Synthesis and anti-parasites efficacy of coumarin derivatives against Dactylogyrus intermedius.

Dactylogyrus is one of the most common parasitic diseases in fish and causes huge losses to the aquaculture industry. With the advantages of safety, low toxicity and easy degradation, plant-derived drugs are ideal for the creation of green aquatic ingredients. The use of plant-derived drugs in aquaculture is limited by their low content and high processing costs, which is a challenge that can be solved by the chemical synthesis of plant-derived drugs. Eleven new coumarin derivatives were synthesized and assessed for their anthelmintic activity in this study. Among them, the derivative 7-((1-tosyl-1H-1,2,3-triazol-4-yl)methoxy)-2H-chromen-2-one (N11) has good anthelmintic activity and its mean anthelmintic efficacy against D. intermedius at a concentration of 10 µM reached 99.84%, which is even better than the anthelmintic activity of the positive control mebendazole. Further studies showed that N11 had concentration values of 3.31 and 1.94 µM for 50% maximal effect (EC50 ) against D. intermedius at 24 and 48 h, respectively. Furthermore, scanning electron microscopy revealed that N11 caused damage to D. intermedius. What is more noteworthy is that a substantial reduction in the ATP content of the parasite was observed following in vitro and in vivo administration of N11. Moreover, it was also found that N11 was able to inhibit the horizontal transmission of D. intermedius. Furthermore, real-time quantitative PCR analysis was utilized to determine the expression profile of genes associated with anti-inflammatory cytokines (IL-10, TGF-ß and IL-4) in goldfish. In all examined organs, it was observed that the expression of anti-inflammatory cytokines increased subsequent to treatment with N11, according to the results. Thus, these results all suggest that N11 possesses good anthelmintic activity and is a potentially effective agent for the control of D. intermedius.

Allelopathy confers an invasive Wedelia higher resistance to generalist herbivore and pathogen enemies over its native congener.

The Novel Defense Hypothesis predicts that introduced plants may possess novel allelochemicals which act as a defense against native generalist enemies. Here, we aim to test if the chemicals involved in allelopathy in the invasive plant Wedelia trilobata can contribute to higher resistance against generalist herbivore and pathogen enemies by comparing with its native congener W. chinensis in controlled laboratory conditions. The allelopathic effects of the leaf extract from W. trilobata on the generalist enemies were also assessed. We showed that the larvae of two moth species preferred W. chinensis over W. trilobata. The growth rate of larvae feeding on W. trilobata leaves was significantly lower than those feeding on W. chinensis leaves. When detached leaves were inoculated with phytopathogens, the infected leaf area of W. trilobata was significantly smaller than that of W. chinensis. In addition, the leaf extract of W. trilobata also effectively inhibited the growth of the larvae and the mycelial growth of the phytopathogens. Our results indicate that the defenses of invasive W. trilobata against generalist herbivore and pathogen enemies are stronger than that of its native congener, which may be attributed to the allelopathic effects. This study provides novel insights that can comprehensively link the Novel Defense, Behavioral Constraint and Enemy Release hypotheses. These combined hypotheses would explain how invasive plants escape from their natural specialist enemies, where their allelopathic chemicals may deter herbivorous insects and inhibit pathogen infection.

Multicolor Tuning in Room-Temperature Self-Activated Ca2 Nb2 O7 Submicroplates by Lanthanide Doping.

Self-activated phosphors are capable of generating optical emissions from the internal ion groups of host lattice before externally introducing luminescent ions. However, numerous self-activated phosphors only show luminescence at low temperature due to the thermally activated energy migration among ion groups at room temperature, severely confining their application conditions. In this letter, we propose a strategy to converting the low-temperature luminescence to a room-temperature one through changing the synthesis conditions to induce structural distortions and thus to limit energy migration. Room-temperature self-activated luminescence of Ca2 Nb2 O7 was accordingly achieved in submicroplates synthesized using the sol-gel method. By further coupling the blue broadband emission from Ca2 Nb2 O7 submicroplates with the characteristic luminescence of Ln3+ (Pr3+ , Sm3+ , and Dy3+ ) dopants, multicolor emissions were successively tuned through adjusting the concentration of Ln3+ . Our results are expected to expand the scope of designing room-temperature self-activated phosphors and tuning multicolor emission.

