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1.
J Virol ; 98(3): e0198223, 2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38411106

RESUMEN

Continuously emerging highly pathogenic coronaviruses remain a major threat to human and animal health. Porcine deltacoronavirus (PDCoV) is a newly emerging enterotropic swine coronavirus that causes large-scale outbreaks of severe diarrhea disease in piglets. Unlike other porcine coronaviruses, PDCoV has a wide range of species tissue tropism, including primary human cells, which poses a significant risk of cross-species transmission. Nucleotide-binding oligomerization domain-like receptor (NLR) family pyrin domain-containing 1 (NLRP1) has a key role in linking host innate immunity to microbes and the regulation of inflammatory pathways. We now report a role for NLRP1 in the control of PDCoV infection. Overexpression of NLRP1 remarkably suppressed PDCoV infection, whereas knockout of NLRP1 led to a significant increase in PDCoV replication. A mechanistic study revealed that NLRP1 suppressed PDCoV replication in cells by upregulating IL-11 expression, which in turn inhibited the phosphorylation of the ERK signaling pathway. Furthermore, the ERK phosphorylation inhibitor U0126 effectively hindered PDCoV replication in pigs. Together, our results demonstrated that NLRP1 exerted an anti-PDCoV effect by IL-11-mediated inhibition of the phosphorylation of the ERK signaling pathway, providing a novel antiviral signal axis of NLRP1-IL-11-ERK. This study expands our understanding of the regulatory network of NLRP1 in the host defense against virus infection and provides a new insight into the treatment of coronaviruses and the development of corresponding drugs.IMPORTANCECoronavirus, which mainly infects gastrointestinal and respiratory epithelial cells in vivo, poses a huge threat to both humans and animals. Although porcine deltacoronavirus (PDCoV) is known to primarily cause fatal diarrhea in piglets, reports detected in plasma samples from Haitian children emphasize the potential risk of animal-to-human spillover. Finding effective therapeutics against coronaviruses is crucial for controlling viral infection. Nucleotide-binding oligomerization-like receptor (NLR) family pyrin domain-containing 1 (NLRP1), a key regulatory factor in the innate immune system, is highly expressed in epithelial cells and associated with the pathogenesis of viruses. We demonstrate here that NLRP1 inhibits the infection of the intestinal coronavirus PDCoV through IL-11-mediated phosphorylation inhibition of the ERK signaling pathway. Furthermore, the ERK phosphorylation inhibitor can control the infection of PDCoV in pigs. Our study emphasizes the importance of NLRP1 as an immune regulatory factor and may open up new avenues for the treatment of coronavirus infection.


Asunto(s)
Infecciones por Coronavirus , Deltacoronavirus , Enfermedades de los Porcinos , Animales , Niño , Humanos , Diarrea , Haití , Interleucina-11/metabolismo , Proteínas NLR/metabolismo , Nucleótidos/metabolismo , Fosforilación , Transducción de Señal , Porcinos , Zoonosis/metabolismo
2.
J Med Virol ; 96(3): e29517, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38476091

RESUMEN

Herbal medicines (HMs) are one of the main sources for the development of lead antiviral compounds. However, due to the complex composition of HMs, the screening of active compounds within these is inefficient and requires a significant time investment. We report a novel and efficient virus-based screening method for antiviral active compounds in HMs. This method involves the centrifugal ultrafiltration of viruses, known as the virus-based affinity ultrafiltration method (VAUM). This method is suitable to identify virus specific active compounds from complex matrices such as HMs. The effectiveness of the VAUM was evaluated using influenza A virus (IAV) H1N1. Using this method, four compounds that bind to the surface protein of H1N1 were identified from dried fruits of Terminalia chebula (TC). Through competitive inhibition assays, the influenza surface protein, neuraminidase (NA), was identified as the target protein of these four TC-derived compounds. Three compounds were identified by high performance liquid chromatography (HPLC) and liquid chromatography/mass spectrometry (LC/MS), and their anti-H1N1 activities were verified by examining the cytopathic effect (CPE) and by performing a virus yield reduction assay. Further mechanistic studies demonstrated that these three compounds directly bind to NA and inhibit its activity. In summary, we describe here a VAUM that we designed, one that can be used to accurately screen antiviral active compounds in HMs and also help improve the efficiency of screening antiviral drugs found in natural products.


