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1.
J Int Med Res ; 49(2): 300060521993315, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33641489

RESUMO

OBJECTIVE: Myocardial ischemia/reperfusion (I/R) injury causes various severe heart diseases, including myocardial infarction. This study aimed to determine the therapeutic effect of atractylenolide I (ATR-I), which is an active ingredient isolated from Atractylodes macrocephala, on myocardial I/R injury. METHODS: Male Sprague-Dawley rats were randomly allocated to the five following groups (nine rats/group): control, I/R, and I/R + ATR-I preconditioning (10, 50, and 250 µg). The effects of ATR-I on rats with I/R injury were verified in cardiomyocytes with hypoxia/reoxygenation. Production of reactive oxygen species was determined. The proliferative ability of cardiomyocytes was detected using the bromodeoxyuridine assay. Mitochondrial membrane potential was measured using flow cytometry. Cellular apoptosis was assessed by flow cytometry and the terminal dUTP-digoxigenin nick end labeling assay. RESULTS: I/R and hypoxia/reoxygenation injury increased mitochondrial dysfunction and activated caspase-3 and Bax/B cell lymphoma 2 expression in vitro and in vivo. ATR-I pretreatment dose-dependently significantly attenuated myocardial apoptosis and suppressed oxidative stress as reflected by increased mitochondrial DNA copy number and superoxide dismutase activity, and decreased reactive oxygen species and Ca2+ content. CONCLUSION: ATR-I protects against I/R injury by protecting mitochondrial function and inhibiting activation of caspase-3.

2.
Environ Int ; 151: 106444, 2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33621917

RESUMO

Oral bioavailability of arsenic (As) determines levels of As exposure via ingestion of As-contaminated soil, however, the role of gut microbiota in As bioavailability has not evaluated in vivo although some in vitro studies have investigated this. Here, we made a comparison in As relative bioavailability (RBA) estimates for a contaminated soil (3913 mg As kg-1) using a mouse model with and without penicillin perturbing gut microbiota and metabolites. Compared to soil exposure alone (2% w/w soil in diets), addition of penicillin (100 or 1000 mg kg-1) reduced probiotic Lactobacillus and sulfate-reducing bacteria Desulfovibrio, enriched penicillin-resistant Enterobacter and Bacteroides, and decreased amino acid concentrations in ileum. With perturbed gut microbiota and metabolic profile, penicillin and soil co-exposed mice accumulated 2.81-3.81-fold less As in kidneys, excreted 1.02-1.35-fold less As in urine, and showed lower As-RBA (25.7-29.0%) compared to mice receiving diets amended with soil alone (56 ± 9.63%). One mechanism accounted for this is the decreased concentrations of amino acids arising from the gut microbiota shift which resulted in elevated iron (Fe) and As co-precipitation, leading to reduced As solubilization in the intestine. Another mechanism was conversion of bioavailable inorganic As to less bioavailable monomethylarsonic acid (MMAV) and dimethylarsinic acid (DMAV) by the antibiotic perturbed microflora. Based on in vivo mouse model, we demonstrated the important role of gut microbiota and gut metabolites in participating soil As solubilization and speciation transformation then affecting As oral bioavailability. Results are useful to better understand the role of gut bacteria in affecting As metabolism and the health risks of As-contaminated soils.

