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1.
Immunity ; 49(2): 326-341.e7, 2018 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-30054204

RESUMO

The maintenance of appropriate arterial tone is critically important for normal physiological arterial function. However, the cellular and molecular mechanisms remain poorly defined. Here, we have shown that in the mouse aorta, resident macrophages prevented arterial stiffness and collagen deposition in the steady state. Using phenotyping, transcriptional profiling, and targeted deletion of Csf1r, we have demonstrated that these macrophages-which are a feature of blood vessels invested with smooth muscle cells (SMCs) in both mouse and human tissues-expressed the hyaluronan (HA) receptor LYVE-l. Furthermore, we have shown they possessed the unique ability to modulate collagen expression in SMCs by matrix metalloproteinase MMP-9-dependent proteolysis through engagement of LYVE-1 with the HA pericellular matrix of SMCs. Our study has unveiled a hitherto unknown homeostatic contribution of arterial LYVE-1+ macrophages through the control of collagen production by SMCs and has identified a function of LYVE-1 in leukocytes.


Assuntos
Colágeno/metabolismo , Glicoproteínas/metabolismo , Receptores de Hialuronatos/metabolismo , Macrófagos/metabolismo , Músculo Liso Vascular/citologia , Miócitos de Músculo Liso/metabolismo , Rigidez Vascular/fisiologia , Animais , Aorta/fisiologia , Feminino , Glicoproteínas/genética , Humanos , Ácido Hialurônico/metabolismo , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Proteínas de Membrana Transportadoras , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/genética
2.
Clin Microbiol Rev ; 37(1): e0000923, 2024 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-38169283

RESUMO

Clonorchis sinensis, Opisthorchis viverrini, and Opisthorchis felineus are important liver flukes that cause a considerable public health burden in eastern Asia, southeastern Asia, and eastern Europe, respectively. The life cycles are complex, involving humans, animal reservoirs, and two kinds of intermediate hosts. An interplay of biological, cultural, ecological, economic, and social factors drives transmission. Chronic infections are associated with liver and biliary complications, most importantly cholangiocarcinoma. With regard to diagnosis, stool microscopy is widely used in epidemiologic surveys and for individual diagnosis. Immunologic techniques are employed for screening purposes, and molecular techniques facilitate species differentiation in reference laboratories. The mainstay of control is preventive chemotherapy with praziquantel, usually combined with behavioral change through information, education and communication, and environmental control. Tribendimidine, a drug registered in the People's Republic of China for soil-transmitted helminth infections, shows potential against both C. sinensis and O. viverrini and, hence, warrants further clinical development. Novel control approaches include fish vaccine and biological control. Considerable advances have been made using multi-omics which may trigger the development of new interventions. Pressing research needs include mapping the current distribution, disentangling the transmission, accurately estimating the disease burden, and developing new diagnostic and treatment tools, which would aid to optimize control and elimination measures.


Assuntos
Clonorquíase , Clonorchis sinensis , Opistorquíase , Opisthorchis , Animais , Humanos , Opistorquíase/diagnóstico , Opistorquíase/tratamento farmacológico , Opistorquíase/epidemiologia , Clonorquíase/diagnóstico , Clonorquíase/tratamento farmacológico , Clonorquíase/epidemiologia , Morbidade
3.
Biomed Eng Online ; 23(1): 16, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38326806

