Maternal obesity disrupts both placental angiogenesis and fetus development. However, the links between adipocytes and endothelial cells in maternal obesity are not fully understood. The aim of this ...study was to characterize exosome-enriched miRNA from obese sow’s adipose tissue and evaluate the effect on angiogenesis of endothelial cells. Plasma exosomes were isolated and analyzed by nanoparticle tracking analysis (NTA), electron morphological analysis, and protein marker expression. The number of exosomes was increased as the gestation of the sows progressed. In addition, we found that exosomes derived from obese sows inhibited endothelial cell migration and angiogenesis. miRNA detection showed that miR-221, one of the miRNAs, was significantly enriched in exosomes from obese sows. Further study demonstrated that exosomal miR-221 inhibited the proliferation and angiogenesis of endothelial cells through repressing the expression of Angptl2 by targeting its 3′ untranslated region. In summary, miR-221 was a key component of the adipocyte-secreted exosomal vesicles that mediate angiogenesis. Our study may be a novel mechanism showing the secretion of “harmful” exosomes from obesity adipose tissues causes placental dysplasia during gestation.
Aim: The purpose of this study was to investigate the effect of esmolol (ES) on LPS-induced cardiac injury and the possible mechanism. Methods: Sepsis was induced by i.p. injection of LPS (10 mg/kg) ...in male Sprague-Dawley rats pretreated with ES, 3-methyladenine or rapamycin. The severity of myocardial damage was analyzed by hematoxylin-eosin staining, and myocardial damage scores were calculated. The concentration of cardiac troponin was measured by enzyme-linked immunosorbent assay. The expression of autophagy-related proteins (beclin-1, LC3-II, p-AMPK, p-ULK1, p-mTOR) in myocardial tissue was detected by Western blotting. Autophagosome formation and the ultrastructural damage of mitochondria were assessed using transmission electron microscopy. Results: LPS induced an increase in myocardial damage score in a time-dependent manner, accompanied with an increase in autophagy at 3 h and decrease in autophagy at 6, 12, and 24 h. Pretreatment of LPS-treated rats with ES or rapamycin reduced myocardial injury (release of cardiac troponin, myocardial damage score) and increased autophagy (LC3-II, beclin-1, p-AMPK, and p-ULK1 levels and autophagosome numbers) at 12 and 24 h. In contrast, 3-methyladenine showed no effect. Conclusion: Esmolol alleviates LPS-induced myocardial damage through activating the AMPK/mTOR/ULK1 signal pathway-regulated autophagy.
Cyclocarya paliurus (Batal.) Iljinskaja, a unique species growing in southern China, is a multi-function tree species with medicinal, healthcare, material, and ornamental values. So far, sexual ...reproduction is the main method for extensive cultivation of
plantations, but this is limited by low seed plumpness resulted from the character of heterodichogamy. Phenological observations have revealed the asynchronism of flower development in this species. However, its molecular mechanism remains largely unknown. To reveal molecular mechanism of heterodichogamy in C. paliurus, transcriptome of female (F) and male (M) buds from two mating types (protandry, PA; protogyny, PG) at bud break stage were sequenced using Illumina Hiseq 4000 platform. The expression patterns of both 32 genes related to flowering and 58 differentially expressed transcription factors (DETFs) selected from 6 families were divided four groups (PG-F, PG-M, PA-F, and PA-M) into two categories: first flowers (PG-F and PA-M) and later flowers (PA-F and PG-M). The results indicated that genes related to plant hormones (IAA, ABA, and GA) synthesis and response, glucose metabolism, and transcription factors (especially in MIKC family) played significant roles in regulating asynchronism of male and female flowers in the same mating type. The expression of DETFs showed two patterns. One contained DETFs up-regulated in first flowers in comparison to later flowers, and the other was the reverse. Nine genes related to flowering were selected for qRT-PCR to confirm the accuracy of RNA-seq, and generally, the RPKM values of these genes were consistent with the result of qRT-PCR. The results of this work could improve our understanding in asynchronism of floral development within one mating type in C. paliurus at transcriptional level, as well as lay a foundation for further study in heterodichogamous plants.
