RESUMO
Many glycine-rich RNA-binding proteins (GR-RBPs) have critical functions in RNA processing and metabolism. Here, we describe a role for the tomato (Solanum lycopersicum) GR-RBP SlRBP1 in regulating mRNA translation. We found that SlRBP1 knockdown mutants (slrbp1) displayed reduced accumulation of total chlorophyll and impaired chloroplast ultrastructure. These phenotypes were accompanied by deregulation of the levels of numerous key transcripts associated with chloroplast functions in slrbp1. Furthermore, native RNA immunoprecipitation-sequencing (nRIP-seq) recovered 61 SlRBP1-associated RNAs, most of which are involved in photosynthesis. SlRBP1 binding to selected target RNAs was validated by nRIP-qPCR. Intriguingly, the accumulation of proteins encoded by SlRBP1-bound transcripts, but not the mRNAs themselves, was reduced in slrbp1 mutants. Polysome profiling followed by RT-qPCR assays indicated that the polysome occupancy of target RNAs was lower in slrbp1 plants than in wild-type. Furthermore, SlRBP1 interacted with the eukaryotic translation initiation factor SleIF4A2. Silencing of SlRBP1 significantly reduced SleIF4A2 binding to SlRBP1-target RNAs. Taking these observations together, we propose that SlRBP1 binds to and channels RNAs onto the SleIF4A2 translation initiation complex and promotes the translation of its target RNAs to regulate chloroplast functions.
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Solanum lycopersicum , Cloroplastos/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Solanum lycopersicum/genética , Fotossíntese/genética , Polirribossomos/metabolismoRESUMO
Dnttip2 is one of the components of the small subunit (SSU) processome. In yeast, depletion of dnttip2 leads to an inefficient processing of pre-rRNA and a decrease in synthesis of the mature 18S rRNA. However, the biological roles of Dnttip2 in higher organisms are poorly defined. In this study, we demonstrate that dnttip2 is a maternal gene in zebrafish. Depletion of Dnttip2 leads to embryonic lethal with severe digestive organs hypoplasia. The loss of function of Dnttip2 also leads to partial defects in cleavage at the A0-site and E-site during 18S rRNA processing. In conclusion, Dnttip2 is essential for 18S rRNA processing and digestive organ development in zebrafish.
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Peixe-Zebra , Animais , Processamento Pós-Transcricional do RNA , RNA Ribossômico 18S/genética , Saccharomyces cerevisiae/metabolismo , Peixe-Zebra/genética , Peixe-Zebra/metabolismoRESUMO
Activating the stimulator of the interferon gene (STING) is a promising immunotherapeutic strategy for converting "cold" tumor microenvironment into "hot" one to achieve better immunotherapy for malignant tumors. Herein, a manganese-based nanotransformer is presented, consisting of manganese carbonyl and cyanine dye, for MRI/NIR-II dual-modality imaging-guided multifunctional carbon monoxide (CO) gas treatment and photothermal therapy, along with triggering cGAS-STING immune pathway against triple-negative breast cancer. This nanosystem is able to transfer its amorphous morphology into a crystallographic-like formation in response to the tumor microenvironment, achieved by breaking metal-carbon bonds and forming coordination bonds, which enhances the sensitivity of magnetic resonance imaging. Moreover, the generated CO and photothermal effect under irradiation of this nanotransformer induce immunogenic death of tumor cells and release damage-associated molecular patterns. Simultaneously, the Mn acts as an immunoactivator, potentially stimulating the cGAS-STING pathway to augment adaptive immunity, resulting in promoting the secretion of type I interferon, the proliferation of cytotoxic T lymphocytes and M2-macrophages repolarization. This nanosystem-based gas-photothermal treatment and immunoactivating therapy synergistic effect exhibit excellent antitumor efficacy both in vitro and in vivo, reducing the risk of triple-negative breast cancer recurrence and metastasis; thus, this strategy presents great potential as multifunctional immunotherapeutic agents for cancer treatment.
