Defensins are small cationic peptides that could be used as the potential substitute for antibiotics. However, there is no efficient method for producing defensins. In this study, we developed a new strategy to produce defensin in nitrate reductase (NR)-deficient C. ellipsoidea (nrm-4). We constructed a plant expression vector carrying mutated NP-1 gene (mNP-1), a mature α-defensin NP-1 gene from rabbit with an additional initiator codon in the 5′-terminus, in which the selection markers were NptII and NR genes. We transferred mNP-1 into nrm-4 using electroporation and obtained many transgenic lines with high efficiency under selection chemicals G418 and NaNO3. The mNP-1 was characterized using N-terminal sequencing after being isolated from transgenic lines. Excitingly, mNP-1 was produced at high levels (approximately 11.42 mg/l) even after 15 generations of continuous fermentation. In addition, mNP-1 had strong activity against Escherichia coli at 5 µg/ml. This research developed a new method for producing defensins using genetic engineering.
Soybean isoflavones are structurally similar to mammalian estrogens and therefore may act as estrogen agonists or antagonists. However, it has not been determined if they have any negative effects on reproductive parameters in male livestock. Therefore, the objective of this study was to evaluate the effects of soybean isoflavones on male reproduction using Chinese mini-pig boars as a model. Fifty Xiang boars were randomly divided into five groups and fed diets containing 0, 125, 250, or 500 ppm soybean isoflavones or 0.5 ppm diethylstilbestrol for 60 days.
Dietary supplementation with 250 ppm of soy isoflavones markedly increased the testis index (P < 0.05), fructose content (P < 0.05), and α-glycosidase content in testicular tissue (P < 0.01), as well as increased the number of viable germ cells (P < 0.01) and the level of Bcl-2 protein (P < 0.01). However, 500 ppm of soybean isoflavones significantly reduced both testis and epididymis indexes (P < 0.05) and lactate dehydrogenase levels (P < 0.01), as well as reduced serum LH and testosterone levels (P < 0.05). High levels of soybean isoflavones also increased malondialdehyde levels (P < 0.05), as well as increased the numbers of early and late apoptotic germ cells (P < 0.01) and the level of Bax proteins (P < 0.05) in the testis.
The results of this study indicate that consumption of soy isoflavones at dietary levels up to 250 ppm did not adversely affect reproductive parameters in Chinese mini-pig boars whereas higher levels of soy isoflavones may adversely affect male reproduction.
Soy isoflavones; Male reproductive function; Pigs
In mammals, hair cells do not undergo spontaneous regeneration when they are damaged and result in permanent hearing loss. Previous studies in cultured Organ of Corti dissected from neonatal animals have shown that both DAPT (r-secretase inhibitor in the Notch signal pathway) treatment and Atoh1 overexpression can induce supernumerary hair cells. The effects of simultaneous DAPT treatment and Atoh1 over expression in the cells of cultured Organ of Corti from neonatal rats are still obscure.
In this study, we set out to investigate the interaction of DAPT treatment and Atoh1 overexpression as well as culture time and the location of basilar fragment isolated form neonatal rat inner ear. Our results showed that DAPT treatment induced more hair cells in the apical turn, while Atoh1 overexpression induced more extra hair cells in the middle turn of the cultured Organ of Corti. When used together, their effects are additive but not synergistic. In addition, the induction of supernumerary hair cells by both DAPT and Atoh1 overexpression is dependent on the treatment time and the location of the cochlear tissue. Moreover, DAPT treatment causes dramatic changes in the orientation of the stereociliary bundles of hair cells, whereas Atoh1 overexpression didn't induce drastic change of the polarity of stereociliary bundles.
Taken together, these results suggest that DAPT treatment are much more potent in inducing supernumerary hair cells than Atoh1 overexpression and that the new hair cells mainly come from the trans-differentiation of supporting cells around hair cells. The orientation change of stereociliary bundle of hair cells may be attributed to the insertion of the newly formed hair cells. The immature hair bundles on the newly formed hair cells may also contribute to the overall chaos of the stereociliary bundle of the sensory epithelia.
To examine the validation and reliability of the distress thermometer (DT) recommended by National Comprehensive Cancer Network (NCCN) in Chinese cancer patients.
