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1.
New Phytol ; 2022 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-34997964

RESUMO

Clarifying the evolutionary processes underlying species diversification and adaptation is a key focus of evolutionary biology. Begonia (Begoniaceae) is one of the most species-rich angiosperm genera with ~2,000 species, most of which are shade-adapted. Here, we present chromosome-scale genome assemblies for four species of Begonia (B. loranthoides, B. masoniana, B. darthvaderiana, and B. peltatifolia), and whole genome shot-gun data for an additional 74 Begonia representatives to investigate lineage evolution and shade adaptation of the genus. The four genome assemblies range in size from 331.75 Mb (B. peltatifolia) to 799.83 Mb (B. masoniana), and harbor 22,059 - 23,444 protein-coding genes. Synteny analysis revealed a lineage specific whole-genome duplication (WGD) that occurred just before the diversification of the Begonia. Functional enrichment of gene families retained after WGD highlight the significance of modified carbohydrate metabolism and photosynthesis possibly linked to shade-adaptation in the genus, which is further supported by expansions of gene families involved in light perception and harvesting. Phylogenomic reconstructions and genomics studies indicate that genomic introgression has also played a role in the evolution of Begonia. Overall, this study provides valuable genomic resources for Begonia and suggests potential drivers underlying the diversity and adaptive evolution of this mega-diverse clade.

2.
Nat Genet ; 54(1): 52-61, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34980918

RESUMO

The gut microbiome has been implicated in a variety of physiological states, but controversy over causality remains unresolved. Here, we performed bidirectional Mendelian randomization analyses on 3,432 Chinese individuals with whole-genome, whole-metagenome, anthropometric and blood metabolic trait data. We identified 58 causal relationships between the gut microbiome and blood metabolites, and replicated 43 of them. Increased relative abundances of fecal Oscillibacter and Alistipes were causally linked to decreased triglyceride concentration. Conversely, blood metabolites such as glutamic acid appeared to decrease fecal Oxalobacter, and members of Proteobacteria were influenced by metabolites such as 5-methyltetrahydrofolic acid, alanine, glutamate and selenium. Two-sample Mendelian randomization with data from Biobank Japan partly corroborated results with triglyceride and with uric acid, and also provided causal support for published fecal bacterial markers for cancer and cardiovascular diseases. This study illustrates the value of human genetic information to help prioritize gut microbial features for mechanistic and clinical studies.

3.
Artigo em Inglês | MEDLINE | ID: mdl-35014784

RESUMO

Due to the declined function of bone marrow mesenchymal stem cells (BMSCs), the repair of bone defects in the elderly is retarded. Elimination of senescent cells emerges as a promising strategy for treating age-related diseases. However, whether the local elimination of senescent BMSCs can promote bone regeneration in the elderly remains elusive. To tackle the above issue, we first screened out the specific senolytics for BMSCs and confirmed their effect of eliminating senescent BMSCs in vitro. Treatment with quercetin, which is determined the best senolytics for senescent BMSCs, efficiently removed senescent cells in the population. Moreover, the self-renewal capacity was restored as well as osteogenic ability of BMSCs after treatment. We then designed a microenvironment-responsive hydrogel based on the MMPs secreted by senescent cells. This quercetin-encapsulated hydrogel exhibited a stable microstructure and responsively released quercetin in the presence of senescence in vitro. In vivo, the quercetin-loaded hydrogel effectively cleared the local senescent cells and reduced the secretion of MMPs in the bone. Due to the removal of local senescent cells, the hydrogel significantly accelerated the repair of bone defects in the femur and skull of old rats. Taken together, our study revealed the role of removing senescent cells in bone regeneration and provided a novel therapeutic approach for bone defects in aged individuals.

