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Skeletal muscle regeneration is essential for maintaining muscle function in injury and muscular disease. Myogenesis plays key roles in forming new myofibers during the process. Here, through bioinformatic screen for the potential regulators of myogenesis from 5 independent microarray datasets, we identify an overlapping differentially expressed gene (DEG) optineurin (OPTN). Optn knockdown (KD) delays muscle regeneration in mice and impairs C2C12 myoblast differentiation without affecting their proliferation. Conversely, Optn overexpression (OE) promotes myoblast differentiation. Mechanistically, OPTN increases nuclear levels of ß-catenin and enhances the T-cell factor/lymphoid enhancer factor (TCF/LEF) transcription activity, suggesting activation of Wnt signaling pathway. The activation is accompanied by decreased protein levels of glycogen synthase kinase 3ß (GSK3ß), a negative regulator of the pathway. We further show that OPTN physically interacts with and targets GSK3ß for autophagic degradation. Pharmacological inhibition of GSK3ß rescues the impaired myogenesis induced by Optn KD during muscle regeneration and myoblast differentiation, corroborating that GSK3ß is the downstream effector of OPTN-mediated myogenesis. Together, our study delineates the novel role of OPTN as a potential regulator of myogenesis and may open innovative therapeutic perspectives for muscle regeneration.
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Autofagia , Proteínas de Ciclo Celular , Glucógeno Sintasa Quinasa 3 beta , Proteínas de Transporte de Membrana , Desarrollo de Músculos , Vía de Señalización Wnt , Animales , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Diferenciación Celular/genética , Glucógeno Sintasa Quinasa 3 beta/genética , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Proteínas de Transporte de Membrana/genética , Proteínas de Transporte de Membrana/metabolismo , Ratones , Desarrollo de Músculos/genética , Músculo Esquelético/metabolismo , Vía de Señalización Wnt/genéticaRESUMEN
BACKGROUND: Multidrug resistance in Enterobacteriaceae including resistance to quinolones is rising worldwide. The development of resistance may lead to the emergence of new transmission mechanisms. In this study, the collection of different E. coli was performed from animals and subjected to subsequent procedures including pulsed-field gel electrophoresis, micro-broth dilution method, polymerase chain reaction. Whole genome sequencing of E. coli C3 was performed to detect the affinity, antimicrobial resistance and major carriers of the isolates. RESULTS: A total of 66 E. coli were isolated and their antibiotic resistance genes, frequency of horizontal transfer and genetic environment of E. coli C3 were determined. The results showed there were both different and same types in PFGE typing, indicating clonal transmission of E. coli among different animals. The detection of antimicrobial resistance and major antibiotic resistance genes and the plasmid transfer results showed that strains from different sources had high levels of resistance to commonly used clinical antibiotics and could be spread horizontally. Whole-genome sequencing discovered a novel ICE mobile element. CONCLUSION: In summary, the antimicrobial resistance of E. coli in northeast China is a serious issue and there is a risk of antimicrobial resistance transmission. Meanwhile, a novel ICE mobile element appeared in the process of antimicrobial resistance formation.
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Infecciones por Escherichia coli , Escherichia coli , Animales , Antibacterianos/farmacología , Farmacorresistencia Bacteriana/genética , Infecciones por Escherichia coli/veterinaria , Enterobacteriaceae , China , Pruebas de Sensibilidad Microbiana/veterinaria , Plásmidos , Electroforesis en Gel de Campo Pulsado/veterinaria , beta-Lactamasas/genéticaRESUMEN
Obesity and related metabolic disorders are associated with intestinal microbiota dysbiosis, disrupted intestinal barrier, and chronic inflammation. Neohesperidin (Neo), a natural polyphenol abundant in citrus fruits, is known for its preventative and therapeutic effects on numerous diseases. Here, we report that Neo administration attenuates weight gain, low-grade inflammation, and insulin resistance in mice fed high-fat diet (HFD). Also, Neo administration substantially restores gut barrier damage, metabolic endotoxemia, and systemic inflammation. Sequencing of 16S rRNA genes in fecal samples revealed that Neo administration reverses HFD-induced intestinal microbiota dysbiosis: an increase in the diversity of gut microbiota and alteration in the composition of intestinal microbiota (particularly in the relative abundances of Bacteroidetes and Firmicutes). Furthermore, systemic antibiotic treatment abolishes the beneficial effects of Neo in body weight control, suggesting that the effect of Neo on obesity attenuation largely depends on the gut microbiota. More importantly, we demonstrate that the impact of Neo on the regulation of obesity could be transferred from Neo-treated mice to HFD-fed mice via fecal microbiota transplantation. Collectively, our data highlight the efficacy of Neo as a prebiotic agent for attenuating obesity, implying a potential mechanism for gut microbiota mediated the beneficial effect of Neo.
