Studies on the risk of chromosomal abnormalities in early spontaneous abortion after assisted reproductive technology (ART) are relatively controversial and insufficient. Thus, to obtain a more precise evaluation of the risk of embryonic chromosomal abnormalities in first-trimester miscarriage after ART, we performed a meta-analysis of all available case–control studies relating to the cytogenetic analysis of chromosomal abnormalities in first-trimester miscarriage after ART.
Literature search in the electronic databases MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) based on the established strategy. Meta-regression, subgroup analysis, and Galbraith plots were conducted to explore the sources of heterogeneity.
A total of 15 studies with 1,896 cases and 1,186 controls relevant to the risk of chromosomal abnormalities in first- trimester miscarriage after ART, and 8 studies with 601 cases and 602 controls evaluating frequency of chromosome anomaly for maternal age≥35 versus <35 were eligible for the meta-analysis. No statistical difference was found in risk of chromosomally abnormal miscarriage compared to natural conception and the different types of ART utilized, whereas the risk of fetal aneuploidy significantly increased with maternal age≥35 (OR 2.88, 95% CI: 1.74–4.77).
ART treatment does not present an increased risk for chromosomal abnormalities occurring in a first trimester miscarriage, but incidence of fetal aneuploidy could increase significantly with advancing maternal age.
Morphine is a potent opioid analgesic. However, the repeated use of morphine causes tolerance and hyperalgesia. Neuroinflammation has been reported to be involved in morphine tolerance and withdrawal-induced hyperalgesia. The complement system is a crucial effector mechanism of immune responses. The present study investigated the roles of complement factor C5a and C5a receptor (C5aR) in the development of morphine tolerance and withdrawal-induced hyperalgesia. In the present study, the levels of C5a and C5aR were increased in the L5 lumbar spinal cords of morphine-tolerant rats. The administration of C5a promoted the development of hyperalgesia and the expression of spinal antinociceptive tolerance to intrathecal morphine in both mechanical and thermal test. However, these phenomena caused by morphine were significantly attenuated by the C5aR antagonist PMX53. These results suggest that complement activation within the spinal cord is involved in morphine tolerance and withdrawal-induced hyperalgesia. C5a and C5aR may serve as novel targets for the control of morphine tolerance and withdrawal-induced hyperalgesia.
morphine; tolerance; hyperalgesia; inflammation; C5a
To characterize microRNA-206 (miR-206) in the development of bronchopulmonary dysplasia (BPD).
We assessed the expression of miR-206 in BPD mouse lung tissues and blood samples of BPD patients by quantitative real-time PCR. Then, the role of miR-206 in regulating cell biology were examined by XTT assay, flow cytometry, transwell invasion assay, wound healing assay and adhesion assay in vitro. Furthermore, luciferase reporter assay, real-time PCR, western blot and Immunofluorescence staining were performed to figure out the target gene of miR-206.
A reduction in expression of miR-206 was observed in BPD mice compared with controls and in BPD patients compared with controls. miR-206 overexpression significantly induced cell apoptosis, reduced cell proliferation, migration and adhesion abilities, whereas the inhibition of miR-206 expression had the opposite effect. Fibronectin 1 (FN1) is a direct target of miR-206, and fn 1 can be transcriptionally and translationally regulated by miR-206. Down-regulation of miR-206 modulates biological functions of the cells, at least in part, by increasing the level of fn 1. Furthermore, fn 1 expression levels were increased in the BPD mice and BPD patients.
The expression of miR-206 and its target gene, fn 1, may contribute to the progression of BPD.
