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Human papillomavirus (HPV) type 81 has recently become one of the most common low-risk HPV types; however, literature focusing on it is limited. This study aimed to analyze the reasons for the increased detection rate of HPV81 and investigate its evolving pathogenicity. We analyzed the detection rates and trends of HPV81 in 229 061 exfoliated cervical cell samples collected from 2014 to 2023; collected samples of HPV81 single infections from two different time periods; and analyzed the allele frequencies, positive selection, viral load, persistent infection capacity, and pathogenicity of E6 and E7 genotypes. We found that the detection rate of HPV81 ranked first among the low-risk types in exfoliated cervical cells and exhibited a significantly increasing trend (p < 0.001). The frequency of the E6 prototype allele of HPV81 (n = 317) was significantly increased (p = 0.018) and demonstrated the strongest adaptive capacity. The viral load and persistent infection capacity of the E6 prototype were significantly higher than those of the mutants, thus serving as key drivers for increasing the detection rate of HPV81 and enhancing its pathogenicity. The viral load was positively correlated with persistent infection capacity and pathogenicity. Persistent infection was a crucial factor in the pathogenicity of HPV81. Successful adaptive evolution of HPV81 is accompanied by enhanced pathogenicity.
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Genotipo , Infecciones por Papillomavirus , Infección Persistente , Polimorfismo Genético , Carga Viral , Humanos , Infecciones por Papillomavirus/virología , Femenino , Infección Persistente/virología , Cuello del Útero/virología , Cuello del Útero/patología , Adulto , Papillomaviridae/genética , Papillomaviridae/patogenicidad , Papillomaviridae/clasificación , Papillomaviridae/aislamiento & purificación , Frecuencia de los Genes , Proteínas Oncogénicas Virales/genética , Virulencia/genética , Alphapapillomavirus/genética , Alphapapillomavirus/patogenicidad , Alphapapillomavirus/clasificación , Alphapapillomavirus/aislamiento & purificación , Virus del Papiloma HumanoRESUMEN
Cold stress is one of the main abiotic stresses that affects rice growth and production worldwide. Dissection of the genetic basis is important for genetic improvement of cold tolerance in rice. In this study, a new source of cold-tolerant accession from the Yunnan plateau, Lijiangxiaoheigu, was used as the donor parent and crossed with a cold-sensitive cultivar, Deyou17, to develop recombinant inbred lines (RILs) for quantitative trait locus (QTL) analysis for cold tolerance at the early seedling and booting stages in rice. In total, three QTLs for cold tolerance at the early seedling stage on chromosomes 2 and 7, and four QTLs at the booting stage on chromosomes 1, 3, 5, and 7, were identified. Haplotype and linear regression analyses showed that QTL pyramiding based on the additive effect of these favorable loci has good potential for cold tolerance breeding. Effect assessment in the RIL and BC3F3 populations demonstrated that qCTB1 had a stable effect on cold tolerance at the booting stage in the genetic segregation populations. Under different cold stress conditions, qCTB1 was fine-mapped to a 341-kb interval between markers M3 and M4. Through the combination of parental sequence comparison, candidate gene-based association analysis, and tissue and cold-induced expression analyses, eight important candidate genes for qCTB1 were identified. This study will provide genetic resources for molecular breeding and gene cloning to improve cold tolerance in rice. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01488-3.
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Emergency granulopoiesis, also known as demand-adapted granulopoiesis, is defined as the response of an organism to systemic bacterial infections, and it results in neutrophil mobilization from reservoir pools and increased myelopoiesis in the bone marrow. Indirect and direct initiating mechanisms of emergency granulopoiesis have been hypothesized. However, the detailed mechanism of hyperactive myelopoiesis in the bone marrow, which leads to granulocyte left shift, remains unknown. In this study, we report that TLR4 is expressed on granulo-monocytic progenitors, as well as mobilized human peripheral blood CD34+ cells, which account for 0.2% of monocytes in peripheral blood, and â¼ 10% in bone marrow. LPS, a component of Gram-negative bacteria that results in a systemic bacterial infection, induces the differentiation of peripheral blood CD34+ cells into myelocytes and monocytes in vitro via the TLR4 signaling pathway. Moreover, CD34+ cells directly responded to LPS stimulation by activating the MAPK and NF-κB signaling pathways, and they produced IL-6 that promotes emergency granulopoiesis by phosphorylating C/EBPα and C/EBPß, and this effect was suppressed by the action of an IL-6 receptor inhibitor. This work supports the finding that TLR is expressed on human hematopoietic stem and progenitor cells, and it provides evidence that human hematopoietic stem and progenitor cells can directly sense pathogens and produce cytokines exerting autocrine and/or paracrine effects, thereby promoting differentiation.
