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1.
Adv Healthc Mater ; : e2000353, 2020 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-32424991

RESUMO

The immunologic response toward chronic inflammation or bone regeneration via the accumulation of M1 or M2 macrophages after injury could determine the fate of biomaterial. Human umbilical cord mesenchymal stem cells (hUCMSCs) have a pivotal immunomodulatory property on directing macrophage behaviors. Herein, for the first time, 3D-printed poly(lactide-co-glycolide) (PLGA) scaffolds modified with hUCMSC-derived extracellular matrix (PLGA-ECM) are prepared by a facile tissue engineering technique with physical decellularization and 2.44 ± 0.29 mg cm-3 proteins immobilized on the PLGA-ECM contain multiple soluble cytokines with a sustainable release profile. The PLGA-ECM not only attenuates the foreign body response, but also improves bone regeneration by increasing the accumulation of M2 macrophages in an improved heterotopic transplantation model of SCID mice. Furthermore, the PLGA-ECM scaffolds with the knockdown of transforming growth factor-ß-induced protein (TGFßI/ßig-H3) demonstrate that M2 macrophage accumulation improved by the PLGA-ECM could be attributed to increasing the migration of M2 macrophages and the repolarization of M1 macrophages to M2 phenotype, which are mediated by multiple integrin signaling pathways involving in integrin ß7, integrin α9, and integrin ß1 in a TGFßI-dependent manner. This study presents an effective surface modification strategy of polymeric scaffolds to initiate tissue regeneration and combat inflammatory response by increasing M2 macrophage accumulation.

2.
J Comput Biol ; 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32392428

RESUMO

Bacterial evolution is an important study field, biological sequences are often used to construct phylogenetic relationships. Multiple sequence alignment is very time-consuming and cannot deal with large scales of bacterial genome sequences in a reasonable time. Hence, a new mathematical method, joining density vector method, is proposed to cluster bacteria, which characterizes the features of coding sequence (CDS) in a DNA sequence. Coding sequences carry genetic information that can synthesize proteins. The correspondence between a genomic sequence and its joining density vector (JDV) is one-to-one. JDV reflects the statistical characteristics of genomic sequence and large amounts of data can be analyzed using this new approach. We apply the novel method to do phylogenetic analysis on four bacterial data sets at hierarchies of genus and species. The phylogenetic trees prove that our new method accurately describes the evolutionary relationships of bacterial coding sequences, and is faster than ClustalW and the existing alignment-free methods.

3.
Phys Chem Chem Phys ; 22(18): 10343-10350, 2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32364215

RESUMO

Cr3+ in the Ca3Sc2Si3O12 garnet (CSSG) has the ability to convert blue light to broadband near-infrared (NIR) emissions, which is a promising strategy for next-generation smart NIR light sources based on blue LEDs. The Cr3+ luminescence strongly depends on temperature due to electron-phonon coupling (EPC). We reveal the EPC mechanism of Cr3+ in CSSG for the first time by temperature-dependent photoluminescence measurement from 77 to 573 K and cathodoluminescence using a scanning electron microscope. Cr3+ occupies the Sc3+ site and experiences a weak crystal field in CSSG, manifesting a broad NIR emission in the 700-900 nm range that originates from the 4T2g→4A2g transition. The zero phonon line (ZPL) of the 4T2 state is observed at ∼713 nm with a vibrational energy of ∼310 cm-1. A strong EPC leads to a large Stokes shift (∼2900 cm-1). The Huang-Rhys parameter (S = 4), crystal field strength (Dq/B), and Racah parameters (B and C) are estimated.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32374679