4.
Br J Ophthalmol ; 2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-35027355

RESUMO

BACKGROUND: Vision-dependent mechanisms play a role in myopia progression in childhood. Thus, we investigated the distribution of ocular and corneal higher-order aberrations (HOAs) in highly myopic Chinese children and adolescents and the relationship between HOA components and 1-year axial eye growth. METHODS: Baseline cycloplegic ocular and corneal HOAs, axial length (AL), spherical equivalent (SE), astigmatism and interpupillary distance (IPD) were determined for the right eyes of 458 highly myopic (SE ≤-5.0D) subjects. HOAs were compared among baseline age groups (≤12 years, 13-15 years and 16-18 years). Ninety-nine subjects completed the 1-year follow-up. Linear mixed model analyses were applied to determine the association between HOA components, other known confounding variables (age, gender, SE, astigmatism and IPD) and axial growth. A comparison with data from an early study of moderate myopia were conducted. RESULTS: Almost all ocular HOAs and few corneal HOAs exhibited significant differences between different age groups (all p<0.05). After 1 year, only ocular HOA components was significantly negative associated with a longer AL, including secondary horizontal comatic aberration (p=0.019), primary spherical aberration (p<0.001) and spherical HOA (p=0.026). Comparing with the moderate myopia data, the association of comatic aberration with AL growth was only found in high myopia. CONCLUSION: In highly myopic children and adolescents, lower levels of annual ocular secondary horizontal comatic aberration changes, besides spherical aberrations, were associated with axial elongation. This suggests that ocular HOA plays a potential role in refractive development in high myopia.

5.
Anal Chem ; 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34852202

RESUMO

The lack of an efficient method for the identification of tumor antigen-specific T cell receptors (TCRs) impedes the development of T cell-based cancer immunotherapies. Here, we introduce a droplet-based microfluidic platform for function-based screening and sorting of tumor antigen-specific T cells with high throughput. We built a reporter cell line by co-transducing the TCR library and reporter genes at the downstream of TCR signaling, and reporter cells fluoresced upon functionally binding with antigens. We co-encapsulated reporter cells and antigen-presenting cells in droplets to allow for stimulation on a single-cell level. Functioning reporter cells specific against the antigen were identified in the microfluidic channel based on the fluorescent signals of the droplets, which were immediately sorted out using dielectrophoresis. We validated the reporter system and sorting results using flow cytometry. We then performed single-cell RNA sequencing on the sorted cells to further validate this platform and demonstrate the compatibility with genetic characterizations. Our platform provides a means for precise and efficient T cell immunotherapy, and the droplet-based high-throughput TCR screening method could potentially facilitate immunotherapeutic screening and promote T cell-based anti-tumor therapies.

6.
Cell Discov ; 7(1): 117, 2021 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-34873157

RESUMO

The oral microbiota contains billions of microbial cells, which could contribute to diseases in many body sites. Challenged by eating, drinking, and dental hygiene on a daily basis, the oral microbiota is regarded as highly dynamic. Here, we report significant human genomic associations with the oral metagenome from more than 1915 individuals, for both the tongue dorsum (n = 2017) and saliva (n = 1915). We identified five genetic loci associated with oral microbiota at study-wide significance (p < 3.16 × 10-11). Four of the five associations were well replicated in an independent cohort of 1439 individuals: rs1196764 at APPL2 with Prevotella jejuni, Oribacterium uSGB 3339 and Solobacterium uSGB 315; rs3775944 at the serum uric acid transporter SLC2A9 with Oribacterium uSGB 1215, Oribacterium uSGB 489 and Lachnoanaerobaculum umeaense; rs4911713 near OR11H1 with species F0422 uSGB 392; and rs36186689 at LOC105371703 with Eggerthia. Further analyses confirmed 84% (386/455 for tongue dorsum) and 85% (391/466 for saliva) of host genome-microbiome associations including six genome-wide significant associations mutually validated between the two niches. As many of the oral microbiome-associated genetic variants lie near miRNA genes, we tentatively validated the potential of host miRNAs to modulate the growth of specific oral bacteria. Human genetics accounted for at least 10% of oral microbiome compositions between individuals. Machine learning models showed that polygenetic risk scores dominated over oral microbiome in predicting risk of dental diseases such as dental calculus and gingival bleeding. These findings indicate that human genetic differences are one explanation for a stable or recurrent oral microbiome in each individual.

