Preconception or prenatal acceptance of SMN1 gene carrier screening and carrier rate of spinal muscular atrophy: a retrospective study in 18,818 reproductive age women in Wuhan area of China.

OBJECTIVE: Spinal muscular atrophy (SMA) is an autosomal recessive disorder mainly affecting the neuromuscular system, which seriously threatens the life and health of patients. But few studies have reported the acceptance rate of SMA gene screening and SMA carrier rate in China. The present study aimed to clarify the two issues in China through a retrospective analysis of 18,818 reproductive age women in Wuhan area of China. METHODS: The copy number (CN) of exons 7 and 8 in survival motor neuron 1 (SMN1) gene was detected by real-time quantitative PCR, and the results were verified by multiplex ligation-dependent probe amplification. RESULTS: Carrier screening was offered to 44,953 women of childbearing age in our medical center from March, 2018, to February, 2022, of whom 18,818 were enrolled in the program. A total of 336 women were identified as carriers (1.73%; 326/18,808; without fertility history of the children with SMA). Among 18,818 reproductive age women, 286 spouses (85.12%; 286/336) were successfully recalled for screening. The results showed 17 couples at high risk of having children with SMA, of whom prenatal diagnosis was implemented in 11, and 6 fetuses were identified with SMA. All the 5 pregnant women bearing the 6 SMA fetuses chose to terminate the pregnancy by artificial abortion. CONCLUSION: Reproductive age women and their spouses in Wuhan area showed a positive attitude toward general screening for SMA carriers. Given the high early mortality of children with SMA, screening for SMA carriers in women of reproductive age is necessary and feasible.

The chromosomal characteristics of spontaneous abortion and its potential associated copy number variants and genes.

PURPOSE: This study aimed to investigate the correlation between chromosomal abnormalities in spontaneous abortion with clinical features and seek copy number variations (CNVs) and genes that might be connected to spontaneous abortion. METHODS: Over 7 years, we used CNV-seq and STR analysis to study POCs, comparing chromosomal abnormalities with clinical features and identifying critical CNVs and genes associated with spontaneous abortion. RESULTS: Total chromosomal variants in the POCs were identified in 66.8% (2169/3247) of all cases, which included 45.2% (1467/3247) numerical abnormalities and 21.6% (702/3247) copy number variants (CNVs). Chromosome number abnormalities, especially aneuploidy abnormalities, were more pronounced in the group of mothers aged ≥ 35 years, the early miscarriage group, and the chorionic villi group. We further analyzed 212 pathogenic and likely pathogenic CNVs in 146 POCs as well as identified 8 statistically significant SORs through comparison with both a healthy population and a group of non-spontaneously aborted fetuses. Our analysis suggests that these CNVs may play a crucial role in spontaneous abortion. Furthermore, by utilizing the RVIS score and MGI database, we identified 86 genes associated with spontaneous abortion, with particular emphasis on PARP6, ISLR, ULK3, FGFRL1, TBC1D14, SCRIB, and PLEC. CONCLUSION: We found variability in chromosomal abnormalities across clinical features, identifying eight crucial copy number variations (CNVs) and multiple key genes that may be linked to spontaneous abortion. This research enhances the comprehension of genetic factors contributing to spontaneous abortion.

Diagnostic yield of copy number variation sequencing in fetuses with increased nuchal translucency: a retrospective study.