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Bacteroidetes/crecimiento & desarrollo , Dieta Alta en Grasa/efectos adversos , Firmicutes/crecimiento & desarrollo , Microbioma Gastrointestinal/efectos de los fármacos , Hesperidina/análogos & derivados , Obesidad , Animales , Hesperidina/farmacología , Masculino , Ratones , Obesidad/inducido químicamente , Obesidad/tratamiento farmacológico , Obesidad/microbiologíaRESUMEN
Mitochondrial aconitase (Aco2) catalyzes the conversion of citrate to isocitrate in the TCA cycle, which produces NADH and FADH2, driving synthesis of ATP through OXPHOS. In this study, to explore the relationship between adipogenesis and mitochondrial energy metabolism, we hypothesize that Aco2 may play a key role in the lipid synthesis. Here, we show that overexpression of Aco2 in 3T3-L1 cells significantly increased lipogenesis and adipogenesis, accompanied by elevated mitochondrial biogenesis and ATP production. However, when ATP is depleted by rotenone, an inhibitor of the respiratory chain, the promotive role of Aco2 in adipogenesis is abolished. In contrast to Aco2 overexpression, deficiency of Aco2 markedly reduced lipogenesis and adipogenesis, along with the decreased mitochondrial biogenesis and ATP production. Supplementation of isocitrate efficiently rescued the inhibitory effect of Aco2 deficiency. Similarly, the restorative effect of isocitrate was abolished in the presence of rotenone. Together, these results show that Aco2 sustains normal adipogenesis through mediating ATP production, revealing a potential mechanistic link between TCA cycle enzyme and lipid synthesis. Our work suggest that regulation of adipose tissue mitochondria function may be a potential way for combating abnormal adipogenesis related diseases such as obesity and lipodystrophy.
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Aconitato Hidratasa/metabolismo , Adenosina Trifosfato/metabolismo , Adipogénesis , Tejido Adiposo/citología , Mitocondrias/enzimología , Células 3T3-L1 , Aconitato Hidratasa/genética , Tejido Adiposo/metabolismo , Animales , Masculino , Ratones , Ratones Endogámicos C57BLRESUMEN
A new compound named koninginin W (1) and four known polyketides (2-5) were isolated from endophytic fungus Trichoderma koningiopsis YIM PH30002 of Panax notoginseng. The structures of 1 - 5, including absolute configuration of 1, were elucidated on the detailed analysis of the HR-ESI-MS, 1D and 2D NMR, and X-ray crystallographic data. Koninginin W (1) presented weak antibacterial activity against Escherichia coli, Bacillus subtilis and Salmonella typhimurium.
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Antibacterianos/farmacología , Bacillus subtilis/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Salmonella typhimurium/efectos de los fármacos , Trichoderma/química , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Pruebas de Sensibilidad Microbiana , Conformación MolecularRESUMEN
Endophytic fungi play important roles for host's stress tolerance including invasion by pathogenic microbes. Small molecules are common weapons in the microbe-microbe interactions. Panax notoginseng is a widely used traditional Chinese medicinal plant and harbors many endophytes, some exert functions against pathogens. Here, we report six new compounds named myrothins A-F (1-6) produced by Myrothecium sp. BS-31, an endophyte isolated from P. notoginseng, and their antifungal activities against pathogenic fungi causing host root-rot disease. Their structures were elucidated with analysis of spectroscopic data including 1D and 2D NMR, HR-ESI-MS. Myrothins B (2) and E (5) showed the weak activity against Fusarium oxysporum and Phoma herbarum, and myrothins F (6) showed weak activity against F. oxysporum.
