Acupuncture therapy for preventive and treatment of postoperative nausea and vomiting(PONV), a condition which commonly present after anaesthesia and surgery is a subject of growing interest.
This paper included a systematic review and meta-analysis on the effect of different type of acupuncture and acupoint selection in PONV prevention and treatment.
Randomised controlled trials(RCTs) comparing acupuncture with non-acupuncture treatment were identified from databases PubMed, Cochrane, EBSCO, Ovid, CNKI and Wanfangdata. Meta-analysis on eligible studies was performed using fixed-effects model with RevMan 5.2. Results were expressed as RR for dichotomous data, with 95%CI.
Thirty RCTs, 1276 patients (intervention) and 1258 patients (control) were identified. Meta-analysis showed that PC6 acupuncture significantly reduced the number of cases of early vomiting (postoperative 0-6h) (RR=0.36, 95%CI 0.19,0.71; P=0.003) and nausea (postoperative 0-24h) (RR=0.25, 95%CI 0.10,0.61; P=0.002), but not early nausea (postoperative 0-6h) (RR=0.64, 95%CI 0.34,1.19; P=0.150) and vomiting (postoperative 0-24h) (RR=0.82, 95%CI 0.48,1.38; P=0.450). PC6 acupressure significantly reduced the number of cases of nausea (RR=0.71, 95%CI 0.57,0.87; P=0.001) and vomiting (RR=0.62, 95%CI 0.49,0.80; P=0.000) at postoperative 0-24h. PC6 electro-acupoint stimulation significantly reduced the number of cases of nausea (RR=0.49, 95%CI 0.38,0.63; P<0.000) and vomiting (RR=0.50, 95%CI 0.36,0.70; P<0.000) at postoperative 0-24h. Stimulation of PC6 with other acupoint(s) significantly reduced the number of cases of nausea and vomiting (RR=0.29, 95%CI 0.17,0.49; P<0.000) at postoperative 0-24h. Stimulation of other acupoint(s)(non PC6) also significantly reduced the number of cases of nausea and vomiting (RR=0.63, 95%CI 0.49,0.81; P=0.000) at postoperative 0-24h. However, the quality of study was generally low in studies of PC6 combined with other acupoint(s) and other acupoint(s). Details of blinding were not reported in most reports.
Besides PC6, PC6 combined with other acupoint(s) and other alternative acupoint(s) might be beneficial in prevention and treatment of PONV, the evidence justifies future high-quality studies.
Proline accumulation was often correlated with drought tolerance of plants infected by arbuscular mycorrhizal fungi (AMF), whereas lower proline in some AM plants including citrus was also found under drought stress and the relevant mechanisms have not been fully elaborated. In this study proline accumulation and activity of key enzymes relative to proline biosynthesis (▵1-pyrroline-5-carboxylate synthetase, P5CS; ornithine-δ-aminotransferase, OAT) and degradation (proline dehydrogenase, ProDH) were determined in trifoliate orange (Poncirus trifoliata, a widely used citrus rootstock) inoculated with or without Funneliformis mosseae and under well-watered (WW) or water deficit (WD). AMF colonization significantly increased plant height, stem diameter, leaf number, root volume, biomass production of both leaves and roots and leaf relative water content, irrespectively of water status. Water deficit induced more tissue proline accumulation, in company with an increase of P5CS activity, but a decrease of OAT and ProDH activity, no matter whether under AM or no-AM. Compared with no-AM treatment, AM treatment resulted in lower proline concentration and content in leaf, root, and total plant under both WW and WD. The AMF colonization significantly decreased the activity of both P5CS and OAT in leaf, root, and total plant under WW and WD, except for an insignificant difference of root OAT under WD. The AMF inoculation also generally increased tissue ProDH activity under WW and WD. Plant proline content significantly positively correlated with plant P5CS activity, negatively with plant ProDH activity, but not with plant OAT activity. These results suggest that AM plants may suffer less from WD, thereby inducing lower proline accumulation, which derives from the integration of an inhibition of proline synthesis with an enhancement of proline degradation.
