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1.
Endocrine ; 2020 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-33011881

RESUMO

PURPOSE: Ultrasound (US) is the most important imaging in the preoperative diagnosis of medullary thyroid carcinoma (MTC). MTC are easy to be misdiagnosed due to lacking typical malignant US features. This study investigated US features, clinical characteristics, prognosis, and detection methods, aimed to explore the association between US features and biological behavior, and improve early diagnosis of MTC. METHODS: A total of 189 MTC patients were enrolled in the study. Based on US features, 29 MTC were categorized as "indeterminate" (i-MTC) and 160 MTC were categorized as "malignant" (m-MTC) according to Thyroid Imaging, Reporting and Data System published by America College of Radiology (ACR TI-RADS). We compared US features, clinical characteristics and prognosis between both groups. We analyzed cytological categories of fine needle aspiration (FNA) within each i-MTC and m-MTC group according to the 2017 Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). We assessed the positive rate of FNA, frozen pathological examination, and preoperative serum calcitonin (Ctn) level in i-MTC and m-MTC groups. RESULTS: Preoperative US features were significantly different in shape, margin, composition, echogenicity, and calcifications between i-MTC and m-MTC (p < 0.05). I-MTC showed a hypoechoic solid or solid-cystic nodule lacking malignant US features. While m-MTC was presented as a solid nodule with obviously malignant US features. There were significant differences in lymph node dissection, extent of tumor, lymph node metastasis, and TNM stage and prognosis between i-MTC and m-MTC (p < 0.05). Compared to m-MTC, i-MTC underwent central neck dissection more frequently rather than lateral neck dissection at the time of the initial operation; i-MTC had less extrathyroidal invasion and lymph node metastasis, earlier stage, higher rate of biochemical cure, and lower rate of structural persistence/recurrence (p < 0.05). The 2017 TBSRTC of i-MTC and m-MTC was significantly different (p < 0.05). Preoperative serum Ctn level had a higher diagnostic sensitivity for both i-MTC and m-MTC when comparing to FNA and frozen pathological examination (p < 0.05). CONCLUSIONS: US features were associated with biological characteristics and prognosis of MTC. I-MTC lack malignant US features, preformed less aggressiveness, and better prognosis. TBSRTC according to FNA combined with serum Ctn were helpful for the detection of i-MTC.

2.
Eur J Ophthalmol ; : 1120672120962065, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33008277

RESUMO

PURPOSE: Treatment of corneal injury depends on the self-proliferation ability of human corneal epithelial cells (HCEp). Our previous study revealed kojic acid had the anti-senescence function on human corneal endothelial cells. In this study, we researched the enhancive proliferation effect of kojic acid in HCEp. METHODS: Cell viability was evaluated by MTT assay. The expression of proliferation-related protein was detected by western blotting and immunofluorescence assay. RESULTS: Kojic acid could enhance HCEp proliferation, characterized by promoting cell proliferation rate, decreasing the expression levels of p21, galectin 8 and ki67, and increasing that of p-p38. The p38 signaling pathway inhibitor, SB203580, could reverse the enhancive proliferation function of kojic acid. Furthermore, knockdown of p21 had similar enhancive proliferation effect to kojic acid. CONCLUSION: Kojic acid might enhance HCEp proliferation through p38 and p21 signaling pathways, potentially via reduced expression levels of galectin 8 and ki67. Hence, kojic acid might be a potential drug to accelerate the healing of corneal epithelial injury.

