Novel methods for the rapid and sensitive detection of Nipah virus based on a CRISPR/Cas12a system.

Nipah virus (NiV), a bat-borne zoonotic viral pathogen with high infectivity and lethality to humans, has caused severe outbreaks in several countries of Asia during the past two decades. Because of the worldwide distribution of the NiV natural reservoir, fruit bats, and lack of effective treatments or vaccines for NiV, routine surveillance and early detection are the key measures for containing NiV outbreaks and reducing its influence. In this study, we developed two rapid, sensitive and easy-to-conduct methods, RAA-CRISPR/Cas12a-FQ and RAA-CRISPR/Cas12a-FB, for NiV detection based on a recombinase-aided amplification (RAA) assay and a CRISPR/Cas12a system by utilizing dual-labeled fluorophore-quencher or fluorophore-biotin ssDNA probes. These two methods can be completed in 45 min and 55 min and achieve a limit of detection of 10 copies per µL and 100 copies per µL of NiV N DNA, respectively. In addition, they do not cross-react with nontarget nucleic acids extracted from the pathogens causing similar symptoms to NiV, showing high specificity for NiV N DNA detection. Meanwhile, they show satisfactory performance in the detection of spiked samples from pigs and humans. Collectively, the RAA-CRISPR/Cas12a-FQ and RAA-CRISPR/Cas12a-FB methods developed by us would be promising candidates for the early detection and routine surveillance of NiV in resource-poor areas and outdoors.

MAIT cells in bacterial infectious diseases: heroes, villains, or both?

Due to the aggravation of bacterial drug resistance and the lag in the development of new antibiotics, it is crucial to develop novel therapeutic regimens for bacterial infectious diseases. Currently, immunotherapy is a promising regimen for the treatment of infectious diseases. Mucosal-associated invariant T (MAIT) cells, a subpopulation of innate-like T cells, are abundant in humans and can mount a rapid immune response to pathogens, thus becoming a potential target of immunotherapy for infectious diseases. At the site of infection, activated MAIT cells perform complex biological functions by secreting a variety of cytokines and cytotoxic substances. Many studies have shown that MAIT cells have immunoprotective effects because they can bridge innate and adaptive immune responses, leading to bacterial clearance, tissue repair, and homeostasis maintenance. MAIT cells also participate in cytokine storm generation, tissue fibrosis, and cancer progression, indicating that they play a role in immunopathology. In this article, we review recent studies of MAIT cells, discuss their dual roles in bacterial infectious diseases and provide some promising MAIT cell-targeting strategies for the treatment of bacterial infectious diseases.

Improving Indoor Pedestrian Dead Reckoning for Smartphones under Magnetic Interference Using Deep Learning.

As micro-electro-mechanical systems (MEMS) technology continues its rapid ascent, a growing array of smart devices are integrating lightweight, compact, and cost-efficient magnetometers and inertial sensors, paving the way for advanced human motion analysis. However, sensors housed within smartphones frequently grapple with the detrimental effects of magnetic interference on heading estimation, resulting in diminished accuracy. To counteract this challenge, this study introduces a method that synergistically employs convolutional neural networks (CNNs) and support vector machines (SVMs) for adept interference detection. Utilizing a CNN, we automatically extract profound features from single-step pedestrian motion data that are then channeled into an SVM for interference detection. Based on these insights, we formulate heading estimation strategies aptly suited for scenarios both devoid of and subjected to magnetic interference. Empirical assessments underscore our method's prowess, boasting an impressive interference detection accuracy of 99.38%. In indoor environments influenced by such magnetic disturbances, evaluations conducted along square and equilateral triangle trajectories revealed single-step heading absolute error averages of 2.1891° and 1.5805°, with positioning errors averaging 0.7565 m and 0.3856 m, respectively. These results lucidly attest to the robustness of our proposed approach in enhancing indoor pedestrian positioning accuracy in the face of magnetic interferences.

