scholarly journals Eleutheroside-b and e in Acanthopanax Senticosus has Anti-PRV Activity via an Enhanced Body Immune Response in Vivo

2020 ◽  
Author(s):  
Zuohua Li ◽  
Xinglong Yu ◽  
Bin Zhang
Keyword(s):  
Survival Time ◽  
Pseudorabies Virus ◽  
Biological Functions ◽  
Acanthopanax Senticosus ◽  
Immunity Response ◽  
Immunity Genes ◽  
Eleutheroside B ◽  
Ifn Γ ◽  
High Level

Abstract BackgroundAcanthopanax senticosus extract (Eleutheroside-b and e, Acanthopanax senticosus extract, AS) is a multi-functional medicine involving in antiviral response in rodents and humans. Pseudorabies virus (PRV) is essential pathogens especially in swine farms. However, little is known about the biological functions of AS in vivo during PRV infection. MethodsIn order to confirm function of AS during PRV infection in vivo. We investigated that AS treatment (2mg/g, 4mg/g and 6mg/g) mice for 5 days affecting the mouse survival time during PRV infection. Furthermore, we investigated that AS treatment (4mg/g) mice for 1 day, 3 days and 5 days, respectively, affected the mouse survival time during PRV infection. We then treated mice with AS (4 mg/g) for 5 days and then challenged with PRV. Three days after PRV infection, we harvested mouse-samples to analyze PRV copies, performed pathological and immunohistochemical assays and the expression of immune-genes.ResultsWe found that AS treatment decreased the PRV copies and degree of pathological damage in mice brains and lungs. The AS treatment also stimulated a high level of IFN-γ, IL-2, and CCL-5 in the rodent serum, but suppressed IL-10 expression, suggesting that AS enhances the immunity response. Conclusionswe showed that AS promoted the anti-PRV ability in vivo by activating the expression of immunity genes. In summary, these findings offer a novel understanding of the immunity response during PRV infection.

Immunomodulation of ALT-2 and TLR may collude in antigen specific T cell hyporesponsiveness: Proposed mechanism for elevated IL-10 levels in Balb/C mice

2014 ◽  
Vol 59 (1) ◽  
Author(s):  
Ramanathan Aparnaa ◽  
Perumal Kaliraj
Keyword(s):  
Cellular Response ◽  
High Titer ◽  
Cell Mediated Immunity ◽  
Control Groups ◽  
Igg Antibody ◽  
Th1 Cytokine ◽  
Protection Efficacy ◽  
Ifn Γ ◽  
High Level

AbstractALT-2, a novel antigen belonging to the chromadorea ALT-2 family of the filarial nematode is proved to clear filarial parasites in Jirds. In order to increase the protection efficacy by stimulating the cell mediated immunity, MPLA a detoxified derivative of LPS known to induce the cellular response, was used in this study as an adjuvant on mice models. ALT-2+MPLA formulation elicited a high titer of total IgG antibody, with profoundly increased levels of IgG2b. Reduced splenocyte proliferation was observed in immunized group when compared to control groups which could be attributed to many in vivo factors. The levels of IFN-γ were high in unstimulated MPLA group compared to ALT-2 stimulated MPLA group, suggesting that the ALT-2 antigen suppressed the IFN-γ levels. A high level of IL-10 was induced by the ALT-2+MPLA formulation, which inhibited the production of Th2 cytokines (IL-4, IL-5) and also reduced the Th1 cytokine (IFN-γ, IL-2) levels which are not in vogue with the classical MPLA adjuvant formulation. We propose a mechanism for this immunomodulation which involves a diminished expression of TLR-4, by which the filarial parasites have evolved to evade host immune mechanism.

scholarly journals Roles of Endogenous Gamma Interferon and Macrophage Microbicidal Mechanisms in Host Response to Chemotherapy in Experimental Visceral Leishmaniasis