3.
Microbiologyopen ; : e1128, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33047890

RESUMO

The black pigmentation-related genes in Porphyromonas gingivalis are primarily involved in regulating gingipain functions. In this study, we identified a pigmentation-related gene, designated as pgn_0361. To characterize the role of pgn_0361 in regulating P. gingivalis-mediated epithelial cell detachment and inhibition of wound closure, PgΔ0361, an isogenic pgn_0361-defective mutant strain, and PgΔ0361C, a complementation strain, were constructed using P. gingivalis ATCC 33277. The gingipain and hemagglutination activities, as well as biofilm formation, were examined in all three strains. The effect of P. gingivalis strains on epithelial cell detachment was investigated using the HO-1-N-1 and Ca9-22 epithelial cell lines. The inhibition of wound closure by heat-killed P. gingivalis cells and culture supernatant was analyzed using an in vitro wound closure assay. Compared to the wild-type strain, the PgΔ0361 strain did not exhibit gingipain or hemagglutination activity but exhibited enhanced biofilm formation. Additionally, the PgΔ0361 strain exhibited attenuated ability to detach the epithelial cells and to inhibit wound closure in vitro. Contrastingly, the culture supernatant of PgΔ0361 exhibited high gingipain activity and strong inhibition of wound closure. The characteristics of PgΔ0361C and wild-type strains were comparable. In conclusion, the pgn_0361 gene is involved in regulating gingipains. The PGN_0361-defective strain exhibited reduced virulence in terms of epithelial cell detachment and inhibition of wound closure. The culture supernatant of the mutant strain highly inhibited wound closure, which may be due to high gingipain activity.

4.
Med Phys ; 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33089513

RESUMO

PURPOSE: Clinically, the risk stratification of thyroid nodules is usually used to formulate the next treatment plan. The American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) is a kind of medical standard widely used in classification diagnosis. It divides the nodule's ACR TI-RADS level into five levels by quantitative scoring, from benign to high suspicion of malignancy. However, such assessment often relies on the radiologists' experience and is time consuming. So Computer Aided Diagnosis is necessary. But many Deep Learning (DL) models are difficult for doctors to understand, limiting their applicability in clinical practice. In this work, we mainly focus on how to achieve automatic thyroid nodules risk stratification based on deep integration of deep learning and clinical experience. METHODS: An automatic hierarchical method of thyroid nodules risk based on deep learning is proposed, called risk stratification network (RS-Net). It incorporates medical experience based on ACR TI-RADS. The convolutional neural network (CNN) is used to classify the five categories in ACR TI-RADS and assign their points respectively. According to the point totals, the level of risk can be obtained. In addition, a dataset involving 13984 thyroid ultrasound images is established to develop and evaluate the proposed method. RESULTS: We have extensively compared the results of this paper with the evaluation results of sonographers. The accuracy of the risk stratification (TR1 to TR5) of the proposed method is 65%, and the mean absolute error (MAE) is 0.54. The MAE of the point totals (0 to 13 points) is 1.67. The Pearson's correlation between our method evaluation and doctor evaluation reached 0.84. For the benign and malignant classification, the performance indices accuracy, sensitivity, specificity, PPV, and NPV were 88.0%, 98.1%, 79.1%, 80.5%, and 97.9%, respectively. Our method's level of thyroid nodules risk stratification is comparable to that of a senior doctor. CONCLUSIONS: This work provides a way to automate the risk stratification of thyroid nodules. Our method can effectively avoid missed diagnosis and misdiagnosis caused by the difference of observers so as to assist doctors to improve efficiency and diagnosis rate. And compared with the previous benign and malignant classification, the proposed method incorporates clinical experience. So it can greatly increase the clinicians' trust in the DL model, thereby improving the applicability of the model in clinical practice.

5.
Plants (Basel) ; 9(10)2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33081176

RESUMO

In plants, light is an important environmental signal that induces meristem development and interacts with endogenous signals, including hormones. We found that treatment with 24 h of low-fluence red light (24 h R) or 24 h of darkness (24 h D) following root excision greatly increased the frequency of shoot generation, while continuous low-fluence red light in callus and shoot induction stages blocked the explants' ability to generate shoots. Shoot generation ability was closely associated with WUS expression and distribution pattern. 1-N-naphthylphtalamic acid (NPA) disrupted the dynamic distribution of the WUS signal induced by early 24 h R treatment, and NPA plus 24 R treatment increased the average shoot number compared with early 24 h R alone. Transcriptome analysis revealed that differentially expressed genes involved in meristem development and hormone signal pathways were significantly enriched during 24 R or 24 D induced shoot regeneration, where early 24 h R or 24 h D treatment upregulated expression of WOX5, LBD16, LBD18 and PLT3 to promote callus initiation and formation of root primordia, and also activated WUS, STM, CUC1 and CUC2 expression, leading to initiation of the shoot apical meristem (SAM). This finding demonstrates that early exposure of explants to transient low-fluence red light or darkness modulates the expression of marker genes related with callus development and shoot regeneration, and dynamic distribution of WUS, leading to an increased ability to generate shoots.