3.
BMC Dev Biol ; 21(1): 4, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33517884

RESUMO

BACKGROUND: Our previous study have shown that the PSMD11 protein was an important survival factor for cancer cells except for its key role in regulation of assembly and activity of the 26S proteasome. To further investigate the role of PSMD11 in carcinogenesis, we constructed a conditional exon 5 floxed allele of PSMD11 (PSMD11flx) in mice. RESULTS: It was found that homozygous PSMD11 flx/flx mice showed normal and exhibited a normal life span and fertility, and showed roughly equivalent expression of PSMD11 in various tissues, suggesting that the floxed allele maintained the wild-type function. Cre recombinase could induce efficient knockout of the floxed PSMD11 allele both in vitro and in vivo. Mice with constitutive single allele deletion of PSMD11 derived from intercrossing between PSMD11flx/flx and CMV-Cre mice were all viable and fertile, and showed apparent growth retardation, suggesting that PSMD11 played a significant role in the development of mice pre- or postnatally. No whole-body PSMD11 deficient embryos (PSMD11-/-) were identified in E7.5-8.5 embryos in uteros, indicating that double allele knockout of PSMD11 leads to early embryonic lethality. To avoid embryonic lethality produced by whole-body PSMD11 deletion, we further developed conditional PSMD11 global knockout mice with genotype Flp;FSF-R26CAG - CreERT2/+; PSMD11 flx/flx, and demonstrated that PSMD11 could be depleted in a temporal and tissue-specific manner. Meanwhile, it was found that depletion of PSMD11 could induce massive apoptosis in MEFs. CONCLUSIONS: In summary, our data demonstrated that we have successfully generated a conditional knockout allele of PSMD11 in mice, and found that PSMD11 played a key role in early and postnatal development in mice, the PSMD11 flx/flx mice will be an invaluable tool to explore the functions of PSMD11 in development and diseases.

4.
J Clin Apher ; 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33587767

RESUMO

BACKGROUND: Since early 2020, convalescent plasma has been widely used for treating coronavirus disease 2019 (COVID-19). There is limited information regarding donor tolerability of convalescent plasma donation. In this study, we evaluated the short-term donor tolerability of convalescent plasma donation. METHODS: A prospective study of 309 convalescent plasma donation related adverse events were conducted at Wuhan Blood Center of China, from February 12 to April 1, 2020. Additionally, up to 28-day post-donation follow-ups were performed on the donors. RESULTS: Sixteen (5.2%) adverse events were reported in 309 donations. All of these were mild vasovagal without loss of consciousness. The frequency of adverse reactions was higher in donors with a per donation volume of >8 mL/kg body weight or ≥ 600 mL, <100 mm Hg in pre-donation systolic blood pressure, or less than 28 days from the onset of COVID-19 symptoms. There was no correlation to donation history, weight, sex, ABO blood type, pre-donation diastolic blood pressure, pulse, or hemoglobin. CONCLUSION: The donation of convalescent plasma is generally safe. Mitigation of risk factors associated with adverse events can further enhance donor tolerability of convalescent plasma donation.

5.
Acta Pharmacol Sin ; 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33589794

RESUMO

Proliferation of vascular smooth muscle cells (VSMCs) greatly contributes to vascular remodeling in hypertension. This study is to determine the roles and mechanisms of miR-135a-5p intervention in attenuating VSMC proliferation and vascular remodeling in spontaneously hypertensive rats (SHRs). MiR-135a-5p level was raised, while fibronectin type III domain-containing 5 (FNDC5) mRNA and protein expressions were reduced in VSMCs of SHRs compared with those of Wistar-Kyoto rats (WKYs). Enhanced VSMC proliferation in SHRs was inhibited by miR-135a-5p knockdown or miR-135a-5p inhibitor, but exacerbated by miR-135a-5p mimic. VSMCs of SHRs showed reduced myofilaments, increased or even damaged mitochondria, increased and dilated endoplasmic reticulum, which were attenuated by miR-135a-5p inhibitor. Dual-luciferase reporter assay shows that FNDC5 was a target gene of miR-135a-5p. Knockdown or inhibition of miR-135a-5p prevented the FNDC5 downregulation in VSMCs of SHRs, while miR-135a-5p mimic inhibited FNDC5 expressions in VSMCs of both WKYs and SHRs. FNDC5 knockdown had no significant effects on VSMC proliferation of WKYs, but aggravated VSMC proliferation of SHRs. Exogenous FNDC5 or FNDC5 overexpression attenuated VSMC proliferation of SHRs, and prevented miR-135a-5p mimic-induced enhancement of VSMC proliferation of SHR. MiR-135a-5p knockdown in SHRs attenuated hypertension, normalized FNDC5 expressions and inhibited vascular smooth muscle proliferation, and alleviated vascular remodeling. These results indicate that miR-135a-5p promotes while FNDC5 inhibits VSMC proliferation in SHRs. Silencing of miR-135a-5p attenuates VSMC proliferation and vascular remodeling in SHRs via disinhibition of FNDC5 transcription. Either inhibition of miR-135a-5p or upregulation of FNDC5 may be a therapeutically strategy in attenuating vascular remodeling and hypertension.