Asunto(s)
Subtipo H1N1 del Virus de la Influenza A , Plantas Medicinales , Humanos , Ultrafiltración , Extractos Vegetales/farmacología , Antivirales/farmacología , Proteínas de la Membrana
3.
J Environ Manage ; 352: 120034, 2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-38232588

RESUMEN

Although the literature predominantly emphasises the crucial role of technological innovation in alleviating resource dependence, limited attention has been given to the pivotal role of capital in driving such innovation. As a critical factor in technological advancements and productivity enhancement, venture capital has a substantial function in the utilisation of resources and the development of sustainable energy sources. Drawing upon panel data from 30 provinces in China, this study explores how venture capital and resource dependence are interrelated. Our research reveals that venture capital effectively mitigates regional resource dependence by facilitating increased investment in innovation channels. However, the weakening of regional human resources mitigates venture capital's diminishing impacts on resource dependence. These findings provide valuable insights for countries seeking to reduce their dependence on natural resources and achieve long-term economic sustainability.


Asunto(s)
Inversiones en Salud , Recursos Naturales , Humanos , China , Fuentes Generadoras de Energía , Invenciones , Desarrollo Económico
4.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(3): 230-235, 2024 Mar 15.
Artículo en Zh | MEDLINE | ID: mdl-38557373

RESUMEN

OBJECTIVES: To explore the risk factors associated with cow's milk protein allergy (CMPA) in infants. METHODS: This study was a multicenter prospective nested case-control study conducted in seven medical centers in Beijing, China. Infants aged 0-12 months were included, with 200 cases of CMPA infants and 799 control infants without CMPA. Univariate and multivariate logistic regression analyses were used to investigate the risk factors for the occurrence of CMPA. RESULTS: Univariate logistic regression analysis showed that preterm birth, low birth weight, birth from the first pregnancy, firstborn, spring birth, summer birth, mixed/artificial feeding, and parental history of allergic diseases were associated with an increased risk of CMPA in infants (P<0.05). Multivariate logistic regression analysis revealed that firstborn (OR=1.89, 95%CI: 1.14-3.13), spring birth (OR=3.42, 95%CI: 1.70-6.58), summer birth (OR=2.29, 95%CI: 1.22-4.27), mixed/artificial feeding (OR=1.57, 95%CI: 1.10-2.26), parental history of allergies (OR=2.13, 95%CI: 1.51-3.02), and both parents having allergies (OR=3.15, 95%CI: 1.78-5.56) were risk factors for CMPA in infants (P<0.05). CONCLUSIONS: Firstborn, spring birth, summer birth, mixed/artificial feeding, and a family history of allergies are associated with an increased risk of CMPA in infants.


Asunto(s)
Hipersensibilidad a la Leche , Nacimiento Prematuro , Lactante , Embarazo , Femenino , Animales , Bovinos , Recién Nacido , Humanos , Hipersensibilidad a la Leche/etiología , Estudios de Casos y Controles , Estudios Prospectivos , Nacimiento Prematuro/inducido químicamente , Factores de Riesgo , Proteínas de la Leche
5.
J Med Virol ; 95(8): e29059, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37635463

RESUMEN

Respiratory syncytial virus (RSV) causes lower respiratory tract diseases and bronchiolitis in children and elderly individuals. There are no effective drugs currently available to treat RSV infection. In this study, we report that Licochalcone A (LCA) can inhibit RSV replication and mitigate RSV-induced cell damage in vitro, and that LCA exerts a protective effect by reducing the viral titer and inflammation in the lungs of infected mice in vivo. We suggest that the mechanism of action occurs through pathways of antioxidant stress and inflammation. Further mechanistic results demonstrate that LCA can induce nuclear factor erythroid 2-related factor 2 (Nrf2) translocation into the nucleus, activate heme oxygenase 1 (HO-1), and inhibit reactive oxygen species-induced oxidative stress. LCA also works to reverse the decrease in I-kappa-B-alpha (IкBα) levels caused by RSV, which in turn inhibits inflammation through the associated nuclear factor kappa B and tumor necrosis factor-α signaling pathways. The combined action of the two cross-talking pathways protects hosts from RSV-induced damage. To conclude, our study is the first of its kind to establish evidence of LCA as a viable treatment for RSV infection.


