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1.
Theranostics ; 11(6): 2691-2705, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33456567

RESUMO

Rationale: Despite landmark therapy of chronic myelogenous leukemia (CML) with tyrosine kinase inhibitors (TKIs), drug resistance remains problematic. Cancer pathogenesis involves epigenetic dysregulation and in particular, histone lysine demethylases (KDMs) have been implicated in TKI resistance. We sought to identify KDMs with altered expression in CML and define their contribution to imatinib resistance. Methods: Bioinformatics screening compared KDM expression in CML versus normal bone marrow with shRNA knockdown and flow cytometry used to measure effects on imatinib-induced apoptosis in K562 cells. Transcriptomic analyses were performed against KDM6A CRISPR knockout/shRNA knockdown K562 cells along with gene rescue experiments using wildtype and mutant demethylase-dead KDM6A constructs. Co-immunoprecipitation, luciferase reporter and ChIP were employed to elucidate mechanisms of KDM6A-dependent resistance. Results: Amongst five KDMs upregulated in CML, only KDM6A depletion sensitized CML cells to imatinib-induced apoptosis. Re-introduction of demethylase-dead KDM6A as well as wild-type KDM6A restored imatinib resistance. RNA-seq identified NTRK1 gene downregulation after depletion of KDM6A. Moreover, NTRK1 expression positively correlated with KDM6A in a subset of clinical CML samples and KDM6A knockdown in fresh CML isolates decreased NTRK1 encoded protein (TRKA) expression. Mechanistically, KDM6A was recruited to the NTRK1 promoter by the transcription factor YY1 with subsequent TRKA upregulation activating down-stream survival pathways to invoke imatinib resistance. Conclusion: Contrary to its reported role as a tumor suppressor and independent of its demethylase function, KDM6A promotes imatinib-resistance in CML cells. The identification of the KDM6A/YY1/TRKA axis as a novel imatinib-resistance mechanism represents an unexplored avenue to overcome TKI resistance in CML.

2.
Epidemiol Infect ; 149: e10, 2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-33397520

RESUMO

This study aims to locate the knots of cumulative coronavirus disease 2019 (COVID-19) case number during the first-level response to public health emergency in the provinces of China except Hubei. The provinces were grouped into three regions, namely eastern, central and western provinces, and the trends between adjacent knots were compared among the three regions. COVID-19 case number, migration scale index, Baidu index, demographic, economic and public health resource data were collected from 22 Chinese provinces from 19 January 2020 to 12 March 2020. Spline regression was applied to the data of all included, eastern, central and western provinces. The research period was divided into three stages by two knots. The first stage (from 19 January to around 25 January) was similar among three regions. However, in the second stage, growth of COVID-19 case number was flatter and lasted longer in western provinces (from 25 January to 18 February) than in eastern and central provinces (from 26 February to around 11 February). In the third stage, the growth of COVID-19 case number slowed down in all the three regions. Included covariates were different among the three regions. Overall, spline regression with covariates showed the different change patterns in eastern, central and western provinces, which provided a better insight into regional characteristics of COVID-19 pandemic.

3.
Sci Rep ; 11(1): 1067, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33441743

RESUMO

The gut microbiota's metabolome is composed of bioactive metabolites that confer disease resilience. Probiotics' therapeutic potential hinges on their metabolome altering ability; however, characterizing probiotics' metabolic activity remains a formidable task. In order to solve this problem, an artificial model of the human gastrointestinal tract is introduced coined the ABIOME (A Bioreactor Imitation of the Microbiota Environment) and used to predict probiotic formulations' metabolic activity and hence therapeutic potential with machine learning tools. The ABIOME is a modular yet dynamic system with real-time monitoring of gastrointestinal conditions that support complex cultures representative of the human microbiota and its metabolome. The fecal-inoculated ABIOME was supplemented with a polyphenol-rich prebiotic and combinations of novel probiotics that altered the output of bioactive metabolites previously shown to invoke anti-inflammatory effects. To dissect the synergistic interactions between exogenous probiotics and the autochthonous microbiota a multivariate adaptive regression splines (MARS) model was implemented towards the development of optimized probiotic combinations with therapeutic benefits. Using this algorithm, several probiotic combinations were identified that stimulated synergistic production of bioavailable metabolites, each with a different therapeutic capacity. Based on these results, the ABIOME in combination with the MARS algorithm could be used to create probiotic formulations with specific therapeutic applications based on their signature metabolic activity.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33395682

