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1.
J Biol Chem ; 299(2): 102829, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36581211

RESUMEN

Candida albicans is a deadly pathogen responsible for millions of mucosal and systemic infections per year. The pathobiology of C. albicans is largely dependent on the damaging and immunostimulatory properties of the peptide candidalysin (CL), a key virulence factor. When CL forms pores in the plasma membrane of epithelial cells, it activates a response network grounded in activation of the epidermal growth factor receptor. Prior reviews have characterized the resulting CL immune activation schemas but lacked insights into the molecular mechanism of CL membrane damage. We recently demonstrated that CL functions by undergoing a unique self-assembly process; CL forms polymers and loops in aqueous solution prior to inserting and forming pores in cell membranes. This mechanism, the first of its kind to be observed, informs new therapeutic avenues to treat Candida infections. Recently, variants of CL were identified in other Candida species, providing an opportunity to identify the residues that are key for CL to function. In this review, we connect the ability of CL to damage cell membranes to its immunostimulatory properties.


Asunto(s)
Candida albicans , Proteínas Fúngicas , Factores de Virulencia , Candida albicans/química , Proteínas Fúngicas/química , Factores de Virulencia/química
2.
Curr Issues Mol Biol ; 46(3): 2027-2042, 2024 Mar 03.
Artículo en Inglés | MEDLINE | ID: mdl-38534747

RESUMEN

Glucose is a major energy substrate for porcine adipocytes and also serves as a regulatory signal for adipogenesis and lipid metabolism. In this study, we combined transcriptome and metabolome analyses to reveal the underlying regulatory mechanisms of high glucose (HG) on adipogenesis by comparing differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs) identified in porcine adipocytes. Results showed that HG (20 mmol/L) significantly increased fat accumulation in porcine adipocytes compared to low glucose (LG, 5 mmol/L). A total of 843 DEGs and 365 DAMs were identified. Functional enrichment analyses of DEGs found that multiple pathways were related to adipogenesis, lipid metabolism, and immune-inflammatory responses. PPARγ, C/EBPα, ChREBP, and FOS were identified as the key hub genes through module 3 analysis, and PPARγ acted as a central regulator by linking genes involved in lipid metabolism and immune-inflammatory responses. Gene-metabolite networks found that PPARγ-13-HODE was the most important interaction relationship. These results revealed that PPARγ could mediate the cross-talk between adipogenesis and the immune-inflammatory response during adipocyte maturation. This work provides a comprehensive view of the regulatory mechanisms of glucose on adipogenesis in porcine adipocytes.

3.
Stroke ; 54(6): 1569-1577, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37165864

RESUMEN

BACKGROUND: The effect of imaging selection paradigms on endovascular thrombectomy outcomes in patients with acute ischemic stroke with large vessel occlusion remains uncertain. The study aimed to assess the effect of basic imaging (noncontrast computed tomography with or without computed tomographic angiography) versus advanced imaging (magnetic resonance imaging or computed tomography perfusion) on clinical outcomes following thrombectomy in patients with stroke with large vessel occlusion in the early and extended windows using a pooled analysis of patient-level data from 2 pivotal randomized clinical trials done in China. METHODS: This post hoc analysis used data from 1182 patients included in 2 multicenter, randomized controlled trials in China that evaluated adjunct therapies to endovascular treatment for acute ischemic stroke (Direct Endovascular Treatment for Large Artery Anterior Circulation Stroke performed from May 20, 2018, through May 2, 2020, and Intravenous Tirofiban Before Endovascular Treatment in Stroke from October 10, 2018, through October 31, 2021). Patients with occlusion of the intracranial internal carotid artery or proximal middle cerebral artery (M1/M2 segments) were categorized according to baseline imaging modality (basic versus advanced) as well as treatment time window (early, 0-6 hours versus extended, 6-24 hours from last known well to puncture). The primary outcome was the proportion of patients with functional independence (modified Rankin Scale score of 0-2) at 90 days. Multivariable Poisson regression analysis was performed to determine the association between imaging selection modality and outcomes after endovascular treatment at each time windows. RESULTS: A total of 1182 patients were included in this cohort analysis, with 648 in the early (471 with basic imaging versus 177 advanced imaging) and 534 in the extended (222 basic imaging versus 312 advanced imaging) time window. There were no differences in 90-day functional independence between the advanced and basic imaging groups in either time windows (early window: adjusted relative risk, 0.99 [95% CI, 0.84-1.16]; P=0.91; extended window: adjusted relative risk, 1.00 [95% CI, 0.84-1.20]; P=0.97). CONCLUSIONS: In this post hoc analysis of 2 randomized clinical trial pooled data involving patients with large vessel occlusion stroke, an association between imaging selection modality and clinical or safety outcomes for patients undergoing thrombectomy in either the early or extended windows was not detected. Our study adds to the growing body of literature on simpler imaging paradigms to assess thrombectomy eligibility across both the early and extended time windows. REGISTRATION: URL: http://www.chictr.org.cn; Unique identifiers: ChiCTR-IOR-17013568 and ChiCTR-INR-17014167.


