Microglia-derived exosomes selective sorted by YB-1 alleviate nerve damage and cognitive outcome in Alzheimer's disease.

BACKGROUND: Neuroinflammation is a characteristic pathological change of Alzheimer's Diseases (AD). Microglia have been reported to participate in inflammatory responses within the central nervous system. However, the mechanism of microglia released exosome (EXO) contribute to communication within AD microenvironment remains obscure. METHODS: The interaction between microglia and AD was investigated in vitro and in vivo. RNA-binding protein immunoprecipitation (RIP) was used to investigate the mechanisms of miR-223 and YB-1. The association between microglia derived exosomal YB-1/miR-223 axis and nerve cell damage were assessed using Western blot, immunofluorescence, RT-PCR, ELISA and wound healing assay. RESULTS: Here, we reported AD model was responsible for the M1-like (pro-inflammatory) polarization of microglia which in turn induced nerve cell damage. While M2-like (anti-inflammatory) microglia could release miR-223-enriched EXO which reduced neuroinflammation and ameliorated nerve damage in AD model in vivo and in vitro. Moreover, YB-1 directly interacted with miR-223 both in cell and EXO, and participated in microglia exosomal miR-223 loading. CONCLUSION: These results indicate that anti-inflammatory microglia-mediated neuroprotection form inflammatory damage involves exporting miR-223 via EXO sorted by YB-1. Consequently, YB-1-mediated microglia exosomal sorting of miR-223 improved the nerve cell damage repair, representing a promising therapeutic target for AD.

Preterm birth associated alterations in brain structure, cognitive functioning and behavior in children from the ABCD dataset.

BACKGROUND: Preterm birth is a global health problem and associated with increased risk of long-term developmental impairments, but findings on the adverse outcomes of prematurity have been inconsistent. METHODS: Data were obtained from the baseline session of the ongoing longitudinal Adolescent Brain and Cognitive Development (ABCD) Study. We identified 1706 preterm children and 1865 matched individuals as Control group and compared brain structure (MRI data), cognitive function and mental health symptoms. RESULTS: Results showed that preterm children had higher psychopathological risk and lower cognitive function scores compared to controls. Structural MRI analysis indicated that preterm children had higher cortical thickness in the medial orbitofrontal cortex, parahippocampal gyrus, temporal and occipital gyrus; smaller volumes in the temporal and parietal gyrus, cerebellum, insula and thalamus; and smaller fiber tract volumes in the fornix and parahippocampal-cingulum bundle. Partial correlation analyses showed that gestational age and birth weight were associated with ADHD symptoms, picvocab, flanker, reading, fluid cognition composite, crystallized cognition composite and total cognition composite scores, and measures of brain structure in regions involved with emotional regulation, attention and cognition. CONCLUSIONS: These findings suggest a complex interplay between psychopathological risk and cognitive deficits in preterm children that is associated with changes in regional brain volumes, cortical thickness, and structural connectivity among cortical and limbic brain regions critical for cognition and emotional well-being.

[Research progress in Astragali Radix and its active ingredients in treatment of lung cancer].

Lung cancer is the leading cause of cancer death, and its effective treatment is a difficult medical problem. Lung cancer belongs to the traditional Chinese medicine(TCM) disease categories of lung accumulation, lung amassment, and overstrain cough. Rich theoretical basis and practical experience have been accumulated in the TCM treatment of lung cancer. Astragali Radix is one of the representatives of Qi-tonifying drugs. It mainly treat the lung cancer with the syndrome of Qi deficiency and pathogen stagnation, following the principle of reinforcing healthy Qi and eliminating patgogenic Qi. Astragali Radix exerts a variety of pharmacological activities in the treatment of lung cancer, including inhibiting tumor cell proliferation and promoting tumor cell apoptosis, inhibiting tumor invasion and migration, regulating the tumor microenvironment, suppressing tumor angiogenesis, modulating autophagy, inducing macrophage polarization, enhancing immunity, inhibiting immune escape, and reversing cisplatin resistance. The active ingredients of Astragali Radix in treating lung cancer include polysaccharides, saponins, and flavonoids. This study reviewed the pharmacological activities and active ingredients of Astragali Radix in the treatment of lung cancer, providing a basis for the development and utilization of Astragali Radix resources and active ingredients and the research and development of anti-tumor drugs.

