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1.
Rapid Commun Mass Spectrom ; : e8959, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33001505

RESUMO

RATIONALE: Iris tectorum Maxim is a traditional medicinal herb that is commonly utilized for treating inflammatory conditions. The present study investigated the fragmentation patterns of isoflavone glycosides and their qualitative analysis. In addition, lipopolysaccharide (LPS)-induced RAW264.7 macrophages were used to evaluat the anti-inflammatory properties of I. tectorum Maxim samples collected at different time points during the year. METHOD: High-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (HPLC/Q-TOF-MS/MS) and HPLC-DAD were employed for the qualitative and quantitative analysis. The fragmentation patterns of these isoflavones were observed in negative electrospray ionization mode with collision-induced dissociation (CID). Their anti-inflammatory activity was assessed via nitric oxide (NO) production in LPS-treated RAW 264.7 macrophages. RESULTS: A total of 15 chemical components were observed and tentatively identified by HPLC/Q-TOF-MS. At low collision energy, the relative abundances of the aglycone radical anion Y0 - , [Y0 -H]-• , [Y0 -CH3 ]-• , and [Y0 -H-CH2 ]-• were used for the structural characterization of tectoridin and tectorigenin-4'-O-ß-D-glucoside. The radical ions [Y0 -CH3 ]-• and [Y0 -H-2CH3 ]-• were also employed to differentiate between iristectorin A and iristectorin B based upon their high energy CID spectra. Levels of 9.02 mg/g of tectoridin and 1.04 mg/g of tectorigenin were found in samples collected in June, which exhibited 69.7% NO inhibitory activity. CONCLUSION: The characteristic fragmentation patterns enabled us to reliably identify isoflavone glycosides. The results of the quantitative determination and NO inhibitory activity offer insight into the optimal I. tectorum Maxim harvesting time.

3.
J Biomater Appl ; : 885328220963934, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33045872

RESUMO

Dental implants are the most innovative and superior treatment modality for tooth replacement. However, titanium implants still suffer from insufficient antibacterial capability and peri-implant diseases remain one of the most common and intractable complications. To prevent peri-implant diseases, a composite coating containing a new antibacterial agent, (Z-)-4-bromo-5-(bromomethylene)-2(5H)-furanone (BBF) was fabricated on titanium. This study was designed to investigate the antibacterial activity of the composite coating against two common peri-implant pathogens (Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans). The morphology of the composite coating showed that BBF-loaded poly(L-lactic acid) nanospheres were well-distributed in the pores of the microarc oxidation coating, and cross-linked with each other and the wall pores by gelatin. A release study indicated that the antibacterial coating could sustain the release of BBF for 60 d, with a slight initial burst release occurring during the first 4 h. The antibacterial rate of the composite coating for adhering bacteria was the highest (over 97%) after 1 d and over 90% throughout a 30-day incubation period. The total fluorescence intensity of the composite coating was the lowest, and the vast majority of the fluorescence was red (dead bacteria). Moreover, real-time polymerase chain reaction analysis confirmed that the relative gene expression of the adherent bacteria on the composite coating was down-regulated. It was therefore concluded that the composite coating fabricated on titanium, which showed excellent and relatively long-term antibacterial activity against Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans, is a potential and promising strategy to be applied on dental implants for the prevention of peri-implant diseases.