A Fusion Positioning Method for Indoor Geomagnetic/Light Intensity/Pedestrian Dead Reckoning Based on Dual-Layer Tent-Atom Search Optimization-Back Propagation.

Indoor positioning using smartphones has garnered significant research attention. Geomagnetic and sensor data offer convenient methods for achieving this goal. However, conventional geomagnetic indoor positioning encounters several limitations, including low spatial resolution, poor accuracy, and stability issues. To address these challenges, we propose a fusion positioning approach. This approach integrates geomagnetic data, light intensity measurements, and inertial navigation data, utilizing a hierarchical optimization strategy. We employ a Tent-ASO-BP model that enhances the traditional Back Propagation (BP) algorithm through the integration of chaos mapping and Atom Search Optimization (ASO). In the offline phase, we construct a dual-resolution fingerprint database using Radial Basis Function (RBF) interpolation. This database amalgamates geomagnetic and light intensity data. The fused positioning results are obtained via the first layer of the Tent-ASO-BP model. We add a second Tent-ASO-BP layer and use an improved Pedestrian Dead Reckoning (PDR) method to derive the walking trajectory from smartphone sensors. In PDR, we apply the Biased Kalman Filter-Wavelet Transform (BKF-WT) for optimal heading estimation and set a time threshold to mitigate the effects of false peaks and valleys. The second-layer model combines geomagnetic and light intensity fusion coordinates with PDR coordinates. The experimental results demonstrate that our proposed positioning method not only effectively reduces positioning errors but also improves robustness across different application scenarios.

Flagellin FljB as an adjuvant to the recombinant adenovirus rabies glycoprotein vaccine increases immune responses against rabies in mice.

Rabies virus (RABV) causes an acute progressive viral encephalitis. Although currently licensed vaccines have an excellent safety and efficacy record, the development of a safer and more cost-effective vaccine is still being sought. An E1-deleted, replication-defective human adenovirus type 5 (HAd5) vector expressing RABV glycoprotein (HAd5-G) is thought to be a promising candidate vaccine for immune prophylaxis against rabies. Salmonella enterica serovar Typhimurium (S. Typhimurium) flagellin is a well-known immune adjuvant. In this work, we have researched the adjuvant effect of flagellins (FljB and FliC) for HAd5 in mice for the first time. We found that the recombinant HAd5 expressing RABV glycoprotein and FljB (HAd5-GB), if administered intramuscularly, but not orally, could induce stronger immune responses and provide better protection against rabies than HAd5-G or the recombinant HAd5 expressing glycoprotein and FliC (HAd5-GC). These results suggest that the recombinant HAd5-GB has potential for development as a promising rabies vaccine.

Band structure modification of the thermoelectric Heusler-phase TiFe2Sn via Mn substitution.

Doping (or substitution)-induced modification of the electronic structure to increase the electronic density of states (eDOS) near the Fermi level is considered as an effective strategy to enhance the Seebeck coefficient, and may consequently boost the thermoelectric performance. Through density-functional theory calculations of Mn-substituted TiFe2-xMnxSn compounds, we demonstrate that the d-states of the substituted Mn atoms induce a strong resonant level near the Fermi energy. Our experimental results are in good agreement with the calculations. They show that Mn substitution results in a large increase of the Seebeck coefficient, arising from an enhanced eDOS in Heusler compounds. The results prove that a proper substitution position and element selection can increase the eDOS, leading to a higher Seebeck coefficient and thermoelectric performance of ecofriendly materials.

Tailoring the structure and thermoelectric properties of BaTiO3via Eu2+ substitution.