Quantitative assessment of translocator protein (TSPO) in the non-human primate brain and clinical translation of [18F]LW223 as a TSPO-targeted PET radioligand.

OBJECTIVES: Translocator protein 18 kDa (TSPO) positron emission tomography (PET) can be harnessed for the non-invasive detection of macrophage-driven inflammation. [18F]LW223, a newly reported TSPO PET tracer which was insensitive to rs6971 polymorphism, showed favorable performance characteristics in a recent imaging study involving a rat myocardial infarction model. To enable quantitative neuroimaging with [18F]LW223, we conducted kinetic analysis in the non-human primate (NHP) brain. Further, we sought to assess the utility of [18F]LW223-based TSPO imaging in a first-in-human study. METHODS: Radiosynthesis of [18F]LW223 was accomplished on an automated module, whereas molar activities, stability in formulation, lipophilicity and unbound free fraction (fu) of the probe were measured. Brain penetration and target specificity of [18F]LW223 in NHPs were corroborated by PET-MR imaging under baseline and pre-blocking conditions using the validated TSPO inhibitor, (R)-PK11195, at doses ranging from 5 to 10 mg/kg. Kinetic modeling was performed using one-tissue compartment model (1TCM), two-tissue compartment model (2TCM) and Logan graphical analyses, using dynamic PET data acquisition, arterial blood collection and metabolic stability testing. Clinical PET scans were performed in two healthy volunteers (HVs). Regional brain standard uptake value ratio (SUVr) was assessed for different time intervals. RESULTS: [18F]LW223 was synthesized in non-decay corrected radiochemical yields (n.d.c. RCYs) of 33.3 ± 6.5% with molar activities ranging from 1.8 ± 0.7 Ci/µmol (n = 11). [18F]LW223 was stable in formulation for up to 4 h and LogD7.4 of 2.31 ± 0.13 (n = 6) and fu of 5.80 ± 1.42% (n = 6) were determined. [18F]LW223 exhibited good brain penetration in NHPs, with a peak SUV value of ca. 1.79 in the whole brain. Pre-treatment with (R)-PK11195 substantially accelerated the washout and attenuated the area under the time-activity curve, indicating in vivo specificity of [18F]LW223 towards TSPO. Kinetic modeling demonstrated that 2TCM was the most suitable model for [18F]LW223-based neuroimaging. Global transfer rate constants (K1) and total volumes of distribution (VT) were found to be 0.10 ± 0.01 mL/cm3/min and 2.30 ± 0.17 mL/cm3, respectively. Dynamic PET data analyses across distinct time windows revealed that the VT values were relatively stable after 60 min post-injection. In a preliminary clinical study with two healthy volunteers, [18F]LW223 exhibited good brain uptake and considerable tracer retention across all analyzed brain regions. Of note, an excellent correlation between SUVr with VT was obtained when assessing the time interval from 20 to 40 min post tracer injection (SUVr(20-40 min), R2 = 0.94, p < 0.0001), suggesting this time window may be suitable to estimate specific binding to TSPO in human brain. CONCLUSION: Our findings indicate that [18F]LW223 is suitable for quantitative TSPO-targeted PET imaging in higher species. Employing state-of-the-art kinetic modeling, we found that [18F]LW223 was effective in mapping TSPO throughout the NHP brain, with best model fits obtained from 2TCM and Logan graphical analyses. Overall, our results indicate that [18F]LW223 exhibits favorable tracer performance characteristics in higher species, and this novel imaging tool may hold promise to provide effective neuroinflammation imaging in patients with neurological disease.

Solution-grown millimeter-scale Mn-doped CsPbBr3/Cs4PbBr6 crystals with enhanced photoluminescence and stability for light-emitting applications.