4.
Sci Total Environ ; 755(Pt 1): 142437, 2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-33011598

RESUMO

As the most widely used method for evaluating heavy metals (HMs) in soil or sediment, the enrichment factor (EF) is prone to bias and even yields misleading assessment results for HM pollution due to data uncertainties, lack of local background values and a failure to assess the comprehensive pollution of multiple HMs. Here, we developed an improved EF model integrating stochastic mathematical methods and geochemical baselines (GBs). First, GBs were obtained using the relative cumulative frequency distribution method. The probability that each HM belongs to each enrichment degree was then quantified based on the probability density function deduced from the maximum entropy method. Furthermore, we defined a synthetic index to reveal the probability that multiple HMs belongs to comprehensive enrichment degree considering the weight of each HM. Finally, the enrichment category for each HM and multiple HMs were determined following the first-order moment principle. The improved EF model was successfully applied to evaluate and predict the HM pollution in sediments collected from Poyang Lake, the largest freshwater lake in China. Slight enrichment (1.88) of multiple HMs was found in sediments from Poyang Lake, characterized by a pronounced probability (0.35) to deteriorate to the "moderate enrichment" category. Among the different HMs, Cd requires more attention considering its dominant contribution (0.51) to the comprehensive pollution and high probability (0.65) for deterioration. Otherwise, assessment results employing the improved EF model agree with the spatial patterns of HM concentrations based on spatial autocorrelation analysis and source apportionment using Pb isotopic signatures and principal component analysis. Compared with the conventional EF method, the assessment results of the improved EF model were more accurate, comprehensive and reliable. In conclusion, the improved EF model has a better capability of evaluating and predicting HM enrichment in sediments and can be helpful for optimizing control measures for HM pollution.

6.
Nat Commun ; 11(1): 3931, 2020 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-32747625

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

7.
J Clin Invest ; 2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32853181

RESUMO

Heterotopic ossification (HO) is pathological bone formation characterized by ossification within muscle, tendons, or other soft tissues. However, the cells of origin and mechanisms involved in the pathogenesis of HO remain elusive. Here we show that deletion of Suppressor of fused (Sufu) in Cathepsin K-Cre-expressing (Ctsk-Cre-expressing) cells resulted in spontaneous and progressive ligament, tendon, and periarticular ossification. Lineage tracing studies and cell functional analysis demonstrated that Ctsk-Cre could label a subpopulation of tendon-derived progenitor cells (TDPCs) marked by tendon marker Scleraxis (Scx). Ctsk+Scx+ TDPCs are enriched for tendon stem cell markers and show the highest self-renewal capacity and differentiation potential. Sufu deficiency caused enhanced chondrogenic and osteogenic differentiation of Ctsk-Cre-expressing tendon-derived cells via upregulating Hedgehog (Hh) signaling. Furthermore, pharmacological intervention of hedgehog signaling using JQ1 suppressed the development of HO. Thus, our results display that Cathepsin K-Cre labels a subpopulation of TDPCs contributing to HO and their cell fate changes are driven by activation of Hh signaling.

8.
Clin Transl Sci ; 2020 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-32770720

RESUMO

Budigalimab (ABBV-181) is a humanized, recombinant, Fc mutated IgG1 monoclonal antibody targeting programmed cell death 1 (PD-1) receptor, currently in phase 1 clinical trials. The safety, efficacy, pharmacokinetics (PK), pharmacodynamics (PD), and budigalimab dose selection from monotherapy dose escalation and multi-histology expansion cohorts were evaluated in patients with previously treated advanced solid tumors who received budigalimab at 1, 3, or 10 mg/kg intravenously every two weeks (Q2W) in dose escalation, including Japanese patients that received 3 and 10 mg/kg Q2W. PK modeling and PK/PD assessments informed the dosing regimen in expansion phase using data from weight-based dosing in the escalation phase, based on which patients in the multi-histology expansion cohort received flat doses of 250 mg Q2W or 500 mg every four weeks (Q4W). Immune related adverse events were reported in 11/59 (18.6%) patients, of which 1/59 (1.7%) was considered Grade ≥ 3 and the safety profile of budigalimab was consistent with other PD-1 targeting agents. No treatment-related Grade 5 adverse events were reported. Four responses per RECIST (v1.1) were reported in the dose escalation cohort and none in the multi-histology expansion cohort. PK of budigalimab was approximately dose proportional and sustained > 99% peripheral PD-1 receptor saturation was observed by 2 hours post dosing, across doses. PK/PD and safety profiles were comparable between Japanese and Western patients, and exposure-safety analyses did not indicate any trends. Observed PK and PD-1 receptor saturation were consistent with model predictions for flat doses and less frequent regimens, validating the early application of PK modeling and PK/PD assessments to inform the recommended dose and regimen, following dose escalation.