6.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(2): 141-144, 2021 Feb 10.
Artigo em Chinês | MEDLINE | ID: mdl-33565067

RESUMO

OBJECTIVE: To investigate the clinical characteristics and genetic variant in a Chinese pedigree affected with thiamine pyrophosphokinase deficiency (TPKD). METHODS: Clinical data of the pedigree were analyzed retrospectively and summarized from the perspectives of clinical manifestation, magnetic resonance imaging (MRI), and genotype. Relevant literature was also reviewed. RESULTS: The proband, a female, has developed paroxysmal ataxia with dystonia at the age of 2-year-and-8-month. The ataxia has recurred for 7-8 times. The child had died at 11 years old due to recurrence and aggravation of the disease. MRI showed diffuse symmetrical lesions of brain parenchyma and spinal cord. Her brother had similar symptoms and died at 6. The parents were consanguineous but healthy. Genetic testing revealed that the girl has carried homozygous c.161C>T variants of the TPK1 gene, suggesting the diagnosis of TPKD. So far 15 cases of TPKD have been reported, among which 9 were from consanguineous marriages. The disease usually occurs before the age of 3, and most patients had featured paroxysmal encephalopathy and recurrent infections. Symmetrical celebral cortex, basal ganglia and cerebellum lesions were common. Missense mutations of the TPK1 gene were common. Vitamin B1 was effective in some cases. CONCLUSION: For infants featuring encephalopathy, ataxia, dystonia and other phenotypes, early genetic testing should be recommended in order to provide guidance for clinical treatment and genetic counseling.


Assuntos
Testes Genéticos , Tiamina Pirofosfoquinase/deficiência , Tiamina Pirofosfoquinase/genética , Criança , China , Feminino , Humanos , Lactente , Imagem por Ressonância Magnética , Masculino , Mutação , Linhagem , Estudos Retrospectivos
7.
Artigo em Inglês | MEDLINE | ID: mdl-33621178

RESUMO

We propose a new video vectorization approach for converting videos in the raster format to vector representation with the benefits of resolution independence and compact storage. Through classifying extracted curves on each video frame as salient ones and non-salient ones, we introduce a novel bipartite diffusion curves (BDCs) representation in order to preserve both important image features such as sharp boundaries and regions with smooth color variation. This bipartite representation allows us to propagate non-salient curves across frames such that the propagation in conjunction with geometry optimization and color optimization of salient curves ensures the preservation of fine details within each frame and across different frames, and meanwhile, achieves good spatial-temporal coherence. Thorough experiments on a variety of videos show that our method is capable of converting videos to the vector representation with low reconstruction errors, low computational cost and fine details, demonstrating our superior performance over the state-of-the-arts. Our approach can also produce comparable results to video super-resolution.