OBJECTIVE: To assess the efficacy of copy number variation sequencing (CNV-seq) and karyotyping for prenatal detection of chromosomal abnormalities in fetuses with increased nuchal translucency. METHODS: Amniotic fluid samples were extracted from 205 fetuses with increased nuchal translucency (NT ≥ 2.5 mm), diagnosed by ultrasound between gestational ages of 11 and 13 + 6 weeks. Karyotyping and CNV-seq were performed for detecting chromosomal abnormalities. RESULTS: There are 40 fetuses (19.51%) showing increased NT detected with chromosomal abnormalities in karyotyping, and trisomy 21 was found to be the most common abnormalities. There are 50 fetuses (24.39%) identified with chromosomal abnormalities by CNV-seq. The detection of the applied techniques indicated that CNV-seq revealed higher chromosomal aberrations. The risk of chromosomal abnormalities was significantly increased with NT thickening, from 13.64% in the NT group of 2.5-3.4 mm, 38.64% in the NT group of 3.5-4.4 mm, and to 51.72% in the NT group of over 4.5 mm (P < 0.05). The investigated cases with increased NT with presence of soft markers in ultrasound or high risk in non-invasive prenatal testing presented chromosomal abnormalities in higher rates, comparing with those with isolated NT or low risk (P < 0.05). CONCLUSION: The results indicated that the risk of chromosomal abnormalities was associated with the NT thickness, detected by karyotype or CNV-seq. The combination application of two analysis was efficient to reveal the possible genetic defects in prenatal diagnosis. The finding suggested that the detection should be considered with ultrasonographic soft markers, and the NT thickness of 2.5-3.4 mm could be a critical value for detecting chromosomal abnormalities to prevent the occurrence of missed diagnosis.

Pregnancy-related venous thromboembolism in Wuhan, China 2010-2022: A case-control study.

OBJECTIVE: To explore the time trends and risk factors for pregnancy-related venous thromboembolism (VTE) in the Chinese population. METHODS: A case-control study was conducted with 120 652 pregnancies between Jan 2010 and June 2022 in Wuhan, China. Medical records from pregnant patients with VTE and patients without VTE were reviewed and analyzed. RESULTS: There were 197 cases of VTE diagnosed during pregnancy or postpartum, with an overall incidence of 1.63 per 1000 pregnancies, and the incidence rate trend of VTE was increasing year by year and then declining. The incidence of deep venous thrombosis (DVT) was 1.24 per 1000 pregnancies (76.1%). Consistent with previous studies, most VTE occurred in the puerperium (1.05 per 1000 pregnancies, 64.5%). Significant risk factors included immobility, previous VTE, systemic infection, BMI over 30, and hypertensive disorders of pregnancy. CONCLUSION: Pregnancy-related VTE is not uncommon in China which is consistent with current foreign reports, and the change in incidence trend may be related to greater physicians' understanding of VTE and effective preventive measures after the publication of Chinese guidelines.

Frailty and long-term survival of patients with colorectal cancer: a meta-analysis.

BACKGROUND: Frailty has been related with the risk of postoperative complication in patients with colorectal cancer (CRC). However, the association between frailty and long-term survival in patients with CRC has not been comprehensively evaluated. We performed a meta-analysis to systematically evaluate the relationship between frailty and long-term survival of these patients. METHODS: Relevant cohort studies with follow-up duration ≥ 1 year were identified from Medline, Embase, and Web of Science. A random-effect model after incorporation of the between-study heterogeneity was selected to pool the results. RESULTS: Ten cohort studies with 35,546 patients were included, and 4100 (11.5%) of them had frailty. Pooled results showed that patients with frailty had worse overall survival compared to those without frailty at baseline (relative risk [RR]: 2.21, 95% confidence interval [CI] 1.43-3.41, P < 0.001; I2 = 92%). Results were consistent for studies adjusting age (RR: 2.20, P < 0.001) or including older cancer patients only (RR: 2.28, P = 0.002). Subgroup analyses showed that difference in study design, follow-up duration, or study quality scores may not significantly affect the findings (P for subgroup analyses all > 0.05). Further meta-analyses with two datasets showed that frailty was also associated with worse cancer-specific survival (RR: 4.60, 95% CI 2.75-7.67, P < 0.001; I2 = 38%) and recurrence-free survival (RR: 1.72, 95% CI 1.30-2.28, P < 0.001; I2 = 0%). CONCLUSIONS: Frailty at admission is associated with worse survival of patients with colorectal cancer.

Physicochemical Characterization of Fucoidans from Sargassum henslowianum C.Agardh and Their Antithrombotic Activity In Vitro.

