Baseline Serum Estradiol Level Is Associated with Acute Kidney Injury in Patients with Moderately Severe and Severe Acute Pancreatitis.

Background: Sexual dimorphism with critical diseases has been documented. However, the role of serum sex hormones for the presence of acute kidney injury (AKI) in moderately or severe acute pancreatitis (MSAP and SAP) patients remains controversial. Here we set out to evaluate whether early (first 48 h) serum estradiol level is associated with AKI in patients with MSAP and SAP. Patients and Methods. We retrospectively collected data from patients with preliminary diagnosis of MSAP and SAP from the Affiliated Hospital of Yangzhou University between January 2014 and June 2018. Serum sex hormones were extracted for further assessment within first 48 h following admission. Logistic regression analysis and the receiving operating characteristic (ROC) curve were applied to evaluate the association and correlation between serum sex hormones and AKI. Results: Data from a total of 122 patients with MSAP or SAP were enrolled in this study. There were no differences in the incidence of AKI between males and females. However, comparing with patients without AKI, those with AKI saw higher estradiol level (p ≤ 0.01) and slight higher progesterone level (p = 0.014) but similar testosterone level (p = 0.668). Interestingly, during both the manual selection and the stepwise backward logistic regression analysis, serum estradiol level was independently associated with AKI in patients with MSAP and SAP (OR 4.699, CI 1.783-12.386, and p = 0.002). Additionally, area under the curve of ROC (AUCROC) showed that serum estradiol level was a proper predictor for AKI (area under the curve 0.875). Specifically, the serum estradiol level of 223.15 pg/mL demonstrated a 92.3% sensitive and a 79.3% specificity in predicting AKI of MSAP and SAP patients, respectively. Conclusions: High baseline serum estradiol level appears to be an independent risk factor for AKI in patients with MSAP and SAP. It also tends to be an appropriate indicator for AKI.

Elevated PCT at ICU discharge predicts poor prognosis in patients with severe traumatic brain injury: a retrospective cohort study.

PURPOSE: Disease severity and inflammatory response status are closely related to a poor prognosis and must be assessed in patients with severe traumatic brain injury (STBI) before intensive care unit (ICU) discharge. Whether elevated serum procalcitonin (PCT) levels can predict a poor prognosis in STBI patients before ICU discharge is unclear. METHODS: This retrospective observational cohort study enrolled 199 STBI patients who were in the ICU for at least 48 hours and survived after discharge. Based on serum PCT levels at discharge, patients were divided into the high-PCT group (PCT ≥ 0.25 ng/mL) and the low-PCT group (PCT < 0.25 ng/mL). We assessed the relationship between serum PCT levels and a poor prognosis. RESULTS: The high-PCT group had a higher rate of adverse outcomes compared with the low-PCT group. Multivariate logistic regression analysis showed that the Acute Physiology and Chronic Health Evaluation II (APACHE II) score, Sequential Organ Failure Assessment (SOFA) score, white blood cell (WBC) count, C-reactive protein (CRP) level, and PCT level at discharge were significantly associated with adverse outcomes. CONCLUSIONS: Elevated PCT levels at ICU discharge were associated with a poor prognosis in STBI patients. The serum PCT level as a single indicator has limited value for clinical decision-making.

Identification of atherosclerosis-related prioritizing metabolites based on a multi-omics composite network.

Metabolites are the final products of cellular regulation processes, their level is the ultimate response of biological systems to environmental and genetic changes. Therefore, the identification of key metabolites is required for the diagnosis and therapy of diseases. In this study, atherosclerosis-related gene expression profile information was extracted from ArrayExpress database (GEOD-57691), and analyzed with limma package. Furthermore, we constructed an intricate multi-omics network involved in genes, phenotypes, metabolites and their associations. To identify the prioritization of atherosclerosis-related metabolites, the relation score of each metabolite in the composite network was computed with the random walk with restart (RWR) method. The top 50 metabolites and top 100 genes were chosen based on the score in the weighted composite network. Consequently, several key metabolites that were ranked in the top 5 of relation score or degree greater than 70 were confirmed. Particularly, metabolites Tretinoin and Estraderm not only have high relation scores, but also contain more degrees. Moreover, we obtained 24 co-expression genes that may be regarded as the targets of atherosclerosis therapy. Therefore, identification of metabolite prioritizations by the composite network integrated the information of genes, phenotypes and metabolites may be available to diagnose atherosclerosis, and can provide the potential therapeutic strategies for atherosclerosis.

Saikosaponin A protects against dextran sulfate sodium-induced colitis in mice.