Phytophthora capsici is a soilborne plant pathogen capable of infecting a wide range of plants, including many solanaceous crops. However, genetic resistance and fungicides often fail to manage P. capsici due to limited knowledge on the molecular biology and basis of P. capsici pathogenicity. To begin to rectify this situation, Illumina RNA-Seq was used to perform massively parallel sequencing of three cDNA samples derived from P. capsici mycelia (MY), zoospores (ZO) and germinating cysts with germ tubes (GC). Over 11 million reads were generated for each cDNA library analyzed. After read mapping to the gene models of P. capsici reference genome, 13,901, 14,633 and 14,695 putative genes were identified from the reads of the MY, ZO and GC libraries, respectively. Comparative analysis between two of samples showed major differences between the expressed gene content of MY, ZO and GC stages. A large number of genes associated with specific stages and pathogenicity were identified, including 98 predicted effector genes. The transcriptional levels of 19 effector genes during the developmental and host infection stages of P. capsici were validated by RT-PCR. Ectopic expression in Nicotiana benthamiana showed that P. capsici RXLR and Crinkler effectors can suppress host cell death triggered by diverse elicitors including P. capsici elicitin and NLP effectors. This study provides a first look at the transcriptome and effector arsenal of P. capsici during the important pre-infection stages.
Microtubule-based molecular motors often work in small groups to transport cargos in cells. A key question in understanding transport (and its regulation in vivo) is to identify the sensitivity of multiple-motor-based motion to various single molecule properties. Whereas both single-motor travel distance and microtubule binding rate have been demonstrated to contribute to cargo travel, the role of single-motor velocity is yet to be explored. Here, we recast a previous theoretical study, and make explicit a potential contribution of velocity to cargo travel. We test this possibility experimentally, and demonstrate a strong negative correlation between single-motor velocity and cargo travel for transport driven by two motors. Our study thus discovers a previously unappreciated role of single-motor velocity in regulating multiple-motor transport.
Cargo Travel; Kinesin; Multiple-Motor Transport; Transport Regulation; Velocity
Kidney stones in patients with autosomal dominant polycystic kidney disease are common, regarded as the consequence of the combination of anatomic abnormality and metabolic risk factors. However, complete staghorn calculus is rare in polycystic kidney disease and predicts a gloomy prognosis of kidney. For general population, recent data showed metabolic factors were the dominant causes for staghorn calculus, but for polycystic kidney disease patients, the cause for staghorn calculus remained elusive.
We report a case of complete staghorm calculus in a polycystic kidney disease patient induced by repeatedly urinary tract infections. This 37-year-old autosomal dominant polycystic kidney disease female with positive family history was admitted in this hospital for repeatedly upper urinary tract infection for 3 years. CT scan revealed the existence of a complete staghorn calculus in her right kidney, while there was no kidney stone 3 years before, and the urinary stone component analysis showed the composition of calculus was magnesium ammonium phosphate.
UTI is an important complication for polycystic kidney disease and will facilitate the formation of staghorn calculi. As staghorn calculi are associated with kidney fibrosis and high long-term renal deterioration rate, prompt control of urinary tract infection in polycystic kidney disease patient will be beneficial in preventing staghorn calculus formation.
Staghorn calculus; Polycystic kidney disease; Urinary tract infection
The Wilms’ tumor suppressor gene (WT1) has been identified as an oncogene in many malignant diseases such as leukaemia, breast cancer, mesothelioma and lung cancer. However, the role of WT1 in non-small-cell lung cancer (NSCLC) carcinogenesis remains unclear. In this study, we compared WT1 mRNA levels in NSCLC tissues with paired corresponding adjacent tissues and identified significantly higher expression in NSCLC specimens. Cell proliferation of three NSCLC cell lines positively correlated with WT1 expression; moreover, these associations were identified in both cell lines and a xenograft mouse model. Furthermore, we demonstrated that up-regulation of Cyclin D1 and the phosphorylated retinoblastoma protein (p-pRb) was mechanistically related to WT1 accelerating cells to S-phase. In conclusion, our findings demonstrated that WT1 is an oncogene and promotes NSCLC cell proliferation by up-regulating Cyclin D1 and p-pRb expression.
Whether acupuncture is efficacious for patients with functional dyspepsia is still controversial. So we designed a randomised controlled trial to settle the problem.