2000 ◽  
Vol 68 (1) ◽  
pp. 288-293 ◽  
Author(s):  
Henry W. Murray ◽  
Sharmaine Delph-Etienne
Keyword(s):  
Visceral Leishmaniasis ◽  
Leishmania Donovani ◽  
Gene Knockout ◽  
Gamma Interferon ◽  
Oxygen Intermediates ◽  
Tissue Macrophage ◽  
Response To Chemotherapy ◽  
Ifn Γ ◽  
High Level

ABSTRACT In experimental visceral leishmaniasis, in which the tissue macrophage is the target, in vivo responsiveness to conventional chemotherapy (pentavalent antimony [Sb]) requires a T-cell-dependent mechanism. To determine if this mechanism involves gamma interferon (IFN-γ)-induced activation and/or specific IFN-γ-regulated macrophage leishmanicidal mechanisms (generation of reactive nitrogen or oxygen intermediates, we treated gene-deficient mice infected withLeishmania donovani. In IFN-γ gene knockout (GKO) mice, Sb inhibited but did not kill intracellular L. donovani(2% killing versus 76% in controls). Sb was active (>94% killing), however, in both inducible nitric oxide synthase (iNOS) knockout (KO) and respiratory burst (phagocyte oxidase)-deficient chronic granulomatous disease (X-CGD) mice. Sb's efficacy was also maintained in doubly deficient animals (X-CGD mice treated with an iNOS inhibitor). In contrast to Sb, amphotericin B (AmB) induced high-level killing in GKO mice; AmB was also fully active in iNOS KO and X-CGD animals. Although resolution of L. donovani infection requires iNOS, residual visceral infection remained largely suppressed in iNOS KO mice treated with Sb or AmB. These results indicate that endogenous IFN-γ regulates the leishmanicidal response to Sb and achieves this effect via a pathway unrelated to the macrophage's primary microbicidal mechanisms. The role of IFN-γ is selective, since it is not a cofactor in the response to AmB. Treatment with either Sb or AmB permits an iNOS-independent mechanism to emerge and control residual intracellular L. donovani infection.

Production and Preliminary In Vivo Evaluations of a Novel in silico-designed L2-based Potential HPV Vaccine

2020 ◽  
Vol 21 (4) ◽  
pp. 316-324
Author(s):  
Manica Negahdaripour ◽  
Navid Nezafat ◽  
Reza Heidari ◽  
Nasrollah Erfani ◽  
Nasim Hajighahramani ◽  
...  
Keyword(s):  
In Silico ◽  
Group Versus ◽  
Tlr Agonists ◽  
E Coli ◽  
Metal Affinity ◽  
Th1 And Th2 Cytokines ◽  
Ifn Γ ◽  
Humoral Responses ◽  
Future Work

Background: L2-based Human Papillomavirus (HPV) prophylactic vaccines, containing epitopes from HPV minor capsid proteins, are under investigation as second-generation HPV vaccines. No such vaccine has passed clinical trials yet, mainly due to the low immunogenicity of peptide vaccines; so efforts are being continued. A candidate vaccine composed of two HPV16 L2 epitopes, flagellin and a Toll-Like Receptor (TLR) 4 agonist (RS09) as adjuvants, and two universal T-helper epitopes was designed in silico in our previous researches. Methods: The designed vaccine construct was expressed in E. coli BL21 (DE3) and purified through metal affinity chromatography. Following mice vaccination, blood samples underwent ELISA and flow cytometry analyses for the detection of IgG and seven Th1 and Th2 cytokines. Results: Following immunization, Th1 (IFN-γ, IL-2) and Th2 (IL-4, IL-5, IL-10) type cytokines, as well as IgG, were induced significantly compared with the PBS group. Significant increases in IFN-γ, IL-2, and IL-5 levels were observed in the vaccinated group versus Freund’s adjuvant group. Conclusion: The obtained cytokine induction profile implied both cellular and humoral responses, with a more Th-1 favored trend. However, an analysis of specific antibodies against L2 is required to confirm humoral responses. No significant elevation in inflammatory cytokines, (IL-6 and TNF-α), suggested a lack of unwanted inflammatory side effects despite using a combination of two TLR agonists. The designed construct might be capable of inducing adaptive and innate immunity; nevertheless, comprehensive immune tests were not conducted at this stage and will be a matter of future work.