RESUMO

BACKGROUND/AIMS: Endoscopic vidian neurectomy (EVN) for allergic rhinitis (AR) has good clinical effects. However, the pathophysiological basis of the effect of EVN on AR is still poorly understood. This study aimed to investigate the efficacy of EVN on house dust mite (HDM)-sensitive AR and the dynamic changes of serum immunoglobulin E and some immune regulatory factors. METHODS: Twenty HDM-sensitive AR patients were treated with bilateral EVN (EVN group), 15 HDM-sensitive AR patients were treated with subcutaneous immunotherapy (SCIT group), and 15 healthy subjects served as healthy controls. Quality of daily life was assessed by the scores of the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQs). The visual analog scale was used to assess clinical efficacy. Serum molecules were measured by ELISA and the UNICAP system. RESULTS: Compared with the SCIT group, the RQLQs in the EVN group were lower 12 months after treatment (both p < 0.05). There was no significant difference in improving nasal itching and sneezing (both p > 0.05), but the clinical efficacy of bilateral EVN was greater than SCIT in improving nasal obstruction, rhinorrhea, eye itching, and lachrymation 12 months after treatment (all p < 0.05). Compared with before treatment, the serum levels of total immunoglobulin E (tIgE), Dermatophagoides pteronyssinus- and Dermatophagoides farinae-specific immunoglobulin E (sIgE), and tumor necrosis factor (TNF)-α in the EVN group and the serum levels of TNF-α and interleukin-4 in the SCIT group were lower 12 months after treatment (all p < 0.05). CONCLUSION: The short-term efficacy of bilateral EVN is more effective than SCIT in treating HDM-sensitive AR. This may be because the surgery reduced the tIgE and sIgE levels. TNF-α may be involved in the therapeutic mechanism.

5.
Life Sci ; 264: 118707, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33144187

RESUMO

Circular RNAs (circRNAs) are formed from the genome through diverse back splicing and feature the closed loop. circRNAs are widely available in a variety of cells and characterized by conservation, structural stability, high abundance and tissue-specific or developmental-specific expression. Recent studies have shown that circRNAs are closely related to liver diseases, such as metabolic-associated fatty liver disease, hepatitis, liver cirrhosis and hepatocellular carcinoma. circRNAs play an important role in the progression of liver diseases, are potential diagnostic and prognostic markers, and have translational value in therapy. This article reviews the research on circRNAs in liver diseases, with a view to providing a theoretical basis and new ideas for future research and treatment of liver diseases.


Assuntos
Hepatopatias/tratamento farmacológico , Hepatopatias/genética , RNA Circular/genética , Exossomos/metabolismo , Humanos , Oncogenes , RNA Circular/biossíntese , RNA Circular/metabolismo
6.
Mol Cancer Res ; 19(1): 74-85, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33004623

RESUMO

Reactivated telomerase is a crucial event in the development and progression of a variety of tumors. However, how telomerase is activated in gastric carcinogenesis has not been fully uncovered yet. Here, we identified a key role of the NF-κB/LIN28A/let-7a axis to promote human telomerase reverse transcriptase (hTERT) expression for gastric cancer initiation. Mechanistically, LIN28A expression was upregulated by H. pylori-induced NF-κB activation. And LIN28A, in turn, suppressed let-7a expression, forming the NF-κB/LIN28A/let-7a axis to regulate gene expression upon H. pylori infection. Of note, we first discovered hTERT as a direct target of let-7a, which inhibited hTERT expression by binding to its 3'UTR of mRNA. Therefore, H. pylori-triggered let-7a downregulation enhanced hTERT protein translation, resulting in telomerase reactivation. Furthermore, hTERT enhanced LIN28A expression, forming the positive feedback regulation between hTERT and NF-κB/LIN28A/let-7a axis to maintain the sustained overexpression of hTERT in gastric cancer. IMPLICATIONS: The NF-κB/LIN28A/Let-7a axis was crucial for the overexpression of hTERT upon H. pylori infection during gastric cancer development and may serve as a potential target to suppress hTERT expression for gastric cancer prevention and treatment.