Asunto(s)
Isquemia Encefálica , Procedimientos Endovasculares , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/cirugía , Procedimientos Endovasculares/métodos , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/cirugía , Trombectomía/métodos , Resultado del Tratamiento , Ensayos Clínicos Controlados Aleatorios como Asunto
4.
PLoS Pathog ; 17(9): e1009884, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34506615

RESUMEN

Vulvovaginal candidiasis (VVC), caused primarily by the human fungal pathogen Candida albicans, results in significant quality-of-life issues for women worldwide. Candidalysin, a toxin derived from a polypeptide (Ece1p) encoded by the ECE1 gene, plays a crucial role in driving immunopathology at the vaginal mucosa. This study aimed to determine if expression and/or processing of Ece1p differs across C. albicans isolates and whether this partly underlies differential pathogenicity observed clinically. Using a targeted sequencing approach, we determined that isolate 529L harbors a similarly expressed, yet distinct Ece1p isoform variant that encodes for a predicted functional candidalysin; this isoform was conserved amongst a collection of clinical isolates. Expression of the ECE1 open reading frame (ORF) from 529L in an SC5314-derived ece1Δ/Δ strain resulted in significantly reduced vaginopathogenicity as compared to an isogenic control expressing a wild-type (WT) ECE1 allele. However, in vitro challenge of vaginal epithelial cells with synthetic candidalysin demonstrated similar toxigenic activity amongst SC5314 and 529L isoforms. Creation of an isogenic panel of chimeric strains harboring swapped Ece1p peptides or HiBiT tags revealed reduced secretion with the ORF from 529L that was associated with reduced virulence. A genetic survey of 78 clinical isolates demonstrated a conserved pattern between Ece1p P2 and P3 sequences, suggesting that substrate specificity around Kex2p-mediated KR cleavage sites involved in protein processing may contribute to differential pathogenicity amongst clinical isolates. Therefore, we present a new mechanism for attenuation of C. albicans virulence at the ECE1 locus.


Asunto(s)
Candida albicans/genética , Candidiasis Vulvovaginal/microbiología , Proteínas Fúngicas/genética , Alelos , Animales , Candida albicans/patogenicidad , Femenino , Variación Genética , Humanos , Ratones , Virulencia
5.
Genet Sel Evol ; 55(1): 18, 2023 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-36944938

RESUMEN

BACKGROUND: Natural and artificial selection for more than 9000 years have led to a variety of domestic pig breeds. Accurate identification of pig breeds is important for breed conservation, sustainable breeding, pork traceability, and local resource registration. RESULTS: We evaluated the performance of four selectors and six classifiers for breed identification using a wide range of pig breeds (N = 91). The internal cross-validation and external independent testing showed that partial least squares regression (PLSR) was the most effective selector and partial least squares-discriminant analysis (PLS-DA) was the most powerful classifier for breed identification among many breeds. Five-fold cross-validation indicated that using PLSR as the selector and PLS-DA as the classifier to discriminate 91 pig breeds yielded 98.4% accuracy with only 3K single nucleotide polymorphisms (SNPs). We also constructed a reference dataset with 124 pig breeds and used it to develop the web tool iDIGs ( http://alphaindex.zju.edu.cn/iDIGs_en/ ) as a comprehensive application for global pig breed identification. iDIGs allows users to (1) identify pig breeds without a reference population and (2) design small panels to discriminate several specific pig breeds. CONCLUSIONS: In this study, we proved that breed identification among a wide range of pig breeds is feasible and we developed a web tool for such pig breed identification.