Asunto(s)
Chalconas , Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Animales , Ratones , Chalconas/farmacología , Chalconas/uso terapéutico , Infecciones por Virus Sincitial Respiratorio/tratamiento farmacológico , Antivirales/farmacología , Antivirales/uso terapéutico , Inflamación
6.
BMC Med Imaging ; 23(1): 186, 2023 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-37968599

RESUMEN

BACKGROUND AND PURPOSE: Renal cell carcinoma (RCC) is a heterogeneous group of cancers. The collagen fiber content in the tumor microenvironment of renal cancer has an important role in tumor progression and prognosis. A radiomics model was developed from dual-energy CT iodine maps to assess collagen fiber content in the tumor microenvironment of ccRCC. METHODS: A total of 87 patients with ccRCC admitted to our hospital were included in this retrospective study. Among them, 59 cases contained large amounts of collagen fibers and 28 cases contained a small amount of collagen fibers. We established a radiomics model using preoperative dual-energy CT scan Iodine map (IV) imaging to distinguish patients with multiple collagen fibers from those with few collagen fibers in the tumor microenvironment of ccRCC. We extracted features from dual-energy CT Iodine map images to evaluate the effects of six classifiers, namely k-nearest neighbor (KNN), support vector machine (SVM), extreme gradient boosting (XGBoost), random forest (RF), logistic regression (LR), and decision tree (DT). The effects of the models built based on the dynamic and venous phases are also compared. Model performance was evaluated using quintuple cross-validation and area under the receiver operating characteristic curve (AUC). In addition, a clinical model was developed to assess the clinical factors affecting collagen fiber content. RESULTS: Compared to KNN, SVM, and LR classifiers, RF, DT, and XGBoost classifiers trained with higher AUC values, with training sets of 0.997, 1.0, and 1.0, respectively. In the validation set, the highest AUC was found in the SVM classifier with a size of 0.722. In the comparative test of the active and intravenous phase models, the SVM classifier had the best effect with its validation set AUC of 0.698 and 0.741. In addition, there was a statistically significant effect of patient age and maximum tumor diameter on the collagen fiber content in the tumor microenvironment of kidney cancer. CONCLUSION: Radionics features based on preoperative dual-energy CT IV can be used to predict the amount of collagen fibers in the tumor microenvironment of renal cancer. This study better informs clinical prognosis and patient management. Iodograms may add additional value to dual-energy CTs.


Asunto(s)
Carcinoma de Células Renales , Yodo , Neoplasias Renales , Humanos , Estudios Retrospectivos , Microambiente Tumoral , Colágeno
7.
Chemistry ; 28(1): e202103402, 2022 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-34693580

RESUMEN

Ligand-controlled regiodivergence has been developed for catalytic semireduction of allenamides with excellent chemo- and stereocontrol. This system also provides an example of catalytic regiodivergent semireduction of allenes for the first time. The divergence of the semireduction is enabled by ligand switch with the same palladium pre-catalyst under operationally simple and mild conditions. Monodentate ligand XPhos exclusively promotes selective 1,2-semireduction to afford allylic amides, while bidentate ligand BINAP completely switched the regioselectivity to 2,3-semireduction, producing (E)-enamide derivatives.


Asunto(s)
Paladio , Catálisis , Ligandos , Estructura Molecular , Estereoisomerismo
8.
BMC Neurol ; 22(1): 37, 2022 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-35078425

RESUMEN

BACKGROUND: Mechanical thrombectomy has been widely performed for large vessel occlusion stroke. The present study aimed to determine whether cumulative experience could improve thrombectomy outcomes. METHODS: In this retrospective single-center analysis, patients who underwent mechanical thrombectomy with the Solitaire stent in 3 years from 25 April 2015 were enrolled in the current study. Patients' characteristics, durations of admission and treatment, recanalization rates, clinical outcomes, and hemorrhage transformation rates were compared among the 3 years. Logistic analysis was used to analyze the independent correlation of the years and procedural outcomes. RESULTS: A total of 222 patients underwent mechanical thrombectomy in the 3 years: 50 in the first year, 68 in the second year, and 104 in the third year. Door-to-puncture time (P < 0.001) and puncture-to-recanalization time (P = 0.033) decreased significantly among the 3 years, while successful recanalization rates increased (P = 0.001). Logistic regression analysis showed an independent increase in the successful recanalization rates in the second year and third year (P = 0.020, P = 0.001) as compared to that in the first year. CONCLUSIONS: Cumulative experience might improve the procedures of mechanical thrombectomy. The current findings suggested a potential benefit for centralization in the treatment of large vessel occlusion stroke.