RESUMO

The invasion of osteoclasts into the cartilage via blood vessels advances the process of endochondral ossification, and dysregulation of dynamic intercellular interactions results in skeletal dysplasias. Although the regulation of osteoclasts by growth plate chondrocytes has been reported in detail, the effect of osteoclasts on chondrocytes remains to be determined. In this study, ATDC5 cells and bone marrow mesenchymal stem cells were differentiated into chondrocytes and treated with conditioned medium obtained from bone marrow macrophages differentiated to osteoclast precursors and osteoclasts. Exosomes were inhibited in conditioned medium or were isolated directly from osteoclasts to further determine whether osteoclast-derived exosomes play an important role in chondrocyte hypertrophy. Additionally, exosomal miRNAs were detected, and let-7a-5p was selected as an miRNA with significantly increased expression in osteoclast-derived exosomes. Experiments were performed to verify the potential target Smad2 and investigate how let-7a-5p affected chondrocytes. The results suggest that both osteoclast precursors and osteoclasts promote chondrocyte hypertrophy and that the promotive effect of osteoclasts is more significant than that of osteoclast precursors. Osteoclast-derived exosomes promote the hypertrophic differentiation of chondrocytes. Moreover, osteoclast-derived exosomal let-7a-5p inhibits Smad2 to decrease the transforming growth factor-ß-induced inhibition of chondrocyte hypertrophy. Our research reveals the role of osteoclasts in the regulation of chondrocytes and provides insights into the highly coordinated intercellular process of endochondral ossification.

5.
BMC Bioinformatics ; 21(1): 158, 2020 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-32334526

RESUMO

BACKGROUND: With the rapid development of single-cell RNA sequencing technology, it is possible to dissect cell-type composition at high resolution. A number of methods have been developed with the purpose to identify rare cell types. However, existing methods are still not scalable to large datasets, limiting their utility. To overcome this limitation, we present a new software package, called GiniClust3, which is an extension of GiniClust2 and significantly faster and memory-efficient than previous versions. RESULTS: Using GiniClust3, it only takes about 7 h to identify both common and rare cell clusters from a dataset that contains more than one million cells. Cell type mapping and perturbation analyses show that GiniClust3 could robustly identify cell clusters. CONCLUSIONS: Taken together, these results suggest that GiniClust3 is a powerful tool to identify both common and rare cell population and can handle large dataset. GiniCluster3 is implemented in the open-source python package and available at https://github.com/rdong08/GiniClust3.

6.
Zhen Ci Yan Jiu ; 45(4): 269-74, 2020 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-32333530

RESUMO

OBJECTIVE: To compare the therapeutic effect of shallow and deep needling at "Neiguan"(PC6) in the treatment of arrhythmia in rabbits. METHODS: Male New Zealand rabbits were randomly divided into saline (n=15), model (n=12), shallow needling (n=13) and deep needling (n=12) groups. The arrhythmia model was established by ear intravenous injection of Barium chloride (0.4%, 1 mL/kg). Acupuncture needle was inserted into the superficial fascia (about 3 mm beneath the skin) or deep layer (5 to 8 mm, near the median nerve) of local PC6 tissue (fore limb), manipulated for a while and then retained for 10 min. Histopathological changes of myocardium was observed after H.E. stain, and the immunoactivity of connexin 43 (Cx43) detected by immunohistochemistry(IHC). RESULTS: Various degrees of arrhythmia and down-regulated expression of myocardial Cx43 were observed in all rabbits after modeling. After EA intervention and compared with the model group, the initial time of arrhythmia and Cx43 expression were obviously increased (P<0.01), and the duration of arrhythmia was significantly shortened in both deep and shallow needling groups (P<0.01). Compared with the shallow needling group, the Cx43 expression was increased in the deep needling group (P<0.01). H.E. staining showed disordered and wavy arrangement of myocardial fibers, with exudation of serous and erythrocytes in the myocardial interstitium in the model group, which was relatively mild in both needling groups. IHC showed disordered distribution of Cx43 in the ventricular myocytes and almost no obvious band-like distribution at the discs in rabbits of the model group, and abundant distribution of Cx43 in the sacral disc in the deep needling group, and strip-shaped, cluster-like, point-like, visible at both end-to-end connections and side-to-side connections in the shallow needling group. CONCLUSION: Both shallow and deep needling can significantly reduce the duration of arrhythmia in arrhythmia rabbits, which may be associated with its effect in up-regulating expression of myocardial Cx43 protein.