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Imunoterapia , Manganês , Terapia Fototérmica , Neoplasias de Mama Triplo Negativas , Neoplasias de Mama Triplo Negativas/terapia , Imunoterapia/métodos , Manganês/química , Humanos , Animais , Terapia Fototérmica/métodos , Linhagem Celular Tumoral , Feminino , Imageamento por Ressonância Magnética/métodos , Camundongos , Microambiente Tumoral , Nanopartículas/química , Fototerapia/métodosRESUMO
Decline in immune function during aging increases susceptibility to different aging-related diseases. However, the underlying molecular mechanisms, especially the genetic factors contributing to imbalance of naïve/memory T-cell subpopulations, still remain largely elusive. Here, we show that loss of DJ-1 encoded by PARK7/DJ-1, causing early-onset familial Parkinson's disease (PD), unexpectedly diminished signs of immunoaging in T-cell compartments of both human and mice. Compared with two gender-matched unaffected siblings of similar ages, the index PD patient with DJ-1 deficiency showed a decline in many critical immunoaging features, including almost doubled non-senescent T cells. The observation was further consolidated by the results in 45-week-old DJ-1 knockout mice. Our data demonstrated that DJ-1 regulates several immunoaging features via hematopoietic-intrinsic and naïve-CD8-intrinsic mechanisms. Mechanistically, DJ-1 depletion reduced oxidative phosphorylation (OXPHOS) and impaired TCR sensitivity in naïve CD8 T cells at a young age, accumulatively leading to a reduced aging process in T-cell compartments in older mice. Our finding suggests an unrecognized critical role of DJ-1 in regulating immunoaging, discovering a potent target to interfere with immunoaging- and aging-associated diseases.
Assuntos
Estresse Oxidativo , Doença de Parkinson , Envelhecimento/genética , Animais , Humanos , Camundongos , Camundongos Knockout , Estresse Oxidativo/genética , Doença de Parkinson/genética , Proteína Desglicase DJ-1/genética , Proteína Desglicase DJ-1/metabolismo , Linfócitos TRESUMO
OBJECTIVE: This study mainly observed the changes in Intersectin-1 (ITSN-1) expression in rat brain tissue after ischemia-reperfusion intervened by Dicyclopentadiene. METHODS: SD rats were randomly divided into non-middle Cerebral Artery Occlusion model group (normal group, sham operation group) and Middle Cerebral Artery Occlusion (MCAO) model group [Ischemia reperfusion (cerebral ischemia reperfusion)] reperfusion,IR) (6h, 24h, 72h, 1w, 2w) group, butylphthalein intervention group], First of all, Use Western The expression of ITSN-1 in the cerebral tissue of infarction side after ischemia-reperfusion injury in each group was measured by blotting, and then the loss and degree of nerve function after ischemia-reperfusion injury in each group was evaluated by Zea-Longa scoring method. The morphological changes of cells in the ischemic penumbra region in the normal group and the MCAO model group for 24h were observed by HE staining. Next, 24h was selected as the reperfusion point for intervention with butylphthalein sodium chloride injection. Finally, Zea-Longa scoring method was used to evaluate whether the rats had neurological impairment and its degree, TTC (Triphenyltetrazolium chloride) staining was used to determine whether the rats had cerebral infarction and its extent, and Western The expression of ITSN-1 in the cerebral tissue of infarcted rats after ischemia-reperfusion injury was measured by blotting. RESULTS: 1. Zea-Longa scoring: Scores, except for the normal group and sham operation group (which scored 0), ranged between 2.75 ± 0.46 in the ischemia-reperfusion 24h group and 1.88 ± 0.35 in the Dicyclopentadiene intervention group, showing statistically significant decreases (P<0.05). 2. HE staining results: The cell structures in the brain tissues of normal group rats were normal with regular nuclear shapes and sizes. There were no obvious abnormal changes. Rats in the ischemia-reperfusion 24h group showed obviously swollen cells, reduced and aggregated nucleus, and cell necrosis in the ischemic penumbra. 3. TTC staining results: Except for the normal group and the sham operation group, which had no infarcts, the ischemia-reperfusion 24h group had the largest volume ratio of cerebral infarction. The volume ratio of cerebral infarction in the Dicyclopentadiene intervention group relatively reduced, making a difference with statistical significance (P<0.05). 4. Western blotting results: After cerebral ischemia-reperfusion in rats, ITSN-1 expression in the infarction-side brain tissue dynamically changed. ITSN-1 expression in the ischemia-reperfusion 24h group was significantly lower among other groups compared to the normal group (P<0.05). After 24 hours, the expression gradually increased after using Dicyclopentadiene intervention, the difference was statistically significant (P<0.05). CONCLUSION: After cerebral ischemia-reperfusion in rats, ITSN-1 expression dynamically changed in the infarction-side brain tissue. Dicyclopentadiene can alleviate ischemia-reperfusion injuries in rats, which might be related to the regulation of ITSN-1 expression.