Sargassum fucoidan is a kind of sulfated heteropolysaccharide with a variety of biological activities. The aim of this study was to investigate the extraction, purification, physicochemical characterization and in vitro antithrombotic activity of fucoidan from Sargassum henslowianum C.Agardh. Hot-water-assisted ultrasound was used to extract fucoidan (F). Fucoidan was purified by DEAE cellulose 52 (F1), Vc-H2O2 (FD1) and Superdex 75 gel (FDS1). The physical and chemical properties of fucoidans were analyzed by chemical composition, monosaccharide composition, average molecular weight (Mw) and FTIR. The sulfate contents of F, F1, FD1 and FDS1 were 11.45%, 16.35% and 17.52%, 9.66%, respectively; the Mw was 5.677 × 105, 4.393 × 105, 2.176 × 104 and 6.166 × 103, respectively. The results of monosaccharide composition showed that the four fucoidans contained l-fucose, d-galactose, l-mannose, d-xylose, l-rhamnose and d-glucose, but the mass fraction ratio was different. The results of FTIR showed that fucoidan contained characteristic peaks of sugar and sulfate. In vitro, F1, FD1 and FDS1 could alleviate HUVEC damage induced by adrenaline (Adr). F1, FD1 and FDS1 decreased vWF and TF and increased the ratio of t-PA/PAI-1 in Adr-induced HUVEC.

Intrauterine administration of peripheral blood mononuclear cells (PBMCs) improves embryo implantation in mice by regulating local Treg/Th17 cell balance.

Immune imbalance of Treg/Th17 cells may contribute to recurrent implantation failure (RIF) during in vitro fertilization and embryo transfer (IVF-ET). In this study, we sought to determine the effect of intrauterine administration of mouse PBMCs prior to embryo implantation on endometrial receptivity and embryo implantation, and examine the underlying mechanism of Treg/Th17 cell balance following intrauterine administration of PBMCs. Pregnant mice were randomly divided into three groups: control group, embryo implantation dysfunction (EID) group, and EID with PBMCs group, and the number of embryo implantation sites was recorded during early pregnancy (Pd7.5). The balance of Treg/Th17 cells in the peripheral blood, spleen, and local implantation sites was detected during the peri-implantation period (Pd4.0) and early pregnancy (Pd7.5). The EID group demonstrated a significant decrease in the number of embryo implantation sites, while the EID with PBMCs group demonstrated higher number of embryo implantation sites compared to the EID group. The balance of Treg/Th17 cells in the peripheral blood and spleen tissues was not significantly different between the aforementioned groups. However, the local uterine ratio of the Treg/Th17 cells increased in the EID with PBMCs group compared to that in the EID group. Collectively, we found that intrauterine administration of PBMCs prior to embryo implantation effectively promotes embryo implantation rates. This may be attributed to the improvement in the local immune balance of Treg and Th17 cells compared with the overall immune balance.

