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1.
Mol Clin Oncol ; 20(5): 34, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38550510

RESUMEN

Flaps are commonly used to repair large tissue defects caused by tumor resection and are often combined with radiotherapy. Relevant explanations for the mechanism underlying the effect of radiotherapy on flaps and the selection of the sequence of flaps and radiotherapy plan have emerged. The combination of flap and radiotherapy is most widely used in breast, head and neck cancers, while free flaps are the most widely used. Although, reduction of the incidence of complications of flap reconstruction, prevention of flap reconstruction failure and best integration of flap reconstruction with radiation therapy remains controversial. In the present review, these questions and debates were addressed by reviewing the literature on radiotherapy and flap reconstruction in cancer treatment.

2.
Biosensors (Basel) ; 14(3)2024 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-38534252

RESUMEN

The rapid and accurate identification of parasites is crucial for prompt therapeutic intervention in parasitosis and effective epidemiological surveillance. For accurate and effective clinical diagnosis, it is imperative to develop a nucleic-acid-based diagnostic tool that combines the sensitivity and specificity of nucleic acid amplification tests (NAATs) with the speed, cost-effectiveness, and convenience of isothermal amplification methods. A new nucleic acid detection method, utilizing the clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas) nuclease, holds promise in point-of-care testing (POCT). CRISPR/Cas12a is presently employed for the detection of Plasmodium falciparum, Toxoplasma gondii, Schistosoma haematobium, and other parasites in blood, urine, or feces. Compared to traditional assays, the CRISPR assay has demonstrated notable advantages, including comparable sensitivity and specificity, simple observation of reaction results, easy and stable transportation conditions, and low equipment dependence. However, a common issue arises as both amplification and cis-cleavage compete in one-pot assays, leading to an extended reaction time. The use of suboptimal crRNA, light-activated crRNA, and spatial separation can potentially weaken or entirely eliminate the competition between amplification and cis-cleavage. This could lead to enhanced sensitivity and reduced reaction times in one-pot assays. Nevertheless, higher costs and complex pre-test genome extraction have hindered the popularization of CRISPR/Cas12a in POCT.


Asunto(s)
Líquidos Corporales , Parásitos , Animales , Sistemas CRISPR-Cas , ARN Guía de Sistemas CRISPR-Cas , Bioensayo , Técnicas de Amplificación de Ácido Nucleico
3.
Plant Cell ; 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38526222

RESUMEN

Histo-specification and morphogenesis of anthers during development in Arabidopsis (Arabidopsis thaliana) are well understood. However, the regulatory mechanism of microsporocyte generation at the pre-meiotic stage remains unclear, especially how archesporial cells are specified and differentiate into two cell lineages with distinct developmental fates. SPOROCYTELESS (SPL) is a key reproductive gene that is activated during early anther development and remains active. In this study, we demonstrated that the EAR motif-containing adaptor protein (ECAP) interacts with the Gro/Tup1 family co-repressor LEUNIG (LUG) and the BES1/BZR1 HOMOLOG3 (BEH3) transcription factor to form a transcription activator complex, epigenetically regulating SPL transcription. SPL participates in microsporocyte generation by modulating the specification of archesporial cells and the archesporial cell-derived differentiation of somatic and reproductive cell layers. This study illustrates the regulation of SPL expression by the ECAP-LUG-BEH3 complex, which is essential for the generation of microsporocytes. Moreover, our findings identified ECAP as a key transcription regulator that can combine with different partners to regulate gene expression in distinct ways, thereby facilitating diverse processes in various aspects of plant development.

4.
Parasitol Res ; 123(2): 132, 2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-38353756

RESUMEN

To determine the genotypes of the epidemic strains of Echinococcus granulosus in livestock in Tibet, samples of E. granulosus cysts were collected from 11 yaks and 62 sheep. Genomic DNA was extracted from these samples, and gene fragments of mitochondrial cytochrome c oxidase subunit I (cox1) and NADH dehydrogenase subunit I (nad1) were amplified by PCR and sequenced. DNASTAR and MAGA7.0 were employed for homology analysis and phylogenetic tree construction. Echinococcus granulosus cysts were detected in 56.2% (41/73) of the samples screened. Of these, 63.4% (26/41) were identified as E. granulosus G1 genotype (common sheep strain), 24.4% (10 /41) as G3 genotype (buffalo strain), and 12.2% (5/41) were G6 genotype (camel strain). The study concludes that yaks and sheep in Langkazi county, Tibet, carry three E. granulosus genotypes (G1, G3, and G6), with the G1 genotype the predominant genotype in the region. This study clarifies the distribution of E. granulosus genotypes, providing genetic data and insight for the surveillance and prevention of echinococcosis.