LC-based targeted metabolomics analysis of nucleotides and identification of biomarkers associated with chemotherapeutic drugs in cultured cell models.

Treatment of mammalian cells with chemotherapeutic drugs can result in perturbations of nucleotide pools. Monitoring these perturbations in cultured tumor cells from human sources is useful for assessment of the effect of drug therapy and a better understanding of the mechanism of action of these drugs. In this study, three classes of chemotherapeutic drugs with different mechanisms of action were used in the development of drug-treated cell models. The LC-based targeted metabolomics analysis of nucleotides in cells of the control group and the drug-treated group was carried out. Several data processing methods were combined for the identification of potential biomarkers associated with the action of drugs, including one-way analysis of variance, principal component analysis, and receiver operating characteristic curves. Intriguingly, tumor cells of both the control group and the drug-treated groups can be distinguished from each other, and several variables were recognized as potential biomarkers, such as ATP, GMP, and UDP for antimetabolite agents, ATP, GMP, and CTP for DNA-damaging agents, as well as GMP, ATP, UDP, and GDP for the mitotic spindle agents. Further validation of the potential biomarkers was performed using the receiver operating characteristic curve. Considering their corresponding area under the curve, which was larger than 0.9, it can be concluded that GMP and ATP are the best potential biomarkers for DNA-damaging drugs, as well as GMP, ATP, and UDP for the other two classes of drugs. This limited nucleotide approach cannot completely distinguish the mechanisms of the nine drugs, but it provides preliminary evidence for the role of pharmacometabolomics in the preclinical development of drugs at least.

The influence of chronic fluorosis on mitochondrial dynamics morphology and distribution in cortical neurons of the rat brain.

The present study was designed to evaluate the effects of chronic fluorosis on the dynamics (including fusion and fission proteins), fragmentation, and distribution of mitochondria in the cortical neurons of the rat brain in an attempt to elucidate molecular mechanisms underlying the brain damage associated with excess accumulation of fluoride. Sixty Sprague-Dawley rats were divided randomly into three groups of 20 each, that is, the untreated control group (drinking water naturally containing <0.5 mg fluoride/l, NaF), the low-fluoride group (whose drinking water was supplemented with 10 mg fluoride/l) and the high-fluoride group (50 mg fluoride/l). After 6 months of exposure, the expression of mitofusin-1 (Mfn1), fission-1 (Fis1), and dynamin-related protein-1 (Drp1) at both the protein and mRNA levels were detected by Western blotting, immunohistochemistry, and real-time PCR, respectively. Moreover, mitochondrial morphology and distribution in neurons were observed by transmission electron or fluorescence microscopy. In the cortices of the brains of rats with chronic fluorosis, the level of Mfn1 protein was clearly reduced, whereas the levels of Fis1 and Drp1 were elevated. The alternations of expression of the mRNAs encoding all three of these proteins were almost the same as the corresponding changes at the protein levels. The mitochondria were fragmented and the redistributed away from the axons of the cortical neurons. These findings indicate that chronic fluorosis induces abnormal mitochondrial dynamics, which might in turn result in a high level of oxidative stress.

Isopropyl 3-(3, 4-dihydroxyphenyl)-2-hydroxypropanoate protects lipopolysaccharide-induced acute lung injury in mice by attenuating pyroptosis.

