CORD-19:01ceb817f8665ed0047c4675e04b67b199e18832
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/CORD-19/sourceid/01ceb817f8665ed0047c4675e04b67b199e18832","sourcedb":"CORD-19","sourceid":"01ceb817f8665ed0047c4675e04b67b199e18832","text":"Journal Pre-proof The Chinese herbal prescription JZ-1 induces autophagy to protect against herpes simplex Virus-2 in human vaginal epithelial cells by inhibiting the PI3K/Akt/mTOR pathway\n\nAbstract\nThe Chinese herbal prescription JZ-1 induces autophagy to protect against herpes simplex Virus-2 in human vaginal epithelial cells by inhibiting the PI3K/Akt/mTOR pathway, Journal of Ethnopharmacology (2020), doi: https://doi.\n\nGenital herpes is one of the most common, persistent and highly contagious The results were analyzed by the 2 −∆∆CT method with β-actin as an internal control.\nThe sequences of the primers used in this study are listed in Table 2 . anti-p-mTOR, anti-mTOR, anti-gD, anti-ICP5 and anti-β-actin) at 4°C. After washing 267 three times with TBST for 10 min each, the membranes were incubated with 268 secondary antibodies for 1 h at room temperature, washed another three times, and 269 then visualized by an Odyssey Infrared Imaging system (LI-COR Biosciences, USA).\nThe band densities were quantified by ImageJ (National Institutes of Health, USA). All the results are presented as the means ± standard deviation (SD) and were 289 analyzed using SPSS 23.0 software. One-way analysis of variance (ANOVA) and 290 Dunnett's t-test were used to evaluate the significant differences among the groups, 291 and p \u003c 0.05 was considered statistically significant. \nTo determine the appropriate timepoint for the virus infection, we exposed 303 VK2/E6E7 cells to HSV-2 for different duration intervals (6-48 h). The western blot 304 results showed that, compared with that of the control group, the expression of 305 endogenous LC3B-II in the HSV-2-infected cells was increased significantly at each \nThe microtubule-associated protein 1 LC3B is synthesized in the form of the 318 LC3B precursor (pro-LC3B), which is proteolytically processed into the cytosolic 319 LC3B-I isoform. When autophagy is induced, LC3B-I is modified into the Baf+HSV-2-treated group (Fig. 4) , which indicated that JZ-1 induced autophagic flux.\nThe above conclusions were confirmed by an increase in Atg5 in the western blot 382 analysis ( Fig. 4A and C) . Altogether, these data demonstrated that JZ-1 has an 383 anti-HSV-2 effect, which may be related to its induction of autophagic flux. Therefore, Rapa also decreased the release of IFN-α, IFN-β and IL-6, but treatment with 3-MA 413 dramatically increased the secretion levels of these cytokines (Fig. 6A) . The kinase mTOR is a complex of two mTOR components, mTORC1 and 417 mTORC2, which have different protein components (Bhaskar and Hay, 2007) . 418 mTORC1 is a major negative regulator of autophagy, and the PI3K/Akt pathway is a major upstream major modulator of mTORC1 (Schmelzle and Hall, 2000) . To 420 investigate the mechanism by which JZ-1 induces autophagy, we assessed the changes 421 in the classic PI3K/Akt/mTOR pathway in the VK2/E6E7 cells. The results from 422 qRT-PCR assays and western blot analyses showed that, compared with that of the 423 control, the expression of PI3K and phosphorylation levels of Akt and mTOR (p-Akt 424 and p-mTOR) in the HSV-2-infected cells were significantly increased, and these 425 proteins all were decreased significantly in the JZ-1+HSV-2 group (Fig. 5B, Fig. 7C ). showed that, compared with that of the HSV-2 group, the expression levels of PI3K, 433 p-Akt and