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Antifúngicos/farmacología , Endófitos/química , Hypocreales/química , Panax notoginseng/microbiología , Antifúngicos/química , Antifúngicos/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Fusarium/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Phoma/efectos de los fármacos , Estereoisomerismo , Relación Estructura-ActividadRESUMEN
Ten compounds (1-10) were obtained from soil-derived Penicillium cremeogriseum W1-1 with the antimicrobial guided isolation procedure. Among them, 4 presented broad-spectrum antimicrobial activities and its preliminary mechanisms were evaluated. Compound 4 showed growth inhibition on drug-resistant pathogenic strains Escherichia coli and Candida albicans with post-contact effect (PCE), changed the morphology and membrane structure, killed cells with leakage, inhibited the growth of C. albicans by eradicating biofilms. Interestingly, the fraction containing 4 presented in vivo anti-pathogenic activities in mice, indicating this indole diterpenoid alkaloid could been used as potential antimicrobial agent.
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Ischemic heart disease is widely considered as a major health threat, which causes a high number of deaths every year worldwide. Much evidence has shown that oxidative stress (OS) is implicated in the pathogenesis of ischemia-reperfusion injury (IRI). This study aims to evaluate the effect of miR-590-3p on the OS of IRI mice through the nuclear factor kappa-B (NF-κB) signaling pathway by targeting receptor-interacting protein kinase 1 (RIPK1). IRI mouse models were established for extracting myocardial tissues and isolating myocardial cells. The expression of inflammatory related-factors was detected by enzyme-linked immunosorbent assay, and superoxide dismutase (SOD) and malondialdehyde (MDA) in tissues were determined. Reverse transcription quantitative polymerase chain reaction and Western blot analysis were performed to assess the role of miR-590-3p in the expression of NF-κB-related factors and apoptosis-related factors. Besides, the regulatory effects of miR-590-3p on myocardial cell proliferation and apoptosis were also assessed. According to the obtained results, we found that IRI mice displayed higher expression of tumor necrosis factor-α, interleukin (IL)-6, and interferon-γ, lower expression of IL-10 in serum, a decreased SOD level, and an increased MDA level. In addition, RIPK1 was determined as a target gene of miR-590-3p. After transfection of overexpressed miR-590-3p or si-RIPK1, declined RIPK1, NF-κB, Toll-like receptor 4, caspase-3, FasL, p53, and c-myc levels, increased B-cell lymphoma-2 level, promoted cell proliferation, promoted cell cycle distribution and inhibited apoptosis of myocardial cells were found. Our study demonstrates that miR-590-3p can alleviate the OS of IRI mice through the inhibition of the RIPK1 and NF-κB signaling pathway. Thus, miR-590-3p represents a potential target for IRI repair.
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Apoptosis , Proliferación Celular , MicroARNs/biosíntesis , Daño por Reperfusión Miocárdica/metabolismo , Miocardio/metabolismo , FN-kappa B/metabolismo , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismo , Transducción de Señal , Animales , Ratones , Ratones Endogámicos BALB C , Daño por Reperfusión Miocárdica/patología , Miocardio/patología , RatasRESUMEN