6.
Autophagy ; : 1-18, 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32910719

RESUMO

Mesenchymal stem cell transplantation (MSCT) has been applied to treat a variety of autoimmune and inflammatory diseases. Psychosocial stress can aggravate disease progression in chronic inflammatory patients. Whether psychological stress affects MSCT is largely unknown. In this study we show that psychological stress attenuates therapeutic effects of MSCT in a DSS-induced colitis mouse model by elevating the levels of exosomal Mir7k/mmu-let-7 k (microRNA 7 k) in circulation. Mechanistically, Mir7k inhibits STAT3 pathway in donor MSCs, leading to upregulated expression of BECN1 (beclin 1, autophagy related) and, thus, activation of macroautophagy/autophagy. Inhibition of autophagy by blocking Mir7k or activating STAT3 signaling can restore MSCT-mediated therapy in psychologically stressed colitis mice. Our study identifies a previously unknown role of autophagy in regulating MSCT therapy via exosomal miRNA Mir7k. Abbreviations: BafA1: bafilomycin A1; BECN1: beclin 1, autophagy related; DAI: disease activity index; DAPI: 4',6-diamidino-2-phenylindole; DSS: dextran sulfate sodium; GFP: green fluorescent protein; HAI: histological activity index; IFNG/IFN-γ: interferon gamma; IL10: interleukin 10; IL1RN/IL-1Rra: interleukin 1 receptor antagonist; KD: knockdown; miRNA: microRNA; MSCs: mesenchymal stem cells; MSCT: mesenchymal stem cell transplantation; NTA: nanoparticle tracking analysis; PGE2: prostaglandin E2; SD: standard deviation; siRNA: small-interfering RNA; STAT3: signal transducer and activator of transcription 3; TEM: transmission electron microscopy; TGFB1/TGF-ß1: transforming growth factor, beta 1; Th17 cell: T helper cell 17; TNF/TNF-α: tumor necrosis factor; TNFAIP6/TSG6: tumor necrosis factor alpha induced protein 6; Tregs: regulatory T cells.

7.
Stem Cell Res Ther ; 11(1): 333, 2020 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-32746910

RESUMO

BACKGROUND: Pulpitis is a common dental disease characterized by sustained inflammation and impaired pulp self-repair. Mesenchymal stem cell-based minimally invasive vital pulp therapy (MSC-miVPT) is a potential treatment method, but its application is limited by the difficulty in acquiring MSCs. We recently revealed the immunomodulatory effects of rat dental follicle stem cells (rDFSCs) on acute lung injury. The present study focused on the paracrine effects of rDFSCs on the inflammation and regeneration of rat injured dental pulp to detect whether DFSCs are a potential candidate for MSC-miVPT. METHODS: Conditioned medium from rDFSCs (rDFSC-CM) was applied to lipopolysaccharide (LPS)-induced inflammatory rat dental pulp cells (rDPCs). The inflammation and regeneration of rDPCs were detected by RT-qPCR, Western blotting, immunofluorescence staining, Cell Counting Kit-8 (CCK-8) assay, flow cytometry, wound-healing assay, and Masson's staining. The effects of rDFSC-CM on inflamed rat dental pulp were further evaluated by hematoxylin-eosin and immunohistochemical staining. RESULTS: rDFSC-CM downregulated the ERK1/2 and NF-κB signaling pathways, which resulted in suppression of the expression of IL-1ß, IL-6, and TNF-α and promotion of the expression of IL-4 and TGF-ß, and these findings lead to the attenuation of rDPC inflammation. rDFSC-CM enhanced the in vitro proliferation, migration, and odontogenic differentiation of inflammatory rDPCs and their in vivo ectopic dentinogenesis. Furthermore, rDFSC-CM inhibited inflammatory cell infiltration in rat pulpitis and triggered Runx2 expression in some of the odontoblast-like cells surrounding the injured site, and these effects were conducive to the repair of inflamed dental pulp. CONCLUSIONS: rDFSC-CM exhibits therapeutic potential by rescuing the regeneration of the inflamed rat dental pulp through an immunomodulatory mechanism, indicating the application prospects of DFSCs in biological regenerative endodontics.

