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1.
Front Psychol ; 15: 1356999, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39114587

RESUMEN

Introduction: The mental health (MH) of college students has long been a crucial concern for families, educational institutions, and society. Extensive research has demonstrated the influential role of exercise motivation in shaping MH. However, further investigation is warranted to ascertain which types of exercise motivation may have more influence on the MH of college students. The present study examined the direct effects of five distinct types of exercise motivation, namely health motivation (HM), appearance motivation (APM), fun motivation (FM), ability motivation (ABM), and social motivation (SM) on MH. Additionally, the study explored the potential mediating role of physical exercise (PE) in these relationships. Methods: An cross-sectional study design was employed. A total of 433 Chinese college students participated in the study and completed our questionnaires, which included the Exercise motivation scale (EM scale), the Physical exercise scale (PE scale), and the Mental health scale (MH scale). Results: The findings revealed a significant and positive relationship between all five categories of exercise motivation and the MH of college students. Specifically, FM was found to have the most pronounced impact on MH, followed by HM, ABM, SM, and APM, in descending order of influence. Furthermore, the impacts of HM, FM, ABM, and SM on MH were found to be partially mediated by PE. However, the association between APM and MH was entirely mediated by PE. Discussion: The present study contributes to enhancing the comprehension of the underlying mechanisms behind different exercise motivations in relation to PE and MH. Additionally, it offers practical implications for developing intervention strategies for improving the MH of college students.

2.
Lung Cancer Manag ; 13(1): LMT64, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38818367

RESUMEN

Managing extensive-stage SCLC (ES-SCLC) has long been challenging for clinicians and oncologists due to its aggressive nature and poor prognosis. We report a case of a 41-year-old female with ES-SCLC who survived for six years, defying the disease's typically poor prognosis. Through a heavy treatment strategy involving chemotherapy, targeted therapy, and immunotherapy, the patient experienced robust responses and avoided distant metastasis, including brain involvement. The long-term survival case in SCLC highlights the need for further research into personalized strategies and prognostic biomarkers. This case holds significant value for both clinicians and researchers as it challenges the conventional strategies for ES-SCLC and sets the stage for future evidence-based studies aimed at extending survival in SCLC.

3.
Acta Biochim Biophys Sin (Shanghai) ; 56(7): 1034-1043, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38655618

RESUMEN

The linear ubiquitin chain assembly complex (LUBAC) is the only known E3 ligase complex in which the ubiquitin-like (UBL) domains of SHARPIN and HOIL-1L interact with HOIP to determine the structural stability of LUBAC. The interactions between subunits within LUBAC have been a topic of extensive research. However, the impact of the LTM motif on the interaction between the UBL domains of SHARPIN and HOIL-1L with HOIP remains unclear. Here, we discover that the absence of the LTM motif in the AlphaFold2-predicted LUBAC structure alters the HOIP-UBA structure. We employ GeoPPI to calculate the changes in binding free energy (ΔG) caused by single-point mutations between subunits, simulating their protein-protein interactions. The results reveal that the presence of the LTM motif decreases the interaction between the UBL domains of SHARPIN and HOIL-1L with HOIP, leading to a decrease in the structural stability of LUBAC. Furthermore, using the AlphaFold2-predicted results, we find that HOIP (629‒695) and HOIP-UBA bind to both sides of HOIL-1L-UBL, respectively. The experiments of Gromacs molecular dynamics simulations, SPR and ITC demonstrate that the elongated domain formed by HOIP (629‒695) and HOIP-UBA, hereafter referred to as the HOIP (466‒695) structure, interacts with HOIL-1L-UBL to form a structurally stable complex. These findings illustrate the collaborative interaction between HOIP-UBA and HOIP (629‒695) with HOIL-1L-UBL, which influences the structural stability of LUBAC.