Methods and analysis
We designed a multicentre, two-arm, sham-controlled clinical trial. 200 participants with functional dyspepsia will be randomly assigned to the true acupuncture (TA) group and sham acupuncture (SA) group in a 1:1 ratio. Participants in the TA group will receive acupuncture at points selected according to syndrome differentiation. Participants in the sham acupuncture group will receive penetrations at sham points. Participants in both groups will receive 20 sessions of electroacupuncture in 4 weeks, five times continuously with a 2 day rest in a week. The primary outcome is the proportion of patients reporting the absence of dyspeptic symptoms at 16 weeks after inclusion. The secondary outcome includes a Short-Form Leeds Dyspepsia Questionnaire, the Chinese version of the 36-Item Short Form Survey, the Chinese version of the Nepean dyspepsia index, etc.
Ethics and dissemination
The study protocol has been approved by the institutional review boards and ethics committees of the first affiliated hospital of Chengdu University of TCM, the first affiliated hospital of Hunan University of TCM and Chongqing Medical University, respectively (from April to August 2012). The results of this trial will be disseminated in a peer-reviewed journal and presented at international congresses.
Complementary Medicine; Epidemiology; Gastroenterology
Bone marrow microenvironment (niche) plays essential roles in the fate of hematopoietic stem cells (HSCs). Intracellular and extracellular redox metabolic microenvironment is one of the critical factors for the maintenance of the niche. Cytochrome P450 reductase (CPR) is an obligate electron donor to all microsomal cytochrome P450 enzymes (P450 or CYP), and contributes to the redox metabolic process. However, its role in maintaining HSCs is unknown.
To examine the effects of low CPR expression on HSCs function using a mouse model of globally suppressed Cpr gene expression (Cpr Low, CL mice).
Hematopoietic cell subpopulations in bone marrow (BM) and peripheral blood (PB) from WT and CL mice were examined for their repopulation and differentiation ability upon BM competitive transplantation and enriched HSC (LKS+) transplantation. Effects of low CPR expression on hematopoiesis were examined by transplanting normal BM cells into CL recipients. Reactive oxygen species (ROS), cell cycle, and apoptosis in CL mice were analyzed by flow cytometry for DCF-DA fluorescence intensity, Ki67 protein, and Annexin-V, respectively.
The levels of ROS in BM cells, HPCs and HSCs were comparable between CL and WT mice. In comparison to WT mice, the number of LT-HSCs or ST-HSCs was lower in CL mice while CMPs, GMPs and MEPs in CL mice were higher than that in WT control. Competitive transplantation assay revealed enhanced repopulation capacity of HSCs with low CPR expression, but no difference in differentiation potential upon in vitro experiments. Furthermore, lymphoid differentiation of donor cells decreased while their myeloid differentiation increased under CL microenvironment although the overall level of donor hematopoietic repopulation was not significantly altered.
Our studies demonstrate that suppressing CPR expression enhances the repopulation efficiency of HSCs and a low CPR expression microenvironment favors the differentiation of myeloid over lymphoid lineage cells.
Synaptic vesicles dock at active zones on the presynaptic plasma membrane of a neuron’s axon terminals as a precondition for fusing with the membrane and releasing their neurotransmitter to mediate synaptic impulse transmission. Typically, docked vesicles are next to aggregates of plasma membrane-bound macromolecules called active zone material (AZM). Electron tomography on tissue sections from fixed and stained axon terminals of active and resting frog neuromuscular junctions has led to the conclusion that undocked vesicles are directed to and held at the docking sites by the successive formation of stable connections between vesicle membrane proteins and proteins in different classes of AZM macromolecules. Using the same nanometer scale 3D imaging technology on appropriately stained frog neuromuscular junctions, we found that ∼10% of a vesicle’s luminal volume is occupied by a radial assembly of elongate macromolecules attached by narrow projections, nubs, to the vesicle membrane at ∼25 sites. The assembly’s chiral, bilateral shape is nearly the same vesicle to vesicle, and nubs, at their sites of connection to the vesicle membrane, are linked to macromolecules that span the membrane. For docked vesicles, the orientation of the assembly’s shape relative to the AZM and the presynaptic membrane is the same vesicle to vesicle, whereas for undocked vesicles it is not. The connection sites of most nubs on the membrane of docked vesicles are paired with the connection sites of the different classes of AZM macromolecules that regulate docking, and the membrane spanning macromolecules linked to these nubs are also attached to the AZM macromolecules. We conclude that the luminal assembly of macromolecules anchors in a particular arrangement vesicle membrane macromolecules, which contain the proteins that connect the vesicles to AZM macromolecules during docking. Undocked vesicles must move in a way that aligns this arrangement with the AZM macromolecules for docking to proceed.