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The dichloromethane fraction of Kadsura heteroclita roots was separated and purified by chromatographic techniques(e.g., silica gel, Sephadex LH-20, ODS, MCI column chromatography) and semi-preparative HPLC. Twenty compounds were isolated from K. heteroclita, and their structures were identified by NMR, MS, UV, and X-ray single crystal diffraction techniques. Twenty compounds were isolated from K. heteroclita, which were identified as xuetongdilactone G(1), mallomacrostin C(2), 3,4-seco(24Z)-cychmrt-4(28),24-diene-3,26-dioic acid 3-methyl ester(3), nigranoic acid(4), methyl ester schizanlactone E(5), schisandronic acid(6), heteroclic acid(7), wogonin(8),(2R,3R)-4'-O-methyldihydroquercetin(9), 15,16-bisnor-13-oxo-8(17),11E-labdadien-19-oic acid(10), stigmast-4-ene-6ß-ol-3-one(11), psoralen(12),(1R,2R,4R)-trihydroxy-p-menthane(13), homovanillyl alcohol(14), 2-(4-hydroxyphenyl)-ethanol(15), coniferaldehyde(16),(E)-7-(4-hydroxy-3-methoxyphenyl)-7-methylbut-8-en-9-one(17), acetovanillone(18), vanillic acid(19) and vanillin(20). Compound 1 is a new compound named xuetongdilactone G. Compounds 2-3 and 8-20 are isolated from K. heteroclita for the first time.
Assuntos
Kadsura , Kadsura/química , Espectroscopia de Ressonância Magnética , Raízes de Plantas/química , Ésteres/análiseRESUMO
High circulating lipids occurring in obese individuals and insulin-resistant patients are considered a contributing factor to type 2 diabetes. Exposure to high lipid concentration is proposed to both protect and damage beta-cells under different circumstances. Here, by feeding mice a high-fat diet (HFD) for 2 weeks to up to 14 months, the study showed that HFD initially causes the beta-cells to expand in population, whereas long-term exposure to HFD is associated with failure of beta-cells and the inability of animals to respond to glucose challenge. To prevent the failure of beta-cells and the development of type 2 diabetes, the molecular mechanisms that underlie this biphasic response of beta-cells to lipid exposure were explored. Using palmitic acid (PA) in cultured beta-cells and islets, the study demonstrated that chronic exposure to lipids leads to reduced viability and inhibition of cell cycle progression concurrent with down-regulation of a pro-growth/survival kinase AKT, independent of glucose. This AKT down-regulation by PA is correlated with the induction of mTOR/S6K activity. Inhibiting mTOR activity with rapamycin induced Raptor and restored AKT activity, allowing beta-cells to gain proliferation capacity that was lost after HFD exposure. In summary, a novel mechanism in which lipid exposure may cause the dipole effects on beta-cell growth was elucidated, where mTOR acts as a lipid sensor. These mechanisms can be novel targets for future therapeutic developments.
