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Article ; Online: Antiviral Effect of Ginsenosides rk1 against Influenza a Virus Infection by Targeting the Hemagglutinin 1-Mediated Virus Attachment

Xia Yang / Hailiang Sun / Zhening Zhang / Weixin Ou / Fengxiang Xu / Ling Luo / Yahong Liu / Weisan Chen / Jianxin Chen

International Journal of Molecular Sciences, Vol 24, Iss 4967, p

2023 Volume 4967

Abstract: Influenza A virus (IAV) infections have been a serious hazard to public health everywhere. With the growing concern of drug-resistant IAV strains, there is an urgent need for novel anti-IAV medications, especially those with alternative mechanisms of ... ...

Abstract	Influenza A virus (IAV) infections have been a serious hazard to public health everywhere. With the growing concern of drug-resistant IAV strains, there is an urgent need for novel anti-IAV medications, especially those with alternative mechanisms of action. Hemagglutinin (HA), an IAV glycoprotein, plays critical roles in the early stage of virus infection, including receptor binding and membrane fusion, making it a good target for developing anti-IAV drugs. Panax ginseng is a widely used herb in traditional medicine with extensive biological effects in various disease models, and its extract was reported to show protection in IAV-infected mice. However, the main effective anti-IAV constituents in panax ginseng remain unclear. Here, we report that ginsenoside rk1 (G-rk1) and G-rg5, out of the 23 screened ginsenosides, exhibit significant antiviral effects against 3 different IAV subtypes (H1N1, H5N1, and H3N2) in vitro. Mechanistically, G-rk1 blocked IAV binding to sialic acid in a hemagglutination inhibition (HAI) assay and an indirect ELISA assay; more importantly, we showed that G-rk1 interacted with HA1 in a dose-dependent manner in a surface plasmon resonance (SPR) analysis. Furthermore, G-rk1 treatment by intranasal inoculation effectively reduced the weight loss and mortality of mice challenged with a lethal dose of influenza virus A/Puerto Rico/8/34 (PR8). In conclusion, our findings reveal for the first time that G-rk1 possesses potent anti-IAV effects in vitro and in vivo. We have also identified and characterized with a direct binding assay a novel ginseng-derived IAV HA1 inhibitor for the first time, which could present potential approaches to prevent and treat IAV infections.
Keywords	ginsenosides ; ginsenoside rk1 ; influenza virus ; entry inhibitors ; hemagglutinin ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	570
Language	English
Publishing date	2023-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Toosendanin activates caspase-1 and induces maturation of IL-1β to inhibit type 2 porcine reproductive and respiratory syndrome virus replication via an IFI16-dependent pathway

Mingxin Zhang / Chunni Lu / Lizhan Su / Feixiang Long / Xia Yang / Xiaofeng Guo / Gaopeng Song / Tongqing An / Weisan Chen / Jianxin Chen

Veterinary Research, Vol 53, Iss 1, Pp 1-

2022 Volume 18

Abstract: Abstract Porcine reproductive and respiratory syndrome virus (PRRSV) is a prevalent and endemic swine pathogen which causes significant economic losses in the global swine industry. Multiple vaccines have been developed to prevent PRRSV infection. ... ...

Abstract	Abstract Porcine reproductive and respiratory syndrome virus (PRRSV) is a prevalent and endemic swine pathogen which causes significant economic losses in the global swine industry. Multiple vaccines have been developed to prevent PRRSV infection. However, they provide limited protection. Moreover, no effective therapeutic drugs are yet available. Therefore, there is an urgent need to develop novel antiviral strategies to prevent PRRSV infection and transmission. Here we report that Toosendanin (TSN), a tetracyclic triterpene found in the bark or fruits of Melia toosendan Sieb. et Zucc., strongly suppressed type 2 PRRSV replication in vitro in Marc-145 cells and ex vivo in primary porcine alveolar macrophages (PAMs) at sub-micromolar concentrations. The results of transcriptomics revealed that TSN up-regulated the expression of IFI16 in Marc-145 cells. Furthermore, we found that IFI16 silencing enhanced the replication of PRRSV in Marc-145 cells and that the anti-PRRSV activity of TSN was dampened by IFI16 silencing, suggesting that the inhibition of TSN against PRRSV replication is IFI16-dependent. In addition, we showed that TSN activated caspase-1 and induced maturation of IL-1β in an IFI16-dependent pathway. To verify the role of IL-1β in PRRSV infection, we analyzed the effect of exogenous rmIL-1β on PRRSV replication, and the results showed that exogenous IL-1β significantly inhibited PRRSV replication in Marc-145 cells and PAMs in a dose-dependent manner. Altogether, our findings indicate that TSN significantly inhibits PRRSV replication at very low concentrations (EC50: 0.16–0.20 μM) and may provide opportunities for developing novel anti-PRRSV agents.
Keywords	Porcine reproductive and respiratory syndrome virus (PRRSV) ; Toosendanin (TSN) ; inhibitory activity ; gamma-interferon-inducible protein 16 (IFI16) ; caspase-1 ; Interleukin-1β (IL-1β) ; Veterinary medicine ; SF600-1100
Subject code	570
Language	English
Publishing date	2022-07-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The medicinal value of tea drinking in the management of COVID-19