Asunto(s)
Unión Proteica , Ubiquitina-Proteína Ligasas , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/química , Ubiquitina-Proteína Ligasas/genética , Humanos , Ubiquitina/metabolismo , Ubiquitina/química , Ubiquitina/genética , Simulación de Dinámica Molecular , Secuencias de Aminoácidos , Ubiquitinas
4.
Pestic Biochem Physiol ; 195: 105539, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37666589

RESUMEN

The fall armyworm, Spodoptera frugiperda, is a highly polyphagous agricultural pest that is widely distributed around the world and causes severe crop yield loss. Carvacrol showed adverse effects on many pests, such as larval death and growth inhibition. While the effects of carvacrol on S. frugiperda larvae are not yet known. In this study, the effects of carvacrol on S. frugiperda, including larval growth inhibition and mortality induction, were observed. The detoxification and digestive enzyme activities of larvae with 1.0 and 2.0 g/kg carvacrol treatments were analyzed. Carvacrol boosted the enzyme activities of carboxylesterase (CarE) and glutathione S-transferase (GST) while decreasing the activities of α-amylase (AMS), lipase (LIP), and trypsin. A total of 3422 differentially expressed genes were identified in the larvae treated with 2.0 g/kg carvacrol, of which the DEGs involved in xenobiotic detoxification, food digestion, and insecticidal targets were further examined. These results suggest that carvacrol could regulate growth and development by affecting the process of food digestion, and exert its toxicity on the larvae through interaction with a variety of insecticidal targets. While the altered expressions of detoxification enzymes might be related to the detoxification and metabolism of carvacrol. Our findings offer a theoretical foundation for the use of carvacrol for S. frugiperda control in the field.


Asunto(s)
Insecticidas , Transcriptoma , Animales , Spodoptera/genética , Agricultura , Carboxilesterasa/genética , Insecticidas/toxicidad , Larva/genética
5.
Pestic Biochem Physiol ; 195: 105537, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37666609

RESUMEN

The fall armyworm, Spodoptera frugiperda, is a polyphagous pest worldwide and feeds on many grain and cash crops, which threatens the safety of agriculture and forestry production. Toosendanin (TSN) is a commercial insecticidal active ingredient used to manage various pests in the field and showed adverse effects against S. frugiperda, while the effects of TSN on the larval midguts are not yet known. In this study, the effects of 10 and 20 mg/kg TSN exposures on the larval midguts were analyzed. The structural changes of the larval midgut induced by TSN treatments were also determined by hematoxylin-eosin staining. Besides, TSN treatments also changed the enzyme activities of three digestive enzymes (α-amylase, lipase, and trypsin) and two detoxification enzymes (CarE and GST). A total of 2868 differentially expressed genes (DEGs) were identified by RNA-Seq in the larval midguts with 20 mg/kg TSN treatment, and the DEGs responsible for food digestion and detoxification were further examined. Our findings revealed the preliminary modes of action of TSN on the larval midguts of S. frugiperda, which provide a preliminary rationale for controlling S. frugiperda with TSN in the field.


Asunto(s)
Agricultura , Productos Agrícolas , Animales , Spodoptera/genética , Larva , Expresión Génica
6.
PLoS One ; 18(8): e0290577, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37624773

RESUMEN

Based on social cognitive theory and gender differences, this study verified a moderated mediation model to explore the relationship between the COVID-19 related stress (CRS) and social network addiction (SNA) and evaluate the mediating role of fear of missing out (FoMO) and the moderating role of gender. A questionnaire survey was conducted, including 702 Chinese university students.This study used PROCESS to test the hypothesis model.The results showed that the CRS significantly and positively affected the SNA of college students and FoMO played a complementary mediating role. Moreover, the analysis of the moderated mediation model showed that gender moderated the relationship between FoMO and SNA; the effect of FoMO was stronger on the SNA of male college students than that of females. The results not only enhanced our understanding of the internal influencing mechanism of the relationship between CRS and SNA but also considered gender differences. In addition, some suggestions were proposed.


Asunto(s)
COVID-19 , Trastorno de Adicción a Internet , Red Social , Estrés Psicológico , Femenino , Humanos , Masculino , Pueblo Asiatico , Conducta Adictiva/epidemiología , Conducta Adictiva/psicología , China/epidemiología , COVID-19/epidemiología , COVID-19/psicología , Estrés Psicológico/epidemiología , Estudiantes/psicología , Universidades , Trastorno de Adicción a Internet/epidemiología , Trastorno de Adicción a Internet/psicología
7.
BMC Urol ; 23(1): 1, 2023 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-36609237

