RESUMO
BACKGROUND: An outbreak of infection caused by SARS-CoV-2 recently has brought a great challenge to public health. Rapid identification of immune epitopes would be an efficient way to screen the candidates for vaccine development at the time of pandemic. This study aimed to predict the protective epitopes with bioinformatics methods and resources for vaccine development. METHODS: The genome sequence and protein sequences of SARS-CoV-2 were retrieved from the National Center for Biotechnology Information (NCBI) database. ABCpred and BepiPred servers were utilized for sequential B-cell epitope analysis. Discontinuous B-cell epitopes were predicted via DiscoTope 2.0 program. IEDB server was utilized for HLA-1 and HLA-2 binding peptides computation. Surface accessibility, antigenicity, and other important features of forecasted epitopes were characterized for immunogen potential evaluation. RESULTS: A total of 63 sequential B-cell epitopes on spike protein were predicted and 4 peptides (Spike315-324, Spike333-338, Spike648-663, Spike1064-1079) exhibited high antigenicity score and good surface accessibility. Ten residues within spike protein (Gly496, Glu498, Pro499, Thr500, Leu1141, Gln1142, Pro1143, Glu1144, Leu1145, Asp1146) are forecasted as components of discontinuous B-cell epitopes. The bioinformatics analysis of HLA binding peptides within nucleocapsid protein produced 81 and 64 peptides being able to bind MHC class I and MHC class II molecules respectively. The peptides (Nucleocapsid66-75, Nucleocapsid104-112) were predicted to bind a wide spectrum of both HLA-1 and HLA-2 molecules. CONCLUSIONS: B-cell epitopes on spike protein and T-cell epitopes within nucleocapsid protein were identified and recommended for developing a protective vaccine against SARS-CoV-2.
Assuntos
Betacoronavirus/genética , Betacoronavirus/imunologia , Biologia Computacional/métodos , Infecções por Coronavirus/prevenção & controle , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito T/imunologia , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinas Virais/imunologia , Sequência de Aminoácidos , COVID-19 , Vacinas contra COVID-19 , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Desenho de Fármacos , Epitopos de Linfócito B/química , Epitopos de Linfócito T/química , Humanos , Imunogenicidade da Vacina/imunologia , Modelos Moleculares , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , SARS-CoV-2 , Alinhamento de Sequência , Análise de Sequência , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Proteínas do Envelope Viral/imunologiaRESUMO
Background: Yanghe Huayan Decoction (YHD), a traditional Chinese medicine, is one of the most common complementary medicine currently used in the treatment of breast cancer (BC). It has been recently linked to suppress precancerous lesion and tumor development. The current study sought to explore the role of YHD on trans-endothelium and angiogenesis of BC. Methods: HER2+ BC cells were treated with YHD, Trastuzumab, or the combination in vitro and in vivo to compare the effects of them on trans-endothelium and angiogenesis features. The present study also investigated the potential molecular mechanism of YHD in inhibiting angiogenesis of BC. Results: YHD significantly suppressed the invasion and angiogenesis of BC cells via elevated pAkt signaling. Administration of YHD in vivo also strikingly repressed angiogenesis in tumor grafts. Conclusion: YHD could partially inhibit and reverse tumorigenesis of BC. It also could inhibit Akt activation and angiogenesis in vitro and in vivo Its effect was superior to trastuzumab. Thus it was suitable for prevention and treatment of BC.