7.
Abdom Radiol (NY) ; 2021 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-34918174

RESUMO

BACKGROUND AND OBJECTIVE: To develop a machine-learning model by integrating clinical and imaging modalities for predicting tumor response and survival of hepatocellular carcinoma (HCC) with transarterial chemoembolization (TACE). METHODS: 140 HCC patients with TACE were retrospectively included from two centers. Tumor response were evaluated using modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria. Response-related radiomics scores (Rad-scores) were constructed on T2-weighted images (T2WI) and dynamic contrast-enhanced (DCE) imaging separately, and then integrated with conventional clinic-radiological variables into a logistic regression (LR) model for predicting tumor response. LR model was trained in 94 patients in center 1 and independently tested in 46 patients in center 2. RESULTS: Among 4 MRI sequences, T2WI achieved better performance than DCE (area under the curve [AUC] 0.754 vs 0.602 to 0.752). LR model by combining Rad-score on T2WI with Barcelona Clinic Liver Cancer (BCLC) stage and albumin-bilirubin (ALBI) grade resulted in an AUC of 0.813 in training and 0.781 in test for predicting tumor response. In survival analysis, progression-free survival (PFS) and overall survival (OS) presented significant difference between LR-predicted responders and non-responders. The ALBI grade and BCLC stage were independent predictors of PFS; and LR-predicted response, ALBI grade, satellite node, and BCLC stage were independent predictors of OS. The resulting Cox model produced concordance-indexes of 0.705 and 0.736 for predicting PFS and OS, respectively. CONCLUSIONS: The model combined MRI radiomics with clinical factors demonstrated favorable performance for predicting tumor response and clinical outcomes, thus may help personalized clinical management.

8.
BMJ Open ; 11(12): e048450, 2021 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-34949607

RESUMO

OBJECTIVES: To report on: (a) overall myopia and high myopia prevalence, and (b) the impact of education on the spherical equivalent refractive error in children across Shanghai. DESIGN: Cross-sectional study. SETTING: Across all 17 districts of Shanghai. PARTICIPANTS: 910 245 children aged 4-14 years from a school-based survey conducted between 2012 and 2013. MAIN OUTCOME MEASURES: Data of children with non-cycloplegic autorefraction, visual acuity assessment and questionnaire were analysed (67%, n=6 06 476). Prevalence of myopia (≤-1.0 D) and high myopia (≤-5.0 D) was determined. We used a regression discontinuity design to determine the impact of school entry cut-off date (1 September) by comparing refractive errors at each age, for children born pre-September to post-1 September, and performed a multivariate analysis to explore risk factors associated with myopia. Data analysis was performed in 2017-2018. RESULTS: Prevalence rates of myopia and high myopia were 32.9% (95% CI: 32.8% to 33.1%) and 4.2% (95% CI: 4.1% to 4.2%), respectively. From 6 years of age onwards, children born pre-September were more myopic compared with those born post-1 September (ahead in school by 1 year, discontinuity at 6 years: -0.19 D (95% CI: -0.09 to -0.30 D); 14 years: -0.67 D (95% CI: -0.21 to -1.14 D)). CONCLUSIONS: Our findings suggest that myopia is associated with education, that is primarily focused on near-based activities. Efforts to reduce the burden should be directed to public awareness, reform of education and health systems.