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Granulocitos/metabolismo , Células Madre Hematopoyéticas/metabolismo , Interleucina-6/metabolismo , Transducción de Señal/fisiología , Células Madre/metabolismo , Receptor Toll-Like 4/metabolismo , Adaptación Fisiológica/fisiología , Antígenos CD34/metabolismo , Médula Ósea/metabolismo , Proteína beta Potenciadora de Unión a CCAAT/metabolismo , Diferenciación Celular/fisiología , Citocinas/metabolismo , Regulación de la Expresión Génica/fisiología , Células Precursoras de Granulocitos/metabolismo , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Monocitos/metabolismo , Mielopoyesis/fisiologíaRESUMEN
BACKGROUND: Insomnia is highly prevalent among patients with allergic disease and asthma; however, few studies have investigated their causal relationship. We aim to explore the causal association between insomnia and allergic disease/asthma by performing bidirectional Mendelian randomization (MR) study. METHODS: Instrumental variables were constructed using single nucleotide polymorphisms (SNPs). Summary statistics for insomnia, allergic disease, and asthma were obtained from four large-scale genome-wide association studies (GWAS) of European ancestry. The pleiotropy analysis was applied by using the MR-Egger intercept test and the MR pleiotropy residual sum and outlier (MR-PRESSO) test. MR analyses were conducted by using inverse variance weighted (IVW), weighted median, and MR-Egger method. RESULTS: Based on the multiplicative random effects IVW method, the MR analysis showed that genetically predicted insomnia was causally associated with an increased risk of allergic disease [odds ratio (OR) = 1.054, 95% confidence interval (CI) = 1.031-1.078, P = 3.817 × 10-06], asthma (OR = 1.043, 95% CI = 1.010-1.077, P = 9.811 × 10-03), moderate-severe asthma (OR = 1.168, 95% CI = 1.069-1.277, P = 6.234 × 10-04), and adult-onset asthma (OR = 1.086, 95% CI = 1.037-1.138, P = 4.922 × 10-04). In bidirectional analyses, we did not find evidence supporting the reverse causality relations. CONCLUSIONS: Our MR study suggested that genetically predicted insomnia was the risk factor for allergic disease and asthma. Improving sleep quality could be one of the cornerstones in the prevention of allergic disease and asthma.
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Asma , Hipersensibilidad , Trastornos del Inicio y del Mantenimiento del Sueño , Adulto , Asma/diagnóstico , Asma/epidemiología , Asma/genética , Estudio de Asociación del Genoma Completo , Humanos , Hipersensibilidad/diagnóstico , Hipersensibilidad/epidemiología , Hipersensibilidad/genética , Análisis de la Aleatorización Mendeliana/métodos , Polimorfismo de Nucleótido Simple/genética , Trastornos del Inicio y del Mantenimiento del Sueño/diagnóstico , Trastornos del Inicio y del Mantenimiento del Sueño/epidemiología , Trastornos del Inicio y del Mantenimiento del Sueño/genéticaRESUMEN
The European LeukemiaNet (ELN) criteria define the adverse genetic factors of acute myeloid leukemia (AML). AML with adverse genetic factors uniformly shows resistance to standard chemotherapy and is associated with poor prognosis. Here, we focus on the biological background and real-world etiology of these adverse genetic factors and then describe a strategy to overcome the clinical disadvantages in terms of targeting pivotal molecular mechanisms. Different adverse genetic factors often rely on common pathways. KMT2A rearrangement, DEK-NUP214 fusion, and NPM1 mutation are associated with the upregulation of HOX genes. The dominant tyrosine kinase activity of the mutant FLT3 or BCR-ABL1 fusion proteins is transduced by the AKT-mTOR, MAPK-ERK, and STAT5 pathways. Concurrent mutations of ASXL1 and RUNX1 are associated with activated AKT. Both TP53 mutation and mis-expressed MECOM are related to impaired apoptosis. Clinical data suggest that adverse genetic factors can be found in at least one in eight AML patients and appear to accumulate in relapsed/refractory cases. TP53 mutation is associated with particularly poor prognosis. Molecular-targeted therapies focusing on specific genomic abnormalities, such as FLT3, KMT2A, and TP53, have been developed and have demonstrated promising results.
