RESUMO
Transforming growth factor-ß (TGF-ß) and heat shock protein 70 (HSP70) are important for the hair follicle (HF) cycle, but it is unclear whether they participate in HF regression in yak skin. In this study, we investigated the role of TGF-ß, TGF-ßRII, and HSP70 in the transition from anagen to catagen of HFs. The results showed that TGF-ß2 transcription was significantly higher than that of TGF-ß1 and TGF-ß3 in the same periods. Meanwhile, the expressions of TGF-ß2, TGF-ßRII, and caspase-3 were higher in the catagen phase than that in mid-anagen, and some TGF-ßRII-positive HF cells were terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL)-positive. Moreover, the HSP70 protein levels in mid-anagen were higher than those in late-anagen and catagen. These results suggested that TGF-ß2 plays a major role in catagen induction in yak HFs, which might be achieved via TGF-ßRII-mediated apoptosis in HF epithelial cells. In contrast, HSP70 might protect epithelial cells from apoptosis and ultimately inhibit HF regression. In conclusion, TGF-ß2 has positive effects, whereas HSP70 has negative effects, on catagen induction.
RESUMO
Bone morphogenetic protein 2 (BMP2), BMP receptor-IA (BMPR-IA), and the BMP2 antagonist Noggin are important proteins involved in regulating the hair follicle (HF) cycle in skin. In order to explore the expression profiles of BMP2, BMPR-IA, and Noggin in the HF cycle of yak skin, we collected adult yak skin in the telogen, proanagen, and midanagen phases of HFs and evaluated gene and protein expression by real-time quantitative polymerase chain reaction (qRT-PCR), western blotting, and immunohistochemistry. qRT-PCR and western blotting results showed that BMP2 and BMPR-IA expression levels were highest in the telogen of HFs and higher than that of Noggin in the same phase. The expression of Noggin was significantly higher in proanagen and midanagen phases of HFs than in the telogen phase, with the highest expression observed in the proanagen phase. Moreover, the expression of Noggin in the proanagen phase was significantly higher than those of BMP2 and BMPR-IA during the same phase. Immunohistochemistry results showed that BMP2, BMPR-IA, and Noggin were expressed in the skin epidermis, sweat glands, sebaceous glands, HF outer root sheath, and hair matrix. In summary, the characteristic expression profiles of BMP2, BMPR-IA, and Noggin suggested that BMP2 and BMPR-IA had inhibitory effects on the growth of HFs in yaks, whereas Noggin promoted the growth of yak HFs, mainly by affecting skin epithelial cell activity. These results provide a basis for further studies of HF development and cycle transition in yak skin.
Assuntos
Proteína Morfogenética Óssea 2/genética , Receptores de Proteínas Morfogenéticas Ósseas Tipo I/genética , Proteínas de Transporte/genética , Bovinos/genética , Folículo Piloso/crescimento & desenvolvimento , Folículo Piloso/metabolismo , Pele/metabolismo , Animais , Western Blotting , Proteína Morfogenética Óssea 2/metabolismo , Receptores de Proteínas Morfogenéticas Ósseas Tipo I/metabolismo , Proteínas de Transporte/metabolismo , Bovinos/metabolismo , Feminino , Perfilação da Expressão Gênica , Imuno-Histoquímica , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
The asymmetric unit of the title compound, C(20)H(16)ClN(3)S, contains two independent mol-ecules, A and B. In mol-ecule A, the dihedral angles between the central benzene ring and the pendant chloro-benzene and phenyl rings are 6.37â (15) and 64.79â (15)°, respectively. The corresponding values in mol-ecule B are 28.21â (14) and 82.11â (16)°, respectively. Each mol-ecule features an intra-molecular N-Hâ¯N hydrogen bond, which generates an S(5) ring. In the crystal, mol-ecules A and B form dimers, being linked by two N-Hâ¯S hydrogen bonds with graph-set notation R(2) (2)(8).
