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1.
Br J Cancer ; 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32606358

RESUMO

BACKGROUND: Toward identifying new strategies to target gastric cancer stem-like cells (CSCs), we evaluated the function of the tumour suppressor CDK5 regulatory subunit-associated protein 3 (CDK5RAP3) in gastric CSC maintenance. METHODS: We examined the expression of CDK5RAP3 and CD44 in gastric cancer patients. The function and mechanisms of CDK5RAP3 were checked in human and mouse gastric cancer cell lines and in mouse xenograft. RESULTS: We show that CDK5RAP3 is weakly expressed in gastric CSCs and is negatively correlated with the gastric CSC marker CD44. CDK5RAP3 overexpression decreased expression of CSC markers, spheroid formation, invasion and migration, and reversed chemoresistance in gastric CSCs in vitro and vivo. CDK5RAP3 expression was found to be regulated by extracellular-related kinase (ERK) signalling. ERK inhibitors decreased spheroid formation, migration and invasion, and the expression of epithelial-to-mesenchymal transition (EMT)-related proteins in both GA cells and organoids derived from a genetically engineered mouse model of GA. Finally, CDK5RAP3 expression was associated with reduced lymph-node metastasis and better prognosis, even in the presence of high expression of the EMT transcription factor Snail, among patients with CD44-positive GA. CONCLUSIONS: Our results demonstrate that CDK5RAP3 is suppressed by ERK signalling and negatively regulates the self-renewal and EMT of gastric CSCs.

2.
Talanta ; 217: 121035, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32498851

RESUMO

Allele fraction measurement is an essential component in nucleic acid analysis. The formation of chimeric amplicons during multiplex PCR amplification, however, greatly affects the allele fraction even before downstream analysis. Previous error correction strategy with unique molecular indexing (UMI) targets mainly points mutations rather than chimeras. Since the mutant allele detection in pregnant women cell-free DNA (cfDNA) is limited by chimeric amplicon contamination, a more direct error correction solution is demanded. Here we demonstrate effective reduction of chimeric amplicon contamination by unique dual indexing. With error corrected deep sequencing analysis, we achieved 100% accuracy in 16 tests of the parental mutation inheritance and de novo mutations in cfDNA of pregnant women, whose fetuses were at risk of tuberous sclerosis complex or Marfan syndrome. Our error correction strategy could offer a versatile solution for accurate multiplex PCR amplification.

3.
Curr Biol ; 30(10): R423-R425, 2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32428467

RESUMO

Wang and Davis provide an overview of the parasite nematode Ascaris, including the history of its role in biological research.

4.
Methods Enzymol ; 635: 251-266, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32122549

RESUMO

Emergency of the CRISPR technology, a new genome editing tool, revolutionized the biomedical research field in the past 6 years. At the same time, recent advances in cancer immunotherapy reinvigorated our hope to cure most if not all cancer patients with further development of various treatment options. A combination of the CRISPR technology with immuno-oncology research will undoubtedly accelerate the development of new cancer therapies. This review will focus on the CRISPR system and its applications in immune-oncology including identification of immune-oncology gene targets, generation of cancer animal models, and enabling better cell design and manufacture for adoptive cellular therapies.

5.
Cell Signal ; 69: 109543, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31958511

RESUMO

The gene trim7 encodes at least four isoforms Glycogenin-interacting protein 1 (GNIP1), GNIP2, GNIP3 and Tripartite motif containing 7 (TRIM7). GNIP1, the longest isoform, has been reported acting as an oncogene. However, it is very interesting that TRIM7, the shortest isoform, only 15 amino acids different from GNIP1 in C-terminal, acts in a completely different way from that of GNIP1 in our present study. TRIM7 expression was decreased in tumor compared with adjacent normal tissues, and the level of TRIM7 was negatively correlated with clinical stage of 94 patients with lung cancer. In vitro, TRIM7 dramatically inhibited the proliferation and migration of tumor cells, and promoted cell apoptosis. Further study showed that TRIM7 interacted with p65 via its C-terminal which is different from GNIP1. The interaction between TRIM7 and p65 promoted the ubiquitination of p65 and finally accelerated the degradation of p65 via 26S proteasome. In vivo, the tumor volume and weight were decreased by TRIM7 stable expression. Meanwhile, Ki67 was down-regulated, thyroid transcription factor 1 (TTF-1) and Caspase 3 were up-regulated in TRIM7 overexpression group in xenograft model. It is very impressive that TRIM7t (a truncated TRIM7 without C-terminal sequence that different with GNIP1) had little effect on the tumor growth in vivo. These findings highlight a curious mechanism for negative regulation of NF-kappa B signaling pathway by TRIM7 and demonstrate that TRIM7 would be a potential therapeutic target for lung cancer.