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Leucemia Mieloide Aguda , Proteínas Proto-Oncogénicas c-akt , Proteínas Cromosómicas no Histona/metabolismo , Proteínas de Fusión bcr-abl/genética , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Mutación , Nucleofosmina , Proteínas Oncogénicas/genética , Proteínas de Unión a Poli-ADP-Ribosa/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Tirosina Quinasa 3 Similar a fms/genéticaRESUMEN
The improvement of cold adaptation has contributed to the increased growing area of rice. Standing variation and de novo mutation are distinct natural sources of beneficial alleles in plant adaptation. However, the genetic mechanisms and evolutionary patterns underlying these sources in a single population during crop domestication remain elusive. Here we cloned the CTB2 gene, encoding a UDP-glucose sterol glucosyltransferase, for cold tolerance in rice at the booting stage. A single standing variation (I408V) in the conserved UDPGT domain of CTB2 originated from Chinese Oryza rufipogon and contributed to the cold adaptation of Oryza sativa ssp. japonica. CTB2 is located in a 56.8 kb region, including the previously reported gene CTB4a in which de novo mutation arose c. 3200 yr BP in Yunnan province, China, conferring cold tolerance. Standing variation of CTB2 and de novo mutation of CTB4a underwent stepwise selection to facilitate cold adaptation to expand rice cultivation from high-altitude to high-latitude regions. These results provide an example of stepwise selection on two kinds of variation and describe a new molecular mechanism of cold adaptation in japonica rice.
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Oryza , Alelos , China , Domesticación , Genes de Plantas , Oryza/genética , Selección GenéticaRESUMEN
Black rice is a rare type of rice germplasm with various health benefits that are largely attributed to anthocyanin pigment accumulation in the pericarps. The anthocyanin biosynthesis in plant tissues is activated mainly by the MBW complexes, consisting of three types of transcription factors R2R3-MYB, bHLH, and WDR. In black rice, the bHLH and WDR components regulating anthocyanin biosynthesis in pericarps have been characterized, while the R2R3-MYB factor remains unknown. By examining the expression correlation between all putative rice MYB genes and anthocyanin biosynthesis-related genes based on transcriptome data of pericarps in combination with further molecular and genetic analysis, we proved that OsMYB3 (LOC_Os03g29614) was the determinant R2R3-MYB gene for anthocyanin biosynthesis in rice pericarps. The expression level of OsMYB3 in pericarps of black rice was significantly higher than that of white rice. The knockout of OsMYB3 in a black rice variety caused significant downregulation of 19 anthocyanin metabolites and many other flavonoids in grains. Our research deepens the understanding of regulatory system for anthocyanin biosynthesis in rice pericarps and provides implications for breeding black rice varieties with high anthocyanin level. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-021-01244-x.
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PURPOSE: Scutellarin, a flavonoid derived from the plant Erigeron breviscapus, is currently widely used to treat cerebrovascular diseases, liver-related diseases, and hyperlipidemia in china and other East Asian countries. This study was to investigate the effect of scutellarin on the uptake of rosuvastatin in HEK293T cells expressing human organic anion transporting polypeptide 1B3 (hOATP1B3) and rat OATP1B2 (rOATP1B2), respectively, and the effect of scutellarin on the pharmacokinetics of rosuvastatin in rats. METHODS: The newly established HEK293T cells expressing hOATP1B3 and rOATP1B2 were used to examine the effects of scutellarin and positive controls on in vitro rosuvastatin transport. After co-feeding with scutellarin, the rosuvastatin area under the plasma concentration-time curve (AUC0-24h), the peak plasma drug concentration (Cmax), elimination half-life (t1/2), time to reach Cmax (tmax), clearance (CL) and apparent clearance (CL/F) of rosuvastatin were determined in rats. RESULTS: Scutellarin inhibited hOATP1B3- and rOATP1B2-mediated rosuvastatin uptake (IC50: 45.54 ± 6.67 µM and 27.58 ± 3.97 µM) in vitro in a concentration-dependent manner. After co-feeding with scutellarin, the AUC0-24h and Cmax of rosuvastatin in rats increased to 27.4% and 37.7%, respectively. The t1/2 and tmax of rosuvastatin showed no significant change. Moreover, scutellarin caused 29.2% and 28.1% decrease in the CL and CL/F of rosuvastatin. CONCLUSION: Scutellarin may inhibit the hOATP1B3- and rOATP1B2-mediated transport of rosuvastatin in vitro, and exerts a moderate inhibitory effect on the pharmacokinetics of rosuvastatin in rats. Scutellarin is highly likely to participate in drug-drug interactions, as mediated by OATP1B3 in humans.