A total of 574 Chinese cancer patients from Beijing Cancer Hospital completed the detection of DT, the Hospital Anxiety and Depression Scale (HADS) and Symptom Checklist 90 (SCL-90), Receiver Operating Characteristic (ROC) curve and Area Under the Curve (AUC) were used to analyze the validation relative to HADS and SCL-90. The patients with DT≥4 and whose distress caused by emotional problems were interviewed with the MiNi International Neuro-psychiatric Interview (MINI) (Chinese Version 5.0). This version was used to analyze cancer patients’ psychological and Psychiatric symptoms during the cancer process; 3. Another 106 cancer patients in rehabilitation stage and stable condition were asked to fill in DT two times, at the base time and after 7-10 days.
Data of ROC indicates that a DT cutoff score of 4 yielded AUC of 0.80 with a optimal sensitivity (0.80) and specificity (0.70) relative to HADS, and AUC of 0.83 with the greatest sensitivity (0.87) and specificity (0.72) against SCL-90. The DT also has acceptable test-retest reliability (r=0.800, P=0.000); According to the interview results, the most common psychiatric problems cancer patients have adjustment disorder, depression, and anxiety.
The data suggest that DT has acceptable overall accuracy and reliability as a screening tool for testing distress severity and specific problems causing distress in Chinese cancer patients. It is worth being used in oncology clinic, the rapid screening and interview could help caregivers to identify psychological and psychiatric problems of cancer patients and provide useful information for further treatment.
Validation; Reliability; Cancer patients; Distress thermometer
Yellow fever virus (YFV) is a mosquito-borne flavivirus that is a major public health problem in tropical areas of Africa and South America. There have been detailed studies on YFV ecology in West Africa and South America, but current understanding of YFV circulation on the African continent is incomplete. This inadequacy is especially notable for East and Central Africa, for which the unpredictability of human outbreaks is compounded by limitations in both historical and present surveillance efforts. Sparse availability of nucleotide sequence data makes it difficult to investigate the dispersal of YFV in these regions of the continent. To remedy this, we constructed Bayesian phylogenetic and geographic analyses utilizing 49 partial genomic sequences to infer the structure of YFV divergence across the known range of the virus on the African continent. Relaxed clock analysis demonstrated evidence for simultaneous divergence of YFV into east and west lineages, a finding that differs from previous hypotheses of YFV dispersal from reservoirs located on edges of the endemic range. Using discrete and continuous geographic diffusion models, we provide detailed structure of YFV lineage diversity. Significant transition links between extant East and West African lineages are presented, implying connection between areas of known sylvatic cycling. The results of demographic modeling reinforce the existence of a stably maintained population of YFV with spillover events into human populations occurring periodically. Geographically distinct foci of circulation are reconstructed, which have significant implications for studies of YFV ecology and emergence of human disease. We propose further incorporation of Bayesian phylogeography into formal GIS analyses to augment studies of arboviral disease.
Yellow fever virus (YFV) is a mosquito-transmitted pathogen of great public health significance, which is endemic to tropical areas of Africa and South America. Despite the availability of an effective vaccine, and programs that exist in many endemic areas to reduce populations of mosquitoes, YFV continues to circulate and emerge in regions with developing public health infrastructures. Periodic outbreaks of YFV into humans are unpredictable and merit thorough investigation of the ecology and genetic diversity of the virus. Our analyses improve the current understanding of African YFV evolution in several respects. We have included unpublished viral sequence data from Central and East Africa, which is significant because the availability of YFV isolates from these regions is extremely limited. We present a modeled geographic structure of African YFV dispersal, and propose a new model for the spread of YFV based on concurrent historical movement of the virus from reservoirs in central African jungles to both eastern and western regions of the continent. Our results provide evidence for the presence of unique genotypes of the virus in both central and east African circulation. The presented findings not only provide insight to estimations of outbreak risk for the regions in question, but also contribute to rational GIS analysis and approaches to vaccination campaigns.