This study aimed to help improve the diagnosis and treatment of isolated myeloid sarcoma. We report the case of a female adolescent patient with isolated meningeal myeloid sarcoma. She was admitted ...to our department because of vomiting, headache and hearing loss. Positron emission tomography-computed tomography and brain magnetic resonance imaging showed multiple intracranial space-occupying lesions. A complete examination, including morphology, cytology, immunophenotyping, cytogenetics and molecular biology tests of cerebrospinal fluid and bone marrow, was conducted. The diagnosis of primary myeloid sarcoma of the central nervous system with mixed lineage leukemia gene rearrangement with AF6 was established. The patient underwent systemic chemotherapy and intrathecal treatment followed by whole-brain radiotherapy. She achieved complete remission for 84 months and has not developed bone marrow involvement during follow-up. The combination of morphology, cytology, flow cytometry, cytogenetics and molecular analysis can improve the definite diagnosis of isolated myeloid sarcoma.
Climactic oscillations during the Quaternary played a significant role in the formation of genetic diversity and historical demography of numerous plant species in northwestern China. In this study, ...we used 11 simple sequence repeats derived from expressed sequence tag (EST-SSR), two chloroplast DNA (cpDNA) fragments, and ecological niche modeling (ENM) to investigate the population structure and the phylogeographic history of
Lycium ruthenicum
, a plant species adapted to the climate in northwestern China. We identified 20 chloroplast haplotypes of which two were dominant and widely distributed in almost all populations. The species has high haplotype diversity and low nucleotide diversity based on the cpDNA data. The EST-SSR results showed a high percentage of total genetic variation within populations. Both the cpDNA and EST-SSR results indicated no significant differentiation among populations. By combining the evidence from ENM and demographic analysis, we confirmed that both the last interglacial (LIG) and late-glacial maximum (LGM) climatic fluctuations, aridification might have substantially narrowed the distribution range of this desert species, the southern parts of the Junggar Basin, the Tarim Basin, and the eastern Pamir Plateau were the potential glacial refugia for
L. ruthenicum
during the late middle Pleistocene to late Pleistocene Period. During the early Holocene, the warm, and humid climate promoted its demographic expansion in northwestern China. This work may provide new insights into the mechanism of formation of plant diversity in this arid region.
The success of future clinical trials with oncolytic viruses depends on the identification and the control of mechanisms that modulate their therapeutic efficacy. In particular, little is known about ...the role of autophagy in infection by attenuated measles virus of the Edmonston strain (MV-Edm). We investigated the interaction between autophagy, innate immune response, and oncolytic activity of MV-Edm, since the antiviral immune response is a known factor limiting virotherapies. We report that MV-Edm exploits selective autophagy to mitigate the innate immune response mediated by DDX58/RIG-I like receptors (RLRs) in non-small cell lung cancer (NSCLC) cells. Both RNA interference (RNAi) and overexpression approaches demonstrate that autophagy enhances viral replication and inhibits the production of type I interferons regulated by RLRs. We show that MV-Edm unexpectedly triggers SQSTM1/p62-mediated mitophagy, resulting in decreased mitochondrion-tethered mitochondrial antiviral signaling protein (MAVS) and subsequently weakening the innate immune response. These results unveil a novel infectious strategy based on the usurpation of mitophagy leading to mitigation of the innate immune response. This finding provides a rationale to modulate autophagy in oncolytic virotherapy.
In vitro studies, preclinical experiments in vivo, and clinical trials with humans all indicate that oncolytic viruses hold promise for cancer therapy. Measles virus of the Edmonston strain (MV-Edm), which is an attenuated virus derived from the common wild-type measles virus, is paradigmatic for therapeutic oncolytic viruses. MV-Edm replicates preferentially in and kills cancer cells. The efficiency of MV-Edm is limited by the immune response of the host against viruses. In our study, we revealed that MV-Edm usurps a homeostatic mechanism of intracellular degradation of mitochondria, coined mitophagy, to attenuate the innate immune response in cancer cells. This strategy might provide a replicative advantage for the virus against the development of antiviral immune responses by the host. These findings are important since they may not only indicate that inducers of autophagy could enhance the efficacy of oncolytic therapies but also provide clues for antiviral therapy by targeting SQSTM1/p62-mediated mitophagy.