Asunto(s)
Bison , Quistes , Echinococcus granulosus , Bovinos , Animales , Ovinos , Tibet/epidemiología , Echinococcus granulosus/genética , Filogenia , China , Genotipo , Búfalos , Camelus , Complejo I de Transporte de Electrón
5.
Plant Physiol ; 2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-38345866

RESUMEN

Brassinosteroids (BRs) are phytohormones that regulate stomatal development BRASSINAZOLE RESISTANT 1. In this study, we report that BR represses stomatal development in etiolated Arabidopsis (Arabidopsis thaliana) cotyledons via transcription factors BRASSINAZOLE RESISTANT 1 (BZR1) and bri1-EMS SUPPRESSOR1 (BES1), which directly target MITOGEN-ACTIVATED PROTEIN KINASE KINASE 9 (MKK9) and FAMA, two important genes for stomatal development. BZR1/BES1 bind MKK9 and FAMA promoters in vitro and in vivo, and mutation of the BZR1/BES1 binding motif in MKK9/FAMA promoters abolishes their transcription regulation by BZR1/BES1 in plants. Expression of a constitutively active MKK9 (MKK9DD) suppressed overproduction of stomata induced by BR deficiency, while expression of a constitutively inactive MKK9 (MKK9KR) induced high-density stomata in bzr1-1D. In addition, bzr-h, a sextuple mutant of the BZR1 family of proteins, produced overabundant stomata, and the dominant bzr1-1D and bes1-D mutants effectively suppressed the stomata-overproducing phenotype of brassinosteroid insensitive 1-116 (bri1-116) and brassinosteroid insensitive 2-1 (bin2-1). In conclusion, our results revealed important roles of BZR1/BES1 in stomatal development, and their transcriptional regulation of MKK9 and FAMA expression may contribute to BR-regulated stomatal development in etiolated Arabidopsis cotyledons.

6.
Ticks Tick Borne Dis ; 15(2): 102311, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38262211

RESUMEN

Ticks are specialized ectoparasites that feed on blood, causing physical harm to the host and facilitating pathogen transmission. The genus Haemaphysalis contains vectors for numerous infectious agents. These agents cause various diseases in humans and animals. Mitochondrial genome sequences serve as reliable molecular markers, forming a crucial basis for evolutionary analyses, studying species origins, and exploring molecular phylogeny. We extracted mitochondrial genome from the enriched mitochondria of Haemaphysalis tibetensis and obtained a 14,714-bp sequence. The mitochondrial genome consists of 13 protein-coding genes (PCGs), two ribosomal RNA, 22 transfer RNAs (tRNAs), and two control regions. The nucleotide composition of H. tibetensis mitochondrial genome was 38.38 % for A, 9.61 % for G, 39.32 % for T, and 12.69 % for C. The A + T content of H. tibetensis mitochondrial genome was 77.7 %, significantly higher than the G + C content. The repeat units of H. tibetensis exhibited two identical repeat units of 33 bp in length, positioned downstream of nad1 and rrnL genes. Furthermore, phylogenetic analyses based on the 13 PCGs indicated that Haemaphysalis tibetensis (subgenus Allophysalis) formed a monophyletic clade with Haemaphysalis nepalensis (subgenus Herpetobia) and Haemaphysalis danieli (subgenus Allophysalis). Although the species Haemaphysalis inermis, Haemaphysalis kitaokai, Haemaphysalis kolonini, and Haemaphysalis colasbelcouri belong to the subgenus Alloceraea, which were morphologically primitive hemaphysalines just like H. tibetensis, these four tick species cannot form a single clade with H. tibetensis. In this study, the whole mitochondrial genome sequence of H. tibetensis from Tibet was obtained, which enriched the mitochondrial genome data of ticks and provided genetic markers to study the population heredity and molecular evolution of the genus Haemaphysalis.


