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Glucagon-like peptide-1 ( GLP-1 ) is secreted by gut enteroendocrine cells. GLP-1 receptor agonists ( GLP-1 RAs) control glucose-related augmentation of insulin and suppress glu-cagon secretion. GLP-lRAs also inhibit gastric emptying, food intake and limit weight gain. In the past decade, significant progresses have been made in the investigation on the effects of GLP-1 RAs on cardiovascular system. The potential advantages of oral small-molecule GLP-1 RAs could improve the application of this class of drugs. This review highlights the multiple cardiovascular profiles of GLP-1 RAs in the treatment of cardiovascular diseases to provide new insights into cardiovascular benefits of GLP-1 RAs.
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Purpose@#Gastric cancer (GC) is the second most lethal cancer globally and is associated with poor prognosis. Fatty acid-binding proteins (FABPs) can regulate biological properties of carcinoma cells. FABP5 is overexpressed in many types of cancers; however, the role and mechanisms of action of FABP5 in GC remain unclear. In this study, we aimed to evaluate the clinical and biological functions of FABP5 in GC. @*Materials and Methods@#We assessed FABP5 expression using immunohistochemical analysis in 79 patients with GC and evaluated its biological functions following in vitro and in vivo ectopic expression. FABP5 targets relevant to GC progression were determined using RNA sequencing (RNA-seq). @*Results@#Elevated FABP5 expression was closely associated with poor outcomes, and ectopic expression of FABP5 promoted proliferation, invasion, migration, and carcinogenicity of GC cells, thus suggesting its potential tumor-promoting role in GC. Additionally, RNA-seq analysis indicated that FABP5 activates immune-related pathways, including cytokinecytokine receptor interaction pathways, interleukin-17 signaling, and tumor necrosis factor signaling, suggesting an important rationale for the possible development of therapies that combine FABP5-targeted drugs with immunotherapeutics. @*Conclusions@#These findings highlight the biological mechanisms and clinical implications of FABP5 in GC and suggest its potential as an adverse prognostic factor and/or therapeutic target.
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Aim To establish a high-throughput screening cell model for GLP-1 receptor agonists. Methods A pEGFP-GLP-1R-3 C recombinant plasmid was constructed and transfected into HEK293T cells. The cells were screened with G418 and flow cytometry. The established stable cell line was named HEK293TGLP-lR-3C-eGFP cell line. The expression level of GLP-1 R-3C-eGFP protein was confirmed by Western blotting and laser confocal microscopy. Then cyclic adenosine monophosphate (cAMP) response element reporter gene was transfected into the HEK293T-GLP-lR-3C-eGFP cells. The luminescence values were detected by One-Step Luciferase Reporter Gene Assay Kit after stimulation with different concentrations of GLP-1 peptide. The luminescence values reflected the cellular cAMP level, which was verified using the cAMP kit (E L I S A). Results HEK293T-GLP-lR-3C-eGFP cell line was successfully constructed. The relative light unit change trend after stimulation with different concentrations of GLP-1 was similar to that of the cellular cAMP level change trend. The value of Z' in this experiment was 0.52. Conclusions A recombinant HEK293T cell line is established, which can be used for high-throughput screening of GLP-1 receptor agonists.
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Dicarabrols B and C (1 and 2), two new carabrane sesquiterpenoid dimers, along with one new carabrane sesquiterpenoid (3) were isolated from the whole plant of Carpesium abrotanoides L. Their full structures were established by extensive analysis of HR-ESI-MS and NMR spectroscopic data, and time-dependent density functional theory (TDDFT) electronic circular dichroism (ECD) calculations. Dicarabrol B possesses a novel C
Subject(s)
Humans , Asteraceae , Circular Dichroism , Molecular Structure , SesquiterpenesABSTRACT
A phytochemical investigation was carried out on the extract of a medicinal plant Callicarpa nudiflora, resulting in the characterization of five new 3, 4-seco-isopimarane (1-5) and one new 3, 4-seco-pimarane diterpenoid (6), together with four known compounds. The structures of the new compounds were fully elucidated by extensive analysis of MS, 1D and 2D NMR spectroscopic data, and time-dependent density functional theory (TDDFT) calculation of electronic circular dichroism (ECD) spectra, and DFT calculations for NMR chemical shifts and optical rotations.