9.
Int J Chron Obstruct Pulmon Dis ; 15: 1813-1822, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32801679

RESUMO

Purpose: Prior studies have indicated that patients with chronic obstructive pulmonary disease (COPD) exhibit significant cognitive defects on neuropsychological testing. Obstructive sleep apnea (OSA) is common in patients with COPD and is associated with reduced cognitive function; however, the combined impact of these two conditions on cognitive function is unknown. The aim of the study was to investigate the impact of OSA on cognitive impairment in patients with COPD. Methods: Sixty-five stable COPD patients aged over 60 years underwent overnight polysomnography (PSG). Global cognitive functions were evaluated using the Mini-Mental State Examination (MMSE). Results: Compared to patients with COPD alone, patients with both COPD and OSA performed worse on the MMSE (25.5±2.9 vs 23.5±3.2; p=0.01) and were more likely to be at risk for developing dementia based on the MMSE score (MMSE≤24) (31% vs 66%; p<0.01), independent of key demographic, educational and medical variables known to affect cognitive function in COPD. COPD patients with an apnea hypopnea index (AHI) of ≥30 events/h had lower MMSE scores than those with an AHI of <15 events/h. In addition to age and education level, the severity of nocturnal intermittent hypoxia is an independent predictor of the risk of dementia in patients with COPD (OR=1.24, 95% CI 1.04-1.48, p = 0.02). Conclusion: The current findings indicate that patients with COPD with comorbid OSA may be at greater risk for global cognitive impairment relative to patients with COPD alone. The mechanisms underlying the exaggerated cognitive dysfunction seem to be related to intermittent hypoxia. Further work is needed to understand the impact of OSA on the specific domains of cognitive impairment and the therapeutic implications of OSA in COPD.

10.
FEBS Open Bio ; 10(10): 2157-2165, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32750222

RESUMO

Vortioxetine is a potent antagonist of the 5-hydroxytryptamine receptor and serotonin transporter and has been reported to function as an antidepressant in the treatment of major depressive disorder. However, its antitumor effects remain unclear. Here, we examined whether vortioxetine affects the characteristics of GC cells. Cell viability was measured by a colony formation assay and, in addition, cell invasion, migration and apoptosis assays were performed with a transwell assay and a flow cytometry assay. Protein levels were measured by western blotting. We found that vortioxetine inhibited the proliferation, invasion and migration abilities of AGS cells. Additionally, vortioxetine could induce apoptosis and autophagy by increasing the levels of Bax, active caspase-3/-9, Beclin-1 and light chain 3, as well as by downregulating Bcl-2 and P62. Further investigations indicated that vortioxetine regulated apoptosis and autophagy via activation of the phosphoinositide 3-kinase/AKT pathway. Taken together, our data suggest that vortioxetine has cytotoxic effects against GC AGS cells as a result of inhibiting proliferation, invasion and migration, as well as by inducing apoptosis and autophagy through the phosphoinositide 3-kinase/AKT pathway.

11.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 34(8): 990-993, 2020 Aug 15.
Artigo em Chinês | MEDLINE | ID: mdl-32794667

RESUMO

Objective: To evaluate the effectiveness of the nose ring drain (NRD) in treatment of severe diabetic foot infection. Methods: The clinical data of 35 patients with severe diabetic foot infection who were treated with NRD between June 2017 and June 2019 were analyzed retrospectively. There were 24 males and 11 females with an average age of 54.5 years (range, 28-82 years). All of them were type 2 diabetic patients. The diabetes duration was 3-20 years, with an average of 9.4 years. The diabetic foot duration was 4 months to 2 years, with an average of 1.16 years. There were 16 cases of left foot and 19 cases of right foot. According to Wagner's grading, there were 11 cases of grade 2, 20 cases of grade 3, and 4 cases of grade 4, all of which were moderate and severe infection of diabetic foot wound. Postoperative wounds were treated with "nibble-like" debridement until the patient's epidermis regenerated and healed. During the treatment process, the indexes of bacterial culture type of wound secretions, duration of antibiotic therapy, wound healing method, healing time, amputation rate, and other indicators were analyzed and summarized. Results: All 35 patients were followed up 3-6 months, with an average of 4.5 months. Postoperative bacterial culture of wounds showed that 5 cases of Staphylococcus aureus, 4 cases of Pseudomonas aeruginosa, 5 cases of Escherichia coli, 3 cases of Enterobacter cloacae, 3 cases of coagulase-negative Staphylococcus, and 15 cases of other types were detected. The duration of antibiotic therapy ranged from 3 to 15 days, with an average of 9.1 days. The wound was autolytically healed without skin grafting, and the healing time was 62-82 days, with an average of 72.3 days. During the follow-up, 3 cases (8.6%) had amputation due to the patient's poor blood glucose control, which led to a large spread of infection. In addition, among the other patients with wound healing, there was no recurrence of wound infection or new ulcer on the original surface. Conclusion: The NRD is a simple operation for treatment of severe diabetic foot infection, which can effectively control wound infections and promote wound healing and regeneration without skin grafting.