Asunto(s)
Isquemia Encefálica , Accidente Cerebrovascular , Humanos , Estudios Retrospectivos , Stents , Accidente Cerebrovascular/cirugía , Trombectomía , Resultado del Tratamiento
9.
Asia Pac J Clin Nutr ; 31(1): 147-155, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35357113

RESUMEN

BACKGROUND AND OBJECTIVES: Cow's milk allergy (CMA) is the most common food allergy in young children. Previous studies have reported that single-nucleotide polymorphisms (SNPs) are associated with CMA. The extent to which SNPs contribute to the occurrence of CMA is unknown. The purpose of this study was to investigate the independent relevance of genetic predisposition to CMA in Chinese children. METHODS AND STUDY DESIGN: 200 infants with CMA and 799 healthy controls aged 0-12 months were included. Five previously identified genetic variants (rs17616434, rs2069772, rs1800896, rs855791 and rs20541) were genotyped. Logistic regression was used to analyze the genetic associations or their interactions with a family history of allergy on CMA. RESULTS: Among the five SNPs, only IL10 rs1800896 was significantly associated with CMA (odds ratio (OR) 1.60, p=0.042). Each 1-risk allele increase in the genetic risk score (GRS) was suggestively associated with an 11% higher risk of CMA (1.11: 0.99-1.27, p=0.069) and a 45% increased risk of CMA in the GRS high-risk group compared to the GRS low-risk group (1.45: 1.02-2.06, p=0.037). Furthermore, parental allergy also increased the risk of CMA among children (1.87: 1.46-2.39, p<0.001). Importantly, parental allergy exacerbated the genetic effect on the risk of CMA. CONCLUSIONS: The rs1800896 variant in the IL-10 gene is associated with CMA in Chinese children. In addition, the GRS had an interaction with parental history of allergy, implying that genetic risk for CMA was exacerbated among those with parental history of allergy.


Asunto(s)
Interleucina-10 , Hipersensibilidad a la Leche , Animales , Bovinos , China , Predisposición Genética a la Enfermedad , Humanos , Lactante , Recién Nacido , Interleucina-10/genética , Hipersensibilidad a la Leche/genética , Polimorfismo de Nucleótido Simple , Factores de Riesgo
10.
Geriatr Nurs ; 46: 13-20, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35580471

RESUMEN

OBJECTIVE: To systematically evaluate the effects of acupuncture in patients with unilateral spatial neglect (USN) after stroke. DATA SOURCES: Relevant English- and Chinese- language studies published until 12th February 2022, were retrieved from China National Knowledge Infrastructure (CNKI), Wanfang, China Scientific Journals Database (VIP), SinoMed, PubMed, Cochrane Library, Embase, Web of Science and OVID. REVIEW METHODS: Randomized controlled trials (RCTs) assessing the effects of acupuncture in patients with USN after stroke were included. Two researchers independently identified eligible studies and extracted the data. The methodological quality of the studies was evaluated using the Cochrane Handbook for Systematic Reviews of Interventions v5.1.0. RESULTS: Twelve studies (731 participants) were included. The meta-analysis found that compared with the control group, acupuncture increased MMSE, BI, MBI, and FMA scores and reduced the USN scores (all P < 0.05). These results indicated that acupuncture improved cognitive function, activities of daily living (ADLs), and motor function and relieved the degree of USN in patients with USN after stroke. CONCLUSION: Acupuncture could promote the rehabilitation of cognitive function, ADLs, and motor function and relieve the symptoms of USN in patients with USN after stroke. It may be a good complementary treatment to rehabilitation therapy for USN.