Asunto(s)
Polimorfismo de Nucleótido Simple , Sus scrofa , Porcinos/genética , Animales , Genotipo , Sus scrofa/genética
6.
JAMA ; 328(6): 543-553, 2022 08 09.
Artículo en Inglés | MEDLINE | ID: mdl-35943471

RESUMEN

Importance: Tirofiban is a highly selective nonpeptide antagonist of glycoprotein IIb/IIIa receptor, which reversibly inhibits platelet aggregation. It remains uncertain whether intravenous tirofiban is effective to improve functional outcomes for patients with large vessel occlusion ischemic stroke undergoing endovascular thrombectomy. Objective: To assess the efficacy and adverse events of intravenous tirofiban before endovascular thrombectomy for acute ischemic stroke secondary to large vessel occlusion. Design, Setting, and Participants: This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 55 hospitals in China, enrolling 948 patients with stroke and proximal intracranial large vessel occlusion presenting within 24 hours of time last known well. Recruitment took place between October 10, 2018, and October 31, 2021, with final follow-up on January 15, 2022. Interventions: Participants received intravenous tirofiban (n = 463) or placebo (n = 485) prior to endovascular thrombectomy. Main Outcomes and Measures: The primary outcome was disability level at 90 days as measured by overall distribution of the modified Rankin Scale scores from 0 (no symptoms) to 6 (death). The primary safety outcome was the incidence of symptomatic intracranial hemorrhage within 48 hours. Results: Among 948 patients randomized (mean age, 67 years; 391 [41.2%] women), 948 (100%) completed the trial. The median (IQR) 90-day modified Rankin Scale score in the tirofiban group vs placebo group was 3 (1-4) vs 3 (1-4). The adjusted common odds ratio for a lower level of disability with tirofiban vs placebo was 1.08 (95% CI, 0.86-1.36). Incidence of symptomatic intracranial hemorrhage was 9.7% in the tirofiban group vs 6.4% in the placebo group (difference, 3.3% [95% CI, -0.2% to 6.8%]). Conclusions and Relevance: Among patients with large vessel occlusion acute ischemic stroke undergoing endovascular thrombectomy, treatment with intravenous tirofiban, compared with placebo, before endovascular therapy resulted in no significant difference in disability severity at 90 days. The findings do not support use of intravenous tirofiban before endovascular thrombectomy for acute ischemic stroke. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR-IOR-17014167.


Asunto(s)
Procedimientos Endovasculares , Accidente Cerebrovascular Isquémico , Inhibidores de Agregación Plaquetaria , Trombectomía , Tirofibán , Administración Intravenosa , Anciano , Arteriopatías Oclusivas/complicaciones , Arteriopatías Oclusivas/tratamiento farmacológico , Arteriopatías Oclusivas/cirugía , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/etiología , Isquemia Encefálica/cirugía , Método Doble Ciego , Procedimientos Endovasculares/métodos , Femenino , Humanos , Hemorragias Intracraneales/inducido químicamente , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/etiología , Accidente Cerebrovascular Isquémico/cirugía , Masculino , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/cirugía , Trombectomía/métodos , Tirofibán/administración & dosificación , Tirofibán/efectos adversos , Tirofibán/uso terapéutico , Resultado del Tratamiento
7.
Zhongguo Zhong Yao Za Zhi ; 47(22): 5978-5990, 2022 Nov.
Artículo en Zh | MEDLINE | ID: mdl-36471923

RESUMEN

Peptide is a compound consisting of 2-50 amino acids, which is intermediate between small molecule and protein. It is characterized by a variety of biological activities, easy absorption, strong specific targeting, and few side effects and has become one of the hotspots in biomedical research in recent years. Chinese medicine contains a large number of peptides. The traditional processing methods such as decocting and boiling can effectively boost peptides to exert their due biological activities. At present, however, the research on Chinese medicinal components in laboratory generally employs high-concentration alcohol extraction method, which may cause the peptides to be ignored in many natural Chinese medicines. Substantial studies have revealed that the peptides in Chinese medicine are important material basis responsible for the traditional efficacy. Based on years of research and literature retrieval, this study put forward the concept of "traditional Chinese medicine(TCM)-peptides", referring to the components consisting of two or more amino acids with molecular weight between small molecules and proteins that can express the efficacy of Chinese medicine. Furthermore, this study also summarized the extraction and separation of TCM-peptides, and structure determination methods and routes, predicted the research prospect of modern research methods of TCM-peptides based on "holistic view" and big data. The artificial intelligence prediction was combined with high-throughput screening technology to improve the discovery efficiency and accuracy of TCM-peptides, and holographic images between TCM-peptides and biological targets were established to provide references for the innovative drug design and related health product development of TCM-peptides based on TCM theories.