7.
Adv Mater ; 32(19): e1907888, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32227397

RESUMO

Y3 Al5 O12 :Ce3+ (YAG:Ce3+ ) transparent ceramic phosphors (TCPs) are regarded as the most promising luminescent converter for laser-driven (LD) lighting. High-quality YAG:Ce3+ TCPs are still urgent for high efficiency LD lighting devices. YAG:Ce3+ TCPs in a vacuum ambience by using nano-sized raw materials are prepared. Controlling defects by adding nano-sized MgO and SiO2 simultaneously enables a high transmittance nearly 80%. After annealing in air furthermore, the luminous efficiency is enhanced greatly from 106 to 223 lm W-1 , which is the best result reported now for LD lighting. These results demonstrate that the optimizing YAG:Ce3+ TCPs in a fitting strategy will brighten once again in the next-generation LD lighting. Based on scanning electron microscopy (SEM) coupled with a cathodoluminescence system, defects and Ce3+ distributions in grains are identified directly for the first time.

8.
Curr Med Sci ; 40(2): 320-326, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32337692

RESUMO

Vascular remodeling is an adaptive response to various stimuli, including mechanical forces, inflammatory cytokines and hormones. In the present study, we investigated the role of angiotensin II type 1 receptor (AT1R) and calcium channel in carotid artery remodeling in response to increased biomechanical forces by using the transverse aortic constriction (TAC) rat model. TAC was induced on ten-week-old male Sprague-Dawley rats and these models were treated with AT1R blocker olmesartan (1 mg/kg/day) or/and calcium channel blocker (CCB) amlodipine (0.5 mg/kg/day) for 14 days. After the treatment, the right common carotid artery proximal to the band (RCCA-B) was collected for further assay. Results showed that olmesartan, but not amlodipine, significantly prevented TAC-induced adventitial hyperplasia. Similarly, olmesartan, but not amlodipine, signifcantly prevented vascular infammation, as indicated by increased tumor necrosis factor α (TNF-α) and increased p65 phosphorylation, an indicator of nuclear factor κ-light-chain-enhancer of activated B cells (NFκB) activation in RCCA-B. In contrast, both olmesartan and amlodipine reversed the decreased expression of endothelial nitric oxidase synthase (eNOS) and improved endothelium-dependent vasodilation, whereas combination of olmesartan and amlodipine showed no further synergistic protective effects. These results suggest that AT1R was involved in vascular remodeling and inflammation in response to pressure overload, whereas AT1R and subsequent calcium channel were involved in endothelial dysfunction.

9.
Int J Clin Pract ; : e13514, 2020 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-32306472

RESUMO

I will prescribe regimen for the good of my patients according to my ability and my judgement and never do harm to anyone. Blood stained the white coat red, Chinese doctors are going forward with a heavy burden of abiding by Hippocratic Oath. On December 26, 2019, an article entitled "a letter to my late father" was published in The Lancet, which has aroused strong repercussions in Chinese medical circles because this is the first time that The Lancet presents the papers of Chinese scholars in the form of all Chinese.

10.
Artigo em Inglês | MEDLINE | ID: mdl-32151651

RESUMO

PURPOSE: The individualized prediction of postoperative symptom severity is essential for selecting interventions after mandibular third molar (M3M) removal. The purpose of the present study was to develop and validate a nomogram for personal prediction of postoperative symptom severity. MATERIALS AND METHODS: A prospective cohort study was performed in the Stomatology Hospital of Tianjin Medical University. The sample was divided into training and testing data sets by time. The demographic, anatomic, radiographic, and operative variables were recorded. The self-reported postoperative symptom severity was recorded and defined as the primary outcome variable. Stepwise forward algorithms were applied to informative predictors based on Akaike's information criterion. Multivariable logistic regression analysis was used to develop the nomogram. An independent testing data set was used to validate the nomogram. Receiver operating characteristic curves and the Hosmer-Lemeshow test were used to assess model performance. P < .05 was considered to indicate statistical significance. RESULTS: The sample included 321 subjects who had undergone M3M removal. An independent validation data set included 103 consecutive patients. The median operation time was 15.0 minutes (interquartile range, 8.3 to 21.6 minutes) in the training data set (n = 218). Patients with serious postoperative symptoms accounted for 48.6 and 47.6% of the training and testing data sets, respectively. Gender, age, smoking status, operation time, Pell-Gregory ramus classification, and preoperative symptoms were identified as predictors and assembled into the nomogram. The area under curve demonstrated adequate discrimination in the validation data set (0.69; 95% confidence interval, 0.59 to 0.80). The nomogram was well calibrated, with a Hosmer-Lemeshow χ2 statistic of 6.33 (P = .78) in the testing data set. The confusion matrix was also summarized, and the accuracy was 63.3 and 65.1% in the training and testing data set, respectively. CONCLUSIONS: The present study has proposed an effective nomogram with potential application in facilitating the individualized prediction of postoperative symptom severity after M3M removal.