Metal halide perovskites are particularly emerging for optoelectronic applications in light-emitting diodes, photodetectors, and solar cells due to their flourishing photophysical properties. However, the poor stability of three-dimensional (3D) lead halide perovskite nanocrystals (NCs) significantly hampers their optoelectronics and photovoltaics applications. Embedding 3D perovskites into zero-dimensional (0D) perovskite crystals and doping ions of appropriate elements into host lattices provide effective approaches to improve the stability and optical-electronic performance. In this study, millimeter-scale Mn-doped and undoped CsPbBr3/Cs4PbBr6 perovskite crystals were successfully fabricated by a one-step slow cooling method. We systematically investigated the effects of Mn2+ ion doping on the PL performance and stability of CsPbBr3/Cs4PbBr6 crystals. Compared with undoped crystals, the existence of Mn2+ ions not only blue-shifted the PL peak but also improved the luminescence performance and stability of the prepared millimeter-sized crystals. Moreover, doping Mn2+ ions can increase the proportion of radiative recombination at low temperature, which may be because Mn2+ ions can effectively accelerate the decay of a dark exciton by the magnetic mixing of bright and dark excitons. In addition, green LED devices with high efficiency packaged as-grown crystals are explored, which promises further application in display backlights.

A new scheme of global feature management improved the performance and stability of radiomics model: a study based on CT images of acute brainstem infarction.

OBJECTIVE: The performance and stability of radiomics model caused by dimension reduction remain being confronted with major challenges. In this study, we aimed to propose a new scheme of global feature management independent of dimension reduction to improve it. METHODS: The non-contrast computed tomography (NCCT) images of acute brainstem infarction (ABI) from two medical centers were used as test and validation sets. A new scheme was constructed based on global feature management, and the traditional scheme dependent on dimension reduction was used as control. The radiomic features of NCCT images were extracted in Matlab R2013a. The performance of prediction model was evaluated by the generalized linear model (GLM) and multivariate logistic regression. And, the stability of radiomics model was evaluated with the difference of area under curve (AUC) between the test and validation sets. RESULTS: Compared with the traditional scheme, the new scheme presented a similar detection performance (AUC: 0.875 vs. 0.883), yet a better performance in predicting prognosis (AUC: 0.864, OR = 0.917, p = 0.021 vs. AUC:0.806, OR = 0.972, p = 0.007). All these results were well verified in an independent validation set. Moreover, the new scheme showed stronger stability in both the detection model (ΔAUC: 0.013 vs. 0.039) and prediction model (ΔAUC = 0.004 vs. 0.044). CONCLUSION: Although there might be several limitations, this study proved that the scheme of global feature management independent of dimension reduction could be a powerful supplement to the radiomics methodology. KEY POINTS: • The new scheme (Swavelet) presented similar detection performances for ABI with the traditional scheme. • A better predictive performance for END was found in the new scheme (Swavelet) compared with the traditional scheme. • Stronger model stability was found in both the detection and prediction models based on the new scheme.

Recombinant Plasminogen Activator Modified Nanoparticles for Targeting Thrombolysis in Branch Retinal Vein Occlusion.

Branch Retinal Vein Occlusion (BRVO) is the second chronic branch retinal vascular disease that causes abnormal vision loss after acute branch retinal disease in type 2 diabetes. There is no scientific conclusion about its specific pathogenic mechanism at present. Most clinical scholars generally support the theory that the partial human anatomical structure and various systemic risk psychological factors cause insufficient oxygen supply and hemostasis in the local branch retinal arteries. The research results of this article aim to reconstruct a non-nanocell-targeted thrombolytic drug delivery system without modification of rtPA without polyethylene glycol-methyl polycaprolactone and to re-evaluate its thrombus targeting and dissolution. The effect and safety of thrombus provide a new strategy for realizing combined treatment of thrombus. It is a study on the targeting of rtPA-NP to thrombus and its thrombolytic properties. HPLC method was used to detect the binding of fibrin clot prepared in vitro with coumarin-6 labeled NP and rtPA-NP; immunofluorescence technique was used to observe the location of nanomedicine and fibrin clot in branch retinal vein occlusion model Condition. The rtPA-NP drug delivery system constructed in this study not only retains the activity of rtPA and good thrombus targeting but also significantly prolongs its half-life and simplifies the way of administration. The therapeutic efficiency of rtPA-NP thrombus targeted administration on branch retinal vein occlusion reached 85.64%. The successful construction of the rtPA-NP thrombus targeted drug delivery system provides a new way for thrombosis treatment and lays the foundation for the future combination of anticoagulants and vascular protection drugs to achieve the combined treatment of thrombosis and the development of safe and efficient thrombolytic drugs.

Neuron secrete exosomes containing miR-9-5p to promote polarization of M1 microglia in depression.