RESUMO

BACKGROUND: Previous studies have reported that abnormal interlimb coordination is a typical characteristic of motor developmental delay (MDD) during human movement, which can be visually manifested as abnormal motor postures. Clinically, the scale assessments are usually used to evaluate interlimb coordination, but they rely heavily on the subjective judgements of therapists and lack quantitative analysis. In addition, although abnormal interlimb coordination of MDD have been studied, it is still unclear how this abnormality is manifested in physiology-related kinematic features. OBJECTIVES: This study aimed to evaluate how abnormal interlimb coordination of MDD during infant crawling was manifested in the stability of joints and limbs, activation levels of synergies and intrasubject consistency from the kinematic synergies of tangential velocities of joints perspective. METHODS: Tangential velocities of bilateral shoulder, elbow, wrist, hip, knee and ankle over time were computed from recorded three-dimensional joint trajectories in 40 infants with MDD [16 infants at risk of developmental delay, 11 infants at high risk of developmental delay, 13 infants with confirmed developmental delay (CDD group)] and 20 typically developing infants during hands-and-knees crawling. Kinematic synergies and corresponding activation coefficients were derived from those joint velocities using the non-negative matrix factorization algorithm. The variability accounted for yielded by those synergies and activation coefficients, and the synergy weightings in those synergies were used to measure the stability of joints and limbs. To quantify the activation levels of those synergies, the full width at half maximum and center of activity of activation coefficients were calculated. In addition, the intrasubject consistency was measured by the cosine similarity of those synergies and activation coefficients. RESULTS: Interlimb coordination patterns during infant crawling were the combinations of four types of single-limb movements, which represent the dominance of each of the four limbs. MDD mainly reduced the stability of joints and limbs, and induced the abnormal activation levels of those synergies. Meanwhile, MDD generally reduced the intrasubject consistency, especially in CDD group. CONCLUSIONS: These features have the potential for quantitatively evaluating abnormal interlimb coordination in assisting the clinical diagnosis and motor rehabilitation of MDD.


Assuntos
Articulação do Cotovelo , Movimento , Humanos , Lactente , Fenômenos Biomecânicos , Movimento/fisiologia , Joelho , Mãos
4.
Nucleic Acids Res ; 50(D1): D1522-D1527, 2022 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-34871441

RESUMO

The rapid development of proteomics studies has resulted in large volumes of experimental data. The emergence of big data platform provides the opportunity to handle these large amounts of data. The integrated proteome resource, iProX (https://www.iprox.cn), which was initiated in 2017, has been greatly improved with an up-to-date big data platform implemented in 2021. Here, we describe the main iProX developments since its first publication in Nucleic Acids Research in 2019. First, a hyper-converged architecture with high scalability supports the submission process. A hadoop cluster can store large amounts of proteomics datasets, and a distributed, RESTful-styled Elastic Search engine can query millions of records within one second. Also, several new features, including the Universal Spectrum Identifier (USI) mechanism proposed by ProteomeXchange, RESTful Web Service API, and a high-efficiency reanalysis pipeline, have been added to iProX for better open data sharing. By the end of August 2021, 1526 datasets had been submitted to iProX, reaching a total data volume of 92.42TB. With the implementation of the big data platform, iProX can support PB-level data storage, hundreds of billions of spectra records, and second-level latency service capabilities that meet the requirements of the fast growing field of proteomics.


Assuntos
Bases de Dados de Proteínas , Proteoma/genética , Proteômica , Software , Big Data , Biologia Computacional/normas , Disseminação de Informação
5.
Immunity ; 41(3): 465-477, 2014 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-25200712

RESUMO

Dendritic cells (DCs), monocytes, and macrophages are leukocytes with critical roles in immunity and tolerance. The DC network is evolutionarily conserved; the homologs of human tissue CD141(hi)XCR1⁺ CLEC9A⁺ DCs and CD1c⁺ DCs are murine CD103⁺ DCs and CD64⁻ CD11b⁺ DCs. In addition, human tissues also contain CD14⁺ cells, currently designated as DCs, with an as-yet unknown murine counterpart. Here we have demonstrated that human dermal CD14⁺ cells are a tissue-resident population of monocyte-derived macrophages with a short half-life of <6 days. The decline and reconstitution kinetics of human blood CD14⁺ monocytes and dermal CD14⁺ cells in vivo supported their precursor-progeny relationship. The murine homologs of human dermal CD14⁺ cells are CD11b⁺ CD64⁺ monocyte-derived macrophages. Human and mouse monocytes and macrophages were defined by highly conserved gene transcripts, which were distinct from DCs. The demonstration of monocyte-derived macrophages in the steady state in human tissue supports a conserved organization of human and mouse mononuclear phagocyte system.