The impact of Zataria multiflora Boiss extract on in vitro and in vivo Th1/Th2 cytokine (IFN-γ/IL4) balance

2013 ◽  
Vol 150 (3) ◽  
pp. 1024-1031 ◽  
Author(s):  
Mohammad Hossein Boskabady ◽  
Sakine Shahmohammadi Mehrjardi ◽  
Abadorrahim Rezaee ◽  
Houshang Rafatpanah ◽  
Sediqeh Jalali
Keyword(s):  
Zataria Multiflora ◽  
Th2 Cytokine ◽  
Ifn Γ ◽  
The Impact

scholarly journals The C-terminal domain of feline and bovine SAMHD1 proteins has a crucial role in lentiviral restriction

2020 ◽  
Vol 295 (13) ◽  
pp. 4252-4264 ◽  
Author(s):  
Chu Wang ◽  
Kaikai Zhang ◽  
Lina Meng ◽  
Xin Zhang ◽  
Yanan Song ◽  
...  
Keyword(s):  
Proteasomal Degradation ◽  
Acid Sites ◽  
Accessory Protein ◽  
Restriction Profile ◽  
Biological Functions ◽  
Terminal Domain ◽  
Functional Regions ◽  
Viral Restriction ◽  
Primate Lentiviruses

SAM and HD domain-containing protein 1 (SAMHD1) is a host factor that restricts reverse transcription of lentiviruses such as HIV in myeloid cells and resting T cells through its dNTP triphosphohydrolase (dNTPase) activity. Lentiviruses counteract this restriction by expressing the accessory protein Vpx or Vpr, which targets SAMHD1 for proteasomal degradation. SAMHD1 is conserved among mammals, and the feline and bovine SAMHD1 proteins (fSAM and bSAM) restrict lentiviruses by reducing cellular dNTP concentrations. However, the functional regions of fSAM and bSAM that are required for their biological functions are not well-characterized. Here, to establish alternative models to investigate SAMHD1 in vivo, we studied the restriction profile of fSAM and bSAM against different primate lentiviruses. We found that both fSAM and bSAM strongly restrict primate lentiviruses and that Vpx induces the proteasomal degradation of both fSAM and bSAM. Further investigation identified one and five amino acid sites in the C-terminal domain (CTD) of fSAM and bSAM, respectively, that are required for Vpx-mediated degradation. We also found that the CTD of bSAM is directly involved in mediating bSAM's antiviral activity by regulating dNTPase activity, whereas the CTD of fSAM is not. Our results suggest that the CTDs of fSAM and bSAM have important roles in their antiviral functions. These findings advance our understanding of the mechanism of fSAM- and bSAM-mediated viral restriction and might inform strategies for improving HIV animal models.

scholarly journals Gamma Interferon Blocks Gammaherpesvirus Reactivation from Latency

2006 ◽  
Vol 80 (1) ◽  
pp. 192-200 ◽  
Author(s):  
Ashley L. Steed ◽  
Erik S. Barton ◽  
Scott A. Tibbetts ◽  
Daniel L. Popkin ◽  
Mary L. Lutzke ◽  
...  
Keyword(s):  
Immune Surveillance ◽  
Viral Gene Expression ◽  
Gamma Interferon ◽  
Viral Gene ◽  
Herpesvirus Infection ◽  
Murine Gammaherpesvirus ◽  
Ifn Γ ◽  
Gammaherpesvirus 68 ◽  
Novel Strategy

ABSTRACT Establishment of latent infection and reactivation from latency are critical aspects of herpesvirus infection and pathogenesis. Interfering with either of these steps in the herpesvirus life cycle may offer a novel strategy for controlling herpesvirus infection and associated disease pathogenesis. Prior studies show that mice deficient in gamma interferon (IFN-γ) or the IFN-γ receptor have elevated numbers of cells reactivating from murine gammaherpesvirus 68 (γHV68) latency, produce infectious virus after the establishment of latency, and develop large-vessel vasculitis. Here, we demonstrate that IFN-γ is a powerful inhibitor of reactivation of γHV68 from latency in tissue culture. In vivo, IFN-γ controls viral gene expression during latency. Importantly, depletion of IFN-γ in latently infected mice results in an increased frequency of cells reactivating virus. This demonstrates that IFN-γ is important for immune surveillance that limits reactivation of γHV68 from latency.