8.
J Biomed Inform ; 115: 103693, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33540076

RESUMO

BACKGROUND: Diabetics has become a serious public health burden in China. Multiple complications appear with the progression of diabetics pose a serious threat to the quality of human life and health. We can prevent the progression of prediabetics to diabetics and delay the progression to diabetics by early identification of diabetics and prediabetics and timely intervention, which have positive significance for improving public health. OBJECTIVE: Using machine learning techniques, we establish the noninvasive diabetics risk prediction model based on tongue features fusion and predict the risk of prediabetics and diabetics. METHODS: Applying the type TFDA-1 Tongue Diagnosis Instrument, we collect tongue images, extract tongue features including color and texture features using TDAS, and extract the advanced tongue features with ResNet-50, achieve the fusion of the two features with GA_XGBT, finally establish the noninvasive diabetics risk prediction model and evaluate the performance of testing effectiveness. RESULTS: Cross-validation suggests the best performance of GA_XGBT model with fusion features, whose average CA is 0.821, the average AUROC is 0.924, the average AUPRC is 0.856, the average Precision is 0.834, the average Recall is 0.822, the average F1-score is 0.813. Test set suggests the best testing performance of GA_XGBT model, whose average CA is 0.81, the average AUROC is 0.918, the average AUPRC is 0.839, the average Precision is 0.821, the average Recall is 0.81, the average F1-score is 0.796. When we test prediabetics with GA_XGBT model, we find that the AUROC is 0.914, the Precision is 0.69, the Recall is 0.952, the F1-score is 0.8. When we test diabetics with GA_XGBT model, we find that the AUROC is 0.984, the Precision is 0.929, the Recall is 0.951, the F1-score is 0.94. CONCLUSIONS: Based on tongue features, the study uses classical machine learning algorithm and deep learning algorithm to maximum the respective advantages. We combine the prior knowledge and potential features together, establish the noninvasive diabetics risk prediction model with features fusion algorithm, and detect prediabetics and diabetics noninvasively. Our study presents a feasible method for establishing the association between diabetics and the tongue image information and prove that tongue image information is a potential marker which facilitates effective early diagnosis of prediabetics and diabetics.

9.
Transl Oncol ; 14(5): 101032, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33618238

RESUMO

BACKGROUND: Machine learning (ML) has been gradually integrated into oncologic research but seldom applied to predict cervical cancer (CC), and no model has been reported to predict survival and site-specific recurrence simultaneously. Thus, we aimed to develop ML models to predict survival and site-specific recurrence in CC and to guide individual surveillance. METHODS: We retrospectively collected data on CC patients from 2006 to 2017 in four hospitals. The survival or recurrence predictive value of the variables was analyzed using multivariate Cox, principal component, and K-means clustering analyses. The predictive performances of eight ML models were compared with logistic or Cox models. A novel web-based predictive calculator was developed based on the ML algorithms. RESULTS: This study included 5112 women for analysis (268 deaths, 343 recurrences): (1) For site-specific recurrence, larger tumor size was associated with local recurrence, while positive lymph nodes were associated with distant recurrence. (2) The ML models exhibited better prognostic predictive performance than traditional models. (3) The ML models were superior to traditional models when multiple variables were used. (4) A novel predictive web-based calculator was developed and externally validated to predict survival and site-specific recurrence. CONCLUSION: ML models might be a better analytic approach in CC prognostic prediction than traditional models as they can predict survival and site-specific recurrence simultaneously, especially when using multiple variables. Moreover, our novel web-based calculator may provide clinicians with useful information and help them make individual postoperative follow-up plans and further treatment strategies.

