RESUMO
Chinese medicinal resources are the material basis for the survival and development of traditional Chinese medicine(TCM)and the sustainable development of Chinese medicinal resources is also an important project for the modernization of TCM in China. With the increasing demand for Chinese medicinal resources in China, over-exploitation has destroyed Chinese medicinal resources, resulting in a shortage of many natural medicinal resources in China and making the sustainable development of TCM in trouble. The introduced new foreign medicinal resources have become effective supplement and replacement for Chinese medicinal resources to some extent. However, the development and utilization of new foreign medicinal resources in China are different. To fully understand the development of new foreign medicinal resources in China, this paper, taking 43 new foreign medicinal resources such as Acacia nilotica as objects, sorted out the introduction forms and policies of new foreign medicinal resources, overviewed its current development status in China, summarized the application experience of new foreign medicinal resources in the place of origin, as well as the research progress and problems of new foreign medicinal resources in China and abroad, and analyzed the research situation, which can enrich Chinese medicinal resources and other uses, promote the sustainable development of Chinese medicinal resources, and provide ideas for further development and research of new foreign medicinal resources.
Assuntos
Medicamentos de Ervas Chinesas , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa , Conservação dos Recursos Naturais , Desenvolvimento Sustentável , Internacionalidade , ChinaRESUMO
A sufficiently stable noncovalent association complex between a covalent inhibitor and its protein target is regarded as a prerequisite for the formation of a covalent complex. As this transient form can hardly be assessed experimentally, computational modeling is required to probe the suitability of a given ligand at this particular stage. To investigate which criteria should be fulfilled by suitable candidates in a molecular dynamics (MD) assessment, a systematic study was conducted with 20 complexes of cathepsin K, a papain-like cysteine protease of pharmaceutical relevance. The covalent inhibitors in these complexes were converted to their pre-reaction states, and the resulting noncovalent complexes were subjected to MD simulations. The critical distance between the electrophilic and nucleophilic reaction partners was monitored as a potential parameter to assess the suitability for covalent bond formation. Across various warhead types, a distance between 3.6 and 4.0 Å, comparable to the sum of the generalized Born radii of carbon and sulfur, was found to be stably maintained under appropriate conditions. The protonation state of the catalytic dyad and the resulting solvation pattern dramatically affected the noncovalent binding mode and the distance of the warhead to the active site. For several complexes, fluctuations in the orientation of the warhead were observed due to torsional rotations in adjacent bonds. This observation helped to explain the gradual transitions from noncovalent to covalent complexes observed in the crystal structures of three closely related nitrile-based inhibitors. According to comparative simulations conducted for a set of 13 cathepsin S complexes, the overall findings of the study appear to be transferable to related cysteine proteases as targets of covalent inhibitors.
Assuntos
Cisteína Proteases , Simulação de Dinâmica Molecular , Catepsina K , Domínio Catalítico , Calpaína/químicaRESUMO
OBJECTIVE: The aim of this study was to explore the value of contrast-enhanced ultrasound (CEUS) combined with 2-D strain imaging in evaluating carotid plaque vulnerability and the correlations among CEUS perfusion parameters, strain parameters and histopathological findings in different plaque segments. METHODS: Patients with carotid artery stenosis who underwent carotid endarterectomy (CEA) at the First Affiliated Hospital of Xinjiang Medical University from September 2020 to June 2021 underwent preoperative carotid artery 2-D ultrasonography and CEUS. The plaques were divided into three segments: the proximal end of the shoulder, central cap and distal end of the shoulder. The peak intensity (PI) value and strain rate parameters of the regions of interest were analyzed. Plaques were divided into a stable group (8 cases) and an unstable group (19 cases). The microvascular density (MVD) and vascular endothelial growth factor (VEGF) expression of each patch in the unstable group were analyzed. RESULTS: The peak strain during the systolic period in each plaque segment in both groups showed the following pattern: proximal end shoulder > distal end shoulder > top (p < 0.05). The PI value for CEUS is also represented. In the unstable group, the PI values of each segment of the plaque were positively correlated with the MVD, near-center PI value and VEGF average optical density value. The average optical density of each segment was positively correlated with the MVD (p < 0.05). There were positive correlations between the PI values of the proximal and distal shoulder and the strain values (p < 0.05), and the MVD value of each segment, VEGF value and strain value were positively correlated (p < 0.05). CONCLUSION: PI and the pathological tissue components represented by CEUS were positively correlated with the mechanical parameters of the plaque along the long axis. There may be overlap between the high shear stress area of the plaque and the neovascular aggregation area, and the combination of the two has certain significance for assessing the vulnerability of the plaque.
Assuntos
Estenose das Carótidas , Endarterectomia das Carótidas , Placa Aterosclerótica , Humanos , Fator A de Crescimento do Endotélio Vascular , Meios de Contraste , Artérias Carótidas/diagnóstico por imagem , Artérias Carótidas/patologia , Ultrassonografia , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/patologia , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/patologia , Neovascularização PatológicaRESUMO
Pancreatic ductal adenocarcinoma (PDAC) has been classified into classical and basal-like transcriptional subtypes by bulk RNA measurements. However, recent work has uncovered greater complexity to transcriptional subtypes than was initially appreciated using bulk RNA expression profiling. To provide a deeper understanding of PDAC subtypes, we developed a multiplex immunofluorescence (mIF) pipeline that quantifies protein expression of six PDAC subtype markers (CLDN18.2, TFF1, GATA6, KRT17, KRT5, and S100A2) and permits spatially resolved, single-cell interrogation of pancreatic tumors from resection specimens and core needle biopsies. Both primary and metastatic tumors displayed striking intratumoral subtype heterogeneity that was associated with patient outcomes, existed at the scale of individual glands, and was significantly reduced in patient-derived organoid cultures. Tumor cells co-expressing classical and basal markers were present in > 90% of tumors, existed on a basal-classical polarization continuum, and were enriched in tumors containing a greater admixture of basal and classical cell populations. Cell-cell neighbor analyses within tumor glands further suggested that co-expressor cells may represent an intermediate state between expression subtype poles. The extensive intratumoral heterogeneity identified through this clinically applicable mIF pipeline may inform prognosis and treatment selection for patients with PDAC. SIGNIFICANCE: A high-throughput pipeline using multiplex immunofluorescence in pancreatic cancer reveals striking expression subtype intratumoral heterogeneity with implications for therapy selection and identifies co-expressor cells that may serve as intermediates during subtype switching.