Short-hairpin RNA (shRNA)-induced RNAi is used for biological discovery and therapeutics. Dicer, whose normal role is to liberate endogenous miRNAs from their precursors, processes shRNAs into different biologically active siRNAs, affecting their efficacy and potential for off-targeting. We found that in cells, Dicer induced imprecise cleavage events around the expected sites based on the previously described 5′/3′-counting rules. These promiscuous non-canonical cleavages were abrogated when the cleavage site was positioned 2 nt from a bulge or loop. Interestingly, we observed that the ~1/3 of mammalian endogenous pre-miRNAs that contained such structures were more precisely processed by Dicer. Implementing a new “loop-counting rule”, we designed potent anti-HCV shRNAs with substantially reduced off-target effects. Our results suggest that Dicer recognizes the loop/bulge structure in addition to the ends of shRNAs/pre-miRNAs for accurate processing. This has important implications for both miRNA processing and future design of shRNAs for RNAi-based genetic screens and therapies.
Dicer; shRNA; microRNA; RNAi; off-target effect; HCV
Zinc finger, BED-type containing 6 (ZBED6) is an important transcription factor in placental mammals, affecting development, cell proliferation and growth. Polymorphisms in its promoter and coding regions are likely to impact ZBED6 transcription and growth traits. In this study, rapid amplification of 5’ cDNA ends (5'-RACE) analysis revealed two transcription start sites (TSS) for the bovine ZBED6 starting within exon 1 of the ZC3H11A gene (TSS-1) and upstream of the translation start codon of the ZBED6 gene (TSS-2). There was one SNP in the promoter and two missense mutations in the coding region of the bovine ZBED6 by sequencing of the pooled DNA samples (Pool-Seq, n = 100). The promoter and coding region are the key regions for gene function; polymorphisms in these regions can alter gene expression. Quantitative real-time PCR (qPCR) analysis showed that ZBED6 has a broad tissue distribution in cattle and is highly expressed in skeletal muscle. Eleven promoter-detection vectors were constructed, which enabled the cloning of putative promoter sequences and analysis of ZBED6 transcriptional activity by luciferase reporter gene assays. The core region of the basal promoter of bovine ZBED6 is located within region -866 to -556. The activity of WT-826G-pGL3 in driving reporter gene transcription is significantly higher than that of the M-826A-pGL3 construct (P < 0.01). Analysis of gene expression patterns in homozygous full-sibling Chinese Qinchuan cattle showed that the mutant-type Hap-AGG exhibited a lower mRNA level than the wild-type Hap-GCA (P < 0.05) in longissimus dorsi muscle (LDM). Moreover, ZBED6 mRNA expression was low in C2C12 cells overexpressing the mutant-type ZBED6 (pcDNA3.1+-Hap-GG) (P < 0.01). Our results suggest that the polymorphisms in the promoter and coding regions may modulate the promoter activity and gene expression of bovine ZBED6 in the skeletal muscles of these cattle breeds.
Background. Efavirenz exhibits marked interindividual variability in plasma levels and toxicities. Prior pharmacogenetic studies usually measure exposure via single plasma levels, examine limited numbers of polymorphisms, and rarely model multiple contributors. We analyzed numerous genetic and nongenetic factors impacting short-term and long-term exposure in a large heterogeneous population of human immunodeficiency virus (HIV)–infected women.
Methods. We performed 24-hour intensive pharmacokinetic studies in 111 women receiving efavirenz under actual-use conditions and calculated the area-under-the-concentration-time curve (AUC) to assess short-term exposure; the efavirenz concentration in hair was measured to estimate long-term exposure. A total of 182 single-nucleotide polymorphisms (SNPs) and 45 haplotypes in 9 genes were analyzed in relationship to exposure by use of multivariate models that included a number of nongenetic factors.
Results. Efavirenz AUCs increased 1.26-fold per doubling of the alanine aminotransferase level and 1.23-fold with orange and/or orange juice consumption. Individuals with the CYP2B6 516TT genotype displayed 3.5-fold increases in AUCs and 3.2-fold increases in hair concentrations, compared with individuals with the TG/GG genotype. Another SNP in CYP2B6 (983TT) and a p-glycoprotein haplotype affected AUCs without substantially altering long-term exposure.
Conclusions. This comprehensive pharmacogenomics study showed that individuals with the CYP2B6 516TT genotype displayed >3-fold increases in both short-term and long-term efavirenz exposure, signifying durable effects. Pharmacogenetic testing combined with monitoring of hair levels may improve efavirenz outcomes and reduce toxicities.