Exendin-4, a glucagon-like peptide-1 receptor agonist, demonstrated cytoprotective actions beyond glycemic control in recent studies. The aims of the present study were to investigate the effects of exendin-4 on high glucose (HG)-induced cardiomyocyte apoptosis and the possible mechanisms. Rat cardiomyocytes were divided into 3 groups: normal glucose group (NG group), HG group and HG +exendin-4 group (HG+Ex Group). Cardiomyocyte apoptosis was evaluated by double-staining with annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) and flow cytometry. Intracellular reactive oxygen species (ROS) production was detected by 2',7'-dichlorodihydrofluorescein diacetate (DCHF-DA) incubation and fluorescence microscopy. LY294002 (LY), a phosphoinositide 3-kinase (PI3K) pathway inhibitor, was added to the medium of the HG+Ex+LY Group for further western blot analysis. The proteins analyzed involved oxidative stress-associated proteins, heme oxygenase-1 (HO-1) and nuclear factor E2-related factor 2 (Nrf-2), and apoptosis-associated proteins, caspase-3, Bax/B-cell lymphoma 2 (Bcl-2) and p-AKT/AKT. HG treatment induced cardiomyocyte apoptosis (P = 0.00) and clearly upregulated ROS production (P = 0.00); exendin-4 co-incubation also ameliorated cardiomyocyte apoptosis (P = 0.004) and decreased ROS (P = 0.00) level significantly. HO-1 and Nrf-2 protein expression levels decreased significantly in the HG group (P < 0.05), but the levels were elevated by exendin-4 intervention (P < 0.05). Furthermore, exendin-4 attenuated HG-induced higher protein expression, including cleaved caspase-3 and Bax, increased the expression of Bcl-2 protein (P < 0.05). However, these impacts of exendin-4 were counteracted significantly by co-incubation with LY294002. In addition, exendin-4 ameliorated HG-induced p-AKT/AKT lower expression, and this impact was also suppressed by LY294002. Exendin-4 ameliorates HG-induced cardiomyocyte apoptosis, and the mechanisms may involve anti-oxidative stress via the HO-1/Nrf-2 system, as well as intervention of the PI3K/AKT signaling pathway.
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Apoptosis/efectos de los fármacos , Glucosa/administración & dosificación , Hemo-Oxigenasa 1/metabolismo , Miocitos Cardíacos/fisiología , Factor 2 Relacionado con NF-E2/metabolismo , Péptidos/administración & dosificación , Fosfatidilinositol 3-Quinasas/metabolismo , Ponzoñas/administración & dosificación , Animales , Células Cultivadas , Exenatida , Miocitos Cardíacos/citología , Miocitos Cardíacos/efectos de los fármacos , Proteína Oncogénica v-akt/metabolismo , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiologíaRESUMEN
BACKGROUND: Cardiac dysfunction in diabetic cardiomyopathy may be associated with abnormal Ca2+ homeostasis. This study investigated the effects of alterations in Ca2+ homeostasis and sarcoplasmic reticulum Ca2+-associated proteins on cardiac function in the development of diabetic cardiomyopathy. METHODS: Sprague-Dawley rats were divided into 4 groups (n = 12, each): a control group, and streptozotocin-induced rat models of diabetes groups, examined after 4, 8, or 12 weeks. Evaluations on cardiac structure and function were performed by echocardiography and hemodynamic examinations, respectively. Cardiomyocytes were isolated and spontaneous Ca2+ spark images were formed by introducing fluorescent dye Fluo-4 and obtained with confocal scanning microscopy. Expressions of Ca2+-associated proteins were assessed by Western blotting. RESULTS: Echocardiography and hemodynamic measurements revealed that cardiac dysfunction is associated with the progression of diabetes, which also correlated with a gradual but significant decline in Ca2+ spark frequency (in the 4-, 8- and 12-week diabetic groups). However, Ca2+ spark decay time constants increased significantly, relative to the control group. Expressions of ryanodine receptor 2 (RyR2), sarcoplasmic reticulum Ca2+-2ATPase (SERCA) and Na+/Ca2+ exchanger (NCX1) were decreased, together with quantitative alterations in Ca2+regulatory proteins, FKBP12.6 and phospholamban progressively and respectively in the diabetic rats. CONCLUSIONS: Ca2+ sparks exhibited a time-dependent decay with progression of diabetic cardiomyopathy, which may partly contribute to cardiac dysfunction. This abnormality may be attributable to alterations in the expressions of some Ca2+-associated proteins.