Assuntos
Receptores de Lipopolissacarídeos/metabolismo , Macrófagos/imunologia , Pele/imunologia , Animais , Antígeno CD11b/biossíntese , Diferenciação Celular/imunologia , Linhagem da Célula/imunologia , Movimento Celular/imunologia , Células Cultivadas , Células Dendríticas/imunologia , Feminino , Humanos , Memória Imunológica/imunologia , Camundongos , Camundongos Transgênicos , Receptores de IgG/biossíntese , Pele/citologia , Linfócitos T/imunologia
6.
Biomed Eng Online ; 22(1): 75, 2023 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-37525241

RESUMO

BACKGROUND: Gait is a complex, whole-body movement that requires the coordinated action of multiple joints and muscles of our musculoskeletal system. In the context of Duchenne muscular dystrophy (DMD), a disease characterized by progressive muscle weakness and joint contractures, previous studies have generally assumed symmetrical behavior of the lower limbs during gait. However, such a symmetric gait pattern of DMD was controversial. One aspect of this is criticized, because most of these studies have primarily focused on univariate variables, rather than on the coordination of multiple body segments and even less investigate gait symmetry under a motor synergy of view. METHODS: We investigated the gait pattern of 20 patients with DMD, compared to 18 typical developing children (TD) through 3D Gait Analysis. Kinematic and muscle synergies were extracted with principal component analysis (PCA) and non-negative matrix factorization (NNMF), respectively. The synergies extracted from the left and right sides were compared with each other to obtain a symmetry value. In addition, bilateral spatiotemporal variables of gait, such as stride length, percentage of stance and swing phase, step length, and percentage of double support phase, were used for calculating the symmetry index (SI) to evaluate gait symmetry as well. RESULTS: Compared with the TD group, the DMD group walked with decreased gait velocity (both p < 0.01), stride length (both p < 0.01), and step length (both p < 0.001). No significant difference was found between groups in SI of all spatiotemporal parameters extracted between the left and right lower limbs. In addition, the DMD group exhibited lower kinematic synergy symmetry values compared to the TD group (p < 0.001), while no such significant group difference was observed in symmetry values of muscle synergy. CONCLUSIONS: The findings of this study suggest that DMD influences, to some extent, the symmetry of synergistic movement of multiple segments of lower limbs, and thus kinematic synergy appears capable of discriminating gait asymmetry in children with DMD when conventional spatiotemporal parameters are unchanged.


Assuntos
Distrofia Muscular de Duchenne , Humanos , Criança , Distrofia Muscular de Duchenne/complicações , Fenômenos Biomecânicos , Marcha/fisiologia , Músculo Esquelético/fisiologia , Extremidade Inferior
7.
8.
Nature ; 546(7660): 662-666, 2017 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-28614294

RESUMO

During gestation the developing human fetus is exposed to a diverse range of potentially immune-stimulatory molecules including semi-allogeneic antigens from maternal cells, substances from ingested amniotic fluid, food antigens, and microbes. Yet the capacity of the fetal immune system, including antigen-presenting cells, to detect and respond to such stimuli remains unclear. In particular, dendritic cells, which are crucial for effective immunity and tolerance, remain poorly characterized in the developing fetus. Here we show that subsets of antigen-presenting cells can be identified in fetal tissues and are related to adult populations of antigen-presenting cells. Similar to adult dendritic cells, fetal dendritic cells migrate to lymph nodes and respond to toll-like receptor ligation; however, they differ markedly in their response to allogeneic antigens, strongly promoting regulatory T-cell induction and inhibiting T-cell tumour-necrosis factor-α production through arginase-2 activity. Our results reveal a previously unappreciated role of dendritic cells within the developing fetus and indicate that they mediate homeostatic immune-suppressive responses during gestation.