RESUMO
The title compound, C(10)H(11)I(2)NO, was prepared by the reaction of 3,5-diiodo-salicyl-aldehyde with propyl-amine in ethanol. The mol-ecule adopts an E conformation with respect to the C=N bond and the aromatic ring. The aromatic ring and the imino unit are close to being coplanar, with a dihedral angle of 2.6â (3)° between their planes. This planarity is assisted by the formation of an intra-molecular O-Hâ¯O hydrogen bond.
RESUMO
Two series of thiazolidinone derivatives designing for potential EGFR and HER-2 kinase inhibitors have been discovered. Some of them exhibited significant EGFR and HER-2 inhibitory activity. Compound 2-(2-(5-bromo-2-hydroxybenzylidene)hydrazinyl)thiazol-4(5H)-one (12) displayed the most potent inhibitory activity (IC(50)=0.09 microM for EGFR and IC(50)=0.42 microM for HER-2), comparable to the positive control erlotinib. Docking simulation was performed to position compound 12 into the EGFR active site to determine the probable binding model. Antiproliferative assay results indicating that some of the thiazolidinone derivatives own high antiproliferative activity against MCF-7. Compound 12 with potent inhibitory activity in tumor growth inhibition would be a potential anticancer agent.
Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Receptores ErbB/antagonistas & inibidores , Receptor ErbB-2/antagonistas & inibidores , Tiazolidinas/química , Tiazolidinas/farmacologia , Antineoplásicos/síntese química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Receptores ErbB/química , Receptores ErbB/metabolismo , Humanos , Modelos Moleculares , Neoplasias/tratamento farmacológico , Ligação Proteica , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Receptor ErbB-2/metabolismo , Relação Estrutura-Atividade , Tiazolidinas/síntese químicaRESUMO
As a naturally wide distributed flavone, chrysin exhibits numerous biological activities including anticancer, anti-inflammatory, and antimicrobials activities. Beta-ketoacyl-acyl carrier protein synthase III (FabH) catalyzes the initial step of fatty acid biosynthesis via a type II fatty acid synthase in most bacteria. The important role of this essential enzyme combined with its unique structural features and ubiquitous occurrence in bacteria has made it an attractive new target for the development of antibacterial agents. We first used a structure-based approach to develop 18 novel chrysin analogues that target FabH for the development of new antibiotics. Structure-based design methods were used for the expansion of the chrysin derivatives including molecular docking and SAR research. Based on the results, 5-hydroxy-2-phenyl-7-(2-(piperazin-1-yl)ethoxy)-4H-chromen-4-one (3g) showed the most potent antibacterial activity with MIC of 1.56-6.25 microg/mL against the test bacterial stains, and docking simulation was performed to position compound 3g into the Escherichia coli FabH active site to determine the probable binding conformation. The biological assays indicated that compound 3g is a potent inhibitor of E.coli FabH as antibiotics.
Assuntos
3-Oxoacil-(Proteína de Transporte de Acila) Sintase/antagonistas & inibidores , Antibacterianos/síntese química , Inibidores Enzimáticos/síntese química , Flavonoides/química , 3-Oxoacil-(Proteína de Transporte de Acila) Sintase/metabolismo , Antibacterianos/química , Antibacterianos/farmacologia , Sítios de Ligação , Simulação por Computador , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Escherichia coli/enzimologia , Flavonoides/síntese química , Flavonoides/farmacologia , Testes de Sensibilidade Microbiana , Relação Estrutura-AtividadeRESUMO
This study aimed to describe the morphology, expression of IgA and IgG in adult yak tonsils. The 12 clinically healthy yak tonsils [3- to 6-year old, n = 12] were examined for morphology using light, and transmission electron microscopes. Expression of IgA and IgG was measured by qRT-PCR, ELISA, and immunohistochemistry. The results showed that the palatine tonsil, the tonsil of the soft palate, and the lingual tonsil were oropharyngeal tonsils. The stratified squamous epithelia covering them had a thick underlying layer of connective tissue and their crypts were heavily infiltrated by lymphocytes. The pharyngeal tonsil and the tubal tonsil were nasopharyngeal tonsils. The epithelia of them was predominantly pseudostratified columnar ciliary epithelium, which were loosely arranged with a number of desmosomes or intermediate junctions variably connecting them. The expression levels of IgA and IgG mRNA and protein from high to low was in the pharyngeal tonsil, palatine tonsil, tonsil of the soft palate, lingual tonsil, and tubal tonsil, respectively. Interestingly, the expression of IgG was very significantly higher than that of IgA in yak tonsils (P < 0.01). Both the IgA and IgG ASCs were distributed in the subepithelial areas of the non-reticular crypt epithelium, especially areas of pseudostratified columnar ciliary epithelium, the reticular crypt epithelium, lymphoid follicles, interfollicular areas, and with some of the positive cells aggregating around the glands. The results indicated that the tonsils were not only typical secondary lymphoid organs but also lymphoepithelial structures. IgG could be a significant component of mucosal immune responses in yak tonsils. Anat Rec, 302:999-1009, 2019. © 2018 Wiley Periodicals, Inc.