RESUMEN

OBJECTIVE: Urethral stenosis caused by pelvic fracture urethral injury (PFUI) is a complex urological disease, especially for the redo cased. However, to find the proximal end of the posterior urethra, and to avoid injury to the rectum and to forecast to remove the inferior pubic margin are two key points for a successful surgery. These steps can be challenging for even the most experienced urologists. This study is to describe a new technique for understanding the three-dimensional (3D) anatomy of the urethra, which will also aid in surgical planning and simplify urethroplasty. MATERIALS AND METHODS: Three patients underwent routine urethroscopy, X ray urethrography and contrast CT urethrography. The 3D images were then reconstructed, and the data were transmitted to a 3D printer. 3D models were printed with polyacrylic acid to simulate the anatomical structure and relationship of urethral stenosis with pubic symphysis and rectum. Various diagnosis methods were compared with the condition in surgery. The patients and trainee questionnaires were performed. RESULTS: Three models of urethral CT were obtained. These models were presented to patients and trainee doctors along with routine urethroscopy, urethrography, and urethral CT. The scores of patients and trainee question forms demonstrated that the 3D printed urethral stenosis model of pelvic fracture has obvious advantages in urethral adjacency and ease of understanding. The 3D printed urethras were easy to show the pubic symphysis and simulate its excision and exposure of urethra. The model could show the precise distance from urethra to rectum to prevent the rectum injury in surgery. CONCLUSIONS: 3D printing technology can be applied to the preoperative evaluation of urethral stenosis caused by PFUI. It can be auxiliary to understand the anatomical structure of the posterior urethra, the direction of urethral displacement, protecting the rectum and the forecasting for pubectomy. It is especially helpful for the accurate preoperative planning of some complex urethral stenosis and redo cases.


Asunto(s)
Fracturas Óseas , Huesos Pélvicos , Estrechez Uretral , Humanos , Uretra/diagnóstico por imagen , Uretra/cirugía , Uretra/lesiones , Estrechez Uretral/diagnóstico por imagen , Estrechez Uretral/etiología , Estrechez Uretral/cirugía , Estudios Retrospectivos , Huesos Pélvicos/diagnóstico por imagen , Huesos Pélvicos/cirugía , Huesos Pélvicos/lesiones , Fracturas Óseas/diagnóstico por imagen , Fracturas Óseas/cirugía , Fracturas Óseas/complicaciones
8.
Appl Immunohistochem Mol Morphol ; 31(1): 17-25, 2023 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-36165833

RESUMEN

Pulmonary sarcomatoid carcinoma (PSC) is characterized by biphasic tumors with epithelial and mesenchymal phenotype. Little is known about the correlation between histologic, immunophenotypic features and the genetic profile of PSC. We analyzed the expression of epithelial-mesenchymal transition-related markers, adenocarcinoma (ADC) and squamous cell carcinoma lineage-specific markers of 205 PSC cases. The alteration of 5 targeted genes was detected by amplification-refractory mutation system-polymerase chain reaction. The intensity of cytokeratin staining was stronger in epithelial carcinoma (EC) than that of the sarcomatoid component (SC) of pleomorphic carcinoma, while vimentin was positive in only 16.3% (17/104) of EC of pleomorphic carcinoma. There is no significant difference between thyroid transcription factor 1 (TTF-1) expression in the SC (46.5%, 33/71) of pleomorphic carcinoma with ADC components and pure PSC (44.2%, 42/95) without p40 expression ( P =0.858). Four cases with ALK rearrangement were confirmed to co-express ALK fusion protein in both the SC and EC. The incidence of EGFR/ALK/KRAS mutation was similar between pleomorphic carcinoma with ADC components (40.6%, 26/64) and TTF-1 + pure PSC (38.2%, 13/34) ( P =0.583). However, higher proportions of TTF-1 + /p40 - PSC patients (44.8%, 39/87) had EGFR/ALK/KRAS mutation than those with TTF-1 - /p40 - PSC (16.7%, 4/24) ( P =0.031). The incidence of EGFR mutation was significantly higher in TTF-1-positive (18.4%, 16/87) than TTF-1-negative (2.7%, 2/74) PSC ( P =0.002). No EGFR and ALK abnormality were observed in 24 pleomorphic carcinoma cases with squamous cell carcinoma components or pure PSC with p40 expression. Our study reveals a close correlation between SC and EC components of pleomorphic carcinoma in terms of immunophenotypic and genetic features, which suggests that pleomorphic carcinoma is potentially derived from the sarcomatoid change of EC cells undergoing epithelial-mesenchymal transition.


