Maternal Serum Macrophage Inhibitory Cytokine-1 as a Biomarker for Ectopic Pregnancy in Women with a Pregnancy of Unknown Location

Background

Ectopic pregnancy (EP) occurs in 1–2% of pregnancies, but is over-represented as a leading cause of maternal death in early pregnancy. It remains a challenge to diagnose early and accurately. Women often present in early pregnancy with a ‘pregnancy of unknown location’ (PUL) and the diagnosis and exclusion of EP is difficult due to a lack of reliable biomarkers. A serum biomarker able to clearly distinguish between EP and other pregnancy outcomes would greatly assist clinicians in diagnosing and safely managing PULs. This study evaluates the ability of maternal serum macrophage inhibitory cytokine-1 (MIC-1) levels to differentiate between EP and other pregnancy outcomes in women with a PUL.

Methods

Sera were collected from 120 women with a PUL at first clinical presentation and assayed for MIC-1 by ELISA. Results were classified according to ultimate pregnancy outcome and the discriminatory ability of MIC-1 to diagnose EP was assessed.

Results

Serum MIC-1 levels were lower in women with histologically confirmed (definite) EP (dEP) (median 552 ng/mL; interquartile range (IQR) 414–693 ng/mL) compared to women with definite viable intra-uterine pregnancies (dVIUPs) (722 ng/mL; IQR 412–1122 ng/mL), and higher when compared to women with definite non-viable intra-uterine pregnancies (dNVIUPs) (465 ng/mL; IQR 341–675 ng/mL). MIC-1 levels were significantly higher in women with dEP compared to women whose PULs resolved without medical intervention (srPUL) (401 ng/mL; IQR 315–475 ng/mL) (p<0.003). There were no women with an ectopic pregnancy where serum MIC-1>1000 ng/mL.

Conclusion

Serum MIC-1 levels in PUL were not able to categorically diagnose EP, however, MIC-1 could distinguish women with an EP that required medical intervention and those women whose PULs spontaneously resolved. A single serum MIC-1 measurement also excluded EP at levels above 1000 ng/mL. MIC-1 may play a role in the development of a combined assay of biomarkers for the diagnosis of EP.     

The Flavonoid Pathway Regulates the Petal Colors of Cotton Flower

Although biochemists and geneticists have studied the cotton flower for more than one century, little is known about the molecular mechanisms underlying the dramatic color change that occurs during its short developmental life following blooming. Through the analysis of world cotton germplasms, we found that all of the flowers underwent color changes post-anthesis, but there is a diverse array of petal colors among cotton species, with cream, yellow and red colors dominating the color scheme. Genetic and biochemical analyses indicated that both the original cream and red colors and the color changes post-anthesis were related to flavonoid content. The anthocyanin content and the expression of biosynthesis genes were both increased from blooming to one day post-anthesis (DPA) when the flower was withering and undergoing abscission. Our results indicated that the color changes and flavonoid biosynthesis of cotton flowers were precisely controlled and genetically regulated. In addition, flavonol synthase (FLS) genes involved in flavonol biosynthesis showed specific expression at 11 am when the flowers were fully opened. The anthocyanidin reductase (ANR) genes, which are responsible for proanthocyanidins biosynthesis, showed the highest expression at 6 pm on 0 DPA, when the flowers were withered. Light showed primary, moderate and little effects on flavonol, anthocyanin and proanthocyanidin biosynthesis, respectively. Flavonol biosynthesis was in response to light exposure, while anthocyanin biosynthesis was involved in flower color changes. Further expression analysis of flavonoid genes in flowers of wild type and a flavanone 3-hydroxylase (F3H) silenced line showed that the development of cotton flower color was controlled by a complex interaction between genes and light. These results present novel information regarding flavonoids metabolism and flower development.     

Ischemic Postconditioning-Mediated miRNA-21 Protects against Cardiac ischemia/reperfusion Injury via PTEN/Akt Pathway

Background

Ischemic postconditioning (IPost) protects the reperfused heart from infarction which has drawn much attention recently. However, studies to date have rarely investigated the role of microRNAs (miRNAs) in IPost. The aims of this study were to investigate whether miR-21 is involved in the protective effect of IPost against myocardial ischemia-reperfusion (I/R) injury and disclose the potential molecular mechanisms involved.

Methods and Results

We found that miR-21 was remarkably up-regulated in mouse hearts after IPost. To determine the protective role of IPost-induced miR-21 up-regulation, the mice were divided into the following four groups: I/R group; I/R+IPost group (I/R mice treated with IPost); Antagomir-21+IPost+I/R group (I/R mice treated with anagomir-21 and IPost); Scramble+IPost+I/R group (I/R mice treated with scramble and IPost). The results showed IPost could reduce I/R injury-induced infarct size of the left ventricle, improve cardiac function, and prevent myocardial apoptosis, while knockdown of miR-21 with antagomir-21 could reverse these protective effects of IPost against mouse I/R injury. Furthermore, we confirmed that miR-21 plays a protective role in myocardial apoptosis through PTEN/Akt signaling pathway, which was abrogated by the PI3K inhibitor LY294002. The protective effect of miR-21 on myocardial apoptosis was further revealed in mouse hearts after IPost treatment in vivo.