Asunto(s)
Terapia por Acupuntura , Trastornos de la Percepción , Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Terapia por Acupuntura/métodos , Humanos , Trastornos de la Percepción/terapia , Ensayos Clínicos Controlados Aleatorios como Asunto , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/terapia , Rehabilitación de Accidente Cerebrovascular/métodos
11.
Opt Express ; 29(18): 28124-28133, 2021 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-34614951

RESUMEN

Optical underwater target imaging and detection have been a tough but significant challenge in deep-sea exploration. Distant reflected signals drown in various underwater noises due to strong absorption and scattering, resulting in degraded image contrast and reduced detection range. Single-photon feature operating at the fundamental limit of the classical electromagnetic waves can broaden the realm of quantum technologies. Here we experimentally demonstrate a thresholded single-photon imaging and detection scheme to extract photon signals from the noisy underwater environment. We reconstruct the images obtained in a high-loss underwater environment by using photon-limited computational algorithms. Furthermore, we achieve a capability of underwater detection down to 0.8 photons per pulse at Jerlov type III water up to 50 meters, which is equivalent to more than 9 attenuation lengths. The results break the limits of classical underwater imaging and detection and may lead to many quantum-enhanced applications, like air-to-sea target tracking and deep-sea optical exploration.

12.
Biosci Biotechnol Biochem ; 85(6): 1395-1404, 2021 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-33784390

RESUMEN

Liraglutide is an analog of human glucagon-like peptide-1 which play essential roles in regulation of glycolipid metabolism. To investigate role of lactic acid bacteria (LAB) in lipid-lowering effect of liraglutide, 40 mice were divided into normal food diet (NFD), high-fat food (HFD), 10.0 mg/kg/d simvastatin-treated HFD (SIM + HFD), 200 and 400 µg/kg/d liraglutide-treated HFD (LL + HFD and HL + HFD) groups for 5 weeks. We found that liraglutide could upregulate cholesterol 7α-hydroxylase (CYP7A1) and LDL-receptor (LDLR), whereas downregulate 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR). Besides, liraglutide enhance abundance of lactobacillaceae in gut of hyperlipidemic mice and increase bile tolerance ability of LAB by upregulating bile salt hydrolases, and the lysate of liraglutide-sensitive LAB could also directly downregulate HMGCR, the key enzyme in cholesterol synthesis, and inhibit hepatocyte steatosis. These findings might provide new theoretical guidance for clinical application of liraglutide and research and development of antiobesity, hypolipidemic, and cholesterol-lowering drugs or functional foods.


Asunto(s)
Bilis/metabolismo , Hipolipemiantes/farmacología , Lactobacillus/efectos de los fármacos , Lactobacillus/metabolismo , Liraglutida/farmacología , Animales , Colesterol/metabolismo , Colesterol 7-alfa-Hidroxilasa/metabolismo , Dieta Alta en Grasa/efectos adversos , Relación Dosis-Respuesta a Droga , Masculino , Ratones
13.
Int J Mol Sci ; 22(9)2021 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-34067160

RESUMEN

Puccinia striiformis f. sp. tritici (Pst) is an important pathogen of wheat (Triticum aestivum L.) stripe rust, and the effector protein secreted by haustoria is a very important component involved in the pathogenic process. Although the candidate effector proteins secreted by Pst haustoria have been predicted to be abundant, few have been functionally validated. Our study confirmed that chitin and flg22 could be used as elicitors of the pathogenic-associated molecular pattern-triggered immune (PTI) reaction in wheat leaves and that TaPr-1-14 could be used as a marker gene to detect the PTI reaction. In addition, the experimental results were consistent in wheat protoplasts. A rapid and efficient method for screening and identifying the effector proteins of Pst was established by using the wheat protoplast transient expression system. Thirty-nine Pst haustorial effector genes were successfully cloned and screened for expression in the protoplast. We identified three haustorial effector proteins, PSEC2, PSEC17, and PSEC45, that may inhibit the response of wheat to PTI. These proteins are localized in the somatic cytoplasm and nucleus of wheat protoplasts and are highly expressed during the infection and parasitism of wheat.