Ulcerative colitis, one of the most important inflammatory bowel diseases, affects millions of people worldwide. The aim of this study was to investigate the effects of Saikosaponin A on dextran sulfate sodium (DSS)-induced colitis in mice. The mice were treated with 2.5% DSS for 5 d to induce acute colitis. Saikosaponin A was given 3 d before and during DSS treatment by intragastric administration. The results showed that Saikosaponin A significantly inhibited DSS-induced body weight loss and shortening of colon length. DSS-induced colonic histological changes and MPO activity were also prevented by treatment of Saikosaponin A. The levels of TNF-α and IL-1ß were increased by DSS and dose-dependently inhibited by Saikosaponin A. Furthermore, Saikosaponin A significantly inhibited DSS-induced NF-κB activation and up-regulated the expression of LXRα. Taken together, our results indicated that Saikosaponin A had protective effects against DSS-induced colitis. Saikosaponin A protected DSS-induced colitis through inhibiting inflammatory response.

Identification of QTN and candidate genes for Salinity Tolerance at the Germination and Seedling Stages in Rice by Genome-Wide Association Analyses.

To facilitate developing rice varieties tolerant to salt stress, a panel of 208 rice mini-core accessions collected from 25 countries were evaluated for 13 traits associated with salt tolerance (ST) at the germination and seedling stages. The rice panel showed tremendous variation for all measured ST traits and eight accessions showing high levels of ST at either and/or both the germination and seedling stages. Using 395,553 SNP markers covering ~372 Mb of the rice genome and multi-locus mixed linear models, 20 QTN associated with 11 ST traits were identified by GWAS, including 6 QTN affecting ST at the germination stage and 14 QTN for ST at the seedling stage. The integration of bioinformatic with haplotype analyses for the ST QTN lets us identify 22 candidate genes for nine important ST QTN (qGR3, qSNK1, qSNK12, qSNC1, qSNC6, qRNK2, qSDW9a, qSST5 and qSST9). These candidate genes included three known ST genes (SKC1, OsTZF1 and OsEATB) for QTN qSNK1 qSST5 and qSST9. Candidate genes showed significant phenotypic differences in ST traits were detected between or among 2-4 major haplotypes. Thus, our results provided useful materials and genetic information for improving rice ST in future breeding and for molecular dissection of ST in rice.

Harnessing the hidden genetic diversity for improving multiple abiotic stress tolerance in rice (Oryza sativa L.).

To develop superior rice varieties with improved yield in most rainfed areas of Asia/Africa, we started an introgression-breeding program for simultaneously improving yield and tolerances of multiple abiotic stresses. Using eight BC1 populations derived from a widely adaptable recipient and eight donors plus three rounds of phenotypic selection, we developed 496 introgression lines (ILs) with significantly higher yield under drought, salt and/or non-stress conditions in 5 years. Six new varieties were released in the Philippines and Pakistan and many more are being evaluated in multi-location yield trials for releasing in several countries. Marker-facilitated genetic characterization revealed three interesting aspects of the breeding procedure: (1) the donor introgression pattern in specific BC populations was characteristic; (2) introgression frequency in different genomic regions varied considerably, resulting primarily from strong selection for the target traits; and (3) significantly lower heterozygosity was observed in BC progenies selected for drought and salinity tolerance. Applying strong phenotypic selection under abiotic stresses in early segregating generations has major advantages for not only improving multiple abiotic stress tolerance but also achieving quicker homozygosity in early generations. This breeding procedure can be easily adopted by small breeding programs in developing countries to develop high-yielding varieties tolerant of abiotic stresses. The large set of trait-specific ILs can be used for genetic mapping of genes/QTL that affect target and non-target traits and for efficient varietal development by designed QTL pyramiding and genomics-based recurrent selection in our Green Super Rice breeding technology.

Comparison of reendothelialization and neointimal formation with stents coated with antibodies against endoglin and CD34 in a porcine model.