Asunto(s)
Carcinoma de Células Escamosas , Transición Epitelial-Mesenquimal , Humanos , Transición Epitelial-Mesenquimal/genética
9.
ISA Trans ; 128(Pt A): 208-219, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34702548

RESUMEN

In this paper, a novel backstepping control law is investigated, which guarantees appointed-time convergence for a two-link manipulator. In contrast to other fixed-time controllers or predefined-time controllers, the practical convergence time can be precisely obtained instead of being estimated. By utilizing a novel appointed-time prescribed performance function, the trajectory tracking error of the manipulator can be previously constrained. Furthermore, the external disturbances have been suppressed by introducing a disturbance observer with the convergence time as a prior control parameter and a switching sliding mode control law. The stability of the controller is analyzed by the Lyapunov method. Various numerical simulation results are carried out to demonstrate the efficacy of the proposed control scheme.

10.
Protein Expr Purif ; 190: 106005, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34695570

RESUMEN

Disulfide bond formed between the cysteine pairs plays a key role in maintaining the integrity of the protein structure and function. The ubiquitin-associated (UBA) domain of human HOIP contains three cysteine residues, Cys504, Cys551, and Cys572. Disulfide bonds formed by Cys504 and Cys551 residues are highly conserved, but the effect of disulfide bonds on the biochemical characteristics of UBA has not been elucidated. In addition, due to the presence of isolated Cys572, inactive inclusion bodies may be formed during protein expression or trigger protein aggregation during protein purification. In this study, the co-expression of SUMO fusion protein combined with SUMO protease (ULP enzyme) in Escherichia coli was successfully applied to improve the soluble expression of UBA domain. Introduced three mutants (UBAC551A, UBAC572A and UBAC551,572A) determined the effects of disulfide bonds on the biochemical characteristics of UBA. Circular dichroism and analytical size exclusion chromatography results showed that the target proteins obtained by co-expression could be folded correctly and had biological activity. Both thermal-induced and urea-induced results demonstrated that the elimination of disulfide bonds would significantly reduce the stability of UBA. Fluorescence spectroscopy result showed that the elimination of disulfide bonds slightly increases the binding affinity of UBA to ligands. In summary, soluble, stable and active UBA domain and its mutants were prepared by co-expression system, which will further contribute to the structural and functional research of UBA.


Asunto(s)
Sustitución de Aminoácidos , Cisteína/química , Disulfuros/química , Mutación Missense , Ubiquitina-Proteína Ligasas/química , Cisteína/genética , Humanos , Dominios Proteicos , Ubiquitina-Proteína Ligasas/genética
11.
Protein Expr Purif ; 192: 106042, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-34965468

RESUMEN

SHARPIN, an accessory subunit of the E3 ligase complex LUBAC, participates in the formation of LUBAC through the ubiquitin-like (UBL) domain located in the central region of SHARPIN and interacts with the ubiquitin-associated domain (UBA) of the catalytic subunit HOIP. However, the role of the N-terminal UBL domain of SHARPIN in stable LUBAC formation has not been clarified. In this study, the 1-127 domain, 128-309 domain, and UBL domain of SHARPIN expression vectors were constructed using the molecular biology method. Then the co-expression of SUMO fusion protein combined with SUMO protease (ULP enzyme) in Escherichia coli was successfully applied to improve the soluble expression of target protein. The results of circular dichroism proved that they all belong to the α+ß class of proteins. The results of size exclusion chromatography showed that 128-309 domain could combine with HOIP and HOIL-1L to participate in the stability of LUBAC. Both thermal-induced and urea-induced unfolding experiment results demonstrated that the existence of the N-terminal UBL domain could make the overall structure more stable than the alone UBL domain. Biosensor experiments indicated that the existence of the N-terminal UBL domain strengthened the binding ability of the UBL domain and the UBA domain. These results were conducive to further study the structure and function of SHARPIN.


Asunto(s)
Ubiquitina/metabolismo , Ubiquitinas/química , Ubiquitinas/metabolismo , Humanos , Unión Proteica , Dominios Proteicos , Ubiquitina-Proteína Ligasas/química , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitinas/genética
13.
Sci Rep ; 5: 11743, 2015 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-26206308

RESUMEN

We aimed to compare the therapeutic effect of recombinant tissue plasminogen activator (rt-PA) administered at different time windows within the first 6 hours after onset of acute ischemic stroke (AIS). A retrospective analysis was performed of data collected from 194 patients who received rt-PA thrombolysis within 4.5 hours after AIS onset and from 29 patients who received rt-PA thrombolysis between 4.5-6 hours after AIS onset. The National Institutes of Health Stroke Scale (NIHSS) scores were statistically decreased in both groups (P < 0.05) at 24 hours and 7 days after onset. There was no statistical difference in the modified Rankin score or mortality at day 90 after treatment between the two groups (P > 0.05). In conclusion, AIS patients who received rt-PA treatment between 4.5-6 hours after onset were similar in therapeutic efficacy to those who received rt-PA within 4.5 hours after onset. Our results suggest that intravenous thrombolytic therapy for AIS within 4.5-6 hours after onset is effective and safe.


