scholarly journals Isolation and Identification of Andrographis paniculata (Chuanxinlian) and Its Biologically Active Constituents Inhibited Enterovirus 71-Induced Cell Apoptosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Wen-Wan Chao ◽  
Yueh-Hsiung Kuo ◽  
Bi-Fong Lin
Keyword(s):  
Antiviral Activity ◽  
Immune Responses ◽  
Enterovirus 71 ◽  
Andrographis Paniculata ◽  
Chinese Herbs ◽  
Luciferase Reporter ◽  
G1 Phase ◽  
G1 Arrest ◽  
Isolation And Identification ◽  
Rd Cells

Aim:Andrographis paniculata (Burm. f.) Nees (also known as Chuanxinlian in Chinese) of Acanthaceae family is one of the Chinese herbs reputed to be effective in the treatment of inflammation, infection, cold, and fever. Enterovirus 71 (EV71) is one of the most important enteroviruses that cause hand, foot, and mouth disease (HFMD) accompanied with neurological complication.Methods: To explore an anti-infective Chinese herb medicine, pure compounds isolated or synthesized analogues from A. paniculata (AP) ethyl acetate (EtOAc) extract are used to explore their anti-EV71-induced cytotoxicity. The antiviral activity was determined by cytopathic effect (CPE) reduction, and sub-G1 assays were used for measuring lysis and apoptosis of EV71-infected rhabdomyosarcoma (RD) cells. IFNγ-driven luciferase reporter assay was used to evaluate their potential roles in activation of immune responses.Results: Our data showed that EV71-induced sub-G1 phase of RD cells was dose dependently increased. Highly apoptotic EV71-infected RD cells were reduced by AP extract treatment. Ergosterol peroxide (4) has the most anti-apoptotic effect among these seven compounds. In addition, 3,19-O-acetyl-14-deoxy-11,12-didehydroandrographolide (8) synthesized from acetylation of compound 7 showed significantly better antiviral activity and the lowest sub-G1 phase of 6%–18%. Further investigation of IFNγ-inducer activity of these compounds showed that compounds 3, 6, 10, 11, and 12 had significantly higher IFNγ luciferase activities, suggesting their potential to promote IFNγ expression and thus activate immune responses for antivirus function.Conclusion: Our study demonstrated that bioactive compounds of AP and its derivatives either protecting EV71-infected RD cells from sub-G1 arrest or possessing IFNγ-inducer activity might be feasible for the development of anti-EV71 agents.

Anti-Enterovirus 71 Activity Screening of Chinese Herbs with Anti-Infection and Inflammation Activities

2009 ◽  
Vol 37 (01) ◽  
pp. 143-158 ◽  
Author(s):  
Tzou-Yien Lin ◽  
Yi-Chun Liu ◽  
Jia-Rong Jheng ◽  
Hui-Ping Tsai ◽  
Jia-Tsrong Jan ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Enterovirus 71 ◽  
Vero Cells ◽  
Chinese Herbs ◽  
Plaque Reduction Assay ◽  
Houttuynia Cordata ◽  
Cytopathic Effects ◽  
Infection And Inflammation ◽  
Activity Screening ◽  
Houttuynia Cordata Thunb

Antipyretic and toxin-eliminating traditional Chinese herbs are believed to possess antiviral activity. In this study, we screened extracts of 22 herbs for activity against enterovirus 71 (EV71). We found that only extracts of Houttuynia cordata Thunb. could neutralize EV71-induced cytopathic effects in Vero cells. The 50% inhibitory concentration of H. cordata extract for EV71 was 125.92 ± 27.84 μg/ml. Antiviral screening of herb extracts was also conducted on 3 genotypes of EV71, coxsackievirus A16 and echovirus 9. H. cordata extract had the highest activity against genotype A of EV71. A plaque reduction assay showed that H. cordata extract significantly reduced plaque formation. Viral protein expression, viral RNA synthesis and virus-induced caspase 3 activation were inhibited in the presence of H. cordata extract, suggesting that it affected apoptotic processes in EV71-infected Vero cells by inhibiting viral replication. The antiviral activity of H. cordata extract was greater in cells pretreated with extract than those treated after infection. We conclude that H. cordata extract has antiviral activity, and it offers a potential to develop a new anti-EV71 agent.