Jiaming Ge / Tianbao Song / Mengyuan Li / Weisan Chen / Jiarong Li / Sihan Gong / Ying Zhao / Lin Ma / Hongjian Yu / Xiankuan Li / Kun Fu

Heliyon, Vol 9, Iss 1, Pp e12968- (2023)

2023

Abstract: Corona Virus Disease 2019 (COVID-19) is presently the largest international public health event, individuals infected by the virus not only have symptoms such as fever, dry cough, and lung infection at the time of onset, but also possibly have sequelae ... ...

Abstract	Corona Virus Disease 2019 (COVID-19) is presently the largest international public health event, individuals infected by the virus not only have symptoms such as fever, dry cough, and lung infection at the time of onset, but also possibly have sequelae in the cardiovascular system, respiratory system, nervous system, mental health and other aspects. However, numerous studies have depicted that the active ingredients in tea show good antiviral effects and can treat various diseases by regulating multiple pathways, and the therapeutic effects are associated with the categories of chemical components in tea. In this review, the differences in the content of key active ingredients in different types of tea are summarized. In addition, we also highlighted their effects on COVID-19 and connected sequelae, further demonstrating the possibility of developing a formulation for the prevention and treatment of COVID-19 and its sequelae through tea extracts. We have a tendency to suggest forestalling and treating COVID-19 and its sequelae through scientific tea drinking.
Keywords	Tea ; COVID-19 ; Sequelae ; Network pharmacology ; Science (General) ; Q1-390 ; Social sciences (General) ; H1-99
Language	English
Publishing date	2023-01-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: FasL+PD‐L2+ Identifies a Novel Immunosuppressive Neutrophil Population in Human Gastric Cancer That Promotes Disease Progression

Zhi‐Guo Shan / Yong‐Liang Zhao / Jin‐Yu Zhang / Zong‐Bao Yan / Ting‐Ting Wang / Fang‐Yuan Mao / Yong‐Sheng Teng / Liu‐Sheng Peng / Wan‐Yan Chen / Pan Wang / Ping Cheng / Wen‐Qing Tian / Jun Chen / Weisan Chen / Yuan Zhuang

Advanced Science, Vol 9, Iss 5, Pp n/a-n/a (2022)

2022

Abstract: Abstract Neutrophils constitute abundant cellular components in human gastric cancer (GC) tissues, but their protumorigenic subset in pathogenesis of GC progression is unclear. Here, it is found that patients with GC show significantly higher neutrophil ... ...

Abstract	Abstract Neutrophils constitute abundant cellular components in human gastric cancer (GC) tissues, but their protumorigenic subset in pathogenesis of GC progression is unclear. Here, it is found that patients with GC show significantly higher neutrophil infiltration in tumors that is regulated by CXCL12‐CXCR4 chemotaxis. These tumor‐infiltrating neutrophils express high level immunosuppressive molecules FasL and PD‐L2, and this FasL+PD‐L2+ neutrophil subset with a unique phenotype constitutes at least 20% of all neutrophils in advanced GC and predicts poor patient survival. Tumor induces neutrophils to express FasL and PD‐L2 proteins with similar phenotype to those in GC tumors in both time‐dependent and dose‐dependent manners. Mechanistically, Th17 cell‐derived IL‐17A and tumor cell‐derived G‐CSF can significantly induce neutrophil FasL and PD‐L2 expression via activating ERK‐NF‐κB and JAK‐STAT3 signaling pathway, respectively. Importantly, upon over‐expressing FasL and PD‐L2, neutrophils acquire immunosuppressive functions on tumor‐specific CD8+ T‐cells and promote the growth and progression of human GC tumors in vitro and in vivo, which can be reversed by blocking FasL and PD‐L2 on these neutrophils. Thus, the work identifies a novel protumorigenic FasL+PD‐L2+ neutrophil subset in GC and provides new insights for human cancer immunosuppression and anti‐cancer therapies targeting these pathogenic cells.
Keywords	FasL ; gastric cancer ; neutrophils ; PD‐L2 ; Science ; Q
Subject code	610
Language	English
Publishing date	2022-02-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The spleen in liver cirrhosis

Liang Li / Mubing Duan / Weisan Chen / An Jiang / Xiaoming Li / Jun Yang / Zongfang Li

Journal of Translational Medicine, Vol 15, Iss 1, Pp 1-

revisiting an old enemy with novel targets

2017 Volume 10

Abstract: Abstract The spleen is a secondary lymphoid organ which can influence the progression of multiple diseases, notably liver cirrhosis. In chronic liver diseases, splenomegaly and hypersplenism can manifest following the development of portal hypertension. ... ...