Since the emergence of drug-resistant mutants has limited the efficacy of non-nucleoside reverse transcriptase inhibitors (NNRTIs), it is essential to develop new antivirals with better drug-resistance and pharmacokinetic profiles. Here we designed and synthesized a series of 1-[(2-benzyloxyl/alkoxyl)methyl]-5-halo-6-aryluracils, the HEPT analogues, and evaluated their biological activity using Nevirapine and 18 (TNK-651) as reference compounds. Most of these compounds, especially 6b, 7b, 9b, 11b and 7c, exhibited highly potent anti-HIV-1 activity against both wild-type and NNRTI-resistant HIV-1 strains. The compound 7b, that had the highest selectivity index (SI = 38,215), is more potent than Nevirapine and 18. These results suggest that introduction of halogen at the C-5 position may contribute to the effectiveness of these compounds against RTI-resistant variants. In addition, m-substituents on the C-6 aromatic moiety could significantly enhance activity against NNRTI-resistant HIV-1 strains. These compounds can be further developed as next-generation NNRTIs with improved antiviral efficacy and drug-resistance profile.
HIV-1; Non-nucleoside reverse transcriptase inhibitors (NNRTIs); Drug-resistance
Genome-wide platforms for high-throughput profiling of circulating miRNA (oligoarray or miR-Seq) offer enormous promise for agnostic discovery of circulating miRNA biomarkers as a pathway for development in breast cancer detection. By harmonizing data from 15 previous reports, we found widespread inconsistencies across prior studies. Whether this arises from differences in study design, such as sample source or profiling platform, is unclear. As a reproducibility experiment, we generated a genome-wide plasma miRNA dataset using the Illumina oligoarray and compared this to a publically available dataset generated using an identical sample size, substrate and profiling platform. Samples from 20 breast cancer patients, 20 mammography-screened controls, as well as 20 breast cancer patients after surgical resection and 10 female lung or colorectal cancer patients were included. After filtering for miRNAs derived from blood cells, and for low abundance miRNAs (non-detectable in over 10% of samples), a set of 522 plasma miRNAs remained, of which 46 were found to be differentially expressed between breast cancer patients and healthy controls (p<0.05), of which only 3 normalized to baseline levels in post-resection cases and were unique to breast cancer vs. lung or colorectal cancer (miR-708*, miR-92b* and miR-568, none previously reported). We were unable to demonstrate reproducibility by various measures between the two datasets. This finding, along with widespread inconsistencies across prior studies, highlight the need for better understanding of factors influencing circulating miRNA levels as prerequisites to progress in this area of translational research.
Abnormal connectivity of the anticorrelated intrinsic networks, the task-negative network (TNN), and the task-positive network (TPN) is implicated in schizophrenia. Comparisons between schizophrenic patients and their unaffected siblings enable further understanding of illness susceptibility and pathophysiology. We examined the resting-state connectivity differences in the intrinsic networks between schizophrenic patients, their unaffected siblings, and healthy controls.
Resting-state functional magnetic resonance images were obtained from 25 individuals in each subject group. The posterior cingulate cortex/precuneus and right dorsolateral prefrontal cortex were used as seed regions to identify the TNN and TPN through functional connectivity analysis. Interregional connectivity strengths were analyzed using overlapped intrinsic networks composed of regions common to all subject groups.
Schizophrenic patients and their unaffected siblings showed increased connectivity in the TNN between the bilateral inferior temporal gyri. By contrast, schizophrenic patients alone demonstrated increased connectivity between the posterior cingulate cortex/precuneus and left inferior temporal gyrus and between the ventral medial prefrontal cortex and right lateral parietal cortex in the TNN. Schizophrenic patients exhibited increased connectivity between the left dorsolateral prefrontal cortex and right inferior frontal gyrus in the TPN relative to their unaffected siblings, though this trend only approached statistical significance in comparison to healthy controls.