8.
Environ Res ; : 110015, 2020 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-32818497

RESUMO

Few prospective cohort studies have investigated associations between environmental tobacco smoke (ETS) and other cancer sites, in addition to lung cancer. We assessed these associations in a population-based prospective cohort study started from 2008 to 2011 with average of 9.1 years of follow-up, in Minhang district, Shanghai, China. The study included a total of 23,415 participants (8,388 men, 15,027 women) and 205,515 person-years. Epidemiological data were collected by a standardized questionnaire including ETS exposure. Newly diagnosed patients with primary cancers and deaths were identified by record linkage system with the Shanghai Cancer Registry and Shanghai Vital Statistics. Hazard ratios (HRs) and their 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression models, adjusting for potential confounders. During the study period, a total of 1,462 patients with diagnoses of primary cancers were identified. Among all participants and non-smokers, ETS was associated with an increased risk of all smoking-related cancers (all: adjusted HR: 1.23, 95% CI: 1.05-1.43 and non-smokers: 1.24, 1.02-1.49), lung cancer (1.29, 0.98-1.71 and 1.27, 0.91-1.77), and stomach cancer (1.86, 1.21-2.85 and 1.75, 1.05-2.91), respectively. Furthermore, associations for lung and stomach cancers were the strongest among non-smoking females. The joint effects of both ETS and active smoking were strongest for all cancers, all smoking-related cancers, lung cancer, and stomach cancer. No clear interactions were observed. These results suggest that ETS exposure may increase the risk of smoking-related cancers in a Chinese population. Further studies on the relationship between ETS exposure and specific cancer sites are warranted to replicate our findings.

9.
Med Sci Monit ; 26: e927007, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32798214

RESUMO

BACKGROUND The number of studies on deep learning in artificial intelligence (AI)-assisted diagnosis of thyroid nodules is increasing. However, it is difficult to explain what the models actually learn in artificial intelligence-assisted medical research. Our aim is to investigate the visual interpretability of the computer-assisted diagnosis of malignant and benign thyroid nodules using ultrasound images. MATERIAL AND METHODS We designed and implemented 2 experiments to test whether our proposed model learned to interpret the ultrasound features used by ultrasound experts to diagnose thyroid nodules. First, in an anteroposterior/transverse (A/T) ratio experiment, multiple models were trained by changing the A/T ratio of the original nodules, and their classification, accuracy, sensitivity, and specificity were tested. Second, in a visualization experiment, class activation mapping used global average pooling and a fully connected layer to visualize the neural network to show the most important features. We also examined the importance of data preprocessing. RESULTS The A/T ratio experiment showed that after changing the A/T ratio of the nodules, the accuracy of the neural network model was reduced by 9.24-30.45%, indicating that our neural network model learned the A/T ratio information of the nodules. The visual experiment results showed that the nodule margins had a strong influence on the prediction of the neural network. CONCLUSIONS This study was an active exploration of interpretability in the deep learning classification of thyroid nodules. It demonstrated the neural network-visualized model focused on irregular nodule margins and the A/T ratio to classify thyroid nodules.