BackgroundHepatitis B virus (HBV) reactivation is commonly seen in HBsAg-positive hematologic patients undergoing immunosuppressive chemotherapy. Little is known about the risk of HBV reactivation ...after chimeric antigen receptor T-cell (CAR T) immunotherapy for the treatment of refractory/relapsed malignant B-cell lymphoma.Case presentationWe report a patient who underwent antiviral prophylaxis for 26 months and who discontinued treatment by herself 1 month after the sequential infusion of two specific, third-generation anti-CD19 and anti-CD22 CAR T cell immunotherapies for refractory/relapsed diffuse large B-cell lymphoma. Remission of the primary disease was achieved after two and half months, but she was admitted with a 7-day history of vomiting, jaundice, itching and dark urine. After excluding other possible causes of acute liver damage, HBV reactivation was suspected. HBV-DNA was 4,497,000 IU/mL at that time. Following the reintroduction of entecavir, a decline in the HBV-DNA copies was observed, but ALT, AST and bilirubin were elevated, and there was no improvement of the clinical conditions. She passed away because of hepatic encephalopathy and multiple organ dysfunction syndrome 40 days after admission.ConclusionsOur study provides the first report of the severe, early reactivation of an inactive HBsAg carrier after CAR T cell therapy in DLBCL.Trial registration ChiCTR-OPN-16008526.
In recent years, symmetrical
α,α′,δ,δ′
-tetramethyl-cucurbit6uril (TMeQ6) has attracted much attention from many researchers due to its interesting assembly pattern. Herein, we have investigated the ...host–guest interactions pattern of the symmetric TMeQ6 with (E)-1-(5-carboxypentyl)-4-(2-(pyridin-4-yl)vinyl)pyridin-1-ium. (ECPP). Furthermore, their binding behaviors were investigated by
1
H NMR spectroscopy, MALDI-TOF mass spectrometry, isothermal titration calorimeter, fluorescence, and UV–vis spectrum. The results indicate that TMeQ6 and ECPP form host–guest complexes in a host/guest molar ratio of 1:1. TMeQ6 is bound with the vinylpyridine group of ECPP. In addition, TMeQ6-ECPP exhibits a high association constant Ka = (1.520 ± 0.58) × 10
6
M
−1
, ΔH = − 53.40 kJ/mol, ΔS = − 60 J/mol·K. which provides a promising foundation for potential studies of the assemblies.
Graphical abstract
Abstract Objective Increased platelet activity predicts adverse cardiovascular events. The objective was to assess the effects of long-chain omega-3 polyunsaturated fatty acid ( n -3 ...PUFA)-supplementation on platelet aggregation. Methods and results We conducted a meta-analysis of randomized controlled trials identified using PubMed, Embase and the Cochrane Library. Fifteen studies were included. In comparison to placebo using the random-effect model, n -3 PUFA-supplementation significantly reduced adenosine diphosphate-induced platelet aggregation (standard mean difference SMD = −1.23 with 95% confidence interval CI −2.24 to −0.23, p = 0.02) and platelet aggregation units, determined using the VerifyNow® rapid platelet-function assay system (SMD = −6.78 with 95% CI −12.58 to −0.98, p = 0.02). There was a trend toward decreased collagen-induced (SMD = −0.70 with 95% CI −0.72 to 0.33, p = 0.18) and arachidonic acid-induced platelet aggregation (SMD = −0.43 with 95% CI −2.26 to 1.40, p = 0.64) compared with controls; however, statistical significance was not reached. Conclusions Our meta-analysis demonstrates that n -3 PUFA-supplementation is associated with a significant reduction in platelet aggregation when the participants were at poor health status, but not in healthy persons. High-risk patients with cardiovascular disease and even diabetics may potentially benefit from n -3 PUFAs therapy. However, n -3 PUFAs may not be effective in primary prevention. Larger trials need to be carried out to confirm the present findings.
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