6.
Proc Natl Acad Sci U S A ; 117(6): 2886-2893, 2020 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-31988135

RESUMO

Transcriptome profiling by RNA sequencing (RNA-seq) has been widely used to characterize cellular status, but it relies on second-strand complementary DNA (cDNA) synthesis to generate initial material for library preparation. Here we use bacterial transposase Tn5, which has been increasingly used in various high-throughput DNA analyses, to construct RNA-seq libraries without second-strand synthesis. We show that Tn5 transposome can randomly bind RNA/DNA heteroduplexes and add sequencing adapters onto RNA directly after reverse transcription. This method, Sequencing HEteRo RNA-DNA-hYbrid (SHERRY), is versatile and scalable. SHERRY accepts a wide range of starting materials, from bulk RNA to single cells. SHERRY offers a greatly simplified protocol and produces results with higher reproducibility and GC uniformity compared with prevailing RNA-seq methods.


Assuntos
DNA/genética , RNA/genética , Análise de Sequência de RNA/métodos , Quimera/genética , DNA Complementar/genética , Biblioteca Gênica , Células HEK293 , Células HeLa , Humanos , Análise de Célula Única , Transposases/metabolismo
7.
FEBS Lett ; 594(3): 452-465, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31561267

RESUMO

In this study, we aimed to determine the mechanisms underlying the initial extramedullary translocation of myeloma cells from bone marrow into peripheral blood. We found that clonal circulating plasma cells (cPCs) are more frequently detected by flow cytometry in extramedullary plasmacytoma (EMP) patients and worsen their prognosis. It is technically much easier to collect single cPCs using FACS than it is to perform EMP biopsy. Therefore, combining EMP imaging with cPC detection may be a promising strategy for prognostic stratification. Here, using single-cell transcriptome analysis, we found that the chemokine CXCL12, a key molecule involved in CXCR4-dependent cell retention in the bone marrow, is abnormally upregulated in cPCs and might initially enable cPCs to evade bone marrow retention and translocate into the bloodstream.

8.
Mol Genet Genomic Med ; 8(1): e1041, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31830381

RESUMO

BACKGROUND: Marfan syndrome (MFS) is an inherited connective tissue disease that mainly involves Fibrillin-1 (FBN1) mutations and aortic manifestations. In this study, we investigated the correlations between the FBN1 genotype-phenotype and aortic events (aortic dissection and aortic aneurysm) in patients with Marfan syndrome. METHODS: Genotype and phenotype information was evaluated in 180 patients with MFS. DNA sequencing was performed on each patient. According to the clinical manifestation, these patients were split into two groups: the aortic dissection group and the aortic aneurysm group. Aortic wall tissue was obtained from Marfan patients who underwent surgery and was used for staining. RESULTS: A total of 180 patients with FBN1 mutations were grouped into four categories: 90 with missense mutations, 32 with splicing mutations, 29 with frameshift mutations, and 29 with nonsense mutations. There was a significantly higher frequency of frameshift and nonsense mutations observed in aortic dissection than in aortic aneurysm (25.58% vs. 4.35%, p = .005; 25.58% vs. 8.70%, p = .033, respectively;), while missense mutations showed a higher frequency in aortic aneurysm than in aortic dissection (69.57% vs. 32.56%, respectively; p < .001) and a higher rate of lens dislocation (34.78% vs. 13.95%, respectively; p = .008). Pathological staining showed that elastic fibers were sparser in patients with a frameshift and nonsense mutations, and the smooth muscle cells were sparser and more disorganized than those observed in patients with missense mutations. CONCLUSION: This study showed that FBN1 gene frameshift and nonsense mutations are more common in patients with aortic dissection and may have meaningful guidance for the treatment of Marfan syndrome patients.