10.
BMC Med Inform Decis Mak ; 21(1): 72, 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33627103

RESUMO

BACKGROUND: Fatigue is a kind of non-specific symptom, which occurs widely in sub-health and various diseases. It is closely related to people's physical and mental health. Due to the lack of objective diagnostic criteria, it is often neglected in clinical diagnosis, especially in the early stage of disease. Many clinical practices and researches have shown that tongue and pulse conditions reflect the body's overall state. Establishing an objective evaluation method for diagnosing disease fatigue and non-disease fatigue by combining clinical symptom, index, and tongue and pulse data is of great significance for clinical treatment timely and effectively. METHODS: In this study, 2632 physical examination population were divided into healthy controls, sub-health fatigue group, and disease fatigue group. Complex network technology was used to screen out core symptoms and Western medicine indexes of sub-health fatigue and disease fatigue population. Pajek software was used to construct core symptom/index network and core symptom-index combined network. Simultaneously, canonical correlation analysis was used to analyze the objective tongue and pulse data between the two groups of fatigue population and analyze the distribution of tongue and pulse data. RESULTS: Some similarities were found in the core symptoms of sub-health fatigue and disease fatigue population, but with different node importance. The node-importance difference indicated that the diagnostic contribution rate of the same symptom to the two groups was different. The canonical correlation coefficient of tongue and pulse data in the disease fatigue group was 0.42 (P < 0.05), on the contrast, correlation analysis of tongue and pulse in the sub-health fatigue group showed no statistical significance. CONCLUSIONS: The complex network technology was suitable for correlation analysis of symptoms and indexes in fatigue population, and tongue and pulse data had a certain diagnostic contribution to the classification of fatigue population.

11.
Int Immunopharmacol ; 93: 107426, 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33550032

RESUMO

Mast cells (MCs) are crucial effectors in inflammation and allergic reactions. The Mas-related G-protein-coupled receptor X2 (MRGPRX2) was the MC-specific receptor and play a key role in IgE-independent allergic reactions. The activation of the Nuclear factor erythroid derived 2-related factor 2 (Nrf2) is involved in IgE-mediated MC degranulation. Resveratrol (Res) is a polyphenolic compound in red wine and has been reported to exert a variety of pharmacological effects. In the current study, we investigated the effect of Res in regulating MRGPRX2-mediated MC activation and its underlyingmechanism. We demonstrated that Res reduced compound 48/80 (C48/80)-induced calcium flux in MCs and inhibited MCs degranulation in vitro. Res also suppressed C48/80-induced hind paw extravasation, active systemic anaphylaxis, and MCs degranulation in mouse models of pseudo-allergy in vivo. Furthermore, PCR and immunohistochemistry assay suggest that Res up-regulates Nrf2 expression and Nrf2 inhibitor attenuates the protective effects of Res. In conclusion, Res exerts an inhibitory effect on MRGPRX2-mediated MCs activation by targeting Nrf2 pathway and may present a promising new therapeutic agent for the treatment of MRGPRX2-dependent anaphylactoid reactions.

12.
Mol Med ; 27(1): 20, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33637046

RESUMO

BACKGROUND: Transplantation of bone marrow-derived mesenchymal stem cells (BM-MSCs) embedded in a bio-compatible matrix has been demonstrated as a promising strategy for the treatment of bone defects. This study was designed to explore the effect and mechanism of exosomes derived from mature dendritic cells (mDC-Exo) on the BM-MSCs-mediated bone regeneration using the matrix support in an athymic rat model of femoral bone defect. METHODS: The BM-MSCs were isolated from rats and incubated with osteoblast induction medium, exosomes derived from immature DCs (imDC-Exo), mDC-Exo, and miR-335-deficient mDC-Exo. BM-MSCs treated without or with mDC-Exo were embedded in a bio-compatible matrix (Orthoss®) and then implanted into the femoral bone defect of athymic rats. RESULTS: mDC-Exo promoted the proliferation and osteogenic differentiation of BM-MSCs by transferring miR-335. Mechanistically, exosomal miR-335 inhibited Hippo signaling by targeting large tongue suppressor kinase 1 (LATS1) and thus promoted the proliferation and osteogenic differentiation of BM-MSCs. Animal experiments showed that mDC-Exo enhanced BM-MSCs-mediated bone regeneration after bone defect, and this effect was abrogated when miR-335 expression was inhibited in mDC-Exo. CONCLUSION: mDC-Exo promoted osteogenic differentiation of BM-MSCs and enhanced BM-MSCs-mediated bone regeneration after femoral bone defect in athymic rats by transferring miR-335.