Assuntos
Regulação para Baixo , Células Secretoras de Insulina/enzimologia , Ácido Palmítico/toxicidade , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ciclina D2/metabolismo , Dieta Hiperlipídica , Regulação para Baixo/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Células Secretoras de Insulina/efeitos dos fármacos , Camundongos , PTEN Fosfo-Hidrolase/metabolismo , Fosforilação/efeitos dos fármacos , Proteína Regulatória Associada a mTOR/metabolismo , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismoRESUMO
Sepsis remains a worldwide public health problem. This study aims to explore the role and mechanism of transcriptional factors (TFs) in sepsis-induced myocardial injury. Firstly, TF KLF13 was selected to explore its role in sepsis-induced myocardial injury. The caecal ligation and puncture (CLP) -induced sepsis mouse model was established and the septic mice were examined using standard histopathological methods. KLF13 expression was detected in the septic mouse heart and was also seen in a lipoploysaccharide (LPS) -induced cellular inflammation model. To explore this further both pro-apoptotic cleaved-caspase3/caspase3 and Bax levels and anti-apoptotic Bcl2 levels were examined, also in both models, In addition inflammatory cytokine (IL-1ß, TNF-α, IL-8 and MCP-1) production and IκB-α protein level and p65 phosphorylation were examined in both septic mice and LPS-induced cells. Thus three parameters - cardiomyocyte apoptosis, inflammatory response and NF-κB pathway activation were evaluated under similar conditions. The septic mice showed significant oedema, disordered myofilament arrangement and degradation and necrosis to varying degrees in the myocardial cells. KLF13 was downregulated in both the septic mouse heart and the LPS-induced cellular inflammation model. Furthermore, both models showed abnormally increased cardiomyocyte apoptosis (increased cleaved-caspase3/caspase and Bax protein levels and decreased Bcl2 level), elevated inflammation (increased production of inflammatory cytokines) and the activated NF-κB pathway (increased p65 phosphorylation and decreased IκB-α protein level). KLF13 overexpression notably ameliorated sepsis-induced myocardial injury in vivo and in vitro. KLF13 overexpression protected against sepsis-induced myocardial injury and LPS-induced cellular inflammation and apoptosis via inhibiting the inflammatory pathways (especially NF-κB signalling) and cardiomyocyte apoptosis.
Assuntos
Apoptose , Fatores de Transcrição Kruppel-Like , Miocárdio , NF-kappa B , Sepse , Animais , Camundongos , Inflamação/patologia , Lipopolissacarídeos , NF-kappa B/metabolismo , Inibidor de NF-kappaB alfa , Sepse/complicações , Fatores de Transcrição Kruppel-Like/genética , Miocárdio/patologiaRESUMO
Project-based learning (PBL) is a dynamic student-centred teaching method that encourages students to solve real-life problems while fostering engagement and critical thinking. Here, we report on a PBL course on metabolic network modelling that has been running for several years within the Master in Integrated Systems Biology (MISB) at the University of Luxembourg. This 2-week full-time block course comprises an introduction into the core concepts and methods of constraint-based modelling (CBM), applied to toy models and large-scale networks alongside the preparation of individual student projects in week 1 and, in week 2, the presentation and execution of these projects. We describe in detail the schedule and content of the course, exemplary student projects, and reflect on outcomes and lessons learned. PBL requires the full engagement of students and teachers and gives a rewarding teaching experience. The presented course can serve as a role model and inspiration for other similar courses.