p-mTOR were significantly reduced in the LY + HSV-2 group, indicating 434 that it indeed inhibited the PI3K/Akt/ mTOR pathway (Fig. 6C, Fig. 7D ). On this 435 basis, we measured the expression levels of LC3B and Atg5 and found that, in the 436 JZ-1 +HSV-2 +LY -treated group, the LC3B and Atg5 mRNA expression levels and 437 the LC3B-II and Atg5 protein expression levels were not different from those in the 438 LY+HSV-2 group (Fig. 6C, Fig. 7D ). As expected, LY pretreatment eliminated the \nThe present study demonstrated that JZ-1 is effective in combating HSV-2 611 infection, and the potential mechanism is associated with inducing autophagy through 612 inhibiting the PI3K/Akt/mTOR pathway. Our findings suggest that JZ-1 is a 613 promising anti-HSV-2 formula to be further researched and developed. Table 2 The ","tracks":[{"project":"CORD-PICO","denotations":[{"id":"p2_i0","span":{"begin":203,"end":235},"obj":"Pharmacological"}],"attributes":[{"subj":"p2_i0","pred":"source","obj":"CORD-PICO"}]},{"project":"CORD-19-Sentences","denotations":[{"id":"TextSentencer_T1","span":{"begin":0,"end":188},"obj":"Sentence"},{"id":"TextSentencer_T2","span":{"begin":190,"end":198},"obj":"Sentence"},{"id":"TextSentencer_T3","span":{"begin":199,"end":425},"obj":"Sentence"},{"id":"TextSentencer_T4","span":{"begin":427,"end":586},"obj":"Sentence"},{"id":"TextSentencer_T5","span":{"begin":587,"end":727},"obj":"Sentence"},{"id":"TextSentencer_T6","span":{"begin":728,"end":989},"obj":"Sentence"},{"id":"TextSentencer_T7","span":{"begin":990,"end":1072},"obj":"Sentence"},{"id":"TextSentencer_T8","span":{"begin":1073,"end":1189},"obj":"Sentence"},{"id":"TextSentencer_T9","span":{"begin":1190,"end":1378},"obj":"Sentence"},{"id":"TextSentencer_T10","span":{"begin":1380,"end":1525},"obj":"Sentence"},{"id":"TextSentencer_T11","span":{"begin":1526,"end":1713},"obj":"Sentence"},{"id":"TextSentencer_T12","span":{"begin":1715,"end":1895},"obj":"Sentence"},{"id":"TextSentencer_T13","span":{"begin":1896,"end":2036},"obj":"Sentence"},{"id":"TextSentencer_T14","span":{"begin":2037,"end":2148},"obj":"Sentence"},{"id":"TextSentencer_T15","span":{"begin":2149,"end":2282},"obj":"Sentence"},{"id":"TextSentencer_T16","span":{"begin":2283,"end":2454},"obj":"Sentence"},{"id":"TextSentencer_T17","span":{"begin":2455,"end":2596},"obj":"Sentence"},{"id":"TextSentencer_T18","span":{"begin":2597,"end":2751},"obj":"Sentence"},{"id":"TextSentencer_T19","span":{"begin":2752,"end":2905},"obj":"Sentence"},{"id":"TextSentencer_T20","span":{"begin":2906,"end":3511},"obj":"Sentence"},{"id":"TextSentencer_T21","span":{"begin":3512,"end":3813},"obj":"Sentence"},{"id":"TextSentencer_T22","span":{"begin":3814,"end":3857},"obj":"Sentence"},{"id":"TextSentencer_T23","span":{"begin":3859,"end":4062},"obj":"Sentence"},{"id":"TextSentencer_T24","span":{"begin":4063,"end":4171},"obj":"Sentence"},{"id":"TextSentencer_T25","span":{"begin":4172,"end":4183},"obj":"Sentence"},{"id":"TextSentencer_T1","span":{"begin":0,"end":188},"obj":"Sentence"},{"id":"TextSentencer_T2","span":{"begin":190,"end":198},"obj":"Sentence"},{"id":"TextSentencer_T3","span":{"begin":199,"end":425},"obj":"Sentence"},{"id":"TextSentencer_T4","span":{"begin":427,"end":586},"obj":"Sentence"},{"id":"TextSentencer_T5","span":{"begin":587,"end":727},"obj":"Sentence"},{"id":"TextSentencer_T6","span":{"begin":728,"end":989},"obj":"Sentence"},{"id":"TextSentencer_T7","span":{"begin":990,"end":1072},"obj":"Sentence"},{"id":"TextSentencer_T8","span":{"begin":1073,"end":1189},"obj":"Sentence"},{"id":"TextSentencer_T9","span":{"begin":1190,"end":1378},"obj":"Sentence"},{