Asunto(s)
Isquemia Encefálica/tratamiento farmacológico , Accidente Cerebrovascular/tratamiento farmacológico , Terapia Trombolítica/métodos , Activador de Tejido Plasminógeno/administración & dosificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteínas Recombinantes/administración & dosificación , Factores de Tiempo
14.
Sci Rep ; 5: 9391, 2015 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-25797521

RESUMEN

We conducted a prospective, observational study to assess the prognostic value of hemostasis-related parameters in unselected ICU patients. We collected baseline characteristics from 497 consecutive unselected medical and trauma patients during their ICU stay. Each hemostasis-related parameter was analyzed alone or combined with APACHE II scores for any association with ICU mortality by calculating the under the curve (AUC) of the ROC curve, the net reclassification improvement (NRI) and integrated discrimination improvement (IDI) indices. Of all hemostasis-related indicators examined, the AUC for fibrin degradation products (FDPs) was less than that for APACHE II scores, but larger than that for disseminated intravascular coagulation (DIC) scores. The prediction power of FDPs is relatively low. Multiple regression analysis revealed that FDPs and APACHE II scores significantly predicted primary outcome. The combined use of FDPs level and APACHE II scores generated an NRI of 9.94% and an IDI of 3.54%. In conclusion, FDP is the best independent indicator of ICU mortality among all hemostasis-related indicators examined. The use of FDP level and APACHE II scores in parallel significantly improves the ability to predict ICU mortality, suggesting the application of these parameters could be used to improve patient care and management in the ICU.


Asunto(s)
APACHE , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Tromboembolia/sangre , Tromboembolia/mortalidad , Trombosis/sangre , Trombosis/mortalidad , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Biomarcadores/análisis , Pruebas de Coagulación Sanguínea , Enfermedad Crítica , Femenino , Humanos , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Curva ROC , Análisis de Supervivencia , Tromboembolia/diagnóstico , Tromboembolia/patología , Trombosis/diagnóstico , Trombosis/patología
15.
J Cell Sci ; 128(9): 1718-31, 2015 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-25749862

RESUMEN

Studies on the mechanism of integrin inside-out activation have been focused on the role of ß-integrin cytoplasmic tails, which are relatively conserved and bear binding sites for the intracellular activators including talin and kindlin. Cytoplasmic tails for α-integrins share a conserved GFFKR motif at the membrane-proximal region and this forms a specific interface with the ß-integrin membrane-proximal region to keep the integrin inactive. The α-integrin membrane-distal regions, after the GFFKR motif, are diverse both in length and sequence and their roles in integrin activation have not been well-defined. In this study, we report that the α-integrin cytoplasmic membrane-distal region contributes to maintaining integrin in the resting state and to integrin inside-out activation. Complete deletion of the α-integrin membrane-distal region diminished talin- and kindlin-mediated integrin ligand binding and conformational change. A proper length and suitable amino acids in α-integrin membrane-distal region was found to be important for integrin inside-out activation. Our data establish an essential role for the α-integrin cytoplasmic membrane-distal region in integrin activation and provide new insights into how talin and kindlin induce the high-affinity integrin conformation that is required for fully functional integrins.