Assuntos
Bovinos/imunologia , Imunidade nas Mucosas , Imunoglobulina A/metabolismo , Imunoglobulina G/metabolismo , Tonsila Palatina/imunologia , Animais , Bovinos/anatomia & histologia , Epitélio/imunologia , Epitélio/metabolismo , Epitélio/ultraestrutura , Feminino , Imunoglobulina A/imunologia , Imunoglobulina G/imunologia , Linfócitos/imunologia , Linfócitos/metabolismo , Masculino , Microscopia Eletrônica de Transmissão , Palato Mole/citologia , Palato Mole/imunologia , Palato Mole/metabolismo , Palato Mole/ultraestrutura , Tonsila Palatina/citologia , Tonsila Palatina/metabolismo , Tonsila Palatina/ultraestrutura , Língua/citologia , Língua/imunologia , Língua/metabolismo , Língua/ultraestruturaRESUMO
Metal-organic frameworks (MOFs) as novel electrode materials have attracted intensive attention; however, low electronic conductivity hinders their practical application in lithium ion batteries (LIBs). This work reports the synthesis of conductive MOF/CNT composites with enhanced electrochemical reactivity. The growth mechanism of the pristine MOF and the correlations of two components are investigated from the viewpoint of crystal engineering. The time dependent morphology evolution experiment reveals that [Ni3(HCOO)6] undergoes an 'aggregation-based nucleation-growth' mechanism. As a result, [Ni3(HCOO)6]/CNT microsized ellipsoidal particles are controllably synthesized by tuning the reaction time and the reagent concentration, where CNTs penetrate the entire particles thoroughly. The obtained [Ni3(HCOO)6]/CNT composites exhibit significantly enhanced electrochemical activity in comparison with the as-synthesized pristine [Ni3(HCOO)6]. This is ascribed to the effective 3D conductive network constructed by CNTs. Our results provide an effective synthetic strategy to construct conductive MOF/CNT composites, which pave the way for developing other conductive MOFs for electrode materials.
RESUMO
Indolizine and annulated indolizine derivatives incorporating a cyclopropylcarbonyl group were synthesized in a one pot procedure by the tanden reactions of [3+2] cycloaddition of the corresponding N-ylide with electron deficient alkene. Seventeen indolizine derivatives were reported for the first time. All the compounds were examined for their antiproliferative activity against the human hepatocellular liver carcinoma (Hep-G2) cell line by MTT method. Among the compounds tested, 5a, 5d, 5 g and 5 j showed the most favorable activities with IC(50) values of 0.39, 0.48, 0.29 and 0.20 microg/mL. Especially, compound 5 j displayed potent antiproliferative activities with IC(50) value of 0.20 microg/mL, and showed significant EGFR kinase inhibitory activity with IC(50) value of 0.085 microM. Docking simulations of 5 j were carried out to illustrate the binding mode of the molecular into the EGFR active site.