11.
Cancer Discov ; 10(5): 702-723, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32193224

RESUMO

Insufficient reactivity against cells with low antigen density has emerged as an important cause of chimeric antigen receptor (CAR) T-cell resistance. Little is known about factors that modulate the threshold for antigen recognition. We demonstrate that CD19 CAR activity is dependent upon antigen density and that the CAR construct in axicabtagene ciloleucel (CD19-CD28ζ) outperforms that in tisagenlecleucel (CD19-4-1BBζ) against antigen-low tumors. Enhancing signal strength by including additional immunoreceptor tyrosine-based activation motifs (ITAM) in the CAR enables recognition of low-antigen-density cells, whereas ITAM deletions blunt signal and increase the antigen density threshold. Furthermore, replacement of the CD8 hinge-transmembrane (H/T) region of a 4-1BBζ CAR with a CD28-H/T lowers the threshold for CAR reactivity despite identical signaling molecules. CARs incorporating a CD28-H/T demonstrate a more stable and efficient immunologic synapse. Precise design of CARs can tune the threshold for antigen recognition and endow 4-1BBζ-CARs with enhanced capacity to recognize antigen-low targets while retaining a superior capacity for persistence. SIGNIFICANCE: Optimal CAR T-cell activity is dependent on antigen density, which is variable in many cancers, including lymphoma and solid tumors. CD28ζ-CARs outperform 4-1BBζ-CARs when antigen density is low. However, 4-1BBζ-CARs can be reengineered to enhance activity against low-antigen-density tumors while maintaining their unique capacity for persistence.This article is highlighted in the In This Issue feature, p. 627.

12.
J Stroke Cerebrovasc Dis ; 29(5): 104649, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32115341

RESUMO

OBJECTIVE: We aimed to develop an early and intense lower extremity training technique using a recumbent cycle ergometer system in patients with acute ischemic stroke. METHODS: This was a pilot, prospective, randomized, controlled study with 2 parallel groups followed for 3 months with blinded assessment of outcomes. Thirty-one eligible patients were randomized to experimental and control groups. To strengthen the motion of the lower extremities within 48 hours after stroke, the control and experimental groups received conventional treatment and additional interventions under a therapist's guidance combined with conventional treatment, respectively. The primary outcome measure was the change in lower extremity motor control from admission to 4 weeks, assessed by the Fugl-Meyer Assessment. Secondary outcomes were the number of days to walking 50 m and the change in the Berg Balance Scale score and Barthel index. The modified Rankin Score was used to assess the overall function and prognosis at 3 months. RESULTS: Fugl-Meyer Assessment and Berg Balance Scale scores and Barthel index increased over time in the experimental group, as did the Berg Balance Scale score and Barthel index in the control group (P < .001). However, Fugl-Meyer Assessment scores in the control group were similar over time (F = 2.303, P = 1.119). Fugl-Meyer Assessment scores in the experimental group were higher than those in the control group after 2 and 4 weeks (P = .084 and .037, respectively). Compared with the control group at 2 weeks or at discharge, the percentage of patients who returned to unassisted walking in the experimental group showed an increasing trend (56.3% versus 26.67%, P = .095), but there was no significant difference between the 2 groups after 3 months (P = .598). The modified Rankin Score at 3 months showed no significant difference between the 2 groups (P > .05). CONCLUSIONS: Our early and intense lower extremity training technique involving a leg cycle ergometer system contributes to the recovery of lower extremity function in patients with acute ischemic stroke. This finding will provide a basis for future investigations on the applicability of the intervention in early lower extremity and walking rehabilitation among individuals with neurological disorder.

