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1.
Cell Mol Life Sci ; 81(1): 113, 2024 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-38436697

RESUMEN

APE1 is an essential gene involved in DNA damage repair, the redox regulation of transcriptional factors (TFs) and RNA processing. APE1 overexpression is common in cancers and correlates with poor patient survival. Stress granules (SGs) are phase-separated cytoplasmic assemblies that cells form in response to environmental stresses. Precise regulation of SGs is pivotal to cell survival, whereas their dysregulation is increasingly linked to diseases. Whether APE1 engages in modulating SG dynamics is worthy of investigation. In this study, we demonstrate that APE1 colocalizes with SGs and promotes their formation. Through phosphoproteome profiling, we discover that APE1 significantly alters the phosphorylation landscape of ovarian cancer cells, particularly the phosphoprofile of SG proteins. Notably, APE1 promotes the phosphorylation of Y-Box binding protein 1 (YBX1) at S174 and S176, leading to enhanced SG formation and cell survival. Moreover, expression of the phosphomutant YBX1 S174/176E mimicking hyperphosphorylation in APE1-knockdown cells recovered the impaired SG formation. These findings shed light on the functional importance of APE1 in SG regulation and highlight the importance of YBX1 phosphorylation in SG dynamics.


Asunto(s)
ADN-(Sitio Apurínico o Apirimidínico) Liasa , Neoplasias Ováricas , Gránulos de Estrés , Proteína 1 de Unión a la Caja Y , Femenino , Humanos , Endodesoxirribonucleasas , Neoplasias Ováricas/genética , Fosforilación , Gránulos de Estrés/metabolismo , Proteína 1 de Unión a la Caja Y/genética , ADN-(Sitio Apurínico o Apirimidínico) Liasa/metabolismo
2.
Annu Rev Biomed Eng ; 25: 185-205, 2023 06 08.
Artículo en Inglés | MEDLINE | ID: mdl-37289556

RESUMEN

Penetrating neural electrodes provide a powerful approach to decipher brain circuitry by allowing for time-resolved electrical detections of individual action potentials. This unique capability has contributed tremendously to basic and translational neuroscience, enabling both fundamental understandings of brain functions and applications of human prosthetic devices that restore crucial sensations and movements. However, conventional approaches are limited by the scarce number of available sensing channels and compromised efficacy over long-term implantations. Recording longevity and scalability have become the most sought-after improvements in emerging technologies. In this review, we discuss the technological advances in the past 5-10 years that have enabled larger-scale, more detailed, and longer-lasting recordings of neural circuits at work than ever before. We present snapshots of the latest advances in penetration electrode technology, showcase their applications in animal models and humans, and outline the underlying design principles and considerations to fuel future technological development.


Asunto(s)
Longevidad , Neurociencias , Animales , Humanos , Electrodos , Encéfalo/fisiología , Potenciales de Acción/fisiología , Electrodos Implantados
3.
Biomacromolecules ; 25(7): 3877-3892, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38388358

RESUMEN

Exploring a novel natural cryoprotectant and understanding its antifreeze mechanism allows the rational design of future sustainable antifreeze analogues. In this study, various antifreeze polysaccharides were isolated from wheat bran, and the antifreeze activity was comparatively studied in relation to the molecular structure. The antifreeze mechanism was further revealed based on the interactions of polysaccharides and water molecules through dynamic simulation analysis. The antifreeze polysaccharides showed distinct ice recrystallization inhibition activity, and structural analysis suggested that the polysaccharides were arabinoxylan, featuring a xylan backbone with a majority of Araf and minor fractions of Manp, Galp, and Glcp involved in the side chain. The antifreeze arabinoxylan, characterized by lower molecular weight, less branching, and more flexible conformation, could weaken the hydrogen bonding of the surrounding water molecules more evidently, thus retarding the transformation of water molecules into the ordered ice structure.