Assuntos
Arginase/metabolismo , Células Dendríticas/enzimologia , Células Dendríticas/imunologia , Feto/imunologia , Tolerância Imunológica , Linfócitos T/imunologia , Adulto , Movimento Celular , Proliferação de Células , Citocinas/biossíntese , Citocinas/imunologia , Feto/citologia , Feto/enzimologia , Humanos , Linfonodos/citologia , Linfonodos/imunologia , Linfócitos T/citologia , Linfócitos T Reguladores/citologia , Linfócitos T Reguladores/imunologia , Receptores Toll-Like/imunologia
9.
BMC Med ; 20(1): 17, 2022 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-35057816

RESUMO

BACKGROUND: With the recent certification by World Health Organization that the People's Republic of China is malaria-free, it is timely to consider how elimination of malaria was completed in People's Republic of China over the last 7 decades. Of the four widespread species of human malaria, Plasmodium vivax was the last to be eliminated by the national program of China. Understanding the incubation periods and relapses patterns of P. vivax through historical data from China is relevant for planning disease elimination in other malaria-endemic countries, with residual P. vivax malaria. METHODS: We collated data from both published and unpublished malaria parasite inoculation experiments conducted between 1979 and 1988 with parasites from different regions of the People's Republic of China. The studies had at least two years of follow-up. We categorized P. vivax incubation patterns via cluster analysis and investigated relapse studies by adapting a published within-host relapse model for P. vivax temperate phenotypes. Each model was fitted using the expectation-maximization (EM) algorithm initialized by hierarchical model-based agglomerative clustering. RESULTS: P. vivax parasites from the seven studies of five southern and central provinces in the People's Republic of China covering geographies ranging from the south temperate to north tropical zones. The parasites belonged to two distinct phenotypes: short- (10-19 days) or long-incubation (228-371 days). The larger the sporozoite inoculation, the more likely short incubation periods were observed, and with more subsequent relapses (Spearman's rank correlation between the number of inoculated sporozoites and the number of relapses of 0.51, p-value = 0.0043). The median of the posterior distribution for the duration of the first relapse interval after primary infection was 168.5 days (2.5% quantile: 89.7; 97.5% quantile: 227.69 days). The predicted survival proportions from the within-host model fit well to the original relapse data. The within-host model also captures the hypnozoite activation rates and relapse frequencies, which consequently influences the transmission possibility of P. vivax. CONCLUSIONS: Through a within-host model, we demonstrate the importance of clearance of hypnozoites. A strategy of two rounds of radical hypnozoite clearance via mass drug administration (MDA) deployed during transmission (summer and autumn) and non-transmission (late spring) seasons had a pronounced effect on outbreaks during the malaria epidemics in China. This understanding can inform malaria control strategies in other endemic countries with similar settings.


Assuntos
Malária Vivax , Malária , Animais , China/epidemiologia , Erradicação de Doenças , Humanos , Malária Vivax/tratamento farmacológico , Malária Vivax/epidemiologia , Malária Vivax/prevenção & controle , Plasmodium vivax , Recidiva , Esporozoítos
11.
Malar J ; 21(1): 38, 2022 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-35135540

RESUMO

Since the 1950s, China has transitioned from a malaria pandemic country with tens of millions of annual cases, through phases of local control and elimination, to sustained national malaria elimination efforts. This marks the first time a country in the World Health Organization (WHO) Western Pacific region has been certified malaria-free in more than 3 decades. This article provides an innovative approach to understanding China's malaria elimination journey. A number of articles and commentaries have analysed the effectiveness of specific technical approaches implemented in China. Our argument is that we need to look beyond these, and consider the ways in which policy development and implementation capacities have been fostered to support the dynamic change management. The article makes a number of arguments. First is the pragmatic adaptiveness of policies and strategies-and implementation capacities. Second, China has invested in building systems as well as capacities to support the elimination of parasitic diseases, including malaria. Third, the country has both benefited from, and contributed to, global health collaboration on malaria elimination. The ongoing work by the authors is identifying a number of key factors.