The MATH (meprin and TRAF-C homology) domain is a fold of seven anti-parallel β-helices involved in protein-protein interaction. Here, we report the identification and characterization of 90 MATH-domain proteins from the Brassica rapa genome. By sequence analysis together with MATH-domain proteins from other species, the B. rapa MATH-domain proteins can be grouped into 6 classes. Class-I protein has one or several MATH domains without any other recognizable domain; Class-II protein contains a MATH domain together with a conserved BTB (Broad Complex, Tramtrack, and Bric-a-Brac ) domain; Class-III protein belongs to the MATH/Filament domain family; Class-IV protein contains a MATH domain frequently combined with some other domains; Class-V protein has a relative long sequence but contains only one MATH domain; Class-VI protein is characterized by the presence of Peptidase and UBQ (Ubiquitinylation) domains together with one MATH domain. As part of our study regarding seed development of B. rapa, six genes are screened by SSH (Suppression Subtractive Hybridization) and their expression levels are analyzed in combination with seed developmental stages, and expression patterns suggested that Bra001786, Bra03578 and Bra036572 may be seed development specific genes, while Bra001787, Bra020541 and Bra040904 may be involved in seed and flower organ development. This study provides the first characterization of the MATH domain proteins in B. rapa
Brassica rapa; Phylogenetic analysis; MATH domain protein; Protein domain organization; Gene expression; Seed development.
Retroperitoneal lymph node and lung metastasis are important prognostic factors for gynecologic cancer. The present study aimed to develop a new animal model for retroperitoneal lymph node and lung metastasis. VX2 squamous cell carcinoma tumor tissues were injected into the left gastrocnemius muscle of 38 healthy female New Zealand white rabbits. Animals were randomized into three groups according to day of sacrifice: 1, day 19; 2, day 22; and 3, day 25. Implanted primary tumor (IPTu), left and right retroperitoneal lymph node volumes and lung wet weights were measured on the day of sacrifice. The IPTu and left and right retroperitoneal lymph node volumes increased in a time-dependent manner. In addition, the proportion of animals with metastasis to the left peritoneal lymph nodes and the number of nodes involved increased over time. For days 19, 22 and 25, the proportion of animals with nodal metastasis was 58.3, 84.6 and 100%, respectively, and the number of affected nodes (range) was 3 (2–3), 3 (3–5) and 4 (4–5), respectively. No metastasis was detected in the right peritoneal lymph nodes. Metastasis to the lungs also increased with time, but was not statistically significant at days 19, 22 and 25 with metastasis present in 33.3, 38.5 and 76.9% of animals, respectively. Rates of metastases to the left retroperitoneal lymph nodes and lungs were found to positively correlate with the volumes (r=0.416 and 0.449, respectively). The current study assessed the characterization of a rabbit VX2 carcinoma model. This animal model is likely to be useful for evaluating retroperitoneal lymph node and lung metastasis.
retroperitoneal lymph nodes; lung metastasis; metastasis; VX2 carcinoma; rabbit model
Glucocorticoids (GC) and 1,25-dihydroxyvitamin D3 (1,25(OH)2 D3) are steroid hormones with anti-inflammatory properties with enhanced effects when combined. We previously showed that transcriptional response to GCs was correlated with inter-individual and inter-ethnic cellular response. Here, we profiled cellular and transcriptional responses to 1,25(OH)2 D3 from the same donors. We studied cellular response to combined treatment with GCs and 1,25(OH)2 D3 in a subset of individuals least responsive to GCs. We found that combination treatment had significantly greater inhibition of proliferation than with either steroid hormone alone. Overlapping differentially expressed (DE) genes between the two hormones were enriched for adaptive and innate immune processes. Non-overlapping differentially expressed genes with 1,25(OH)2 D3 treatment were enriched for pathways involving the electron transport chain, while with GC treatment, non-overlapping genes were enriched for RNA-related processes. These results suggest that 1,25(OH)2 D3 enhances GC anti-inflammatory properties through a number of shared and non-shared transcriptionally-mediated pathways.
We have developed an amplified chemiluminescence turn-on sensing platform that relies on single-walled carbon nanotube for ultrasensitive DNA detection. This new type of assay exhibits high detection sensitivity over traditional biosensors three orders of magnitude and high specificity for target molecules.