Anti-CD34 coated stents are the only commercialized antibody-coated stents currently used for coronary artery diseases with various limitations. Endoglin plays important roles in the proliferation of endothelial cells and vascular remodeling and could be an ideal target surface molecule. The objective of this study was to investigate the efficacy of stents coated with anti-endoglin antibodies (ENDs) in terms of endothelial recovery and the reduction of neointimal formation. The performance of ENDs was evaluated by comparing with stents coated with anti-CD34 antibodies (CD34s), sirolimus-eluting stents (SESs), and bare metal stents (BMSs). Stents were randomly assigned and placed in the coronary arteries of juvenile pigs. Histomorphometric analysis and scanning electron microscopy were performed after stent implantation. Our results showed at 14 days after stent implantation, the neointima area and percent area stenosis in ENDs and CD34s were remarkably decreased compared with those in BMSs and SESs (P<0.05). Moreover, the percentage of reendothelialization was significantly higher in ENDs and CD34s than that in SESs or BMSs at both 7 and 14 days (P<0.05). There was no difference in the neointima area, percent area stenosis, and percentage of reendothelialization in ENDs compared with CD34s. The artery injury and the inflammation scores were similar in all groups at both 7 and 14 days. Our results demonstrate that the performance of ENDs is similar to the commercial CD34s, without the disadvantages of CD34s, and both are better than SESs and BMSs. ENDs potentially offer an alternative approach to reduce restenotic process and enhance reendothelialization after stent implantation.

A novel stent coated with antibodies to endoglin inhibits neointimal formation of porcine coronary arteries.

Endoglin/CD105 is an accessory protein of the transforming growth factor-ß receptor system that plays a critical role in proliferation of endothelial cells and neovasculature. Here, we aimed to assess the effect of novel stents coated with antibodies to endoglin (ENDs) on coronary neointima formation. Thirty ENDs, thirty sirolimus-eluting stents (SESs), and thirty bare metal stents (BMSs) were randomly assigned and placed in the coronary arteries in 30 juvenile pigs. Histomorphometric analysis and scanning electron microscopy were performed after stent implantation. Our results showed that after 7 days, there was no difference in the neointimal area and percent area stenosis in ENDs compared with SMSs or BMSs. After 14 days, the neointima area and percent area stenosis in ENDs were markedly decreased than those in BMSs or SESs (P < 0.05). Moreover, the percentage of reendothelialization was significantly higher in ENDs than that in SESs or BMSs (P < 0.01) at 7 and 14 days. The artery injury and the inflammation scores were similar in all groups at 7 and 14 days. In conclusion, our results demonstrated for the first time to our knowledge that endoglin antibody-coated stents can markedly reduce restenosis by enhancing reendothelialization in the porcine model and potentially offer a new approach to prevent restenosis.

Role of LM23 in cell proliferation and apoptosis and its expression during the testis development.

LM23, a gene expressed specifically in the testis in a stage-specific manner, has a diverse range of functions that are important in both the life and death of spermatogenic cells. The aim of this study was to further investigate the expression of LM23 in the developing rat testis and the biological function of LM23 in proliferation and antiapoptosis in vitro. Semiquantitative reverse transcription (RT)-PCR and real-time PCR were used to examine the expression of LM23 in testis at different developmental stages. The results suggested that LM23 mRNA levels in the testis increased progressively after birth. The role of LM23 in proliferation was analyzed with cell counting kit-8 (CCK8), colony-forming efficiency (CFE) and flow cytometry assays. The results indicated that ectopic expression of LM23 in 293T cells significantly promoted cell proliferation by increasing cell numbers in S phase. Several methods were used, including CCK8, annexin V and propidium iodide staining and western blotting, to determine the role of LM23 in apoptosis. The results showed that LM23 played a protective role in H2O2-induced apoptosis of 293T cells, mediated at least in part through the Akt/PI3K signal pathway. Taken together, these results provide new insights into the role of LM23 in the development of the testes and spermatogenesis.

[Small RNA molecules and regulation of spermatogenesis].

Small RNA molecules (small RNAs) have recently emerged as important regulators of gene expression at the post-transcriptional or translation level. Significant progress has recently been made in utilizing small RNAs to elucidate the molecular mechanisms regulating spermatogenesis. There are three major small RNAs: small interfering RNAs (siRNAs), microRNAs (miRNAs), and piwi-interacting RNAs (piRNAs). Small-RNAs have diverse biological functions in meiosis and spermatogenesis, In vitro or in vivo, use of siRNA to knockdown genes is a way to study the function of genes of interest in spermatogenesis. miRNA can be involved in the regulation of mitosis, meiosis, and postmeiosis in spermatogenesis. piRNAs are mainly involved in regulating the process of meiosis and postmeiosis, and repressing retrotransposon transposition in male germline cells. In this paper, we reviewed recent works on the synthesis, mechanism, function, and outlook of small RNAs.

[Efficacy of stents coated with antibody against CD105 on preventing restenosis and thrombosis in minipigs].