9.
Methods Mol Biol ; 2055: 301-322, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31502158

RESUMO

Recent advances in cancer immunotherapy have shed new light on the possibility to cure most, if not all, cancer patients with further development of various treatment options. The emergency of a new genome editing tool, the clustered regularly interspaced short palindromic repeats (CRISPR) technology, revolutionized the biomedical research field. We envision application of the CRISPR technology in cancer research, diagnosis, and therapy will markedly speed up the development of new treatment options for cancer patients. The CRISPR system and its applications in biomedical research will be discussed with an emphasis on cancer immunotherapy and biomarker development.

10.
Nature ; 577(7790): 416-420, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31875850

RESUMO

Humoral immune responses to immunization and infection and susceptibilities to antibody-mediated autoimmunity are generally lower in males1-3. However, the mechanisms underlying such sexual dimorphism are not well understood. Here we show that there are intrinsic differences between the B cells that produce germinal centres in male and female mice. We find that antigen-activated male B cells do not position themselves as efficiently as female B cells in the centre of follicles in secondary lymphoid organs, in which germinal centres normally develop. Moreover, GPR174-an X-chromosome-encoded G-protein-coupled receptor-suppresses the formation of germinal centres in male, but not female, mice. This effect is intrinsic to B cells, and correlates with the GPR174-enhanced positioning of B cells towards the T-cell-B-cell border of follicles, and the distraction of male, but not female, B cells from S1PR2-driven follicle-centre localization. Biochemical fractionation of conditioned media that induce B-cell migration in a GPR174-dependent manner identifies CCL21 as a GPR174 ligand. In response to CCL21, GPR174 triggers a calcium flux and preferentially induces the migration of male B cells; GPR174 also becomes associated with more Gαi protein in male than in female B cells. Male B cells from orchidectomized mice exhibit impaired GPR174-mediated migration to CCL21, and testosterone treatment rescues this defect. Female B cells from testosterone-treated mice exhibit male-like GPR174-Gαi association and GPR174-mediated migration. Deleting GPR174 from male B cells causes more efficient positioning towards the follicular centre, the formation of more germinal centres and an increased susceptibility to B-cell-dependent experimental autoimmune encephalomyelitis. By identifying GPR174 as a receptor for CCL21 and demonstrating its sex-dependent control of B-cell positioning and participation in germinal centres, we have revealed a mechanism by which B-cell physiology is fine-tuned to impart sexual dimorphism to humoral immunity.


Assuntos
Quimiocina CCL21/imunologia , Imunidade Humoral , Receptores Acoplados a Proteínas-G/imunologia , Caracteres Sexuais , Animais , Linfócitos B/imunologia , Movimento Celular , Células Cultivadas , Quimiocina CCL21/genética , Suscetibilidade a Doenças , Encefalomielite Autoimune Experimental/genética , Encefalomielite Autoimune Experimental/imunologia , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Receptores Acoplados a Proteínas-G/genética
11.
Artigo em Inglês | MEDLINE | ID: mdl-31633846

RESUMO

OBJECTIVES: Few data is available for the contribution of single-gene defects to congenital heart defects including left-sided lesions (LSLs) in the fetal population, a segment of the human population not well studied. The aim of this study was to explore the contribution of single-gene defects, and to evaluate the incremental diagnostic yield of whole-exome sequencing (WES) for single-gene defects in fetal LSLs without aneuploidy or a pathogenic copy number variant (pCNV). METHODS: Between April 10, 2015, and October 30, 2018, we recruited 80 fetuses with a LSL leading to termination of pregnancy. Copy number variation sequencing (CNV-Seq) and WES were performed sequentially on specimens from these fetuses and their parents. CNV-seq was used to identify aneuploidies and pCNVs. WES was used to identify diagnostic genetic variants in cases without aneuploidies or pCNVs. RESULTS: Overall, 27 (33.8%) cases had a genetic diagnosis. CNV-seq analyses identified 6 (7.5%) aneuploidies and 8 (10.0%) pCNVs. WES analyses of the remaining 66 cases revealed diagnostic genetic variants in 13 (19.7%) cases, indicating an incremental yield of 16.3% for the entire cohort. KMT2D was the most frequently mutated gene (7/66, 10.6%), followed by NOTCH1 (4/66, 6.1%). HLHS was most prevalent (4/7) in cases with KMT2D mutation in this cohort. 6 (9.1%) cases were found to have potentially deleterious variants in candidate genes. CONCLUSIONS: Single-gene defects contribute a substantial fraction to the etiology of fetal LSLs. KMT2D mutations accounted for approximately 10% of LSLs in the fetal setting. WES has the potential to provide genetic diagnoses in fetal LSLs without aneuploidies or pCNVs. This article is protected by copyright. All rights reserved.