Asunto(s)
Proteínas Fúngicas/metabolismo , Inmunidad , Moléculas de Patrón Molecular Asociado a Patógenos/metabolismo , Protoplastos/microbiología , Puccinia/fisiología , Triticum/inmunología , Triticum/microbiología , Núcleo Celular/efectos de los fármacos , Núcleo Celular/metabolismo , Quitina/farmacología , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Genes de Plantas , Inmunidad/efectos de los fármacos , Enfermedades de las Plantas/microbiología , Inmunidad de la Planta/efectos de los fármacos , Hojas de la Planta/efectos de los fármacos , Hojas de la Planta/genética , Hojas de la Planta/inmunología , Hojas de la Planta/microbiología , Protoplastos/efectos de los fármacos , Puccinia/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Reproducibilidad de los Resultados , Fracciones Subcelulares/efectos de los fármacos , Fracciones Subcelulares/metabolismo , Transcripción Genética/efectos de los fármacos , Triticum/efectos de los fármacos , Triticum/genética
14.
Int J Med Microbiol ; 310(5): 151432, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32654774

RESUMEN

The extracellular signal-regulated kinases (ERKs) serve as important determinants of cellular signal transduction pathways, and hence may play important roles during infections. Previous work suggested that putative ERK7 of Toxoplasma gondii is required for efficient intracellular replication of the parasite. However, the antigenic and immunostimulatory properties of TgERK7 protein remain unknown. The objective of this study was to produce a recombinant TgERK7 protein in vitro and to evaluate its effect on the induction of humoral and T cell-mediated immune responses against T. gondii infection in BALB/c mice. Immunization using TgERK7 mixed with Freund's adjuvants significantly increased the ratio of CD3e+CD4+ T/CD3e+CD8a+ T lymphocytes in spleen and elevated serum cytokines (IFN-γ, IL-2, IL-4, IL-10, IL-12p70, IL-23, MCP-1, and TNF-α) in immunized mice compared to control mice. On the contrary, immunization did not induce high levels of serum IgG antibodies. Five predicted peptides of TgERK7 were synthesized and conjugated with KLH and used to analyze the antibody specificity in the sera of immunized mice. We detected a progressive increase in the antibody level only against TgERK7 peptide A (DEVDKHVLRKYD). Antibody raised against this peptide significantly decreased intracellular proliferation of T. gondii in vitro, suggesting that peptide A can potentially induce a protective antibody response. We also showed that immunization improved the survival rate of mice challenged with a virulent strain and significantly reduced the parasite cyst burden within the brains of chronically infected mice. Our data show that TgERK7-based immunization induced TgERK7 peptide A-specific immune responses that can impart protective immunity against T. gondii infection. The therapeutic potential of targeting ERK7 signaling pathway for future toxoplasmosis treatment is warranted.


Asunto(s)
Antígenos de Protozoos/inmunología , Quinasas MAP Reguladas por Señal Extracelular/inmunología , Toxoplasma/inmunología , Toxoplasmosis Animal/inmunología , Animales , Anticuerpos Antiprotozoarios/sangre , Antígenos de Protozoos/genética , Citocinas/sangre , Quinasas MAP Reguladas por Señal Extracelular/genética , Femenino , Inmunidad Celular , Inmunidad Humoral , Inmunización , Inmunoglobulina G/sangre , Ratones , Ratones Endogámicos BALB C , Péptidos/química , Péptidos/genética , Conformación Proteica , Vacunas Antiprotozoos/inmunología , Conejos , Proteínas Recombinantes/inmunología , Toxoplasma/genética
15.
Exp Parasitol ; 211: 107843, 2020 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-32044321

RESUMEN

The intracellular protozoan Toxoplasma gondii infects approximately one-third of the world's population as well as various animals, causing toxoplasmosis. However, there remains a need to define the functions of newly identified genes of T. gondii. In the present study, a novel molecule, immune mapped protein 1 of T. gondii (TgIMP1), was devitalized by CRISPR/Cas9 system to investigate the phenotypic changes of the parasite. We found that the virulence of ΔTgIMP1 knockout strain was reduced in comparison with wild-type GT1 tachyzoites, showing a statistically decreased plaque in HFF cells and a significantly prolonged survival period of mice (P < 0.05). Moreover, the data of phenotype analyses in vitro showed a different level of the intracellular proliferation and the subsequent egress between ΔTgIMP1 and wild-type GT1 strain (P < 0.05); while no statistically significant difference was detected during the process of attachment or invasion. These results suggested that TgIMP1 is closely associated with the intracellular proliferation of this parasite.