Ultrasonic-assisted extraction (UAE) was developed to extract phenolic and flavonoid antioxidants from Clerodendrum cyrtophyllum Turcz leaves. The optimal experimental parameters for antioxidant extraction from C. cyrtophyllum leaves were measured using single-factor experimentation combined with response surface methodology (RSM). Total phenolic content (TPC) and total flavonoid content (TFC) assays were used to quantify antioxidant compounds. Next, antioxidant radical scavenging capacity was measured using 2,2′-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′ -azino-bis(3-ethylbenzothiazoline-6-sulphonicacid) (ABTS) radicals. Optimized extraction conditions for UAE from C. cyrtophyllum leaves were as follows: 60.9% ethanol, 85.4 min, and 63.3°C for maximal TPC extraction (16.8±0.2 mg GAE/g DW); 67.7% ethanol, 82.9 min, and 63.0°C for maximal TFC extraction (49.3±0.4 mg RT/g DW); 48.8% ethanol, 85.1 min, and 63.9°C for maximal DPPH radical-scavenging capacity (86.8±0.2%); and 50.6% ethanol, 81.3 min, and 63.4°C for maximal ABTS radical-scavenging capacity (92.9±0.5%). Ethanol concentration was the most important factor in the extraction process. Our work offers optimal extraction conditions for C. cyrtophyllum as a potential source of natural antioxidants.
Previous studies have reported a discrepancy in baseline characteristics and outcomes after percutaneous coronary intervention between men and women. However, this finding has never been verified in the Chinese population. The present study analyzed two-year clinical outcomes after placement of coronary drug-eluting stents in Chinese men and women.
From January 2005 to December 2010, a total of 3804 Chinese patients (2776 men, 1028 women) who underwent drug-eluting stent implantation were studied prospectively. The primary endpoint was the composite major adverse cardiac event (MACE) rate, including myocardial infarction, cardiac death, and target vessel revascularization at two years. Stent thrombosis served as the safety endpoint. Propensity score matching was used to compare the adjusted MACE rate between the two groups.
At two-year follow-up, unadjusted rates of myocardial infarction, non-ST segment elevation myocardial infarction, target vessel revascularization, and MACE were significantly different between men (6.84%, 4.6%, 13.1%, and 21.7%, respectively) and women (3.8% [P = 0.001], 2.0% [P < 0.001] 10.3% [P = 0.025], and 16.3% [P < 0.001], respectively). After propensity score matching, there were no significant differences in composite MACE and individual endpoints at two years between the genders.
Despite all the unfavorable risk factor clustering in women and complex coronary disease in men, the two-year clinical outcomes after coronary stent placement were comparable between Chinese women and men.
drug-eluting stent; major adverse cardiac event; gender difference; clinical follow-up
This study explored whether expression of aldehyde dehydrogenase 1 (ALDH1A1) in the primary tumor correlated with lymph node metastasis (LNM) of squamous cell carcinoma of the head and neck (HNSCC). We used both quantum dot (QD)-based immunohistofluorescence (IHF) and conventional immunohistochemistry (IHC) to quantify ALDH1A1 expression in primary tumor samples taken from 96 HNSCC patients, 50 with disease in the lymph nodes and 46 without. The correlation between the quantified level of ALDH1A1 expression and LNM in HNSCC patients was evaluated with univariate and multivariate analysis. The prognostic value of ALDH1A1 was examined by Kaplan-Meier analysis and Wald test. ALDH1A1 was highly correlated with LNM in HNSCC patients (p < 0.0001 by QD-based IHF and 0.039 by IHC). The two methods (QD-based IHF and conventional IHC) for quantification of ALDH1A1 were found to be comparable (R = 0.75, p < 0.0001), but QD-IHF was more sensitive and objective than IHC. The HNSCC patients with low ALDH1A1 expression had a higher 5-year survival rate than those with high ALDH1A1 level (p = 0.025). Our study suggests that ALDH1A1 is a potential biomarker for predicting LNM in HNSCC patients, though it is not an independent prognostic factor for survival of HNSCC patients. Furthermore, QD-IHF has advantages over IHC in quantification of ALDH1A1 expression in HNSCC tissues.