Hepatotoxicity with epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer patients: A network meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: The efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in patients diagnosed with non-small-cell lung cancer (NSCLC) has been confirmed by a large number of studies. However, hepatotoxicity caused by EGFR-TKIs has not been widely investigated. This review compares the hepatotoxicity of different EGFR-TKIs through a network meta-analysis. METHODS: PubMed, EMBASE, Cochrane Library and ClinicalTrials.gov were systematically searched from their individual inceptions to 20 May 2020 with the goal of identifying randomized controlled trials (RCTs) reporting hepatotoxicity in NSCLC patients receiving EGFR-TKIs. A random-effects pairwise meta-analysis and network meta-analysis were performed within a frequentist framework. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated. RESULTS: Twelve eligible RCTs, including data from 6,280 patients diagnosed with NSCLC, were analysed. In our network meta-analysis, gefitinib was associated with a higher risk for hepatotoxicity compared to placebo (RR, 2.55; 95% CI, 1.32-4.89) and dacomitinib (RR, 2.60; 95% CI, 1.30-5.20) in terms of all-grades alanine transaminase (ALT) elevation. As for all-grades aspartate transaminase (AST) elevation, gefitinib and erlotinib showed a significantly increased risk for hepatotoxicity compared to afatinib, dacomitinib and placebo (erlotinib vs. afatinib: RR, 1.85; 95% CI, 1.05-3.24; erlotinib vs. dacomitinib: RR, 1.68; 95% CI, 1.19-2.36; erlotinib vs. placebo: RR, 3.38; 95% CI, 1.69-6.73; gefitinib vs. afatinib: RR, 2.23; 95% CI, 1.32-3.79; gefitinib vs. dacomitinib: RR, 2.03; 95% CI, 1.51-2.73; gefitinib vs. placebo: RR, 4.08; 95% CI, 2.11-7.91). There was a high risk of high-grade ALT elevation in patients treated with gefitinib compared to patients treated with erlotinib (RR, 4.31; 95% CI, 2.15-8.66), dacomitinib (RR, 6.95; 95% CI, 1.85-26.05) or placebo (RR, 8.38; 95% CI, 1.56-45.01). No statistically significant differences were identified among the five agents analysed in terms of all-grades TB elevation and high-grade AST elevation. The surface under the cumulative ranking curve (SUCRA) revealed that gefitinib showed a potentially higher risk for ALT and AST elevation compared to other EGFR-TKIs regardless of grade. WHAT IS NEW AND CONCLUSION: Current evidence indicates that the association between afatinib or dacomitinib and risk of liver enzyme elevation remains uncertain in patients diagnosed with NSCLC. Some evidence suggests that gefitinib and erlotinib may be associated with a significantly increased risk for hepatotoxicity in patients with NSCLC. However, given that the elevation of liver enzymes was not definitely associated with EGFR-TKIs and publication bias, further studies are required to confirm these results.

Application of Nano-Hydroxyapatite Derived from Oyster Shell in Fabricating Superhydrophobic Sponge for Efficient Oil/Water Separation.

The exploration of nonhazardous nanoparticles to fabricate a template-driven superhydrophobic surface is of great ecological importance for oil/water separation in practice. In this work, nano-hydroxyapatite (nano-HAp) with good biocompatibility was easily developed from discarded oyster shells and well incorporated with polydimethylsiloxane (PDMS) to create a superhydrophobic surface on a polyurethane (PU) sponge using a facile solution-immersion method. The obtained nano-HAp coated PU (nano-HAp/PU) sponge exhibited both excellent oil/water selectivity with water contact angles of over 150° and higher absorption capacity for various organic solvents and oils than the original PU sponge, which can be assigned to the nano-HAp coating surface with rough microstructures. Moreover, the superhydrophobic nano-HAp/PU sponge was found to be mechanically stable with no obvious decrease of oil recovery capacity from water in 10 cycles. This work presented that the oyster shell could be a promising alternative to superhydrophobic coatings, which was not only beneficial to oil-containing wastewater treatment, but also favorable for sustainable aquaculture.

Phosphorus Co-Existing in Water: A New Mechanism to Boost Boron Removal by Calcined Oyster Shell Powder.

The removal of boron (B) from water by co-precipitation with hydroxyapatite (HAP) has been extensively studied due to its low cost, ease of use and high efficiency. However, there is no explicit mechanism to express how resolved B was trapped by HAP. Thus, in this work, the process of removing B from water was studied using a low-cost calcium (Ca) precipitation agent derived from used waste oyster shells. The results showed that the removal rate of B in the simulated wastewater by calcined oyster shell (COS) in the presence of phosphorus (P) is up to more than 90%, as opposed to virtually no removal without phosphate. For B removal, the treated water needs to be an alkaline solution with a high pH above 12, where B is removed as [CaB(OH)4]+ but is not molecular. Finally, the synergistic mechanism of co-precipitation between HAP and dissolved B, occlusion co-precipitation, was explained in detail. The proposed method discovered the relationship between Ca, P and B, and was aimed at removing B without secondary pollution through co-precipitation.

Disappearance of SARS-CoV-2 Antibodies in Infants Born to Women with COVID-19, Wuhan, China.