Assuntos
Diabetes Mellitus , Pé Diabético , Adulto , Idoso , Idoso de 80 Anos ou mais , Amputação , Drenagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Cicatrização
12.
J Chem Inf Model ; 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32804489

RESUMO

To efficiently save cost and reduce risk in drug research and development, there is a pressing demand to develop in silico methods to predict drug sensitivity to cancer cells. With the exponentially increasing number of multi-omics data derived from high-throughput techniques, machine learning-based methods have been applied to the prediction of drug sensitivities. However, these methods have drawbacks either in the interpretability of the mechanism of drug action or limited performance in modeling drug sensitivity. In this paper, we presented a pathway-guided deep neural network (DNN) model to predict the drug sensitivity in cancer cells. Biological pathways describe a group of molecules in a cell that collaborates to control various biological functions like cell proliferation and death, thereby abnormal function of pathways can result in disease. To take advantage of the excellent predictive ability of DNN and the biological knowledge of pathways, we reshaped the canonical DNN structure by incorporating a layer of pathway nodes and their connections to input gene nodes, which makes the DNN model more interpretable and predictive compared to canonical DNN. We have conducted extensive performance evaluations on multiple independent drug sensitivity data sets and demonstrated that our model significantly outperformed the canonical DNN model and eight other classical regression models. Most importantly, we observed a remarkable activity decrease in disease-related pathway nodes during forward propagation upon inputs of drug targets, which implicitly corresponds to the inhibition effect of disease-related pathways induced by drug treatment on cancer cells. Our empirical experiments showed that our method achieves pharmacological interpretability and predictive ability in modeling drug sensitivity in cancer cells. The web server, the processed data sets, and source codes for reproducing our work are available at http://pathdnn.denglab.org.

13.
J Orthop Res ; 2020 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-32672867

RESUMO

Congenital scoliosis (CS) is a spinal deformity present at birth due to underlying congenital vertebral malformation (CVM) that occurs during embryonic development. Hemivertebrae is the most common anomaly that causes CS. Recently, compound heterozygosity in TBX6 has been identified in Northern Chinese, Japanese, and European CS patient cohorts, which explains about 7%-10% of the affected population. In this report, we recruited 67 CS patients characterized with hemivertebrae in the Southern Chinese population and investigated the TBX6 variant and risk haplotype. We found that two patients with hemivertebrae in the thoracic spine and one patient with hemivertebrae in the lumbar spine carry the previously defined pathogenic TBX6 compound heterozygous variants. In addition, whole exome sequencing of patients with CS and their family members identified a de novo missense mutation (c.G47T: p.R16L) in another member of the T-box family, TBXT. This rare mutation compromised the binding of TBXT to its target sequence, leading to reduced transcriptional activity, and exhibited dominant-negative effect on wild-type TBXT. Our findings further highlight the importance of T-box family genes in the development of congenital scoliosis.