Resting-state hyperconnectivity of the intrinsic networks may disrupt network coordination and thereby contribute to the pathophysiology of schizophrenia. Similar, though milder, hyperconnectivity of the TNN in unaffected siblings of schizophrenic patients may contribute to the identification of schizophrenia endophenotypes and ultimately to the determination of schizophrenia risk genes.
schizophrenia; unaffected sibling; default mode network; functional connectivity; resting-state
Prdm1/Blimp-1 is a master regulator of gene expression in diverse tissues of the developing embryo and adult organism. Its C-terminal zinc finger domain mediates nuclear import, DNA binding, and recruitment of the corepressors G9a and HDAC1/2. Alternatively spliced transcripts lacking exon 7 sequences encode a structurally divergent isoform (Blimp-1Δexon7) predicted to have distinct functions. Here we demonstrate that the short Blimp-1Δexon7 isoform lacks DNA binding activity and fails to bind G9a or HDAC1/2 but retains the ability to interact with PRMT5. To investigate functional roles of alternative splicing in vivo, we engineered novel mouse strains via embryonic stem (ES) cell technology. Like null mutants, embryos carrying a targeted deletion of exon 7 and exclusively expressing Blimp-1Δexon7 die at around embryonic day 10.5 (E10.5) due to placental defects. In heterozygous Δexon7 mice, there is no evidence of dominant-negative effects. Mice carrying a knock-in allele with an exon 6-exon 7 fusion express full-length Blimp-1 only, develop normally, are healthy and fertile as adults, and efficiently generate mature plasma cells. These findings strongly suggest that the short Blimp-1Δexon7 isoform is dispensable. We propose that developmentally regulated alternative splicing is influenced by chromatin structure at the locus and fine-tunes Blimp-1's functional capabilities.
Objective: To investigate the periodontal status and associated risk factors among women of childbearing age to increase the awareness of oral health. Methods: The study was conducted on childbearing age women in Cixi, a city in Zhejiang Province in the southeast of China. A total of 754 women participated in periodontal examination while receiving prenatal care. Data of the women were collected from the Cixi Family Planning Commission and during an interview. Clinical periodontal indices, such as bleeding on probing (BOP), probing depth (PD), and clinical attachment level (CAL) were measured during the examination. Statistical analysis on subject-based data was performed. Results: The prevalence of periodontal disease among childbearing age women in Cixi was high (84.7%). A significant association was found between the disease and educational level, pregnancy, taking oral contraceptives, stress, alcohol consumption, overweight, dental visit, and teeth brushing (P<0.05). Women who suffered periodontal disease showed deep PD, obvious BOP, and clinical attachment loss. Among this population, pregnancy was closely associated with higher BOP percentage; teeth brushing no more than once per day or brushing for less than 1 min (P<0.001) after adjusting for age and stress. Conclusions: The periodontal status of childbearing age women in Cixi needs to be improved urgently. Attention towards the periodontal health should be warranted, especially for those in special statuses and with poor awareness.
Periodontal status; Childbearing age women; Risk factors; Pregnancy
The heart’s rhythm is initiated and regulated by a group of specialized cells in the sinoatrial node (SAN), the primary pacemaker of the heart. Abnormalities in the development of the SAN can result in irregular heart rates (arrhythmias). Although several of the critical genes important for SAN formation have been identified, our understanding of the transcriptional network controlling SAN development remains at a relatively early stage. The homeodomain transcription factor Shox2 is involved in the specification and patterning of the SAN. While the Shox2 knockout in mice results in embryonic lethality due to severe cardiac defects including improper SAN development, Shox2 knockdown in zebrafish causes a reduced heart rate (bradycardia). In order to gain deeper insight into molecular pathways involving Shox2, we compared gene expression levels in right atria of wildtype and Shox2−/− hearts using microarray experiments and identified the LIM homeodomain transcription factor Islet1 (Isl1) as one of its putative target genes. The downregulation of Isl1 expression in Shox2−/− hearts was confirmed and the affected region narrowed down to the SAN by whole-mount in situ hybridization. Using luciferase reporter assays and EMSA studies, we identified two specific SHOX2 binding sites within intron 2 of the ISL1 locus. We also provide functional evidence for Isl1 as a transcriptional target of Shox2 by rescuing the Shox2-mediated bradycardia phenotype with Isl1 using zebrafish as a model system. Our findings demonstrate a novel epistatic relationship between Shox2 and Isl1 in the heart with important developmental consequences for SAN formation and heart beat.
Electronic supplementary material
The online version of this article (doi:10.1007/s00395-013-0339-z) contains supplementary material, which is available to authorized users.