Asunto(s)
Medicamentos Herbarios Chinos , Medicina Tradicional China , Inteligencia Artificial , Medicamentos Herbarios Chinos/química , Proyectos de Investigación , Péptidos , Proteínas , Aminoácidos
8.
Infect Immun ; 89(2)2021 01 19.
Artículo en Inglés | MEDLINE | ID: mdl-33106292

RESUMEN

While human vaginal pH in childbearing-age women is conclusively acidic, the mouse vaginal pH is reported as being near neutral. However, this information appears to be somewhat anecdotal with respect to vulvovaginal candidiasis, as such claims in the literature frequently lack citations of studies that specifically address this physiological factor. Given the disparate pH between mice and humans, the role of exogenous hormones and colonization by the fungal pathogen Candida albicans in shaping vaginal pH was assessed. Use of a convenient modified vaginal lavage technique with the pH indicator dye phenol red demonstrated that indeed vaginal pH was near neutral (7.2 ± 0.24) and was not altered by delivery of progesterone or estrogen in C57BL/6 mice. These trends were conserved in DBA/2 and CD-1 mouse backgrounds, commonly used in the mouse model of vaginitis. It was also determined that vaginal colonization with C. albicans did not alter the globally neutral vaginal pH over the course of one week. Construction and validation of a C. albicans reporter strain expressing GFPy, driven by the pH-responsive PHR1 promoter, confirmed the murine vaginal pH to be at least ≥6.0. Collectively, our data convincingly demonstrate a stable and conserved near neutrality of the mouse vaginal pH during vulvovaginal candidiasis and should serve as a definitive source for future reference. Implications and rationale for disparate pH in this model system are also discussed.


Asunto(s)
Candidiasis Vulvovaginal/microbiología , Candidiasis Vulvovaginal/fisiopatología , Estradiol/fisiología , Concentración de Iones de Hidrógeno/efectos de los fármacos , Vagina/fisiología , Adulto , Animales , Modelos Animales de Enfermedad , Femenino , Humanos , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos DBA
9.
J Anim Breed Genet ; 138(3): 291-299, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33089920

RESUMEN

Genomic selection (GS) using the whole-genome molecular makers to predict genomic estimated breeding values (GEBVs) is revolutionizing the livestock and plant breeding. Seeking out novel strategies with higher prediction accuracy for GS has been the ultimate goal of breeders. With the rapid development of artificial intelligence, machine learning algorithms were applied to estimate the GEBVs increasingly. Although some machine learning methods have better performance in phenotype prediction, there is still considerable room for improvement. In this study, we applied an ensemble-learning algorithm, Adaboost.RT, which integrated support vector regression (SVR), kernel ridge regression (KRR) and random forest (RF), to predict genomic breeding values of three economic traits (carcass weight, live weight, and eye muscle area) in Chinese Simmental beef cattle. Predictive accuracy measured as the Pearson correlation between the corrected phenotypes and predicted GEBVs. Moreover, we compared the reliability of SVR, KRR, RF, Adaboost.RT and GBLUP methods. The result showed that machine learning methods outperformed GBLUP, and the average improvement of four machine learning methods over the GBLUP was 12.8%, 14.9%, 5.4% and 14.4%, respectively. Among the four machine learning methods, the reliability of Adaboost.RT was comparable to KRR with higher stability. We therefore believe that the Adaboost.RT algorithm is a reliable and efficient method for GS.