A series of Ba1-xEuxTiO3-δ (0.1 ≤ x ≤ 0.9) phases with ∼40 nm particle size were synthesized via a Pechini method followed by annealing and sintering under a reducing atmosphere. The effects of Eu2+ substitution on the BaTiO3 crystal structure and the thermoelectric transport properties were systematically investigated. According to synchrotron X-ray diffraction data only cubic perovskite structures were observed. On the local scale below about 20 Å (equal to ∼5 unit cells) deviations from the cubic structure model (Pm3[combining macron]m) were detected by evaluation of the pair distribution function (PDF). These deviations cannot be explained by a simple symmetry breaking model like in EuTiO3-δ. The best fit was achieved in the space group Amm2 allowing for a movement of Ti and Ba/Eu along 〈110〉 of the parent unit cell as observed for BaTiO3. Density functional calculations delivered an insight into the electronic structure of Ba1-xEuxTiO3-δ. From the obtained density of states a significant reduction of the band gap by the presence of filled Eu2+ 4f states at the top of the valence band was observed. The physical property measurements revealed that barium-europium titanates exhibit n-type semiconducting behavior and at high temperature the electrical conductivity strongly depended on the Eu2+ content. Activation energies calculated from the electrical conductivity and Seebeck coefficient data indicate that at high temperatures (800 K < T < 1123 K) the conduction mechanism of Ba1-xEuxTiO3-δ (0.1 ≤ x ≤ 0.9) is a polaron hopping when 0 < x ≤ 0.6 and is a thermally activated process when 0.6 < x < 1. Besides, the thermal conductivity increases with increasing Eu2+ concentration. Due to a remarkable improvement of the power factor, Ba0.1Eu0.9TiO3-δ showed a ZT value of 0.24 at 1123 K.

Immunoenhancement with flagellin as an adjuvant to whole-killed rabies vaccine in mice.

Vaccination is the most effective method for preventing rabies virus (RABV) infection in both humans and animals; however, no satisfactory vaccine has been developed for use worldwide. In the present study, we investigated the immunoadjuvant properties of Salmonella Typhimurium flagellin (FljB, FliC, and FljB'-FliC) to improve immune responses against the rabies vaccine (RV) and the protective efficacy of the whole-killed rabies vaccine (WKRV) with or without flagellins in BALB/c mice. We also compared the differences among the three flagellins in terms of immunoadjuvant properties to RV. FljB can cause the WKRV to induce stronger humoral and cellular immune responses than WKRV alone or WKRV with FliC or FljB'-FliC can. Mice immunized with WKRV and FljB produced higher levels of virus-neutralizing antibody (VNA) against RABV than those in the other groups did. Although mice in all treatment groups survived RABV challenge, the body weight loss in the group immunized with WKRV and FljB was lower than in the other groups. These results indicate that FljB is a promising adjuvant for use in the development of effective rabies vaccines.

Restoration of miR-299-3p promotes macrophage phagocytosis and suppresses malignant phenotypes in breast cancer carcinogenesis via dual-targeting CD47 and ABCE1.

Immunoevasion has been a severe obstacle for the clinical treatment of breast cancer (BC). CD47, known as an anti-phagocytic molecule, plays a key role in governing the evasion of tumor cells from immune surveillance by interacting with signal-regulated protein α (SIRPα) on macrophages. Here, we report for the first time that miR-299-3p is a direct regulator of CD47 with tumor suppressive effects both in vitro and in vivo. miRNA expression profiles and overall survival of BC cohorts from the Cancer Genome Atlas, METABRIC, or GSE19783 datasets showed that miR-299-3p is downregulated in BC tissues and that BC patients with low levels of miR-299-3p have poorer prognoses. Using dual-luciferase reporter, qRT-PCR, Western blot, and phagocytosis assays, we proved that restoration of miR-299-3p can suppress CD47 expression by directly targeting the predicted seed sequence "CCCACAU" in its 3'-UTR, leading to phagocytosis of BC cells by macrophages, whereas miR-299-3p inhibition or deletion reversed this effect. Additionally, Gene Ontology (GO) analysis and a variety of confirmatory experiments revealed that miR-299-3p was inversely correlated with cell proliferation, migration, and the cell cycle process. Mechanistically, miR-299-3p can also directly target ABCE1, an essential ribosome recycling factor, alleviating these malignant phenotypes of BC cells. In vivo BC xenografts based on nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice further proved that restoration of miR-299-3p resulted in a significant suppression of tumorigenesis and a promotion of macrophage activation and infiltration. Overall, our study suggested that miR-299-3p is a potent inhibitor of CD47 and ABCE1 to exhibit bifunctional BC-suppressing effects through immune activation conjugated with malignant behavior inhibition in breast carcinogenesis and thus can potentially serve as a novel therapeutic target for BC.