Asunto(s)
Fibras de la Dieta , Xilanos , Fibras de la Dieta/análisis , Xilanos/química , Polisacáridos/química , Crioprotectores/química , Cristalización , Enlace de Hidrógeno , Agua/química , Simulación de Dinámica Molecular , Proteínas Anticongelantes/química , Hielo
4.
Am J Respir Crit Care Med ; 208(8): 879-895, 2023 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-37676930

RESUMEN

Rationale: Immune dysregulation is a common feature of pulmonary arterial hypertension (PAH). Histone deacetylase (HDAC)-dependent transcriptional reprogramming epigenetically modulates immune homeostasis and is a novel disease-oriented approach in modern times. Objectives: To identify a novel functional link between HDAC and regulatory T cells (Tregs) in PAH, aiming to establish disease-modified biomarkers and therapeutic targets. Methods: Peripheral blood mononuclear cells were isolated from patients with idiopathic PAH (IPAH) and rodent models of pulmonary hypertension (PH): monocrotaline rats, Sugen5416-hypoxia rats, and Treg-depleted mice. HDAC inhibitor vorinostat (suberoylanilide hydroxamic acid, SAHA) was used to examine the immune modulatory effects in vivo, ex vivo, and in vitro. Measurements and Main Results: Increased HDAC expression was associated with reduced Foxp3+ Tregs and increased PD-1 (programmed cell death-1) signaling in peripheral blood mononuclear cells from patients with IPAH. SAHA differentially modified a cluster of epigenetic-sensitive genes and induced Foxp3+ Treg conversion in IPAH T cells. Rodent models recapitulated these epigenetic aberrations and T-cell dysfunction. SAHA attenuated PH phenotypes and restored FOXP3 transcription and Tregs in PH rats; interestingly, the effects were more profound in female rats. Selective depletion of CD25+ Tregs in Sugen5416-hypoxia mice neutralized the effects of SAHA. Furthermore, SAHA inhibited endothelial cytokine/chemokine release upon stimulation and subsequent immune chemotaxis. Conclusions: Our results indicated HDAC aberration was associated with Foxp3+ Treg deficiency and demonstrated an epigenetic-mediated mechanism underlying immune dysfunction in PAH. Restoration of Foxp3+ Tregs by HDAC inhibitors is a promising approach to resolve pulmonary vascular pathology, highlighting the potential benefit of developing epigenetic therapies for PAH.

5.
J Integr Neurosci ; 23(6): 119, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38940087

RESUMEN

OBJECTIVES: The majority of neuromyelitis optica spectrum disorders (NMOSD) patients are seropositive for aquaporin-4 (AQP4)-specific antibodies [also named neuromyelitis optica immunoglobulin G antibodies (NMO-IgG)]. Although NMO-IgG can induce pathological changes in the central nervous system (CNS), the immunological changes in the CNS and peripheral tissue remain largely unknown. We investigated whether NMO-IgG binds to tissue expressing AQP4 and induces immunological changes in the peripheral tissue and CNS. METHODS: C57BL/6 female mice were assigned into an NMOSD or control group. Pathological and immunological changes in peripheral tissue and CNS were measured by immunostaining and flow cytometry, respectively. Motor impairment was measured by open-field test. RESULTS: We found that NMO-IgG did bind to astrocyte- and AQP4-expressing peripheral tissue, but induced glial fibrillary acidic protein and AQP4 loss only in the CNS. NMO-IgG induced the activation of microglia and modulated microglia polarization toward the classical (M1) phenotype, but did not affect innate or adaptive immune cells in the peripheral immune system, such as macrophages, neutrophils, Th17/Th1, or IL-10-producing B cells. In addition, NMOSD mice showed significantly less total distance traveled and higher immobility time in the open field. CONCLUSIONS: We found that injection of human NMO-IgG led to astrocytopathic lesions with microglial activation in the CNS. However, there were no significant pathological or immunological changes in the peripheral tissues.


Asunto(s)
Acuaporina 4 , Inmunoglobulina G , Ratones Endogámicos C57BL , Neuromielitis Óptica , Animales , Neuromielitis Óptica/inmunología , Neuromielitis Óptica/patología , Acuaporina 4/inmunología , Femenino , Humanos , Ratones , Modelos Animales de Enfermedad , Microglía/metabolismo , Microglía/inmunología , Microglía/efectos de los fármacos , Autoanticuerpos/inmunología , Astrocitos/inmunología , Astrocitos/metabolismo , Astrocitos/patología , Proteína Ácida Fibrilar de la Glía/metabolismo , Proteína Ácida Fibrilar de la Glía/inmunología , Sistema Nervioso Central/inmunología , Sistema Nervioso Central/metabolismo , Sistema Nervioso Central/patología
6.
Ann Surg ; 278(4): e870-e875, 2023 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-36825502