Asunto(s)
Genómica , Aprendizaje Automático , Animales , Bovinos , China , Genotipo , Fenotipo , Reproducibilidad de los Resultados
10.
BMC Genet ; 21(1): 32, 2020 03 14.
Artículo en Inglés | MEDLINE | ID: mdl-32171250

RESUMEN

BACKGROUND: Body size traits as one of the main breeding selection criteria was widely used to monitor cattle growth and to evaluate the selection response. In this study, body size was defined as body height (BH), body length (BL), hip height (HH), heart size (HS), abdominal size (AS), and cannon bone size (CS). We performed genome-wide association studies (GWAS) of these traits over the course of three growth stages (6, 12 and 18 months after birth) using three statistical models, single-trait GWAS, multi-trait GWAS and LONG-GWAS. The Illumina Bovine HD 770 K BeadChip was used to identify genomic single nucleotide polymorphisms (SNPs) in 1217 individuals. RESULTS: In total, 19, 29, and 10 significant SNPs were identified by the three models, respectively. Among these, 21 genes were promising candidate genes, including SOX2, SNRPD1, RASGEF1B, EFNA5, PTBP1, SNX9, SV2C, PKDCC, SYNDIG1, AKR1E2, and PRIM2 identified by single-trait analysis; SLC37A1, LAP3, PCDH7, MANEA, and LHCGR identified by multi-trait analysis; and P2RY1, MPZL1, LINGO2, CMIP, and WSCD1 identified by LONG-GWAS. CONCLUSIONS: Multiple association analysis was performed for six growth traits at each growth stage. These findings offer valuable insights for the further investigation of potential genetic mechanism of growth traits in Simmental beef cattle.


Asunto(s)
Tamaño Corporal/genética , Bovinos/genética , Estudio de Asociación del Genoma Completo , Sitios de Carácter Cuantitativo/genética , Animales , Cruzamiento , Bovinos/crecimiento & desarrollo , Genómica , Haplotipos/genética
11.
Heredity (Edinb) ; 124(2): 288-298, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31641238

RESUMEN

Linear mixed models (LMM) that tests trait association one marker at a time have been the most popular methods for genome-wide association studies. However, this approach has potential pitfalls: over conservativeness after Bonferroni correction, ignorance of linkage disequilibrium (LD) between neighboring markers, and power reduction due to overfitting SNP effects. So, multiple locus models that can simultaneously estimate and test all markers in the genome are more appropriate. Based on the multiple locus models, we proposed a bin model that combines markers into bins based on their LD relationships. A bin is treated as a new synthetic marker and we detect the associations between bins and traits. Since the number of bins can be substantially smaller than the number of markers, a penalized multiple regression method can be adopted by fitting all bins to a single model. We developed an innovative method to bin the neighboring markers and used the least absolute shrinkage and selection operator (LASSO) method. We compared BIN-Lasso with SNP-Lasso and Q + K-LMM in a simulation experiment, and showed that the new method is more powerful with less Type I error than the other two methods. We also applied the bin model to a Chinese Simmental beef cattle population for bone weight association study. The new method identified more significant associations than the classical LMM. The bin model is a new dimension reduction technique that takes advantage of biological information (i.e., LD). The new method will be a significant breakthrough in associative genomics in the big data era.


Asunto(s)
Bovinos/genética , Estudios de Asociación Genética/veterinaria , Genómica/métodos , Modelos Genéticos , Animales , Simulación por Computador , Genotipo , Modelos Lineales , Desequilibrio de Ligamiento , Polimorfismo de Nucleótido Simple
12.
Zhongguo Zhong Yao Za Zhi ; 45(24): 5890-5897, 2020 Dec.
Artículo en Zh | MEDLINE | ID: mdl-33496129

RESUMEN

Andrographis Herba is a commonly used plant medicine, and has been recorded in pharmacopeias of different countries. However, there are some differences in the quality standards. Based on this, this paper compare the quality standards of Andrographis Herba between Chinese Pharmacopoeia, Hong Kong Chinese Materia Medica Standards, United States Pharmacopoeia, European Pharmacopoeia and Indian Pharmacopoeia, including origin, botanical characteristics, identification(microscopic identification and chromatographic identification), content determination, specific test(such as impurities, loss on drying, extractives, pesticides, heavy metals, mycotoxins, and other items) and storage requirements, so as to provide a reference for studying international quality standards of Andrographis.