Global crotonylome identifies EP300-regulated ANXA2 crotonylation in cumulus cells as a regulator of oocyte maturation.

Lysine crotonylation (Kcr), a newly discovered post-translational modification, played a crucial role in physiology and disease progression. However, the roles of crotonylation in oocyte meiotic resumption remain elusive. As abnormal cumulus cell development will cause oocyte maturation arrest and female infertility, we report that cumulus cells surrounding human meiotic arrested oocytes showed significantly lower crotonylation, which was associated with decreased EP300 expression and blocked cumulus cell expansion. In cultured human cumulus cells, exogenous crotonylation or EP300 activator promoted cell proliferation and reduced cell apoptosis, whereas EP300 knockdown induced the opposite effect. Transcriptome profiling analysis in human cumulus cells indicated that functions of crotonylation were associated with activation of epidermal growth factor receptor (EGFR) pathway. Importantly, we characterized the Kcr proteomics landscape in cumulus cells by LC-MS/MS analysis, and identified that annexin A2 (ANXA2) was crotonylated in cumulus cells in an EP300-dependent manner. Crotonylation of ANXA2 enhanced the ANXA2-EGFR binding, and then activated the EGFR pathway to affect cumulus cell proliferation and apoptosis. Using mouse oocytes IVM model and EP300 knockout mice, we further confirmed that crotonylation alteration in cumulus cells affected the oocyte maturation. Together, our results indicated that EP300-mediated crotonylation is important for cumulus cells functions and oocyte maturation.

High-throughput nanopore targeted sequencing for efficient drug resistance assay of Mycobacterium tuberculosis.

Drug-resistant tuberculosis (TB), especially multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB), is one of the urgent clinical problems and public health challenges. Culture-based phenotypic drug susceptibility testing (pDST) is time-consuming, and PCR-based assays are limited to hotspot mutations. In this study, we developed and validated a convenient and efficient approach based on high-throughput nanopore sequencing technology combined with multiplex PCR, namely nanopore targeted sequencing (NTS), to simultaneously sequence 18 genes associated with antibiotic resistance in Mycobacterium tuberculosis (MTB). The analytical performance of NTS was evaluated, and 99 clinical samples were collected to assess its clinical performance. The NTS results showed that MTB and its drug resistance were successfully identified in approximately 7.5 h. Furthermore, compared to the pDST and Xpert MTB/RIF assays, NTS provided much more drug resistance information, covering 14 anti-TB drugs, and it identified 20 clinical cases of drug-resistant MTB. The mutations underlying these drug-resistant cases were all verified using Sanger sequencing. Our approach for this TB drug resistance assay offers several advantages, including being culture-free, efficient, high-throughput, and highly accurate, which would be very helpful for clinical patient management and TB infection control.

Infectious Disease Diagnosis and Pathogen Identification Platform Based on Multiplex Recombinase Polymerase Amplification-Assisted CRISPR-Cas12a System.

Controlling and mitigating infectious diseases caused by multiple pathogens or pathogens with several subtypes require multiplex nucleic acid detection platforms that can detect several target genes rapidly, specifically, sensitively, and simultaneously. Here, we develop a detection platform, termed Multiplex Assay of RPA and Collateral Effect of Cas12a-based System (MARPLES), based on multiplex nucleic acid amplification and Cas12a ssDNase activation to diagnose these diseases and identify their pathogens. We use the clinical specimens of hand, foot, and mouth disease (HFMD) and influenza A to evaluate the feasibility of MARPLES in diagnosing the disease and identifying the pathogen, respectively, and find that MARPLES can accurately diagnose the HFMD associated with enterovirus 71, coxsackievirus A16 (CVA16), CVA6, or CVA10 and identify the exact types of H1N1 and H3N2 in an hour, showing high sensitivity and specificity and 100% predictive agreement with qRT-PCR. Collectively, our findings demonstrate that MARPLES is a promising multiplex nucleic acid detection platform for disease diagnosis and pathogen identification.