Assuntos
Malária , China/epidemiologia , Saúde Global , Humanos , Malária/epidemiologia , Malária/prevenção & controle , Organização Mundial da Saúde
12.
Parasitology ; 149(2): 218-233, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35234601

RESUMO

Schistosomiasis has been subjected to extensive control efforts in the People's Republic of China (China) which aims to eliminate the disease by 2030. We describe baseline results of a longitudinal cohort study undertaken in the Dongting and Poyang lakes areas of central China designed to determine the prevalence of Schistosoma japonicum in humans, animals (goats and bovines) and Oncomelania snails utilizing molecular diagnostics procedures. Data from the Chinese National Schistosomiasis Control Programme (CNSCP) were compared with the molecular results obtained.Sixteen villages from Hunan and Jiangxi provinces were surveyed; animals were only found in Hunan. The prevalence of schistosomiasis in humans was 1.8% in Jiangxi and 8.0% in Hunan determined by real-time polymerase chain reaction (PCR), while 18.3% of animals were positive by digital droplet PCR. The CNSCP data indicated that all villages harboured S. japonicum-infected individuals, detected serologically by indirect haemagglutination assay (IHA), but very few, if any, of these were subsequently positive by Kato-Katz (KK).Based on the outcome of the IHA and KK results, the CNSCP incorporates targeted human praziquantel chemotherapy but this approach can miss some infections as evidenced by the results reported here. Sensitive molecular diagnostics can play a key role in the elimination of schistosomiasis in China and inform control measures allowing for a more systematic approach to treatment.


Assuntos
Schistosoma japonicum , Esquistossomose Japônica , Esquistossomose , Animais , Bovinos , China/epidemiologia , Humanos , Estudos Longitudinais , Prevalência , Reação em Cadeia da Polimerase em Tempo Real , Schistosoma japonicum/genética , Esquistossomose/epidemiologia , Esquistossomose Japônica/epidemiologia , Esquistossomose Japônica/veterinária , Caramujos
14.
BMC Urol ; 22(1): 120, 2022 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-35922856

RESUMO

OBJECTIVE: To investigate the expression intensity of carbonic anhydrase IX (CA-IX) in bladder urothelial carcinoma and its predictive value for the recurrence after transurethral resection of bladder tumor. METHODS: A retrospective analysis was made of 194 specimens who underwent transurethral resection of bladder tumors in our hospital from January 2014 to January 2016 and completed follow-up. The expression intensity of CA-IX and the clinical data of the patients were analyzed, and the subjects were divided into positive group and negative group according to the expression intensity of CA-IX. The age, gender, T stage, degree of differentiation, tumor number, tumor diameter, recurrence of each group was analyzed. Logistic univariate and multivariate analysis was used successively to find independent influencing factors for predicting the recurrence of bladder urothelial carcinoma after resection. The Kaplan-Meier survival curve was drawn according to the relationship between CA-IX expression intensity and postoperative recurrence. RESULTS: The positive expression rates of CA-IX in bladder urothelial carcinomas were 68.1% (132/194). The positive expression of CA-IX had no statistical significance with age, gender and tumor diameter (P > 0.05), while the positive expression of CA-IX had statistical significance with tumor T stage, tumor differentiation, tumor number and recurrence (P < 0.05); Logistic regression analysis showed that clinical T stage, tumor differentiation, tumor number, and CA-IX expression intensities were independent risk factors for predicting recurrence of bladder urothelial carcinoma after resection (P < 0.05); There were 59 cases of recurrence in the positive expression of CA-IX group, with a recurrence rate of 44.69% (59/132), and 17 cases of recurrence in the negative expression group, with a recurrence rate of 27.41% (17/62). The mean recurrence time of CA-IX positive group was 29.93 ± 9.86 (months), and the mean recurrence time of CA-IX negative group was 34.02 ± 12.44 (months). The Kaplan-Meier survival curve showed that the recurrence rate and recurrence time of patients with positive expression of CA-IX in bladder urothelial carcinomas were significantly higher than those of patients with negative expression of CA-IX. CONCLUSION: CA-IX is highly expressed in bladder urothelial carcinoma, is a good tumor marker, and can be used as a good indicator for predicting the recurrence of bladder urothelial carcinoma after transurethral resection of bladder tumor.