9.
Nat Commun ; 12(1): 6930, 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34836973

RESUMO

Chloranthales remain the last major mesangiosperm lineage without a nuclear genome assembly. We therefore assemble a high-quality chromosome-level genome of Chloranthus spicatus to resolve enigmatic evolutionary relationships, as well as explore patterns of genome evolution among the major lineages of mesangiosperms (eudicots, monocots, magnoliids, Chloranthales, and Ceratophyllales). We find that synteny is highly conserved between genomic regions of Amborella, Vitis, and Chloranthus. We identify an ancient single whole-genome duplication (WGD) (κ) prior to the divergence of extant Chloranthales. Phylogenetic inference shows Chloranthales as sister to magnoliids. Furthermore, our analyses indicate that ancient hybridization may account for the incongruent phylogenetic placement of Chloranthales + magnoliids relative to monocots and eudicots in nuclear and chloroplast trees. Long genes and long introns are found to be prevalent in both Chloranthales and magnoliids compared to other angiosperms. Overall, our findings provide an improved context for understanding mesangiosperm relationships and evolution and contribute a valuable genomic resource for future investigations.

10.
Hum Immunol ; 2021 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-34785098

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the pandemic of coronavirus disease 2019 (COVID-19). Great international efforts have been put into the development of prophylactic vaccines and neutralizing antibodies. However, the knowledge about the B cell immune response induced by the SARS-CoV-2 virus is still limited. Here, we report a comprehensive characterization of the dynamics of immunoglobin heavy chain (IGH) repertoire in COVID-19 patients. By using next-generation sequencing technology, we examined the temporal changes in the landscape of the patient's immunological status and found dramatic changes in the IGH within the patient's immune system after the onset of COVID-19 symptoms. Although different patients have distinct immune responses to SARS-CoV-2 infection, by employing clonotype overlap, lineage expansion, and clonotype network analyses, we observed a higher clonotype overlap and substantial lineage expansion of B cell clones 2-3 weeks after the onset of illness, which is of great importance to B-cell immune responses. Meanwhile, for preferences of V gene usage during SARS-CoV-2 infection, IGHV3-74 and IGHV4-34, and IGHV4-39 in COVID-19 patients were more abundant than those of healthy controls. Overall, we present an immunological resource for SARS-CoV-2 that could promote both therapeutic development as well as mechanistic research.

11.
Phys Med Biol ; 66(24)2021 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-34787107

RESUMO

Choroid thickness measured from optical coherence tomography (OCT) images has emerged as a vital metric in the management of retinal diseases such as high myopia. In this paper, we propose a novel group-wise context selection network (referred to as GCS-Net) to segment the choroid of either normal or high myopia eyes. To deal with the diverse choroid thickness and the variable shape of the pathological retina, GCS-Net adopts the group-wise channel dilation (GCD) module and the group-wise spatial dilation module, which can automatically select group-wise multi-scale information under the guidance of channel attention or spatial attention, and enhance the consistency between the receptive field and the target area. Furthermore, a boundary optimization network with a new edge loss is incorporated to improve the resulting choroid boundary by deep supervision. Experimental results evaluated on a dataset composed of 1650 clinically obtained OCT B-scans show that the proposed GCS-Net can achieve a Dice similarity coefficient of 95.97 ± 0.54%, which outperforms some state-of-the-art segmentation networks.

12.
J Phys Condens Matter ; 34(7)2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34757949

RESUMO

Heterostructures of two-dimensional (2D) layered materials with selective compositions play an important role in creating novel functionalities. Effective interface coupling between 2D ferromagnet and electronic materials would enable the generation of exotic physical phenomena caused by intrinsic symmetry breaking and proximity effect at interfaces. Here, epitaxial growth of bilayer Bi(110) on 2D ferromagnetic Fe3GeTe2(FGT) with large magnetic anisotropy has been reported. Bilayer Bi(110) islands are found to extend along fixed lattice directions of FGT. The six preferred orientations could be divided into two groups of three-fold symmetry axes with the difference approximately to 26°. Moreover, dI/dVmeasurements confirm the existence of interface coupling between bilayer Bi(110) and FGT. A variation of the energy gap at the edges of bilayer Bi(110) is also observed which is modulated by the interface coupling strengths associated with its buckled atomic structure. This system provides a good platform for further study of the exotic electronic properties of epitaxial Bi(110) on 2D ferromagnetic substrate and promotes potential applications in the field of spin devices.