14.
Mol Med Rep ; 22(3): 2496-2506, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32705196

RESUMO

Acute pancreatitis (AP) is a common digestive disorder with high morbidity and mortality. The present study aimed to investigate the expression of early growth response protein 1 (Egr1), and the effect of competing endogenous (ce)RNA network on trypsinogen activation. Pancreatic acinar intracellular trypsinogen activation (PAITA) is an important event in the early stage of AP; however, the underlying mechanisms remain unclear. The present study used taurolithocholic acid 3­sulfate (TLC­S)­treated AR42J cells (pancreatic cell line) to establish a PAITA model. A gene microarray and bioinformatics analysis was performed to identify the potential key targets in PAITA. The results demonstrated that Egr1, an important transcription factor, was significantly overexpressed in PAITA. In Egr1 small interfering (si)RNA­transfected cells, Egr1 expression was decreased and trypsinogen activation was significantly decreased compared with negative control siRNA­transfected cells, indicating that in TLC­S­induced PAITA, overexpression of Egr1 enhanced trypsinogen activation. A ceRNA network [mRNA­microRNA (miRNA/miR)­long non­coding (lnc)RNA] generated using the PAITA model revealed that the effects of Egr1 on PAITA may be regulated by multiple ceRNA pairs, and the lncRNAs (including NONRATT022624 and NONRATT031002) and miRNAs [including Rattus norvegicus (rno)­miR­214­3p and rno­miR­764­5p] included in the ceRNA pairs may serve roles in PAITA by regulating the expression of Egr1. The results of the present study may provide novel targets for researching the underlying mechanisms of, and developing treatments for AP.

15.
Nat Commun ; 11(1): 3642, 2020 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-32686688

RESUMO

Carpal tunnel syndrome (CTS) is the most common peripheral nerve entrapment syndrome, affecting a large proportion of the general population. Genetic susceptibility has been implicated in CTS, but the causative genes remain elusive. Here, we report the identification of two mutations in cartilage oligomeric matrix protein (COMP) that segregate with CTS in two large families with or without multiple epiphyseal dysplasia (MED). Both mutations impair the secretion of COMP by tenocytes, but the mutation associated with MED also perturbs its secretion in chondrocytes. Further functional characterization of the CTS-specific mutation reveals similar histological and molecular changes of tendons/ligaments in patients' biopsies and the mouse models. The mutant COMP fails to oligomerize properly and is trapped in the ER, resulting in ER stress-induced unfolded protein response and cell death, leading to inflammation, progressive fibrosis and cell composition change in tendons/ligaments. The extracellular matrix (ECM) organization is also altered. Our studies uncover a previously unrecognized mechanism in CTS pathogenesis.


Assuntos
Síndrome do Túnel Carpal , Proteína de Matriz Oligomérica de Cartilagem , Animais , Síndrome do Túnel Carpal/etiologia , Síndrome do Túnel Carpal/genética , Síndrome do Túnel Carpal/metabolismo , Síndrome do Túnel Carpal/patologia , Proteína de Matriz Oligomérica de Cartilagem/genética , Proteína de Matriz Oligomérica de Cartilagem/metabolismo , Condrócitos/patologia , Estresse do Retículo Endoplasmático/fisiologia , Matriz Extracelular/patologia , Humanos , Inflamação , Ligamentos/citologia , Ligamentos/patologia , Mutação , Osteocondrodisplasias/genética , Osteocondrodisplasias/patologia , Tendões/citologia , Tendões/patologia , Tenócitos/patologia
16.
Eur J Nucl Med Mol Imaging ; 47(11): 2525-2532, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32666395

RESUMO

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) is an emerging worldwide threat to public health. While chest computed tomography (CT) plays an indispensable role in its diagnosis, the quantification and localization of lesions cannot be accurately assessed manually. We employed deep learning-based software to aid in detection, localization and quantification of COVID-19 pneumonia. METHODS: A total of 2460 RT-PCR tested SARS-CoV-2-positive patients (1250 men and 1210 women; mean age, 57.7 ± 14.0 years (age range, 11-93 years) were retrospectively identified from Huoshenshan Hospital in Wuhan from February 11 to March 16, 2020. Basic clinical characteristics were reviewed. The uAI Intelligent Assistant Analysis System was used to assess the CT scans. RESULTS: CT scans of 2215 patients (90%) showed multiple lesions of which 36 (1%) and 50 patients (2%) had left and right lung infections, respectively (> 50% of each affected lung's volume), while 27 (1%) had total lung infection (> 50% of the total volume of both lungs). Overall, 298 (12%), 778 (32%) and 1300 (53%) patients exhibited pure ground glass opacities (GGOs), GGOs with sub-solid lesions and GGOs with both sub-solid and solid lesions, respectively. Moreover, 2305 (94%) and 71 (3%) patients presented primarily with GGOs and sub-solid lesions, respectively. Elderly patients (≥ 60 years) were more likely to exhibit sub-solid lesions. The generalized linear mixed model showed that the dorsal segment of the right lower lobe was the favoured site of COVID-19 pneumonia. CONCLUSION: Chest CT combined with analysis by the uAI Intelligent Assistant Analysis System can accurately evaluate pneumonia in COVID-19 patients.


