Discovery of Novel Marine-Derived Phidiandine/Lipoic Acid Hybrid as a Potential Anti-Atherosclerosis Agent: Design, Synthesis and in Vitro/in Vivo Evaluation.

In the present study, a novel derivative, IOP-LA, was prepared by hybridizing antioxidant lipoic acid (LA) and our recently reported antioxidative marine phidianidine B-inspired indole/1,2,4-oxadiazole derivative. Our results demonstrated that IOP-LA could protect vascular endothelial cells (VECs) from oxidized low-density lipoprotein (oxLDL)-induced oxidative stress by activating the Nrf2 pathway, inhibit the production of atherosclerotic plaque, and promote the stability of atherosclerotic plaque in apoE-/- mice. Moreover, the protective effect of IOP-LA was superior to LA at the same concentration. Mechanistic studies revealed that IOP-LA significantly inhibited the increase of reactive oxygen species (ROS) levels and the translocation of nuclear factor kappa-B (NF-κB) nuclear induced by oxLDL through the nuclear factor erythroid2-related factor 2 (Nrf2) pathway. In summary, the data demonstrate that IOP-LA, as a new antioxidant, protects VECs from oxLDL-induced oxidative stress by activating the Nrf2 pathway. It is worth noting that this study provides a promising lead compound for the prevention and treatment of atherosclerosis.

Administration of olaquindox impairs spermatogenesis and sperm quality by increasing oxidative stress and early apoptosis in mice.

Olaquindox (OLA), a potent antibacterial agent, has been widely used as a feed additive and growth promoter in animal husbandry. Our previous study has shown that OLA administration in female mice could markedly cause sub-fertility. Here we established the model in male mice to investigate the toxic effects of OLA on mammalian spermatozoa quality and fetal development. After continuous 45 days of OLA gavage, the dosage of 60 mg/kg/day (high dose) significantly affected body weight, organ weights and coefficients, and the morphology of the testis seminiferous tubule in male mice. Dosage of 60 mg/kg/day also reduced sperm count, motility, and viability. OLA at both low-dose (5 mg/kg/day) and high-dose induced peroxidation, early apoptosis, and abnormal mitochondrial membrane potential in sperm. Significantly, high-dose OLA impaired in vitro fertilized embryo development, indicated by the decreased percentages of 2-cell and blastocyst formation. Surprisingly, the natural fertility of males was unaffected after OLA gavage, which was indicated by the comparable litter size after mating. However, paternal gavage of OLA significantly decreased the survival rate of the offspring from the age of 4 weeks. In sum, our study showed that OLA gavage in male mice damages sperm quality and offspring survival, illustrating the use of OLA as a feed additive should be strictly restricted.

[A Meta analysis of risk factors for asthma in Chinese children].

OBJECTIVE: To investigate the main risk factors for asthma in Chinese children, and to provide a reference for the prevention and treatment of asthma. METHODS: The databases including CNKI, Wanfang Data, China Biology Medicine disc, VIP Database for Chinese Technical Periodicals, Web of Science, and PubMed were searched for studies on risk factors for asthma in Chinese children published up to September 2017. Stata 12.0 was used for the Meta analysis. RESULTS: A total of 24 case-control studies were included, with 5 309 cases in the case group and 6 404 cases in the control group. The Meta analysis showed that a family history of asthma (OR=5.246, 95%CI: 3.435-8.011), a family history of allergy (OR=4.627, 95%CI: 2.450-8.738), atopic constitution (OR=4.659, 95%CI: 2.511-8.644), allergic rhinitis (OR=11.510, 95%CI: 6.769-19.574), a history of eczema/dermatitis (OR=4.919, 95%CI: 3.514-6.886), a history of allergies (OR=4.732, 95%CI: 2.802-7.989), a history of food allergies (OR=5.890, 95%CI: 3.412-10.166), a history of drug allergies (OR=4.664, 95%CI: 2.637-8.252), mold contamination at home (OR=2.483, 95%CI: 1.671-3.690), flowers at home (OR=1.748, 95%CI: 1.383-2.209), a history of house decoration (OR=2.823, 95%CI: 2.206-3.935), and cesarean section (OR=1.894, 95%CI: 1.166-3.077) were risk factors for asthma in children, while breastfeeding was a protective factor against asthma (OR=0.508, 95%CI: 0.396-0.653). CONCLUSIONS: The development of asthma in Chinese children is associated with a variety of factors, among which a family history of asthma, a family history of allergy, atopic constitution, a history of allergies, allergic comorbidities, cesarean section, and bad family environment can increase the risk of asthma in children, while breastfeeding can reduce the risk.