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Redes e Vias Metabólicas , Aprendizagem Baseada em Problemas , Biologia de Sistemas/educação , Humanos , Estudantes , PensamentoRESUMO
BACKGROUND: The aim of this study was to investigate the related influencing factors of neuropathic pain (NP) in patients with spinal cord injury (SCI). METHODS: Patients diagnosed with SCI between January 2016 and December 2019 in the Department of Rehabilitation Medicine, Affiliated Hospital of Guizhou Medical University, were screened for NP by using the Douleur Neuropathique 4 (DN4) questionnaire. A total of 133 patients diagnosed with SCI with NP were finally included in the study. We collected the patients' basic information, including gender, age, body mass index (BMI), disease course, injury segment, American Spinal Injury Association (ASIA) grade, occupation, educational level, whether painkillers were used, stability of economic support, and pain level. Univariate and multiple ordered logistic regression analyses were used to examine the influencing factors of NP in the patients with SCI. RESULTS: The chi-square test revealed that disease course, injury level, severity of SCI (ASIA classification), stable economic support during hospitalization, and the use of painkillers had statistical significance (p < .01). A multivariate logistic regression analysis was performed to analyze the influencing factors of NP. ASIA grade, stable economic support, and use of painkillers were independent influencing factors of NP in patients with SCI, among which injury severity was the independent risk factor (odds ratio [OR] > 1). Stable economic support and painkiller use were protective factors (OR < 1). CONCLUSIONS: In this study, we found no significant correlation between NP after SCI and sex, age, BMI, disease course, injury level, and occupation. However, the injury severity was an independent risk factor, and stable economic support and painkiller use were protective factors.
Assuntos
Neuralgia , Traumatismos da Medula Espinal , Humanos , Estudos Retrospectivos , Neuralgia/epidemiologia , Neuralgia/etiologia , Traumatismos da Medula Espinal/complicações , Hospitalização , Progressão da DoençaRESUMO
In view of the difficulty of using raw 3D point clouds for component detection in the railway field, this paper designs a point cloud segmentation model based on deep learning together with a point cloud preprocessing mechanism. First, a special preprocessing algorithm is designed to resolve the problems of noise points, acquisition errors, and large data volume in the actual point cloud model of the bolt. The algorithm uses the point cloud adaptive weighted guided filtering for noise smoothing according to the noise characteristics. Then retaining the key points of the point cloud, this algorithm uses the octree to partition the point cloud and carries out iterative farthest point sampling in each partition for obtaining the standard point cloud model. The standard point cloud model is then subjected to hierarchical multi-scale feature extraction to obtain global features, which are combined with local features through a self-attention mechanism, while linear interpolation is used to further expand the perceptual field of local features of the model as a basis for segmentation, and finally the segmentation is completed. Experiments show that the proposed algorithm could deal with the scattered bolt point cloud well, realize the segmentation of train bolt and background, and could achieve high segmentation accuracy, which has important practical significance for train safety detection.
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OBJECTIVE: This study aimed to investigate the outcomes of using a novel nasal clip designed for nostril retention after primary unilateral cleft rhinoplasty. DESIGN: This is a retrospective study. SETTING: Department of Cleft Lip and Palate in a stomatological hospital. PATIENTS: A retrospective study was conducted on 57 patients who had a unilateral complete cleft lip without cleft palate and underwent primary surgical repair. INTERVENTIONS: The patients were categorized into 3 groups: the group in which the conventional nasal retainer was used, that in which the nasal clip was used, and the control group in which no postoperative nasal retainer was used. The nasal retainer or our nasal clip was applied 7 days after primary surgical repair and kept in the nostrils of children from 6 to 12 months. MAIN OUTCOME MEASURES: Noses underwent photogrammetry preoperatively, postoperatively, and at follow-up. The nose was also subjectively scored at the follow-up. RESULTS: The nasal retainer and the nasal clip significantly minimized relapse as determined by nasal tip deviation. The nasal clip sustained nasal symmetry, as determined by the postoperative nostril width ratio, better than did the conventional retainer. After 6 to 12 months, the nasal clip achieved better columellar morphology and a more symmetric nasal base than did the conventional nasal retainer. Statistical differences in subjective scores between the control and nostril retention groups were noted. CONCLUSION: The application of the novel nasal clip after primary unilateral cleft rhinoplasty preserves nasal morphology and reduces postoperative relapse without the need for adhesive tape.