12.
Nat Chem Biol ; 15(11): 1110-1119, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31591565

RESUMO

RNA molecules are highly compartmentalized in eukaryotic cells, with their localizations intimately linked to their functions. Despite the importance of RNA targeting, our current knowledge of the spatial organization of the transcriptome has been limited by a lack of analytical tools. In this study, we develop a chemical biology approach to label RNAs in live cells with high spatial specificity. Our method, called CAP-seq, capitalizes on light-activated, proximity-dependent photo-oxidation of RNA nucleobases, which could be subsequently enriched via affinity purification and identified by high-throughput sequencing. Using this technique, we investigate the local transcriptomes that are proximal to various subcellular compartments, including the endoplasmic reticulum and mitochondria. We discover that messenger RNAs encoding for ribosomal proteins and oxidative phosphorylation pathway proteins are highly enriched at the outer mitochondrial membrane. Due to its specificity and ease of use, CAP-seq is a generally applicable technique to investigate the spatial transcriptome in many biological systems.


Assuntos
Luz , RNA/efeitos da radiação , Transcriptoma , Humanos , RNA/genética
13.
Curr Pharm Des ; 25(33): 3590-3596, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31538886

RESUMO

BACKGROUND: Pioglitazone is mainly used for the management of type 2 diabetes and other insulinassociated diseases. However, the molecular mechanism of pioglitazone can lead to an imbalance in bone metabolism, thus decreasing bone mass density (BMD) and increasing the risk for fractures. OBJECTIVE: To demonstrate the effect of pioglitazone therapy on bone metabolism and fat mass. METHODS: A comprehensive search of the PubMed, EMBASE, Web of Science and Cochrane Central databases for randomized controlled trials (RCTs) on the effect of pioglitazone therapy on BMD and fat mass was performed. The primary outcome measures were the measured values of BMD, percentage changes in BMD, measured values of bone turnover markers and bone metabolic hormones, changes in BMI, body and leg fat mass, and fracture rates. The final search was performed in May 2019. RESULTS: Six RCTs were included. A total of 749 patients met the inclusion criteria. Pioglitazone therapy was shown to significantly reduce the BMD of the whole body, lumbar spine, and total hip and serum PTH levels and increase BMI, total body fat mass and leg fat mass. In addition, 30 mg/d and 30 mg/d initially for one month followed by 45 mg/d pioglitazone could reduce the BMD of the lumbar spine. Pioglitazone therapy exerted no significant influence on the BMD of the femoral neck, serum BSAP or 25-OHD levels, or fracture rates. CONCLUSION: Compared with placebo, pioglitazone therapy reduced BMD and serum PTH levels and increased fat mass and BMI with no difference in serum BSAP or 25-OHD levels or fracture rates; 30 mg/d pioglitazone was sufficient to reduce the BMD of the lumbar spine.

14.
Elife ; 82019 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-31549962

RESUMO

Tapeworms grow at rates rivaling the fastest-growing metazoan tissues. To propagate they shed large parts of their body; to replace these lost tissues they regenerate proglottids (segments) as part of normal homeostasis. Their remarkable growth and regeneration are fueled by adult somatic stem cells that have yet to be characterized molecularly. Using the rat intestinal tapeworm, Hymenolepis diminuta, we find that regenerative potential is regionally limited to the neck, where head-dependent extrinsic signals create a permissive microenvironment for stem cell-driven regeneration. Using transcriptomic analyses and RNA interference, we characterize and functionally validate regulators of tapeworm growth and regeneration. We find no evidence that stem cells are restricted to the regeneration-competent neck. Instead, lethally irradiated tapeworms can be rescued when cells from either regeneration-competent or regeneration-incompetent regions are transplanted into the neck. Together, the head and neck tissues provide extrinsic cues that regulate stem cells, enabling region-specific regeneration in this parasite.