13.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(2): 162-165, 2020 Feb 10.
Artigo em Chinês | MEDLINE | ID: mdl-32034746

RESUMO

OBJECTIVE: To explore the genetic basis for a neonate featuring global developmental delay. METHODS: Clinical and laboratory tests were carried out for the patient. Peripheral venous blood samples were collected from the neonate and his parents for the extraction of DNA. Potential variant was detected by using targeted capture and next generation sequencing for a panel of genes associated with nervous system diseases. Suspected variant was validated by Sanger sequencing. RESULTS: The nine-month-old boy manifested global developmental delay and was unstable to sit alone and distinguish strangers from acquaintance. Genetic testing revealed two novel variants of the SLC19A3 gene in him, namely c.448G>A and c.169C>T. The amino acids encoded by the two codons are highly conservative, and both variants were predicted to be pathogenic by bioinformatic analysis. CONCLUSION: The compound heterozygous c.448G>A and c.169C>T variants probably underlay the onset of disease in the patient. Above finding also enriched the variant spectrum of SLC19A3 gene underlying Biotin-thiamine responsive basal ganglia disease.


Assuntos
Doenças dos Gânglios da Base , Proteínas de Membrana Transportadoras/genética , Doenças dos Gânglios da Base/genética , Biotina , Encéfalo , Humanos , Lactente , Imagem por Ressonância Magnética , Masculino , Mutação , Tiamina
14.
Stem Cell Res ; 43: 101709, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32058304

RESUMO

Methylmalonic acidemia and homocystinuria, cblC type is a rare autosomal recessive inheritance disease. Its clinical phenotype involves multiple systems with varying degrees of severity. The disease is caused by the mutations in the MMACHC gene located on chromosome 1p34.1. Here we report the generation of an iPSC line from the PBMCs of a patient with compound heterozygous mutations in the MMACHC gene. This new iPSC line will allow a better understanding of the MMA disease.

15.
Cell Biol Int ; 44(5): 1193-1203, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32039527

RESUMO

Dental pulp stem cells (DPSCs) are considered a remarkable source for the regeneration of dental pulp tissues, but their therapeutic effectiveness remains limited, especially in elderly people. Previous studies found that senescence has a negative effect on the proliferation and differentiation potential of DPSCs. Moreover, numerous long non-coding RNA (lncRNA) and messenger RNA were significantly differentially regulated in DPSCs from young and elderly donors. However, the changes in DPSCs protein during senescence have not been addressed. In this study, differences in DPSC protein expression profiles and coexpression of protein and lncRNA were analyzed using proteomics and bioinformatics. The results showed 75 upregulated proteins and 69 downregulated proteins in DPSCs from elderly donors. Vasopressin-regulated water reabsorption, Parkinson's disease, Alzheimer's disease, and protein export were the top four functional pathways associated with DPSCs. High mobility group N1 (HMGN1), HMGN2, UCHL1, and the family with sequence similarity 96 member B homeobox gene (FAM96B) were associated with DPSCs senescence. Then, we investigated FAM96B function in DPSCs. After FAM96B depletion, telomerase reverse transcriptase (TERT) activity decreased, but the number of senescence-associated ß-galactosidase (SA-ß-gal) positive cells and the protein levels of p16, p53 were significantly increased. Gain-of-function assays suggested that FAM96B overexpression was positively correlated with TERT activity, but negatively correlated with the number of SA-ß-gal positive cells and the protein levels of P16 and P53. Moreover, after FAM96B overexpression, the results showed a significant increase in alkaline phosphatase activity and an enhanced mineralization ability of DPSCs. The reverse-transcription polymerase chain reaction results also showed that dentin sialophosphoprotein and osteocalcin were expressed at greater levels. The carboxyfluorescein succinimidyl ester (CFSE) results displayed that FAM96B increased the proliferation potential of DPSCs. Our study revealed candidate proteins that might be related to DPSCs senescence and provided information to elucidate the mechanism of the biological changes in DPSCs' aging. Moreover, FAM96B was demonstrated to play an important role in suppressing DPSCs senescence and promoting osteogenic differentiation and proliferation.