Assuntos
Fenda Labial , Fissura Palatina , Rinoplastia , Criança , Humanos , Fenda Labial/cirurgia , Fissura Palatina/cirurgia , Estudos Retrospectivos , Nariz/cirurgia , Septo Nasal/cirurgia , Instrumentos Cirúrgicos , Resultado do TratamentoRESUMO
Norditerpenes are considered to be a common and widely studied class of bioactive compounds in plants, exhibiting a wide array of complex and diverse structural types and originating from various sources. Based on the number of carbons, norditerpenes can be categorized into C19, C18, C17, and C16 compounds. Up to now, 557 norditerpenes and their derivatives have been found in studies published between 2010 and 2023, distributed in 51 families and 132 species, with the largest number in Lamiaceae, Euphorbiaceae, and Cephalotaxaceae. These norditerpenes display versatile biological activities, including anti-tumor, anti-inflammatory, antimicrobial, and antioxidant properties, as well as inhibitory effects against HIV and α-glucosidase, and can be considered as an important source of treatment for a variety of diseases that had a high commercial value. This review provides a comprehensive summary of the plant sources, chemical structures, and biological activities of norditerpenes derived from natural sources, serving as a valuable reference for further research development and application in this field.
Assuntos
Diterpenos , Euphorbiaceae , Lamiaceae , Humanos , Antioxidantes/farmacologia , CarbonoRESUMO
Stress hormones are believed to skew the CD4 T-cell differentiation towards a Th2 response via a T-cell-extrinsic mechanism. Using isolated primary human naïve and memory CD4 T cells, here we show that both adrenergic- and glucocorticoid-mediated stress signalling pathways play a CD4 naïve T-cell-intrinsic role in regulating the Th1/Th2 differentiation balance. Both stress hormones reduced the Th1 programme and cytokine production by inhibiting mTORC1 signalling via two parallel mechanisms. Stress hormone signalling inhibited mTORC1 in naïve CD4 T cells (1) by affecting the PI3K/AKT pathway and (2) by regulating the expression of the circadian rhythm gene, period circadian regulator 1 (PER1). Both stress hormones induced the expression of PER1, which inhibited mTORC1 signalling, thus reducing Th1 differentiation. This previously unrecognized cell-autonomous mechanism connects stress hormone signalling with CD4 T-cell differentiation via mTORC1 and a specific circadian clock gene, namely PER1.
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Linfócitos T CD4-Positivos , Células Th1 , Diferenciação Celular , Hormônios , Humanos , Alvo Mecanístico do Complexo 1 de Rapamicina , Proteínas Circadianas Period/genética , Fosfatidilinositol 3-Quinases , Células Th2RESUMO
A novel high-throughput aptamer microarray fluorescent method based on thioflavin T (ThT) was established for the sensitive detection of phoxim, parathion, fensulfothion, and isocarbophos. In this work, the aptamers in binding buffer tended to have the antiparallel G-quadruplex structure, which can bind ThT and release its potential fluorescence signal. However, when the organophosphorus pesticides (OPs) were present, partial aptamers preferred to bind them, forcing the displacement of ThT from the G-quadruplex and resulting in the significant decrease in fluorescence signal. Under optimal experimental conditions (12T spacer, 300 nM aptamer, and 80 µM ThT), the OP aptamer microarray has low limits of detection of 25.4 ng/mL for phoxim, 12.0 ng/mL for parathion, 7.7 ng/mL for fensulfothion, and 9.9 ng/mL for isocarbophos. The accuracy and reliability of the method is further verified by testing the recovery rate of OPs spiked in two different complicated sample matrices (pears and radishes). It is worth mentioning that not only the developed aptamer microarray technology has low sensitivity and a broad spectrum, but it also allows for high-throughput and rapid analysis of a variety OPs, which overcomes some of the shortcomings of other OP detection methods.