RESUMEN

OBJECTIVE: To report an innovative endoscopic surgery for subcutaneous vascular malformations and intramuscular fibro-adipose vascular anomaly (FAVA) at our center. BACKGROUND: Historically, open surgical resection has been the treatment of choice. Recent advances in minimally invasive surgery have led to the successful application of endoscopic resection techniques for the surgical management of diseases of soft tissue. METHODS: Patients who underwent endoscopic resection of vascular anomalies were included in this retrospective review. Data were extracted from our Vascular Anomalies Center database between September 2019 and October 2022, including sex, age, symptoms, diagnosis, sites of surgery, previous treatment, surgery, and follow-up. RESULTS: There were 13 females and 15 males in the current study, with ages ranging from 1 to 17 years. The diagnoses included microcystic lymphatic malformation (LM) (n = 8), Klippel-Trénaunay syndrome (n = 7), venous malformation (n = 6), FAVA (n = 6), and mixed cystic LM (n = 1). Surgical sites included the lower extremity (n = 24), abdominal wall (n = 2), upper extremity (n = 1), and thoracic wall (n = 1). Five patients had an intramuscular lesion (FAVA). The endoscopic technique used 2 or 3 small ports in a gas inflation manner. Surgery included thrombectomy, radical resection, and debulking of vascular anomalies. Postoperative sclerotherapy with bleomycin was performed through a drainage tube in 6 patients with microcystic LM. Technical success was obtained in 27 patients. The conversion to open surgery was performed in one patient owing to the deep location of the lesion. No wound-related complication was observed. CONCLUSIONS: Endoscopic surgery is a minimally invasive, effective, and safe treatment for subcutaneous vascular malformations and intramuscular FAVA. This approach can set a new standard that minimizes wound complications and reduces recovery time in patients undergoing resection for benign soft-tissue lesions.


Asunto(s)
Anomalías Linfáticas , Malformaciones Vasculares , Masculino , Femenino , Niño , Humanos , Bleomicina , Escleroterapia/métodos , Malformaciones Vasculares/diagnóstico , Malformaciones Vasculares/cirugía , Anomalías Linfáticas/diagnóstico , Anomalías Linfáticas/patología , Endoscopía , Estudios Retrospectivos , Resultado del Tratamiento
7.
Nucleic Acids Res ; 49(21): 12358-12376, 2021 12 02.
Artículo en Inglés | MEDLINE | ID: mdl-34792171

RESUMEN

The rapid transport of ribosomal proteins (RPs) into the nucleus and their efficient assembly into pre-ribosomal particles are prerequisites for ribosome biogenesis. Proteins that act as dedicated chaperones for RPs to maintain their stability and facilitate their assembly have not been identified in filamentous fungi. PlCYP5 is a nuclear cyclophilin in the nematophagous fungus Purpureocillium lilacinum, whose expression is up-regulated during abiotic stress and nematode egg-parasitism. Here, we found that PlCYP5 co-translationally interacted with the unassembled small ribosomal subunit protein, PlRPS15 (uS19). PlRPS15 contained an eukaryote-specific N-terminal extension that mediated the interaction with PlCYP5. PlCYP5 increased the solubility of PlRPS15 independent of its catalytic peptide-prolyl isomerase function and supported the integration of PlRPS15 into pre-ribosomes. Consistently, the phenotypes of the PlCYP5 loss-of-function mutant were similar to those of the PlRPS15 knockdown mutant (e.g. growth and ribosome biogenesis defects). PlCYP5 homologs in Arabidopsis thaliana, Homo sapiens, Schizosaccharomyces pombe, Sclerotinia sclerotiorum, Botrytis cinerea and Metarhizium anisopliae were identified. Notably, PlCYP5-PlRPS15 homologs from three filamentous fungi interacted with each other but not those from other species. In summary, our data disclosed a unique dedicated chaperone system for RPs by cyclophilin in filamentous fungi.


Asunto(s)
Ciclofilinas/genética , Proteínas Fúngicas/genética , Hypocreales/genética , Chaperonas Moleculares/genética , Proteínas Ribosómicas/genética , Ribosomas/genética , Secuencia de Aminoácidos , Núcleo Celular/genética , Núcleo Celular/metabolismo , Ciclofilinas/metabolismo , Proteínas Fúngicas/metabolismo , Regulación Fúngica de la Expresión Génica , Hypocreales/metabolismo , Hypocreales/patogenicidad , Chaperonas Moleculares/metabolismo , Mutación , Micelio/metabolismo , Filogenia , Polirribosomas/genética , Polirribosomas/metabolismo , Unión Proteica , Biosíntesis de Proteínas/genética , RNA-Seq/métodos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Proteínas Ribosómicas/clasificación , Proteínas Ribosómicas/metabolismo , Ribosomas/metabolismo , Homología de Secuencia de Aminoácido , Virulencia/genética
8.
Pediatr Dermatol ; 40(2): 265-269, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36444750