7.
Biomaterials ; 268: 120605, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33360073

RESUMO

Platelet lysate (PL) as a cost-effective cocktail of growth factors is an emerging ingredient in regenerative medicine, especially in cartilage tissue engineering. However, most studies fail to pay attention to PL's intrinsic characteristics and incorporate it directly with scaffolds or hydrogels by simple mixture. Currently, the particle size distribution of PL was determined to be scattered. Directly introducing PL into a thermosensitive poly(d,l-lactide)-poly(ethylene glycol)-poly(d,l-lactide) (PLEL) hydrogel disturbed its sol-gel transition. Electrostatic self-assembly heparin (Hep) and ε-poly-l-lysine (EPL) nanoparticles (NPs) were fabricated to improve the dispersity of PL. Such PL-NPs-incorporated PLEL gels retained the initial gelling capacity and showed a long-term PL-releasing ability. Moreover, the PL-loaded composite hydrogels inhibited the inflammatory response and dedifferentiation of IL-1ß-induced chondrocytes. For in vivo applications, the PLEL@PL-NPs system ameliorated the early cartilage degeneration and promoted cartilage repair in the late stage of osteoarthritis. RNA sequencing analysis indicated that PL's protective effects might be associated with modulating hyaluronan synthase 1 (HAS-1) expression. Taken together, these results suggest that well-dispersed PL by Hep/EPL NPs is a preferable approach for its incorporation into hydrogels and the constructed PLEL@PL-NPs system is a promising cell-free and stepwise treatment option for cartilage tissue engineering.

8.
Pestic Biochem Physiol ; 171: 104720, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33357542

RESUMO

Chilo suppressalis Walker (Lepidoptera: Crambidae) is a widely destructive pest occurring in rice, particularly in the rice-growing regions of Asia. In recent years, C. suppressalis has developed resistance to several insecticides because of the extensive use of insecticides. The resistance levels to four insecticides were determined among populations from different regions of Sichuan Province, China, using a drop-method bioassay. Based on LC50 values of a laboratory susceptible strain, all field populations showed moderate level of resistance to triazophos (23.9- to 83.5-fold) and were either susceptible or had a low level of resistance to abamectin (2.1- to 5.8-fold). All field-collected populations had a low or moderate level of resistance to chlorpyrifos (1.7- to 47.1-fold) and monosultap (2.7- to 13.5-fold). The synergism experiment indicated that the resistance of the XW19 to triazophos may be associated with cytochrome P450 monooxygenases (P450s), with the highest synergistic ratio (SR) of 3.05-fold and increased ratio (IR) of 2.28-fold for piperonylbutoxide (PBO). The P450 activity of the TJ19 population was the greatest among the six field populations. Moreover, the relative expression levels of four resistance-related P450 genes were detected with qRT-PCR, and the results indicated that CYP324A12, CYP321F3 and CYP9A68 were overexpressed in the resistant population, especially in the XW19 population (by 1.2-, 3.4 -, and 18.0-fold, respectively). In addition, the relative expression levels of CYP9A68 among the CZ19 and TJ19 populations were also enhanced 10.5- and 24.9-fold, respectively. These results suggested that CYP324A12, CYP321F3 and CYP9A68 may be related to the resistance development of C. suppressalis to triazophos.


Assuntos
Clorpirifos , Inseticidas , Lepidópteros , Mariposas , Oryza , Animais , China , Clorpirifos/farmacologia , Resistência a Inseticidas/genética , Inseticidas/farmacologia , Mariposas/genética , Oryza/genética
10.
J Formos Med Assoc ; 120(1 Pt 3): 737-743, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32855036