Asunto(s)
Genoma Mitocondrial , Ixodidae , Animales , Humanos , Filogenia , ARN Ribosómico/genética , Tibet
7.
New Phytol ; 241(4): 1492-1509, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38095247

RESUMEN

During abscisic acid (ABA) signaling, reversible phosphorylation controls the activity and accumulation of class III SNF1-RELATED PROTEIN KINASE 2s (SnRK2s). While protein phosphatases that negatively regulate SnRK2s have been identified, those that positively regulate ABA signaling through SnRK2s are less understood. In this study, Arabidopsis thaliana mutants of Clade E Growth-Regulating 1 and 2 (EGR1/2), which belong to the protein phosphatase 2C family, exhibited reduced ABA sensitivity in terms of seed germination, cotyledon greening, and ABI5 accumulation. Conversely, overexpression increased these ABA-induced responses. Transcriptomic data revealed that most ABA-regulated genes in egr1 egr2 plants were expressed at reduced levels compared with those in Col-0 after ABA treatment. Abscisic acid up-regulated EGR1/2, which interact directly with SnRK2.2 through its C-terminal domain I. Genetic analysis demonstrated that EGR1/2 function through SnRK2.2 during ABA response. Furthermore, SnRK2.2 de-phosphorylation by EGR1/2 was identified at serine 31 within the ATP-binding pocket. A phospho-mimic mutation confirmed that phosphorylation at serine 31 inhibited SnRK2.2 activity and reduced ABA responsiveness in plants. Our findings highlight the positive role of EGR1/2 in regulating ABA signaling, they reveal a new mechanism for modulating SnRK2.2 activity, and provide novel insight into how plants fine-tune their responses to ABA.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Fosforilación , Ácido Abscísico/farmacología , Ácido Abscísico/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Serina/metabolismo , Regulación de la Expresión Génica de las Plantas , Proteínas Serina-Treonina Quinasas/metabolismo
8.
J Integr Plant Biol ; 66(1): 20-35, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37905451

RESUMEN

Thermomorphogenesis and the heat shock (HS) response are distinct thermal responses in plants that are regulated by PHYTOCHROME-INTERACTING FACTOR 4 (PIF4) and HEAT SHOCK FACTOR A1s (HSFA1s), respectively. Little is known about whether these responses are interconnected and whether they are activated by similar mechanisms. An analysis of transcriptome dynamics in response to warm temperature (28°C) treatment revealed that 30 min of exposure activated the expression of a subset of HSFA1 target genes in Arabidopsis thaliana. Meanwhile, a loss-of-function HSFA1 quadruple mutant (hsfa1-cq) was insensitive to warm temperature-induced hypocotyl growth. In hsfa1-cq plants grown at 28°C, the protein and transcript levels of PIF4 were greatly reduced, and the circadian rhythm of many thermomorphogenesis-related genes (including PIF4) was disturbed. Additionally, the nuclear localization of HSFA1s and the binding of HSFA1d to the PIF4 promoter increased following warm temperature exposure, whereas PIF4 overexpression in hsfa1-cq partially rescued the altered warm temperature-induced hypocotyl growth of the mutant. Taken together, these results suggest that HSFA1s are required for PIF4 accumulation at a warm temperature, and they establish a central role for HSFA1s in regulating both thermomorphogenesis and HS responses in Arabidopsis.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Fitocromo , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Fitocromo/genética , Vernalización , Respuesta al Choque Térmico/genética , Temperatura , Hipocótilo/metabolismo , Regulación de la Expresión Génica de las Plantas
9.
Genes (Basel) ; 14(12)2023 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-38137020