Isopropyl 3-(3,4-dihydroxyphenyl)-2-hydroxypropanoate (IDHP) is one of the main bioactive metabolites of the Chinese medicinal herb Danshen, which can be absorbed into blood compounds by oral administration of Compound Danshen dripping pills (CDDPs). Previous study showed that IDHP exerted anti-inflammatory effects by abolishing the secretion of proinflammatory factors stimulated by lipopolysaccharide (LPS). However, the effects of IDHP on LPS-induced acute lung injury (ALI) are not fully understood. In the present study, we observed the effects of IDHP on mortality and lung injury in LPS-treated mice and on LPS-induced THP-1 macrophages. Pretreatment with high dose of IDHP was found to reduce the mortality of ALI mice, significantly improve LPS-induced pathological changes, and reduce protein leakage and inhibited myeloperoxidase (MPO) activity in lung tissue. IDHP also inhibited the release of inflammatory factors in bronchoalveolar lavage fluid (BALF) and lung tissue. Meanwhile, IDHP treatment significantly reduced the expression of active-caspase1, Nlrp3, Asc speck formation, Gsdmd (part of the canonical pyroptosis pathway), caspase4 (part of the non-canonical pyroptosis pathway), therefore decreasing IL-1ß, IL-18, and ROS secretion in LPS-stimulated THP-1 macrophages. Moreover, after co-culturing endothelial/epithelial cells with conditioned medium (CM) from LPS-stimulated THP-1 macrophages, we found that the protein levels of occludin and Zonula occludens-1 (Zo-1) were increased in IDHP CM-treated endothelial cells compared to those that were LPS CM-treated. Lactic dehydrogenase (LDH) assay shows that IDHP also alleviated LPS-induced endothelial/epithelial cell injury. These findings indicate that the protective effect of IDHP on LPS-induced lung injury may be partly due to the inhibition of pyroptosis pathways.

Complete genome sequence of Acinetobacter baumannii MDR-TJ and insights into its mechanism of antibiotic resistance.

OBJECTIVES: To determine the genome sequence of Acinetobacter baumannii strain MDR-TJ and characterize the mechanisms of multidrug resistance in this strain. METHODS: The whole-genome sequence was determined using Roche 454 GS FLX Titanium. Subsequently, the gaps were closed by sequencing PCR products. The genome of strain MDR-TJ was annotated using IMG ER, the RAST annotation server and the BASys bacterial annotation system. The comM gene of MDR-TJ was examined to identify a possible antibiotic resistance island. Based on the results of multilocus sequence typing, we investigated seven multidrug-resistant A. baumannii strains belonging to global clone 2 (GC2) isolated from Asia, Australia and Europe to determine the backbone shared by resistance islands of GC2 isolates. RESULTS: The A. baumannii strain MDR-TJ genome consists of a circular chromosome and a plasmid, pABTJ1. Strain MDR-TJ was assigned to sequence type ST2. Strain MDR-TJ harbours a 41.6 kb resistance island designated RI(MDR-TJ), which can be derived from the backbone of Tn6167 through the insertion of a Tn6022 into the 3'-end of the tetA(B) gene. Comparative analysis showed that transposon Tn6022 and its truncated forms prevailed in the antibiotic resistance islands of GC2 isolates. The carbapenem resistance gene bla(OXA-23) carried by transposon Tn2009 is located on a putatively conjugative plasmid, pABTJ1. CONCLUSIONS: A. baumannii strain MDR-TJ belongs to GC2 and is resistant to multiple antibiotics. A. baumannii MDR-TJ harbours a genomic resistance island that interrupts the comM gene. The carbapenem resistance of MDR-TJ is mediated by a putatively conjugative plasmid, pABTJ1.

Asymmetric bioreduction of activated alkenes by a novel isolate of Achromobacter species producing enoate reductase.

The strain Achromobacter sp. JA81, which produced enoate reductase, was applied in the asymmetric reduction of activated alkenes. The strain could catalyze the bioreduction of alkenes to form enantiopure (R)-ß-aryl-ß-cyano-propanoic acids, a precursor of (R)-γ-amino butyric acids, including the pharmaceutically active enantiomer of the chiral drug (R)-baclofen with excellent enantioselectivity. It could catalyze as well the stereoselective bioreduction of other activated alkenes such as cyclic imides, ß-nitro acrylates, and nitro-alkenes with up to >99 % ee and >99 % conversion. The draft genome sequencing of JA81 revealed six putative old yellow enzyme homologies, and the transcription of one of them, Achr-OYE3, was detected using reverse transcription polymerase chain reaction. The recombinant Escherichia coli expressing Achr-OYE3 displayed enoate reductase activity toward (Z)-3-cyano-3-phenyl-propenoic acid (2a).

Development of protective agents against ovarian injury caused by chemotherapeutic drugs.