Arrhythmia; Gene regulation; Islet1; Shox2; Sinoatrial node; Transcription factors
Polyaniline composite films incorporated with aligned multi-walled carbon nanotubes (MWCNTs) are synthesized through an easy electrodeposition process. These robust and electrically conductive films are found to function as effective electrodes to fabricate transparent and flexible supercapacitors with a maximum specific capacitance of 233 F/g at a current density of 1 A/g. It is 36 times of bare MWCNT sheet, 23 times of pure polyaniline and 3 times of randomly dispersed MWCNT/polyaniline film under the same conditions. The novel supercapacitors also show a high cyclic stability.
To explore the inhibitory effect of a sustained cyclosporin A (CsA) delivery microsphere (CsA-MS) on posterior capsular opacification (PCO) in rabbit eyes after cataract extraction.
Twenty New Zealand white rabbits accepted cataract extraction plus intraocular lens implantation and their left eyes were intraoperatively injected CsA-MS prepared using polymer polylactioglycolic acid (PLGA) as a carrier and their right eyes were injected with empty MS. The changes in cornea, anterior chamber reaction, intraocular pressure, PCO and CsA concentration in aqueous humor were examined postoperatively and all the eyes were enucleated 3 months after surgery for histopathological and morphological examination with light microscopy and electron microscopy.
Conjunctival hyperemia, corneal edema, intraocular pressure and anterior chamber response of experimental and control eyes were similar, while PCO in CsA-MS injected eyes was greatly improved compared with that in control eyes. Posterior capsules in CsA-MS injected eyes were smooth and lens epithelial cells (LEC) did not proliferate significantly (P>0.05), while LEC in posterior capsule of control eyes had different degrees of proliferation and cortical regeneration. LEC in CsA-MS injected eyes were not functionally active and underwent apoptosis, whereas LEC in control eyes were functionally active (F-test, P=0.025). In addition, the corneal ultrastructure showed no differences between CsA-MS and MS injected eyes.
CsA-MS has high bioavailability in rabbit eyes and could inhibit postoperative PCO occurrence and development during the study period, suggesting that CsA-MS may be a promising, effective and safe administration route to prevent PCO in clinic.
sustained cyclosporine A delivery microsphere; posterior capsular opacification; rabbit eyes
To identify the function of ST2 and explore the role of IL-33/ST2 signaling in regulating the pro-allergic cytokine production in human corneal epithelial cells (HCECs).
Human corneal tissues and cultured primary HCECs were treated with IL-33 in different concentrations without or with different inhibitors to evaluate the expression, location and signaling pathways of ST2 in regulating production of pro-allergic cytokine and chemokine. The expression of mRNA was determined by reverse transcription and real time PCR, and protein production was measured by enzyme-linked immunosorbent assay (ELISA), immunohistochemical and immunofluorescent staining. ST2 protein was detected in donor corneal epithelium, and ST2 signal was enhanced by exposure to IL-33.
IL-33 significantly stimulated production of pro-allergic cytokines thymic stromal lymphopoietin (TSLP) and chemokine (CCL2, CCL20, CCL22) in HCECs at both mRNA and protein levels. These stimulated productions of pro-allergic mediators by IL-33 were blocked by ST2 antibody or soluble ST2 protein (P<0.05). Interestingly, the IκB-α inhibitor BAY11-7082 or NF-κB activation inhibitor quinazoline blocked NF-κB p65 protein nuclear translocation, and also suppressed the productions of these pro-allergic cytokines and chemokine induced by IL-33.
These findings demonstrate that IL-33/ST2 signaling plays an important role in regulating IL-33 induced pro-allergic responses. IL-33 and ST2 could become novel molecular targets for the intervention of allergic diseases in ocular surface.
ST2; interleukin 33; human; cornea; epithelium; allergic diseases; NF-κB
To investigate the expression of dendritic cell-associated C-type lectin-1(dectin-1) at the early period of Aspergillus fumigatus infection in rat's corneal epithelium.
A total of 72 Wistar rats were randomly divided into three groups: A, B and C. The right eyes were chosen as experimental eyes. Group A was control group. Rats in group B were not inoculated with Aspergillus fumigatus. Group C was taken as Aspergillus fumigatus keratitis model. Rats in group B and C (six from each group) were executed randomly at 4, 8, 16 and 24 hours after experimental model being established to assess the expression of dectin-1 mRNA through real-time PCR. Another six rats in group B and C were executed randomly at 24 hours to assess the expression of dectin-1 protein through immunohistochemistry.