BACKGROUND: Neuroinflammation is an important component mechanism in the development of depression. Exosomal transfer of MDD-associated microRNAs (miRNAs) from neurons to microglia might exacerbate neuronal cell inflammatory injury. RESULTS: By sequence identification, we found significantly higher miR-9-5p expression levels in serum exosomes from MDD patients than healthy control (HC) subjects. Then, in cultured cell model, we observed that BV2 microglial cells internalized PC12 neuron cell-derived exosomes while successfully transferring miR-9-5p. MiR-9-5p promoted M1 polarization in microglia and led to over releasing of proinflammatory cytokines, such as interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), which exacerbated neurological damage. Furthermore, we identified suppressor of cytokine signaling 2 (SOCS2) as a direct target of miR-9-5p. Overexpression of miR-9-5p suppressed SOCS2 expression and reactivated SOCS2-repressed Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) pathways. Consistently, we confirmed that adeno-associated virus (AAV)-mediated overexpression of miR-9-5p polarized microglia toward the M1 phenotype and exacerbated depressive symptoms in chronic unpredictable mild stress (CUMS) mouse mode. CONCLUSION: MiR-9-5p was transferred from neurons to microglia in an exosomal way, leading to M1 polarization of microglia and further neuronal injury. The expression and secretion of miR-9-5p might be novel therapeutic targets for MDD.

Application of CycleGAN and transfer learning techniques for automated detection of COVID-19 using X-ray images.

Coronavirus (which is also known as COVID-19) is severely impacting the wellness and lives of many across the globe. There are several methods currently to detect and monitor the progress of the disease such as radiological image from patients' chests, measuring the symptoms and applying polymerase chain reaction (RT-PCR) test. X-ray imaging is one of the popular techniques used to visualise the impact of the virus on the lungs. Although manual detection of this disease using radiology images is more popular, it can be time-consuming, and is prone to human errors. Hence, automated detection of lung pathologies due to COVID-19 utilising deep learning (Bowles et al.) techniques can assist with yielding accurate results for huge databases. Large volumes of data are needed to achieve generalizable DL models; however, there are very few public databases available for detecting COVID-19 disease pathologies automatically. Standard data augmentation method can be used to enhance the models' generalizability. In this research, the Extensive COVID-19 X-ray and CT Chest Images Dataset has been used and generative adversarial network (GAN) coupled with trained, semi-supervised CycleGAN (SSA- CycleGAN) has been applied to augment the training dataset. Then a newly designed and finetuned Inception V3 transfer learning model has been developed to train the algorithm for detecting COVID-19 pandemic. The obtained results from the proposed Inception-CycleGAN model indicated Accuracy = 94.2%, Area under Curve = 92.2%, Mean Squared Error = 0.27, Mean Absolute Error = 0.16. The developed Inception-CycleGAN framework is ready to be tested with further COVID-19 X-Ray images of the chest.

Comparative study on the gastrointestinal- and immune- regulation functions of Hedysari Radix Paeparata Cum Melle and Astragali Radix Praeparata cum Melle in rats with spleen-qi deficiency, based on fuzzy matter-element analysis.

CONTEXT: Hedysari Radix Praeparata Cum Melle (HRPCM) and Astragali Radix Praeparata Cum Melle (ARPCM) are used interchangeably in clinics to treat spleen-qi deficiency (SQD) symptom mainly including gastrointestinal dysfunction and decreased immunity, which has unknown differences in efficacy. OBJECTIVE: To investigate the differences between HRPCM and ARPCM on intervening gastrointestinal- and immune-function with SQD syndrome. MATERIALS AND METHODS: After the SQD model was established, the Sprague-Dawley (SD) rats were randomly divided into nine groups (n = 10): normal; model; Bu-Zhong-Yi-Qi Pills; 18.9, 12.6 and 6.3 g/kg dose groups of HRPCM and ARPCM. Gastrointestinal function including d-xylose, gastrin, amylase vasoactive intestinal peptide, motilin, pepsin, H+/K+-ATPase, Na+/K+-ATPase, sodium-glucose cotransporter 1 (SGLT1), glucose transporter 2 (GLUT2) and immune function including spleen and thymus index, blood routine, interleukin (IL)-2, IL-6, interferon-γ (IFN-γ), tumour necrosis factor-α (TNF-α), immunoglobulin (Ig) M, IgA, IgG and delayed-type hypersensitivity (DTH) were detected. Finally, the efficacy differences were analysed comprehensively by the fuzzy matter-element method. RESULTS: In regulating immune, the doses differences in efficacy between HRPCM and ARPCM showed in the high-dose (18.9 g/kg), but there were no differences in the middle- and low- dose (12.6 and 6.37 g/kg); the efficacy differences were primarily reflected in levels of IL-6, IFN-γ, TNF-α and IgM in serum, and the mRNA expression of IL-6 and IFN-γ in the spleen. In regulating gastrointestinal, the efficacy differences were primarily reflected in the levels of D-xylose, MTL, and GAS in serum, and the mRNA and protein expression of SGLT1 and GLUT2 in jejunum and ileum. DISCUSSION AND CONCLUSIONS: HRPCM is more effective than ARPCM on regulating gastrointestinal function and immune function with SQD syndrome. Therefore, we propose that HRPCM should be mainly used to treat SQD syndrome in the future.