Assuntos
Estruturas Animais/crescimento & desenvolvimento , Hymenolepis diminuta/crescimento & desenvolvimento , Regeneração , Células-Tronco/fisiologia , Estruturas Animais/efeitos da radiação , Animais , Hymenolepis diminuta/efeitos da radiação
15.
Nat Prod Res ; : 1-8, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31502473

RESUMO

Five new ent-pimarane diterpenoids ent-16-nor-2-oxopimar-8(14)-ene-15,19-dial (1), ent-16-nor-2α,19-dihydroxypimar-8-en-15-al (2), 3-O-acetyldarutigenol (3), 19-O-acetylkirenol (4), ent-16-nor-3ß,15-dihydroxypimar-8(14)-ene (5) were isolated and characterized from the ethanol extract of Sigesbeckia pubescens. Their structures were elucidated on the basis of spectroscopic analysis. The absolute configuration of C-15 in compounds 3 and 4 was assigned using Snatzke's method. All these compounds were assessed for their anti-inflammatory potential by measuring the inhibitory effects on NO production in LPS-induced RAW 264.7 macrophage cells and compound 4 showed significantly inhibitory activity with IC50 value of 5.9 µM.

16.
Pathol Res Pract ; 215(10): 152592, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31474315

RESUMO

Breast cancer is the most common malignant tumor among women in China, which seriously threatens women's physical and mental health. Tumorigenesis is closely related to the dysregulation of cell cycle. The cell cycle progression includes interphase and mitotic phase (M phase). Cyclin B1 is a key protein in regulating M phase, which is essential for the whole cell cycle progression. CyclinB1 can be degraded through ubiquitination mediated by the anaphase promoting complex/cyclosome (APC/C). However, the mechanism of how CyclinB1 is deubiquitinated in breast cancer still remains unclear. In this study, we discovered that CyclinB1 interacted with ubiquitin-specific peptidase 14 (USP14). Based on the deubiquitinating function of USP14, we detected the effect of USP14 on the ubiquitination of CyclinB1. Inhibiting the activity of USP14 or USP14 knockdown significantly increased the ubiquitination of CyclinB1. In accordance with this, knocking down USP14 arrested cell cycle at G2/M phase. Knocking down USP14 with siRNAs significantly inhibited the proliferation and migration of breast cancer cells. In conclusion, our study demonstrated that USP14 regulated the cell cycle of breast cancer cells by regulating the ubiquitination of CyclinB1, which will provide a solid theoretical basis for the development of anti-cancer drugs targeting USP14.


Assuntos
Neoplasias da Mama/metabolismo , Ciclo Celular/fisiologia , Ciclina B1/metabolismo , Ubiquitina Tiolesterase/metabolismo , Ubiquitinação , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Ciclina B1/genética , Feminino , Humanos , Ubiquitina Tiolesterase/genética
17.
Ann Transl Med ; 7(12): 267, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31355234

RESUMO

Background: The National Natural Science Foundation of China (NSFC) plays an important role in supporting scientific research. And numerous scientists and researchers are concerned about the applications and funding. Methods: Annual reports of 2014-2018 were searched respectively from the NSFC official website. Further analysis was made to discover the regularity and trend of projects funded by NSFC. Results: The funding by NSFC continuously increased rapidly since its establishment. Recently, the annual amount, which is still on the rise, has reached more than 20 billion CNY. From the year 2014 to 2018 multifarious projects types were set up by NSFC to support scientific research of different level and multiple dimensions. Conclusions: In the past years, NSFC had provides strong support to basic scientific research in all fronts and provided a mechanism for fair competition.