Assuntos
Inibidores da Angiogênese/farmacologia , Neoplasias da Mama/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Neovascularização Patológica/tratamento farmacológico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Inibidores da Angiogênese/administração & dosagem , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias da Mama/irrigação sanguínea , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Medicamentos de Ervas Chinesas/administração & dosagem , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/patologia , Feminino , Células Endoteliais da Veia Umbilical Humana , Humanos , Camundongos Nus , Receptor ErbB-2/metabolismo , Trastuzumab/administração & dosagem , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVE: To explore the effect of Yanghe Huayan Decoction (YHD, a representative recipe for warming yang mass dissipating) in inhibiting precancerosis of breast cancer (PBC) and on the protein and mRNA expression of ki67. METHODS: The PBC rat model was established by dimethylbenzanthracene (DMBA), and 9 weeks later rats were randomly divided into the blank control group, the model group, the YHD group, the Sanjie Huatan Decoction group (SHD), the Pingxiao Tablet group (PT), and the tamoxifen group. Rats in the model group were administered with water by gastrogavage. Rats in the YHD group received YHD (deglued antler powder 12 g, prepared rhizome of rehmannia 9 g, cassia bark 6 g, white mustard seed 3 g, zedoary root 12 g, appendiculate cremastra pseudobulb 15 g, chekiang fritillary bulb 9 g, licorice root 6 g) at the daily dose of 7.2 g/kg by gastrogavage. Rats in the SHD group received SHD (oldenlandia diffusa 15 g, Scutellaria Barbata 15 g, Trichosanthes Kirilowii 15 g, pinellia 9 g) at the daily dose of 5.4 g/kg by gastrogavage. Rats in the PT group received PT at the daily dose of 144 mg/kg by gastrogavage. Those in the tamoxifen group received tamoxifen at the daily dose of 4 mg/kg by gastrogavage. Pathomorphological changes of the breast tissue were observed by HE staining. The positive rate and the gray value of ki67 expression were detected by immunohistochemical assay. And the expression of ki67 mRNA was detected by q-PCR. RESULTS: Compared with the model group, the general hyperplasia and the occurrence rate of precancerous lesion were higher and the occurrence rate of invasive carcinoma was lower in each treatment group (P < 0.05). Except the SHD group, the intensity of ki67 grey value increased in each treatment group (P < 0.05, P < 0.01). Except the PT group, the positive rate of ki67 and mRNA expression of ki67 increased in the rest treatment groups (P < 0.05, P < 0.01). Compared with the YHD group, there was no statistical difference in the occurrence rate of infiltration or the occurrence rate of precancerous lesion (P > 0.05). The positive rate of ki67 expression and mRNA expression of ki67 increased in the PT group, showing statistical difference (P < 0.05). CONCLUSIONS: YHD could partially inhibit and reverse canceration of breast cancer. It also could inhibit ki67 protein and mRNA expression. Its effect was similar to tamoxifen and superior to PT. So it was suitable for prevention and treatment of precancerous lesion of breast cancer.
Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Antígeno Ki-67/metabolismo , Neoplasias Mamárias Experimentais/tratamento farmacológico , Lesões Pré-Cancerosas/tratamento farmacológico , Animais , Modelos Animais de Doenças , Feminino , Neoplasias Mamárias Experimentais/induzido quimicamente , Neoplasias Mamárias Experimentais/metabolismo , Lesões Pré-Cancerosas/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
Different levels (0, 90, 180, and 270 g per tree) of compound fertilizer containing 15% N, 15% P2O5, and 15% K2O were applied to young Eucalyptus grandis to study the diurnal variations of its leaf stomatal conductance (Gs), intercellular CO2 concentration (Ci), net photosynthesis rate (Pn), transpiration rate (Tr), water use efficiency (WUE), and vapor pressure deficit on leaf surface (Vpdl) as well as the variation of leaf chlorophyll content, aimed to approach the relationships of E. grandis photosynthesis with fertilization and environmental factors. In all treatments, the diurnal variation of Pn presented a single-peak curve, with the peak at 14:00 and not showing midday depression. The Gs, Tr, and Vpdl showed the similar trend with Pn, while the Ci had a minimum value at 14:00. The WUE demonstrated a double-peak curve, with the first and second peak occurred at 10:00 and 14:00, respectively. Comparing with the control, the mean values of Gs, Pn, Tr, WUE, and chlorophyll a, chlorophyll b, and total chlorophyll contents under fertilization increased by 4.6%-15.9%, 7.8%-21.8%, 4.8%-11.6%, 3.2%-8.8%, 15.5%-62.0%, 14.5%-44.5% and 15.3%-57.1%, respectively, and the increment increased with fertilization level. By contrast, the mean values of Ci and VPdl decreased by 14.5%-44.5% and 15.3%-57.1%, respectively, and the decrement increased with fertilization level. The Gs, Pn, and Tr were significantly correlated with air temperature, relative humidity (RH), and photosynthetic active radiation (PAR), and also, the Gs was significantly correlated with Pn and Tr. It was suggested that fertilization could promote E. grandis growth and enhance its WUE and biological carbon sequestration, and air temperature, RH, PAR, and Gs were the main factors causing the diurnal variations of photosynthesis and transpiration of E. grandis.