CRISPR/Cas9-mediated disruption of SHANK3 in monkey leads to drug-treatable autism-like symptoms.

Monogenic mutations in the SHANK3 gene, which encodes a postsynaptic scaffold protein, play a causative role in autism spectrum disorder (ASD). Although a number of mouse models with Shank3 mutations have been valuable for investigating the pathogenesis of ASD, species-dependent differences in behaviors and brain structures post considerable challenges to use small animals to model ASD and to translate experimental therapeutics to the clinic. We have used clustered regularly interspersed short palindromic repeat/CRISPR-associated nuclease 9 to generate a cynomolgus monkey model by disrupting SHANK3 at exons 6 and 12. Analysis of the live mutant monkey revealed the core behavioral abnormalities of ASD, including impaired social interaction and repetitive behaviors, and reduced brain network activities detected by positron-emission computed tomography (PET). Importantly, these abnormal behaviors and brain activities were alleviated by the antidepressant fluoxetine treatment. Our findings provide the first demonstration that the genetically modified non-human primate can be used for translational research of therapeutics for ASD.

Abnormalities in FGF family members and their roles in modulating depression-related molecules.

The role of the fibroblast growth factor (FGF) system in depression has received considerable attention in recent years. To understand the role of this system, it is important to identify the specific members of the FGF family that have been implicated and the various mechanisms that they modulated. Here, we review the role of FGFs in depression and integrate evidence from clinical and basic research. These data suggest that changes in the FGF family are involved in depression and possibly in a wider range of psychiatric disorders. We analyse the abnormalities of FGF family members in depression and their roles in modulating depression-related molecules. The role of the FGF family in depression and related disorders needs to be studied in more detail.

Deviations in the gut microbiota of neonates affected by maternal group B Streptococcus colonization.

BACKGROUND: Group B Streptococcus (GBS) infection is the leading cause of septicemia, meningitis, and pneumonia in neonates. Aberrant gut colonization in early life may predispose children to various diseases in adulthood. However, the associations between gut microbial changes and GBS colonization is still unclear. RESULTS: The composition and diversity of meconium microbiota in GBS group were similar to that of healthy controls. However, we identified several specific taxa that were differentially abundant between the two groups (linear discriminant analysis (LDA) effect size (LEfSe): p < 0.05, LDA > 2.0). Particularly, the relative abundance of Lactobacillus paracasei was significantly reduced, indicating a role in GBS colonization. CONCLUSIONS: Our study presented a series of bacterial species colonized by GBS, thus providing novel evidence in support of initial intestinal microbiota dysbiosis in the neonates with mother's GBS colonization.

Predicting Alzheimer's Disease from Spoken and Written Language Using Fusion-Based Stacked Generalization.