RESUMO

BACKGROUND/PURPOSE: The pharmacokinetics of vancomycin in patients who undergo sustained low efficiency daily diafiltration (SLEDD-f) is not clear. This study aimed to determine the appropriate vancomycin dosage regimen for patients receiving SLEDD-f. METHODS: This prospectively observational study enrolled critically ill patients older than 18 years old that used SLEDD-f as renal replacement therapy and received vancomycin treatment. An 8-h SLEDD-f was performed with FX-60 (high-flux helixone membrane, 1.4 m2). Serial blood samples were collected before, during, and after SLEDD-f to analyse vancomycin serum concentrations. Effluent fluid samples (a mixture of dialysate and ultrafiltrate) were also collected to determine the amount of vancomycin removal. RESULTS: Seventeen patients were enrolled, and 10 completed the study. The amount of vancomycin removal was 447.4 ± 88.8 mg (about 78.4 ± 18.4% of the dose administered before SLEDD-f). The vancomycin concentration was reduced by 57.5 ± 14.9% during SLEDD-f, and this reduction was followed by a rebound with duration of one to three hours. The elimination half-life of vancomycin decreased from 64.1 ± 35.7 h before SLEDD-f to 7.0 ± 3.0 h during SLEDD-f. CONCLUSION: Significant amount of vancomycin removed during SLEDD-f. Despite the existence of post-dialysis rebound, a sufficient supplemental dose is necessary to maintain therapeutic range.

11.
Dev Comp Immunol ; 114: 103869, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32950537

RESUMO

Integrins are transmembrane glycoproteins that are broadly distributed in living organisms. As a heterodimer, they contain an α and a ß subunit, which are reported to be associated with various physiological and pathological processes. In the present study, a 2502 bp full-length cDNA sequence of Bmintegrin ß1 was obtained from the silkworm, Bombyx mori. Bmintegrin ß1 belongs to the ß subunit of the integrin family and contains several typical structures of integrins. Gene expression profile analysis demonstrated that Bmintegrin ß1 was ubiquitously expressed in all tested tissues and organs, with the maximum expression levels in fat body and hemocytes. The immunofluorescence results showed that Bmintegrin ß1 was located in the cell membrane and widely distributed in fat bodies and different types of hemocytes. Bmintegrin ß1 expression was remarkably increased after challenging with different kinds of bacteria and pathogen-associated molecular patterns (PAMPs). Further investigation revealed that Bmintegrin ß1 could participate in the agglutination of pathogenic bacteria possibly through direct binding with the relative bacteria and PAMPs. Altogether, this study provides a novel insight into the immune functional features of Bmintegrin ß1.

12.
Front Chem ; 8: 593261, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33282834

RESUMO

We report here the synthesis of a 1,3-alternate calix[4]arene 8, with bis-pyrazolylmethylpyrenes on the one end and bis-triazolylmethylphenyls on the other end, as a homoditropic fluorescent sensor for both Hg2+ and Ag+ ions. Calix[4]arene 3, with lower-rim bis-pyrazolylmethylpyrenes in cone conformation, was also synthesized as a control compound. UV-Vis and fluorescence spectra were used for metal ions screening, and we found that both ligands 8 and 3 showed strong excimer emission of pyrenes when they are as a free ligand in CHCl3/MeOH (v/v, 3:1) solution; however, they both showed a high selectivity toward Hg2+ and Ag+ ions with strong fluorescence quenching and yet with different binding ratios. The fluorescence of ligand 8 was strongly quenched by Hg2+ but was only partially quenched by Ag+ ions; however, the fluorescence of ligand 3 was strongly quenched by Hg2+, Ag+, and Cu2+ ions. Job plot experiments showed that ligand 8 formed a 1:2 complex with both Hg2+ and Ag+ ions; ligand 3 formed a 1:1 complex with Hg2+, but it formed a 2:3 complex with Ag+. The binding constant of ligand 3 with Hg2+ and Ag+ ions was determined by the Benesi-Hildebrand plot of UV-vis titration experiments to be 2.99 × 103 and 3.83 × 103 M-1, respectively, while the association constant of ligand 8 with Hg2+ and Ag+ was determined by Hill plot to be 1.46 × 1012 and 9.24 × 1011 M-2, respectively. Ligand 8 forms a strong complex with either two Hg2+ or two Ag+ ions using both the upper and lower rims of the 1,3-alternate calix[4]arene as the binding pockets; hence, it represents one of the highly selective fluorescent sensors for the homoditropic sensing of Hg2+ and Ag+ ions.