RESUMEN

Eurytrema coelomaticum, a pancreatic fluke, is recognized as a causative agent of substantial economic losses in ruminants. This infection, commonly referred to as eurytrematosis, is a significant concern due to its detrimental impact on livestock production. However, there is a paucity of knowledge regarding the mitochondrial genome of E. coelomaticum. In this study, we performed the initial sequencing of the complete mitochondrial genome of E. coelomaticum. Our findings unveiled that the mitochondrial genome of E. coelomaticum spans a length of 15,831 bp and consists of 12 protein-coding genes, 22 tRNA genes, two rRNA genes, and two noncoding regions. The A+T content constituted 62.49% of the genome. Moreover, all 12 protein-coding genes of E. coelomaticum exhibit the same arrangement as those of E. pancreaticum and other published species belonging to the family Dicrocoeliidae. The presence of a short string of additional amino acids (approximately 20~23 aa) at the N-terminal of the cox1 protein in both E. coelomaticum and E. pancreaticum mitochondrial genomes has contributed to the elongation of the cox1 gene in genus Eurytrema, surpassing that of all previously sequenced Dicrocoeliidae. The phylogenetic analysis displayed a close relationship between E. coelomaticum and E. pancreaticum, along with a genus-level association between Eurytrema and Lyperosomum. These findings underscore the importance of mitochondrial genomic data for comparative studies of Dicrocoeliidae and even Digenea, offering valuable DNA markers for future investigations in the systematic, epidemiological, and population genetic studies of this parasite and other digenean trematodes.


Asunto(s)
Dicrocoeliidae , Genoma Mitocondrial , Trematodos , Animales , Dicrocoeliidae/genética , Filogenia , Genoma Mitocondrial/genética , Trematodos/genética , Secuencia de Bases
10.
Front Oncol ; 13: 1244488, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37941555

RESUMEN

Ultra-high dose rate radiotherapy (FLASH-RT) is an external beam radiotherapy strategy that uses an extremely high dose rate (≥40 Gy/s). Compared with conventional dose rate radiotherapy (≤0.1 Gy/s), the main advantage of FLASH-RT is that it can reduce damage of organs at risk surrounding the cancer and retain the anti-tumor effect. An important feature of FLASH-RT is that an extremely high dose rate leads to an extremely short treatment time; therefore, in clinical applications, the steps of radiotherapy may need to be adjusted. In this review, we discuss the selection of indications, simulations, target delineation, selection of radiotherapy technologies, and treatment plan evaluation for FLASH-RT to provide a theoretical basis for future research.

11.
Front Plant Sci ; 14: 1187605, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37441172

RESUMEN

Introduction: With the warming global climate, drought stress has become an important abiotic stress factor limiting plant growth and crop yield. As the most rapidly drought-sensing organs of plants, roots undergo a series of changes to enhance their ability to absorb water, but the molecular mechanism is unclear. Results and methods: In this study, we found that PLT1 and PLT2, two important transcription factors of root development in Arabidopsis thaliana, are involved in the plant response to drought and are inhibited by BR signaling. PLT1- and PLT2-overexpressing plants showed greater drought tolerance than wild-type plants. Furthermore, we found that BZR1 could bind to the promoter of PLT1 and inhibit its transcriptional activity in vitro and in vivo. PLT1 and PLT2 were regulated by BR signaling in root development and PLT2 could partially rescue the drought sensitivity of bes1-D. In addition, RNA-seq data analysis showed that BR-regulated root genes and PLT1/2 target genes were also regulated by drought; for example, CIPK3, RCI2A, PCaP1, PIP1;5, ERF61 were downregulated by drought and PLT1/2 but upregulated by BR treatment; AAP4, WRKY60, and AT5G19970 were downregulated by PLT1/2 but upregulated by drought and BR treatment; and RGL2 was upregulated by drought and PLT1/2 but downregulated by BR treatment. Discussion: Our findings not only reveal the mechanism by which BR signaling coordinates root growth and drought tolerance by suppressing the expression of PLT1 and PLT2 but also elucidates the relationship between drought and root development. The current study thus provides an important theoretical basis for the improvement of crop yield under drought conditions.

12.
Nat Commun ; 14(1): 3091, 2023 05 29.
Artículo en Inglés | MEDLINE | ID: mdl-37248257

RESUMEN

Understanding the molecular mechanisms that regulate grain yield is important for improving agricultural productivity. Protein ubiquitination controls various aspects of plant growth but lacks understanding on how E2-E3 enzyme pairs impact grain yield in major crops. Here, we identified a RING-type E3 ligase SGD1 and its E2 partner SiUBC32 responsible for grain yield control in Setaria italica. The conserved role of SGD1 was observed in wheat, maize, and rice. Furthermore, SGD1 ubiquitinates the brassinosteroid receptor BRI1, stabilizing it and promoting plant growth. Overexpression of an elite SGD1 haplotype improved grain yield by about 12.8% per plant, and promote complex biological processes such as protein processing in endoplasmic reticulum, stress responses, photosystem stabilization, and nitrogen metabolism. Our research not only identifies the SiUBC32-SGD1-BRI1 genetic module that contributes to grain yield improvement but also provides a strategy for exploring key genes controlling important traits in Poaceae crops using the Setaria model system.