Antiviral Essential Oils Incorporated in Nanocarriers: Strategy for Prevention from COVID-19 and Future Infectious Pandemics

2020 ◽  
Vol 8 (6) ◽  
pp. 437-451
Author(s):  
Malkiet Kaur ◽  
Gayatri Devi ◽  
Manju Nagpal ◽  
Manjinder Singh ◽  
Gitika A. Dhingra ◽  
...  
Keyword(s):  
Phenolic Compounds ◽  
Antiviral Activity ◽  
Essential Oils ◽  
Bacterial Infections ◽  
Biological Properties ◽  
Vital Role ◽  
Chinese Herbs ◽  
Active Constituents ◽  
Prevention And Treatment ◽  
Low Solubility

Background: Coronavirus has become a life-threatening disease and it is caused by severe acute respiratory syndrome (SARS). This new strain of coronavirus is not completely understood and to date, there is no treatment for coronavirus. Traditional ayurvedic medicines, mainly essential oils and Chinese herbs, have always played a vital role in the prevention and treatment of several epidemics and pandemics. In the meantime, guidelines of the ministry of AYUSH (Ayurveda, yoga, unani, siddha and homoepathy) include a traditional medicinal treatment for flu and fever and also recommended to boost immunity to prevent the spread of coronavirus. It is not possible to find which essential oil will offer the best level of protection. However, it is likely to assume that some essential oils are likely to offer a measurable level of defense in the same way they do with many other known viruses. Methods: Literature relevant to various essential oils having antiviral activity has been collected and compiled. Various nanocarriers of essential oils have also been stated. The database was collected using various search engines such as J-Gate, Google Scholar, Sci-Hub, PubMed, ScienceDirect, etc. Results: Essential oils contain active constituents such as phenolic compounds, terpenoids, alkaloids, phenyl propanoids, etc., which are responsible for their biological properties such as antiviral, antibacterial, antimicrobial, antioxidant activities and many more. However, the use of essential oils has always been limited due to poor solubility, solvent toxicity, volatility and low solubility. Many nanotechnology based carriers especially, liposomes, dendrimers, nanoparticles, nanoemulsion and microemulsion, etc. have been evidenced to overcome limitations associated with essential oils. Conclusion: Several essential oils possess potent antiviral activity and are characterized by fewer side effects and are safe for human use. The nanocarrier systems of these oils have proved the potential to treat viral and bacterial infections. Lay Summary: Current COVID-19 era demands traditional treatment for immunity boost up as support therapy. Traditional ayurvedic medicines, mainly essential oils and Chinese herbs, have always played a vital role in the prevention and treatment of several epidemics and pandemics. Therefore, authors have summarized various essential oils having antiviral activity in current manuscript. Various nanocarriers of essential oils have been reported. Essential oils contain active constituents such as phenolic compounds, terpenoids, alkaloids, phenyl propanoids, etc., which are responsible for their biological properties such as antiviral, antibacterial, antimicrobial, antioxidant activity. However, the use of essential oils has always been limited due to poor solubility, solvent toxicity, volatility and low solubility. Many nanotechnology based carriers especially, liposomes, dendrimers, nanoparticles, nanoemulsion and microemulsion, etc. have been evidenced to overcome limitations associated with essential oils. The nanocarrier systems of these oils have proved the potential to treat viral and bacterial infections.

scholarly journals Honeysuckle Aqueous Extracts Induced let-7a Suppress EV71 Replication and Pathogenesis In Vitro and In Vivo and Is Predicted to Inhibit SARS-CoV-2

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 308
Author(s):  
Ying-Ray Lee ◽  
Chia-Ming Chang ◽  
Yuan-Chieh Yeh ◽  
Chi-Ying F. Huang ◽  
Feng-Mao Lin ◽  
...  
Keyword(s):  
Protein Expression ◽  
Western Blotting ◽  
Expression Profiles ◽  
Plaque Assay ◽  
Virus Titer ◽  
Enterovirus 71 ◽  
Luciferase Reporter ◽  
Pathogen Invasion