Assuntos
Anidrases Carbônicas , Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Anidrase Carbônica IX , Anidrases Carbônicas/metabolismo , Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/cirurgia , Humanos , Prognóstico , Estudos Retrospectivos , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/patologia
15.
BMC Ophthalmol ; 22(1): 2, 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34980022

RESUMO

BACKGROUND: Implantable Collamer lens (ICL) vaulting is one of the most important parameters for the safety, aqueous humor circulation, and lens transparency after ICL implantation. This study aimed to investigate the factors associated with the actual vaulting after refractive EVO-ICL surgery. METHODS: This retrospective study included patients who underwent EVO-ICL surgery at a tertiary eye hospital between October and December 2019. A RESCAN 700 was used for the intraoperative and CIRRUS HD-OCT was used for postoperative observation of vaulting. Subjective and objective refractions, anterior ocular segment, corneal morphology, intraocular pressure (IOP), anterior chamber volume (ACV), crystalline lens rise (CLR), white-to-white distance (WTW), anterior chamber depth (ACD), axial length, corneal endothelial cell density (ECD), and fundoscopy were examined. A multivariable analysis was performed to determine the factors independently associated with 1-month postoperative vaulting. RESULTS: Fifty-one patients (102 eyes) were included. Compared with the eyes with normal vaulting, those with high vaulting had higher preoperative diopter values (P = 0.039), lower preoperative corrected visual acuity (P = 0.006), lower preoperative IOP (P = 0.029), higher preoperative ACD (P = 0.004), lower preoperative CLR (P = 0.046), higher ICL spherical equivalent (P = 0.030), higher intraoperative vaulting (P < 0.001), and lower IOP at 1 month (P = 0.045). The multivariable analysis showed that the only factor independently associated with high vaulting at 1 month after surgery was the intraoperative vaulting value (odds ratio = 1.005, 95% confidence interval: 1.002-1.007, P < 0.001). The intraoperative and 1-month postoperative vaulting values were positively correlated (R2 = 0.562). CONCLUSIONS: The RESCAN700 system can be used to perform intraoperative optical coherence tomography to predict the vaulting value of ICL at 1 month.


Assuntos
Miopia , Lentes Intraoculares Fácicas , Humanos , Implante de Lente Intraocular , Miopia/cirurgia , Refração Ocular , Estudos Retrospectivos
16.
Mem Inst Oswaldo Cruz ; 117: e200409, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35613154

RESUMO

The multiplicity of epidemiological scenarios shown by Chagas Disease, derived from multiple transmission routes of the aetiological agent, occurring on multiple geo-ecobiosocial settings determines the complexity of the disease and reveal the difficulties for its control. From the first description of the link between the parasite, the vector and its domestic habitat and the disease that Carlos Chagas made in 1909, the epidemiological scenarios of the American Trypanosomiasis has shown a dynamic increasing complexity. These scenarios changed with time and geography because of new understandings of the disease from multiple studies, because of policies change at the national and international levels and because human movements brought the parasite and vectors to new geographies. Paradigms that seemed solid at a time were broken down, and we learnt about the global dispersion of Trypanosoma cruzi infection, the multiplicity of transmission routes, that the infection can be cured, and that triatomines are not only a health threat in Latin America. We consider the multiple epidemiological scenarios through the different T. cruzi transmission routes, with or without the participation of a Triatominae vector. We then consider the scenario of regions with vectors without the parasite, to finish with the consideration of future prospects.