Asunto(s)
Oryza , Proteínas de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Grano Comestible/metabolismo , Semillas/genética , Productos Agrícolas/genética , Productos Agrícolas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo , Oryza/metabolismo , Regulación de la Expresión Génica de las Plantas
13.
Int Immunopharmacol ; 117: 110006, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37012879

RESUMEN

INTRODUCTION: Novel mechanistic insights into the effects of circular RNAs (circRNAs) on the physiology and pathology of cardiovascular diseases are under increasingly active investigation. This study defined the cardioprotective role and mechanistic actions of circ_0002612 in myocardial ischemia/reperfusion injury (MI/RI). METHODS: MI/RI was induced in mice by ligation of the left anterior descending (LAD) artery followed by reperfusion, and the in vitro model was established in cultured cardiomyocytes under hypoxia/reoxygenation (H/R) conditions. Interaction among circ_0002612, miR-30a-5p, Ppargc1a, and NLRP3 was predicted by bioinformatics analysis and further experimentally identified. Gain- and loss-of-function experiments were performed to evaluate the effect of the circ_0002612/miR-30a-5p/Ppargc1a/NLRP3 axis on the cardiac function and myocardial infarction of I/R-injured mice, as well as viability and apoptosis of H/R-challenged cardiomyocytes. RESULTS: In the myocardial tissues of MI/RI mice, miR-30a-5p was negatively correlated with circ_0002612 or Ppargc1a, but circ_0002612 was positively correlated with the expression of Ppargc1a. circ_0002612 competitively bound to miR-30a-5p to release expression of its target gene Ppargc1a. circ_0002612 promoted cardiomyocyte viability while suppressing the apoptosis by impairing the miR-30a-5p-mediated inhibition of Ppargc1a. Additionally, Ppargc1a inhibited the expression of NLRP3 and consequently facilitated cardiomyocyte proliferation while suppressing cell apoptosis. By inhibiting the expression of NLRP3, circ_0002612 protected mice from MI/RI. CONCLUSION: Overall, this study demonstrates the cardioprotective role of circ_0002612 against MI/RI, which may be a viable target for MI/RI.


Asunto(s)
MicroARNs , Infarto del Miocardio , Daño por Reperfusión Miocárdica , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma , ARN Circular , Animales , Ratones , Apoptosis/genética , Hipoxia/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Infarto del Miocardio/patología , Daño por Reperfusión Miocárdica/metabolismo , Miocitos Cardíacos/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , ARN Circular/genética , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo
14.
Plant Commun ; 4(4): 100593, 2023 07 10.
Artículo en Inglés | MEDLINE | ID: mdl-36945776

RESUMEN

A better understanding of wheat functional genomics can improve targeted breeding for better agronomic traits and environmental adaptation. However, the lack of gene-indexed mutants and the low transformation efficiency of wheat limit in-depth gene functional studies and genetic manipulation for breeding. In this study, we created a library for KN9204, a popular wheat variety in northern China, with a reference genome, transcriptome, and epigenome of different tissues, using ethyl methyl sulfonate (EMS) mutagenesis. This library contains a vast developmental diversity of critical tissues and transition stages. Exome capture sequencing of 2090 mutant lines using KN9204 genome-designed probes revealed that 98.79% of coding genes had mutations, and each line had an average of 1383 EMS-type SNPs. We identified new allelic variations for crucial agronomic trait-related genes such as Rht-D1, Q, TaTB1, and WFZP. We tested 100 lines with severe mutations in 80 NAC transcription factors (TFs) under drought and salinity stress and identified 13 lines with altered sensitivity. Further analysis of three lines using transcriptome and chromatin accessibility data revealed hundreds of direct NAC targets with altered transcription patterns under salt or drought stress, including SNAC1, DREB2B, CML16, and ZFP182, factors known to respond to abiotic stress. Thus, we have generated and indexed a KN9204 EMS mutant library that can facilitate functional genomics research and offer resources for genetic manipulation of wheat.