RESUMEN

OBJECTIVE: To describe the curettage and sclerotherapy technique, a hybrid approach to treatment for superficial lymphatic malformations. METHODS: A retrospective analysis of a lymphatic malformation data base was performed. Patients with superficial lymphatic malformation treated by curettage and sclerotherapy technique with bleomycin were included in this study. Safety and efficacy of the curettage and sclerotherapy technique with bleomycin were evaluated. RESULTS: Between September 2019 and October 2021, 10 consecutive patients (male/female ratio: 4:6; mean age, 10.9 years; range, 3-35 years) presented with superficial lymphatic malformations that were subsequently treated by curettage and sclerotherapy technique with bleomycin. All lesions were located on the trunk and extremities. Each patient received one treatment session and a mean follow-up of 12 months. We observed minor complications. No postoperative infections occurred in this series. No patient developed skin ulceration or necrosis. Scarring and recurrence occurred in one patient. Complete regression was confirmed for all 10 patients by photographic evaluation. CONCLUSION: A curettage and sclerotherapy technique is proposed to treat superficial lymphatic malformation in this study. This technique seems to be safe and highly effective.


Asunto(s)
Anomalías Linfáticas , Escleroterapia , Humanos , Masculino , Femenino , Niño , Escleroterapia/métodos , Estudios Retrospectivos , Anomalías Linfáticas/terapia , Bleomicina , Legrado
9.
J Sci Food Agric ; 103(2): 648-656, 2023 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-36053964

RESUMEN

BACKGROUND: Ultraviolet B (UV-B) radiation can enhance the accumulation of phenolic compounds (PCs) in barley seedling, although this may result in severe oxidative damage. In the present study, the role of spermidine in alleviating oxidative damage and regulating synthesis of PCs in barley seedlings under UV-B stress was investigated. RESULTS: Exogenous spermidine increased the length and fresh weight as well as PCs contents of barley seedlings under UV-B stress. Application of dicyclohexylamine, an inhibitor of endogenous spermidine synthesis, significantly inhibited the growth and PC accumulation of barley seedlings under UV-B stress, although this inhibitory effect can be alleviated by exogenous spermidine. Exogenous spermidine increased the contents of vanillic acid, syringic acid, protocatechuic acid and p-coumaric acid in barley seedlings under UV-B stress by 20-200% through enhancing the activities of enzymes related to synthesis of these acids. In addition, exogenous spermidine enhanced activities and gene expression of antioxidant enzymes in barley seedlings under UV-B stress, including peroxidase, glutathione reductase and glutathione S-transferase. CONCLUSION: Spermidine can alleviate oxidative damage of barley seedlings under UV-B stress and enhance the accumulation of PCs. © 2022 Society of Chemical Industry.


Asunto(s)
Hordeum , Plantones , Espermidina/farmacología , Hordeum/metabolismo , Estrés Oxidativo , Antioxidantes/farmacología , Antioxidantes/metabolismo , Fenoles/farmacología , Fenoles/metabolismo , Peróxido de Hidrógeno/metabolismo
10.
Nutr Metab Cardiovasc Dis ; 32(5): 1210-1217, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35277327

RESUMEN

BACKGROUND AND AIMS: As a new simple anthropometric index, the weight-adjusted-waist index (WWI) appears to be superior to body mass index (BMI) and waist circumference (WC) in assessing both muscle and fat mass. We aimed to explore the association of WWI with all-cause and cardiovascular mortality in southern China. METHODS AND RESULTS: A total of 12,447 participants (mean age, 59.0 ± 13.3 years; 40.6% men) in Jiangxi Province from the China Hypertension Survey study were included. WWI was defined as WC divided by the square root of weight. The outcome was all-cause and cardiovascular mortality. During a median follow-up of 5.6 years, 838 all-cause deaths occurred, with 390 cardiovascular deaths. Overall, there was a nonlinear positive relationship of WWI with all-cause and cardiovascular mortality. Accordingly, compared with participants in quartiles 1-3 (<11.2 cm/√kg), a significant higher risk of all-cause mortality (HR: 1.36, 95% CI: 1.17, 1.58) and cardiovascular mortality (HR: 1.43, 95% CI: 1.15, 1.77) were found in quartile 4 (≥11.2 cm/√kg). Further adjustment for BMI and WC did not substantially alter the results. No significant interactions were found in any of the subgroups (sex, age, area, physical activity, current smoking, current alcohol drinking, hypertension, and stroke). CONCLUSION: Higher WWI levels (≥11.2 cm/√kg) were associated with increased the risk of all-cause and cardiovascular mortality in southern China. These findings, if confirmed by further studies, suggested that WWI may serve as a simple and effective anthropometric index in clinical practice.