Conclusions

Our data clearly demonstrate that miR-21 is involved in IPost-mediated cardiac protection against I/R injury and dysfunction through the PTEN/Akt signaling pathway in vivo. Identifying the beneficial roles of IPost-regulated miRNAs in cardiac protection, which may be a rational target selection for ischemic cardioprotection.     

Outcome Comparison between Laparoscopic and Open Appendectomy: Evidence from a Nationwide Population-Based Study

Background

Mounting evidence supports the use of laparoscopic techniques for the treatment of simple appendicitis. However, most of the advantages of these techniques are of limited clinical relevance. This study compares the treatment outcomes of laparoscopic appendectomies and open appendectomies performed in Taiwan.

Methods

This study uses data from the 2007 to 2009 Taiwan National Health Insurance Research Database. The study sample included 65,339 patients, hospitalized with a discharge diagnosis of acute appendicitis (33.8% underwent laparoscopic appendectomy). A generalized estimated equation (GEE) was performed to explore the relationship between the use of laparoscopy and 30-day re-admission. Hierarchical linear regressions were performed to examine the relationship between the use of laparoscopy, the length of stay (LOS), and the cost per discharge.

Results

A significantly lower proportion of patients undergoing laparoscopic appendectomies were re-admitted within 30 days of their index appendectomy, in comparison to patients undergoing open appendectomies (0.66% versus 1.925, p<0.001). Compared with patients undergoing open appendectomies, patients undergoing laparoscopic appendectomies had a shorter LOS (4.01 versus 5.33 days, p<0.001) and a higher cost per discharge (NT$40,554 versus NT$38,509, p<0.001. In 2007, the average exchange rate was US$1 = NT$31.0). GEE revealed that the odds ratio of 30-day readmission for patients undergoing laparoscopic appendectomy was 0.38 (95% CI = 0.33–0.46) that of patients undergoing open appendectomies, after adjusting for surgeon, hospital, and patient characteristics, as well as for the clustering effect of particular surgeons and the propensity score.

Conclusion

This study found that laparoscopic appendectomies had a lower 30-day re-admission rate, and a shorter LOS, but a slightly higher cost per discharge than open appendectomies.     

Docosahexaenoic acid synthesis from alpha-linolenic acid is inhibited by diets high in polyunsaturated fatty acids

The conversion of the plant-derived omega-3 (n-3) α-linolenic acid (ALA, 18:3n-3) to the long-chain eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) can be increased by ALA sufficient diets compared to ALA deficient diets. Diets containing ALA above an optimal level result in no further increase in DHA levels in animals and humans. The present study evaluates means of maximizing plasma DHA accumulation by systematically varying both linoleic acid (LA, 18:2n-6) and ALA dietary level. Weanling rats were fed one of 54 diets for three weeks. The diets varied in the percentage of energy (en%) of LA (0.07–17.1 en%) and ALA (0.02–12.1 en%) by manipulating both the fat content and the balance of vegetable oils. The peak of plasma phospholipid DHA (>8% total fatty acids) was attained as a result of feeding a narrow dietary range of 1–3 en% ALA and 1–2 en% LA but was suppressed to basal levels (～2% total fatty acids) at dietary intakes of total polyunsaturated fatty acids (PUFA) above 3 en%. We conclude it is possible to enhance the DHA status of rats fed diets containing ALA as the only source of n-3 fatty acids but only when the level of dietary PUFA is low (<3 en%).     

Pyrimidone-based series of glucokinase activators with alternative donor–acceptor motif

Glucokinase activators are a class of experimental agents under investigation as a therapy for Type 2 diabetes mellitus. An X-ray crystal structure of a modestly potent agent revealed the potential to substitute the common heterocyclic amide donor–acceptor motif for a pyridone moiety. We have successfully demonstrated that both pyridone and pyrimidone heterocycles can be used as a potent donor–acceptor substituent. Several sub-micromolar analogs that possess the desired partial activator profile were synthesized and characterized. Unfortunately, the most potent activators suffered from sub-optimal pharmacokinetic properties. Nonetheless, these donor–acceptor motifs may find utility in other glucokinase activator series or beyond.     

The discovery of novel N-(2-pyrimidinylamino) benzamide derivatives as potent hedgehog signaling pathway inhibitors

Hedgehog signaling pathway inhibitors are emerging as new therapeutic intervention against cancer. A novel series of N-(2-pyrimidinylamino) benzamide derivatives as hedgehog signaling pathway inhibitors were designed and synthesized. Most compounds presented significant inhibitory effect on hedgehog signaling pathway, among which 21 compounds exhibited more potent than vismodegib. Furthermore, compound 6a showed moderate pharmacokinetic properties in vivo, representing a promising lead compound for further exploration.     

A novel,major, and validated QTL for the effective tiller number located on chromosome arm 1BL in bread wheat

Plant Molecular Biology - A novel and major QTL for the effective tiller number was identified on chromosomal arm 1BL and validated in two genetic backgrounds The effective tiller number (ETN)...     

A comparative look at structural variation among RC–LH1 ‘Core’ complexes present in anoxygenic phototrophic bacteria

Photosynthesis Research - All purple photosynthetic bacteria contain RC–LH1 ‘Core’ complexes. The structure of this complex from Rhodobacter sphaeroides, Rhodopseudomonas...