Aldehyde dehydrogenase 1; biomarker; metastasis; immunohistochemistry; head and neck cancer; quantum dot; nanotechnology
Background: ISL1, as a member of the LIM homeodomain transcription factor family, is expressed in a distinct population of undifferentiated cardiac progenitors and plays a pivotal role in cardiogenesis. Lacking ISL1 expression results in growth arrest or displays profound defects in heart development, including atria, ventricle, and the inflow and outflow tracts, which constitute a major form of congenital heart disease (CHD). Recently, an important study by Stevens et al. found that genetic variation in ISL1 is associated with risk of CHD in white and black/African American populations; this observation led us to hypothesize that ISL1 common variants might influence susceptibility to sporadic CHD in our Chinese population. Methods: We conducted a case–control study of CHD in Chinese to test our hypothesis by genotyping ISL1 common variant rs1017 in 1003 CHD cases and 1012 non-CHD controls. Results: We found that rs1017 was not associated with the risk of CHD (p=0.213). When we performed stratified analyses according to subjects' age, sex, and CHD classifications, we found no overall heterogeneity of risk in different subgroups. Conclusions: This is the first study which indicates that ISL1 common variant rs1017 may not play a role in sporadic CHD susceptibility in the Chinese population.
An H10N9 avian influenza virus (AIV) strain, A/Chicken/Jiangsu/RD5/2013, was isolated in China. The hemagglutinin (HA) and neuraminidase (NA) genes in this strain originated from H10N1 and H7N9 AIVs, respectively, and the other genes derived from H7N3 AIVs. Sequence analysis implies that the H10N9 AIV may be an NA gene donor for the human H7N9 influenza viruses.
The plant hormone abscisic acid (ABA) is involved in a wide variety of plant processes, including the initiation of stress-adaptive responses to various environmental cues. Recently, ABA also emerged as a central factor in the regulation and integration of plant immune responses, although little is known about the underlying mechanisms. Aiming to advance our understanding of ABA-modulated disease resistance, we have analyzed the impact, dynamics and interrelationship of ABA and the classic defense hormone salicylic acid (SA) during progression of rice infection by the leaf blight pathogen Xanthomonas oryzae pv. oryzae (Xoo). Consistent with ABA negatively regulating resistance to Xoo, we found that exogenously administered ABA renders rice hypersusceptible to infection, whereas chemical and genetic disruption of ABA biosynthesis and signaling, respectively, led to enhanced Xoo resistance. In addition, we found successful Xoo infection to be associated with extensive reprogramming of ABA biosynthesis and response genes, suggesting that ABA functions as a virulence factor for Xoo. Interestingly, several lines of evidence indicate that this immune-suppressive effect of ABA is due at least in part to suppression of SA-mediated defenses that normally serve to limit pathogen growth. Resistance induced by the ABA biosynthesis inhibitor fluridone, however, appears to operate in a SA-independent manner and is likely due to induction of non-specific physiological stress. Collectively, our findings favor a scenario whereby virulent Xoo hijacks the rice ABA machinery to cause disease and highlight the importance of ABA and its crosstalk with SA in shaping the outcome of rice-Xoo interactions.