Proteomic analysis of lettuce seed germination and thermoinhibition by sampling of individual seeds at germination and removal of storage proteins by polyethylene glycol fractionation.

Germination and thermoinhibition in lettuce (Lactuca sativa 'Jianyexianfeng No. 1') seeds were investigated by a proteomic comparison among dry seeds, germinated seeds at 15°C, at 15°C after imbibition at 25°C for 48 h, or at 25°C in KNO3 (all sampled individually at germination), and ungerminated seeds at 25°C, a thermoinhibitory temperature. Before two-dimensional gel electrophoresis analysis, storage proteins (greater than 50% of total extractable protein) were removed by polyethylene glycol precipitation, which significantly improved the detection of less abundant proteins on two-dimensional gels. A total of 108 protein spots were identified to change more than 2-fold (P<0.05) in abundance in at least one germination treatment. Nineteen proteins increasing and one protein decreasing in abundance during germination had higher abundance in germinated 15°C, 15°C after imbibition at 25°C for 48 h, and 25°C in KNO3 seeds than in ungerminated 25°C seeds. Gene expression of 12 of those proteins correlated well with the protein accumulation. Methionine metabolism, ethylene production, lipid mobilization, cell elongation, and detoxification of aldehydes were revealed to be potentially related to lettuce seed germination and thermoinhibition. Accumulation of three proteins and expression of five genes participating in the mevalonate (MVA) pathway of isoprenoid biosynthesis correlated positively with seed germinability. Inhibition of this pathway by lovastatin delayed seed germination and increased the sensitivity of germination to abscisic acid. MVA pathway-derived products, cytokinins, partially reversed the lovastatin inhibition of germination and released seed thermoinhibition at 25°C. We conclude that the MVA pathway for isoprenoid biosynthesis is involved in lettuce seed germination and thermoinhibition.

A proteomic analysis of rice seed germination as affected by high temperature and ABA treatment.

Seed germination is a critical phase in the plant life cycle, but the specific events associated with seed germination are still not fully understood. In this study, we used two-dimensional gel electrophoresis followed by mass spectrometry to investigate the changes in the proteome during imbibition of Oryza sativa seeds at optimal temperature with or without abscisic acid (ABA) and high temperature (germination thermoinhibition) to further identify and quantify key proteins required for seed germination. A total of 121 protein spots showed a significant change in abundance (1.5-fold increase/decrease) during germination under all conditions. Among these proteins, we found seven proteins specifically associated with seed germination including glycosyl hydrolases family 38 protein, granule-bound starch synthase 1, Os03g0842900 (putative steroleosin-B), N-carbamoylputrescine amidase, spermidine synthase 1, tubulin α-1 chain and glutelin type-A; and a total of 20 imbibition response proteins involved in energy metabolism, cell growth, cell defense and storage proteins. High temperature inhibited seed germination by decreasing the abundance of proteins involved in methionine metabolism, amino acid biosynthesis, energy metabolism, reserve degradation, protein folding and stress responses. ABA treatment inhibited germination and decreased the abundance of proteins associated with methionine metabolism, energy production and cell division. Our results show that changes in many biological processes including energy metabolism, protein synthesis and cell defense and rescue occurred as a result of all treatments, while enzymes involved in methionine metabolism and weakening of cell wall specifically accumulated when the seeds germinated at the optimal temperature.

The long coiled-coil protein NECC2 regulates oxLDL-induced endothelial oxidative damage and exacerbates atherosclerosis development in apolipoprotein E -/- mice.