Asunto(s)
Hipertensión , Anciano , Índice de Masa Corporal , China/epidemiología , Femenino , Humanos , Hipertensión/diagnóstico , Hipertensión/epidemiología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Circunferencia de la Cintura
11.
Neurol Sci ; 43(3): 1831-1838, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34518934

RESUMEN

OBJECTIVE: We investigated rate-dependent depression (RDD) of the Hoffman reflex (H-reflex) in patients with amyotrophic lateral sclerosis (ALS), a degenerative disease with ventral horn involvement. PATIENTS AND METHODS: In this case-control study, we enrolled 27 patients with ALS and 30 matched healthy control subjects. Clinical and electrophysiological assessments, as well as RDD in response to various stimulation frequencies (0.5 Hz, 1 Hz, 3 Hz and 5 Hz), were compared between groups. Multiple clinical and electrophysiological factors were also explored to determine any underlying associations with RDD. RESULTS: The ALS group showed a significant loss of RDD across all frequencies compared to the control group, most notably following 1 Hz stimulation (19.1 ± 20.3 vs. 34.0 ± 13.7%, p = 0.003). Among factors that might influence RDD, the enlargement of the motor unit potential (MUP) showed a significant relationship with RDD following multifactor analysis of variance (p = 0.007) and Pearson correlation analysis (ρ = - 0.70, p < 0.001), while various upper motor neuron manifestations were not correlated with RDD values (p > 0.05). CONCLUSION: We report a loss of RDD in patients with ALS. The strong correlation detected between the RDD deficit and increased MUP suggests that RDD is a sensitive indicator of underlying spinal disinhibition in ALS. TRIAL REGISTRATION: ChiCTR2000038848, 10/7/2020 (retrospectively registered), http://www.chictr.org.cn/ .


Asunto(s)
Esclerosis Amiotrófica Lateral , Esclerosis Amiotrófica Lateral/complicaciones , Estudios de Casos y Controles , Depresión , Fenómenos Electrofisiológicos , Humanos , Neuronas Motoras/fisiología
12.
Molecules ; 27(20)2022 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-36296459

RESUMEN

Deficiency of folates can cause various health problems, and germination is a potential way to enrich folates in grain-based food materials. In the present study, the effects of six amino acids (phenylalanine, tyrosine, tryptophan, glutamate, γ-aminobutyric acid, and p-aminobenzoic acid) on folate accumulation during wheat germination under red light radiation were investigated, and an optimized combination of amino acids for promoting folate enrichment was established. The results showed that applying phenylalanine, tyrosine, tryptophan, glutamate, or p-aminobenzoic acid to wheat seedlings during germination can significantly increase the content of total folates through activating the synthesis of the precursors for folate synthesis (pterin and p-aminobenzoic acid) or condensation of these two moieties. Meanwhile, up-regulation of corresponding genes was observed by measuring their expressions to investigate the mechanism for promoting the accumulation of folates. The highest content of folates (ca. 417 µg/100 g DW) was observed when the germinated wheat was cultured with a mixture of 1.5 mM phenylalanine, 0.5 mM tyrosine, 0.5 mM tryptophan, 0.75 mM p-aminobenzoic acid, and 0.5 mM glutamic acid, which was 50% higher than the control seedlings. This study established a promising and practical approach to enhance the accumulation of folates in wheat seedlings.