"id":"TextSentencer_T10","span":{"begin":1380,"end":1525},"obj":"Sentence"},{"id":"TextSentencer_T11","span":{"begin":1526,"end":1713},"obj":"Sentence"},{"id":"TextSentencer_T12","span":{"begin":1715,"end":1895},"obj":"Sentence"},{"id":"TextSentencer_T13","span":{"begin":1896,"end":2036},"obj":"Sentence"},{"id":"TextSentencer_T14","span":{"begin":2037,"end":2148},"obj":"Sentence"},{"id":"TextSentencer_T15","span":{"begin":2149,"end":2282},"obj":"Sentence"},{"id":"TextSentencer_T16","span":{"begin":2283,"end":2454},"obj":"Sentence"},{"id":"TextSentencer_T17","span":{"begin":2455,"end":2596},"obj":"Sentence"},{"id":"TextSentencer_T18","span":{"begin":2597,"end":2751},"obj":"Sentence"},{"id":"TextSentencer_T19","span":{"begin":2752,"end":2905},"obj":"Sentence"},{"id":"TextSentencer_T20","span":{"begin":2906,"end":3511},"obj":"Sentence"},{"id":"TextSentencer_T21","span":{"begin":3512,"end":3813},"obj":"Sentence"},{"id":"TextSentencer_T22","span":{"begin":3814,"end":3857},"obj":"Sentence"},{"id":"TextSentencer_T23","span":{"begin":3859,"end":4062},"obj":"Sentence"},{"id":"TextSentencer_T24","span":{"begin":4063,"end":4171},"obj":"Sentence"},{"id":"TextSentencer_T25","span":{"begin":4172,"end":4183},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"attributes":[{"subj":"TextSentencer_T1","pred":"source","obj":"CORD-19-Sentences"},{"subj":"TextSentencer_T2","pred":"source","obj":"CORD-19-Sentences"},{"subj":"TextSentencer_T3","pred":"source","obj":"CORD-19-Sentences"},{"subj":"TextSentencer_T4","pred":"source","obj":"CORD-19-Sentences"},{"subj":"TextSentencer_T5","pred":"source","obj":"CORD-19-Sentences"},{"subj":"TextSentencer_T6","pred":"source","obj":"CORD-19-Sentences"},{"subj":"TextSentencer_T7","pred":"source","obj":"CORD-19-Sentences"},{"subj":"TextSentencer_T8","pred":"source","obj":"CORD-19-Sentences"},{"subj":"TextSentencer_T9","pred":"source","obj":"CORD-19-Sentences"},{"subj":"TextSentencer_T10","pred":"source","obj":"CORD-19-Sentences"},{"subj":"TextSentencer_T11","pred":"source","obj":"CORD-19-Sentences"},{"subj":"TextSentencer_T12","pred":"source","obj":"CORD-19-Sentences"},{"subj":"TextSentencer_T13","pred":"source","obj":"CORD-19-Sentences"},{"subj":"TextSentencer_T14","pred":"source","obj":"CORD-19-Sentences"},{"subj":"TextSentencer_T15","pred":"source","obj":"CORD-19-Sentences"},{"subj":"TextSentencer_T16","pred":"source","obj":"CORD-19-Sentences"},{"subj":"TextSentencer_T17","pred":"source","obj":"CORD-19-Sentences"},{"subj":"TextSentencer_T18","pred":"source","obj":"CORD-19-Sentences"},{"subj":"TextSentencer_T19","pred":"source","obj":"CORD-19-Sentences"},{"subj":"TextSentencer_T20","pred":"source","obj":"CORD-19-Sentences"},{"subj":"TextSentencer_T21","pred":"source","obj":"CORD-19-Sentences"},{"subj":"TextSentencer_T22","pred":"source","obj":"CORD-19-Sentences"},{"subj":"TextSentencer_T23","pred":"source","obj":"CORD-19-Sentences"},{"subj":"TextSentencer_T24","pred":"source","obj":"CORD-19-Sentences"},{"subj":"TextSentencer_T25","pred":"source","obj":"CORD-19-Sentences"},{"subj":"TextSentencer_T1","pred":"source","obj":"CORD-19-Sentences"},{"subj":"TextSentencer_T2","pred":"source","obj":"CORD-19-Sentences"},{"subj":"TextSentencer_T3","pred":"source","obj":"CORD-19-Sentences"},{"subj":"TextSentencer_T4","pred":"source","obj":"CORD-19-Sentences"},{"subj":"TextSentencer_T5","pred":"source","obj":"CORD-19-Sentences"},{"subj":"TextSentencer_T6","pred":"source","obj":"CORD-19-Sentences"},{"subj":"TextSentencer_T7","pred":"source","obj":"CORD-19-Sentences"},{"subj":"TextSentencer_T8","pred":"source","obj":"CORD-19-Sentences"},{"subj":"TextSentencer_T9","pred":"source","obj":"CORD-19-Sentences"},{"subj":"TextSentencer_T10","pred":"source","obj":"CORD-19-Sentences"},{"subj":"TextSentencer_T11","pred":"source","obj":"CORD-19-Sentences"},{"subj":"TextSentencer_T12","pred":"source","obj":"CORD-19-Sentences"},{"subj":"TextSentencer_T13","pred":"source","obj":"CORD-19-Sentences"},{"subj":"TextSentencer_T14","pred":"source","obj":"CORD-19-Sentences"},{"subj":"TextSentencer_T15","pred":"source","obj":"CORD-19-Sentences"},{"subj":"TextSentencer_T16","pred":"source","obj":"CORD-19-Sentences"},{"subj":"TextSentencer_T17","pred":"source","obj":"CORD-19-Sentences"},{"subj":"TextSentencer_T18","pred":"source","obj":"CORD-19-Sentences"},{"subj":"TextSentencer_T19","pred":"source","obj":"CORD-19-Sentences"},{"subj":"TextSentencer_T20","pred":"source","obj":"CORD-19-Sentences"},{"subj":"TextSentencer_T21","pred":"source","obj":"CORD-19-Sentences"},{"subj":"TextSentencer_T22","pred":"source","obj":"CORD-19-Sentences"},{"subj":"TextSentencer_T23","pred":"source","obj":"CORD-19-Sentences"},{"subj":"TextSentencer_T24","pred":"source","obj":"CORD-19-Sentences"},{"subj":"TextSentencer_T25","pred":"source","obj":"CORD-19-Sentences"}]},{"project":"Epistemic_Statements","denotations":[{"id":"T1","span":{"begin":2149,"end":2282},"obj":"Epistemic_statement"},{"id":"T2","span":{"begin":2455,"end":2596},"obj":"Epistemic_statement"},{"id":"T3","span":{"begin":3814,"end":3858},"obj":"Epistemic_statement"},{"id":"T4","span":{"begin":3859,"end":4062},"obj":"Epistemic_statement"},{"id":"T5","span":{"begin":4063,"end":4171},"obj":"Epistemic_statement"}],"attributes":[{"subj":"T1","pred":"source","obj":"Epistemic_Statements"},{"subj":"T2","pred":"source","obj":"Epistemic_Statements"},{"subj":"T3","pred":"source","obj":"Epistemic_Statements"},{"subj":"T4","pred":"source","obj":"Epistemic_Statements"},{"subj":"T5","pred":"source","obj":"Epistemic_Statements"}]},{"project":"CORD-19_Custom_license_subset","denotations":[{"id":"T1","span":{"begin":0,"end":188},"obj":"Sentence"},{"id":"T2","span":{"begin":190,"end":198},"obj":"Sentence"},{"id":"T3","span":{"begin":199,"end":425},"obj":"Sentence"},{"id":"T4","span":{"begin":427,"end":586},"obj":"Sentence"},{"id":"T5","span":{"begin":587,"end":727},"obj":"Sentence"},{"id":"T6","span":{"begin":728,"end":989},"obj":"Sentence"},{"id":"T7","span":{"begin":990,"end":1072},"obj":"Sentence"},{"id":"T8","span":{"begin":1073,"end":1189},"obj":"Sentence"},{"id":"T9","span":{"begin":1190,"end":1378},"obj":"Sentence"},{"id":"T10","span":{"begin":1380,"end":1525},"obj":"Sentence"},{"id":"T11","span":{"begin":1526,"end":1713},"obj":"Sentence"},{"id":"T12","span":{"begin":1715,"end":1895},"obj":"Sentence"},{"id":"T13","span":{"begin":1896,"end":2036},"obj":"Sentence"},{"id":"T14","span":{"begin":2037,"end":2148},"obj":"Sentence"},{"id":"T15","span":{"begin":2149,"end":2282},"obj":"Sentence"},{"id":"T16","span":{"begin":2283,"end":2454},"obj":"Sentence"},{"id":"T17","span":{"begin":2455,"end":2596},"obj":"Sentence"},{"id":"T18","span":{"begin":2597,"end":2751},"obj":"Sentence"},{"id":"T19","span":{"begin":2752,"end":2905},"obj":"Sentence"},{"id":"T20","span":{"begin":2906,"end":3511},"obj":"Sentence"},{"id":"T21","span":{"begin":3512,"end":3813},"obj":"Sentence"},{"id":"T22","span":{"begin":3814,"end":3857},"obj":"Sentence"},{"id":"T23","span":{"begin":3859,"end":4062},"obj":"Sentence"},{"id":"T24","span":{"begin":4063,"end":4171},"obj":"Sentence"},{"id":"T25","span":{"begin":4172,"end":4183},"obj":"Sentence"}],"attributes":[{"subj":"T1","pred":"source","obj":"CORD-19_Custom_license_subset"},{"subj":"T2","pred