13.
Curr Med Sci ; 40(6): 1114-1120, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33263178

RESUMO

Angiopoietin-like protein 2 (ANGPTL2) stimulates inflammation and is important in the pathogenesis of diabetic kidney disease (DKD). Irbesartan is helpful in reducing diabetes-induced renal damage. In this study, the effects of irbesartan on DKD and its renal protective role involving ANGPTL2 in DKD rats were examined. Wistar rats were divided into normal, DKD, and DKD + irbesartan groups. The DKD + irbesartan group was treated once daily for 8 weeks with 50 mg/kg irbesartan via intragastric gavage. The 24-h urinary albumin was determined each week, renal pathological changes were observed, and expression of ANGPTL2 and nuclear factor-kappa B (NF-κB) in rat renal tissue was assessed by immunohistochemistry. Mouse podocytes cultured in a high concentration of glucose were classified into four groups based on the irbesartan concentrations (0, 25, 50, and 75 ºg/mL). Expression of ANGPTL2 and phosphorylated IκB-α was assessed by Western blotting. The mRNA levels of ANGPTL2 and monocyte chemotactic protein 1 (MCP-1) were assessed by real-time polymerase chain reaction. The DKD rats displayed proteinuria, podocyte injury, and increased ANGPTL2 and NF-κB expression. All were relieved by irbesartan treatment. In podocytes cultured in elevated glucose, ANGPTL2 and phosphorylated IκB-α were overexpressed at the protein level, and ANGPTL2 and MCP-1 were highly expressed at the mRNA level. Irbesartan down-regulated ANGPTL2 and phosphorylated IκB-αexpression at the protein level and inhibited ANGPTL2 and MCP-1 expression at the mRNA level. The ameliorative effects of irbesartan against DKD involves podocyte protection and suppression of ANGPTL2.

14.
Cell Transplant ; 29: 963689720973647, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33300392

RESUMO

The healing of tendon-bone in the rotator cuff is featured by the formation of the scar tissues in the interface after repair. This study aimed to determine if the 3D-printed poly lactic-co-glycolic acid (PLGA) scaffolds loaded with bone marrow-derived mesenchymal stem cells (BMSCs) could augment the rotator cuff repair in the rabbits. PLGA scaffolds were generated by the 3D-printed technology; Cell Counting Kit-8 assay evaluated the proliferation of BMSCs; the mRNA and protein expression levels were assessed by quantitative real-time polymerase chain reaction and western blot, respectively; immunohistology evaluated the rotator cuff repair; biomechanical characteristics of the repaired tissues were also assessed. 3D-printed PLGA scaffolds showed good biocompatibility without affecting the proliferative ability of BMSCs. BMSCs-PLGA scaffolds implantation enhanced the cell infiltration into the tendon-bone injunction at 4 weeks after implantation and improved the histology score in the tendon tissues after implantation. The mRNA expression levels of collagen I, III, tenascin, and biglycan were significantly higher in the scaffolds + BMSCs group at 4 weeks post-implantation than that in the scaffolds group. At 8 and 12 weeks after implantation, the biglycan mRNA expression level in the BMSCs-PLGA scaffolds group was significantly lower than that in the scaffolds group. BMSCs-PLGA scaffolds implantation enhanced collagen formation and increased collagen dimeter in the tendon-bone interface. The biomechanical analysis showed that BMSCs-PLGA scaffolds implantation improved the biomechanical properties of the regenerated tendon. The combination of 3D-printed PLGA scaffolds with BMSCs can augment the tendon-bone healing in the rabbit rotator cuff repair model.