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Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Praguicidas , Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais/métodos , Corantes Fluorescentes/química , Compostos Organofosforados/análise , Praguicidas/análise , Reprodutibilidade dos Testes , Espectrometria de Fluorescência/métodosRESUMO
The estrogen-related receptor (ERR) family of orphan nuclear receptors are transcriptional activators for genes involved in mitochondrial bioenergetics and metabolism. The goal of this study was to explore the role of ERRα in lipid metabolism and the potential effect of inhibiting ERRα on the development of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). In the current study, three experimental mouse models: high-fat diet, high-carbohydrate diet, and a genetic model of hepatic insulin resistance where the liver hyperinsulinemia signal is mimicked via hepatic deletion of Pten (phosphatase and tensin homolog deleted on chromosome 10), the negative regulator of the insulin/phosphatidylinositol 3-kinase signaling pathway, were used. A recently developed small-molecule inhibitor for ERRα was used to demonstrate that inhibiting ERRα blocked NAFLD development induced by either high-carbohydrate diet or high-fat diet feeding. ERRα inhibition also diminished lipid accumulation and attenuated NASH development in the Pten null mice. Glycerolipid synthesis was discovered as an additional mechanism for ERRα-regulated NAFLD/NASH development and glycerophosphate acyltransferase 4 was identified as a novel transcriptional target of ERRα. In summary, these results establish ERRα as a major transcriptional regulator of lipid biosynthesis in addition to its characterized primary function as a regulator for mitochondrial function. This study recognizes ERRα as a potential target for NAFLD/NASH treatment and elucidates novel signaling pathways regulated by ERRα.
Assuntos
Metabolismo dos Lipídeos/fisiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Receptores de Estrogênio/metabolismo , Triglicerídeos/biossíntese , Animais , Regulação da Expressão Gênica/fisiologia , Lipogênese/fisiologia , Masculino , Camundongos , Receptor ERRalfa Relacionado ao EstrogênioRESUMO
The novel coronavirus disease 2019 (COVID-19) vaccination is now an essential strategy for controlling the COVID-19 epidemic. This study included 132 cases of adverse skin reactions after the injection of COVID-19 vaccination from January 2021 to January 2022. The rate of adverse skin reactions after the 1st, 2nd, and 3rd doses of the COVID-19 vaccine were 52%, 40%, and 8% of total adverse skin reactions, respectively. The Urticaria-like rash was the most common manifestation of all adverse skin reactions, accounting for 40.15% of all adverse reactions. The Eczema-like rash was 27.27%. The rates of adverse skin reactions after vaccination with the COVID-19 vaccine in patients with a previous skin disease was 12.12%. Other rare skin adverse reactions after COVID-19 vaccination included herpes zoster, pityriasis rosea, erythema multiforme, chickenpox, herpes simplex, psoriasis, erythrodermatitis, arthus reaction, lichen planus recurrence, measles-like rash, frostbite rash, seborrhea, and vitiligo. There were 23 cases of adverse skin reactions in the same individual after two doses of COVID-19 vaccine. There were three cases of adverse skin reactions in the same person after three doses of the vaccine. Treatment measures are mostly mild regimens, such as oral antihistamines, compounded glycopyrrolate and topical weak to moderately potent corticosteroid creams. The total duration of these skin adverse reactions ranged from 2 weeks to 1 month.