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Calcio/fisiología , Cardiomiopatías Diabéticas/diagnóstico por imagen , Cardiomiopatías Diabéticas/metabolismo , Progresión de la Enfermedad , Homeostasis/fisiología , Animales , Masculino , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Ratas , Ratas Sprague-Dawley , UltrasonografíaRESUMEN
BACKGROUND: Toxoplasma gondii is an important protozoan pathogen with medical and veterinary importance worldwide. Drugs currently used for treatment of toxoplasmosis are less effective and sometimes cause serious side effects. There is an urgent need for the development of more effective drugs with relatively low toxicity. METHODS: The effect of tylosin on the viability of host cells was measured using CCK8 assays. To assess the inhibition of tylosin on T. gondii proliferation, a real-time PCR targeting the B1 gene was developed for T. gondii detection and quantification. Total RNA was extracted from parasites treated with tylosin and then subjected to transcriptome analysis by RNA sequencing (RNA-seq). Finally, murine infection models of toxoplasmosis were used to evaluate the protective efficacy of tylosin against T. gondii virulent RH strain or avirulent ME49 strain. RESULTS: We found that tylosin displayed low host toxicity, and its 50% inhibitory concentration was 175.3 µM. Tylsoin also inhibited intracellular T. gondii tachyzoite proliferation, with a 50% effective concentration of 9.759 µM. Transcriptome analysis showed that tylosin remarkably perturbed the gene expression of T. gondii, and genes involved in "ribosome biogenesis (GO:0042254)" and "ribosome (GO:0005840)" were significantly dys-regulated. In a murine model, tylosin treatment alone (100 mg/kg, i.p.) or in combination with sulfadiazine sodium (200 mg/kg, i.g.) significantly prolonged the survival time and raised the survival rate of animals infected with T. gondii virulent RH or avirulent ME49 strain. Meanwhile, treatment with tylosin significantly decreased the parasite burdens in multiple organs and decreased the spleen index of mice with acute toxoplasmosis. CONCLUSIONS: Our findings suggest that tylosin exhibited potency against T. gondii both in vitro and in vivo, which offers promise for treatment of human toxoplasmosis.
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Toxoplasma , Toxoplasmosis , Humanos , Animales , Ratones , Tilosina/farmacología , Tilosina/uso terapéutico , Toxoplasmosis/tratamiento farmacológico , Toxoplasmosis/parasitología , Sulfadiazina/farmacología , Sulfadiazina/uso terapéutico , BazoRESUMEN
Toxoplasma gondii is an important protozoan pathogen, which can cause severe diseases in the newborns and immunocompromised individuals. Developing an effective vaccine against Toxoplasma infection is a critically important global health priority. Immunofluorescence staining analysis revealed that TgSAG2 and TgSRS2 are membrane associated and displayed on the surface of the parasite. Immunizations with pBud-SAG2, pBud-SRS2 and pBud-SAG2-SRS2 DNA vaccines significantly increased the production of specific IgG antibodies. Immunization with pBud-SAG2-SRS2 elicited cellular immune response with higher concentrations of IFN-γ and IL-4 compared to the control group. Antigen-specific lymphocyte proliferations in the pBud-SRS2 and pBud-SAG2-SRS2 groups were significantly higher compared to that in the control group. Furthermore, 30 % of mice immunized with pBud-SAG2-SRS2 survived after the challenge infection with virulent T. gondii RH tachyzoites. This study revealed that immunization with pBud-SAG2-SRS2 induced potent immune responses, and has the potential as a promising vaccine candidate for the control of T. gondii infection.