Honeysuckle (Lonicera japonica Thunb) is a traditional Chinese medicine (TCM) with an antipathogenic activity. MicroRNAs (miRNAs) are small non-coding RNA molecules that are ubiquitously expressed in cells. Endogenous miRNA may function as an innate response to block pathogen invasion. The miRNA expression profiles of both mice and humans after the ingestion of honeysuckle were obtained. Fifteen overexpressed miRNAs overlapped and were predicted to be capable of targeting three viruses: dengue virus (DENV), enterovirus 71 (EV71) and SARS-CoV-2. Among them, let-7a was examined to be capable of targeting the EV71 RNA genome by reporter assay and Western blotting. Moreover, honeysuckle-induced let-7a suppression of EV71 RNA and protein expression as well as viral replication were investigated both in vitro and in vivo. We demonstrated that let-7a targeted EV71 at the predicted sequences using luciferase reporter plasmids as well as two infectious replicons (pMP4-y-5 and pTOPO-4643). The suppression of EV71 replication and viral load was demonstrated in two cell lines by luciferase activity, RT-PCR, real-time PCR, Western blotting and plaque assay. Furthermore, EV71-infected suckling mice fed honeysuckle extract or inoculated with let-7a showed decreased clinical scores and a prolonged survival time accompanied with decreased viral RNA, protein expression and virus titer. The ingestion of honeysuckle attenuates EV71 replication and related pathogenesis partially through the upregulation of let-7a expression both in vitro and in vivo. Our previous report and the current findings imply that both honeysuckle and upregulated let-7a can execute a suppressive function against the replication of DENV and EV71. Taken together, this evidence indicates that honeysuckle can induce the expression of let-7a and that this miRNA as well as 11 other miRNAs have great potential to prevent and suppress EV71 replication.

scholarly journals Resveratrol Inhibits Venezuelan Equine Encephalitis Virus Infection by Interfering with the AKT/GSK Pathway

Plants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 346
Author(s):  
Caitlin W. Lehman ◽  
Kylene Kehn-Hall ◽  
Megha Aggarwal ◽  
Nicole R. Bracci ◽  
Han-Chi Pan ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Fluorescent Protein ◽  
Glycogen Synthase ◽  
Venezuelan Equine Encephalitis Virus ◽  
Encephalitis Virus ◽  
Host Cells ◽  
Dynamics Simulation ◽  
Luciferase Reporter ◽  
Venezuelan Equine Encephalitis ◽  
Equine Encephalitis Virus

The host proteins Protein Kinase B (AKT) and glycogen synthase kinase-3 (GSK-3) are associated with multiple neurodegenerative disorders. They are also important for the replication of Venezuelan equine encephalitis virus (VEEV), thereby making the AKT/GSK-3 pathway an attractive target for developing anti-VEEV therapeutics. Resveratrol, a natural phytochemical, has been shown to substantially inhibit the AKT pathway. Therefore, we attempted to explore whether it exerts any antiviral activity against VEEV. In this study, we utilized green fluorescent protein (GFP)- and luciferase-encoding recombinant VEEV to determine the cytotoxicity and antiviral efficacy via luciferase reporter assays, flow cytometry, and immunofluorescent assays. Our results indicate that resveratrol treatment is capable of inhibiting VEEV replication, resulting in increased viability of Vero and U87MG cells as well as reduced virion production and viral RNA contents within host cells for at least 48 h with a single treatment. Furthermore, the suppression of apoptotic signaling adaptors, caspase-3, caspase-7, and annexin V may also be implicated in resveratrol-mediated antiviral activity. We found that decreased phosphorylation of the AKT/GSK-3 pathway, mediated by resveratrol, can be triggered during the early stages of VEEV infection, suggesting that resveratrol disrupts the viral replication cycle and consequently promotes cell survival. Finally, molecular docking and dynamics simulation studies revealed that resveratrol can directly bind to VEEV glycoproteins, which may interfere with virus attachment and entry. In conclusion, our results suggest that resveratrol exerts inhibitory activity against VEEV infection and upon further modification could be a useful compound to study in neuroprotective research and veterinary sciences.

Effects of Herbal Medicinal Formulas on Suppressing Viral Replication and Modulating Immune Responses

2010 ◽  
Vol 38 (01) ◽  
pp. 173-190 ◽  
Author(s):  
Hui-Fen Liao ◽  
Min-Chi Lu ◽  
Hon-Chou Chang ◽  
Cheng-Chung Wei ◽  
Chih-Hsiung Kao ◽  
...  
Keyword(s):  
Immune Responses ◽  
Mononuclear Cells ◽  
Enterovirus 71 ◽  
Immune Functions ◽  
Herpes Simplex Virus 1 ◽  
Human Neuroblastoma ◽  
Radix Isatidis ◽  
Herbal Medicinal ◽  
Simplex Virus ◽  
Virus Suppression