scholarly journals Aberrantly high activation of a FoxM1–STMN1 axis contributes to progression and tumorigenesis in FoxM1-driven cancers

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Jun Liu ◽  
Jipeng Li ◽  
Ke Wang ◽  
Haiming Liu ◽  
Jianyong Sun ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Poor Prognosis ◽  
Soft Agar ◽  
Transcriptional Level ◽  
Regulation Mechanism ◽  
Strong Positive Correlation ◽  
Cell Viability Assay ◽  
High Level

AbstractFork-head box protein M1 (FoxM1) is a transcriptional factor which plays critical roles in cancer development and progression. However, the general regulatory mechanism of FoxM1 is still limited. STMN1 is a microtubule-binding protein which can inhibit the assembly of microtubule dimer or promote depolymerization of microtubules. It was reported as a major responsive factor of paclitaxel resistance for clinical chemotherapy of tumor patients. But the function of abnormally high level of STMN1 and its regulation mechanism in cancer cells remain unclear. In this study, we used public database and tissue microarrays to analyze the expression pattern of FoxM1 and STMN1 and found a strong positive correlation between FoxM1 and STMN1 in multiple types of cancer. Lentivirus-mediated FoxM1/STMN1-knockdown cell lines were established to study the function of FoxM1/STMN1 by performing cell viability assay, plate clone formation assay, soft agar assay in vitro and xenograft mouse model in vivo. Our results showed that FoxM1 promotes cell proliferation by upregulating STMN1. Further ChIP assay showed that FoxM1 upregulates STMN1 in a transcriptional level. Prognostic analysis showed that a high level of FoxM1 and STMN1 is related to poor prognosis in solid tumors. Moreover, a high co-expression of FoxM1 and STMN1 has a more significant correlation with poor prognosis. Our findings suggest that a general FoxM1-STMN1 axis contributes to cell proliferation and tumorigenesis in hepatocellular carcinoma, gastric cancer and colorectal cancer. The combination of FoxM1 and STMN1 can be a more precise biomarker for prognostic prediction.

scholarly journals Sarcoma IL-12 overexpression facilitates NK cell immunomodulation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mary Jo Rademacher ◽  
Anahi Cruz ◽  
Mary Faber ◽  
Robyn A. A. Oldham ◽  
Dandan Wang ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Lines ◽  
Nk Cell ◽  
Autologous Tumor ◽  
Murine Models ◽  
Lentiviral Transduction ◽  
Ifn Γ ◽  
Human Sarcoma

AbstractInterleukin-12 (IL-12) is an inflammatory cytokine that has demonstrated efficacy for cancer immunotherapy, but systemic administration has detrimental toxicities. Lentiviral transduction eliciting IL-12-producing human sarcoma for autologous reintroduction provides localized delivery for both innate and adaptive immune response augmentation. Sarcoma cell lines and primary human sarcoma samples were transduced with recombinant lentivirus engineering expression of human IL-12 (hu-IL-12). IL-12 expressing sarcomas were assessed in vitro and in vivo following implantation into humanized NSG and transgenic human IL-15 expressing (NSG.Tg(Hu-IL-15)) murine models. Lentiviral transduction (LV/hu-IL-12) of human osteosarcoma, Ewing sarcoma and rhabdomyosarcoma cell lines, as well as low-passage primary human sarcomas, engendered high-level expression of hu-IL-12. Hu-IL-12 demonstrated functional viability, eliciting specific NK cell-mediated interferon-γ (IFN-γ) release and cytotoxic growth restriction of spheroids in vitro. In orthotopic xenograft murine models, the LV/hu-IL-12 transduced human sarcoma produced detectable IL-12 and elicited an IFN-γ inflammatory immune response specific to mature human NK reconstitution in the NSG.Tg(Hu-IL-15) model while restricting tumor growth. We conclude that LV/hu-IL-12 transduction of sarcoma elicits a specific immune reaction and the humanized NSG.Tg(Hu-IL-15) xenograft, with mature human NK cells, can define in vivo anti-tumor effects and systemic toxicities. IL-12 immunomodulation through autologous tumor transduction and reintroduction merits exploration for sarcoma treatment.