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Apigenina/farmacología , Glucuronatos/farmacología , Rosuvastatina Cálcica/farmacocinética , Miembro 1B3 de la Familia de los Transportadores de Solutos de Aniones Orgánicos/antagonistas & inhibidores , Animales , Área Bajo la Curva , Interacciones Farmacológicas , Células HEK293 , Semivida , Humanos , Masculino , Ratas , Proteínas Recombinantes/metabolismo , Rosuvastatina Cálcica/administración & dosificación , Miembro 1B3 de la Familia de los Transportadores de Solutos de Aniones Orgánicos/metabolismoAsunto(s)
Quimioterapia Combinada , Inmunosupresores , Ácido Micofenólico , Prednisolona , Ácido Micofenólico/uso terapéutico , Ácido Micofenólico/administración & dosificación , Humanos , Prednisolona/administración & dosificación , Prednisolona/uso terapéutico , Quimioterapia Combinada/métodos , Inmunosupresores/administración & dosificación , Inmunosupresores/uso terapéutico , AnimalesAsunto(s)
Anticuerpos Monoclonales/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Citomegalovirus , Mieloma Múltiple/tratamiento farmacológico , Activación Viral , Anciano , Antineoplásicos Inmunológicos/uso terapéutico , Citomegalovirus/efectos de los fármacos , Citomegalovirus/fisiología , Infecciones por Citomegalovirus/virología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/virología , Activación Viral/efectos de los fármacosAsunto(s)
Leucemia-Linfoma Linfoblástico de Células Precursoras , Piridazinas , Anciano , Anciano Frágil , Humanos , Imidazoles , Cromosoma Filadelfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Inhibidores de Proteínas Quinasas/uso terapéutico , Piridazinas/uso terapéutico , Esteroides/uso terapéuticoRESUMEN
A 64-year-old woman was admitted to our hospital to undergo allogeneic stem cell transplantation. She was diagnosed with polycythemia vera with a JAK2 V617F mutation 7 years ago. She was administered ruxolitinib for splenomegaly two years prior to admission but this was discontinued because of progressive pancytopenia. One months after cessation of ruxolitinib, she developed acute myeloid leukemia transformed from post-polycythemia vera myelofibrosis. Although she achieved complete remission after induction therapy, 8-finger-breadth splenomegaly remained below the left costal margin. Ruxolitinib was re-administered following two courses of consolidation therapy. She underwent unrelated peripheral blood stem cell transplantation. Ruxolitinib was administered until the day before transplantation, and the spleen was palpated in 4-finger breadth below costal arc. Neutrophil engraftment was achieved 13 days after transplantation. In allogeneic stem cell transplantation, splenomegaly is one of the risk factors for engraftment failure and/or therapy-related mortality. Hence, a smaller spleen size can theoretically improve the outcome after transplantation. The administration of ruxolitinib prior to transplantation may have contributed to engraftment with a non-invasive reduction in the size of the spleen.