The results of real-time PCR indicated that dectin-1 mRNA expression was low in corneal epithelium of normal rats'. There was no significantly difference of dectin-1 mRNA expression in group A and B (P>0.05). The expression of Aspergillus fumigatus infected corneal epithelium increased gradually after 8 hours in group C. The synchronous expression of group A and C had significant difference (P<0.01). Immunohistochemisty discovered that dectin-1 receptor existed in normal rat's corneal epithelium. Dectin-1 protein increased after 24 hours in group C. There was a significant difference of synchronous expression in group B and C (P<0.01).
Dectin-1 exists in rat's corneal epithelium and its expression significantly increases at the early period of Aspergillus fumigatus infection. Dectin-1 is a pattern recognition receptor that expresses in corneal epithelium and involves in immune response to Aspergillus fungal keratitis.
keratitis; Aspergillus fumigatus; dectin-1; rat
Lead is a heavy metal and important environmental toxicant and nerve poison that can destruction many functions of the nervous system. Lead poisoning is a medical condition caused by increased levels of lead in the body. Lead interferes with a variety of body processes and is toxic to many organs and issues, including the central nervous system. It interferes with the development of the nervous system, and is therefore particularly toxic to children, causing potentially permanent neural and cognitive impairments. In this study, we investigated the relationship between lead poisoning and the intellectual and neurobehavioral capabilities of children.
The background characteristics of the research subjects were collected by questionnaire survey. Blood lead levels were detected by differential potentiometric stripping analysis (DPSA). Intelligence was assessed using the Gesell Developmental Scale. The Achenbach Child Behavior Checklist (CBCL) was used to evaluate each child’s behavior.
Blood lead levels were significantly negatively correlated with the developmental quotients of adaptive behavior, gross motor performance, fine motor performance, language development, and individual social behavior (P < 0.01). Compared with healthy children, more children with lead poisoning had abnormal behaviors, especially social withdrawal, depression, and atypical body movements, aggressions and destruction.
Lead poisoning has adverse effects on the behavior and mental development of 2–4-year-old children, prescribing positive and effective precautionary measures.
Child; Lead poisoning; Intelligence development; Neurobehavioral ability
Our previous work indicated that TWEAK is associated with various types of cutaneous vasculitis (CV). Herein, we investigate the effects of TWEAK on vascular injury and adhesion molecule expression in CV mice. We showed that TWEAK priming in mice induced a local CV. Furthermore, TWEAK priming also increased the extravasation of FITC-BSA, myeloperoxidase activity and the expression of E-selectin and ICAM-1. Conversely, TWEAK blockade ameliorated the LPS-induced vascular damage, leukocyte infiltrates and adhesion molecules expression in LPS-induced CV. In addition, TWEAK treatment of HDMECs up-regulated E-selectin and ICAM-1 expression at both mRNA and protein levels. TWEAK also enhanced the adhesion of PMNs to HDMECs. Finally, western blot data revealed that TWEAK can induce phosphorylation of p38, JNK and ERK in HDMECs. These data suggest that TWEAK acted as an inducer of E-selectin and ICAM-1 expression in CV mice and HDMECs, may contribute to the development of CV.
Homonymous hemianopia (HH) is an anisotropic visual impairment characterized by the binocular inability to see one side of the visual field. Patients with HH often misperceive visual space. Here we investigated how HH affects visual motor control.
Methods and Findings
Seven patients with complete HH and no neglect or cognitive decline and seven gender- and age-matched controls viewed displays in which a target moved randomly along the horizontal or the vertical axis. They used a joystick to control the target movement to keep it at the center of the screen. We found that the mean deviation of the target position from the center of the screen along the horizontal axis was biased toward the blind side for five out of seven HH patients. More importantly, while the normal vision controls showed more precise control and larger response amplitudes when the target moved along the horizontal rather than the vertical axis, the control performance of the HH patients was not different between these two target motion experimental conditions.