Small RNAs regulate genetic networks through a ribonucleo-protein complex called the RNA-induced silencing complex (RISC), which, in mammals, contains at its center one of four Argonaute proteins (Ago1–Ago4) (reviewed in [1–4]). A key regulatory event in the RNA interference (RNAi) and microRNA (miRNA) pathways is Ago loading, wherein double-stranded small-RNA duplexes are incorporated into RISC (pre-RISC) and then become single-stranded (mature RISC), a process that is not well understood [5, 6]. The Agos contain an evolutionarily conserved PAZ (Piwi/Argonaute/Zwille) domain [7, 8] whose primary function is to bind the 3′ end of small RNAs [9–13]. We created multiple PAZ-domain-disrupted mutant Ago proteins and studied their biochemical properties and biological functionality in cells. We found that the PAZ domain is dispensable for Ago loading of slicing-competent RISC. In contrast, in the absence of slicer activity or slicer-substrate duplex RNAs, PAZ-disrupted Agos bound duplex small interfering RNAs, but were unable to unwind or eject the passenger strand and form functional RISC complexes. We have discovered that the highly conserved PAZ domain plays an important role in RISC activation, providing new mechanistic insights into how miRNAs regulate genes, as well as new insights for future design of miRNA- and RNAi-based therapeutics.
Rationale: An increased tricuspid regurgitation jet velocity (TRV > 2.5 m/s) and pulmonary hypertension defined by right heart catheterization both independently confer increased mortality in sickle cell disease (SCD).
Objectives: We explored the usefulness of peripheral blood mononuclear cell–derived gene signatures as biomarkers for an elevated TRV in SCD.
Methods: Twenty-seven patients with SCD underwent echocardiography and peripheral blood mononuclear cell isolation for expression profiling and 112 patients with SCD were genotyped for single-nucleotide polymorphisms.
Measurements and Main Results: Genome-wide gene and miRNA expression profiles were correlated against TRV, yielding 631 transcripts and 12 miRNAs. Support vector machine analysis identified a 10-gene signature including GALNT13 (encoding polypeptide N-acetylgalactosaminyltransferase 13) that discriminates patients with and without increased TRV with 100% accuracy. This finding was then validated in a cohort of patients with SCD without (n = 10) and with pulmonary hypertension (n = 10, 90% accuracy). Increased TRV-related miRNAs revealed strong in silico binding predictions of miR-301a to GALNT13 corroborated by microarray analyses demonstrating an inverse correlation between their expression. A genetic association study comparing patients with an elevated (n = 49) versus normal (n = 63) TRV revealed five significant single-nucleotide polymorphisms within GALNT13 (P < 0.005), four trans-acting (P < 2.1 × 10−7) and one cis-acting (P = 0.6 × 10−4) expression quantitative trait locus upstream of the adenosine-A2B receptor gene (ADORA2B).
Conclusions: These studies validate the clinical usefulness of genomic signatures as potential biomarkers and highlight ADORA2B and GALNT13 as potential candidate genes in SCD-associated elevated TRV.
microarray; candidate gene approach; eQTL; pulmonary hypertension
The inhibitory effects of vitamin D on colitis have been previously documented. Global vitamin D receptor (VDR) deletion exaggerates colitis, but the relative anticolitic contribution of epithelial and nonepithelial VDR signaling is unknown. Here, we showed that colonic epithelial VDR expression was substantially reduced in patients with Crohn’s disease or ulcerative colitis. Moreover, targeted expression of human VDR (hVDR) in intestinal epithelial cells (IECs) protected mice from developing colitis. In experimental colitis models induced by 2,4,6-trinitrobenzenesulfonic acid, dextran sulfate sodium, or CD4+CD45RBhi T cell transfer, transgenic mice expressing hVDR in IECs were highly resistant to colitis, as manifested by marked reductions in clinical colitis scores, colonic histological damage, and colonic inflammation compared with WT mice. Reconstitution of Vdr-deficient IECs with the hVDR transgene completely rescued Vdr-null mice from severe colitis and death, even though the mice still maintained a hyperresponsive Vdr-deficient immune system. Mechanistically, VDR signaling attenuated PUMA induction in IECs by blocking NF-κB activation, leading to a reduction in IEC apoptosis. Together, these results demonstrate that gut epithelial VDR signaling inhibits colitis by protecting the mucosal epithelial barrier, and this anticolitic activity is independent of nonepithelial immune VDR actions.