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Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda/terapia , Mielofibrosis Primaria/complicaciones , Pirazoles/uso terapéutico , Esplenomegalia/tratamiento farmacológico , Femenino , Humanos , Leucemia Mieloide Aguda/etiología , Persona de Mediana Edad , Nitrilos , Pirimidinas , Acondicionamiento Pretrasplante , Trasplante HomólogoRESUMEN
Hemophagocytic syndrome (HPS) is frequently associated with hematopoietic stem cell transplantation and is treated with some benefit derived from TNF-α inhibitors. However, the mechanisms of how HPS occurs and how a TNF-α inhibitor exerts some benefit to HPS management have remained unclear. We evaluated the effect of toll-like receptor (TLR) ligands, especially focusing on cytosine-phosphorothionate-guanine oligodeoxynucleotide (CpG), a TLR9 ligand, on HPS in mice that underwent transplantation with syngeneic or allogeneic bone marrow (BM) cells (Syn-BMT, Allo-BMT), or with allogeneic BM cells plus splenocytes to promote graft-versus-host disease (GVHD mice). Hemophagocytosis was a common feature early after all BMT, but it subsided in Syn-BMT and Allo-BMT mice. In GVHD mice, however, hemophagocytosis persisted and was accompanied by upregulated production of IFN-γ but not TNF-α, and it was suppressed by blockade of IFN-γ but not TNF-α. A single injection of the TLR9 ligand CpG promoted HPS in all BMT mice and was lethal in GVHD mice, accompanied by greatly upregulated production of TNF-α, IL-6, and IFN-γ. Blocking of TNF-α, but not IL-6 or IFN-γ, suppressed CpG-induced HPS in all BMT mice and rescued GVHD mice from CpG-induced mortality. Thus, TLR9 signaling mediates TNF-α-driven HPS in BMT mice and is effectively treated through TNF-α inhibition.
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Trasplante de Médula Ósea/métodos , Linfohistiocitosis Hemofagocítica/inmunología , Oligodesoxirribonucleótidos/farmacología , Receptor Toll-Like 9/inmunología , Factor de Necrosis Tumoral alfa/inmunología , Animales , Anticuerpos Monoclonales/farmacología , Células de la Médula Ósea/citología , Células de la Médula Ósea/inmunología , Trasplante de Médula Ósea/efectos adversos , Islas de CpG/inmunología , Etanercept/farmacología , Rayos gamma , Regulación de la Expresión Génica , Enfermedad Injerto contra Huésped/inmunología , Enfermedad Injerto contra Huésped/patología , Interferón gamma/antagonistas & inhibidores , Interferón gamma/genética , Interferón gamma/inmunología , Interleucina-6/genética , Interleucina-6/inmunología , Linfocitos/citología , Linfocitos/inmunología , Linfohistiocitosis Hemofagocítica/etiología , Linfohistiocitosis Hemofagocítica/patología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Noqueados , Oligodesoxirribonucleótidos/antagonistas & inhibidores , Transducción de Señal , Receptor Toll-Like 9/genética , Trasplante Homólogo , Trasplante Isogénico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/genética , Irradiación Corporal TotalRESUMEN
OBJECTIVE: To evaluate signal intensity-time (SI-Time) curve and quantitative dynamic contrast-enhanced 3.0T magnetic resonance imaging in diagnosis and differentiating neoplasm of uterus.â© METHODS: A total of 42 cases of uterine neoplasm (20 were malignant and 22 were benign) were evaluated in our study. All cases received dynamic contrast-enhanced scanning on 3.0T MRI. The raw data was processed by Siemens Tissue 4D software and the SI-Time curve was obtained and analyzed. Pharmacokinetic modeling of Tofts with a modeled vascular input function was used for calculating volume parameters: volume transfer constant (Ktrans), reverse volume transfer constant (Kep), the extravascular extracellular space volume per unit volume of tissue (Ve). The correlation of these parameters at each groups were investigated. The SI-Time curve and the data of perfusion parameters between the 2 groups were compared by T test.â© RESULTS: Among 20 malignant tumors, 12 were cervical carcinoma and 8 were endometrial cancer. Among the benign tumors, 13 were leiomyomas, 3 were endometrial polyp, 3 were endometrial hyperplasia, and 3 were adenomyosis. 59.1% cases of benign tumors belong to Type I curve and 65% cases of malignant tumors belong to Type II curve. There was significant difference in SI-Time curve between benign and malignant tumors (P=0.011). If Type I curve was used as diagnostic criteria for benign tumors, and Type II and III curve were for malignant tumors, the diagnostic sensitivity, specificity, positive predictive value, negative predictive value were 90.0%, 59.1%, 66.7%, and 86.7%, respectively. Ve was 0.477 ± 0.143 in malignant and 0.614 ± 0.146 in control group with significant difference (P=0.004). Ve was 0.477 ± 0.143 in malignant and 0.589 0.176 in benign group with significant difference (P=0.004). Ktrans was (0.178 ± 0.067) min⻹ in malignant and (0.263 ± 0.111) min⻹ in control group with significant difference (P=0.003). Ktrans was (0.182 ± 0.096) min⻹ in benign and (0.263 ± 0.111) min⻹ in control group with significant difference (P=0.011). â© CONCLUSION: The type of SI-Time curve and perfusion parameters were important for differentiating benign and malignant uterine tumors in dynamic enhanced MRI. These parameters provide a supplement for conventional morphological MR diagnosis.