Oxidized low density lipoprotein (oxLDL)-induced endothelial oxidative damage promotes the development of atherosclerosis. Caveolae play an essential role in maintaining the survival and function of vascular endothelial cell (VEC). It is reported that the long coiled-coil protein NECC2 is localized in caveolae and is associated with neural cell differentiation and adipocyte formation, but its role in VECs needs to be clarified. Our results showed NECC2 expression increased in the endothelium of plaque-loaded aortas and oxLDL-treated HUVECs. Down-regulation of NECC2 by NECC2 siRNA or compound YF-307 significantly inhibited oxLDL-induced VEC apoptosis and the adhesion factors expression. Remarkably, inhibition of NECC2 expression in the endothelium of apoE-/- mice by adeno-associated virus (AAV)-carrying NECC2 shRNA or compound YF-307 alleviated endothelium injury and restricted atherosclerosis development. The immunoprecipitation results confirmed that NECC2 interacted with Tyk2 and caveolin-1(Cav-1) in VECs, and NECC2 further promoted the phosphorylation of Cav-1 at Tyr14 b y activating Tyk2 phosphorylation. On the other hand, inhibiting NECC2 levels suppressed oxLDL-induced phosphorylation of Cav-1, uptake of oxLDL by VECs, accumulation of intracellular reactive oxygen species and activation of NF-κB. Our findings suggest that NECC2 may contribute to oxLDL-induced VEC injury and atherosclerosis via modulating Cav-1 phosphorylation through Tyk2. This work provides a new concept and drug target for treating atherosclerosis.

Epigenetic changes during disease progression in a murine model of human chronic lymphocytic leukemia.

Epigenetic alterations, including gain or loss of DNA methylation, are a hallmark of nearly every malignancy. Changes in DNA methylation can impact expression of cancer-related genes including apoptosis regulators and tumor suppressors. Because such epigenetic changes are reversible, they are being aggressively investigated as potential therapeutic targets. Here we use the Emu-TCL1 transgenic mouse model of chronic lymphocytic leukemia (CLL) to determine the timing and patterns of aberrant DNA methylation, and to investigate the mechanisms that lead to aberrant DNA methylation. We show that CLL cells from Emu-TCL1 mice at various stages recapitulate epigenetic alterations seen in human CLL. Aberrant methylation of promoter sequences is observed as early as 3 months of age in these animals, well before disease onset. Abnormally methylated promoter regions include binding sites for the transcription factor FOXD3. We show that loss of Foxd3 expression due to an NF-kappaB p50/p50:HDAC1 repressor complex occurs in TCL1-positive B cells before methylation. Therefore, specific transcriptional repression is an early event leading to epigenetic silencing of target genes in murine and human CLL. These results provide strong rationale for the development of strategies to target NF-kappaB components in CLL and potentially other B-cell malignancies.

Diet and gastric cancer risk: an umbrella review of systematic reviews and meta-analyses of prospective cohort studies.

BACKGROUND: Several systematic reviews and meta-analyses evaluated the associations between dietary factors and the incidence of gastric cancer (GC). OBJECTIVES: To evaluate the strength and validity of existing evidence, we conducted an umbrella review of published systematic reviews and meta-analyses that investigated the association between diets and GC incidence. METHODS: We searched the PubMed, Embase, and Cochrane databases for systematic reviews and meta-analyses of prospective cohort studies investigating the association between dietary factors and GC risk. For each association, we recalculated the adjusted summary estimates with their 95% confidence interval (CI) and 95% prediction interval (PI) using a random-effects model. We used the I2 statistic and Egger's test to assess heterogeneity and small-study effects, respectively. We also assessed the methodological quality of each study and the quality of evidence. RESULTS: Finally, we identified 16 meta-analyses that described 57 associations in this umbrella review. Of the 57 associations, eight were statistically significant using random-effects, thirteen demonstrated substantial heterogeneity between studies (I2 > 50%), and three found small-study effects. The methodological quality of meta-analyses was classified as critically low for two (13%), low for thirteen (81%), and only one (6%) was rated as high confidence. Quality of evidence was rated high for a positive association for GC incidence with a higher intake of total alcohol (RR = 1.19, 95% CI 1.06-1.34) and moderate-quality evidence to support that increased processed meat consumption can increase GC incidence. Three associations (total fruit, vitamin E, and carotenoids) were determined to be supported by low-quality evidence, and two (pickled vegetables/foods and citrus fruit) were supported by very low-quality. CONCLUSIONS: Our findings support the dietary recommendations for preventative GC, emphasizing lower intake of alcohol and foods preserved by salting. New evidence suggests a possible role for total fruit, citrus fruit, carotenoids, and vitamin E. More research is needed on diets with lower quality evidence. REGISTRATION NUMBER: CRD42021255115.