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Anticuerpos Antiprotozoarios , Antígenos de Protozoos , Inmunoglobulina G , Proteínas Protozoarias , Vacunas Antiprotozoos , Toxoplasma , Toxoplasmosis Animal , Vacunas de ADN , Animales , Vacunas de ADN/inmunología , Vacunas de ADN/genética , Vacunas de ADN/administración & dosificación , Antígenos de Protozoos/inmunología , Antígenos de Protozoos/genética , Proteínas Protozoarias/inmunología , Proteínas Protozoarias/genética , Toxoplasma/inmunología , Toxoplasma/genética , Anticuerpos Antiprotozoarios/sangre , Vacunas Antiprotozoos/inmunología , Vacunas Antiprotozoos/administración & dosificación , Vacunas Antiprotozoos/genética , Ratones , Inmunoglobulina G/sangre , Femenino , Toxoplasmosis Animal/prevención & control , Toxoplasmosis Animal/inmunología , Ratones Endogámicos BALB C , Interferón gamma/inmunología , Modelos Animales de Enfermedad , Proliferación Celular , Interleucina-4/inmunología , Análisis de SupervivenciaRESUMEN
A hybrid was at first synthesized by a postfunctionalization of an aminomethane trisalkoxo-functionalized Anderson-type polyoxometalate (POM) encapsulated by three tetrabutylammonium ions using a 3,5-bis(tetradecyloxy)benzoic acid by amidation. Then the three TBA(+) counter cations were programmatically replaced by protons (H(+)) following a molecule-to-amphiphile conversion. In this way one hybrid and three POM-containing hybrid amphiphiles (PCHAs) were acquired by adjusting the number (n) of TBA(+) ions and number (3 - n) of H(+) ions (n = 3, 2, 1, and 0). These compounds can be spread onto a water surface to form a Langmuir monolayer film at the air-water interface. Surface pressure-molecular area measurements exhibit the TBA(+) (H(+)) number playing an important role in the forming ability and stability of Langmuir monolayer films. Also, the Langmuir-Blodgett (LB) technique has been used to transfer the monolayer film onto solid supports to fabricate solid multilayer films. It was found that the PCHA with three H(+) ions had the best Langmuir film-forming ability and thus formed stable LB films with a two-dimensional ordered structure. Our findings are instructive in fabricating and using solid films of the amphiphiles with POM headgroups.
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Protones , Compuestos de Amonio Cuaternario/química , Tensoactivos/química , Compuestos de Tungsteno/química , Aire , Microscopía Electrónica de Transmisión , Estructura Molecular , Propiedades de Superficie , AguaRESUMEN
A mitochondrial manganese superoxide dismutase from an invasive species of the whitefly Bemisia tabaci complex (Bt-mMnSOD) was cloned and analyzed. The full length cDNA of Bt-mMnSOD is 1210 bp with a 675 bp open reading frame, corresponding to 224 amino acids, which include 25 residues of the mitochondrial targeting sequence. Compared with various vertebrate and invertebrate animals, the MnSOD signature (DVWEHAYY) and four conserved amino acids for manganese binding (H54, H102, D186 and H190) were observed in Bt-mMnSOD. Recombinant Bt-mMnSOD was overexpressed in Escherichia coli, and the enzymatic activity of purified mMnSOD was assayed under various temperatures. Quantitative real-time PCR analysis with whiteflies of different development stages showed that the mRNA levels of Bt-mMnSOD were significantly higher in the 4th instar than in other stages. In addition, the in vivo activities of MnSOD in the whitefly were measured under various conditions, including exposure to low (4 °C) and high (40 °C) temperatures, transfer from a favorable to an unfavorable host plant (from cotton to tobacco) and treatment with pesticides. Our results indicate that the whitefly MnSOD plays an important role in cellular stress responses and anti-oxidative processes and that it might contribute to the successful worldwide distribution of the invasive whitefly.
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Hemípteros/genética , Proteínas de Insectos/genética , Proteínas Mitocondriales/genética , Superóxido Dismutasa/genética , Secuencias de Aminoácidos/genética , Animales , Sitios de Unión/genética , Clonación Molecular , Estabilidad de Enzimas , Regulación del Desarrollo de la Expresión Génica , Regulación Enzimológica de la Expresión Génica , Hemípteros/enzimología , Hemípteros/crecimiento & desarrollo , Proteínas de Insectos/metabolismo , Manganeso/metabolismo , Proteínas Mitocondriales/metabolismo , Proteínas Recombinantes/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Superóxido Dismutasa/metabolismo , TemperaturaRESUMEN
Toxoplasma gondii is an obligate intracellular protozoan parasite which seriously threatens the health of domestic animals and humans. Long non-coding RNAs (lncRNAs) are non-protein-coding transcripts greater than 200 nucleotides, which are widely involved in transcriptional and epigenetic regulations. However, little is known about the roles of host lncRNAs in the response to T. gondii infections. In this study, using Illumina sequencing technology, we analyzed the expression profiles of mRNAs and lncRNAs in BALB/c mouse brain following infection by T. gondii PRU strain (type II genotype) cysts. The identified differentially expressed (DE) RNAs were subjected to bioinformatics analysis. A total of 2,090 annotated lncRNAs along with 3,577 novel lncRNAs were identified. In the acutely infected mouse brain, a total of 330 mRNAs and 19 lncRNAs were dys-regulated, whereas 136 DE mRNAs and 9 DE lncRNAs were identified in chronically infected mouse brain. GO analysis revealed that these DE mRNAs identified at acute infection stage were involved in immune response, whereas DE mRNAs found at chronic infection stage were mostly enriched in response to protozoan. KEGG analysis showed that DE mRNAs were significantly enriched in disease related pathways. In addition, the putative mRNA-lncRNA co-expression network was constructed, and several hub regulatory RNAs were identified based on the transcriptome data. This study firstly characterized the co-expression profile of mRNAs and lncRNAs in mouse brain infected with T. gondii and provided a framework for further studies of the roles of lncRNAs in host neuropathology during toxoplasmosis progression.