13.
Int Heart J ; 62(1): 181-185, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33518657

RESUMO

Libman-Sacks endocarditis, characterized by verrucous vegetations formation, is a typical cardiac manifestation of autoimmune diseases such as systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). Although typically mild and asymptomatic, Libman-Sacks endocarditis can lead to serious complications, including thromboembolic events, superimposed bacterial endocarditis, and severe valvular regurgitation and/or stenosis, and valve surgery may be required. Here, we report a case of mitral valve repair for a large Libman-Sacks vegetation in a 29-year-old woman with a history of APS with cerebral infarction. Transesophageal echocardiography (TEE) demonstrated an isolated large mobile vegetation on the atrial side of posterior mitral valve leaflet, with severe mitral regurgitation. Next, we organized a multidisciplinary team meeting to better evaluate the case before performing the surgery. To prevent further thromboembolic events, and due to the insufficiency of the mitral valve, the patient was accepted for mitral valve surgery, and she was discharged uneventfully 10 days after successful surgery. She was managed with long-term anticoagulation medicine after surgery and followed up for 2 years with no complications. The present case showed mitral repair is feasible and effective in young female patients of child-bearing age, and the lesion only localized mitral valve abnormalities caused by Libman-Sacks endocarditis.


Assuntos
Síndrome Antifosfolipídica/complicações , Endocardite/cirurgia , Anuloplastia da Valva Mitral , Adulto , Ecocardiografia , Endocardite/diagnóstico por imagem , Endocardite/etiologia , Feminino , Humanos
14.
Nano Lett ; 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33622034

RESUMO

Nanoscale artificial antigen-presenting cells (aAPCs) are promising to activate T cells directly for cancer immunotherapy, while feasible and flexible strategy to develop nanoscale aAPCs remains highly desirable. Metabolic glycoengineering is used to decorate chemical tags on cells which enables bioorthogonal chemical conjugation of functional molecules. Herein, we develop a nanoscale aAPC by metabolic dendritic cell (DC) labeling to mobilize T-cell based antitumor immunity. We coat azido-labeled DC membrane on imiquimod-loaded polymeric nanoparticles and sequentially modify anti-CD3ε antibody via click chemistry. The nanoscale aAPCs perform improved distribution in lymph nodes and stimulate T cells and resident APCs. Significant inhibition of tumor inoculation and growth is observed after the vaccination, which can be further improved by combining antiprogrammed cell death receptor 1 (PD1) therapy. Our results demonstrate the promising application of metabolically labeled DCs for designing nanoscale aAPCs, which provide a simple and general strategy to potentiate cancer immunotherapy.

15.
J Med Virol ; 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33580518

RESUMO

Since December 2019, the new coronavirus (also known as severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2, 2019-nCoV])-induced disease, COVID-19, has spread rapidly worldwide. Studies have reported that the traditional Chinese medicine Salvia miltiorrhiza possesses remarkable antiviral properties; however, the anti-coronaviral activity of its main components, salvianolic acid A (SAA), salvianolic acid B (SAB), and salvianolic acid C (SAC) is still debated. In this study, we used Cell Counting Kit-8 staining and flow cytometry to evaluate the toxicity of SAA, SAB, and SAC on ACE2 (angiotensin-converting enzyme 2) high-expressing HEK293T cells (ACE2h cells). We found that SAA, SAB, and SAC had a minor effect on the viability of ACE2h cells at concentrations below 100 µM. We further evaluated the binding capacity of SAA, SAB, and SAC to ACE2 and the spike protein of 2019-nCoV using molecular docking and surface plasmon resonance. They could bind to the receptor-binding domain (RBD) of the 2019-nCoV with a binding constant (KD ) of (3.82 ± 0.43) e-6 M, (5.15 ± 0.64)e-7 M, and (2.19 ± 0.14)e-6 M; and bind to ACE2 with KD (4.08 ± 0.61)e-7 M, (2.95 ± 0.78)e-7 M, and (7.32 ± 0.42)e-7 M, respectively. As a result, SAA, SAB, and SAC were determined to inhibit the entry of 2019-nCoV Spike pseudovirus with an EC50 of 11.31, 6.22, and 10.14 µM on ACE2h cells, respectively. In conclusion, our study revealed that three Salvianolic acids can inhibit the entry of 2019-nCoV spike pseudovirus into ACE2h cells by binding to the RBD of the 2019-nCoV spike protein and ACE2 protein.