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Medios de Contraste , Imagen por Resonancia Magnética , Neoplasias Uterinas/diagnóstico , Útero/patología , Femenino , Humanos , Sensibilidad y EspecificidadRESUMEN
Mammalian erythroblasts undergo enucleation, a process thought to be similar to cytokinesis. Although an assemblage of actin, non-muscle myosin II, and several other proteins is crucial for proper cytokinesis, the role of non-muscle myosin II in enucleation remains unclear. In this study, we investigated the effect of various cell-division inhibitors on cytokinesis and enucleation. For this purpose, we used human colony-forming unit-erythroid (CFU-E) and mature erythroblasts generated from purified CD34(+) cells as target cells for cytokinesis and enucleation assay, respectively. Here we show that the inhibition of myosin by blebbistatin, an inhibitor of non-muscle myosin II ATPase, blocks both cell division and enucleation, which suggests that non-muscle myosin II plays an essential role not only in cytokinesis but also in enucleation. When the function of non-muscle myosin heavy chain (NMHC) IIA or IIB was inhibited by an exogenous expression of myosin rod fragment, myosin IIA or IIB, each rod fragment blocked the proliferation of CFU-E but only the rod fragment for IIB inhibited the enucleation of mature erythroblasts. These data indicate that NMHC IIB among the isoforms is involved in the enucleation of human erythroblasts.
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Eritroblastos/citología , Eritroblastos/metabolismo , Eritropoyesis , Miosina Tipo IIB no Muscular/metabolismo , Amidas/farmacología , Aminoquinolinas/farmacología , Células Cultivadas , Citocinesis/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Eritroblastos/efectos de los fármacos , Células Precursoras Eritroides/citología , Células Precursoras Eritroides/efectos de los fármacos , Células Precursoras Eritroides/metabolismo , Eritropoyesis/efectos de los fármacos , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Compuestos Heterocíclicos de 4 o más Anillos/farmacología , Humanos , Proteínas de Microfilamentos/antagonistas & inhibidores , Miosinas/antagonistas & inhibidores , Miosina Tipo IIA no Muscular/antagonistas & inhibidores , Miosina Tipo IIA no Muscular/genética , Miosina Tipo IIA no Muscular/metabolismo , Miosina Tipo IIB no Muscular/antagonistas & inhibidores , Miosina Tipo IIB no Muscular/genética , Fragmentos de Péptidos/genética , Fragmentos de Péptidos/metabolismo , Isoformas de Proteínas/antagonistas & inhibidores , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Piridinas/farmacología , Pirimidinas/farmacología , Proteínas Recombinantes de Fusión/metabolismo , Proteína de Unión al GTP rac1/antagonistas & inhibidores , Quinasas Asociadas a rho/antagonistas & inhibidoresRESUMEN
BACKGROUND: Organophosphorus pesticides (OPPs) are widely used in the world, however, OPP poisoning often occurs because of improper use and lack of protective measures. Cardiotoxicity injury induced by OPPs is insidious, and it does not receive attention until the end stage of OPP poisoning. Heart failure or arrhythmia gradually becomes the main lethal cause of OPP poisoning patients. METHODS: In this study, network toxicology and molecular docking were employed to investigate the non-acetylcholinesterase targets and mechanisms of cardiotoxicity injury induced by OPPs. RESULTS: One hundred twenty-three targets of dichlorvos, 205 targets of methidathion, and 337 targets of malathion were searched from SwissTargetPreict, STITCH and PharmMapper database. Additionally, 1379 targets related to cardiotoxicity injury were acquired from GeneCards and OMIM database. Ninety-six mutual targets between OPPs and cardiotoxicity injury were considered as the potential cardiotoxicity injury targets induced by OPPs. The protein-protein interaction (PPI) network was constructed using STING database, and 21 core targets were identified by Cytoscape software, such as AKT1, ESR1, HSP90AA1, MAPK1, MMP9, and MAPK8. Gene ontology and KEGG enrichment analysis revealed that cell migration, apoptotic process, protein phosphorylation and signal transduction were the major biological functions associated with OPPs-induced cardiotoxicity injury, and OPPs-induced cardiotoxicity injury might be regulated by MAPK, PI3K-Akt, VEGF signaling pathway. Docking results manifested that the best binding target for dichlorvos, methidathion and malathion were MAPK9 (-7.1 kcal/mol), MAPK1 (-8.1 kcal/mol) and HSP90AA1 (-8.6 kcal/mol) with the lowest affinity, respectively. CONCLUSION: The core targets and non-AchE mechanisms were explored by network toxicology and molecular docking, providing a theoretical basis for the treatment of OPP-induced cardiotoxicity injury.