The Chinese medicinal herbs Radix Isatidis and Viola yedoensis Makino have been suggested to possess antiviral activity. This study tests whether these and other Chinese and Western herbal medicinal formulas can modulate the immune functions involving virus-suppression in BALB/c mouse. We first confirmed the extract from Viola yedoensis Makino, but not from Radix Isatidis, the traditional Chinese medicine (TCM) formula Chui-Uren-Chien (CUC), or a Western homeopathic medicinal drink Método Canova, could inhibit the replications of herpes simplex virus-1 and enterovirus 71 in the human neuroblastoma SK-N-SH cell line. Subsequently, the same herbal extracts and drink underwent toxicity and immunomodulatory tests on mice of 5–7 weeks old. After 8 weeks of feeding different herbal medicinal formulas, no hepatic or renal toxicity was noted in any tested animal; whereas among the immune function evaluations, only the mice treated with CUC extract were found to be associated with significant increases (p < 0.05) in both the level of plasma IgG and the percentage of monocyte in blood mononuclear cells as well as the activation of macrophage Raw264.7 cells for nitric oxide production, suggesting its role in modulating the non-specific immune response. Analyses using protein arrays showed CUC was the most potent herbal medicinal formula eliciting fluctuations in plasma cytokine and chemokine concentrations. Taking all experimental data together, we conclude Chui-Uren-Chien possesses immunomodulatory capability in mouse, but none of the herbal medicinal formulas tested here are involved in strengthening antiviral immunity.

scholarly journals Thymosin-β4 Mediates Hepatic Stellate Cell Activation by Interfering with CircRNA-0067835/miR-155/FoxO3 Signaling Pathway

2018 ◽  
Vol 51 (3) ◽  
pp. 1389-1398 ◽  
Author(s):  
Lili Zhu ◽  
Tingting Ren ◽  
Zixin Zhu ◽  
Mingliang  Cheng ◽  
Qiuju Mou ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Cell Activation ◽  
Stellate Cell ◽  
Circular Rna ◽  
Fine Tuning ◽  
Differentially Expressed ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
G1 Arrest

Background/Aims: Hepatic stellate cells (HSCs) are the primary cell type responsible for liver fibrosis. Our study proved that thymosin beta 4 (Tβ4) has anti-fibrogenic effects in HSCs through PI3K/AKT pathway. However, the underlying mechanisms are not fully elucidated. Circular RNAs (circRNAs) play important roles in fine-tuning gene expression and are often deregulated in cancers. However, the expression profile and clinical significance of in liver fibrosis is still unknown. Therefore, we hypothesize that Tβ4 influences circRNAs in liver fibrosis. Methods: Circular RNA microarray was conducted to identify Tβ4-related circRNAs. Pathway analysis and miRNA response elements analysis was conducted to predict the potential roles of differentially expressed circRNAs in liver fibrosis. CCK8 assays and flow cytometric assays were conducted to clarify the role of circRNA in liver fibrosis. Bioinformatics analysis and in vitro experiments were conducted to clarify the mechanism of circRNA-mediated gene regulation in liver fibrosis. Results: A total of 644 differentially expressed circRNAs were identified between the Tβ4-depleted LX-2 cells and the control LX2 cells. The expression of circRNA-0067835 was significantly increased in the Tβ4-depleted LX-2 cells compared with control. Knockdown of circRNA-0067835 observably decreased LX-2 cell proliferation by causing G1 arrest and promoting apoptosis. Bioinformatics online programs predicted that circRNA-0067835 acted as miR-155 sponge to regulate FOXO3a expression, which was validated using luciferase reporter assay. Conclusion: Our experiments showed that circRNA-0067835 regulated liver fibrosis progression by acting as a sponge of miR-155 to promote FOXO3a expression, indicating that circRNA-0067835 may serve as a potential therapeutic target for patients with liver fibrosis.

scholarly journals Integrating miRNA and mRNA Profiling to Assess the Potential miRNA–mRNA Modules Linked With Testicular Immune Homeostasis in Sheep