Roles and regulation of histone acetylation in hepatocellular carcinoma.

Hepatocellular Carcinoma (HCC) is the most frequent malignant tumor of the liver, but its prognosis is poor. Histone acetylation is an important epigenetic regulatory mode that modulates chromatin structure and transcriptional status to control gene expression in eukaryotic cells. Generally, histone acetylation and deacetylation processes are controlled by the opposing activities of histone acetyltransferases (HATs) and histone deacetylases (HDACs). Dysregulation of histone modification is reported to drive aberrant transcriptional programmes that facilitate liver cancer onset and progression. Emerging studies have demonstrated that several HDAC inhibitors exert tumor-suppressive properties via activation of various cell death molecular pathways in HCC. However, the complexity involved in the epigenetic transcription modifications and non-epigenetic cellular signaling processes limit their potential clinical applications. This review brings an in-depth view of the oncogenic mechanisms reported to be related to aberrant HCC-associated histone acetylation, which might provide new insights into the effective therapeutic strategies to prevent and treat HCC.

The α-Helical Cap Domain of a Novel Esterase from Gut Alistipes shahii Shaping the Substrate-Binding Pocket.

The human gut microbiota regulates nutritional metabolism, especially by encoding specific ferulic acid esterases (FAEs) to release functional ferulic acid (FA) from dietary fiber. In our previous study, we observed seven upregulated FAE genes during in vitro fecal slurry fermentation using wheat bran. Here, a 29 kDa FAE (AsFAE) from Alistipes shahii of Bacteroides was characterized and identified as the type-A FAE. The X-ray structure of AsFAE has been determined, revealing a unique α-helical domain comprising five α-helices, which was first characterized in FAEs from the gut microbiota. Further molecular docking analysis and biochemical studies revealed that Tyr100, Thr122, Tyr219, and Ile220 are essential for substrate binding and catalytic efficiency. Additionally, Glu129 and Lys130 in the cap domain shaped the substrate-binding pocket and affected the substrate preference. This is the first report on A. shahii FAE, providing a theoretical basis for the dietary metabolism in the human gut.

[Study on the in-depth composition of beads formed by fuse breaking of electric wire at different oxygen concentrations by Auger electron spectroscopy].

The ambience has a critical effect on the characteristic of bead formed by fuse breaking of the electric copper wire in fire. In order to study the influence of oxygen concentration in surroundings on the characteristic of bead formed by fuse breaking, firstly, the oxygen concentration of typical things such as wood, paper, foam, rubber and plastic etc when they were burning was measured. The extreme conditions of oxygen concentration of typical things were ascertained when they were burning. Accordingly the oxygen concentration of simulated environment (100% N2, 10% O2 + 90% N2, and 20% O2 + 80% N2) was determined. Secondly, the in-depth composition of beads formed by fuse breaking of the electric copper wire in different circumstances was studied by AES. The relationship is almost linearity between the average oxygen concentration and the ambient oxygen concentration. Consequently, from the measured oxygen concentration, the authors can deduce the ambient oxygen concentration and the fire cause.

Blastocyst hatching site is regularly distributed and does not influence foetal development in mice.

Hatching out from the zona pellucida (ZP) is a crucial step for blastocyst implantation and development. However, it is still unknown whether the location of the hatching site relative to the inner cell mass (ICM) affects embryo implantation and foetal development. Here, we classified hatching blastocysts into three categories, 0° ≤ θ ≤ 30°, 30° < θ ≤ 60°, and 60° < θ ≤ 90°, in which θ is determined based on the relative position of the hatching site to the arc midpoint of the ICM. Non-surgical embryo transfer (NSET) devices were employed to evaluate blastocyst implantation and embryo development. Of 1,827 hatching blastocysts, 43.84%, 30.60%, and 21.67% were categorized as 30° < θ ≤ 60°, 0° ≤ θ ≤ 30°, and 60° < θ ≤ 90°, respectively. Embryos with different hatching sites showed no distinct differences in blastocyst implantation; surrogate female pregnancy; embryo development to term; litter size, or offspring survival, gender, or body weight. Our results indicate that mouse blastocyst hatching site is not randomly distributed. Embryo implantation and development are not correlated with the blastocyst hatching site in mice. Thus, assessment of the blastocyst hatching site should not be recommended to evaluate mouse blastocyst implantation and developmental potential.