BACKGROUND: Chemotherapy is one of the causes of ovarian injury and infertility. Although assisted reproductive technology helps young female patients with cancer become pregnant, preventing chemotherapy-induced ovarian injury will often possess even more significant benefits. OBJECTIVE: We aimed at demonstrating the hazardous effects and mechanisms of ovarian injury by chemotherapeutic agents, as well as demonstrating agents that protect the ovary from chemotherapy-induced injury. RESULTS: Chemotherapeutic agents cause death or accelerate activation of follicles and damage to the blood vessels in the ovary, resulting in inflammation. These often require drug development to protect the ovaries from injury. CONCLUSIONS: Our findings provide a basis for the development of drugs to protect the ovaries from injury. Although there are many preclinical studies on potential protective drugs, there is still an urgent need for a large number of clinical experiments to verify their potential use.

Genome sequence of Acinetobacter baumannii MDR-TJ.

Acinetobacter baumannii is a pathogenic species of bacteria, identified as an aerobic gram-negative bacterium, that is resistant to most antibiotics. In this study, the MDR-TJ strain was isolated at the Second Hospital of Tianjin Medical University, China, and was found to be resistant to penicillin, cephalosporins, aminoglycosides, quinolones, and also imipenem. The genome sequence of Acinetobacter baumannii strain MDR-TJ was determined by using a combination of 454 pyrosequencing and paired-end sequencing performed with the Roche Genome Sequencer FLX system to generate a scaffolded assembly.

Dietary inclusion of glucose oxidase supplementation to corn-wheat-based diet enhance growth performance, nutrient digestibility, blood profile of lactating sows.

The objective of this study is to investigate the effect of dietary glucose oxidase (GOx) supplementation on the reproductive performance, litter performance, total tract digestibility, and blood profile of lactating sows fed corn-wheat-based diet. A total of twenty multiparous sows (Landrace × Yorkshire) were allocated into one of four treatments with five replicates per treatment. The dietary treatments were as follows: CON (Basal diet), GO1 (basal diet + 200 U GOx/kg), GO2 (basal diet + 300 U GOx/kg), GO3 (basal diet + 400 U Gox/kg). Dietary GOx supplementation did not affect lactating sow's reproduction performance as well as body weight, backfat thickness, and body condition score during pre and post farrowing, and at weaning (p > 0.05). However, after farrowing to weaning period lactating sow's fed GOx supplement has linearly (p = 0.0196) decreased the bodyweight loss. While, there were no effects (p > 0.05) observed on sows backfat thickness loss, average daily feed intake, and estrus interval among treatment groups. Dietary supplementation of GOx has linearly improved the body weight gain (p = 0.049) and average daily gain (p = 0.040) of suckling piglets. The total tract digestibility of dry matter and nitrogen was linearly increased with the graded level of GOx supplement. Also, a linear effect was observed on the glucose and superoxide dismutase of blood profile with the dietary inclusion of GOx. In summary, our finding indicates that the dietary inclusion of GOx supplement with corn-wheat-based diet had a beneficial effect on the nutrient digestibility and blood profile of lactating sows and improved the growth performance of suckling piglets.

Molecular determinants of Kv1.5 channel block by diphenyl phosphine oxide-1.

Kv1.5 channels conduct the ultra-rapid delayed rectifier current (I(Kur)) that contributes to action potential repolarization of human atrial myocytes. Block of these channels has been proposed as a treatment for atrial arrhythmias. Diphenyl phosphine oxide-1 (DPO-1) is a novel and potent inhibitor of Kv1.5 potassium channels. The present study was undertaken to characterize the mechanisms and molecular determinants of channel block by DPO-1. Experiments were carried out on wild-type and mutant Kv1.5 channels expressed in Xenopus laevis oocytes using the standard two microelectrode voltage clamp technique. DPO-1 blocked Kv1.5 current in oocytes with an IC(50) of 0.78+/-0.12 microM at +40 mV. Block was enhanced by higher rates of stimulation, consistent with preferential binding of the drug to the open state of the channel. Ala-scanning mutagenesis of the pore domain of Kv1.5 identified the residues Thr480, Leu499, Leu506, Ile508, Leu510 and Val514 as components of the putative binding site for DPO-1, partially overlapping the site previously defined for the Kv1.5 channel blockers AVE0118 and S0100176. Block of Kv1.5 by DPO-1 was significantly reduced in the presence of Kvbeta1.3.