We report the detection and decline over time of severe acute respiratory syndrome coronavirus 2 antibodies in infants born to women with coronavirus disease. Among 11 infants tested at birth, all had detectable IgG and 5 had detectable IgM. IgG titers with positive IgM declined more slowly than those without.

Dual-Carbon Batteries: Materials and Mechanism.

Various carbon nanomaterials are being widely studied for applications in supercapacitors and Li-ion batteries as well as hybrid energy storage devices. Dual-carbon batteries (DCBs), in which both electrodes are composed of functionalized carbon materials, are capable of delivering high energy/power and stable cycles when they are rationally designed. This Review focuses on the electrochemical reaction mechanisms and energy storage properties of various carbon electrode materials in DCBs, including graphite, graphene, hard and soft carbon, activated carbon, and their derivatives. The interfacial chemistry between carbon electrodes and electrolyte is also discussed. The perspective for further development of DCBs is presented at the end.

Simple and rapid nicotine analysis using a disposable silica nanochannel-assisted electrochemiluminescence sensor.

Nicotine analysis is essential to medicine, toxicology and the tobacco industry. However, no simple, portable and disposable method was developed to meet their demands. Here, we report a simple, rapid and disposable silica nanochannel (SAN)-based electrochemiluminescence (ECL) sensor for nicotine analysis by simply assembling a SAN electrode with a paper cover. The sensing principle of the disposable sensor is based on the size exclusion effect and charge selectivity, which obviously prolong the sensor service time. We find that the sensor exhibits good specificity to nicotine, and most of the complex matrices are unlikely to impact the detection. The performance of the disposable sensor in cigarettes, e-cigarettes, nicotine gums, and lozenges is fully validated, showing satisfactory linearity, sensitivity (a limit of detection of 27.82 nM), and accuracy (a recovery between 96.00% and 106.51%). The disposable sensor can be potentially applied for on-site nicotine analysis.

Clinical Characteristics and Outcomes of Childbearing-Age Women With COVID-19 in Wuhan: Retrospective, Single-Center Study.

BACKGROUND: Since December 2019, an outbreak of the coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly in Wuhan and worldwide. However, previous studies on pregnant patients were limited. OBJECTIVE: The aim of this study is to evaluate the clinical characteristics and outcomes of pregnant and nonpregnant women with COVID-19. METHODS: This study retrospectively collected epidemiological, clinical, laboratory, imaging, management, and outcome data of 43 childbearing-age women patients (including 17 pregnant and 26 nonpregnant patients) who presented with laboratory-confirmed COVID-19 in Tongji Hospital, Wuhan, China from January 19 to March 2, 2020. Clinical outcomes were followed up to March 28, 2020. RESULTS: Of the 43 childbearing-age women in this study, none developed a severe adverse illness or died. The median ages of pregnant and nonpregnant women were 33.0 and 33.5 years, respectively. Pregnant women had a markedly higher proportion of history exposure to hospitals within 2 weeks before onset compared to nonpregnant women (9/17, 53% vs 5/26, 19%, P=.02) and a lower proportion of other family members affected (4/17, 24% vs 19/26, 73%, P=.004). Fever (8/17, 47% vs 18/26, 69%) and cough (9/17, 53% vs 12/26, 46%) were common onsets of symptoms for the two groups. Abdominal pain (n=4, 24%), vaginal bleeding (n=1, 6%), reduced fetal movement (n=1, 6%), and increased fetal movement (n=2, 13%) were observed at onset in the 17 pregnant patients. Higher neutrophil and lower lymphocyte percent were observed in the pregnant group compared to the nonpregnant group (79% vs 56%, P<.001; 15% vs 33%, P<.001, respectively). In both groups, we observed an elevated concentration of high-sensitivity C-reactive protein, erythrocyte sedimentation rate, aminotransferase, and lactate dehydrogenase. Concentrations of alkaline phosphatase and D-dimer in the pregnant group were significantly higher than those of the nonpregnant group (119.0 vs 48.0 U/L, P<.001; 2.1 vs 0.3µg/mL, P<.001, respectively). Both pregnant (4/10, 40%) and nonpregnant (8/15, 53%) women tested positive for influenza A virus. A majority of pregnant and nonpregnant groups received antiviral (13/17, 76% vs 25/26, 96%) and antibiotic (13/17, 76% vs 23/26, 88%) therapy. Additionally, both pregnant (2/11, 18%) and nonpregnant (2/19, 11%) recovered women redetected positive for SARS-CoV-2 after discharge. CONCLUSIONS: The epidemiology and clinical and laboratory features of pregnant women with COVID-19 were diverse and atypical, which increased the difficulty of diagnosis. Most pregnant women with COVID-19 were mild and moderate, and rarely developed severe pneumonia or severe adverse outcomes.