The importance of automating the diagnosis of Alzheimer disease (AD) towards facilitating its early prediction has long been emphasized, hampered in part by lack of empirical support. Given the evident association of AD with age and the increasing aging population owing to the general well-being of individuals, there have been unprecedented estimated economic complications. Consequently, many recent studies have attempted to employ the language deficiency caused by cognitive decline in automating the diagnostic task via training machine learning (ML) algorithms with linguistic patterns and deficits. In this study, we aim to develop multiple heterogeneous stacked fusion models that harness the advantages of several base learning algorithms to improve the overall generalizability and robustness of AD diagnostic ML models, where we parallelly utilized two different written and spoken-based datasets to train our stacked fusion models. Further, we examined the effect of linking these two datasets to develop a hybrid stacked fusion model that can predict AD from written and spoken languages. Our feature spaces involved two widely used linguistic patterns: lexicosyntactics and character n-gram spaces. We firstly investigated lexicosyntactics of AD alongside healthy controls (HC), where we explored a few new lexicosyntactic features, then optimized the lexicosyntactic feature space by proposing a correlation feature selection technique that eliminates features based on their feature-feature inter-correlations and feature-target correlations according to a certain threshold. Our stacked fusion models establish benchmarks on both datasets with AUC of 98.1% and 99.47% for the spoken and written-based datasets, respectively, and corresponding accuracy and F1 score values around 95% on spoken-based dataset and around 97% on the written-based dataset. Likewise, the hybrid stacked fusion model on linked data presents an optimal performance with 99.2% AUC as well as accuracy and F1 score falling around 97%. In view of the achieved performance and enhanced generalizability of such fusion models over single classifiers, this study suggests replacing the initial traditional screening test with such models that can be embedded into an online format for a fully automated remote diagnosis.

[Prediction of Q-markers of Astragali Radix based on network pharmacology and fingerprint].

Astragali Radix is one of the most commonly used medicinal materials. In recent years, its cultivated varieties and a variety of adulterants have flooded the market, which makes its quality uneven, and the development of quality control methods has become a research hotspot. Therefore, figuring out the quality markers of Astragali Radix is of great significance for its comprehensive evaluation. In this study, the fingerprints of 15 batches of Astragali Radix were established by HPLC, and the main components causing intergroup differences were screened out by PLS-DA. On the basis of literature review and network pharmacology analysis, the targets and pathways of active ingredients were obtained from SwissTargetPrediction, PubChem Compound and other databases, and then the "component-target-pathway" network was constructed with Cytoscape 3.7.1 for the prediction of potential quality markers. Twenty-eight common peaks were identified in the established fingerprint, and three differential components were selected as potential quality markers for Astragali Radix, which were astragaloside Ⅳ, calycosin-7-O-ß-D-glucoside and ononin. The proposed method based on HPLC fingerprint of Astragali Radix is convenient and feasible, facilitating the improvement in its quality control.

[Comparative study of Astragali Radix Praeparata cum Melle and Hedysari Radix Praeparata cum Melle on spleen Qi deficiency rats].

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Advance of sporadic Alzheimer's disease animal models.

Alzheimer's disease (AD), the most common form of dementia, is a progressive neurodegenerative disease. In the past decades, numbers of promising drug candidates showed significant anti-AD effects in preclinical studies but failed in clinical trials. One of the major reasons might be the limitation of appropriate animal models for evaluating anti-AD drugs. More than 95% of AD cases are sporadic AD (sAD). However, the anti-AD drug candidates were mainly tested in the familial AD (fAD) animal models. The diversity between the sAD and fAD might lead to a high failure rate during the development of anti-AD drugs. Therefore, an ideal sAD animal model is urgently needed for the development of anti-AD drugs. Here, we summarized the available sAD animal models, including their methodology, pathologic features, and potential underlying mechanisms. The limitations of these sAD animal models and future trends in the field were also discussed.

Bone marrow mesenchymal stem cell-derived exosomal miR-144-5p improves rat ovarian function after chemotherapy-induced ovarian failure by targeting PTEN.

Chemotherapy-induced premature ovarian failure (POF) in women is currently clinically irreversible. Bone marrow mesenchymal stem cells (BMSCs) are a promising cellular therapeutic strategy for POF. However, the underlying mechanism governing the efficacy of BMSCs in treating POF has not been determined. In this study, we show that BMSC and BMSC-derived exosome transplantation can significantly recover the estrus cycle, increase the number of basal and sinus follicles in POF rats, increase estradiol (E2) and anti-Mullerian hormone (AMH) levels, and reduce follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels in the serum. Furthermore, we demonstrate that BMSC-derived exosomes prevent ovarian follicular atresia in cyclophosphamide (CTX)-treated rats via the delivery of miR-144-5p, which can be transferred to cocultured CTX-damaged granulosa cells (GCs) to decrease GC apoptosis. A functional assay revealed that overexpression of miR-144-5p in BMSCs showed efficacy against CTX-induced POF, and the improvement in the repair was related to the inhibition of GC apoptosis by targeting PTEN. The opposite effect was exhibited when miR-144-5p was inhibited. Taken together, our experimental results provide new information regarding the potential of using exosomal miR-144-5p to treat ovarian failure.