Asunto(s)
Germinación , Plantones , Plantones/metabolismo , Triticum/química , Aminoácidos/metabolismo , Ácido 4-Aminobenzoico , Triptófano/metabolismo , Ácido Fólico/metabolismo , Grano Comestible/metabolismo , Ácido gamma-Aminobutírico/metabolismo , Tirosina/metabolismo , Fenilalanina/metabolismo , Glutamatos/metabolismo
13.
J Transl Med ; 19(1): 223, 2021 05 26.
Artículo en Inglés | MEDLINE | ID: mdl-34039371

RESUMEN

BACKGROUND: Experimental autoimmune encephalomyelitis (EAE) is a model for inflammatory demyelinating diseases of the central nervous system (CNS), a group of autoimmune diseases characterized by inflammatory infiltration, demyelination, and axonal damage. miR-20a is dysregulated in patients with CNS inflammatory demyelinating diseases; however, the function of miR-20a remains unclear. In this study, we intended to explore the role of miR-20a in EAE. METHODS: The expression of miR-20a was detected by quantitative real-time PCR (qRT-PCR) in EAE mice and patients with MOG antibody-associated demyelinating diseases. CD4+ T cells of EAE mice were sorted, stimulated, and polarized with miR-20a knockdown. Activation and differentiation of CD4+ T cells were analyzed by flow cytometry. The expression of target gene Map3k9 was detected by qRT-PCR and western blot experiments. The binding of miR-20a to the 3' UTR of Map3k9 was tested by luciferase assays. The feasibility of miR-20a as a therapeutic target to alleviate the severity of EAE was explored by intravenous administration of miR-20a antagomirs to EAE mice. RESULTS: miR-20a was upregulated in splenocytes and lymph node cells, CD4+ T cells, and spinal cords of EAE mice. Moreover, miR-20a knockdown did not influence the activation of antigen-specific CD4+ T cells but promoted their differentiation into Treg cells. Map3k9 was predicted to be a target gene of miR-20a. The expressions of Map3k9 and miR-20a were negatively correlated, and miR-20a knockdown increased the expression of Map3k9. In addition, miR-20a binded to the 3' UTR of Map3k9, and simultaneous knockdown of miR-20a and Map3k9 counteracted the enhanced differentiation of Tregs observed when miR-20a was knocked down alone. Furthermore, injection of miR-20a antagomirs to EAE mice reduced the severity of the disease and increased the proportion of Treg cells in peripheral immune organs. CONCLUSIONS: miR-20a suppresses the differentiation of antigen-specific CD4+ T cells into Tregs in EAE by decreasing the expression of Map3k9. miR-20a antagomirs alleviate EAE, suggesting a new therapy for EAE and CNS inflammatory demyelinating diseases.


Asunto(s)
Encefalomielitis Autoinmune Experimental , MicroARNs , Animales , Diferenciación Celular , Encefalomielitis Autoinmune Experimental/genética , Humanos , Quinasas Quinasa Quinasa PAM , Ratones , Ratones Endogámicos C57BL , MicroARNs/genética , Linfocitos T Reguladores
14.
Neurol Sci ; 42(6): 2223-2233, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33782779

RESUMEN

There are bunch of autoantibodies, particularly autoantibodies against proteins located at the node of Ranvier, have been discovered and transformed the clinical management of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Neurofascin (NF) plays an important role in both the nodal and paranodal regions of the node of Ranvier. In this review, we focus on the two characteristic forms of neurofascin: NF186 and NF155, comparing the similarities and differences between them, reviewing the current knowledge on genetic backgrounds, pathogenesis, clinical manifestations, and management of patients with anti-neurofascin positive CIDP. Autoantibodies against neurofascin were mainly IgG4 isotype. Mutation of NFASC gene in human causes severe neurodevelopment disorders, and HLA DRB1*15 may be a strong risk factor for the development of anti-NF155 antibodies. Motor impairment, sensory ataxia, and tremor were the typical presentations of patients with anti-NF155+ CIDP, while tetraplegia and cranial nerve involvement were more common in patients with anti-NF186+ CIDP. Recent studies have depicted a relatively clear picture of anti-NF155+ CIDP, and the strong clinical correlation of NF186 with CIDP remains unclear. The genetic background of neurofascin will assist in future explorations.