Identification of biomarkers and regulatory networks for cartilage damage patients.

BACKGROUND: The aim of this study was to mine cartilage damage and regeneration-related biomarkers and identify the gene regulatory networks of cartilage damage. METHODS: A gene expression data set (GSE129147) containing damaged and control samples collected from the knee of the same patients was employed. R package limma was used to identify differentially expressed genes (DEGs), and clusterProfiler was performed for the GO and KEGG functional enrichment analysis. Cytoscape plug-ins of CytoHubba and MCODE were applied to investigate protein-protein interaction (PPI) network, modules, and hub genes. RESULTS: We identified 422 DEGs that were involved in skeletal system development, bone development, ossification, mesenchyme development, mesenchymal cell differentiation, connective tissue development, osteoblast differentiation, and extracellular matrix. We dug out 30 hub genes, identified three PPI modules, and constructed a miRNA regulatory network for DEGs. The miRNAs of the DEGs were predicted by miRNet, and the miRNA-mRNA network displayed some important miRNAs such as miR-335-5p, miR-92a-3p, and miR-98-5p. CONCLUSIONS: Collectively, these results have the potential to clarify the mechanism of cartilage damage and to assist us in discovering the damage and repair-related biomarkers.

PDGFRB is a potential prognostic biomarker and correlated with immune infiltrates in gastric cancer.

Gastric cancer (GC) is a common cancer with high mortality and morbidity rates worldwide. Although medical and surgical treatments have improved, the mechanisms of the progression of GC remain unclear. Platelet-derived growth factor receptor-ß (PDGFRB) plays a pivotal role in angiogenesis and tumor cell proliferation and has been suggested as a prognostic marker of cancer. This study aimed to explore the relationship of PDGFRB expression with clinicopathologic characteristics, immune cell infiltration status, and prognosis in GC. In this study, we visualized the expression and prognostic values of PDGFRB in GC using the Oncomine, UALCAN, GEPIA, and Kaplan-Meier Plotter databases. And then we explored the potential relationships between PDGFRB expression and the levels of immune cell infiltration using the TIMER, GEPIA databases and CIBERSORT algorithm. Furthermore, LinkedOmics analysis was performed to explore the functions for PDGFRB. The results showed close correlations between PDGFRB and immune cell infiltration especially M2 Macrophage infiltration in GC. High PDGFRB expression was related to poor outcomes in GC. High PDGFRB expression can negatively affect GC prognosis by promoting angiogenesis and modulating the tumor immune microenvironment. These results strongly suggest that PDGFRB can be used as a prognostic biomarker of GC and provide novel insights into possible immunotherapeutic targets.

A novel detection method for the pathogenic Aeromonas hydrophila expressing aerA gene and/or hlyA gene based on dualplex RAA and CRISPR/Cas12a.

Aeromonas hydrophila is an emerging waterborne and foodborne pathogen with pathogenicity to humans and warm water fishes, which severely threatens human health, food safety and aquaculture. A novel method for the rapid, accurate, and sensitive detection of pathogenic A. hydrophila is still needed to reduce the impact on human health and aquaculture. In this work, we developed a rapid, accurate, sensitive, and visual detection method (dRAA-CRISPR/Cas12a), without elaborate instruments, integrating the dualplex recombinase-assisted amplification (dRAA) assay and CRISPR/Cas12a system to detect pathogenic A. hydrophila expressing aerA and/or hlyA virulence genes. The dRAA-CRISPR/Cas12a method has high sensitivity, which can rapidly detect (about 45 min) A. hydrophila with the limit of detection in 2 copies of genomic DNA per reaction, and has high specificity for three pathogenic A. hydrophila strains (aerA+hlyA- , aerA-hlyA+ , and aerA+hlyA+ ). Moreover, dRAA-CRISPR/Cas12a method shows satisfactory practicability in the analysis of the spiked human blood and stool and fish samples. These results demonstrate that our developed pathogenic A. hydrophila detection method, dRAA-CRISPR/Cas12a, is a promising potential method for the early diagnosis of human A. hydrophila infection and on-site detection of A. hydrophila in food and aquaculture.