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ARN Largo no Codificante , Toxoplasma , Toxoplasmosis , Humanos , Ratones , Animales , ARN Largo no Codificante/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Toxoplasmosis/genética , Ratones Endogámicos BALB C , Encéfalo/metabolismo , Perfilación de la Expresión GénicaRESUMEN
BACKGROUND: Traditional treatments for major depressive disorder (MDD), including medication and therapy, often fail and have undesirable side effects. Electroconvulsive therapy (ECT) uses electrical currents to induce brief seizures in the brain, resulting in rapid and potent antidepressant effects. However, owing to misconceptions and controversies, ECT is not as widely used as it could and often faces stigmatization. AIM: To evaluate the efficacy and safety of ECT compared to those of medication and/or therapy in patients with severe MDD. METHODS: This prospective cohort study included 220 individuals with severe MDD who were divided into the ECT and non-ECT groups. The patients in the ECT group underwent bilateral ECT three times a wk until they either achieved remission or reached a maximum of 12 sessions. The non-ECT group received medication and/or therapy according to clinical guidelines for MDD. The primary outcome was the variation in the hamilton depression rating scale (HDRS) score from treatment/ECT initiation to week 12. In addition, patients' quality of life, cognitive abilities, and biomarkers were measured throughout the study. RESULTS: Although both groups showed significant improvements in their HDRS scores over time, the improvement was more pronounced in the ECT group than in the non-ECT group. Additionally, the ECT group exhibited a more substantial improvement in the quality of life and cognitive function than those of the non-ECT group. Compared with the non-ECT group, the ECT group exhibited evi-dently lower variations in the brain-derived neurotrophic factor (BDNF) and cytokine interleukin-6 (IL-6) levels. The side effects were generally mild and comparable between the two groups. ECT is safer and more potent than medication and/or therapy in mitigating depressive symptoms, enhancing well-being, and bolstering cognitive capabilities in individuals with severe MDD. ECT may also affect the levels of BDNF and IL-6, which are indicators of neuroplasticity and inflammation, respectively. CONCLUSION: ECT has emerged as a potentially advantageous therapeutic approach for patients with MDD who are unresponsive to alternative treatments.
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The begomoviruses are the largest and most economically important group of plant viruses transmitted exclusively by the whitefly Bemisia tabaci in a circulative, persistent manner. The circulation of the viruses within the insect vectors involves complex interactions between virus and vector components; however, the molecular mechanisms of these interactions remain largely unknown. Here we investigated the transcriptional response of the invasive B. tabaci Middle East-Asia Minor 1 species to Tomato yellow leaf curl China virus (TYLCCNV) using Illumina sequencing technology. Results showed that 1,606 genes involved in 157 biochemical pathways were differentially expressed in the viruliferous whiteflies. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that TYLCCNV can perturb the cell cycle and primary metabolism in the whitefly, which explains the negative effect of this virus on the longevity and fecundity of B. tabaci. Our data also demonstrated that TYLCCNV can activate whitefly immune responses, such as autophagy and antimicrobial peptide production, which might lead to a gradual decrease of viral particles within the body of the viruliferous whitefly. Furthermore, PCR results showed that TYLCCNV can invade the ovary and fat body tissues of the whitefly, and Lysotracker and Western blot analyses revealed that the invasion of TYLCCNV induced autophagy in both the ovary and fat body tissues. Surprisingly, TYLCCNV also suppressed the whitefly immune responses by downregulating the expression of genes involved in Toll-like signaling and mitogen-activated protein kinase (MAPK) pathways. Taken together, these results reveal the relationship of coevolved adaptations between begomoviruses and whiteflies and will provide a road map for future investigations into the complex interactions between plant viruses and their insect vectors.