16.
Cardiovasc Res ; 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32049355

RESUMO

AIMS: Aging is a risk factor for cardiovascular diseases and adaptive immunity has been implicated in angiotensin (Ang) II-induced target-organ dysfunction. Herein, we sought to determine the role of T-cell senescence in Ang II-induced target organ impairment and to explore the underlying mechanisms. METHODS AND RESULTS: Flow cytometric analysis revealed that T cell derived from aged mice exhibited immuno-senescence. Adoptive transfer of aged T cells to immunodeficient RAG1 KO mice accelerates Ang II-induced cardiovascular and renal fibrosis compared with young T cell transfer. Aged T cells also promote inflammatory factor expression and superoxide production in these target organs. In vivo and in vitro studies revealed that Ang II promotes IFN-γ production in the aged T cells comparing to young T cells. Importantly, transfer of senescent T cell that IFN-γ KO mitigates the impairment. Aged T cell-conditioned medium stimulates inflammatory factor expression and oxidative stress in Ang II-treated renal epithelial cells compared with young T cells, and these effects of aged T cell-conditioned medium are blunted after IFN-γ-neutralizing antibody pretreatment. CONCLUSIONS: These results provide a significant insight into the contribution of senescent T cells to Ang II-induced cardiovascular dysfunction and provide an attractive possibility that targeting T cell specifically might be a potential strategy to treat elderly hypertensive patients with end-organ dysfunction. TRANSLATIONAL PERSPECTIVE: Aging is a risk factor for cardiovascular diseases. Adaptive immunity has been implicated in Ang II-induced target-organ dysfunction. Here, we utilized adoptive transfer of young or aged T cell into RAG1-/- mice and provide the direct evidence that senescent T-cell was more sensitive to Ang II stimulation and exerted an adverse impact on target-organ, in which senescent T cell-derived IFN-γ may play a critical role. These findings might shed new light on the contribution of T-cell senescence to target-organ injury in age-related hypertension.

17.
Adv Med Sci ; 65(1): 86-92, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31923771

RESUMO

PURPOSE: The aim of this study is to establish a rapid antibody-free diagnostic method of malaria infection with Plasmodium falciparum and Plasmodium vivax in whole blood with Surface-enhanced Raman Spectroscopy using Nanostructured Gold Substrate. MATERIALS AND METHODS: The blood samples collected from patients were first lysed and centrifuged before dropping on the gold nano-structure (AuNS) substrate. Malaria diagnosis was performed by detecting Raman peaks from Surface Enhanced Raman Spectroscopy (SERS) with a 532 nm laser excitation. RESULTS: Raman peaks at 1370 cm-1, 1570 cm-1, and 1627 cm-1, known to have high specificity against interference from other mosquito-borne diseases such as Dengue and West Nile virus infection, were selected as the fingerprint markers associated with P. falciparum and P. vivax infection. The limit of detection was 10-5 dilution, corresponding to the concentration of parasitized blood cells of 100/mL. A total number of 25 clinical samples, including 5 from patients with P. falciparum infection, 10 with P. vivax infection and 10 from healthy volunteers, were evaluated to support its clinical practical use. The whole assay on malaria detection took 30 min to complete. CONCLUSIONS: While the samples analyzed in this work have strong clinical relevance, we have clearly demonstrated that sensitive malaria detection using AuNS-SERS is a practical direction for rapid in-field diagnosis of malaria infection.