scholarly journals CRISPR/Cas9-based generation of a recombinant double-reporter pseudorabies virus and its characterization in vitro and in vivo

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Peng-Fei Fu ◽  
Xuan Cheng ◽  
Bing-Qian Su ◽  
Li-Fang Duan ◽  
Cong-Rong Wang ◽  
...  
Keyword(s):  
Pseudorabies Virus ◽  
Fluorescent Protein ◽  
Antiviral Agents ◽  
Firefly Luciferase ◽  
Inhibitory Effect ◽  
Economic Losses ◽  
Green Fluorescent ◽  
Swine Herds

AbstractPseudorabies, caused by pseudorabies virus (PRV) variants, has broken out among commercial PRV vaccine-immunized swine herds and resulted in major economic losses to the pig industry in China since late 2011. However, the mechanism of virulence enhancement of variant PRV is currently unclear. Here, a recombinant PRV (rPRV HN1201-EGFP-Luc) with stable expression of enhanced green fluorescent protein (EGFP) and firefly luciferase as a double reporter virus was constructed on the basis of the PRV variant HN1201 through CRISPR/Cas9 gene-editing technology coupled with two sgRNAs. The biological characteristics of the recombinant virus and its lethality to mice were similar to those of the parental strain and displayed a stable viral titre and luciferase activity through 20 passages. Moreover, bioluminescence signals were detected in mice at 12 h after rPRV HN1201-EGFP-Luc infection. Using the double reporter PRV, we also found that 25-hydroxycholesterol had a significant inhibitory effect on PRV both in vivo and in vitro. These results suggested that the double reporter PRV based on PRV variant HN1201 should be an excellent tool for basic virology studies and evaluating antiviral agents.

scholarly journals Identification of the Active Ingredient and Beneficial Effects of Vitex rotundifolia Fruits on Menopausal Symptoms in Ovariectomized Rats

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1033
Author(s):  
Ji Hwan Lee ◽  
Sullim Lee ◽  
Quynh Nhu Nguyen ◽  
Hung Manh Phung ◽  
Myoung-Sook Shin ◽  
...  
Keyword(s):  
Weight Gain ◽  
Body Weight Gain ◽  
Animal Experiments ◽  
Ovariectomized Rats ◽  
Biological Functions ◽  
Menopausal Syndrome ◽  
Active Constituents ◽  
Mcf 7

Estrogen replacement therapy is a treatment to relieve the symptoms of menopause. Many studies suggest that natural bioactive ingredients from plants resemble estrogen in structure and biological functions and can relieve symptoms of menopause. The fruit of V. rotundifolia, called “Man HyungJa” in Korean, is a traditional medicine used to treat headache, migraine, eye pain, neuralgia, and premenstrual syndrome in Korea and China. The aim of the present study was to confirm that V. rotundifolia fruit extract (VFE) exerts biological functions similar to those of estrogen in menopausal syndrome. We investigated its in vitro effects on MCF-7 cells and in vivo estrogen-like effects on weight gain and uterine contraction in ovariectomized rats. Using the polar extract, the active constituents of VFE (artemetin, vitexicarpin, hesperidin, luteolin, vitexin, and vanillic acid) with estrogen-like activity were identified in MCF-7 cells. In animal experiments, the efficacy of VFE in ameliorating body weight gain was similar to that of estrogen, as evidenced from improvements in uterine atrophy. Vitexin and vitexicarpin are suggested as the active constituents of V. rotundifolia fruits.

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