Rapid and Sensitive Detection of Vibrio vulnificus Using CRISPR/Cas12a Combined With a Recombinase-Aided Amplification Assay.

Vibrio vulnificus is an important zoonotic and aquatic pathogen and can cause vibriosis in humans and aquatic animals (especially farmed fish and shrimp species). Rapid and sensitive detection methods for V. vulnificus are still required to diagnose human vibriosis early and reduce aquaculture losses. Herein, we developed a rapid and sensitive diagnostic method comprising a recombinase-aided amplification (RAA) assay and the CRISPR/Cas12a system (named RAA-CRISPR/Cas12a) to detect V. vulnificus. The RAA-CRISPR/Cas12a method allows rapid and sensitive detection of V. vulnificus in 40 min without a sophisticated instrument, and the limit of detection is two copies of V. vulnificus genomic DNA per reaction. Meanwhile, the method shows satisfactory specificity toward non-target bacteria and high accuracy in the spiked blood, stool, and shrimp samples. Therefore, our proposed rapid and sensitive V. vulnificus detection method, RAA-CRISPR/Cas12a, has great potential for early diagnosis of human vibriosis and on-site V. vulnificus detection in aquaculture and food safety control.

RAA-Cas12a-Tg: A Nucleic Acid Detection System for Toxoplasma gondii Based on CRISPR-Cas12a Combined with Recombinase-Aided Amplification (RAA).

Toxoplasmosis, caused by the intracellular protozoon Toxoplasma gondii, is a significant parasitic zoonosis with a world-wide distribution. As a main transmission route, human infection can be acquired by the ingestion of T. gondii oocysts from the environment (e.g., soil, water, fruits and vegetables). Regarding the detection of T. gondii oocysts in environmental samples, the development of a time-saving, cost-effective and highly sensitive technique is crucial for the surveillance, prevention and control of toxoplasmosis. In this study, we developed a new method by combining recombinase-aided amplification (RAA) with CRISPR-Cas12a, designated as the RAA-Cas12a-Tg system. Here, we compared this system targeting the 529 bp repeat element (529 bp-RE) with the routine PCR targeting both 529 bp-RE and ITS-1 gene, respectively, to assess its ability to detect T. gondii oocysts in soil samples. Our results indicated that the 529 bp RE-based RAA-Cas12a-Tg system was able to detect T. gondii successfully in nearly an hour at body temperature and was more sensitive than the routine PCR assay. The sensitivity of this system reached as low as 1 fM with high specificity. Thus, RAA-Cas12a-Tg system provided a rapid, sensitive and easily operable method for point-of-care detection of T. gondii oocysts in soil, which will facilitate the control of T. gondii infection in humans and animals.

Effects of Nanodomains on Local and Long-Range Phase Transitions in Perovskite-Type Eu0.8Ca0.2TiO3-δ.