Asunto(s)
Andrographis , Medicamentos Herbarios Chinos , Materia Medica , Estándares de Referencia
13.
Physiol Genomics ; 51(5): 137-144, 2019 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-30925123

RESUMEN

Carcass meat yield is an important carcass trait that contributes to the production efficiency and economic benefits in beef cattle. It is therefore critical to identify quantitative trait loci associated with carcass traits to enable selection. Our previous studies have identified several causal variants within the pleomorphic adenoma gene 1 (PLAG1) and coiled-coil-helix-coiled-coil-helix domain-containing 7 (CHCHD7) genes on BTA14 for carcass traits in Chinese Simmental. In the current study, we carried out a genome-wide association study for carcass meat yield in 472 Wagyu cattle with Bovine HD SNP array. Our results showed that 27 single nucleotide polymorphisms (SNPs) were identified for tenderloin weight (TDW), striploin weight (SPW), chuck roll weight (CRW), bicep weight (BPW), knuckle weight (KCW), and flank steak weight (FSW) in Wagyu cattle. Of these SNPs, 10 distinct SNPs were detected within the oxidation resistance 1 (OXR1), fatty acid binding protein 5 (FABP5), TNF receptor superfamily member 11b (TNFRSF11B), and zinc finger CCCH-type containing 3 (ZC3H3) genes on BTA14. Notably, three significant SNPs, BovineHD1400016738, BovineHD1400016743, and BovineHD1400016665 within OXR1, were shown strong linkage disequilibrium (r2 > 0.8) and significantly associated with CRW (P = 1.37 × 10-8 ~ 1.94 × 10-8). Moreover, Ingenuity Pathway Analysis showed that OXR1, FABP5, and CAP1A genes were involved in a single network and FABP5 may regulate the expression of OXR1 gene via node gene, peroxisome proliferator-activated receptor gamma (PPARG). Overall, this study suggests that OXR1 and FABP5 are candidate genes affecting carcass traits in Wagyu and the PLAG1-OXR1 region on BTA14 as a putative susceptibility locus for carcass meat yield for both Chinese Simmental and Wagyu.


Asunto(s)
Estudio de Asociación del Genoma Completo/métodos , Carne , Sitios de Carácter Cuantitativo/genética , Peso Corporal/genética , Peso Corporal/fisiología , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Genotipo , Humanos , Desequilibrio de Ligamiento/genética , Proteínas Mitocondriales/genética , Proteínas Mitocondriales/metabolismo , Fenotipo , Polimorfismo de Nucleótido Simple/genética
14.
J Bioenerg Biomembr ; 51(3): 239-248, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-31062127

RESUMEN

Hypoxia inducible factor-1α (HIF-1α) plays a central role in cell survival, invasion, metastasis and angiogenesis, and also is emerging as an important target in anti-cancer drug discovery. In the present study, bishonokiol A, a dimeric neolignan isolated from Magnolia grandiflora, was identified as a novel HIF-1α inhibitor. We here demonstrated that in a dose-dependent manner, bishonokiol A inhibited metastasis-related cell invasion and migration of cobalt chloride (CoCl2)-induced MCF-7 and MDA-MB-231 cells, associating with the reduction in HIF-1α levels. Transfection of MDA-MB-231 cells with HIF-1α small interfering ribonucleic acid (siRNA) resulted in a reduction in cell invasion and migration. Furthermore, we found that bishonokiol A not only inhibited the synthesis of HIF-1α protein and protein kinase B (AKT-473) phosphorylation without affecting the expression of HIF-1α mRNA or ubiquitination degradation, but also inhibited the expression of matrix metalloproteinase-9 (MMP-9) and promoter activity. Nude mice bearing MDA-MB-231 cells incubation were treated with bishonokiol A and results showed that bishonokiol A exhibited potent antitumor activity and low toxicity. Therefore, we suggest that bishonokiol A may be a potential inhibitor of HIF-1α and effective antitumor agent for breast cancer.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Movimiento Celular/efectos de los fármacos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Lignanos/farmacología , Proteínas de Neoplasias/metabolismo , Animales , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Femenino , Humanos , Células MCF-7 , Ratones , Ratones Desnudos , Invasividad Neoplásica , Ensayos Antitumor por Modelo de Xenoinjerto
15.
Entropy (Basel) ; 21(7)2019 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-33267364

RESUMEN

A complete quantum cooling cycle may be a useful platform for studying quantum thermodynamics just as the quantum heat engine does. Entropy change is an important feature which can help us to investigate the thermodynamic properties of the single ion cooling process. Here, we analyze the entropy change of the ion and laser field in the single ion cooling cycle by generalizing the idea in Reference (Phys. Rev. Lett. 2015, 114, 043002) to a single ion system. Thermodynamic properties of the single ion cooling process are discussed and it is shown that the Second and Third Laws of Thermodynamics are still strictly held in the quantum cooling process. Our results suggest that quantum cooling cycles are also candidates for the investigation on quantum thermodynamics besides quantum heat engines.