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Cardiotoxicidad , Simulación del Acoplamiento Molecular , Compuestos Organofosforados , Plaguicidas , Humanos , Mapas de Interacción de ProteínasRESUMEN
Introduction: This study investigated the effects of dietary energy level on the antioxidant capability, immune function, and rectal microbiota in donkey jennets during the last 60 days of gestation. Methods: Fifteen pregnant DeZhou donkeys with age of 6.0 ± 0.1 years, body weight of 292 ± 33 kg, parity of 2.7 ± 0.1 parities and similar expected date of confinement (74 ± 4 days) were randomly allocated to three groups and feed three diets: high energy (10.92 MJ/kg, H), medium energy (10.49 MJ/kg, M), and low energy (9.94 MJ/kg, L). Results and Discussion: The serum activity of catalase (CAT), total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC) in group M was significantly higher, whereas the concentrations of malondialdehyde (MDA), interleukin 1 (IL-1), IL-2, and IL-6 were lower than those recorded for groups H and L (p ≤ 0.05). The dietary energy level significantly affected rectal microbial community structure in the jennet donkeys 35 days and 7 days before the parturition (p ≤ 0.05). The abundances of norank_f_norank_o_Coriobacteriales genus was significantly higher (p ≤ 0.05) in group H, and the abundances of norank_f_norank_o_Mollicutes_RF39 and the Candidatus_Saccharimonas were higher in group L (p ≤ 0.05). The abundance of Fibrobacter in group M was significantly increased (p ≤ 0.05). The abundance of norank_f_norank_o_Coriobacteriales was positively correlated with average daily gain (ADG) and tumor necrosis factor-α (TNF-α) concentrations (p ≤ 0.05). The abundance of norank_f_norank_o_Mollicutes_RF39 was positively correlated with IL-2 and IL-6 concentrations. The abundance of Candidatus_Saccharimonas was positively correlated with CAT, T-SOD and GSH-Px activities (p ≤ 0.05). The abundance of Fibrobacter was positively correlated with CAT and T-SOD activities (p ≤ 0.05), but negatively correlated with IL-2 concentration (p ≤ 0.05). In conclusion, an appropriate dietary with an energy content of 10.49 MJ/kg for jennet donkeys during late gestation increased the prenatal antioxidant capacity, reduced inflammatory cytokines, and promoted fetal growth, and these changes were related to diet-induced changes in rectal microbiota compositions.