13.
Acta Ophthalmol ; 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34605605

RESUMO

PURPOSE: To investigate the percentages and risk factors for visual impairment (VI) across age groups in a highly myopic cohort with a wide range of age (18-93 years). METHODS: A total of 2099 eyes (1220 participants) were enrolled. All participants underwent detailed ocular examinations. Myopic maculopathy (MM) was assessed as myopic atrophy maculopathy (MAM), myopic traction maculopathy (MTM) or myopic neovascular maculopathy (MNM) based on the ATN system. RESULTS: Most participants younger than 50 years had normal vision, while the cumulative risk of VI and blindness gradually increased after 50-59 years. The percentage of each type of MM increased nonlinearly with ageing (all p < 0.001), with an accelerated period of increase after 45 years for MAM, and after 50 years for MTM and MNM. Axial length (AL) ≥30 mm was the only associated factor for mild VI or worse in participants aged 18-39 years (p < 0.001). Older age, AL ≥30 mm and the presence of MAM were predictors for mild VI or worse in the group aged 40-49 years (all p < 0.05). In participants aged ≥50 years, older age, female sex, longer AL and increased severity of MM were risk factors for VI and blindness (all p < 0.05). CONCLUSION: The percentages of MM and related VI increased nonlinearly with older age, with a turning point at 45 years for MAM, preceding that of MTM, MNM and VI by 5 years, warranting future longitudinal studies to confirm. Different age groups presented different risk factors for VI. Timely screening should be in place for middle-aged high myopes.

14.
iScience ; 24(10): 103186, 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34608450

RESUMO

The COVID-19 pandemic has caused over 220 million infections and 4.5 million deaths worldwide. Current risk factor cannot fully explain the diversity in disease severity. Here, we present a comprehensive analysis of a broad range of patients' laboratory and clinical assessments to investigate the genetic contributions to COVID-19 severity. By performing GWAS analysis, we discovered several concrete associations for laboratory traits and used Mendelian randomization (MR) analysis to further investigate the causality of traits on disease severity. Two causal traits, WBC counts and cholesterol levels, were identified based on MR study, and their functional genes are located at genes MHC complex and ApoE, respectively. Our gene-based analysis and GSEA revealed four interferon pathways, including type I interferon receptor binding and SARS coronavirus and innate immunity. We hope that our work will contribute to studying the genetic mechanisms of disease and serve as a useful reference for COVID-19 diagnosis and treatment.

15.
Int J Nanomedicine ; 16: 6681-6692, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34616151

RESUMO

Purpose: Extracellular vesicles (EVs) are membrane-encapsulated nanoparticles that function as carriers and play a role in intercellular communication. There are a large number of EVs in the blood and serve as an indicator of pathophysiological conditions. Studies on the basics and application of EVs are hampered by the limitations of current protocols to isolate EVs from blood. However, current isolation methods are difficult to achieve a balance between yield and purity. Methods: Firstly, we use Sepharose-4B to build a self-made size exclusion chromatography (SEC) column and perform separation and characteristics. Then, we use the SEC column to systematically compare the efficiency with the most common EV isolation methods: Ultracentrifugation (UC) and total exosomes isolation commercial kit (TEI). The EVs isolated through different methods were characterized the yield and size of EVs, analyzed their protein profiles, the morphology and purity were observed under the transmission electron microscope. To further improve the quality and purity, we combined SEC and UC methods and established a two-steps method to isolated EVs from serum. Results: Self-made SEC column can well separate EVs from complex serum protein, and EVs enriched in the 8-13 fractions with good morphology and yield. By systematically compare SEC with the commonly used UC and TEI kit, SEC is outstanding in all aspects and balances both isolation purity and yield. However, using the SEC method alone still has certain limitations and residual impurities. The SEC+UC combined method can cleverly solve the shortcomings of SEC and optimize the quality and purity of EVs from serum, which is much better than using one method alone. Conclusion: Our study presents the combination of size-exclusion chromatography and ultracentrifugation as a feasible and time-saving method to isolate high-quality and purity extracellular vesicles from serum.