We propose a novel compressive sensing (CS) method on spectral domain optical coherence tomography (SDOCT). By replacing the widely used uniform discrete Fourier transform (UDFT) matrix with a new sensing matrix which is a modification of the non-uniform discrete Fourier transform (NUDFT) matrix, it is shown that undersampled non-linear wavenumber spectral data can be used directly in the CS reconstruction. Thus k-space grid filling and k-linear mask calibration which were proposed to obtain linear wavenumber sampling from the non-linear wavenumber interferometric spectra in previous studies of CS in SDOCT (CS-SDOCT) are no longer needed. The NUDFT matrix is modified to promote the sparsity of reconstructed A-scans by making them symmetric while preserving the value of the desired half. In addition, we show that dispersion compensation can be implemented by multiplying the frequency-dependent correcting phase directly to the real spectra, eliminating the need for constructing complex component of the real spectra. This enables the incorporation of dispersion compensation into the CS reconstruction by adding the correcting term to the modified NUDFT matrix. With this new sensing matrix, A-scan with dispersion compensation can be reconstructed from undersampled non-linear wavenumber spectral data by CS reconstruction. Experimental results show that proposed method can achieve high quality imaging with dispersion compensation.
(170.4500) Optical coherence tomography; (100.3010) Image reconstruction techniques
Hand-held OCT systems that offer physicians greater freedom to access imaging sites of interest could be useful for many clinical applications. In this study, by incorporating the theoretical speckle model into the decorrelation function, we have explicitly correlated the cross-correlation coefficient to the lateral displacement between adjacent A-scans. We used this model to develop and study a freehand-scanning OCT system capable of real-time scanning speed correction and distortion-free imaging—for the first time to the best our knowledge. To validate our model and the system, we performed a series of calibration experiments. Experimental results show that our method can extract lateral scanning distance. In addition, using the manually scanned hand-held OCT system, we obtained OCT images from various samples by freehand manual scanning, including images obtained from human in vivo.
(170.4500) Optical coherence tomography; (120.5800) Scanners; (030.6140) Speckle; (330.4150) Motion detection
The Oriental garden lizard (Calotes versicolor) is one of the few non-gekkonid lizards that are geographically widespread in the tropics. We investigated its population dynamics on Hainan Island and the adjacent mainland of China and Vietnam, focusing on the impact of cyclic upheaval and submergence of land bridges during the Pleistocene. Our Bayesian phylogenetic analysis reveals two mitochondrial lineages, A and B, which are estimated to have coalesced about 0.26 million years ago (95% credibility interval: 0.05–0.61 million years ago). Lineage A contains individuals mainly from central and southern Wuzhi Mountain on Hainan Island, whereas lineage B mainly comprises individuals from other sites on the island plus the adjacent mainland. The estimated coalescence times within lineages A (0.05 million years ago) and B (0.13 million years ago) fall within a period of cyclical land-bridge formation and disappearance in the Pleistocene. A spatial analysis of molecular variance identified two distinct population groupings: I, primarily containing lineage A, and II, mainly consisting of lineage B. However, haplotypes from lineages A and B occur sympatrically, suggesting that gene flow is ongoing. Neither Wuzhi Mountain nor Qiongzhou Strait and Gulf of Tonkin act as barriers to gene flow among C. versicolor populations. Analyses of the data using mismatch distributions and extended Bayesian skyline plots provide evidence of a relatively stable population size through time for Group I, and moderate population expansions and contractions during the end of the Pleistocene for Group II. We conclude that the phylogeographical patterns of C. versicolor are the combined product of Pleistocene sea-level oscillations and nonphysical barriers to gene flow.
Two brothers (case 1 and case 2) with erythema nodosum were diagnosed with thromboangiitis obliterans (TAO). The patients were treated with compounds including Danshen Dripping Pills, Fufang Danshen Diwan and Salvia tetramethylpyrazine. The patients were also treated with fibro-blast growth factor to promote epidermal growth and Bayaspirin enteric-coated tablets to reduce platelet aggregation. The polysaccharide nucleic acid fraction of Bacillus Calmette-Guérin and compound glycyrrhizin tablets were taken to improve immune function. Following treatment, case 2 had reduced pain levels in the left foot. The ulcer on the first toe of the left foot had decreased in size, with a reduction in pus secretions and inflammation. Case 1 demonstrated a reduction in pus secretion from the ulcer. However, the area of the ulcer had increased, spreading to the fifth toe with gangrene. A tendon had become exposed on the right foot, which was broken and induced severe pain.
erythema nodosum; thromboangiitis obliterans; case report
Melioidosis, caused by Burkholderia pseudomallei, is considered to be endemic to Northern Australia and Southeast Asia, with high mortality and relapse rates, regardless of powerful antibiotic therapy. Here we report the first genome sequence of Burkholderia pseudomallei strain BPC006, obtained from a melioidosis patient in Hainan, China. The genome sizes of the 2 chromosomes were determined to be 4,001,777 bp and 3,153,284 bp.