Phenols are present in the environment and commonly in contact with humans and animals because of their wide applications in many industries. In a previous study, we reported that uridine diphosphate-glucose-dependent glucosyltransferase PtUGT72B1 from Populus trichocarpa has high activity in detoxifying trichlorophenol by conjugating glucose. In this study, more experiments were performed to determine the substrate specificity of PtUGT72B1 towards phenolic compounds. Among seven phenols tested, three were glucosylated by PtUGT72B1 including phenol, hydroquinone, and catechol. Transgenic Arabidopsis plants expressing the enzyme PtUGT72B1 showed higher resistance to hydroquinone and catechol but more sensitivity to phenol than wild type plants. Transgenic Pichia pastoris expressing PtUGT72B1 showed enhanced resistance to all three phenols. Compared with wild type Arabidopsis plants, transgenic Arabidopsis plants showed higher removal efficiencies and exported more glucosides of phenol, phenyl β-D-glucopyranoside, to the medium after cultured with the three phenols. Protein extracts from transgenic Arabidopsis plants showed enhanced conjugating activity towards phenol, hydroquinone and catechol. PtUGT72B1 showed much higher expression level in Pichia pastoris than in Arabidopsis plants. Kinetic analysis of the PtUGT72B1 was also performed.
Bone morphorgenetic protein (BMP)-4 has been shown to play a pivotal role in eye development; however, its role in mature retina or ocular angiogenic diseases is unclear. Activating downstream Smad signaling, BMP4 can be either pro-angiogenic or anti-angiogenic, depending on the context of cell types and associated microenvironment. In this study, we generated transgenic mice over-expressing BMP4 in retinal pigment epithelial (RPE) cells (Bmp4-Vmd2 Tg mice), and used the laser-induced choroidal neovascularization (CNV) model to study the angiogenic properties of BMP4 in adult eyes. Bmp4-Vmd2 Tg mice displayed normal retinal histology at 10 weeks of age when compared with age-matched wildtype mice. Over-expression of BMP4 in RPE in the transgenic mice was confirmed by real-time PCR and immunostaining. Elevated levels of Smad1,5 phosphorylation were found in BMP4 transgenic mice compared to wildype mice. Over-expression of BMP4 was associated with less severe CNV as characterized by fluorescein angiography, CNV volume measurement and histology. While control mice showed increased levels of vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)-9 after laser injury, Bmp4-Vmd2 Tg showed no increase in either VEGF or MMP-9. Further, we found that TNF-induced MMP-9 secretion in vitro was reduced by pretreatment of RPE cells with BMP4. The inhibition of MMP-9 was Smad-dependent because BMP4 failed to repress TNF-induced MMP-9 expression when Smad1,5 was silenced by siRNA. In summary, our studies identified an anti-angiogenic role for BMP4 in laser-induced CNV, mediated by direct inhibition of MMP-9 and indirect inhibition of VEGF.
BMP4; MMP-9; VEGF; Choroidal neovascularization (CNV); Retinal pigment epithelium (RPE)
Herein we report the fabrication of protein (bovine serum albumin, BSA) particles which were rendered transiently insoluble using a novel, reductively labile disulfide-based cross-linker. After being cross-linked, the protein particles retain their integrity in aqueous solution and dissolve preferentially under a reducing environment. Our data demonstrates that cleavage of the cross-linker leaves no chemical residue on the reactive amino group. Delivery of a self-replicating RNA was achieved via the transiently insoluble PRINT protein particles. These protein particles can provide new opportunities for drug and gene delivery.
Soft lithography; PRINT; protein; cross-linker; disulfide
Epidemiological and clinico-pathological studies indicate a causal relationship between heart disease and Alzheimer’s disease (AD). To learn whether heart disease causes an onset of AD, mice with myocardial infarction (MI) and congestive heart failure (HF) were used to test neuropsychiatric and cognitive behaviors as well as for measurements of AD related protein markers. To this end, adult mice were subjected to ligation of left anterior descending artery (LAD) and about two weeks later high-frequency echocardiography was performed to exam the resulting cardiac structure and function. Three months after successful induction of chronic heart failure (CHF) these mice showed an impairment of learning in the Morris Water Maze task. In addition, the expression of selected molecules, which are involved in β-amyloid metabolism, apoptosis and inflammation on the level of gene transcription and translation, was altered in CHF mice. Our findings provide a plausible explanation that CHF increases the risk of cognitive impairments and alters cerebral β-amyloid metabolism. In addition, our data indicate that the cerebral compensatory mechanisms in response to CHF are brain area and gender specific.