Subject(s)
Abietanes/isolation & purification , Callicarpa/chemistry , Diterpenes/isolation & purification , Molecular Structure , Phytochemicals/isolation & purification , Plant LeavesABSTRACT
A metabolomics method was used to search for chemical markers in prepared slices of Glycyrrhiza uralensis with different degrees of honey processing. Coupled with these metabolomics analytical methods, ultra-performance liquid chromatography with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF/MS) was used to generate global chemical profiles of the raw material of Glycyrrhiza uralensis and the prepared slices. The samples were collected in Shanxi, Hebei Zhangjiakou and Inner Mongolia. A total of 57 chemical components were identified in Glycyrrhiza uralensis by using the UNIFI theoretical database combined with the library of reference samples. Among them, 37 compounds were identified in positive ion mode and 56 compounds were identified in negative ion mode. Unsupervised principal component analysis (PCA) showed that the chemical ingredients differed considerably depending on the extent of processing. Supervised orthogonal partial least squares discriminant analysis (OPLS-DA) was used to differentiate the moderate processing group and the raw group, and partial least squares discriminant analysis (PLS-DA) was used to differentiate the less, the moderate, and the excessive processing groups. The results showed that the contents of glycyrrhizic acid, licoricesaponin G2, and licoricesaponin E2 varied with the extent of processing. The content of these components increased after processing, and reached the highest level when the extent of processing was moderate (P < 0.05). Glycyrrhizic acid, licoricesaponin G2 and licoricesaponin E2 can be regarded as the chemical markers to differentiate the samples with different degrees of processing. These three compounds can be used to monitor the processing of Glycyrrhiza uralensis.
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The main lysosomal protease cathepsin D (cathD) is essential for maintaining tissue homeostasis via its degradative function, and its loss leads to ceroid accumulation in the mammalian nervous system, which results in progressive neurodegeneration. Increasing evidence implies non-proteolytic roles of cathD in regulating various biological processes such as apoptosis, cell proliferation, and migration. Along these lines, we here showed that cathD is required for modulating dendritic architecture in the nervous system independent of its traditional degradative function. Upon cathD depletion, class I and class III arborization (da) neurons in Drosophila larvae exhibited aberrant dendritic morphology, including over-branching, aberrant turning, and elongation defects. Re-introduction of wild-type cathD or its proteolytically-inactive mutant dramatically abolished these morphological defects. Moreover, cathD knockdown also led to dendritic defects in the adult mushroom bodies, suggesting that cathD-mediated processes are required in both the peripheral and central nervous systems. Taken together, our results demonstrate a critical role of cathD in shaping dendritic architecture independent of its proteolytic function.
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Objective To discuss the changes and significance of interleukin-17 (IL-17) in perioperative period of congenital heart disease patients with pulmonary hypertension. Methods A total of forty patients with congenital heart disease underwent cardiopulmonary bypass (CPB) were included in this study. According to the pulmonary artery systolic pressure (PASP), patients were divided into non-pulmonary hypertension group (group Ⅰ, PASP < 30 mmHg) and pulmonary hypertension group (groupⅡ, PASP≥30 mmHg). Blood samples were taken before anesthesia (T1), start CPB (T2), 30 min after CPB (T3), 6 h (T4), 24 h (T5) and 7 d (T6) after operation. The concentration of IL-17 was detected by ELISA. Arterial oxygen partial pressure [p(O2)] and arterial carbon dioxide partial pressure [p(CO2)] during the first five time points were recorded. Oxygen index (OI) and alveolar arterial oxygen tension difference (AaDO2) were calculated. Results The plasma IL-17 levels in perioperative period were significantly higher in group Ⅱ than those of group Ⅰ (P < 0.05). The highest concentration of IL-17 emerged at T3, then decreased gradually in both groups. At this time point, the OI decreased, and AaDO2 increased significantly in both groups. Compared with groupⅠ, the OI decreased, while AaDO2 increased at T5 in groupⅡ(P<0.05). Conclusion The high level of IL-17 promotes the formation of pulmonary hypertension in congenital heart disease and leads to the lung injury during CPB, which can be used as a clinical monitoring indicator of evaluating severity.
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Objective To discuss the changes and significance of interleukin-17 (IL-17) in perioperative period of congenital heart disease patients with pulmonary hypertension. Methods A total of forty patients with congenital heart disease underwent cardiopulmonary bypass (CPB) were included in this study. According to the pulmonary artery systolic pressure (PASP), patients were divided into non-pulmonary hypertension group (group Ⅰ, PASP < 30 mmHg) and pulmonary hypertension group (groupⅡ, PASP≥30 mmHg). Blood samples were taken before anesthesia (T1), start CPB (T2), 30 min after CPB (T3), 6 h (T4), 24 h (T5) and 7 d (T6) after operation. The concentration of IL-17 was detected by ELISA. Arterial oxygen partial pressure [p(O2)] and arterial carbon dioxide partial pressure [p(CO2)] during the first five time points were recorded. Oxygen index (OI) and alveolar arterial oxygen tension difference (AaDO2) were calculated. Results The plasma IL-17 levels in perioperative period were significantly higher in group Ⅱ than those of group Ⅰ (P < 0.05). The highest concentration of IL-17 emerged at T3, then decreased gradually in both groups. At this time point, the OI decreased, and AaDO2 increased significantly in both groups. Compared with groupⅠ, the OI decreased, while AaDO2 increased at T5 in groupⅡ(P<0.05). Conclusion The high level of IL-17 promotes the formation of pulmonary hypertension in congenital heart disease and leads to the lung injury during CPB, which can be used as a clinical monitoring indicator of evaluating severity.