Assuntos
Exossomos , Vesículas Extracelulares , Proteínas Sanguíneas , Cromatografia em Gel , Ultracentrifugação
16.
BMC Ophthalmol ; 21(1): 353, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34610801

RESUMO

BACKGROUND: The aim of this study is to identify the genetic defect in a Chinese family with congenital aniridia combined with cataract and nystagmus. METHODS: Complete ophthalmic examinations, including slit-lamp biomicroscopy, dilated indirect ophthalmoscopy, anterior segment photography, and anterior segment optical coherence tomography (OCT) were performed. Blood samples were collected from all family members and genomic DNA was extracted. Genome sequencing was performed in all family members and Sanger sequencing was used to verify variant breakpoints. RESULTS: All the thirteen members in this Chinese family, including seven patients and six normal people, were recruited in this study. The ophthalmic examination of affected patients in this family was consistent with congenital aniridia combined with cataract and nystagmus. A novel heterozygous deletion (NC_000011.10:g.31802307_31806556del) containing the 5' region of PAX6 gene was detected that segregated with the disease. CONCLUSION: We detected a novel deletion in PAX6 responsible for congenital aniridia in the affected individuals of this Chinese family. The novel 4.25 kb deletion in PAX6 gene of our study would further broaden the genetic defects of PAX6 associated with congenital aniridia.


Assuntos
Aniridia , Catarata , Proteínas do Olho , Fator de Transcrição PAX6 , Aniridia/complicações , Aniridia/genética , Catarata/complicações , Catarata/genética , China , Proteínas do Olho/genética , Humanos , Fator de Transcrição PAX6/genética , Linhagem
17.
IEEE Trans Image Process ; 30: 8702-8712, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34665728

RESUMO

State-of-the-art methods for semantic segmentation are based on deep neural networks trained on large-scale labeled datasets. Acquiring such datasets would incur large annotation costs, especially for dense pixel-level prediction tasks like semantic segmentation. We consider region-based active learning as a strategy to reduce annotation costs while maintaining high performance. In this setting, batches of informative image regions instead of entire images are selected for labeling. Importantly, we propose that enforcing local spatial diversity is beneficial for active learning in this case, and to incorporate spatial diversity along with the traditional active selection criterion, e.g., data sample uncertainty, in a unified optimization framework for region-based active learning. We apply this framework to the Cityscapes and PASCAL VOC datasets and demonstrate that the inclusion of spatial diversity effectively improves the performance of uncertainty-based and feature diversity-based active learning methods. Our framework achieves 95% performance of fully supervised methods with only 5 - 9% of the labeled pixels, outperforming all state-of-the-art region-based active learning methods for semantic segmentation.

18.
Sensors (Basel) ; 21(19)2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34640723

RESUMO

Load identification is a very important and challenging indirect load measurement method because load identification is an inverse problem solution with ill-conditioned characteristics. A new method of load identification is proposed here, in which a virtual function was introduced to establish integral structure equations of motion, and partial integration was applied to reduce the response types in the equations. The effects of loading duration, the type of basis function, and the number of basis function expansion items on the calculation efficiency and the accuracy of load identification were comprehensively taken into account. Numerical simulation and experimental results showed that our algorithm could not only effectively identify periodic and random loads, but there was also a trade-off between the calculation efficiency and identification accuracy. Additionally, our algorithm can improve the ill-conditionedness of the solution of load identification equations, has better robustness to noise, and has high computational efficiency.