15.
J Thorac Oncol ; 2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33309987

RESUMO

INTRODUCTION: The treatment of patients with EGFR-mutant NSCLC with vascular endothelial growth factor (VEGF) inhibitors in combination with EGFR inhibitors provides a greater benefit than EGFR inhibition alone, suggesting that EGFR mutation status may define a patient subgroup with greater benefit from VEGF blockade. The mechanisms driving this potentially enhanced VEGF dependence are unknown. METHODS: We analyzed the effect of EGFR inhibition on VEGF and HIF-1α in NSCLC models in vitro and in vivo. We determined the efficacy of VEGF inhibition in xenografts and analyzed the impact of acquired EGFR inhibitor resistance on VEGF and HIF-1α. RESULTS: NSCLC cells with EGFR-activating mutations exhibited altered regulation of VEGF compared with EGFR wild-type cells. In EGFR-mutant cells, EGFR, not hypoxia, was the dominant regulator of HIF-1α and VEGF. NSCLC tumor models bearing classical or exon 20 EGFR mutations were more sensitive to VEGF inhibition than EGFR wild-type tumors, and a combination of VEGF and EGFR inhibition delayed tumor progression. In models of acquired EGFR inhibitor resistance, whereas VEGF remained overexpressed, the hypoxia-independent expression of HIF-1α was delinked from EGFR signaling, and EGFR inhibition no longer diminished HIF-1α or VEGF expression. CONCLUSIONS: In EGFR-mutant NSCLC, EGFR signaling is the dominant regulator of HIF-1α and VEGF in a hypoxia-independent manner, hijacking an important cellular response regulating tumor aggressiveness. Cells with acquired EGFR inhibitor resistance retained elevated expression of HIF-1α and VEGF, and the pathways were no longer EGFR-regulated. This supports VEGF targeting in EGFR-mutant tumors in the EGFR inhibitor-naive and refractory settings.

16.
Huan Jing Ke Xue ; 41(12): 5470-5479, 2020 Dec 08.
Artigo em Chinês | MEDLINE | ID: mdl-33374063

RESUMO

In recent years, quinolone antibiotics (QNs), which easily bioaccumulate in aquatic organisms, have been widely detected in lake ecosystems, and the bioaccumulation and trophic transfer behavior are obviously spatiotemporally different. In this study, the bioaccumulation and trophic transfer behavior of fourteen QNs in nine dominant fish species were studied, the correlation with environmental factors was analyzed, and the health risk of QNs was evaluated in Baiyangdian Lake. The results showed that the mass concentrations of ∑QNs in water varied from 0.7400 to 1590 ng·L-1. Furthermore, the detected frequencies of flumequine (FLU), oxolinic acid (OXO), and ofloxacin (OFL) were higher, and the average mass concentration of FLU was the highest. The content of ∑QNs in fish ranged from 17.1 to 146 ng·g-1, and the average contents of ciprofloxacin (CIP) and OFL were higher. The bioaccumulation factors (BAF) were in the range of 96.2 (BAFMAR)-489 (BAFCIP) L·kg-1, indicating the bioaccumulation of QNs was low in dominant fish species. The trophic magnification factors (TMF) of five QNs (enrofloxacin (ENR), FLU, marbofloxacin (MAR), norfloxacin (NOR), and OFL) varied from 0.714 (TMFMAR) to 1.33 (TMFENR), indicating ENR exhibited trophic magnification, while FLU, MAR, and ∑QNs exhibited trophic dilution. The results of correlation analysis between environmental parameters and BAF/TMF showed that pH, T, SD, DO, COD, TP, TN, NH4+-N, NO3--N, and PO43--P were significantly related to the bioaccumulation of QNs in fish. The results of human health risk showed that the hazard quotient (HQ) of CIP (0.0040-0.026) was significantly higher than that of other QNs (≤ 0.0050), and the hazard indices (HI) ranged from 0.0010 to 0.035, indicating a high level of health risk. Therefore, to reduce the health risk, the standard and residue limits of QNs should be set in Baiyangdian Lake.


Assuntos
Quinolonas , Poluentes Químicos da Água , Animais , Bioacumulação , China , Ecossistema , Monitoramento Ambiental , Peixes , Cadeia Alimentar , Humanos , Lagos , Quinolonas/análise , Poluentes Químicos da Água/análise
17.
BMC Bioinformatics ; 21(Suppl 21): 563, 2020 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-33371868

RESUMO

The International Association for Intelligent Biology and Medicine (IAIBM) is a nonprofit organization that promotes intelligent biology and medical science. It hosts an annual International Conference on Intelligent Biology and Medicine (ICIBM), which was initially established in 2012. Due to the coronavirus (COVID-19) pandemic, the ICIBM 2020 was held for the first time as a virtual online conference on August 9 to 10. The virtual conference had ~ 300 registered participants and featured 41 online real-time presentations. ICIBM 2020 received a total of 75 manuscript submissions, and 12 were selected to be published in this special issue of BMC Bioinformatics. These 12 manuscripts cover a wide range of bioinformatics topics including network analysis, imaging analysis, machine learning, gene expression analysis, and sequence analysis.