16.
Parasitol Res ; 119(11): 3771-3776, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32914221

RESUMEN

Toxoplasma gondii causes serious clinical toxoplasmosis in humans mostly due to its asexual life cycles, which can be artificially divided into five tightly coterminous stages. Any radical or delay for the stage will result in tremendous changes immediately behind. We previously demonstrated that TgERK7 is associated with the intracellular proliferation of T. gondii, but during the process, other stages before were not meanwhile determined. To further clarify the function of ERK7 gene in T. gondii, the complemental strain of ΔTgERK7 tachyzoites created previously was engineered via electric transfection with the recombinant pUC/Tgerk7 plasmid, named pUC/TgERK7 strain in this study, and was used together with ΔTgERK7 and wild-type GT1 strains to retrospect the phenotypic changes including invasion and attachment. The results showed that TgERK7 protein can be re-expressed in the ΔTgERK7 tachyzoites and eradication of this protein leads to significantly lower invasion of T. gondii at 1 h and 2 h post-infection (P < 0.05), which is the key factor causing the following slow intracellular proliferation, in comparison with wild-type GT1 and pUC/TgERK7 parasites; noteworthily, at other early time points including 15 min for attachment assay was no statistical difference (P > 0.05). The data suggested that ERK7 protein in T. gondii is an important virulence factor that participates in the invasion of this parasite.


Asunto(s)
Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Proteínas Protozoarias/metabolismo , Toxoplasma/patogenicidad , Animales , Quinasas MAP Reguladas por Señal Extracelular/genética , Prueba de Complementación Genética , Humanos , Estadios del Ciclo de Vida/genética , Mutación , Proteínas Protozoarias/genética , Toxoplasma/genética , Toxoplasma/crecimiento & desarrollo , Toxoplasmosis/parasitología , Virulencia/genética
17.
J Am Chem Soc ; 141(40): 15730-15736, 2019 10 09.
Artículo en Inglés | MEDLINE | ID: mdl-31536341

RESUMEN

Ru(II)-catalyzed enantioselective C-H activation/hydroarylation has been developed for the first time, allowing for highly enantioselective synthesis of indoline derivatives via catalytic C-H activation. Commercially available Ru(II) arene complexes and chiral α-methylamines were employed as highly enantioselective catalysts. Based on a sterically rigidified chiral transient directing group, multisubstituted indolines were produced in up to 92% yield with 96% ee. Further transformation of the resulting 4-formylindoline enables access to an optically active tricyclic compound that is of potential biological and pharmaceutical interest.

18.
BMC Biotechnol ; 19(1): 59, 2019 08 09.
Artículo en Inglés | MEDLINE | ID: mdl-31399136

RESUMEN

BACKGROUND: Heparinase I from Pedobacter heparinus (Ph-HepI), which specifically cleaves heparin and heparan sulfate, is one of the most extensively studied glycosaminoglycan lyases. Enzymatic degradation of heparin by heparin lyases not only largely facilitates heparin structural analysis but also showed great potential to produce low-molecular-weight heparin (LMWH) in an environmentally friendly way. However, industrial applications of Ph-HepI have been limited by their poor yield and enzyme activity. In this work, we improve the specific enzyme activity of Ph-HepI based on homology modeling, multiple sequence alignment, molecular docking and site-directed mutagenesis. RESULTS: Three mutations (S169D, A259D, S169D/A259D) exhibited a 50.18, 40.43, and 122.05% increase in the specific enzyme activity and a 91.67, 108.33, and 75% increase in the yield, respectively. The catalytic efficiencies (kcat/Km) of the mutanted enzymes S169D, A259D, and S169D/A259D were higher than those of the wild-type enzyme by 275, 164, and 406%, respectively. Mass spectrometry and activity detection showed the enzyme degradation products were in line with the standards of the European Pharmacopoeia. Protein structure analysis showed that hydrogen bonds and ionic bonds were important factors for improving specific enzyme activity and yield. CONCLUSIONS: We found that the mutant S169D/A259D had more industrial application value than the wild-type enzyme due to molecular modifications. Our results provide a new strategy to increase the catalytic efficiency of other heparinases.