We announce the draft genome sequence of Borrelia garinii strain NMJW1, isolated from Ixodes persulcatus in northeastern China. The 902,789-bp linear chromosome (28.4% GC content) contains 813 open reading frames, 33 tRNAs, and 4 complete rRNAs.
T7-like bacteriophages are a class of virulent bacteriophages which have a clearer genetic background and smaller genomes than other phages. In addition, it grows faster and is easier to culture than other phages. At present, the numbers of available T7-like bacteriophage genomes and Stenotrophomonas maltophilia genomes are small, and IME15 is the first T7-like virulent Stenotrophomonas phage whose sequence has been reported. It shows effective lysis of S. maltophilia. Here we announce its complete genome, and major findings from its annotation are described.
N4-like bacteriophages are a class of virulent Podoviridae phages for which few genome sequences are present in GenBank. IME11, a novel lytic Escherichia bacteriophage with a wide host range, was isolated, and the whole genome was sequenced. It has a circular double-stranded DNA genome of 72,570 bp. Genomic analysis showed that it resembles another Escherichia phage, vB_EcoP_G7C. Here we announce its complete genome and major findings from its annotation.
Nutrition has been known for ages to shield the immune system against several formulations that deregulate normal DNA repair mechanisms, and induce tumorigenesis. Vitamins and in specific Vit E and its members tocopherols (α-, β-, γ-, δ-) and tocotrienols (α-, β-, γ-, δ-) have demonstrated strong association with the prevention of cancer and inhibition of tumor, both in vitro and in vivo. Vitamin E has also demonstrated effective role against chemotherapy resistant cancer cell evolution and a protective role in acute interstitial disease. Several formulations of Vitamin E have been investigated conjugated with different carriers as nano-formulations and administered in different forms. Additionally, several tumorigenic pathways have been investigated separately in an effort to identify which member of Vitamin E inhibits efficiently every pathway. Vitamin E presented efficiency against specific subhistology types of lung cancer. Finally, in the current work up to date information regarding novel formulations with Vitamin E and inhibition pathways are going to be presented and commented.
Vitamin E; tocopherol; tocotrienol; lung cancer; nutrition; nanomedicine
Retroperitoneal lymph node (RLN) metastasis is an important indicator of endometrial cancer (EC) prognosis. Because vascular endothelial growth factor c (VEGF-c) is known to influence lymphangiogenesis and thereby lymph node metastasis, this study assessed the relationship of VEGF-c mRNA expression with RLN metastasis in EC.
The uterine muscularis mucosae of New Zealand white rabbits were inoculated with a VX2 tumor cell suspension after which they were sacrificed at 15, 18, 21, 24, 27 and 30 days. Control groups consisted of those receiving no treatment or an injection of saline. EC and metastatic RLN tissues along with peripheral blood samples were collected, and VEGF-c mRNA expression was evaluated using fluorescence real-time quantitative PCR.
The establishment of an in vivo model of EC with complete RLN metastasis was pathologically confirmed at day 21 post-injection with VX2 cells. As compared to the control groups, VEGF-c mRNA expression increased significantly over time in the tumor site, RLN, and peripheral white blood cells of EC rabbits. Significantly higher VEGF-c mRNA expression was observed in metastatic RLNs as compared to those without metastasis (P < 0.001). In addition, increased VEGF-c mRNA expression was observed in peripheral white blood cells of rabbits with RLN metastasis (P < 0.002).
Injection of a VX2 cell suspension is a simple method of establishing an in vivo EC model. VEGF-c may play an important role in the development of EC and its metastasis to RLN and may be useful marker to predict RLN metastasis.