Assuntos
Betacoronavirus , Infecções por Coronavirus/diagnóstico por imagem , Aprendizado Profundo , Pulmão/diagnóstico por imagem , Tomografia Computadorizada Multidetectores/métodos , Pandemias , Pneumonia Viral/diagnóstico por imagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus/isolamento & purificação , Criança , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Software , Adulto Jovem
17.
BMJ Open ; 10(7): e036335, 2020 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-32709647

RESUMO

OBJECTIVES: Bioelectrical impedance analysis (BIA) is a simple and inexpensive method to estimate body composition. However, the accuracy of BIA is unknown. We aimed to assess the accuracy of BIA in estimating visceral fat area (VFA) in patients with gastric cancer. STUDY DESIGN: This was a cross-sectional study comparing the accuracy of BIA in estimating VFA with the gold standard method measured by CT. VFA was measured in enrolled patients both by CT and BIA. VFA by CT at umbilical level ≥100 cm2 was considered as visceral obesity. Reliability between the two methods was assessed by intraclass correlation coefficient (ICC) and consistency was assessed by Bland-Altman method (95% limits of agreement). The area under the receiver operating characteristic curve (AUROC) was used to assess the performance of BIA in diagnosing visceral obesity. SETTING: The study was conducted in China. PARTICIPANTS: From 1 January 2017 to 1 December 2018, a total of 157 patients diagnosed with gastric cancer were enrolled. RESULTS: Overall, VFA by CT and BIA in patients was 84.39±46.43 cm2 and 71.94±22.44 cm2, respectively. VFA estimated by BIA was positively correlated with VFA measured by CT using Pearson's test (r=0.650, p<0.001). Overall, ICC for the two methods was 0.675. The mean bias between the two measurements was 12.45±36.13 cm2. The 95% limits of agreement ranged from -58.36 cm2 to 83.26 cm2. The cut-off value for diagnosing visceral obesity by BIA was 81 cm2 (AUROC: 0.822, p<0.001, 95% CI 0.758 to 0.887). CONCLUSIONS: VFA measured by BIA showed satisfactory reliability with that measured by CT. However, the absolute values of the two methods were not interchangeable. The cut-off value for VFA by BIA in diagnosing visceral obesity was 81 cm2 for patients with gastric cancer in the Chinese population.

18.
Genome Biol Evol ; 12(7): 1060-1073, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32602886

RESUMO

Although the DD41D (named as Visitor, VS) family of Tc1/mariner transposons was discovered in Arthropods and Mollusca, the evolution profile of this family is still largely unknown. We found that VS is widespread in the animal kingdom, including 140 species of 18 orders in invertebrates and 30 species of 12 orders in vertebrates, and one land plant species. Our data revealed multiple horizontal transfer events in both invertebrates and vertebrates and invasion into multiple lineages of mammals, including Chiroptera (seven species), Dasyuromorphia/Marsupialia (one species), Didelphimorphia/Marsupialia (one species), Diprotodontia/Marsupialia (two species), and Primates (one species). Phylogenetic analysis revealed a close relationship of VSs to DD37D/maT and DD34D/mariner and confirmed that VSs with the DD40D signature identified previously are not a distinct family but originated from DD41D/VS. Age analysis revealed that the most recent invasion of VSs was found in ray-finned fishes and a toad, followed by relatively young invasions in bats and marsupials, whereas VSs in mammals, jawless fishes, and lizards were mainly represented by ancient copies, suggesting old age. Phylogenetic analyses and comparison of pairwise distances between VSs and recombination-activating gene 1 (RAG1) support horizontal transfer events of VSs in vertebrates. The intact VSs from bats were nonfunctional as determined by the transposition activity assay. Some vertebrate lineages and species were identified as the hot hosts of Tc1/mariner transposons. Overall, our study presents the evolution profile of VSs and suggests that VSs play roles in diversifying and shaping the genomes of diverse animal lineages.