Phycocyanin Improves Reproductive Ability in Obese Female Mice by Restoring Ovary and Oocyte Quality.

Reproductive dysfunction associated with obesity is increasing among women of childbearing age. Emerging evidence indicates that maternal obesity impairs embryo development and offspring health, and these defects are linked to oxidative stress in the ovary and in oocytes. Phycocyanin (PC) is a biliprotein from Spirulina platensis that possesses antioxidant, anti-inflammatory, and radical-scavenging properties. Our previous studies have shown that PC can reduce reactive oxygen species (ROS) accumulation in oocytes in D-gal-induced aging mice. Here, at the Institute of Cancer Research (ICR) mice fed a high-fat diet (HFD) to model obesity were used to test the effect of PC on reversing the fertility decline caused by obesity. We observed a significant increase in litter size and offspring survival rates after PC administration to obese mice. Further, we found that PC not only ameliorated the level of ovarian antioxidant enzymes, but also reduced the occurrence of follicular atresia in obese female mice. In addition, the abnormal morphology of the spindle-chromosome complex (SCC), and the abnormal mitochondrial distribution pattern in oocytes both recovered. The obesity-related accumulation of ROS, increased number of early apoptotic cells, and the abnormal expression of H3K9me3 in oocytes were all partially reversed after PC administration. In summary, this is the first demonstration that PC can improve fertility by partially increasing ovarian and oocyte quality in obese female mice and provides a new strategy for clinically treating obesity-related infertility in females.

Chidamide increases the sensitivity of refractory or relapsed acute myeloid leukemia cells to anthracyclines via regulation of the HDAC3 -AKT-P21-CDK2 signaling pathway.

BACKGROUND: Induction therapy for acute myeloid leukemia (AML) is an anthracycline-based chemotherapy regimen. However, many patients experience a relapse or exhibit refractory disease (R/R). There is an urgent need for more effective regimens to reverse anthracycline resistance in these patients. METHODS: In this paper, Twenty-seven R/R AML patients with anthracycline resistance consecutively received chidamide in combination with anthracycline-based regimen as salvage therapy at the Chinese PLA General Hospital. RESULTS: Of the 27 patients who had received one course of salvage therapy, 13 achieved a complete response and 1 achieved a partial response. We found that the HDAC3-AKT-P21-CDK2 signaling pathway was significantly upregulated in anthracycline-resistant AML cells compared to non-resistant cells. AML patients with higher levels of HDAC3 had lower event-free survival (EFS) and overall survival (OS) rates. Moreover, anthracycline-resistant AML cells are susceptible to chidamide, a histone deacetylase inhibitor which can inhibit cell proliferation, increase cell apoptosis and induce cell-cycle arrest in a time- and dose-dependent manner. Chidamide increases the sensitivity of anthracycline-resistant cells to anthracycline drugs, and these effects are associated with the inhibition of the HDAC3-AKT-P21-CDK2 signaling pathway. CONCLUSION: Chidamide can increase anthracycline drug sensitivity by inhibiting HDAC3-AKT-P21-CDK2 signaling pathway, thus demonstrating the potential for application.

The Role of BRAF V600E in Reducing AUS/FLUS Diagnosis in Thyroid Fine Needle Aspiration.

BRAF V600E mutations are common in papillary thyroid carcinoma (PTC) and some de-differentiated thyroid cancers. In this study, we summarize AUS/FLUS diagnosed cases from thyroid fine needle aspirations in our center from 2015 to 2017 to explore the impact of BRAF V600E detection on the cytopathological diagnosis of PTC. BRAF V600E detection could significantly reduce the AUS/FLUS diagnosis rates from 11.59 to 8.42% when all BRAF V600E-mutated AUS/FLUS cases were diagnosed as conforming to PTC (20.01 to 19.13% in 2016 and 10.92 to 7.93% in 2017, respectively). The AUS/M rates decreased from 0.67 to 0.64 in 2016 and from 0.33 to 0.23 in 2017. We further discuss a case with a single BRAF V600E cytological mutant lacking a postoperative PTC diagnosis and discuss the limitations of BRAF V600E detection using puncture elution fluid. Our findings support the notion that BRAF V600E detection can effectively reduce the diagnostic rates of AUS/FLUS and help clinicians decide both treatment strategies and patient prognosis.

miR­15a­3p affects the proliferation, migration and apoptosis of lens epithelial cells.