Asunto(s)
Citoplasma/química , Cadenas alfa de Integrinas/química , Cadenas alfa de Integrinas/metabolismo , Animales , Proteínas Portadoras/metabolismo , Humanos , Integrina beta3/química , Integrina beta3/metabolismo , Células K562 , Ratones , Proteínas Mutantes/metabolismo , Mutación/genética , Unión Proteica/efectos de los fármacos , Multimerización de Proteína/efectos de los fármacos , Estructura Terciaria de Proteína , Eliminación de Secuencia , Relación Estructura-Actividad , Talina/metabolismo , Acetato de Tetradecanoilforbol/farmacología
16.
J Thorac Dis ; 7(12): E672-7, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26793388

RESUMEN

To date, data regarding the pulmonary histopathology of human H7N9 disease are scarce. We herein describe a patient with a severe case of avian influenza A (H7N9). A chest computerized tomography (CT) scan showed diffuse ground-glass opacities and consolidation throughout the lungs. A resection of pulmonary bullae in the right middle lobe was performed by video-assisted thoracic surgery (VATS) based on the extracorporeal membrane oxygenation (ECMO) supportive technique on the 23(rd) day after the onset of symptoms because of a right pneumothorax persistent air leak. The histopathological findings of the resected lung tissue revealed pneumocyte hyperplasia and fibroproliferative changes along with diffuse alveolar damage. Bronchoalveolar lavage fluid (BALF) specimens for influenza A (H7N9) virus were continuously positive for more than three weeks, despite oseltamivir treatment, and continuous viral replication significantly prolonged the course of the disease. The patient's clinical status continuously deteriorated, with the development of refractory hypoxemia due to progressive and rapid lung fibrosis, which was confirmed by the final histological changes observed from a limited post-mortem biopsy of lung tissue. Pre-terminally, he developed multi-organ failure and died on the 39(th) day after symptom onset, despite corticosteroid treatment.

17.
Acta Pharmacol Sin ; 35(5): 697-706, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24632844

RESUMEN

AIM: To test the hypothesis that the traditional Chinese medicine Cordyceps sinensis could improve the metabolic function of extrarenal organs to achieve its anti-chronic kidney disease (CKD) effects. METHODS: Male SD rats were divided into CKD rats (with 5/6-nephrectomy), CKD rats treated with Cordyceps sinensis (4 mg•kg-1•d-1, po), and sham-operated rats. After an 8-week treatment, metabolites were extracted from the hearts and livers of the rats, and then subjected to (1)H-NMR-based metabolomic analysis. RESULTS: Oxidative stress, energy metabolism, amino acid and protein metabolism and choline metabolism were considered as links between CKD and extrarenal organ dysfunction. Within the experimental period of 8 weeks, the metabolic disorders in the liver were more pronounced than in the heart, suggesting that CKD-related extrarenal organ dysfunctions occurred sequentially rather than simultaneously. Oral administration of Cordyceps sinensis exerted statistically significant rescue effects on the liver and heart by reversely regulating levels of those metabolites that are typically perturbed in CKD. CONCLUSION: Oral administration of Cordyceps sinensis significantly attenuates the liver and heart injuries in CKD rats. The (1)H NMR-based metabolomic approach has provided a systematic view for understanding of CKD and the drug treatment, which can also be used to elucidate the mechanisms of action of other traditional Chinese medicines.


Asunto(s)
Cordyceps/metabolismo , Lesiones Cardíacas/tratamiento farmacológico , Hepatopatías/tratamiento farmacológico , Metaboloma/efectos de los fármacos , Sustancias Protectoras/farmacología , Insuficiencia Renal Crónica/tratamiento farmacológico , Animales , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/farmacología , Corazón , Lesiones Cardíacas/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Hepatopatías/metabolismo , Masculino , Medicina Tradicional China/métodos , Metabolómica/métodos , Ratas , Insuficiencia Renal Crónica/metabolismo
18.
CNS Neurosci Ther ; 20(2): 154-64, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24397751

RESUMEN

AIMS: Several lines of evidence demonstrated that endothelial nitric oxide synthase (eNOS) confers protective effects during cerebral ischemia. In this study, we explored the underlying cellular and molecular mechanisms of neuroprotection by eNOS. METHODS: A series of in vivo and in vitro ischemic models were employed to study the role of eNOS in maintaining neuronal survival and to identify the downstream factors. RESULTS: The current data showed that pretreatment with a specific eNOS inhibitor, L-N5-(1-iminoethyl) ornithine (L-NIO), aggravated the neuronal loss in the rat cerebral ischemic model, accompanied by reduction in brain-derived neurotrophic factor (BDNF) level, which was consistent with the findings in an oxygen-glucose deprivation model (OGD) with two neuronal cells: primary rat cortical neurons and human neuroblastoma SH-SY5Y cells. Furthermore, the extensive neuronal loss induced by L-NIO was totally abolished by exogenous BDNF in both in vitro and in vivo models. On the other hand, eNOS overexpression through an adenoviral vector exerted a prominent protective effect on the neuronal cells subject to OGD, and the protective effect was totally abrogated by a neutralizing anti-BDNF antibody. CONCLUSION: Collectively, our results indicate that the neuroprotection of neuron-derived eNOS against the cerebral ischemia was mediated through the regulation of BDNF secretion. In conclusion, our discovery provides a novel explanation for the neuroprotective effect of eNOS under pathological ischemic conditions such as stroke.