Abstract	Abstract The spleen is a secondary lymphoid organ which can influence the progression of multiple diseases, notably liver cirrhosis. In chronic liver diseases, splenomegaly and hypersplenism can manifest following the development of portal hypertension. These splenic abnormalities correlate with and have been postulated to facilitate the progression of liver fibrosis to cirrhosis, although precise mechanisms remain poorly understood. In this review, we summarize the literature to highlight the mechanistic contributions of splenomegaly and hypersplenism to the development of liver cirrhosis, focusing on three key aspects: hepatic fibrogenesis, hepatic immune microenvironment dysregulation and liver regeneration. We conclude with a discussion of the possible therapeutic strategies for modulating splenic abnormalities, including the novel potential usage of nanomedicine in non-surgically targetting splenic disorders for the treatment of liver cirrhosis.
Keywords	Splenomegaly ; Hypersplenism ; Liver cirrhosis ; Hepatic fibrogenesis ; Hepatic immune microenvironment ; Liver regeneration ; Medicine ; R
Subject code	610
Language	English
Publishing date	2017-05-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Chenodeoxycholic Acid from Bile Inhibits Influenza A Virus Replication via Blocking Nuclear Export of Viral Ribonucleoprotein Complexes

Ling Luo / Weili Han / Jinyan Du / Xia Yang / Mubing Duan / Chenggang Xu / Zhenling Zeng / Weisan Chen / Jianxin Chen

Molecules, Vol 23, Iss 12, p

2018 Volume 3315

Abstract: Influenza A virus (IAV) infection is still a major global threat for humans, especially for the risk groups: young children and the elderly. The currently licensed antiviral drugs target viral factors and are prone to viral resistance. In recent years, a ...

Abstract	Influenza A virus (IAV) infection is still a major global threat for humans, especially for the risk groups: young children and the elderly. The currently licensed antiviral drugs target viral factors and are prone to viral resistance. In recent years, a few endogenous small molecules from host, such as estradiol and omega-3 polyunsaturated fatty acid (PUFA)-derived lipid mediator protection D1 (PD1), were demonstrated to be capable of inhibiting IAV infection. Chenodeoxycholic acid (CDCA), one of the main primary bile acids, is synthesized from cholesterol in the liver and classically functions in emulsification and absorption of dietary fats. Clinically, CDCA has been used in the treatment of patients with cholesterol gallstones for more than five decades. In this study, we showed that CDCA attenuated the replication of three subtypes of influenza A virus, including a highly pathogenic H5N1 strain, in A549 and MDCK cell cultures with IC 50 ranging from 5.5 to 11.5 μM. Mechanistically, CDCA effectively restrained the nuclear export of viral ribonucleoprotein (vRNP) complexes. In conclusion, as an endogenous physiological small molecule, CDCA can inhibit IAV replication in vitro, at least in part, by blocking vRNP nuclear export, and affords further studies for development as a potential antiviral agent against IAV infections.
Keywords	chenodeoxycholic acid (CDCA) ; influenza A virus ; A549 cells ; MDCK cells ; nuclear export of viral ribonucleoprotein (vRNP) ; Organic chemistry ; QD241-441
Subject code	570
Language	English
Publishing date	2018-12-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: HLA-A*11:01-restricted CD8+ T cell immunity against influenza A and influenza B viruses in Indigenous and non-Indigenous people.

Jennifer R Habel / Andrea T Nguyen / Louise C Rowntree / Christopher Szeto / Nicole A Mifsud / E Bridie Clemens / Liyen Loh / Weisan Chen / Steve Rockman / Jane Nelson / Jane Davies / Adrian Miller / Steven Y C Tong / Jamie Rossjohn / Stephanie Gras / Anthony W Purcell / Luca Hensen / Katherine Kedzierska / Patricia T Illing

PLoS Pathogens, Vol 18, Iss 3, p e

2022 Volume 1010337

Abstract: HLA-A*11:01 is one of the most prevalent human leukocyte antigens (HLAs), especially in East Asian and Oceanian populations. It is also highly expressed in Indigenous people who are at high risk of severe influenza disease. As CD8+ T cells can provide ... ...

