Coumarins are fused benzene and pyrone ring systems with a wide spectrum of bioactivities, including antitumor, anti-inflammation, antiviral, and antibacterial effects. In this paper, the current development of coumarin-based drugs is introduced, and their structure-activity relationship is discussed by reviewing the relevant literature published in the past 20 years. Coumarin molecules can be customized by the target site to prevent systemic side effects by virtue of structural modification. The ortho-phenolic hydroxyl on the benzene ring has remarkable antioxidant and antitumor activities. Coumarins with aryl groups at the C-4 position have good activities in anti-HIV, antitumor, anti-inflammation, and analgesia. C-3 phenylcoumarins have strong anti-HIV and antioxidant effects. Tetracycline pyranocoumarins can significantly inhibit HIV; osthol structural analogues have antimicrobial activity. Praeruptorin C and its derivatives play an important role in lowering blood pressure and dilating coronary arteries, and khellactone derivatives have significant inhibitory effects on AIDS, cancer, and cardiovascular diseases. It is concluded that the specific site on the core structure of coumarin exhibits one or more activities due to the electronic or steric effects of the substituents. This review is intended to be conducive to rational design and development of more active and less toxic agents with a coumarin scaffold.

Dens invaginatus is a malformation with varying anatomical features, posing challenges to treatment. Early and accurate diagnosis plays a significant role in selecting the appropriate treatment. The diagnosis of teeth with a complex root canal system including dens invaginatus has made progress with the application of three-dimensional imaging techniques in endodontics. Advanced treatment options provide hope for teeth that could not be saved before. This review discusses diagnostic methods and treatment options for teeth with dens invaginatus, and provides guidelines for the management of dens invaginatus cases in clinic. Current as well as traditional diagnostic techniques are summarized. Treatment options including state-of-the-art alternatives are presented for coronal dens invaginatus and radicular dens invaginatus.

No abstract

This study was to test the hypothesis that oxidized low-density lipoprotein (ox-LDL) modified the behavior of bone marrow stem cells, including proliferation, Oct-4 expression, and their endothelial differentiation through reactive oxygen species (ROS) formation in vitro. Rat bone marrow multipotent adult progenitor cells (MAPCs) were treated with ox-LDL with or without the antioxidant N-acetylcysteine (NAC). Ox-LDL generated a significant amount of ROS in the culture system as measured with electron paramagnetic resonance spectroscopy, and substantially inhibited the proliferation, Oct-4 expression, and endothelial differentiation of MAPCs. ROS production from ox-LDL in the culture system was completely prevented by NAC (1 mM). NAC treatment completely restored endothelial differentiation potential of MAPCs that was diminished by low-dose ox-LDL. NAC also significantly, but not completely, reversed the inhibitory effect of ox-LDL on proliferation and Oct-4 expression in MAPCs. NAC treatment only slightly restored Akt phosphorylation impaired by ox-LDL in the cells. ROS formation was important in the action of ox-LDL on MAPCs, including Oct-4 expression, proliferation, and endothelial differentiation. However, other mechanism(s) like Akt signaling and apoptosis might also play a critical role in mediating the effect of ox-LDL on these cells. Antioxid. Redox Signal. 13, 1845-1856.

No abstract

Mitochondria play a critical role in cell function and embryo development. Recently, increasing studies have investigated whether mitochondrial DNA (mtDNA) can be used as a predictive biomarker of embryo implantation. However, the results of its effect on implantation are still controversial. To further understand the clinical application value of mtDNA content for reproductive potential, we analyzed the influence of relative mtDNA quantity on embryo quality and transfer outcomes based on the results of second-generation sequencing of preimplantation genetic testing patients in our center. Biopsied trophectoderm (TE) from aneuploid blastocysts contained much larger amounts of mtDNA than those from euploid blastocysts ( p < 0.000). In an analysis of only euploid blastocysts (n = 769), female age had no effect on mtDNA content ( p = 0.216). TE cells biopsied on day 5 (n = 355) contained significantly higher amounts of mtDNA compared to those biopsied on day 6 (n = 388) or day 7 (n = 26) ( p < 0.000). Higher quality trophoblast was associated with lower mtDNA content ( p = 0.026), but quality of inner cell mass was not correlated with quantity of mtDNA ( p = 0.112). For transferred embryos, the biopsied date and mtDNA content were significantly associated with embryo implantation and live birth outcomes. Day-5 euploid blastocysts with lower quantities of mtDNA exhibited higher implantation rate and live birth rate. However, our data indicated that mtDNA content may not be considered an independent predictive marker, it may be a useful reference for the selection of day-5 transferred euploid blastocysts.

Cytochrome P450 enzymes are required for the synthesis of cholesterol and steroid hormones. Cytochrome P450 oxidoreductase (POR) donates electrons to microsomal cytochrome P450 enzymes. POR deficiency (PORD) is a rare autosomal recessive disease. In patients with PORD, steroid hormone synthesis is disrupted, which can cause infertility. The objective of this study was to report on a case of in vitro fertilization-frozen embryo transfer (IVF-FET) in a patient with PORD. The patient's hormone (i.e. 17α-hydroxyprogesterone) and electrolyte levels were within normal ranges ordinarily. Upon controlled ovarian stimulation, follicle growth was normal, but serum estrogen and progesterone levels were low and high, respectively. The serum progesterone level was elevated after long-acting gonadotropin-releasing hormone agonist treatment, and an endometrial biopsy showed a change in the proliferative phase. Genetic tests detected homozygous mutations (c.976 T > G, p.Y326D) in exon 10 of the POR gene. The frozen embryo was transferred during the administration of hormone replacement therapy. No significant morphological or metabolic abnormalities were observed in the neonate. Our findings suggest that infertile women with normal hormone levels may have metabolic diseases such as PORD. Further studies are needed to determine the cause of these diseases and to assist pregnancy in such women.

Cryopreservation of few spermatozoa is still a major challenge for male fertility preservation. This study reports use a new micro-straw (LSL straw) for freezing few spermatozoa for intracytoplasmic sperm injection (ICSI). Semen samples from 22 fertile donors were collected, and each semen sample was diluted and mixed with cryoprotectant in a ratio of 1:1, and then frozen using three different straws such as LSL straw (50–100 μl), traditional 0.25 ml and 0.5 ml straws. For freezing, all straws were fumigated with liquid nitrogen, with temperature directly reducing to −130–−140°C. Sperm concentration, progressive motility, morphology, acrosome integrity, and DNA fragmentation index were evaluated before and after freezing. After freezing-thawing, LSL straw group had significantly higher percentage of sperm motility than traditional 0.25 ml and 0.5 ml straw groups (38.5% vs 27.4% and 25.6%, P < 0.003). Sperm motility and acrosomal integrity after freezing-thawing were significantly lower than that of before freezing. However, there was no significant difference in morphology, acrosome, and DNA integrity between the three types of straws (P > 0.05). As LSL straws were thinner and hold very small volume, the freezing rate of LSL straw was obviously faster than 0.25 ml straw and 0.5 ml straws. In conclusion, LSL micro-straws may be useful to store few motile spermatozoa with good recovery of motility for patients undergoing ICSI treatment.