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This study investigated the effects of dietary energy levels during late gestation on mineral content in the plasma, colostrum, and milk of jennies postpartum. Twenty-four pregnant multiparous DeZhou jennies, aged 6.0 ± 0.1 years, with a body weight of 292 ± 33 kg, an average parity number of 2.7 ± 0.1, and similar expected dates of confinement (74 ± 4 days), were randomly allocated to three groups and fed three diets: high energy (12.54 MJ/kg, HE), medium energy (12.03 MJ/kg, ME), and low energy (11.39 MJ/kg, LE). Blood samples were collected from the jugular vein of each jenny at time points of 0 h, 24 h, 48 h, 5 d, 7 d, and 14 d after parturition. Additionally, milk samples were collected through manual milking, and an analysis of the mineral content was conducted. The results showed that compared with HE, both ME and LE significantly increased the levels of calcium (Ca), phosphorus (P), zinc (Zn), selenium (Se), molybdenum (Mo), and cobalt (Co) in the plasma and Ca, P, magnesium (Mg), copper (Cu), manganese (Mn), Zn, selenium (Se), molybdenum (Mo), and Co in the milk of jennies postpartum (p < 0.05); ME also increased the levels of potassium (K), iron (Fe), and Mn in plasma and K and Fe in milk (p < 0.05). The levels of Ca, K, Mg, P, Fe, Cu, Mn, Co, Se, Zn, and Mo in plasma and milk gradually decreased with increasing postpartum time. Their contents were the highest at 0 h postpartum, rapidly decreased after 24 h postpartum, and declined to the lowest on day 14 postpartum. The interaction between dietary energy level and postpartum time showed that although the concentrations of the minerals Ca, P, K, Mg, Fe, Cu, Mn, Zn, Co, Se, and Mo decreased in jennies' plasma and milk in the treatment groups with different energy levels as postpartum time increased, the pattern of change was also influenced by dietary energy level. The influence of dietary energy level in late gestation on the mineral content of milk and plasma during the postpartum colostrum phase was higher than that during the milk phase. In conclusion, this study demonstrated that, under the current experimental conditions, the mineral content of the colostrum, milk, and plasma of jennies after parturition was dependent on the dietary energy level during late gestation.
RESUMEN
An interfacial C-S bond bridged ZnS/C3N5 heterojunction was constructed for photocatalytic H2 evolution. Different from traditional type-II ZnS/C3N4 heterojunction, the electron transfer followed S-scheme pathway, due to opposite internal-electric-field (IEF) directions in these two heterojunctions. The C-S bond formation was carefully investigated, and they were susceptive to the preparation temperatures. In photocatalytic reaction, C-S bond was functioned as the "high-speed channel" for electron separation and transfer, and the IEF strength in ZnS/C3N5 was 1.86 × 108 V/m, 2.6 times higher than that in ZnS/C3N4. Moreover, the C-S bond also altered the surface molecular structure of ZnS/C3N5, and hence the surface reaction was accelerated via improving H2O adsorption and activation behaviors. Benefiting from the S-scheme pathway, enhanced IEF strength, and accelerated surface reaction, the photocatalytic H2 production over ZnS/C3N5 reached up to 20.18 mmol/g/h, 3.2 and 2.5 times higher than those of ZnS/C3N4 and ZnS/C3N5-300 without C-S bond.
RESUMEN
Donkey milk is a traditional medicinal food with various biological activities. However, its production is very low, and lactating donkeys often experience oxidative stress, leading to a further decline in milk yield. In this study, we supplemented the diets of lactating donkeys with yeast selenium (SY) to investigate its effects on lactation performance, antioxidant status, and immune responses, and we expected to determine the optimum additive level of SY in the diet. For this study, 28 healthy lactating Dezhou donkeys with days in milk (DIM, 39.93 ± 7.02 d), estimated milk yield (EMY, 3.60 ± 0.84 kg/d), and parity (2.82 ± 0.48) were selected and randomly divided into 4 groups of 7 donkeys in each: Group SY-0 (control), Group SY-0.15, Group SY-0.3, and Group SY-0.5, with selenium supplementation of 0, 0.15, 0.3, and 0.5 mg of Se/kg DM (in form of SY) to the basal diet, respectively. The results showed a dose-dependent increase in milk yield, milk component yield, milk protein production efficiency, milk production efficiency, the activities of glutathione peroxidases (GSH-Px), catalase (CAT), and total antioxidant capacity (T-AOC), as well as the content of serum interleukin-10 (IL-10), white blood cells (WBC), lymphocytes (LYM), red blood cells (RBC), hematocrit, plasma selenium, and milk selenium. Conversely, it presented a dose-dependent decrease in the activity of nitric oxide synthase (iNOS) and the contents of malondialdehyde (MDA), reactive oxygen species (ROS), nitric oxide (NO), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and interferon-γ (IFN-γ). In conclusion, the results confirmed that dietary supplementation with SY can improve lactation performance, antioxidant status, and immune responses in lactating donkeys, and the recommended dose of SY was 0.3 mg/kg.