18.
Am J Med Genet B Neuropsychiatr Genet ; 183(4): 217-226, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31953991

RESUMO

Chromosome 15q24 microdeletion syndrome is characterized by developmental delay, facial dysmorphism, hearing loss, hypotonia, recurrent infection, and other congenital malformations including microcephaly, scoliosis, joint laxity, digital anomalies, as well as sometimes having autism spectrum disorder (ASD) and attention deficit hyperactivity disorder. Here, we report a boy with a 2.58-Mb de novo deletion at chromosome 15q24. He is diagnosed with ASD and having multiple phenotypes similar to those reported in cases having 15q24 microdeletion syndrome. To delineate the critical genes and region that might be responsible for these phenotypes, we reviewed all previously published cases. We observe a potential minimum critical region of 650 kb (LCR15q24A-B) affecting NEO1 among other genes that might pertinent to individuals with ASD carrying this deletion. In contrast, a previously defined minimum critical region downstream of the 650-kb interval (LCR15q24B-D) is more likely associated with the developmental delay, facial dysmorphism, recurrent infection, and other congenital malformations. As a result, the ASD phenotype in this individual is potentially attributed by genes particularly NEO1 within the newly proposed critical region.

19.
Chemosphere ; 246: 125820, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31918111

RESUMO

[Background] Melamine and phthalates have been reported to damage renal function in children. This association is scarce in general adults. [Method] A cross-sectional subsample population of 611 adults participating in the 2012 Shanghai Food Consumption Survey (SHFCS) was analyzed for urinary biomarkers of melamine, metabolites of phthalates, and renal function parameters. The correlations between renal function parameters and chemical exposure (either independently or interactively) were explored by linear regression models. To simplify the analysis, phthalate metabolites were dimensionally reduced using principal component analysis (PCA) method. [Result] Urinary melamine was positively associated with renal function parameters of both albumin-to-creatinine ratio (ACR) and ß2-microglobulin (B2M) in multivariate linear regression models (P < 0.05). A PCA pattern characterized by high-molecular-weight phthalates (HMWP) was positively associated with all three parameters of renal function (ACR, B2M, and N-acetyl-ß-d-glucosaminidase (NAG)). The co-exposure to melamine and HMWP presented an additive effect on increasing these parameters (ACR, B2M, and NAG). [Conclusion] Impaired renal function in Shanghai adults was associated with exposure to both melamine and HMWP.


Assuntos
Exposição Ambiental/estatística & dados numéricos , Poluentes Ambientais/metabolismo , Rim/fisiologia , Ácidos Ftálicos/metabolismo , Triazinas/metabolismo , Acetilglucosaminidase , Adulto , Biomarcadores/metabolismo , Criança , Pré-Escolar , China , Estudos Transversais , Feminino , Humanos , Modelos Lineares , Urinálise
20.
J Gastroenterol Hepatol ; 35(2): 334-342, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31271681

RESUMO

BACKGROUND AND AIM: Biliary atresia (BA) is a progressive fibro-inflammatory cholangiopathy with an unclear etiology. Various liver disorders are associated with an altered microbiome. However, gut microbiome in BA remains unknown. Here, we performed a case-control study to investigate the gut microbiota in BA. METHODS: A cross-sectional analysis was first conducted for 34 BA patients and 34 healthy controls. Then we investigated the shift in gut microbiota 2 weeks after the Kasai procedure in 16 BA patients. Gut microbiome was initially analyzed using 16S ribosome RNA gene sequencing and further validated by metagenomic sequencing. Fecal bile acids were determined using ultra-high performance liquid chromatography. RESULTS: Compared with healthy controls, BA showed lower diversity and significant structural segregation in the microbiome. At phylum level, Proteobacteria numbers increased, whereas those of Bacteroidetes decreased in BA. At genus level, several potential pathogens such as Streptococcus and Klebsiella thrived in BA, while numbers for Bifidobacterium and several butyrate-producing bacteria declined. The microbiome was also disturbed after the Kasai procedure. Operational taxonomic units responding to BA showed significant correlation with liver function. Furthermore, the abundance ratio of Streptococcus/Bacteroides showed great promise in distinguishing BA from healthy controls. Intestinal bile acids were dramatically decreased in BA, and Clostridium XIVa positively correlated with the ratio of primary/secondary bile acids. CONCLUSIONS: Gut microbial dysbiosis, may be caused by decreased bile acids, was associated with liver function and had a good diagnostic potential for BA. Therefore, further exploration of gut microbiota may provide important insights into their potential diagnostic and therapeutic benefits.

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