Compared with normal vision controls, HH affected patients' control performance when the target moved horizontally (i.e., along the axis of their visual impairment) rather than vertically. We conclude that hemianopia affects the use of visual information for online control of a moving target specific to the axis of visual impairment. The implications of the findings for driving in hemianopic patients are discussed.
Cupriavidus sp. HMR-1 was isolated from a heavy metal-enriched culture of activated sludge from a wastewater treatment plant in Hong Kong. Here, we release the HMR-1 genome to provide basic genetic characteristics for a better understanding of its multiple heavy metal resistance properties.
Accumulating evidence reveals that intrauterine growth retardation (IUGR) can cause varying degrees of pulmonary arterial hypertension (PAH) later in life. Moreover, epigenetics plays an important role in the fetal origin of adult disease. The goal of this study was to investigate the role of epigenetics in the development of PAH following IUGR.
The IUGR rats were established by maternal undernutrition during pregnancy. Pulmonary vascular endothelial cells (PVEC) were isolated from the rat lungs by magnetic-activated cell sorting (MACS). We investigated epigenetic regulation of the endothelin-1 (ET-1) gene in PVEC of 1-day and 6-week IUGR rats, and response of IUGR rats to hypoxia.
The maternal nutrient restriction increased the histone acetylation and hypoxia inducible factor-1α (HIF-1α) binding levels in the ET-1 gene promoter of PVEC in IUGR newborn rats, and continued up to 6 weeks after birth. These epigenetic changes could result in an IUGR rat being highly sensitive to hypoxia later in life, causing more significant PAH or pulmonary vascular remodeling.
These findings suggest that epigenetics is closely associated with the development of hypoxic PAH following IUGR, further providing a new insight for improved prevention and treatment of IUGR-related PAH.
Epigenetics; Pulmonary arterial hypertension; Endothelial cells; Endothelin-1; Intrauterine growth retardation
In this study, we examined anti-fungal and anti-inflammatory effects of the synthetic melanocortin peptide (Ac-Cys-Lys-Pro-Val-NH2)2 or (CKPV)2 against Candida albicans vaginitis. Our in vitro results showed that (CKPV)2 dose-dependently inhibited Candida albicans colonies formation. In a rat Candida albicans vaginitis model, (CKPV)2 significantly inhibited vaginal Candida albicans survival and macrophages sub-epithelial mucosa infiltration. For mechanisms study, we observed that (CKPV)2 inhibited macrophages phagocytosis of Candida albicans. Meanwhile, (CKPV)2 administration inhibited macrophage pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) release, while increasing the arginase activity and anti-inflammatory cytokine IL-10 production, suggesting macrophages M1 to M2 polarization. Cyclic AMP (cAMP) production was also induced by (CKPV)2 administration in macrophages. These above effects on macrophages by (CKPV)2 were almost reversed by melanocortin receptor-1(MC1R) siRNA knockdown, indicating the requirement of MC1R in the process. Altogether, our results suggest that (CKPV)2 exerted anti-fungal and anti-inflammatory activities against Candida albicans vaginitis probably through inducing macrophages M1 to M2 polarization and MC1R activation.
The aim of this study was to learn about the progress of the prevention and control of major non-communicable diseases (NCDs) in China from 1990 to 2009 and to determine what prevention and control gaps remain based on the opinions of a group of panellists.
Sixty-four panellists, who are members of the Subcommittee of the Non-Communicable Diseases, the Expert Committee on Disease Control and Prevention established by China's Ministry of Health in 2010, were invited to participate in an email-based, two-round Delphi survey. In each round, a structured questionnaire was given to participants, who were asked to rate the importance and practical implementation of items relevant to the prevention and control of NCDs over two periods, 1990–1999 and 2000–2009, on a 10-point scale.
Of the 64 panellists invited, 20 (31.3%) completed the first-round survey, and, of those, 14 (70.0%) completed the second-round survey. Of the 237 common variables in the two survey rounds, there were 161 (67.9%) and 209 (88.2%) with an interquartile range ≤2 in the first round and second round, respectively. These results indicated a better expert consensus in the second round. There were 92 items in total in the second round of the questionnaire, 88 (95.7%) of which had median importance rating scores of equal to or greater than 7.00. The median scores for the practical implementation items during 2000–2009 were greater than those for the 1990–1999 period. The results indicate improved implementation in the recent decade.