18F-FDG uptake velocity but not uptake level is associated with progression of carotid plaque.

OBJECTIVES: The objective of this study was to evaluate whether baseline 18F-fluorodeoxyglucose (FDG) uptake is associated with carotid plaque progression. METHODS: A total of 156 subjects with carotid plaque were enrolled and underwent carotid magnetic resonance imaging (MRI) (at baseline and the 12-month follow-up) and positron emission tomography-computed tomography (PET-CT) (baseline). Carotid plaque progression was evaluated by two indices (the incidence of plaque progression and percentage of plaque increase) with three-dimensional (3D) imaging, while the 18F-FDG uptake was evaluated by the 18F-FDG uptake levels and 18F-FDG uptake velocity. The association between plaque progression and 18F-FDG uptake was investigated by the trend test and multivariate logistic regression analysis. RESULTS: Of the 156 subjects, 80 (51.3%) showed carotid plaque progression during the 12-month follow-up. Firstly, no association was found between 18F-FDG uptake levels and plaque progression. Secondly, significant differences in the incidence of plaque progression were observed among the groups with different uptake velocities, showing a significant decreasing trend ranging from high to intermediate to low (p = 0.002, trend test). After adjusting for covariates, an adequate prediction of the 18F-FDG uptake velocity for the incidence of plaque progression was revealed (OR = 0.682, p < 0.05). In addition, no association was found between the 18F-FDG uptake velocity and the percentage of plaque increase in the subjects with plaque progression (p = 0.757, trend test). CONCLUSIONS: Our findings suggest 18F-FDG uptake velocity is independently associated with the incidence of carotid plaque progression. Additionally, the 18F-FDG uptake velocity, as another important parameter of PET-CT, warrants further study in future clinical research. KEY POINTS: • The18F-FDG uptake levels were not associated with the carotid plaque progression. • The18F-FDG uptake velocity could predict the incidence of carotid plaque progression. • The18F-FDG uptake velocity with related factors warrants more attention in future clinical research.

Anti-ß2GPI antibodies enhance atherosclerosis in ApoE-deficient mice.

Accelerated atherosclerosis often occurs in patients with antiphospholipid syndrome (APS), and auto-antibodies to ß2 glycoprotein I (anti-ß2GPI) are confirmed as pathogenic antibodies to APS. Our previous studies have demonstrated that the conversion of mouse peritoneal macrophages into foam cells could be enhanced by co-existence of ß2GPI and anti-ß2GPI IgG, but this phenomenon has not been explored in vivo. Here, we present a mouse model to observe the effect of anti-ß2GPI IgG in the development of atherosclerosis. Male ApoE-deficient mice were intraperitoneally injected with anti-ß2GPI IgG (100 µg/mouse) and homologous control IgG (100 µg/mouse) every week for 16 weeks. Plasma lipid composition, magnetic resonance imaging (MRI) and histological staining were used to evaluate vascular inflammation, lumen stenosis and plaque stability. The results showed that the levels of total cholesterol, triglycerol and low-density lipoprotein-cholesterol in plasma were not changed in all mice fed with high-fat diet, but the level of high-density lipoprotein-cholesterol was lower and the atherosclerosis index was significantly increased in HD + anti-ß2GPI group than in other high-fat diet groups. In addition, compared with NR IgG-treated mice, anti-ß2GPI IgG-treated mice showed more lipid deposition in the carotid artery, markedly narrowed arteriolar lumen as well as higher MMP-9 expression, more macrophages and fewer collagen fibers in the aortic arch root. Furthermore, the aortic mRNA levels of TNF-α, IL-1ß, and MCP-1 were significantly increased in anti-ß2GPI IgG-treated mice. Together, these data indicate that anti-ß2GPI IgG increases vascular inflammation, aggravates atherosclerosis and promotes the formation of vulnerable plaque in ApoE-deficient mice.