Assuntos
Doença de Chagas , Triatominae , Trypanosoma cruzi , Animais , Doença de Chagas/parasitologia , Vetores de Doenças , Ecossistema , Humanos , Triatominae/parasitologia
17.
J Clin Immunol ; 41(5): 1016-1030, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33651234

RESUMO

Acute graft-versus-host disease (aGVHD) is a significant complication of allogeneic hematopoietic stem cell transplant (HSCT) and negatively affects T cell reconstitution. Extracorporeal photopheresis (ECP) reduces aGVHD, but the mechanisms remain incompletely understood. Our objective was to examine the impact of ECP on thymopoiesis in pediatric aGVHD and the mechanisms at a cellular and transcriptional level. Sixteen pediatric HSCT patients were recruited: 6 with ECP-treated aGVHD, 5 without aGVHD, and 5 with aGVHD treated with corticosteroids only. Thymopoiesis was evaluated by measuring naive T cells, TRECs, IL-7, and T cell receptor repertoire diversity. Regulatory T cell (Treg) enumeration and function and dendritic cell (DC) enumeration and phenotype were analyzed using flow cytometry. T cell transcriptome analysis was performed on ECP patients after treatment and responders pre- and post-treatment. Four ECP responders demonstrated thymic-dependent T cell recovery, and superior median naïve T cell numbers at 8 and 12 months post-HSCT compared to the aGVHD corticosteroid group. Increased Tregs and Treg suppressive function, reduced cDC/pDC and DC co-stimulatory marker expression in ECP responders suggest upregulated peripheral tolerance; these findings were not observed in partial responders. Responder post-ECP CD3+ T cell transcriptional profile demonstrated 3333 downregulated and 364 upregulated genes, with significant downregulation of ERRα and GαS pathways, and reduced expression of pro-inflammatory and adhesion proteins.Thymic function improves with successful ECP treatment. ECP reduces T cell activation and impacts peripheral tolerance via DCs and Tregs. Differences in thymic recovery, DC, and Treg cellular patterns and the T cell transcriptome were observed between ECP responders and partial responders and require further validation and investigation in additional patients.


Assuntos
Células Dendríticas/imunologia , Doença Enxerto-Hospedeiro/terapia , Fotoferese , Linfócitos T/imunologia , Adolescente , Criança , Pré-Escolar , Feminino , Doença Enxerto-Hospedeiro/sangue , Doença Enxerto-Hospedeiro/imunologia , Humanos , Lactente , Interleucina-7/sangue , Masculino , Receptores de Antígenos de Linfócitos T/imunologia , Timo/citologia , Transcriptoma
18.
Bioinformatics ; 36(17): 4576-4582, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32467966

RESUMO

MOTIVATION: RNA secondary structure plays a vital role in fundamental cellular processes, and identification of RNA secondary structure is a key step to understand RNA functions. Recently, a few experimental methods were developed to profile genome-wide RNA secondary structure, i.e. the pairing probability of each nucleotide, through high-throughput sequencing techniques. However, these high-throughput methods have low precision and cannot cover all nucleotides due to limited sequencing coverage. RESULTS: Here, we have developed a new method for the prediction of genome-wide RNA secondary structure profile from RNA sequence based on the extreme gradient boosting technique. The method achieves predictions with areas under the receiver operating characteristic curve (AUC) >0.9 on three different datasets, and AUC of 0.888 by another independent test on the recently released Zika virus data. These AUCs are consistently >5% greater than those by the CROSS method recently developed based on a shallow neural network. Further analysis on the 1000 Genome Project data showed that our predicted unpaired probabilities are highly correlated (>0.8) with the minor allele frequencies at synonymous, non-synonymous mutations, and mutations in untranslated regions, which were higher than those generated by RNAplfold. Moreover, the prediction over all human mRNA indicated a consistent result with previous observation that there is a periodic distribution of unpaired probability on codons. The accurate predictions by our method indicate that such model trained on genome-wide experimental data might be an alternative for analytical methods. AVAILABILITY AND IMPLEMENTATION: The GRASP is available for academic use at https://github.com/sysu-yanglab/GRASP. SUPPLEMENTARY INFORMATION: Supplementary data are available online.