Asunto(s)
Genómica , Triticum , Triticum/genética , Mutación , Mutagénesis , Fenotipo
15.
Pharmaceutics ; 15(2)2023 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-36839784

RESUMEN

Drug and radiotherapy resistance is the primary cause of treatment failure and poor prognosis in patients with tumors. Exosomes are extracellular vesicles loaded with substances such as nucleic acids, lipids, and proteins that transmit information between cells. Studies have found that exosomes are involved in tumor therapy resistance through drug efflux, promotion of drug resistance phenotypes, delivery of drug-resistance-related molecules, and regulation of anti-tumor immune responses. Based on their low immunogenicity and high biocompatibility, exosomes have been shown to reduce tumor therapy resistance by loading nucleic acids, proteins, and drugs inside xosomes or expressing tumor-specific antigens, target peptides, and monoclonal antibodies on their phospholipid bimolecular membranes. Consequently, future research on genetically engineered exosomes is expected to eliminate resistance to tumor treatment, improving the overall prognosis of patients with tumors.

16.
Microb Pathog ; 175: 105954, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36574865

RESUMEN

BACKGROUND: Babesiosis is an emerging zoonosis worldwide that is caused by tick-borne apicomplexans, Babesia spp., which threatens the health of domesticated and wild mammals and even humans. Although it has done serious harm to animal husbandry and public health, the study of Babesia is still progressing slowly. Until now, no effective anti-Babesia vaccines have been available, and administration of combined drugs tends to produce side effects. Therefore, non-targeted metabolomics was employed in the present study to examine the temporal dynamic changes in the metabolic profile of the infected erythrocytes. The goal was to obtain new insight into pathogenesis of Babesia and to explore vaccine candidates or novel drug targets. METHODS: C57BL/6 mice were infected with B. microti and erythrocytes at different time points (0, 3, 6 , 9, 12, and 22-days post-infection) were subjected to parasitemia surveillance and then metabolomics analysis using liquid chromatography-mass spectrometry (LC-MS). Multivariate statistical analyses were performed to clearly separate and identify dysregulated metabolites in Babesia-infected mice. The analyses included principal components analysis (PCA) and orthogonal partial least squares-discrimination analysis (OPLS-DA). The time-series trends of the impacted molecules were analyzed using the R package Mfuzz and the fuzzy clustering principle. The temporal profiling of amino acids, lipids, and nucleotides in blood cells infected with B. microti were also investigated. RESULTS: B. microti infection resulted in a fast increase of parasitemia and serious alteration of the mouse metabolites. Through LC-MS metabolomics analysis, 10,289 substance peaks were detected and annotated to 3,705 components during the analysis period. There were 1,166 dysregulated metabolites, which were classified into 8 clusters according to the temporal trends. Consistent with the trend of parasitemia, the numbers of differential metabolites reached a peak of 525 at 6-days post-infection (dpi). Moreover, the central carbon metabolism in cancer demonstrated the most serious change during the infection process except for that observed at 6 dpi. Sabotage occurred in components involved in the TCA cycle, amino acids, lipids, and nucleotide metabolism. CONCLUSION: Our findings revealed a great alteration in the metabolites of Babesia-infected mice and shed new light on the pathogenesis of B. microti at the metabolic level. The results might lead to novel information about the mechanisms of pathopoiesis, babesisosis, and anti-parasite drug/vaccine development in the future.


Asunto(s)
Babesia microti , Humanos , Animales , Ratones , Parasitemia , Ratones Endogámicos C57BL , Eritrocitos/parasitología , Lípidos , Mamíferos
17.
HLA ; 101(5): 537-538, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36479925

RESUMEN

The HLA-B*15:504:02 allele differs from HLA-B*15:504:01 by one nucleotide substitution at position 165 within exon 2.