Discovery of potent epidermal growth factor receptor (EGFR) degraders by proteolysis targeting chimera (PROTAC).

Epidermal growth factor receptor (EGFR), a member of the HER family, is closely related to the development of multiple cancers. Herein, we report the discovery of small molecule EGFR degraders based on the proteolysis targeting chimera (PROTAC) strategy. In the present study, 13 EGFR degraders containing pyrido[3,4-d] pyrimidine moiety were designed and synthesized. Promising PROTACs 2 and 10 induced degradation of EGFR in HCC827 cells with the DC50 values of 45.2 and 34.8 nM, respectively. Cellular protein-controlling machinery ubiquitin proteasome system (UPS) was involved in the degradation process. Furthermore, the degraders 2 and 10 could significantly induce the apoptosis of HCC827 cells and arrest the cells in G1 phase. These findings demonstrated that compounds 2 and 10 could serve as effective EGFRdel19-targeting degraders in HCC827 cells. v.

Discovery of novel 9-heterocyclyl substituted 9H-purines as L858R/T790M/C797S mutant EGFR tyrosine kinase inhibitors.

Targeting L858R/T790M/C797S mutant EGFR is a major challenge in the new-generation EGFR tyrosine kinase inhibitors development for conquering drug resistant NSCLC. In this study, a series of novel 9-heterocyclyl substituted 9H-purine derivatives were designed as EGFRL858 R/T790 M/C797S tyrosine kinase inhibitors. Among these compounds, D4, D9, D11 and D12 showed significantly potent anti-proliferation and EGFRL858 R/T790 M/C797S inhibition activity. In particular, the most potent compound D9 showed anti-proliferation against HCC827 and H1975 cell lines with the IC50 values of 0.00088 and 0.20 µM, respectively. And D9 inhibited the EGFRL858R/T790M/C797S with an IC50 value of 18 nM. Furtherly, D9 could significantly suppress the EGFR phosphorylation, induce the apoptosis, arrest cell cycle at G0/G1, and inhibit colony formation in HCC827 cell line by a concentration-dependent manner. Molecular docking indicated that the introduction of a cyclopropylsulfonamide group in D9 led to the formation of additional two hydrogen bonds with mutant Ser797 which played key roles in generating efficient EGFRL858 R/T790 M/C797S inhibitory activity. These findings strongly indicated that 9-heterocyclyl substituted 9H-purine derivatives were promising L858R/T790M/C797S mutant EGFR-TKIs. The introduction of extra hydrogen bond interaction with mutant Ser797 is efficient method for the design of the fourth-generation EGFR-TKIs.

Failure of Less-Invasive Stabilization System (LISS) plating for periprosthetic distal femur fractures: Three case reports.

RATIONALE: Less-Invasive Stabilization System (LISS) plate is an internal fixation commonly used for the periprosthetic distal femur fractures. Failure associated with LISS plate has been rarely reported, and the reasons for LISS plate failure are multitudinous. Various advantages have been reported, but failures continue. PATIENT CONCERNS: We present 3 cases illustrating the failure of Less-Invasive Stabilization System (LISS) plating for periprosthetic distal femur fractures. The shaft screws of the LISS plate broke in 2 cases, and the plate placement was incorrect in 1 case. Early weight bearing, obesity, osteoporosis, and lateral collateral ligament injury due to incorrect plate placement constituted the etiologies of LISS plate failure. DIAGNOSIS: Failure of Less-Invasive Stabilization System (LISS) plating for periprosthetic distal femur fractures after Total knee arthroplasty. INTERVENTIONS: Three patients underwent Less-Invasive Stabilization System plates removal with replacement of the total knee arthroplasty revision surgery with rotating hinged knee prosthesis. OUTCOMES: After completing the total knee arthroplasty revision surgery, all patients underwent regular follow-up examinations. Case 2 could walk unaided, without pain, final union was confirmed for both case 1 and case 3. CONCLUSION: Less-Invasive Stabilization System (LISS) plate provides satisfactory results in periprosthetic fractures after Total knee arthroplasty (TKA). The LISS plate has many advantages, but failures continue to occur. The causes for failure were early weight bearing, obesity, osteoporosis, and lateral collateral ligament (LCL) injury due to incorrect plate placement in our series. We recommend that protection or properly delay of weight-bearing, active anti-osteoporosis treatment, and intraoperative fluoroscopy are the effective methods to avoid failure.