2021 ◽  
Vol 8 ◽  
Author(s):  
Taotao Li ◽  
Xia Wang ◽  
Ruirui Luo ◽  
Xuejiao An ◽  
Yong Zhang ◽  
...  
Keyword(s):  
Immune Responses ◽  
Germ Cells ◽  
Expression Profiles ◽  
Immune Privilege ◽  
Functional Enrichment ◽  
Immunofluorescent Staining ◽  
Luciferase Reporter ◽  
Immune Homeostasis ◽  
Schematic Model ◽  
Mrna Levels

Beyond its well-known role in spermatogenesis and androgen production, mammalian testes are increasingly recognized as an immune-privileged organ for protecting autoantigenic germ cells, especially meiotic and postmeiotic germ cells, from systemic immune responses. Despite its importance, the molecular mechanisms underlying this regulation in mammals, including sheep, are far from known. In this study, we searched for the genes associated with testicular immune privilege and assessed their possible modulating mechanisms by analyzing systematic profiling of mRNAs and miRNAs on testicular tissues derived from prepubertal and postpubertal Tibetan sheep acquired by RNA sequencing. We identified 1,118 differentially expressed (DE) mRNAs associated with immunity (245 increased mRNAs and 873 decreased mRNAs) and 715 DE miRNAs (561 increased miRNAs and 154 decreased miRNAs) in postpubertal testes compared with prepuberty. qPCR validations for 20 DE mRNAs and 16 miRNAs showed that the RNA-seq results are reliable. By using Western blot, the postpubertal testes exhibited decreased protein abundance of CD19 and TGFBR2 (two proteins encoded by DE mRNAs) when compared with prepuberty, consistent with mRNA levels. The subsequent immunofluorescent staining showed that the positive signals for the CD19 protein were observed mainly in Sertoli cells and the basement membrane of pre- and postpubertal testes, as well as the prepubertal testicular vascular endothelium. The TGFBR2 protein was found mostly in interstitial cells and germ cells of pre- and postpubertal testes. Functional enrichment analysis indicated that DE mRNAs were mainly enriched in biological processes or pathways strongly associated with the blood–testis barrier (BTB) function. Many decreased mRNAs with low expression abundance were significantly enriched in pathways related to immune response. Also, multiple key miRNA-target negative correlation regulatory networks were subsequently established. Furthermore, we verified the target associations between either oar-miR-29b or oar-miR-1185-3p and ITGB1 by dual-luciferase reporter assay. Finally, a putative schematic model of the miRNA-mRNA-pathway network mediated by immune homeostasis-related genes was proposed to show their potential regulatory roles in sheep testicular privilege. Taken together, we conclude that many immune-related genes identified in this study are negatively regulated by potential miRNAs to participate in the homeostatic regulation of testicular immune privilege of sheep by sustaining BTB function and inhibiting immune responses under normal physiological conditions. This work offers the first global view of the expression profiles of miRNAs/mRNAs involved in sheep testicular immune privilege and how the genes potentially contribute to immune-homeostatic maintenance.

scholarly journals Targeting MM at the Nexus between Cell Cycle and Transcriptional Regulation Via CDK7 Inhibition

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 1-2
Author(s):  
Yao Yao ◽  
Woojun D Park ◽  
Eugenio Morelli ◽  
Mehmet Kemal Samur ◽  
Nicholas P Kwiatkowski ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Board Of Directors ◽  
Cell Lines ◽  
Mononuclear Cells ◽  
Luciferase Reporter ◽  
G1 Arrest ◽  
Normal Donor ◽  
Private Company ◽  
Advisory Committees