[Stimulus and reward information encoded by population neurons in the primate prefrontal cortex and striatum].

It has been reported that single-unit activity in the prefrontal cortex (PFC) and striatum represented visual stimulus and reward information. But how to encode these pieces of information is quite complex from the view of single-neuron activity. Different neurons represented stimulus or reward information in different task epochs with increasing or decreasing their activities relative to their baseline firing rates. The present paper was aimed to study whether population neurons in the two brain areas could stably encode task-relevant parameters in a whole trial period. We recorded single-unit activities in the lateral PFC (LPFC) and striatum while the monkey was performing a stimulus- reward prediction task, and analyzed the neuronal activities by the method of a multi-variable regression model and the linear support vector machine. The results showed that, although proportions of task-related neurons in the two areas varied largely in the whole trial period, LPFC population neurons encoded reward and stimulus information stably and reliably. Population neurons in the striatum encoded only reward information, not stimulus information. A group of neurons in the two areas represented combined information of stimulus and reward. Further analysis showed that LPFC neurons encoded reward information for a group of relevant stimuli, while striatal neurons encoded reward information for a specific stimulus. These results suggest that both LPFC and striatal population neurons are able to stably represent task-relevant information, but from different aspects of the task. The different strategies to encode information in the LPFC and striatum suggest their different contributions in reward-based decision making.

The role of lipid rafts in cell entry of human metapneumovirus.

Human metapneumovirus (hMPV) is a crucial pathogen in children. A cell entry is the first step for infection. Our previous study indicated that there was an endocytosis pathway for hMPV cell entry. Lipid raft is a specific structure at the cell surface and it has been demonstrated to play an important role in endocytosis process of many viruses. In this study, we investigated whether and how lipid raft can take part in the hMPV entry. The confocal microscope was used to detect colocalization of hMPV and lipid raft marker. We demonstrated that colocalizations were increased along with the viral infection and hMPV particles transferred to the perinuclear region with lipid raft. When specific lipid raft inhibitors: methyl-ß cyclodextrin and nystatin were used, hMPV cell entry was inhibited and viral titer decreased dramatically. With the replenishment of exogenous cholesterol, hMPV recovered quickly. These data suggest that lipid raft plays an important role in hMPV endocytosis and maybe one of the pathways for hMPV cell entry.

Ultrastable Potassium Storage Performance Realized by Highly Effective Solid Electrolyte Interphase Layer.

Potassium ion-batteries (PIBs) have attracted tremendous attention recently due to the abundance of potassium resources and the low standard electrode potential of potassium. Particularly, the solid-electrolyte interphase (SEI) in the anode of PIBs plays a vital role in battery security and battery cycling performance due to the highly reactive potassium. However, the SEI in the anode for PIBs with traditional electrolytes is mainly composed of organic compositions, which are highly reactive with air and water, resulting in inferior cycle performance and safety hazards. Herein, a highly stable and effective inorganic SEI layer in the anode is formed with optimized electrolyte. As expected, the PIBs exhibit an ultralong cycle performance over 14 000 cycles at 2000 mA g-1 and an ultrahigh average coulombic efficiency over 99.9%.

Association between cyclooxygenase-2 (COX-2) 8473 T > C polymorphism and cancer risk: a meta-analysis and trial sequential analysis.