Assuntos
Algoritmos , Simulação por Computador
19.
Front Cell Infect Microbiol ; 11: 708088, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34692558

RESUMO

Comprehensive analyses of multi-omics data may provide insights into interactions between different biological layers concerning distinct clinical features. We integrated data on the gut microbiota, blood parameters and urine metabolites of treatment-naive individuals presenting a wide range of metabolic disease phenotypes to delineate clinically meaningful associations. Trans-omics correlation networks revealed that candidate gut microbial biomarkers and urine metabolite feature were covaried with distinct clinical phenotypes. Integration of the gut microbiome, the urine metabolome and the phenome revealed that variations in one of these three systems correlated with changes in the other two. In a specific note about clinical parameters of liver function, we identified Eubacteriumeligens, Faecalibacteriumprausnitzii and Ruminococcuslactaris to be associated with a healthy liver function, whereas Clostridium bolteae, Tyzzerellanexills, Ruminococcusgnavus, Blautiahansenii, and Atopobiumparvulum were associated with blood biomarkers for liver diseases. Variations in these microbiota features paralleled changes in specific urine metabolites. Network modeling yielded two core clusters including one large gut microbe-urine metabolite close-knit cluster and one triangular cluster composed of a gut microbe-blood-urine network, demonstrating close inter-system crosstalk especially between the gut microbiome and the urine metabolome. Distinct clinical phenotypes are manifested in both the gut microbiome and the urine metabolome, and inter-domain connectivity takes the form of high-dimensional networks. Such networks may further our understanding of complex biological systems, and may provide a basis for identifying biomarkers for diseases. Deciphering the complexity of human physiology and disease requires a holistic and trans-omics approach integrating multi-layer data sets, including the gut microbiome and profiles of biological fluids. By studying the gut microbiome on carotid atherosclerosis, we identified microbial features associated with clinical parameters, and we observed that groups of urine metabolites correlated with groups of clinical parameters. Combining the three data sets, we revealed correlations of entities across the three systems, suggesting that physiological changes are reflected in each of the omics. Our findings provided insights into the interactive network between the gut microbiome, blood clinical parameters and the urine metabolome concerning physiological variations, and showed the promise of trans-omics study for biomarker discovery.


Assuntos
Doenças das Artérias Carótidas , Microbioma Gastrointestinal , Biomarcadores , Clostridiales , Humanos , Metaboloma , Metabolômica
20.
Front Cell Dev Biol ; 9: 740303, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34692698

RESUMO

Brain tumors in children and adults are challenging tumors to treat. Malignant primary brain tumors (MPBTs) such as glioblastoma have very poor outcomes, emphasizing the need to better understand their pathogenesis. Developing novel strategies to slow down or even stop the growth of brain tumors remains one of the major clinical challenges. Modern treatment strategies for MPBTs are based on open surgery, chemotherapy, and radiation therapy. However, none of these treatments, alone or in combination, are considered effective in controlling tumor progression. MicroRNAs (miRNAs) are 18-22 nucleotide long endogenous non-coding RNAs that regulate gene expression at the post-transcriptional level by interacting with 3'-untranslated regions (3'-UTR) of mRNA-targets. It has been proven that miRNAs play a significant role in various biological processes, including the cell cycle, apoptosis, proliferation, differentiation, etc. Over the last decade, there has been an emergence of a large number of studies devoted to the role of miRNAs in the oncogenesis of brain tumors and the development of resistance to radio- and chemotherapy. Wherein, among the variety of molecules secreted by tumor cells into the external environment, extracellular vesicles (EVs) (exosomes and microvesicles) play a special role. Various elements were found in the EVs, including miRNAs, which can be transported as part of these EVs both between neighboring cells and between remotely located cells of different tissues using biological fluids. Some of these miRNAs in EVs can contribute to the development of resistance to radio- and chemotherapy in MPBTs, including multidrug resistance (MDR). This comprehensive review examines the role of miRNAs in the resistance of MPBTs (e.g., high-grade meningiomas, medulloblastoma (MB), pituitary adenomas (PAs) with aggressive behavior, and glioblastoma) to chemoradiotherapy and pharmacological treatment. It is believed that miRNAs are future therapeutic targets in MPBTs and such the role of miRNAs needs to be critically evaluated to focus on solving the problems of resistance to therapy this kind of human tumors.

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