Asunto(s)
Liasa de Heparina/metabolismo , Heparina/metabolismo , Secuencia de Aminoácidos , Calcio/metabolismo , Heparina/química , Liasa de Heparina/química , Humanos , Concentración de Iones de Hidrógeno , Espectrometría de Masas , Simulación del Acoplamiento Molecular , Datos de Secuencia Molecular , Mutagénesis Sitio-Dirigida , Mutación , Estructura Secundaria de Proteína , Temperatura
19.
Pharm Biol ; 57(1): 498-506, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31401925

RESUMEN

Context: Charcoal of Chinese drugs is a kind of special processing product in Chinese medicine and used for treatment of haemoptysis, hematemesis and haemorrhage in the clinic during ancient times. During carbonizing, significant changes occur in chemical constituents and the efficacy of haemostasis will be enhanced. But the quality control standard of 'carbonizing retains characteristics' should be followed. Objective: This review introduces the typical methods of carbonizing, which highlight current research progress on haemostatic substances of charcoal drugs so as to provide a reasonable explanation for the theory of haemostasis treated by charcoal medicine. Methods: English and Chinese literature from 2004 to 2019 was collected from databases including Web of Science, PubMed, Elsevier and CNKI (Chinese). Charcoal drug, chemical constituents, processing, haemostasis and carbon dots were used as the key words. Results: Charcoal drugs mainly play a haemostatic role and the effect can be classified into four types to stop bleeding: removing blood stasis, cooling blood, warming meridians and astringing. Changes in composition lead to changes in pharmacodynamics. Carbonizing methods and basic research on haemostasis material in charcoal drugs have also been summarized. Conclusions: This review summarizes the classification of charcoal drugs and highlights the possible material bases for the haemostatic effect of charcoal drugs in recent years, providing new insights to future research.


Asunto(s)
Carbón Orgánico/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Hemostasis/efectos de los fármacos , Hemorragia/tratamiento farmacológico , Medicina Tradicional China , Control de Calidad
20.
Clin Rehabil ; 32(12): 1569-1580, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30088421

RESUMEN

OBJECTIVE:: To estimate the effectiveness of MOTOmed® movement therapy in increasing mobility and activities of daily living in stroke patients with hemiplegia. DESIGN:: Systematic review. DATA SOURCES:: English- and Chinese-language articles published from the start of database coverage through 20 June 2018 were retrieved from the Embase, Web of Science, PubMed, OVID, Cochrane Central Register of Controlled Trials, Cochrane Systematic Reviews, Wanfang, Chinese National Knowledge Infrastructure, VIP, and Chinese Biomedicine databases. Articles were also retrieved by manual searches of Rehabilitation Medicine and Chinese journals. METHODS:: Randomized control trials examining MOTOmed movement therapy interventions for patients with post-stroke hemiplegia were included in this review. The risk of bias assessment tool was utilized in accordance with Cochrane Handbook 5.1.0. All included studies reported mobility effects as primary outcomes. Standardized mean differences or mean differences with the corresponding 95% confidence intervals (CIs) were calculated. Review Manager 5.3 was utilized for meta-analysis. RESULTS:: In total, 19 trials involving a total of 1099 patients were included in the analysis. All studies were of moderate quality, based on the Cochrane Handbook for Systematic Reviews of Intervention: Part 2:8.5. MOTOmed movement therapy resulted in a merged mean difference in the Fugl-Meyer Assessment score of 5.51 (95% CI: 4.03 to 6.98). Comparison of groups treated with and without MOTOmed movement therapy yielded the following mean differences: Modified Ashworth Scale, -1.13 (95% CI: -1.37 to -0.89); Berg Balance Scale, 13.66 (95% CI: 10.47-16.85); Functional Ambulation Category Scale, 0.85 (95% CI: 0.68-1.03); 10-m walk test, 10.15 (95% CI: 5.72-14.58); Barthel Index, 14.82 (95% CI: 12.96-16.68); and Modified Barthel Index, 11.49 (95% CI: 8.96-14.03). CONCLUSION:: MOTOmed movement therapy combined with standard rehabilitation improves mobility and activities of daily living in stroke patients with hemiplegia.


Asunto(s)
Actividades Cotidianas , Hemiplejía/rehabilitación , Modalidades de Fisioterapia , Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular/complicaciones , Caminata , Humanos
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