Deregulated transcription and cell cycle control are hallmarks of cancer that are especially frequent in multiple myeloma (MM). Largely non-overlapping sets of cyclin-dependent kinases (CDKs) regulate cell division and RNA polymerase II (Pol II)-dependent transcription; and targeting of cell cycle CDKs has been long pursued as an attractive therapeutic strategy. Among CDKs, CDK7 presents a unique therapeutic opportunity as it functions as a CDK activating kinase (CAK), licensing the activity of cell cycle CDKs, and also serves as a core component of the general transcription factor TFIIH. Here we elucidated the biological role of CDK7 and its transcriptional regulatory landscape in MM, using genetic as well chemical approaches, including tools for CDK7 rapid protein degradation (dTAG) and the selective covalent inhibitor YKL-5-124 that targets a cysteine residue (C312) located outside of the kinase domain. We have observed that CDK7 inhibition via YKL-5-124 robustly inhibited the phosphorylation of the CDK1, 2 and 4 activation loops in a representative panel of MM cell lines at concentrations as low as 50 nM. This reduction was not observed in MM cells expressing a resistant mutation in the reactive cysteine (C312S). Consistent with decrease of CAK activity, we observed G1 arrest and S phase loss after CDK7 inhibition, which was also associated with a rapid and transient loss of Ser2 and Ser5 phosphorylation of the RNA Pol2 C-terminal domain. To understand the effect of CDK7 inhibition on MM cell growth and viability, we evaluated activity of YKL-5-124 across a large panel of 25 MM cell lines and observed a significant inhibition of MM cell proliferation, with a significantly lower IC50 compared to PHA-activated normal donor peripheral blood mononuclear cells (PBMCs), suggesting a specific sensitivity of MM cells to CDK7 inhibition. Longer exposure to YKL-5-124 caused apoptotic cell death in MM cells; however treatment with an inactive analog or in cells expressing the C312S mutation failed to inhibit MM cell proliferation, confirming that the antiproliferative potency of YKL-5-124 resides in its unique characteristic to covalently bind to C312 domain. Importantly, CDK7 inhibition impaired primary MM cells proliferation alone and when cultured in the presence of BM microenvironment. Selective pharmacological degradation of endogenously tagged CDK7 confirmed impact of CDK7 inhibition on MM cell proliferation via inhibition of CDK7 transcriptional and cell cycle activities. To complement the pharmacological studies, we have established MM cells to express inducible CRISPR/Cas9 constructs encoding 4 independent small guide RNAs targeting CDK7, resulting in the reduction of the abundance of CDK7 protein by 20-60% which was sufficient to inhibit MM cell viability over time, phenocopying pharmacologic inhibition of CDK7. These results support the view that CDK7 is a pharmacologically relevant target for MM. Gene expression analysis after CDK7 inhibition in MM1S and H929 cells revealed that transcripts for only a subset of genes were substantially affected by treatment with low dose of YKL-5-124, showing a strong leading-edge enrichment for downregulation of E2F expression program, cell cycle, DNA damage, and MYC targets. We have indeed confirmed a potent reduction in phosphorylation of RB protein, with consequent decrease of E2F activity in MM cells confirmed using E2F-driven luciferase reporter. These data suggest significant role for CDK7 in the CDK-pRB-E2F pathway in MM, which was strengthened by the observation of a positive correlation between expression of CDK7 and expression of E2F target genes in primary MM cells (n=409). Finally, we have evaluated the in vivo effect of CDK7 inhibition in several murine models of human MM. In the localized subcutaneous model, and the disseminated MM model where treatment with YKL-5-124 decreased tumor burden and improved survival. The effect of CDK7 inhibition explored in an aggressive, genetically engineered model of Myc-dependent MM, revealed evidence of response by decline in measurement of monotypic serum immunoglobulins. In conclusion, our study demonstrates that CDK7 contributes to the 'transcriptional addiction' and the cell cycle deregulation frequently observed in MM and represents an attractive molecular vulnerability to be exploited therapeutically. Disclosures Anderson: Millenium-Takeda: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Sanofi-Aventis: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Oncopep and C4 Therapeutics.: Other: Scientific Founder of Oncopep and C4 Therapeutics.; Celgene: Membership on an entity's Board of Directors or advisory committees. Munshi:Takeda: Consultancy; Karyopharm: Consultancy; AbbVie: Consultancy; Amgen: Consultancy; Legend: Consultancy; Adaptive: Consultancy; Janssen: Consultancy; C4: Current equity holder in private company; OncoPep: Consultancy, Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; BMS: Consultancy. Fulciniti:NIH: Research Funding.

scholarly journals Enterovirus 71 Represses Interleukin Enhancer-Binding Factor 2 Production and Nucleus Translocation to Antagonize ILF2 Antiviral Effects

Viruses ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 22
Author(s):  
Jing Jin ◽  
Wenbiao Wang ◽  
Sha Ai ◽  
Weiyong Liu ◽  
Yu Song ◽  
...  
Keyword(s):  
Nonstructural Protein ◽  
Enterovirus 71 ◽  
Ev71 Infection ◽  
Health It ◽  
Antiviral Effects ◽  
Distinct Mechanism ◽  
Binding Factor ◽  
2B Protein ◽  
Rd Cells ◽  
Hand Foot Mouth Disease