Asunto(s)
Factor Neurotrófico Derivado del Encéfalo/metabolismo , Encéfalo/patología , Regulación de la Expresión Génica/fisiología , Ataque Isquémico Transitorio/patología , Ataque Isquémico Transitorio/prevención & control , Neuronas/fisiología , Óxido Nítrico Sintasa de Tipo III/metabolismo , Animales , Anticuerpos/farmacología , Anticuerpos/uso terapéutico , Encéfalo/efectos de los fármacos , Factor Neurotrófico Derivado del Encéfalo/inmunología , Caspasa 3/metabolismo , Células Cultivadas , Corteza Cerebral , Modelos Animales de Enfermedad , Inhibidores Enzimáticos/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Glucosa/deficiencia , Humanos , Hipoxia/patología , Hipoxia/prevención & control , Masculino , Neuronas/efectos de los fármacos , Óxido Nítrico Sintasa de Tipo III/inmunología , Ornitina/análogos & derivados , Ornitina/farmacología , Ratas , Ratas Sprague-Dawley
19.
J Cell Sci ; 126(Pt 24): 5735-47, 2013 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-24144695

RESUMEN

How conformational signals initiated from one end of the integrin are transmitted to the other end remains elusive. At the ligand-binding ßI domain, the α1/α1'-helix changes from a bent to a straightened α-helical conformation upon integrin headpiece opening. We demonstrated that a conserved glycine at the α1/α1' junction is crucial for maintaining the bent conformation of the α1/α1'-helix in the resting state. Mutations that facilitate α1/α1'-helix unbending rendered integrin constitutively active; however, mutations that block the α1/α1'-helix unbending abolished soluble ligand binding upon either outside or inside stimuli. Such mutations also blocked ligand-induced integrin extension from outside the cell, but had no effect on talin-induced integrin extension from inside the cell. In addition, integrin-mediated cell spreading, F-actin stress fiber and focal adhesion formation, and focal adhesion kinase activation were also defective in these mutant integrins, although the cells still adhered to immobilized ligands at a reduced level. Our data establish the structural role of the α1/α1' junction that allows relaxation of the α1/α1'-helix in the resting state and transmission of bidirectional conformational signals by helix unbending upon integrin activation.


Asunto(s)
Cadenas beta de Integrinas/metabolismo , Secuencia de Aminoácidos , Sustitución de Aminoácidos , Animales , Células CHO , Adhesión Celular , Cricetinae , Cricetulus , Fibrinógeno/metabolismo , Células HEK293 , Humanos , Cadenas beta de Integrinas/química , Cadenas beta de Integrinas/genética , Ligandos , Datos de Secuencia Molecular , Mutagénesis Sitio-Dirigida , Unión Proteica , Estructura Secundaria de Proteína , Transducción de Señal
20.
World J Emerg Med ; 4(3): 205-9, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-25215120

RESUMEN

BACKGROUND: The study aimed to compare the therapeutic effect of recombinant tissue plasminogen activator (rt-PA) on the onset of acute cerebral infarction (ACI) at different time points of the first 6 hours. METHODS: A retrospective analysis was conducted in 74 patients who received rt-PA thrombolysis treatment within 4.5 hours after ACI and another 15 patients who received rt-PA thrombolysis treatment between 4.5-6 hours after ACI. RESULTS: National Institute of Health Stroke Scale (NIHSS) scores were statistically decreased in both groups (P>0.05) at 24 hours and 7 days after ACI. There was no significant difference in modified ranking scores and mortality at 90 days after the treatment between the two groups (P>0.05). CONCLUSIONS: The therapeutic effect and mortality of rt-PA treatment in patients with ACI between 4.5-6 hours after the onset of the disease were similar to those in patients who received rt-PA within 4.5 hours after the onset of this disease. Therefore, intravenous thrombolytic therapy for ACI within 4.5-6 hours after ACI was effective and safe.

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