":"source","obj":"CORD-19_Custom_license_subset"},{"subj":"T3","pred":"source","obj":"CORD-19_Custom_license_subset"},{"subj":"T4","pred":"source","obj":"CORD-19_Custom_license_subset"},{"subj":"T5","pred":"source","obj":"CORD-19_Custom_license_subset"},{"subj":"T6","pred":"source","obj":"CORD-19_Custom_license_subset"},{"subj":"T7","pred":"source","obj":"CORD-19_Custom_license_subset"},{"subj":"T8","pred":"source","obj":"CORD-19_Custom_license_subset"},{"subj":"T9","pred":"source","obj":"CORD-19_Custom_license_subset"},{"subj":"T10","pred":"source","obj":"CORD-19_Custom_license_subset"},{"subj":"T11","pred":"source","obj":"CORD-19_Custom_license_subset"},{"subj":"T12","pred":"source","obj":"CORD-19_Custom_license_subset"},{"subj":"T13","pred":"source","obj":"CORD-19_Custom_license_subset"},{"subj":"T14","pred":"source","obj":"CORD-19_Custom_license_subset"},{"subj":"T15","pred":"source","obj":"CORD-19_Custom_license_subset"},{"subj":"T16","pred":"source","obj":"CORD-19_Custom_license_subset"},{"subj":"T17","pred":"source","obj":"CORD-19_Custom_license_subset"},{"subj":"T18","pred":"source","obj":"CORD-19_Custom_license_subset"},{"subj":"T19","pred":"source","obj":"CORD-19_Custom_license_subset"},{"subj":"T20","pred":"source","obj":"CORD-19_Custom_license_subset"},{"subj":"T21","pred":"source","obj":"CORD-19_Custom_license_subset"},{"subj":"T22","pred":"source","obj":"CORD-19_Custom_license_subset"},{"subj":"T23","pred":"source","obj":"CORD-19_Custom_license_subset"},{"subj":"T24","pred":"source","obj":"CORD-19_Custom_license_subset"},{"subj":"T25","pred":"source","obj":"CORD-19_Custom_license_subset"}]},{"project":"CORD-19-PD-MONDO","denotations":[{"id":"T1","span":{"begin":92,"end":106},"obj":"Disease"},{"id":"T2","span":{"begin":273,"end":287},"obj":"Disease"},{"id":"T3","span":{"begin":427,"end":441},"obj":"Disease"},{"id":"T4","span":{"begin":1337,"end":1340},"obj":"Disease"},{"id":"T5","span":{"begin":1427,"end":1442},"obj":"Disease"},{"id":"T6","span":{"begin":1433,"end":1442},"obj":"Disease"},{"id":"T7","span":{"begin":1678,"end":1681},"obj":"Disease"},{"id":"T8","span":{"begin":3936,"end":3945},"obj":"Disease"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MONDO_0004609"},{"id":"A2","pred":"mondo_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/MONDO_0004609"},{"id":"A3","pred":"mondo_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/MONDO_0005770"},{"id":"A4","pred":"mondo_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/MONDO_0010518"},{"id":"A5","pred":"mondo_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/MONDO_0005108"},{"id":"A6","pred":"mondo_id","subj":"T6","obj":"http://purl.obolibrary.org/obo/MONDO_0005550"},{"id":"A7","pred":"mondo_id","subj":"T7","obj":"http://purl.obolibrary.org/obo/MONDO_0010518"},{"id":"A8","pred":"mondo_id","subj":"T8","obj":"http://purl.obolibrary.org/obo/MONDO_0005550"},{"subj":"T1","pred":"source","obj":"CORD-19-PD-MONDO"},{"subj":"T2","pred":"source","obj":"CORD-19-PD-MONDO"},{"subj":"T3","pred":"source","obj":"CORD-19-PD-MONDO"},{"subj":"T4","pred":"source","obj":"CORD-19-PD-MONDO"},{"subj":"T5","pred":"source","obj":"CORD-19-PD-MONDO"},{"subj":"T6","pred":"source","obj":"CORD-19-PD-MONDO"},{"subj":"T7","pred":"source","obj":"CORD-19-PD-MONDO"},{"subj":"T8","pred":"source","obj":"CORD-19-PD-MONDO"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"CORD-PICO","color":"#a1ec93","default":true},{"id":"CORD-19-Sentences","color":"#ec93bb"},{"id":"Epistemic_Statements","color":"#93d5ec"},{"id":"CORD-19_Custom_license_subset","color":"#ece993"},{"id":"CORD-19-PD-MONDO","color":"#cf93ec"}]}]}}