Asunto(s)
Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante , Autoanticuerpos , Moléculas de Adhesión Celular/genética , Antecedentes Genéticos , Humanos , Factores de Crecimiento Nervioso/genética , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/genética
15.
Neurol Sci ; 42(11): 4673-4681, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33723708

RESUMEN

INTRODUCTION: Neurofascin (NF) is critical for the formation and maintenance of Ranvier nodes. NF186, the neuronal form of NF, localizes in the initial segment of axon and Ranvier node. NF186 antibody has been detected in demyelinating diseases of both central nervous system (CNS) and peripheral nervous system (PNS). AIMS: To evaluate the clinical features of patients with anti-NF186 IgG neuropathy. METHODS: Sixteen patients (16/138) with serum-positive anti-NF186 IgG were included and divided into groups of either CNS or PNS-involved according to their clinical manifestations. Anti-NF186 IgG was detected by cell-based assays. RESULTS: In 7 patients who were confirmed to have CNS involvement, the most frequent symptoms were dizziness (57%) and vision impairment (43%); lesions in centrum semiovale, cerebellum, and meninges were shown by magnetic resonance imaging (MRI). In comparison, limb weakness (78%) and numbness (78%) were the most common symptoms in PNS-involved patients; axonal loss and demyelination were confirmed by nerve conduction examinations. Elevated level of cerebrospinal fluid (CSF) protein was found in 12 cases without statistically significant difference between the CNS and PNS groups. Meanwhile, CSF white blood cell counts were found significantly elevated in CNS-involved patients compared with patients of PNS group. Thirteen patients received immunomodulating treatments, and patients with chronic onset and progressive course showed poor response to the therapies. CONCLUSIONS: Patients with anti-NF186 IgG neuropathy showed no specific symptoms or signs. It is worth noting that quite a few patients show CNS-impaired signs only, and cranial MRI is essential for the screening of CNS involvement.


Asunto(s)
Factores de Crecimiento Nervioso , Enfermedades del Sistema Nervioso Periférico , Moléculas de Adhesión Celular , Sistema Nervioso Central , Humanos , Nódulos de Ranvier
16.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 38(6): 1163-1172, 2021 Dec 25.
Artículo en Zh | MEDLINE | ID: mdl-34970900

RESUMEN

Entropy model is widely used in epileptic electroencephalogram (EEG) analysis, but there are few reports on how to objectively select the parameters to compute the entropy model in the analysis of resting-state functional magnetic resonance imaging (rfMRI). Therefore, an optimization algorithm to confirm the parameters in multi-scale entropy (MSE) model was proposed, and the location of epileptogenic hemisphere was taken as an example to test the optimization effect by supervised machine learning. The rfMRI data of 20 temporal lobe epilepsy (TLE) patients with hippocampal sclerosis, positive on structural magnetic resonance imaging, were divided into left and right groups. Then, the parameters in MSE model were optimized by the receiver operating characteristic curves (ROC) and area under ROC curve (AUC) values in sensitivity analysis, and the entropy value of the brain regions with statistically significant difference between the groups were taken as sensitive features to epileptogenic hemisphere lateral. The optimized entropy values of these bio-marker brain areas were considered as feature vectors input into the support vector machine (SVM). Finally, combining optimized MSE model with SVM could accurately distinguish epileptogenic hemisphere in TLE at an average accuracy rate of 95%, which was higher than the current level. The results show that the MSE model parameter optimization algorithm can accurately extract the functional imaging markers sensitive to the epileptogenic hemisphere, and achieve the purpose of objectively selecting the parameters for MSE in rfMRI, which provides the basis for the application of entropy in advanced technology detection.


Asunto(s)
Epilepsia del Lóbulo Temporal , Encéfalo/diagnóstico por imagen , Mapeo Encefálico , Entropía , Epilepsia del Lóbulo Temporal/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética
17.
J Exp Bot ; 71(14): 4010-4019, 2020 07 06.
Artículo en Inglés | MEDLINE | ID: mdl-32242227

RESUMEN

The ubiquitin (Ub)/26S proteasome system (UPS) plays a key role in plant growth, development, and survival by directing the turnover of numerous regulatory proteins. In the UPS, the ubiquitin-like (UBL) and ubiquitin-associated (UBA) domains function as hubs for ubiquitin-mediated protein degradation. Radiation sensitive 23 (RAD23), which has been identified as a UBL/UBA protein, contributes to the progression of the cell cycle, stress responses, ER proteolysis, and DNA repair. Here, we report that pollen development is arrested at the microspore stage in a rad23b null mutant. We demonstrate that RAD23B can directly interact with KIP-related protein 1 (KRP1) through its UBL-UBA domains. In addition, plants overexpressing KRP1 have defects in pollen development, which is a phenotype similar to the rad23b mutant. RAD23B promotes the degradation of KRP1 in vivo, which is accumulated following treatment with the proteasome inhibitor MG132. Our results indicate that RAD23B plays an important in pollen development by controlling the turnover of the key cell cycle protein, KRP1.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Proteínas de Ciclo Celular , Proteínas de Unión al ADN , Polen/genética , Complejo de la Endopetidasa Proteasomal/genética , Ubiquitina
18.
Biotechnol Bioeng ; 117(6): 1738-1746, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32048725