F10, a new camptothecin derivative, was identified as a new orally-bioavailable, potent antitumor agent.

Topoisomerases are interesting targets for drug discovery. In the present study, we attached saturated carbon atoms to the 10-position of camptothecin and synthesized 10 new camptothecin derivatives from 10-HCPT or SN-38. The activities of new compounds were evaluated both in vitro and in vivo. The most promising compound F10, 7-ethyl-10-(2-oxo-2-(piperidin-1-yl)ethoxy)camptothecin, inhibited cancer cells growth with the IC50 of 0.002, 0.003, 0.011 and 0.081 µM on Raji, HCT116, A549 and Lovo cells, respectively. Meanwhile, oral administration of F10 remarkably suppressed the HCT116-xenograft tumor growth in the nude-mice model at the dosage of 0.5, 2.0 and 8.0 mg/kg in vivo. Intraperitoneal administration of F10 can completely inhibit Raji-xenograft tumor growth in established NPG mouse model at 2.0 and 4.0 mg/kg. In addition, the minimum lethal doses of F10 and SN-38 in mice by intravenous administration were 80 and 40 mg/kg (or 0.155, 0.102 mmol/kg), respectively. The solubility of F10 reached 9.86 µg/mL in a buffer solution of pH 4.5. The oral bioavailability of F10 achieved 22.4% in mice. The molecular docking model revealed that F10 can interact with topoisomerase I-DNA complex. Our findings indicate that F10 is a new orally-oavailable antitumor agent with potent anticancer effect. Furthermore, attaching a ring hydrophobic moiety to the 10-position of camptothecin provides a favorable approach in the optimization of camptothecin.

Hypoxia-Induced Cleavage Of Soluble ephrinA1 From Cancer Cells Is Mediated By MMP-2 And Associates With Angiogenesis In Oral Squamous Cell Carcinoma.

INTRODUCTION: ephrinA1 plays important roles in tumor angiogenesis. Matrix metalloproteases (MMPs) can cleave ephrinA1 from the cell membrane into extracellular environment. However, how soluble ephrinA1 is modulated by hypoxia and whether MMPs participate in this hypoxic process remains to be investigated in detail. METHODS: Thirty-seven patients with oral squamous cell carcinoma (OSCC) were included in the present study for HIF-1α, MMP-2, MMP-9 and ephrinA1 detection by immunohistochemistry. Serum samples from 35 patients were collected both preoperatively and postoperatively to confirm the existence of soluble ephrinA1 by ELISA. Block assay and Western blot analysis were further carried out to elucidate the proteolysis mechanism of ephrinA1 under hypoxic condition in vitro. RESULTS: Our data demonstrated that HIF-1α, MMP-2, MMP-9 and ephrinA1 expressed positively, and correlated with microvessel density in OSCCs, except for MMP-9. The serum expression level of ephrinA1 in OSCC patients decreased significantly after surgical removal of the solid tumors. In vitro experiments indicated that GM6001, a MMP-specific inhibitor, could reduce hypoxia-induced soluble ephrinA1 secretion from SCC cells. Further Western blot analysis confirmed that both HIF-1α and MMP-2 were up-regulated by hypoxia in a similar time-dependent manner, with the MMP-9 expression unchanged during this course. CONCLUSION: These results suggested a possible novel mechanism that ephrinA1 secretion is mediated by HIF-1α/MMP-2 signaling cascade which may play pivotal roles in OSCC neovascularization in a paracrine manner.

[The study of combined unilateral intraoral and extraoral reduction approach in the treatment of anterior temporo-mandibular joint dislocation].