The determination of reversible phase transitions in the perovskite-type thermoelectric oxide Eu0.8Ca0.2TiO3-δ is fundamental, since structural changes largely affect the thermal and electrical transport properties. The phase transitions were characterized by heat capacity measurements, Rietveld refinements, and pair distribution function (PDF) analysis of the diffraction data to achieve information on the phase transition temperatures and order as well as structural changes on the local level and the long range. On the long-range scale, Eu0.8Ca0.2TiO3-δ showed a phase transition sequence during heating from cubic at 100 < T < 592 K to tetragonal and finally back to cubic at T > 846 K. The phase transition at T = 592 K (diffraction)/606 K (thermal analysis) was reversible with a very small thermal hysteresis of about 2 K. The local structure at 100 K was composed of a complex nanodomain arrangement of Amm2- and Pbnm-like local structures with different coherence lengths. Since in Eu0.8Ca0.2TiO3-δ the amount of Pbnm domains was too small to percolate, the competition of ferroelectrically distorted octahedra (Amm2 as in BaTiO3) and rigid, tilted octahedra (Pbnm as in CaTiO3) resulted in a cubic long-range structure at low temperatures.

The Effect of Sex Differences on Endothelial Function and Circulating Endothelial Progenitor Cells in Hypertriglyceridemia.

BACKGROUND: Men have a higher risk and earlier onset of cardiovascular diseases compared with premenopausal women. Hypertriglyceridemia is an independent risk factor for the occurrence of ischemic heart disease. Endothelial dysfunction is related to the development of ischemic heart disease. Whether sex differences will affect the circulating endothelial progenitor cells (EPCs) and endothelial function in hypertriglyceridemia patients or not is not clear. METHODS: Forty premenopausal women and forty age- and body mass index (BMI)-matched men without cardiovascular and metabolic disease were recruited and then divided into four groups: normotriglyceridemic women (women with serum triglycerides level <150 mg/dl), hypertriglyceridemic women (women with serum triglycerides level ≥150 mg/dl), normotriglyceridemic men (men with serum triglycerides level <150 mg/dl), and hypertriglyceridemic men (men with serum triglycerides level ≥150 mg/dl). Peripheral blood was obtained and evaluated. Flow-mediated dilatation (FMD), the number and activity of circulating EPCs, and the levels of nitric oxide (NO), vascular endothelial growth factor (VEGF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) in plasma and culture medium were measured. RESULTS: The number and activity of circulating EPCs, as well as the level of NO in plasma or culture medium, were remarkably increased in premenopausal females compared with those in males both in the hypertriglyceridemic group and the normotriglyceridemic group. The EPC counts and activity, as well as the production of NO, were restored in hypertriglyceridemic premenopausal women compared with those in normal women. However, in hypertriglyceridemic men, the EPC counts and activity, as well as levels of NO, were significantly reduced. The values of VEGF and GM-CSF were without statistical change. CONCLUSIONS: The present study firstly demonstrated that there were sex differences in the number and activity of circulating EPCs in hyperglyceridemia patients. Hypertriglyceridemic premenopausal women displayed restored endothelial functions, with elevated NO production, probably mediated by estradiol. We provided a new insight to explore the clinical biomarkers and therapeutic strategies for hypertriglyceridemia-related vascular damage.

Smoking-Induced Inhibition of Number and Activity of Endothelial Progenitor Cells and Nitric Oxide in Males Were Reversed by Estradiol in Premenopausal Females.

OBJECTIVES: The number and activity of circulating EPCs were enhanced in premenopausal women contrast to postmenopausal females and age-matched males. Here, we investigated whether this favorable effect exists in premenopausal women and age-matched men with cigarette smoking. METHODS: In a cross-sectional study, the number and activity of circulating EPCs and nitric oxide production (NO) as well as flow-mediated vasodilation (FMD) in both premenopausal women and age-matched men with or without cigarette smoking were studied. RESULTS: Compared with age-matched men with or without smoking, the number and function of circulating EPCs as well as NO level in premenopausal women were obviously higher than that in the former and not affected by smoking. The number and function of circulating EPCs as well as NO level in male smokers were shown to be the most strongly inhibited. Furthermore, there was significant correlation between EPC number and activity, plasma NO level, and NO secretion by EPCs and FMD. CONCLUSIONS: Estradiol was deemed to play an important role in enhancing the number and activity of EPCs and NO production in premenopausal women even when affected by smoking, which may be the important mechanisms underlying vascular protection of estradiol in premenopausal women, but not in age-matched men.