18.
Sci Adv ; 5(7): eaaw7935, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31355338

RESUMO

The transient receptor potential canonical subfamily member 5 (TRPC5), one of seven mammalian TRPC members, is a nonselective calcium-permeant cation channel. TRPC5 is of considerable interest as a drug target in the treatment of progressive kidney disease, depression, and anxiety. Here, we present the 2.8-Å resolution cryo-electron microscopy (cryo-EM) structure of the mouse TRPC5 (mTRPC5) homotetramer. Comparison of the TRPC5 structure to previously determined structures of other TRPC and TRP channels reveals differences in the extracellular pore domain and in the length of the S3 helix. The disulfide bond at the extracellular side of the pore and a preceding small loop are essential elements for its proper function. This high-resolution structure of mTRPC5, combined with electrophysiology and mutagenesis, provides insight into the lipid modulation and gating mechanisms of the TRPC family of ion channels.


Assuntos
Sequência Conservada , Microscopia Crioeletrônica , Canais de Cátion TRPC/metabolismo , Canais de Cátion TRPC/ultraestrutura , Animais , Sítios de Ligação , Cátions , Gadolínio/farmacologia , Células HEK293 , Humanos , Ativação do Canal Iônico/efeitos dos fármacos , Cinética , Lantânio/farmacologia , Lipídeos/química , Camundongos , Mutação/genética , Relação Estrutura-Atividade , Canais de Cátion TRPC/química , Canais de Cátion TRPC/genética
19.
Angew Chem Int Ed Engl ; 58(34): 11763-11767, 2019 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-31240809

RESUMO

The subcellular organization of biomolecules such as proteins and nucleic acids is intimately linked to their biological functions. APEX2, an engineered ascorbate peroxidase that enables proximity-dependent labeling of proteins in living cells, has emerged as a powerful tool for deciphering the molecular architecture of various subcellular structures. However, only phenolic compounds have thus far been employed as APEX2 substrates, and the resulting phenoxyl radicals preferentially react with electron-rich amino acid residues. This narrow scope of substrates could potentially limit the application of APEX2. In this study, we screened a panel of aromatic compounds and identified biotin-conjugated arylamines as novel probes with significantly higher reactivity towards nucleic acids. As a demonstration of the spatial specificity and depth of coverage in mammalian cells, we applied APEX2 labeling with biotin-aniline (Btn-An) in the mitochondrial matrix, capturing all 13 mitochondrial messenger RNAs and none of the cytoplasmic RNAs. APEX2-mediated Btn-An labeling of RNA is thus a promising method for mapping the subcellular transcriptome, which could shed light on its functions in cell physiology.

20.
PLoS Pathog ; 15(6): e1007817, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31163079

RESUMO

Schistosome infection persists for decades. Parasites are in close contact with host peripheral blood immune cells, yet little is known about the regulatory interactions between parasites and these immune cells. Here, we report that extracellular vesicles (EVs) released from Schistosoma japonicum are taken up primarily by macrophages and other host peripheral blood immune cells and their miRNA cargo transferred into recipient cells. Uptake of S. japonicum EV miR-125b and bantam miRNAs into host cells increased macrophage proliferation and TNF-α production by regulating the corresponding targets including Pros1, Fam212b, and Clmp. Mice infected with S. japonicum exhibit an increased population of monocytes and elevated levels of TNF-α. Reduction of host monocytes and TNF-α level in S. japonicum infected mice led to a significant reduction in worm and egg burden and pathology. Overall, we demonstrate that S. japonicum EV miRNAs can regulate host macrophages illustrating parasite modulation of the host immune response to facilitate parasite survival. Our findings provide valuable insights into the schistosome-host interaction which may help to develop novel intervention strategies against schistosomiasis.


Assuntos
Vesículas Extracelulares/imunologia , Macrófagos/imunologia , MicroRNAs/imunologia , RNA de Helmintos/imunologia , Schistosoma japonicum/imunologia , Animais , Proteínas de Transporte/imunologia , Proteína de Membrana Semelhante a Receptor de Coxsackie e Adenovirus/imunologia , Macrófagos/parasitologia , Camundongos , Monócitos/imunologia , Monócitos/parasitologia , Células RAW 264.7 , Coelhos , Fator de Necrose Tumoral alfa/imunologia
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