RESUMEN

In the initial step of sugar metabolism, sugar-specific transporters play a decisive role in the passage of sugars through plasma membranes into cytoplasm. The SecY complex (SecYEG) in bacteria forms a membrane channel responsible for protein translocation. The present work shows that permeabilized SecY channels can be used as nonspecific sugar transporters in Escherichia coli. SecY with the plug domain deleted allowed the passage of glucose, fructose, mannose, xylose, and arabinose, and, with additional pore-ring mutations, facilitated lactose transport, indicating that sugar passage via permeabilized SecY was independent of sugar stereospecificity. The engineered E. coli showed rapid growth on a wide spectrum of monosaccharides and benefited from the elimination of transport saturation, improvement in sugar tolerance, reduction in competitive inhibition, and prevention of carbon catabolite repression, which are usually encountered with native sugar uptake systems. The SecY channel is widespread in prokaryotes, so other bacteria may also be engineered to utilize this system for sugar uptake. The SecY channel thus provides a unique sugar passageway for future development of robust cell factories for biotechnological applications.


Asunto(s)
Proteínas de Escherichia coli/metabolismo , Escherichia coli/metabolismo , Canales de Translocación SEC/metabolismo , Azúcares/metabolismo , Arabinosa/metabolismo , Transporte Biológico , Escherichia coli/genética , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/genética , Glucosa/metabolismo , Monosacáridos/metabolismo , Mutación , Dominios Proteicos , Transporte de Proteínas , Canales de Translocación SEC/química , Canales de Translocación SEC/genética , Xilosa/metabolismo
19.
IEEE Sens J ; 19(22)2019.
Artículo en Inglés | MEDLINE | ID: mdl-32116472

RESUMEN

Advances in sensing technology raise the possibility of creating neural interfaces that can more effectively restore or repair neural function and reveal fundamental properties of neural information processing. To realize the potential of these bioelectronic devices, it is necessary to understand the capabilities of emerging technologies and identify the best strategies to translate these technologies into products and therapies that will improve the lives of patients with neurological and other disorders. Here we discuss emerging technologies for sensing brain activity, anticipated challenges for translation, and perspectives for how to best transition these technologies from academic research labs to useful products for neuroscience researchers and human patients.

20.
Int J Mol Sci ; 20(24)2019 Dec 09.
Artículo en Inglés | MEDLINE | ID: mdl-31818016

RESUMEN

Electro-actuated polymer (EAP) can change its shape or volume under the action of an external electric field and shows similar behavioral characteristics with those of biological muscles, and so it has good application prospects in aerospace, bionic robots, and other fields. The properties of cellulose-based electroactive materials are similar to ionic EAP materials, although they have higher Young's modulus and lower energy consumption. However, cellulose-based electroactive materials have a more obvious deficiency-their actuation performance is often more significantly affected by ambient humidity due to the hygroscopicity caused by the strong hydrophilic structure of cellulose itself. Compared with cellulose, chitosan has good film-forming and water retention properties, and its compatibility with cellulose is very excellent. In this study, a chitosan/cellulose composite film doped with ionic liquid, 1-ethyl-3-methylimidazolium acetate ([EMIM]Ac), was prepared by co-dissolution and regeneration process using [EMIM]Ac as the solvent. After that, a conductive polymer, poly(3,4-ethylenedioxythiophene)/poly (styrene sulfonate) (PEDOT: PSS), was deposited on the surface of the resulted composite, and then a kind of cellulose-based electroactive composites were obtained. The results showed that the end bending deformation amplitude of the resulted material was increased by 2.3 times higher than that of the pure cellulose film under the same conditions, and the maximum deformation amplitude reached 7.3 mm. The tensile strength of the chitosan/cellulose composite film was 53.68% higher than that of the cellulose film, and the Young's modulus was increased by 72.52%. Furthermore, in comparison with the pure cellulose film, the water retention of the composite film increased and the water absorption rate decreased obviously, which meant that the resistance of the material to changes in environmental humidity was greatly improved.


Asunto(s)
Celulosa/química , Quitosano/química , Imidazoles/química , Módulo de Elasticidad , Fenómenos Mecánicos , Resistencia a la Tracción , Agua/química , Humectabilidad
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