10.
Endocrine ; 2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32852733

RESUMO

PURPOSE: To establish a practical and simplified Chinese thyroid imaging reporting and data system (C-TIRADS) based on the Chinese patient database. METHODS: A total of 2141 thyroid nodules that were neither cystic nor spongy were used in the current study. These specimens were derived from 2141 patients in 131 alliance hospitals of the Chinese Artificial Intelligence Alliance for Thyroid and Breast Ultrasound. The ultrasound features, including location, orientation, margin, halo, composition, echogenicity, echotexture, echogenic foci and posterior features were assessed. Univariate and multivariate analyses were performed to investigate the association between ultrasound features and malignancy. The regression equation, the weighting, and the counting methods were used to determine the malignant risk of the thyroid nodules. The areas under the receiver operating characteristic curve (Az values) were calculated. RESULTS: Of the 2141 thyroid nodules, 1572 were benign, 565 were malignant, and 4 were borderline. Vertical orientation, ill-defined, or irregular margin (including extrathyroidal extension), microcalcifications, solid, and markedly hypoechoic were positively associated with malignancy, while comet-tail artifacts were negatively associated with malignancy. The logistic regression equation yielded the highest Az value of 0.913, which was significantly higher than that obtained using the weighting method (0.893) and the counting method (0.890); however, no significant difference was found between the latter two. The C-TIRADS, based on the counting method, was designed following the principle of balancing the diagnostic performance and sensitivity of the risk stratification with the ease of use. CONCLUSIONS: A relatively simple C-TIRADS was established using the counting value of positive and negative ultrasound features.

11.
Med Biol Eng Comput ; 58(11): 2641-2656, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32840765

RESUMO

During thyroid ultrasound diagnosis, radiologists add markers such as pluses or crosses near a nodule's edge to indicate the location of a nodule. For computer-aided detection, deep learning models achieve classification, segmentation, and detection by learning the thyroid's texture in ultrasound images. Experiments show that manual markers are strong prior knowledge for data-driven deep learning models, which interferes with the judgment mechanism of computer-aided detection systems. Aiming at this problem, this paper proposes cascade marker removal algorithm for thyroid ultrasound images to eliminate the interference of manual markers. The algorithm consists of three parts. First, in order to highlight marked features, the algorithm extracts salient features in thyroid ultrasound images through feature extraction module. Secondly, mask correction module eliminates the interference of other features besides markers' features. Finally, the marker removal module removes markers without destroying the semantic information in thyroid ultrasound images. Experiments show that our algorithm enables classification, segmentation, and object detection models to focus on the learning of pathological tissue features. At the same time, compared with mainstream image inpainting algorithms, our algorithm shows better performance on thyroid ultrasound images. In summary, our algorithm is of great significance for improving the stability and performance of computer-aided detection systems. Graphical Abstract During thyroid ultrasound diagnosis, doctors add markers such as pluses or crosses near nodule's edge to indicate the location of nodule. Manual markers are strong prior knowledge for data-driven deep learning models, which interferes the judgment mechanism of computer-aided diagnosis system based on deep learning. Markers make models overfit the specific labeling forms easily, and performs poorly on unmarked thyroid ultrasound images. Aiming at this problem, this paper proposes a cascade marker removal algorithm to eliminate the interference of manual markers. Our algorithm make deep learning models pay attention on nodules' features of thyroid ultrasound images, which make computer-aided diagnosis system performs good in both marked imaging and unmarked imaging.

12.
Endocrine ; 70(2): 256-279, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32827126

RESUMO

Thyroid nodules are very common all over the world, and China is no exception. Ultrasound plays an important role in determining the risk stratification of thyroid nodules, which is critical for clinical management of thyroid nodules. For the past few years, many versions of TIRADS (Thyroid Imaging Reporting and Data System) have been put forward by several institutions with the aim to identify whether nodules require fine-needle biopsy or ultrasound follow-up. However, no version of TIRADS has been widely adopted worldwide till date. In China, as many as ten versions of TIRADS have been used in different hospitals nationwide, causing a lot of confusion. With the support of the Superficial Organ and Vascular Ultrasound Group of the Society of Ultrasound in Medicine of the Chinese Medical Association, the Chinese-TIRADS that is in line with China's national conditions and medical status was established based on literature review, expert consensus, and multicenter data provided by the Chinese Artificial Intelligence Alliance for Thyroid and Breast Ultrasound.