Assuntos
Infecção por Zika virus , Zika virus , Sequência de Bases , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Redes Neurais de Computação , RNA/genética , Software
19.
Immunity ; 37(1): 60-73, 2012 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-22795876

RESUMO

Dendritic cell (DC)-mediated cross-presentation of exogenous antigens acquired in the periphery is critical for the initiation of CD8(+) T cell responses. Several DC subsets are described in human tissues but migratory cross-presenting DCs have not been isolated, despite their potential importance in immunity to pathogens, vaccines, and tumors and tolerance to self. Here, we identified a CD141(hi) DC present in human interstitial dermis, liver, and lung that was distinct from the majority of CD1c(+) and CD14(+) tissue DCs and superior at cross-presenting soluble antigens. Cutaneous CD141(hi) DCs were closely related to blood CD141(+) DCs, and migratory counterparts were found among skin-draining lymph node DCs. Comparative transcriptomic analysis with mouse showed tissue DC subsets to be conserved between species and permitted close alignment of human and mouse DC subsets. These studies inform the rational design of targeted immunotherapies and facilitate translation of mouse functional DC biology to the human setting.


Assuntos
Antígenos CD/metabolismo , Apresentação Cruzada/imunologia , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Cadeias alfa de Integrinas/metabolismo , Animais , Antígenos/imunologia , Movimento Celular/imunologia , Quimiocina CXCL10/biossíntese , Perfilação da Expressão Gênica , Humanos , Imunofenotipagem , Células de Langerhans/imunologia , Células de Langerhans/metabolismo , Linfonodos/imunologia , Linfonodos/metabolismo , Camundongos , Pele/imunologia , Transcriptoma , Fator de Necrose Tumoral alfa/biossíntese
20.
Malar J ; 20(1): 73, 2021 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-33549122

RESUMO

BACKGROUND: The emergence and spread of multidrug resistance poses a significant risk to malaria control and eradication goals in the world. There has been no indigenous malaria cases reported in China since 2017, and China is approaching national malaria elimination. Therefore, anti-malarial drug resistance surveillance and tracking the emergence and spread of imported drug-resistant malaria cases will be necessary in a post-elimination phase in China. METHODS: Dried blood spots were obtained from Plasmodium falciparum-infected cases returned from Africa to China between 2012 and 2015, prior to anti-malarial drug treatment. Whole DNA were extracted and known polymorphisms relating to drug resistance of pfcrt, pfmdr1 gene, and the propeller domain of pfk13 were evaluated by nested PCR and sequencing. The haplotypes and prevalence of these three genes were evaluated separately. Chi-squared test and Fisher's exact test were used to evaluate differences among the different sub-regions of Africa. A P value < 0.05 was used to evaluate differences with statistical significance. The maps were created using ArcGIS. RESULTS: A total of 731 P. falciparum isolates were sequenced at the pfcrt locus. The wild type CVMNK was the most prevalent haplotype with prevalence of 62.8% and 29.8% of the isolates showed the triple mutant haplotype CVIET. A total of 434 P. falciparum isolates were successfully sequenced and pfmdr1 allelic variants were observed in only codons 86, 184 and 1246. Twelve haplotypes were identified and the prevalence of the wild type pfmdr1 NYD was 44.1%. The single mutant pfmdr1 in codons 86 and 184 was predominant but the haplotype NYY with single mutation in codon 1246 was not observed. The double mutant haplotype YFD was common in Africa. About 1,357 isolates were successfully sequenced of pfk13-propeller domain, the wild type was found in 1,308 samples (96.4%) whereby 49 samples (3.6%) had mutation in pfk13. Of 49 samples with pfk13 mutations, 22 non-synonymous and 4 synonymous polymorphic sites were confirmed. The A578S was the most common mutation in pfk13-propeller domain and three mutations associated with artemisinin resistance (M476I, R539T, P553L) were identified in three isolates. CONCLUSION: This study provides evidence that could give insight into potential issues with anti-malarial drug resistance to inform national drug policy in China in order to treat imported cases.


Assuntos
Plasmodium falciparum/genética , Proteínas de Protozoários/análise , África , China , Monitoramento Epidemiológico , Proteínas de Membrana Transportadoras/análise , Proteínas Associadas à Resistência a Múltiplos Medicamentos/análise
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