16.
J Matern Fetal Neonatal Med ; : 1-9, 2021 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-33491517

RESUMO

OBJECTIVE: Preeclampsia (PE) is a disorder that occurs during the pregnancy and could affect the maternal and perinatal mortality as well as morbidity. The aim of our study is to investigate the associations between the hypertension susceptibility genes ITGA9, MOV10 and CACNB2 with PE in Chinese Han population. METHODS: A case-control study including 178 PE patients and 202 healthy controls was conducted to assess the associations between three loci (ITGA9 rs155524, MOV10 rs2932538 and CACNB2 rs4373814) and PE. The TaqMan probe assay was applied for genotyping in our study. Quantitative real-time PCR was performed to detect the mRNA expression levels of ITGA9, MOV10 and CACNB2. ELISA was carried out to detect the concentration of serum sFlt-1 or PLGF. RESULTS: Our study detected no significant differences in allelic frequencies of three SNPs between PE patients and healthy controls. In the genetic model, the results showed that the patients with ITGA9 rs155524 GA or AA genotypes had a higher risk of PE development compared to those with GG genotype in codominant model. And PE patients had a higher frequency of GA + AA genotypes based on the dominant model. Subgroup analysis showed ITGA9 rs155524 was associated with early-onset PE but not with late-onset PE. No association was observed between MOV10 and CACNB2 with PE in any genetic model and subgroup analysis. Quantitative real-time PCR results showed that ITGA9 mRNA expression level was apparently increased in the placental tissues of PE patients. In addition, ITGA9 expression levels of GA + AA subjects were apparently higher than that in the genotype GG of placental tissues. sFlt-1/PLGF ratio was higher in GA + AA subjects than that in GG subjects. Regression analysis revealed that ratio of sFlt-1/PLGF was positively correlated with ITGA9 mRNA expression level. CONCLUSION: This study has identified ITGA9 is a promising candidate susceptibility gene for early-onset PE. Our findings demonstrated that the high expression of ITGA9 might be associated with an increased risk of PE.

17.
Vox Sang ; 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-33423307

RESUMO

BACKGROUND AND OBJECTIVES: Haemovigilance involves surveillance of the whole chain of blood transfusion with the aim of identifying adverse events and errors and improving outcomes for patients. The Chinese Haemovigilance Network, founded in August 2017, has witnessed a rapid development in the last three years. MATERIALS AND METHODS: Based on the 1,022 cases in 2019, we analysed the adverse reactions (ARs) by blood component, clinical outcome severity and demography of recipients in an effort to publish the first annual Chinese haemovigilance report. RESULTS: The AR rate associated with blood transfusion in 2019 was 0·2% in China. Allergic reactions and FNHTR were the two most common adverse symptoms, accounting for 97·7% of the reports. Two-thirds of the TAD, AHTR and TACO and all of the HTR and DHTR resulted in hospitalization or prolongation of hospitalization. Plasma and AP were usually associated with allergic reaction (81·1%), whereas red cells more commonly cause FNHTR (68·8%) and all the AHTR, HTR, DSTR and DHTR. 84·1% of patients were aged 16 years or over, and the majority of the TAD, AHTR, TACO and HTR involved patients aged 60 and above. The ratio of serious adverse reactions (SARs) was 8·2%. Allergic reaction and FNHTR were top two (85·7%) SARs. The first case related to anti-D immunoglobulin was detected in a DHTR report. CONCLUSION: This report provides the world's first overview of transfusion-related adverse reactions in China. This report is useful for better understanding transfusion risks in China.