Enterovirus 71 (EV71) infection causes hand-foot-mouth disease (HFMD), meningoencephalitis, neonatal sepsis, and even fatal encephalitis in children, thereby presenting a serious risk to public health. It is important to determine the mechanisms underlying the regulation of EV71 infection. In this study, we initially show that the interleukin enhancer-binding factor 2 (ILF2) reduces EV71 50% tissue culture infective dose (TCID50) and attenuates EV71 plaque-formation unit (PFU), thereby repressing EV71 infection. Microarray data analyses show that ILF2 mRNA is reduced upon EV71 infection. Cellular studies indicate that EV71 infection represses ILF2 mRNA expression and protein production in human leukemic monocytes (THP-1) -differentiated macrophages and human rhabdomyosarcoma (RD) cells. In addition, EV71 nonstructural protein 2B interacts with ILF2 in human embryonic kidney (HEK293T) cells. Interestingly, in the presence of EV71 2B, ILF2 is translocated from the nucleus to the cytoplasm, and it colocalizes with 2B in the cytoplasm. Therefore, we present a distinct mechanism by which EV71 antagonizes ILF2-mediated antiviral effects by inhibiting ILF2 expression and promoting ILF2 translocation from the nucleus to the cytoplasm through its 2B protein.

scholarly journals Synergistic Impact of Xanthorrhizol and d-δ-tocotrienol on the Proliferation of Murine B16 Melanoma Cells and Human DU145 Prostate Carcinoma Cells (P06-042-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Maureen Beebe ◽  
Rami Najjar ◽  
Darren Chan ◽  
Chappell Madhani ◽  
Manal Elfakhani ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Synergistic Effect ◽  
Tumor Cells ◽  
Prostate Carcinoma ◽  
B16 Melanoma ◽  
Carcinoma Cells ◽  
G1 Phase ◽  
G1 Arrest ◽  
Funding Sources ◽  
Georgia State University

Abstract Objectives Xanthorrhizol, a sesquiterpene, and d-δ-tocotrienol, a vitamin E molecule, each suppresses the proliferation of a number of tumor cells. This study aims to examine the potentially synergistic effect of xanthorrhizol and d-δ-tocotrienol in tumor cells. Methods Murine B16 melanoma and human DU145 prostate carcinoma cells were incubated for 48 h (B16) or 72 h (DU145) with xanthorrhizol or d-δ-tocotrienol before cell populations were determined by CellTiter 96â Aqueous One Solution. Cells incubated with the agents for 24 hours were stained with propidium iodide and analyzed for cell cycle using flow cytometry and MultiCycle AV. Isobologram and combination index (CI) were used to demonstrate their synergistic anti-proliferative impacts. Results Xanthorrhizol (0–200 µmol/L) and d-δ-tocotrienol (0–40 µmol/L) each elicited a concentration-dependent suppression of the proliferation of B16 cells. A blend of 16.25 µmol/L xanthorrhizol and 10 µmol/L d-δ-tocotrienol achieved 69% (P < 0.05) growth suppression of B16 cells, exceeding the sum of individual effects. B16 cells incubated with 5 and 10 µmol/L d-δ-tocotrienol for 24-h had a concentration-dependent increase in the percentage of cells in the G1 phase with a concomitant decrease in the percentage of cells in the S phase. The G1/S ratio, an indicator of cell cycle arrest at the G1 phase, increased from 1.73 ± 0.05 (Control) to 2.01 ± 0.10 (5 µmol/L) and 2.73 ± 0.05 (10 µmol/L). A parallel pattern of concentration-dependent increase in the G1/S ratio was induced by xanthorrhizol at concentrations equivalent to 25% (16.25 µmol/L) and 50% (32.5 µmol/L) of its IC50 value. A blend of 5 µmol/L d-δ-tocotrienol and 16.25 µmol/L xanthorrhizol, each at no-effect concentrations, significantly increased the percentage of B16 cells in the G1 phase to 62.6 ± 0.6%. Isobologram and CI confirmed the synergistic effect of xanthorrhizol (50 and 100 μmol/L) and d-δ-tocotrienol (10 and 20 μmol/L) on the proliferation of DU145 cells. Conclusions Xanthorrhizol and d-δ-tocotrienol synergistically suppress tumor cell proliferation by inducing G1 arrest and may have potential in cancer prevention and therapy. Funding Sources American River Nutrition, Inc. and the University Assistantship Program and the Department of Nutrition of Georgia State University.

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