Assuntos
Biologia Computacional/métodos , Congressos como Assunto , Internacionalidade , Medicina , Pesquisa , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Aprendizado de Máquina , Análise de Sequência
18.
BMC Bioinformatics ; 21(Suppl 21): 535, 2020 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-33371873

RESUMO

BACKGROUND: Although genetic risk factors and network-level neuroimaging abnormalities have shown effects on cognitive performance and brain atrophy in Alzheimer's disease (AD), little is understood about how apolipoprotein E (APOE) ε4 allele, the best-known genetic risk for AD, affect brain connectivity before the onset of symptomatic AD. This study aims to investigate APOE ε4 effects on brain connectivity from the perspective of multimodal connectome. RESULTS: Here, we propose a novel multimodal brain network modeling framework and a network quantification method based on persistent homology for identifying APOE ε4-related network differences. Specifically, we employ sparse representation to integrate multimodal brain network information derived from both the resting state functional magnetic resonance imaging (rs-fMRI) data and the diffusion-weighted magnetic resonance imaging (dw-MRI) data. Moreover, persistent homology is proposed to avoid the ad hoc selection of a specific regularization parameter and to capture valuable brain connectivity patterns from the topological perspective. The experimental results demonstrate that our method outperforms the competing methods, and reasonably yields connectomic patterns specific to APOE ε4 carriers and non-carriers. CONCLUSIONS: We have proposed a multimodal framework that integrates structural and functional connectivity information for constructing a fused brain network with greater discriminative power. Using persistent homology to extract topological features from the fused brain network, our method can effectively identify APOE ε4-related brain connectomic biomarkers.


Assuntos
Alelos , Apolipoproteína E4/genética , Encéfalo/diagnóstico por imagem , Conectoma , Adulto , Idoso , Encéfalo/fisiopatologia , Imagem de Difusão por Ressonância Magnética , Feminino , Heterozigoto , Humanos , Imagem por Ressonância Magnética , Masculino
19.
BMC Med Genomics ; 13(Suppl 11): 189, 2020 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-33371870

RESUMO

This editorial summarizes eight research articles included in this supplement issue for the 2020 International Conference on Intelligent Biology and Medicine (ICIBM 2020) conference, that was held on August 9-10, 2020 (virtual conference), with a topic on data-driven analytics in biomedical genomics. These articles cover a wide range of topics in medical genomics that focus on integrative analysis of genomics data together with other types of data toward understanding complex human diseases, including cancer. With the growing importance of data analytics in biomedical science, we expect this collection of research articles provides scientific discussions in this direction.

20.
BMC Genomics ; 21(Suppl 11): 831, 2020 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-33372588

RESUMO

In this introduction article, we summarize the 2020 International Conference on Intelligent Biology and Medicine (ICIBM 2020) conference which was held on August 9-10, 2020 (virtual conference). We then briefly describe the nine research articles included in this supplement issue. ICIBM 2020 hosted four scientific sections covering current topics in bioinformatics, computational biology, genomics, biomedical informatics, among others. A total of 75 original manuscripts were submitted to ICIBM 2020. All the papers were under rigorous review (at least three reviewers), and highly ranked manuscripts were selected for oral presentation and supplement issues. This genomics supplement issue included nine manuscripts. These articles cover methods and applications for single cell RNA sequencing, multi-omics data integration for gene regulation, gene fusion detection from long-read RNA sequencing, gene co-expression analysis of metabolic pathways in cancer, integrative genome-wide association studies (GWAS) of subcortical imaging phenotype in Alzheimer's disease, as well as deep learning methods for protein structure prediction, metabolic pathway membership inference, and horizontal gene transfer (HGT) insertion sites prediction.

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