13.
FASEB J ; 2020 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-32619083

RESUMO

Chronic stress-evoked depression has been implied to associate with the decline of adult hippocampal neurogenesis. Caffeine has been known to combat stress-evoked depression. Herein, we aim to investigate whether the protective effect of caffeine on depression is related with improving adult hippocampus neurogenesis and explore the mechanisms. Mouse chronic water immersion restraint stress (CWIRS) model, corticosterone (CORT)-established cell stress model, a coculture system containing CORT-treated BV-2 cells and hippocampal neural stem cells (NSCs) were utilized. Results showed that CWIRS caused obvious depressive-like disorders, abnormal 5-HT signaling, and elevated-plasma CORT levels. Notably, microglia activation-evoked brain inflammation and inhibited neurogenesis were also observed in the hippocampus of stressed mice. In comparison, intragastric administration of caffeine (10 and 20 mg/kg, 28 days) significantly reverted CWIRS-induced depressive behaviors, neurogenesis recession and microglia activation in the hippocampus. Further evidences from both in vivo and in vitro mechanistic experiments demonstrated that caffeine treatment significantly suppressed microglia activation via the A2AR/MEK/ERK/NF-κB signaling pathway. The results suggested that CORT-induced microglia activation contributes to stress-mediated neurogenesis recession. The antidepression effect of caffeine was associated with unlocking microglia activation-induced neurogenesis inhibition.

14.
Phytomedicine ; 77: 153281, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32707370

RESUMO

BACKGROUND: Oxidative damage of dopaminergic neurons is the fundamental causes of Parkinson's disease (PD) that has no standard cure at present. Theacrine, a purine alkaloid from Chinese tea Kucha, has been speculated to benefit the neurodegeneration in PD, through similar actions to its chemical analogue caffeine, albeit excluding side effects. Theacrine has nowadays gained a lot of interest for its multiple benefits, while the investigations are weak and insufficient. HYPOTHESIS/PURPOSE: It is well-known that tea has a wide range of functions, especially in the prevention and treatment of neurodegenerative diseases. Theacrine is an active monomer compound in Camellia assamica var. kucha Hung T. Chang & H.S.Wang (Kucha), which appears to be effective and safe in PD therapy. The aim of this study is to examine its actions in diverse PD models and explore the mechanisms. STUDY DESIGN: For determination of theacrine's effects, we employed diverse oxidative damage-associated PD models, including 6-OHDA-treated rats, MPTP-treated mice/zebrafish and MPP+-treated SH-SY5Y cells, and using caffeine, selegiline and depranyl as positve control. For investigation and verification of the mechanisms, we utilized approaches testing mitochondrial function-related parameters and enzyme activity as well as applied gene knockdown and overexpression. METHODS: We employed behavioral tests including spontaneous activity, pole, swimming, rotarod and gait, immunohistochemistry, HPLC, flow cytometry, immunohistochemistry, Western blot, gene knockdown by siRNA and overexpression by plasmid in this study. RESULTS: Theacrine is demonstrated to retrieve the loss of dopaminergic neurons and the damages of behavioral performance in multiple animal models of PD (6-OHDA-treated rats and in MPTP-treated mice and zebrafish). The followed data of MPP+-treated SH-SY5Y cells indicate that theacrine relieves apoptosis resulted from oxidative damage and mitochondrial dysfunction. Further investigations illustrate that theacrine activates SIRT3 directly. It is of advantage to prevent apoptosis through SIRT3-mediated SOD2 deacetylation that reduces ROS accumulation and restores mitochondrial function. This concept is elaborated by 3TYP that inhibits SIRT3 enzyme activity and knockdown/overexpression of SIRT3 gene, demonstrating a crucial role of SIRT3 in theacrine-benefited dopaminergic neurons. CONCLUSION: Theacrine prevents apoptosis of dopaminergic neurons through directly activating SIRT3 which deacetylating SOD2 and restoring mitochondrial functions.

