, little accumulation of PrPSc is repeatedly observed in some kinds of natural and experimental prion diseases, including some special genetic human prion diseases. One of the specific topology forms of PrP, CtmPrP, representing a key neurotoxic intermediate in prion disorders, has been testified in cell-free translation systems and transgenic mice models. Recently, some studies have showed that point-mutations within the hydrophobic transmembrane region increase the amount of CtmPrP in cells, such as human homologue A117V which is associated with GSS and G114V associated with gCJD, while the mutations outsides transmembrane region do not. The retention of the CtmPrP in ER subsequently is able to induce ER stress and apoptosis, which is supported by upregulation of ER chaperone synthesis, such as Grp78, Grp58, Grp94, Bip and the transcription factor CHOP/GADD153. In conclusion, some kinds of intermediate forms of PrPSc, including CtmPrP, may work as the ultimate cause of neurodegeneration.
prion; CtmPrP; ER stress; transmembrane region; mutant
A case of Creutzfeldt-Jakob disease (CJD) with a rare mutation of the prion protein (PrP) gene (PRNP) at codon 208 (R208H), while the codon 129 was a methionine homozygous genotype is reported. The patient initial displayed hand tremor, dizziness and progressive cognitive dysfunction. Subsequently, other symptoms gradually appeared, including cerebellar ataxia and mental disorder. No periodic activity was recorded at electroencephalography (EEG) and 14-3-3 protein in cerebrospinal fluid was negative. Total clinical course was about four months. Retrospective investigation of this family across seven generations did not figure out clear family history. However, genetic analyses revealed six first-degree family members with the R208H allele.
creutzfeldt-Jakob disease; PRNP; R208H
To examine the relations between lymphangiogenesis and the size of pterygium.
Tissues from 88 primary and 34 recurrent pterygia were evaluated, and those from 7 nasal epibulbar conjunctiva segments were used as controls. Pterygium slices from each patient were stained with LYVE-1 monoclonal antibodies to identify lymphatic microvessel for calculating lymph-vascular area (LVA), lymph-microvascular density (LMD) and lymph-vascular luminal diameter (LVL). Also, the relations between lymphangiogenesis (measuring by LVA, LMD and LVL) and the size of pterygium (extension, width and area) were explored.
There were a few LYVE-1(+) lymphatic vessels in normal epibulbar conjunctiva segments. However, the number of lymphatic vessels slightly increased in primary pterygia and dramatically increased in recurrent pterygia. LVA, LMD and LVL significantly increased in recurrent pterygia in comparison with primary pterygia (all P<0.05). Both LMD and LVA were correlated with the width and area of pterygia (both P< 0.05), and LVA was also correlated with the extension of pterygia(P<0.05).
Lymphangiogenesis is correlated with the size of pterygium. The outgrowth of lymphatic vessels might contribute to the development of pterygia.
pterygia; lymphatic vessel; size
In the title complex, [Ni(C6H5O2N2)2], the NiII atom is situated on an inversion centre and is coordinated in a square-planar geometry by four O atoms and two N atoms of the chelating ligands.
Porcine circovirus type 2 (PCV2) is a primary etiological agent of post-weaning multi-systemic wasting syndrome (PMWS), which is a disease of increasing importance to the pig industry worldwide. Hollow mesoporous silica nanoparticles (HMSNs) have gained increasing interest for use in vaccines.
To study the potential of HMSNs for use as a protein delivery system or vaccine carriers. HMSNs were synthesized by a sol–gel/emulsion(oil-in-water/ethanol) method, purified PCV2 GST-ORF2-E protein was loaded into HMSNs, and the resulting HMSN/protein mixture was injected into mice. The uptake and release profiles of protein by HMSNs in vitro were investigated. PCV2 GST-ORF2-E specific antibodies and secretion of IFN-γ were detected by enzyme-linked immunosorbent assays, spleen lymphocyte proliferation was measured by the MTS method, and the percentage of CD4+ and CD8+ were determined by flow cytometry.
HMSNs were found to yield better binding capacities and delivery profiles of proteins; the specific immune response induced by PCV2 GST-ORF2-E was maintained for a relatively long period of time after immunization with the HMSN/protein complex.
The findings suggest that HMSNs are good protein carriers and have high potential for use in future applications in therapeutic drug delivery.
Hollow mesoporous silica nanoparticles (HMSNs); Porcine circovirus type 2 (PCV2): ORF2; Delivery; Immunization; Mice
Coronary heart disease (CHD) is the leading causes of morbidity and mortality in China. The diagnosis of CHD in Traditional Chinese Medicine (TCM) was mainly based on experience in the past. In this paper, we proposed four MI-based association algorithms to analyze phenotype networks of CHD, and established scale of syndromes to automatically generate the diagnosis of patients based on their phenotypes. We also compared the change of core syndromes that CHD were combined with other diseases, and presented the different phenotype spectra.