19.
J Neuroinflammation ; 17(1): 178, 2020 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-32513185

RESUMO

BACKGROUND: Major depressive disorder (MDD) is a highly prevalent psychiatric disorder, and inflammation has been considered crucial components of the pathogenesis of depression. NLRP1 inflammasome-driven inflammatory response is believed to participate in many neurological disorders. However, it is unclear whether NLRP1 inflammasome is implicated in the development of depression. METHODS: Animal models of depression were established by four different chronic stress stimuli including chronic unpredictable mild stress (CUMS), chronic restrain stress (CRS), chronic social defeat stress (CSDS), and repeat social defeat stress (RSDS). Depressive-like behaviors were determined by sucrose preference test (SPT), forced swim test (FST), tail-suspension test (TST), open-field test (OFT), social interaction test (SIT), and light-dark test (LDT). The expression of NLRP1 inflammasome complexes, BDNF, and CXCL1/CXCR2 were tested by western blot and quantitative real-time PCR. The levels of inflammatory cytokines were tested by enzyme-linked immunosorbent assay (ELISA) kits. Nlrp1a knockdown was performed by an adeno-associated virus (AAV) vector containing Nlrp1a-shRNA-eGFP infusion. RESULTS: Chronic stress stimuli activated hippocampal NLRP1 inflammasome and promoted the release of pro-inflammatory cytokines IL-1ß, IL-18, IL-6, and TNF-α in mice. Hippocampal Nlrp1a knockdown prevented NLRP1 inflammasome-driven inflammatory response and ameliorated stress-induced depressive-like behaviors. Also, chronic stress stimuli caused the increase in hippocampal CXCL1/CXCR2 expression and low BDNF levels in mice. Interestingly, Nlrp1a knockdown inhibited the up-regulation of CXCL1/CXCR2 expression and restored BDNF levels in the hippocampus. CONCLUSIONS: NLRP1 inflammasome-driven inflammatory response contributes to chronic stress induced depressive-like behaviors and the mechanism may be related to CXCL1/CXCR2/BDNF signaling pathway. Thus, NLRP1 inflammasome could become a potential antidepressant target.

20.
Carcinogenesis ; 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32531052

RESUMO

Dual oxidase 2 (DUOX2) is an important regulatory protein in the organic process of thyroid hormone iodine. Mounting evidence suggests that DUOX2 plays a crucial role in the occurrence and development of cancers. However, the function and mechanism of DUOX2 in colorectal cancer (CRC) has not been fully clarified. In the present study, the relationship between the expression of DUOX2 and the clinicopathological features and prognosis of CRC patients was analyzed. Furthermore, the effects of DUOX2 on proliferation and invasion in vitro and in vivo were examined. DUOX2-associated proteins were identified by immunoprecipitation (IP). Next-generation sequencing (NGS) detection was performed to illustrate the mechanism of DUOX2 in CRC cells. It was found that the expression levels of DUOX2 in metastatic sites were significantly higher than those in primary tumor tissues, and this was demonstrated to be associated with poor prognosis. The knockdown of DUOX2 inhibited the invasion and migration of CRC cells. Furthermore, DUOX2 regulated the stability of ribosomal protein uL3 (RPL3) by affecting the ubiquitination status of RPL3, and the invasion and migration ability of DUOX2 can be reversed by the overexpression of RPL3. The downregulation of DUOX2 can affect the expression level of a large number of genes, and a number of these are enriched in the PI3K-AKT pathway. Some of the changes caused by DUOX2 can be reversed by RPL3. In summary, DUOX2 exhibits a significantly higher expression in CRC tumor samples, and facilitates the invasion and metastasis ability of CRC cells by interacting with RPL3.

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