Vascular endothelial growth factor c; Endometrial cancer; Fluorescence real-time quantitative PCR; Disease animal model; Animal; Rabbit
Adult-onset autosomal-dominant leukodystrophy (ADLD) is a progressive and fatal
neurological disorder characterized by early autonomic dysfunction, cognitive
impairment, pyramidal tract and cerebellar dysfunction, and white matter loss in the
central nervous system. ADLD is caused by duplication of the LMNB1
gene, which results in increased lamin B1 transcripts and protein expression. How
duplication of LMNB1 leads to myelin defects is unknown. To address
this question, we developed a mouse model of ADLD that overexpresses lamin B1. These
mice exhibited cognitive impairment and epilepsy, followed by age-dependent motor
deficits. Selective overexpression of lamin B1 in oligodendrocytes also resulted in
marked motor deficits and myelin defects, suggesting these deficits are cell
autonomous. Proteomic and genome-wide transcriptome studies indicated that lamin B1
overexpression is associated with downregulation of proteolipid protein, a highly
abundant myelin sheath component that was previously linked to another myelin-related
disorder, Pelizaeus-Merzbacher disease. Furthermore, we found that lamin B1
overexpression leads to reduced occupancy of Yin Yang 1 transcription factor at the
promoter region of proteolipid protein. These studies identify a mechanism by which
lamin B1 overexpression mediates oligodendrocyte cell–autonomous
neuropathology in ADLD and implicate lamin B1 as an important regulator of myelin
formation and maintenance during aging.
Catalase (CAT) breaks down H2O2 into H2O and O2 to protects cells from oxidative damage. However, its translational potential is limited because exogenous CAT cannot enter living cells automatically. This study is aimed to investigate if PEP-1-CAT fusion protein can effectively protect cardiomyocytes from oxidative stress due to hypoxia/reoxygenation (H/R)-induced injury.
H9c2 cardomyocytes were pretreated with catalase (CAT) or PEP-1-CAT fusion protein followed by culturing in a hypoxia and re-oxygenation condition. Cell apoptosis were measured by Annexin V and PI double staining and Flow cytometry. Intracellular superoxide anion level was determined, and mitochondrial membrane potential was measured. Expression of apoptosis-related proteins including Bcl-2, Bax, Caspase-3, PARP, p38 and phospho-p38 was analyzed by western blotting.
PEP-1-CAT protected H9c2 from H/R-induced morphological alteration and reduced the release of lactate dehydrogenase (LDH) and malondialdehyde content. Superoxide anion production was also decreased. In addition, PEP-1-CAT inhibited H9c2 apoptosis and blocked the expression of apoptosis stimulator Bax while increased the expression of Bcl-2, leading to an increased mitochondrial membrane potential. Mechanistically, PEP-1-CAT inhibited p38 MAPK while activating PI3K/Akt and Erk1/2 signaling pathways, resulting in blockade of Bcl2/Bax/mitochondrial apoptotic pathway.
Our study has revealed a novel mechanism by which PEP-1-CAT protects cardiomyocyte from H/R-induced injury. PEP-1-CAT blocks Bcl2/Bax/mitochondrial apoptotic pathway by inhibiting p38 MAPK while activating PI3K/Akt and Erk1/2 signaling pathways.
Cell-penetrating peptide; PEP-1; Catalase; Cardiomyocyte; Apoptosis; MAPK
Previous work demonstrated that both the opioid antagonist (−)-naloxone and the nonopioid (+)-naloxone inhibit toll-like receptor 4 (TLR4) signaling and reverse neuropathic pain expressed shortly after chronic constriction injury. The present studies reveal that the TLR4 contributes to neuropathic pain in another major model (spinal nerve ligation) and to long established (2–4 mon) neuropathic pain, not just to pain shortly after nerve damage. Additionally, analyses of plasma levels of (+)-naloxone after subcutaneous administration indicate that (+)-naloxone has comparable pharmacokinetics to (−)-naloxone with a relatively short half-life. This finding accounts for the rapid onset and short duration of allodynia reversal produced by subcutaneous (+)-naloxone. Given that TLR2 has also recently been implicated in neuropathic pain, cell lines transfected with either TLR4 or TLR2, necessary co-signaling molecules, and a reporter gene were used to define whether (+)-naloxone effects could be accounted for by actions at TLR2 in addition to TLR4. (+)-Naloxone inhibited signaling by TLR4 but not TLR2. These studies provide evidence for broad involvement of TLR4 in neuropathic pain, both early after nerve damage and months later. Additional, they provide further support for the TLR4 inhibitor (+)-naloxone as a novel candidate for the treatment of neuropathic pain.
TLR4; neuropathic pain; chronic constriction injury; spinal nerve ligation; HEK293-TLR4