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Vacinas contra COVID-19 , COVID-19 , Exantema , Humanos , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Exantema/induzido quimicamente , Exantema/diagnóstico , Exantema/epidemiologia , Vacinação/efeitos adversosRESUMO
To date, no vaccine or monoclonal antibody (mAb) against Staphylococcus aureus has been approved for use in humans. Our laboratory has developed a 5-antigen S. aureus vaccine (rFSAV), which is now under efficacy evaluation in a phase 2 clinical trial. In the current study, using overlapping peptides and antiserum from rFSAV-immunized volunteers, we identified 7 B-cell immunodominant epitopes on 4 antigens in rFSAV, including 5 novel epitopes (Hla48-65, IsdB402-419, IsdB432-449, SEB78-95, and MntC7-24). Ten immunodominant epitope mAbs were generated against these epitopes, and all of them exhibited partial protection in a mouse sepsis model. Four robust mAbs were used together as an mAb cocktail to prevent methicillin-resistant S. aureus strain 252 infection. The results showed that the mAb cocktail was efficient in combating S. aureus infection and that its protective efficacy correlated with a reduced bacterial burden and decreased infection pathology, which demonstrates that the mAb cocktail is a promising S. aureus vaccine candidate.
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Anticorpos Monoclonais/farmacologia , Bacteriemia , Epitopos de Linfócito B , Epitopos Imunodominantes , Infecções Estafilocócicas , Animais , Anticorpos Antibacterianos , Bacteriemia/prevenção & controle , Modelos Animais de Doenças , Staphylococcus aureus Resistente à Meticilina , Camundongos , Camundongos Endogâmicos BALB C , Infecções Estafilocócicas/prevenção & controle , Staphylococcus aureusRESUMO
Polymer micelles formed by self-assembly of amphiphilic polymers are widely used in drug delivery, gene delivery and biosensors, due to their special hydrophobic core/hydrophilic shell structure and nanoscale. However, the structural stability of polymer micelles can be affected strongly by environmental factors, such as temperature, pH, shear force in the blood and interaction with non-target cells, leading to degradations and drug leakage as drug carriers. Therefore, researches on the structural integrity and in vivo distribution of micelle-based carriers are very important for evaluating their therapeutic effect and clinical feasibility. At present, fluorescence resonance energy transfer (FRET) technology has been widely used in real-time monitoring of aggregation, dissociation and distribution of polymer micelles ( in vitro and in vivo). In this review, the polymer micelles, characteristics of FRET technology, structure and properties of the FRET-polymer micelles are briefly introduced. Then, methods and mechanism for combinations of several commonly used fluorescent probes into polymer micelles structures, and progresses on the stability and distribution studies of FRET-polymer micelles ( in vitro and in vivo) as drug carriers are reviewed, and current challenges of FRET technology and future directions are discussed.
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Portadores de Fármacos , Micelas , Portadores de Fármacos/química , Polímeros/química , Transferência Ressonante de Energia de Fluorescência , Polietilenoglicóis/químicaRESUMO
The current study set out to elucidate the function of epigallocatechin gallate (EGCG) against peritoneal fibrosis in peritoneal dialysis (PD) patients. Firstly, human peritoneal mesothelial cells (HPMCs) were pretreated with 0, 12.5, 25, 50 or 100µmol/L EGCG. Epithelial-mesenchymal transition (EMT) models were induced by advanced glycation end products (AGEs). Untreated-cells were regarded as the blank control group. Changes in proliferation and migration were analyzed by MTT assay and scratch test and levels of HPMC epithelial and interstitial molecular marker proteins were measured by Western blot assay and immunofluorescence, while trans-endothelial resistance was assessed using an epithelial trans membrane cell resistance meter. Inhibition rates of HPMCs, migration numbers and the levels of Snail, E-cadherin, CK and ZO-1 were all decreased, while the levels of α-SMA and FSP1 and trans cellular resistance values were increased in treatment groups (P<0.05). With the increase of EGCG concentrations, HPMCs growth inhibition rates and migration numbers, the levels of α-SMA and FSP1 and TER values were decreased and the levels of Snail, E-cadherin, CK and ZO-1 were enhanced (P<0.05). Overall, the current study highlights that EGCG effectively inhibits the proliferation and migration of HPMCs, increases permeability, suppresses EMT and ultimately delays peritoneal fibrosis.