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Adaptación Biológica , Begomovirus/patogenicidad , Perfilación de la Expresión Génica , Hemípteros/virología , Interacciones Huésped-Patógeno , Animales , Begomovirus/inmunología , Evolución Biológica , Hemípteros/genética , Hemípteros/inmunología , Secuenciación de Nucleótidos de Alto Rendimiento/métodosRESUMEN
In a Tesla-type pulse generator, self-inductance of the primary coil is a crucial parameter to determine the final oscillating condition. However, the accurate value of this inductance might be changed due to the uneven primary current distribution caused by practical configuration of the primary side. Consequently, in order to precisely design the transformer, it is helpful to evaluate the primary inductance based on electromagnetic simulation instead of conventional approximate calculation. In this paper, a simulation model based on the finite integration technique is established to solve the uneven primary current problem. A primary coil with multiple contacting points is designed, and hexahedral mesh generation of the coil is also discussed. Hence, a series of verification tests using different primary structures are performed to support the results of simulation. Both results of the simulation model and the verification test presented that the variation of the primary inductance will affect the performance of the generator, and the number of contacting points is the main cause to determine the maximum current density of the coil.
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Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) and progressive external ophthalmoplegia (PEO) are established phenotypes of mitochondrial disorders. They are maternally-inherited, multisystem disorder that is characterized by variable clinical, biochemical, and imaging features. We described the clinical and genetic features of a Chinese patient with late-onset MELAS/PEO overlap syndrome, which has rarely been reported. The patient was a 48-year-old woman who presented with recurrent ischemic strokes associated with characteristic brain imaging and bilateral ptosis. We assessed her clinical characteristics and performed mutation analyses. The main manifestations of the patient were stroke-like episodes and seizures. A laboratory examination revealed an increased level of plasma lactic acid and a brain MRI showed multiple lesions in the cortex. A muscle biopsy demonstrated ragged red fibers. Genetic analysis from a muscle sample identified two mutations: TL1 m.3243A>G and POLG c.3560C>T, with mutation loads of 83 and 43%, respectively. This suggested that mitochondrial disorders are associated with various clinical presentations and an overlap between the syndromes and whole exome sequencing is important, as patients may carry multiple mutations.
RESUMEN
OBJECTIVES: By measuring left ventricular diastolic function and arterial stiffness, this study aims to probe into the effect of diabetes mellitus (DM) on left ventricular diastolic function and arterial stiffness, and evaluate the correlation between left ventricular diastolic function and arterial stiffness. METHODS: Seventy-six inpatients were enrolled. According to their coronary angiography, OGTT test results and past history of DM, patients were divided into controlled, CHD (coronary heart disease with no DM), and CHD + DM groups. Through invasive hemodynamic monitoring during left ventricular angiography, left ventricular end-diastolic pressure (LVEDP) and tau index were collected. Carotid-femoral pulse wave velocity (c-f PWV), reflected wave augmentation index (AIx@75) and other data reflecting the degree of arterial stiffness were collected bedside with non-invasive means. SPSS 18.0 was used for statistical analysis. RESULTS: No significant difference was found between groups for LVEDP, tau index, and AIx@75. In terms of c-f PMV, The CHD + DM group (8.79 ± 1.59) cm/s differed significantly from the CHD group (7.43 ± 1.42) cm/s and the controlled group (6.83 ± 1.14) cm/s. No correlations were found between c-f PMV and LVEDP or tau index. A positive correlation was found between AIx@75 and tau index. CONCLUSIONS: Compared with the controlled group and CHD patients with no DM, CHD + DM patients show worse arterial stiffness with no difference in ventricular diastolic function. There is a positive correlation between arterial stiffness and diastolic dysfunction.