The present study investigated the effect of microRNA (miR)­15a­3p on the proliferation, migration and apoptosis of lens epithelial cells and its potential mechanism, in order to further elucidate the pathogenesis of age­related cataracts (ARCs). The HLE­B3 human lens epithelial cell line was transfected with miR­15a­3p mimic. Expression of the miR­15a­3p mimic was measured by fluorescence­based reverse transcription­quantitative polymerase chain reaction analysis. Cell proliferation, apoptosis, invasion and migration were investigated using MTT and plate clone formation assays, terminal deoxynucleotidyl transferase dUTP nick end labeling and flow cytometry, and a wound healing assay and Transwell assay, respectively. The protein expression levels of B­cell lymphoma 2 (BCL2) and myeloid cell leukemia sequence 1 (MCL1) were also compared between transfected and wild­type HLE­B3 cells by western blot analysis. The results showed that transfection with the miR­15a­3p mimic significantly suppressed the proliferation of HLE­B3 cells, induced cell apoptosis and increased the proportion of early apoptotic cells. The migration of HLE­B3 cells was significantly inhibited following transfection with miR­15a­3p mimic (P<0.01), whereas cell invasion was unaffected (P>0.05). In addition, reduced protein levels of BCL2 and MCL1 were observed in the miR­15a­3p mimic­transfected HLE­B3 cells (P<0.01). In conclusion, miR­15a­3p may suppress cell proliferation and migration, and induce cell apoptosis in lens epithelial cells through inhibiting the expression of BCL2 and MCL1, which contributes to the onset of ARCs.

[Monitoring of Coagulation Status and Evaluation of Antiplatelet Aggregation in Patients with CHD by Using TEG].

OBJECTIVE: To evaluate the performance of thromboelastography (TEG) to monitor in vivo blood coagulation status and the efficacy of antiplatelet aggregation drugs in the patients with coronary heart disease (CHD) after oral anticoagulation. METHODS: Seventy one CHD patients were enrolled in CHD group and 380 healthy persons with normal TEG were enrolled in the control group. After admission, all CHD patients were administrated with routine anti-platelet aggregation drugs at a clinically recommended dose. Then, TEG was applied to monitor the basic blood coagulation indexes, such as R value, K value, α angle, MA value, CI value and a series of related indexes on platelet inhibition. RESULTS: Above 80% of the basic blood coagulation indexes in TEG were within normal reference range in the CHD group. the R value, MA value, α angle and CI value in the CHD group were not significanly different, from that in the control group, but the K value significantly increased (P<0.05). Compared with the control group, relatively higher ratio of male was included in the CHD patients at much older age (P<0.05), 83.1% of the CHD patients achieved significant anti-platelet aggregation effect (platelet inhibition rate>50%). Other antiplatelet aggregation indexes, MAADP, MAck and MAA suggested a 9.86%, 4.23% and 12.68% risk of thrombogenesis, respectively. Among all the related antiplatelet aggregation indexes, MAck showed the strongest correlation with age (correlation coefficient, 0.111), and ADP% most highly correlated with body mass (correlation coefficient, 0.160). CONCLUSION: TEG results can provide valuable coagulation information for clinicians, thus certainly guiding in the treatment for CHD patients receiving anti-platelet therapy. Moreover, the application of TEG can also provide accurate information for further individualized treatment of CHD patients, which would funther inprove the safety of anti-thrombotic therapy.

Glial cell line-derived neurotrophic factor supplementation promotes bovine in vitro oocyte maturation and early embryo development.