18.
J Transl Med ; 19(1): 30, 2021 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-33413461

RESUMO

BACKGROUND: COVID-19 has caused a global pandemic and the death toll is increasing. However, there is no definitive information regarding the type of clinical specimens that is the best for SARS-CoV-2 detection, the antibody levels in patients with different duration of disease, and the relationship between antibody level and viral load. METHODS: Nasopharyngeal swabs, anal swabs, saliva, blood, and urine specimens were collected from patients with a course of disease ranging from 7 to 69 days. Viral load in different specimen types was measured using droplet digital PCR (ddPCR). Meanwhile, anti-nucleocapsid protein (anti-N) IgM and IgG antibodies and anti-spike protein receptor-binding domain (anti-S-RBD) IgG antibody in all serum samples were tested using ELISA. RESULTS: The positive detection rate in nasopharyngeal swab was the highest (54.05%), followed by anal swab (24.32%), and the positive detection rate in saliva, blood, and urine was 16.22%, 10.81%, and 5.41%, respectively. However, some patients with negative nasopharyngeal swabs had other specimens tested positive. There was no significant correlation between antibody level and days after symptoms onset or viral load. CONCLUSIONS: Other specimens could be positive in patients with negative nasopharyngeal swabs, suggesting that for patients in the recovery period, specimens other than nasopharyngeal swabs should also be tested to avoid false negative results, and anal swabs are recommended. The antibody level had no correlation with days after symptoms onset or the viral load of nasopharyngeal swabs, suggesting that the antibody level may also be affected by other factors.


Assuntos
Anticorpos Antivirais/sangue , /virologia , /isolamento & purificação , Carga Viral , Adulto , Idoso , Idoso de 80 Anos ou mais , Canal Anal/virologia , Sangue/virologia , China/epidemiologia , Reações Falso-Negativas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nasofaringe/virologia , Pandemias , Saliva/virologia , Manejo de Espécimes , Fatores de Tempo , Pesquisa Médica Translacional , Urina/virologia
19.
Pharmacol Res Perspect ; 9(1): e00703, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33421306

RESUMO

Pulmonary arterial hypertension (PAH) is a progressive cardiovascular disease with high mortality. However, there were no efficient medical drugs for PAH to enormously improve the survival and quality of life measures. The present study aimed to explore the protective effect of baicalin against experimental PAH in vivo and vitro. All the experimental rats received intraperitoneal injection of monocrotaline (MCT) to induce PAH model. Baicalin was given by intragastric administration from 2 days after MCT injection. Forty animals were randomly divided into four groups: Control, MCT, saline-, and baicalin-treated groups (n = 10 in each). Post-operation, hemodynamic data, and index of right ventricular hypertrophy (RVHI) were recorded to evaluate the inhibition of baicalin on MCT-induced PAH. Furthermore, pulmonary artery smooth muscle cells (PASMCs) model induced by tumor necrosis factor-α (TNF-α) was used to observe the inhibition of vascular cells proliferation in vitro. The results demonstrated that baicalin significantly attenuated MCT-induced right ventricular systolic pressure (RVSP), the index of right ventricular hypertrophy, and vessel wall thickness; inhibit inflammatory and cell proliferation induced by MCT or TNF-α, respectively. In addition, we found that baicalin might protect against experimental PAH via regulating the TNF-α/BMPR2 signaling pathway.

20.
Mol Med Rep ; 23(3): 1, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33398372

RESUMO

Brain 4 (Brn4) is a transcription factor belonging to the POU3 family, and it is important for the embryonic development of the neural tube, inner ear and pancreas. In addition, it serves a crucial role in neural stem cell differentiation and reprogramming. The present review aimed to summarize the chromosomal location, species homology, protein molecular structure and tissue distribution of Brn4, in addition to its biological processes, with the aim of providing a reference of its structure and function for further studies, and its potential use as a gene therapy target.

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