15.
Aging (Albany NY) ; 12(14): 14365-14375, 2020 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-32680978

RESUMO

More and more findings illustrate the critical roles of circular RNA (circRNA) in diabetes mellitus (DM) and its complications. A major pathological characteristic for DM is the apoptosis of endothelial cells (ECs) induced by high glucose (HG), however, the function of circRNA in the ECs' phenotypes is still elusive. Here, this study identified an up-regulated circRNA (circVEGFC) in the HG-induced human umbilical vein endothelial cells (HUVECs). Functionally, knockdown of circVEGFC alleviated the apoptosis and recovered the proliferation in HUVECs induced by HG administration. Mechanistically, circVEGFC functioned as the sponge of miR-338-3p, and miR-338-3p was found to target the 3'-Untranslated Regions (3'-UTR) of hypoxia inducible factor 1 alpha (HIF-1α). HIF-1α, a critical transcription factor in DM, could activate the transcription of vascular endothelial growth factor A (VEGFA) and promote its protein product. In conclusion, these findings reveal the promotion of circVEGFC/miR-338-3p/HIF-1α/VEGFA axis in the HG-induced ECs' apoptosis, providing a potential treatment strategy for ECs' damage in DM.

16.
Hemoglobin ; 44(4): 259-263, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32646243

RESUMO

Thalassemia is the most common monogenic disorder around the world. Based on the principle of genotype-phenotype correlation, identification of thalassemia mutations is the essential prerequisite for clinical diagnosis and management. Because only common mutations are routinely detected, the identification of rare or undetermined mutations is a challenge for clinical laboratories. Herein, a proband presenting with inconsistent phenotype-genotype correlation after routine molecular screening was investigated by multiplex ligation-dependent probe amplification (MLPA), targeted-next generation sequencing (targeted-NGS), gap-polymerase chain reaction (gap-PCR) and Sanger sequencing. Eventually, a novel 71.8 kb deletion (- -71.8) was identified and characterized, which included HBZ (ζ), HBA2 (α2), and HBA1 (α1) genes and was causing α0-thalassemia (α0-thal). Furthermore, we summarized a practical procedure based on accumulated experience in studies and clinical practice, which can be a guide for molecular screening and clinical diagnosis of thalassemia, especially for identification of undetermined or novel mutations.

17.
Cancer Sci ; 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32530556

RESUMO

Alternative splicing (AS) provides the primary mechanism for producing protein diversity. There is growing evidence that AS is involved in the development and progression of cancers. The rapid accumulation of high-throughput sequencing technologies and clinical data sets offers an opportunity to systematically profile the relationship between mRNA variants and clinical outcomes. However, there is a lack of systematic analysis of AS in prostate cancer: Download RNA-seq data and clinical information from The Cancer Genome Atlas (TCGA) data portal. Evaluate RNA splicing patterns by SpliceSeq and calculate splicing percentage (PSI) values. Different expressions were identified as differently expressed AS events (DEAs) based on PSI values. Bioinformatics methods were used for further analysis of DEAs and their splicing networks. Kaplan-Meier, Cox proportional regression, and unsupervised cluster analysis were used to assess the correlation between DEAs and clinical characteristics. In total, 43 834 AS events were identified, of which 1628 AS events were differentially expressed. The parental genes of these DEAs played a significant role in the regulation of prostate cancer-related processes. In total, 226 DEAs events were found to be associated with disease-free survival. Four clusters of molecules with different survival modes were revealed by unsupervised cluster analysis of DEAs. AS events may be important determinants of prognosis and bio-modulation in prostate cancer. In this study, we established strong prognostic predictors, discovered a splicing network that may be a potential mechanism, and provided further validated therapeutic targets.