Artificial chordae replacement is an effective technique for mitral valve repair, however, it is difficult to accurately determine the length of artificial chordae. This study aimed to assess the reliability and accuracy of real-time three-dimensional transesophageal echocardiography (TEE) to predict the length of artificial chordae preoperatively.
From December 2008 to December 2010, 48 patients with severe mitral regurgitation successfully underwent mitral valve repair using artificial chordae replacement. The patients were divided into a TEE pre-measurement group (n = 26) and a direct measurement group (n = 22), according to the method used to determine the length of artificial chordae. Cardiopulmonary bypass time, aortic cross-clamp time, and the recurrence rate of moderate or severe mitral regurgitation were compared between the two groups.
There were no operative deaths in either group. The mean cardiopulmonary bypass time was 113.0 ± 18.7 min and 127.0 ± 28.9 min (p < 0.05), and the aortic cross-clamp time was 70.0 ± 16.6 min and 86.0 ± 20.7 min (p < 0.05) in the TEE pre-measurement group and direct measurement group, respectively. The difference between the pre-measured artificial chordal length and actual constructed artificial chordal length was not significant in the TEE pre-measurement group (p > 0.05). Although the difference in the incidence of moderate or severe mitral regurgitation between the two groups was not significant (p > 0.05), the incidence in the TEE pre-measurement group (3.8%) was lower than that in the direct measurement group (18.2%).
Real-time three-dimensional transesophageal echocardiography can accurately predict the length of artificial chordae required for mitral valve repair, and shortens cardiopulmonary bypass time and aortic cross-clamp time while improving the results of mitral valve repair.
Artificial chordae replacement; Mitral valve repair; Real-time three-dimensional transesophageal echocardiography
Gene therapy has shown a tremendous potential to benefit patients in a variety of disease conditions. However, finding a safe and effective systemic delivery system is the major obstacle in this area. Although viral vectors showed promise for high transfection rate, the immunogenicity associated with these systems has hindered further development. As an alternative to viral gene delivery, this review focuses on application of novel safe and effective non-condensing polymeric systems that have shown high transgene expression when administered systemically or by the oral route. Type B gelatin-based engineered nanocarriers were evaluated for passive and active tumor-targeted delivery and transfection using both reporter and therapeutic plasmid DNA. Additionally, we have shown that nanoparticles-in-microsphere oral system (NiMOS) can efficiently deliver reporter and therapeutic gene constructs in the gastrointestinal tract. Additionally, there has been a significant recent interest in the use small interfering RNA (siRNA) as a therapeutic system for gene silencing. Both gelatin nanoparticles and NiMOS have shown activity in systemic and oral delivery of siRNA, respectively.
Non-viral gene delivery; non-condensing polymers; type B gelatin; nanoparticles; nanoparticles-in-microsphere oral system (NiMOS)
To examine whether the peroxisome proliferator–activated receptor-γ coactivator-1α (PGC-1α), a key regulator linking angiogenesis and metabolism, could enhance the engraftment and angiogenesis of mesenchymal stem cells (MSCs) in diabetic hindlimb ischemia, we engineered the overexpression of PGC-1α within MSCs using an adenoviral vector encoding green fluorescent protein and PGC-1α, and then tested the survivability and angiogenesis of MSCs in vitro and in vivo. Under the condition of hypoxia concomitant with serum deprivation, the overexpression of PGC-1α in MSCs resulted in a higher expression level of hypoxia-inducible factor-1α (Hif-1α), a greater ratio of B-cell lymphoma leukemia-2 (Bcl-2)/Bcl-2–associated X protein (Bax), and a lower level of caspase 3 compared with the controls, followed by an increased survival rate and an elevated expression level of several proangiogenic factors. In vivo, the MSCs modified with PGC-1α could significantly increase the blood perfusion and capillary density of ischemic hindlimb of the diabetic rats, which was correlated to an improved survivability of MSCs and an increased level of several proangiogenic factors secreted by MSCs. We identified for the first time that PGC-1α could enhance the engraftment and angiogenesis of MSCs in diabetic hindlimb ischemia.