Asunto(s)
Genes MHC Clase I , Antígenos HLA-B , Humanos , Alelos , Prueba de Histocompatibilidad , Antígenos HLA-B/genética , Exones
18.
Clin Exp Med ; 23(3): 777-785, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35867200

RESUMEN

Previous studies have shown that the gene AT-rich interactive domain-containing protein 1A (ARID1A) is a subunit of SWI/SNF chromatin remodeling complex that acts as a tumor suppressor gene in several cancers and plays a vital role in tumorigenesis. However, its biological functions in acute myeloid leukemia (AML) are still unclear. Here, we tried to elaborate the expression of ARID1A in patients with AML, in leukemia cells, as well as the molecular mechanisms. Our results indicated that the expression of ARID1A was significantly downregulated in the bone marrow of patients with AML and relapsed patients compared with healthy subjects and patients in complete remission. Meantime, receiver operating characteristic curve analysis showed that the expression of ARID1A could be used to discriminate between patients with AML and patients in complete remission. We further constructed a knockdown cell model to determine the regulatory mechanisms of ARID1A in AML cells. We found that the decreased expression of ARID1A promoted cell proliferation, suppressed cellular apoptosis, and impeded cell cycle arrest via TGF-ß1/SMAD3 signaling pathway. These results revealed that the reduced expression of ARID1A promoted cell proliferation via the TGF-ß1/SMAD3 cascade and served as a prognostic biomarker for AML and therapeutic targets.


Asunto(s)
Leucemia Mieloide Aguda , Factor de Crecimiento Transformador beta1 , Humanos , Factor de Crecimiento Transformador beta1/genética , Pronóstico , Transducción de Señal , Proliferación Celular , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Línea Celular Tumoral , Proteína smad3/genética , Proteínas de Unión al ADN/genética , Factores de Transcripción/genética
19.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 39(12): 1402-1405, 2022 Dec 10.
Artículo en Chino | MEDLINE | ID: mdl-36453968

RESUMEN

OBJECTIVE: To explore the genetic etiology of a child featuring recurrent oral ulcer. METHODS: Clinical data of the child was collected. Whole exome sequencing was carried out for her. Candidate variant was verified by low-coverage massive parallel copy number variation sequencing (CNV-seq) of the family trio. RESULTS: The child, a 6-year-old girl, has featured recurrent fever and ulcers of the oral mucosa, vulvar and perianal regions. No pathogenic variant was found by whole exome sequencing. However, analysis of chromosome copy number variation using the whole exome sequencing data has revealed mosaicism of trisomy 8. CNV-seq assay has verified the variant in the child, with the percentage of mosaicism being 73%. No abnormality was found in neither of her parents. CONCLUSION: A case of mosaicism trisomy 8 with recurrent oral ulcer as the first symptom was diagnosed, which has enriched the phenotypic data of trisomy 8 syndrome.


Asunto(s)
Úlceras Bucales , Trisomía , Humanos , Niño , Femenino , Trisomía/genética , Cromosomas Humanos Par 8/genética , Variaciones en el Número de Copia de ADN , Mosaicismo
20.
Nat Commun ; 13(1): 7946, 2022 12 26.
Artículo en Inglés | MEDLINE | ID: mdl-36572668

RESUMEN

Earth's climate during the last 4.6 billion years has changed repeatedly between cold (icehouse) and warm (greenhouse) conditions. The hottest conditions (supergreenhouse) are widely assumed to have lacked an active cryosphere. Here we show that during the archetypal supergreenhouse Cretaceous Earth, an active cryosphere with permafrost existed in Chinese plateau deserts (astrochonological age ca. 132.49-132.17 Ma), and that a modern analogue for these plateau cryospheric conditions is the aeolian-permafrost system we report from the Qiongkuai Lebashi Lake area, Xinjiang Uygur Autonomous Region, China. Significantly, Cretaceous plateau permafrost was coeval with largely marine cryospheric indicators in the Arctic and Australia, indicating a strong coupling of the ocean-atmosphere system. The Cretaceous permafrost contained a rich microbiome at subtropical palaeolatitude and 3-4 km palaeoaltitude, analogous to recent permafrost in the western Himalayas. A mindset of persistent ice-free greenhouse conditions during the Cretaceous has stifled consideration of permafrost thaw as a contributor of C and nutrients to the palaeo-oceans and palaeo-atmosphere.


Asunto(s)
Hielos Perennes , Océanos y Mares , Clima , Atmósfera , Regiones Árticas
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