China has made progress in the prevention and control of NCDs during the 21st century. However, these intuitive rating results indicate that there are still large action gaps in the fight against epidemic NCDs in China.
non-communicable diseases; prevention and control; Delphi survey; China; developing countries
Epidemiological studies have evaluated the association between nicotinamide adenine dinucleotide phosphate (NADPH) oxidase p22phox C242T polymorphism and risk of ischemic cerebrovascular disease (ICVD), but the results remain inconclusive. This meta-analysis was therefore designed to clarify these controversies.
Systematic searches of electronic databases Embase, PubMed and Web of Science, as well as hand searching of the references of identified articles and the meeting abstracts were performed. Statistical analyses were performed using software Review Manager (Version 5.1.7) and Stata (Version 11.0). The pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) were performed. Fixed or random effects model was separately used depending on the heterogeneity between studies. Publication bias was tested by Begg's funnel plot and Egger's regression test. A total of 6 studies including 1,948 cases and 2,357 controls were combined showing no statistical evidence of association between NADPH oxidase p22phox C242T polymorphism and overall ICVD (allelic model: OR = 1.08, 95%CI = 0.93–1.26; additive model: OR = 1.33, 95%CI = 0.81–2.17; dominant model: OR = 1.00, 95%CI = 0.86–1.15; recessive model: OR = 1.06, 95%CI = 0.77–1.45). Significant association was found in large-artery atherosclerotic stroke subgroup (allelic model: OR = 1.12, 95%CI = 0.88–1.41; additive model: OR = 1.36, 95%CI = 0.60–3.09; dominant model: OR = 1.25, 95%CI = 0.74–2.11; recessive model: OR = 2.17, 95%CI = 1.11–4.23). No statistical evidence of significant association was observed for small-vessel occlusive stroke, as well as Asian subgroup and Caucasian subgroup. Statistical powers on the combined sample size (total and subgroup) were all lower than 80%.
This meta-analysis indicates that NADPH oxidase p22phox C242T polymorphism is more associated with large-artery atherosclerotic stroke than small-vessel occlusive stroke. However, this conclusion should be interpreted with caution due to the small sample size. Larger sample-size studies with homogeneous ICVD patients and well-matched controls are required.
Sacbrood virus (SBV) is a picorna-like virus that affects honey bees (Apis mellifera) and results in the death of the larvae. Several procedures are available to detect Chinese SBV (CSBV) in clinical samples, but not to estimate the level of CSBV infection. The aim of this study was develop an assay for rapid detection and quantification of this virus. Primers and probes were designed that were specific for CSBV structural protein genes. A TaqMan minor groove binder (MGB) probe-based, fluorescence real-time quantitative PCR was established. The specificity, sensitivity and stability of the assay were assessed; specificity was high and there were no cross-reactivity with healthy larvae or other bee viruses. The assay was applied to detect CSBV in 37 clinical samples and its efficiency was compared with clinical diagnosis, electron microscopy observation, and conventional RT-PCR. The TaqMan MGB-based probe fluorescence real-time quantitative PCR for CSBV was more sensitive than other methods tested. This assay was a reliable, fast, and sensitive method that was used successfully to detect CSBV in clinical samples. The technology can provide a useful tool for rapid detection of CSBV. This study has established a useful protocol for CSBV testing, epidemiological investigation, and development of animal models.
Microarray data are high dimension with high noise ratio and relatively small sample size, which makes it a challenge to use microarray data to identify candidate disease genes. Here, we have presented a hybrid method that combines estimation of distribution algorithm with support vector machine for selection of key feature genes. We have benchmarked the method using the microarray data of both diffuse B cell lymphoma and colon cancer to demonstrate its performance for identifying key features from the profile data of high-dimension gene expression. The method was compared with a probabilistic model based on genetic algorithm and another hybrid method based on both genetics algorithm and support vector machine. The results showed that the proposed method provides new computational strategy for hunting candidate disease genes from the profile data of disease gene expression. The selected candidate disease genes may help to improve the diagnosis and treatment for diseases.