16.
Physiol Genomics ; 50(7): 523-531, 2018 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-29676954

RESUMEN

Cattle internal organs as accessible raw materials have a long history of being widely used in beef processing, feed and pharmaceutical industry. These traits not only are of economic interest to breeders, but they are intrinsically linked to many valuable traits, such as growth, health, and productivity. Using the Illumina Bovine HD 770K SNP array, we performed a genome-wide association study for heart weight, liver weight, spleen weight, lung weight, and kidney weight in 1,217 Simmental cattle. In our research, 38 significant single nucleotide polymorphisms (SNPs) ( P < 1.49 × 10-6) were identified for five internal organ weight traits. These SNPs are within or near 13 genes, and some of them have been reported previously, including NDUFAF4, LCORL, BT.94996, SLIT2, FAM184B, LAP3, BBS12, MECOM, CD300LF, HSD17B3, TLR4, MXI1, and MB21D2. In addition, we detected four haplotype blocks on BTA6 containing 18 significant SNPs associated with spleen weight. Our results offer worthy insights into understanding the genetic mechanisms of internal organs' development, with potential application in breeding programs of Simmental beef cattle.


Asunto(s)
Bovinos/genética , Estudio de Asociación del Genoma Completo/métodos , Polimorfismo de Nucleótido Simple , Sitios de Carácter Cuantitativo/genética , Carne Roja , Animales , Cruzamiento/métodos , Bovinos/fisiología , Haplotipos , Corazón/crecimiento & desarrollo , Riñón/crecimiento & desarrollo , Hígado/crecimiento & desarrollo , Pulmón/crecimiento & desarrollo , Tamaño de los Órganos/genética , Bazo/crecimiento & desarrollo
17.
Microb Pathog ; 125: 246-251, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30243550

RESUMEN

As a typical Gram-positive microorganism, S. aureus was recognized as common foodborne pathogenic bacteria in food industry. To study their individuality and pathogenicity mechanism, thirty-three Staphylococci strains were applied to the investigation with the identification of MRSA by PCR targeting on S. aureus specific 16S rRNA and femA genes as well as methicillin-resistant mecA and orfX elements by multiplex-PCR assay. Fingerprinting mapping was then employed using three typing systems (KZ/M13, IS256 and ERIC2) to genotype 33 MRSA strains. As the result indicated, all 33 Staphylococci strains were identified as MRSA. However, diversity occurred among different fingerprinting system results. KZ/M13 system and IS256 system both typed 10 genotypes while ERIC2 system had 8 genotypes. Based on the genotyping results, a discussion was performed in typing ability, discriminatory ability and accordance ratio. Given the above studies, a novel rapid detection method for MRSA was conducted with multiplex-PCR, which possessed rapidity and accuracy. Meanwhile, three fingerprinting systems showed high sensitivity, resolution and classification ratio in MRSA typing. These methods have a broad application prospect in food safety and epidemiology in the future.


Asunto(s)
Dermatoglifia del ADN/métodos , Variación Genética , Técnicas de Genotipaje/métodos , Staphylococcus aureus Resistente a Meticilina/clasificación , Staphylococcus aureus Resistente a Meticilina/genética , Tipificación Molecular/métodos , Proteínas Bacterianas/genética , Genotipo , Reacción en Cadena de la Polimerasa Multiplex , ARN Ribosómico 16S/genética
18.
Zhongguo Zhong Yao Za Zhi ; 43(11): 2216-2223, 2018 Jun.
Artículo en Zh | MEDLINE | ID: mdl-29945370