Paracrine factors such as glial cell line-derived neurotrophic factor (GDNF), which was originally derived from the supernatants of a rat glioma cell line, play pivotal roles in oocyte maturation and early embryo development in mammals, such as mice, rats, pigs, sheep, and even humans. However, whether GDNF facilitates in vitro oocyte maturation or early embryo development in bovines is not yet known. We show for the first time that GDNF and its receptor, GDNF family receptor alpha-1 (GFRA1), are presented in ovarian follicles at different stages as well as during oocyte maturation and early embryo development. Immunostaining results revealed the subcellular localizations of GDNF and GFRA1 in oocytes throughout follicle development, first in germinal vesicles and during blastocyst embryo stages. The ability of exogenously applied GDNF to promote oocyte maturation and early embryo development was evaluated in culture, where we found that an optimal concentration of 50 ng/mL promotes the maturation of cumulus-oocyte complexes and the nuclei of denuded oocytes as well as the development of embryos after IVF. To further investigate the potential mechanism by which GDNF promotes oocyte maturation, bovine oocytes were treated with morpholinos targeting Gfra1. The suppression of GFRA1 presence blocked endogenous and exogenous GDNF functions, indicating that the effects of GDNF that are essential and beneficial for bovine oocyte maturation and early embryo development occur through this receptor. Furthermore, we show that supplementation with GDNF improves the efficiency of bovine IVF embryo production.

Proteome analysis reveals an energy-dependent central process for Populus×canadensis seed germination.

Poplar (Populus×canadensis) seeds rapidly germinated in darkness at 10, 15, and 20°C and reached 50% seed germination after about 22, 4.5, and 3.5h, respectively. Germination of poplar seeds was markedly inhibited by abscisic acid (ABA) at 50µM and cycloheximide (CHX) at 100µM, and these inhibitive roles were temperature-dependent. In the present study, mature poplar seeds were used to investigate the differentially changed proteome of seeds germinating in water, ABA, and CHX. A total of 130 protein spots showed a significant change (1.5-fold increase/decrease, P<0.05) in abundance, and 101 protein spots were successfully identified. Most of the proteins were associated with cell defense and rescue (21%), storage proteins (21%), protein synthesis and destination (20%), metabolism (16%), and energy (14%). The germination of poplar seeds is closely related with the increase in those proteins involved in amino acid and lipid metabolism, the tricarboxylic acid cycle and pentose phosphate pathway, protein synthesis and destination, cell defense and rescue, and degradation of storage proteins. ABA and CHX inhibit the germination of poplar seeds by decreasing the protein abundance associated with protein proteolysis, protein folding, and storage proteins. We conclude that poplar seed germination is an energy-dependent active process, and is accompanied by increasing amino acid activation, protein synthesis and destination, as well as cell defense and rescue, and degradation of storage proteins.

Novel Curcumin Liposome Modified with Hyaluronan Targeting CD44 Plays an Anti-Leukemic Role in Acute Myeloid Leukemia in Vitro and in Vivo.

Curcumin has been widely used as a food additive for centuries and has been recently explored for its anti-inflammatory and antitumor properties. Although curcumin is pharmacologically safe and efficacious to certain cancers, its role against acute myeloid leukemia (AML) still remains unclear, and it lacks clinical application due to low water solubility and low in vivo bioavailability. To address these issues, we developed a novel curcumin liposome modified with hyaluronan (HA-Cur-LPs) to specifically deliver curcumin to AML by targeting CD44 on AML cell surface. When compared with free curcumin and nontargeted liposome (Cur-LPs), the HA-Cur-LPs exhibited good stability, high affinity to CD44, increased cellular uptake, and more potent activity on inhibiting AML cell proliferation. The KG-1 cell implanted AML mice had significantly delayed, or even prevented, AML progression following treatment with 50 mg/kg of curcumin dose in the HA-Cur-LPs every 2 days for 2 weeks. Mechanistically, the anti-AML effects of HA-Cur-LPs were achieved by inhibiting Akt/ERK pathways and activating caspase-dependent apoptosis. Moreover, HA-Cur-LPs played a critical role in downregulation of DNMT1 expression in AML, leading to DNA hypomethylation and reactivation of tumor suppressor genes such as miR-223. The development and assessment of the HA-Cur-LPs in this study provide another potential choice for AML therapy, using HA-Cur-LPs as either a single treatment agent or in combination with other treatments.