BACKGROUND: Numerous studies have investigated the relationship between COX-2 8473 T > C polymorphism and cancer susceptibility, however, the results remain controversial. Therefore, we carried out the present meta-analysis to obtain a more accurate assessment of this potential association. METHODS: In this meta-analysis, 79 case-control studies were included with a total of 38,634 cases and 55,206 controls. We searched all relevant articles published in PubMed, EMBASE, OVID, Web of Science, CNKI and Wanfang Data, till September 29, 2017. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of the association. We performed subgroup analysis according to ethnicity, source of controls, genotyping method and cancer type. Moreover, Trial sequential analysis (TSA) was implemented to decrease the risk of type I error and estimate whether the current evidence of the results was sufficient and conclusive. RESULTS: Overall, our results indicated that 8473 T > C polymorphism was not associated with cancer susceptibility. However, stratified analysis showed that the polymorphism was associated with a statistically significant decreased risk for nasopharyngeal cancer and bladder cancer, but an increased risk for esophageal cancer and skin cancer. Interestingly, TSA demonstrated that the evidence of the result was sufficient in this study. CONCLUSION: No significant association between COX-2 8473 T > C polymorphism and cancer risk was detected.

Expression of ADAMTS13 in Normal and Abnormal Placentae and Its Potential Role in Angiogenesis and Placenta Development.

OBJECTIVE: ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 repeats, member 13) is primarily synthesized in liver. The biosynthesis of ADAMTS13 and its physiological role in placenta are not known. APPROACH AND RESULTS: We used real-time polymerase chain reaction, immunohistochemistry, and Western blotting analyses, as well as proteolytic cleavage of FRETS (fluorescent resonance energy transfers)-VWF73, to determine ADAMTS13 expression in placenta and trophoblasts obtained from individuals with normal pregnancy and patients with severe preeclampsia. We also determined the role of ADAMTS13 in extravillous trophoblasts using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, wound scratch assay, transwell migration assay, tube formation assay, and tissue outgrowth assays. We showed that full-length and proteolytically active ADAMTS13 was expressed in normal human placenta, primarily in the trophoblasts and villous core fetal vessel endothelium during pregnancy. Placental expression of ADAMTS13 mRNA, protein, and proteolytic activity was at the highest levels during the first trimester and significantly reduced at the term of gestation. Additionally, significantly reduced levels of placental ADAMTS13 expression was detected under hypoxic conditions and in patients with preeclampsia. In addition, recombinant ADAMTS13 protease stimulated proliferation, migration, invasion, and network formation of trophoblastic cells in culture. Finally, knockdown of ADAMTS13 expression attenuated the ability of tube formation in trophoblast (HTR-8/SVNEO) cells and the extravillous trophoblast outgrowth in placental explants. CONCLUSIONS: Our results demonstrate for the first time the expression of ADAMTS13 mRNA and protein in normal and abnormal placental tissues and its role in promoting angiogenesis and trophoblastic cell development. The findings support the potential role of the ADAMTS13-von Willebrand factor pathway in normal pregnancy and pathogenesis of preeclampsia.

Characterization of Curcumin/Cyclodextrin Polymer Inclusion Complex and Investigation on Its Antioxidant and Antiproliferative Activities.

The aims of this study were to characterize the curcumin/cyclodextrin polymer inclusion complex using X-ray diffractometry (XRD), Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and UV⁻vis spectroscopy, and to determine the antioxidant activity of this complex by methods of scavenging 2,2-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radicals assays and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals assays. The inhibitory effect of inclusion complex on A375 cells was also investigated by CCK-8 assay, Annexin-V/PI staining assay, and caspase activity assay. The results showed that the complex exhibited different physicochemical characteristics from that of free curcumin. Moreover, the inclusion complex exhibited novel antioxidant activity by scavenging the ABTS and DPPH free radicals and displayed higher antiproliferative activity on A375 cells. Further investigation revealed that inclusion complex could induce A375 cell apoptosis. These findings suggest that inclusion complex could be developed as a novel natural antioxidant with potential applications in cancer chemoprevention.