18.
Med Sci Monit ; 26: e926096, 2020 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-32555130

RESUMO

BACKGROUND Thyroid nodules are extremely common and typically diagnosed with ultrasound whether benign or malignant. Imaging diagnosis assisted by Artificial Intelligence has attracted much attention in recent years. The aim of our study was to build an ensemble deep learning classification model to accurately differentiate benign and malignant thyroid nodules. MATERIAL AND METHODS Based on current advanced methods of image segmentation and classification algorithms, we proposed an ensemble deep learning classification model for thyroid nodules (EDLC-TN) after precise localization. We compared diagnostic performance with four other state-of-the-art deep learning algorithms and three ultrasound radiologists according to ACR TI-RADS criteria. Finally, we demonstrated the general applicability of EDLC-TN for diagnosing thyroid cancer using ultrasound images from multi medical centers. RESULTS The method proposed in this paper has been trained and tested on a thyroid ultrasound image dataset containing 26 541 images and the accuracy of this method could reach 98.51%. EDLC-TN demonstrated the highest value for area under the curve, sensitivity, specificity, and accuracy among five state-of-the-art algorithms. Combining EDLC-TN with models and radiologists could improve diagnostic accuracy. EDLC-TN achieved excellent diagnostic performance when applied to ultrasound images from another independent hospital. CONCLUSIONS Based on ensemble deep learning, the proposed approach in this paper is superior to other similar existing methods of thyroid classification, as well as ultrasound radiologists. Moreover, our network represents a generalized platform that potentially can be applied to medical images from multiple medical centers.

19.
J Int Med Res ; 48(5): 300060520925594, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32459112

RESUMO

OBJECTIVE: Clinical diagnostics often requires the detection of multiple bacterial species in limited clinical samples with a single DNA extraction method. This study aimed to compare the bacterial DNA extraction efficiency of two lysis methods automated with the MagNA-Pure LC instrument. The samples included five oral bacterial species (three Gram-positive and two Gram-negative) with or without human saliva background. METHODS: Genomic DNA (gDNA) was extracted from bacterial cultures by bead-beating lysis (BMP) or chemical lysis (MP), followed by automated purification and measurement by quantitative PCR. RESULTS: For pure bacterial cultures, the MP method yielded higher quantities of extracted DNA and a lower detection limit than the BMP method, except where the samples contained high numbers of Gram-positive bacteria. For bacterial cultures with a saliva background, no difference in gDNA extraction efficacy was observed between the two methods. CONCLUSIONS: The efficiency of a bacterial DNA extraction method is not only affected by the bacterial cell wall structure but also by the sample milieu. The MP method provided superior gDNA extraction efficiency when the samples contained a single bacterial species, whereas either of the BMP and MP methods could be applied with similar efficiencies to samples containing multiple species of bacteria.

20.
Acta Neuropathol Commun ; 8(1): 32, 2020 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-32169121

RESUMO

Charcot-Marie-Tooth disease (CMT) is a group of inherited neurological disorders of the peripheral nervous system. CMT is subdivided into two main types: a demyelinating form, known as CMT1, and an axonal form, known as CMT2. Nearly 30 genes have been identified as a cause of CMT2. One of these is the 'dehydrogenase E1 and transketolase domain containing 1' (DHTKD1) gene. We previously demonstrated that a nonsense mutation [c.1455 T > G (p.Y485*)] in exon 8 of DHTKD1 is one of the disease-causing mutations in CMT2Q (MIM 615025). The aim of the current study was to investigate whether human disease-causing mutations in the Dhtkd1 gene cause CMT2Q phenotypes in a mouse model in order to investigate the physiological function and pathogenic mechanisms associated with mutations in the Dhtkd1 gene in vivo. Therefore, we generated a knock-in mouse model with the Dhtkd1Y486* point mutation. We observed that the Dhtkd1 expression level in sciatic nerve of knock-in mice was significantly lower than in wild-type mice. Moreover, a histopathological phenotype was observed, reminiscent of a peripheral neuropathy, including reduced large axon diameter and abnormal myelination in peripheral nerves. The knock-in mice also displayed clear sensory defects, while no abnormalities in the motor performance were observed. In addition, accumulation of mitochondria and an elevated energy metabolic state was observed in the knock-in mice. Taken together, our study indicates that the Dhtkd1Y486* knock-in mice partially recapitulate the clinical phenotypes of CMT2Q patients and we hypothesize that there might be a compensatory effect from the elevated metabolic state in the knock-in mice that enables them to maintain their normal locomotor function.

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