OBJECTIVE: To observe the clinical outcomes of a combined unilateral intraoral and extraoral reduction approach in the treatment of anterior temporomandibular joint (TMJ) dislocation. METHODS: Postural muscular chains were utilized in the biomechanical analysis of stomatognathic systems for improving TMJ repositioning approaches. A total of 87 patients with anterior TMJ dislocation were included in the present study. A combined unilateral intraoral and extraoral reduction approach was applied, and the clinical effects were evaluated. RESULTS: Biomechanical analysis reveal that reflexive contrac-tion of the maxillary muscle group was blocked sufficiently during the combined unilateral intraoral and extraoral reduction process. All dislocated TMJs were set successfully and efficiently with few complications. CONCLUSIONS: Combined unilateral intraoral and extraoral reduction approach is an effective, convenient, and minimally invasive way to treat anterior TMJ dislo-cations.

Oxidative stress might be a mechanism connected with the decreased alpha 7 nicotinic receptor influenced by high-concentration of fluoride in SH-SY5Y neuroblastoma cells.

The possible mechanism concerning decreased alpha 7 nicotinic acetylcholine receptor (nAChR) influenced by fluorosis was investigated. SH-SY5Y cells were exposed to fluoride within the range of 0.05-5 mM [corrected] or ferrous iron (1-100 mM) [corrected] a free radical inducer. The levels of alpha 7 nAChR expression, lipid peroxidation and protein oxidation were detected. The results showed that both high-concentrations of fluoride and ferrous iron induced increased levels of lipid peroxidation and protein oxidation in SH-SY5Y cells with concentration-dependent manners. In addition, inhibition of alpha 7 nAChR at protein level was observed in the cells exposed to high amounts of fluoride or ferrous iron. Furthermore, a declined value of Bmax in [125I]alpha-bungarotoxin binding sites was found in the cells treated with the high-concentration of fluoride. Interestingly, antioxidants (vitamin E and glutathione) can attenuate the inhibition of the receptor induced by fluoride. These findings suggest that oxidative stress resulted from fluorosis might directly induce the deficit of alpha 7 nAChR.

Correlation between Sex and Prognosis of Acute Aortic Dissection in the Chinese Population.

BACKGROUND: The prevalence, presentation, management, and prognosis of coronary heart disease differ according to sex. Greater understanding on the differences between men and women with acute aortic dissection (AAD) is needed. We aimed to investigate whether sex disparities are found in patients with AAD, and to study sex differences in complications, mortality in-hospital, and long-term. METHODS: We included 884 patients enrolled in our institute between June 2002 and May 2016. Considering psychosocial factors, treatments, and the outcomes in men versus those in women with AAD, we explored the association of sex with psychosocial characteristics and mortality risk. For categorical variables, significant differences between groups were assessed with the Chi-square test or Fisher's exact test, and continuous parameters were assessed with Student's t-test. Univariate and stratified survival statistics were computed using Kaplan-Meier analysis. RESULTS: A total of 884 patients (76.1% male, mean age 51.4 ± 11.8 years) were included in this study. There were fewer current smokers in female compared with male (17.5% vs. 67.2%, χ2 = 160.06, P < 0.05). The percentage of men who reported regular alcohol consumption was significantly higher than that in women (40.6% vs. 3.8%, χ2 = 100.18, P < 0.05). About 6.2% (55 of 884) of patients with AAD died before vascular or endovascular surgery was performed, 34.4% (304 of 884) of patients underwent surgical procedures, and 52.7% (466 of 884) and 12.8% (113 of 884) of patients received endovascular treatment and medication. Postoperative mortality similar (6.0% vs. 5.6%, respectively, χ2 = 0.03, P = 0.91) between men and women. Follow-up was completed in 653 of 829 patients (78.8%). Adjustment for age, history of coronary disease, hypertension, smoking and drinking, Type A and use of beta-blocker, angiotensin II receptor blockers, angiotensin converting enzyme (ACE) inhibitor, calcium-channel blockers and statins by multivariate logistic regression analysis suggested that age (odds ratios [OR s], 1.04; 95% confidence interval [CI], 1.01-1.07; P < 0.05), using of calcium-channel blockers (OR, 0.37; 95% CI, 0.18-0.74; P < 0.05), at discharge were independent predictors of late mortality, ACE inhibitors (OR, 1.91; 95% CI, 1.03-3.54; P = 0.04) was independent risk factor of late mortality. CONCLUSIONS: In Chinese with AAD, sex is not independently associated with long-term clinical outcomes. Age, the intake of calcium-channel blockers at discharge might help to improve long-term outcomes.