OBJECTIVE: Novel stents loaded with antibody against CD105 were analyzed for their potential to limit coronary neointima formation and to accelerate endothelialization by attracting activated endothelial cell. METHODS: Thirty Stents coated with antibody against CD105, thirty unloaded polymer, and thirty bare metal stents were deployed in 90 coronary arteries of 30 minipigs. Oral aspirin (300 mg before operation and 100 mg post operation) and clopidogrel (300 mg before operation and 75 mg post operation) were orally administrated. Coronary artery quantitative analysis was completed by coronary arteriography, the vascular endothelium changes were observed under scanning electron microscope and the vascular morphological changes were observed under light microscope 7 and 14 days after operation. RESULTS: Complete procedural and angiographic success was achieved in all 30 minipigs. There were no major adverse cardiac and cerebrovascular events. At 7 days, there was no difference for mean neointimal area and percent area stenosis among various groups. At 14 days, endothelialization scores were significantly higher in the CD105 antibody-loaded stents and bare metal stents group than in sirolimus-eluting stents group (1.78 ± 0.49, 1.50 ± 0.67 vs. 1.08 ± 0.29, all P < 0.05), mean percent area stenosis in the CD105 antibody-loaded stents, sirolimus-eluting stents group were less than that in bare metal stents group [(23.8 ± 4)%, (24.2 ± 2)% vs. (38.0 ± 3)%, all P < 0.05], mean angiographic late luminal loss in the CD105 antibody-loaded stents, sirolimus-eluting stents group were less than that in bare metal stents group [(0.29 ± 0.28) mm, (0.28 ± 0.02) mm vs. (0.41 ± 0.01) mm, all P < 0.05]. There was no difference for mean percent area stenosis in the CD105 antibody-loaded stents and sirolimus-eluting stents group. The mean neointimal area in the CD105 antibody-loaded stents, and sirolimus-eluting stents group were less than that in bare metal stents group [(0.88 ± 0.08) mm(2), (0.89 ± 0.12mm)(2) vs. (1.00 ± 0.14) mm(2), all P < 0.05] and there was no difference for the mean neointimal area in the CD105 antibody-loaded stents and sirolimus-eluting stents group. At 7 and 14 days, there was no difference for the injury score and the inflammation score among various groups, scanning electron microscopy evidenced enhanced endothelial coverage on CD105 antibody-loaded stents compared to sirolimus-eluting stents group. CONCLUSION: Stent coated with antibody against CD105 could effectively reduce in-stent restenosis and accelerate endothelialization in the minipigs.

Relationship among soluble CD105, hypersensitive C-reactive protein and coronary plaque morphology: an intravascular ultrasound study.

BACKGROUND: Rupture of unstable plaque with subsequent thrombus formation is the common pathophysiological substrate of acute coronary syndrome (ACS). It is of potential significance to explore the blood indexes predicting plaque characteristics. We investigated the relationship among soluble CD105, hypersensitive C-reactive protein (hs-CRP), and coronary plaque morphology. METHODS: A clinical study from April 2004 to December 2006 was conducted in 130 patients who were divided into 3 groups: 56 patients (43.1%) in stable angina (SA) group, 52 patients (40.0%) in unstable angina (UA) group and 22 patients (16.9%) in acute myocardial infarction group. The concentrations of soluble CD105 and hs-CRP were measured in all of the patients by cardioangiography (CAG). Plasma samples of arterial blood were collected prior to the procedure. The levels of soluble CD105 and hs-CRP were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Unstable and ruptured plaque was found more frequently in patients with acute myocardial infarction and UA. External elastic membrane cross-sectional area (EEM CSA), plaque area, lipid pool area and plaque burden were significantly larger in the ruptured and unstable plaque group. Positive remodeling, thinner fabric-cap, smaller minimal lumen cross-sectional area (MLA), dissection and thrombus were significantly more frequent in the ruptured and unstable plaque group. Remodeling index (RI) was positively correlated with the levels of soluble CD105 in the UA group (r = 0.628, P < 0.01) and the acute myocardial infarction group (r = 0.639, P < 0.01). The levels of soluble CD105 and hs-CRP were higher in the ruptured plaque group. Soluble CD105 > 4.3 ng/ml was used to predict ruptured plaque with a receiver operating characteristic (ROC) curve area of 0.77 (95% confidence interval (CI), 66.8% - 87.2%), a sensitivity of 72.8%, a specificity of 78.0% and an accuracy of 70.2% (P < 0.01), similarly for hs-CRP > 5.0 mg/ml with a ROC curve area of 0.70 (95% CI, 59.2% - 80.2%), a sensitivity of 70.2%, a specificity of 76.2% and an accuracy of 67.2% (P < 0.01). CONCLUSIONS: The plaque characteristics correlate with the clinical presentation. The elevation of soluble CD105 and hs-CRP is related to the plaque instability and rupture.