RESUMEN

Spatholobi Caulis, the vine stem of Spatholobus suberectus and widely used in China and Southeast Asian nations, has the effects on nourishing the blood and promoting blood flow, regulating menstruation and relieving pain, and invigorating the nerves. Through consulting the herbal textual and local chronicles, we summarized the original textual research and medicinal evolution on Spatholobi Caulis to analyze the changes of varieties in different historical periods. Further, the major active ingredient in Spatholobi Caulis was discussed. According to the literature to date, 60 flavonoids compounds have been isolated and could be divided into isoflavones, dihydroflavones, flavanols, dihydroflavonols, procyaninides, chalcones, pterocarpans, isoflavanols, isoflavanones and aurone according to their molecular structures. These indicative ingredients in Spatholobi Caulis showed pharmacological activities on regulation of the blood system, anti-tumor, anti-oxidation, anti-virus, anti-bacteria and inhibition of melanin deposition. This review will provide reference and basis for the sustainable use of resources and industry development on Spatholobi Caulis.


Asunto(s)
Medicamentos Herbarios Chinos/farmacología , Fabaceae/química , Flavonoides/análisis , China , Humanos , Tallos de la Planta/química
19.
Microb Pathog ; 107: 397-403, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28414166

RESUMEN

Staphylococcus aureus is recognized as a typical food-born pathogen in food safety, and its rapid detection and typing methods are in desperate need. To study their evolution characteristics and drug resistance condition, Staphylococci isolates were subject to the investigation. Strain identification were subjected to standard procedures (colony morphology, Gram staining, Vitek 2 automated system and the API commercial kit), and fingerprinting was then performed with RAPD-PCR amplification. In this study, 179 isolated staphylococci were identified as MRSA. In addition, Staphylococci isolates were subjected to three different fingerprinting system (ERIC2, AP1 and AP7) and then genotyped based on significant diversities. Nosocomial epidemiology was then conducted according to the fingerprint result. To sum up, the RAPD method subjected for MRSA rapid genotyping have a broad application prospect in food safety and epidemiology.


Asunto(s)
Infección Hospitalaria/epidemiología , Genotipo , Staphylococcus aureus Resistente a Meticilina/genética , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Epidemiología Molecular , Infecciones Estafilocócicas/epidemiología , Técnicas de Tipificación Bacteriana , China/epidemiología , Dermatoglifia del ADN/métodos , ADN Bacteriano , Inocuidad de los Alimentos , Genoma Bacteriano , Humanos , Staphylococcus aureus Resistente a Meticilina/patogenicidad , Tipificación de Secuencias Multilocus , Técnica del ADN Polimorfo Amplificado Aleatorio/métodos
20.
Microb Pathog ; 107: 17-28, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28284852

RESUMEN

Methicillin-resistant Staphylococcus aureus (MRSA) is a common pathogen in hospitals and the community. As the rapid spread and wide distribution of antimicrobial resistance (such as MRSA), treatment for infectious diseases caused by microorganisms has become a vital threat. Thus, early identification and genotyping are essential for further therapeutic treatment and the control of rapid expansion of MRSA. In combination with applications and data feedbacks, this review focused on the currently available molecular-based assays on their utility and performance for rapid typing of MRSA, especially on effective molecular-based methods. Besides, a common mobile element SCCmec and prevalence of HA-MRSA, LA-MRSA and CA-MRSA were introduced in this review in order to provide a more complete profile of MRSA.


Asunto(s)
Técnicas de Tipificación Bacteriana/métodos , Infección Hospitalaria/microbiología , Genotipo , Técnicas de Genotipaje/métodos , Staphylococcus aureus Resistente a Meticilina/genética , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Infecciones Estafilocócicas/microbiología , Análisis del Polimorfismo de Longitud de Fragmentos Amplificados/métodos , Antígenos Bacterianos/genética , Proteínas Bacterianas/genética , Técnicas de Tipificación Bacteriana/instrumentación , Coagulasa/genética , Infección Hospitalaria/diagnóstico , Electroforesis en Gel de Campo Pulsado/métodos , Técnicas de Genotipaje/instrumentación , Humanos , Staphylococcus aureus Resistente a Meticilina/clasificación , Tipificación de Secuencias Multilocus/métodos , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Proteínas de Unión a las Penicilinas/genética , Polimorfismo Genético , Polimorfismo de Longitud del Fragmento de Restricción , Técnica del ADN Polimorfo Amplificado Aleatorio/métodos , Infecciones Estafilocócicas/diagnóstico , Transactivadores/genética
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