Abstract	HLA-A11:01 is one of the most prevalent human leukocyte antigens (HLAs), especially in East Asian and Oceanian populations. It is also highly expressed in Indigenous people who are at high risk of severe influenza disease. As CD8+ T cells can provide broadly cross-reactive immunity to distinct influenza strains and subtypes, including influenza A, B and C viruses, understanding CD8+ T cell immunity to influenza viruses across prominent HLA types is needed to rationally design a universal influenza vaccine and generate protective immunity especially for high-risk populations. As only a handful of HLA-A11:01-restricted CD8+ T cell epitopes have been described for influenza A viruses (IAVs) and epitopes for influenza B viruses (IBVs) were still unknown, we embarked on an epitope discovery study to define a CD8+ T cell landscape for HLA-A11:01-expressing Indigenous and non-Indigenous Australian people. Using mass-spectrometry, we identified IAV- and IBV-derived peptides presented by HLA-A11:01 during infection. 79 IAV and 57 IBV peptides were subsequently screened for immunogenicity in vitro with peripheral blood mononuclear cells from HLA-A11:01-expressing Indigenous and non-Indigenous Australian donors. CD8+ T cell immunogenicity screening revealed two immunogenic IAV epitopes (A11/PB2320-331 and A11/PB2323-331) and the first HLA-A11:01-restricted IBV epitopes (A11/M41-49, A11/NS1186-195 and A11/NP511-520). The immunogenic IAV- and IBV-derived peptides were >90% conserved among their respective influenza viruses. Identification of novel immunogenic HLA-A11:01-restricted CD8+ T cell epitopes has implications for understanding how CD8+ T cell immunity is generated towards IAVs and IBVs. These findings can inform the development of rationally designed, broadly cross-reactive influenza vaccines to ensure protection from severe influenza disease in HLA-A11:01-expressing individuals.
Keywords	Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
Subject code	570 ; 610
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Platelet Depletion is Effective in Ameliorating Anxiety-Like Behavior and Reducing the Pro-Inflammatory Environment in the Hippocampus in Murine Experimental Autoimmune Encephalomyelitis

Pece Kocovski / Xiangrui Jiang / Claretta S. D’Souza / Zhenjiang Li / Phuc T. Dang / Xiaowei Wang / Weisan Chen / Karlheinz Peter / Matthew W. Hale / Jacqueline M. Orian

Journal of Clinical Medicine, Vol 8, Iss 2, p

2019 Volume 162

Abstract: The neuropsychiatric symptoms of multiple sclerosis (MS), such as anxiety and depression, can result from disease activity itself as well as psychological reaction to an unfavorable diagnosis. Accordingly, the literature reports evidence of increased ... ...

Abstract	The neuropsychiatric symptoms of multiple sclerosis (MS), such as anxiety and depression, can result from disease activity itself as well as psychological reaction to an unfavorable diagnosis. Accordingly, the literature reports evidence of increased anxiety-like behavior in experimental autoimmune encephalomyelitis (EAE), an accepted MS model. Due to the recently described critical role of platelets in inflammation and autoimmune disease, we examined the relationship between platelets, inflammation, and anxiety-like behavior in EAE. In the elevated plus maze, EAE-induced C57BL/6J mice showed decreased time spent in the open arms relative to vehicle-only controls, demonstrating an increase in anxiety-like behavior. This effect occurred in the presence of platelet⁻neuron association, but absence of lymphocytic infiltration, in the hippocampal parenchyma. Platelet depletion at the pre-clinical disease stage, using antibody-mediated lysis prevented the EAE-induced increase in anxiety-like behavior, while no significant difference in distance moved was recorded. Furthermore, platelet depletion was also associated with reduction of the pro-inflammatory environment to control levels in the hippocampus and prevention of EAE disease symptomology. These studies demonstrate the high efficacy of a platelet-targeting approach in preventing anxiety-like symptoms and clinical manifestations of EAE and have implications for the treatment of neuropsychiatric symptoms in MS.
Keywords	platelets ; neuroinflammation ; EAE ; EPM ; hippocampus ; MS ; anxiety-like behavior ; C57BL/6 ; autoimmune disease ; MS therapy ; Medicine ; R
Subject code	630
Language	English
Publishing date	2019-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Broad CD8+ T cell cross-recognition of distinct influenza A strains in humans

Emma J. Grant / Tracy M. Josephs / Liyen Loh / E. Bridie Clemens / Sneha Sant / Mandvi Bharadwaj / Weisan Chen / Jamie Rossjohn / Stephanie Gras / Katherine Kedzierska

Nature Communications, Vol 9, Iss 1, Pp 1-

2018 Volume 16

Abstract: Mutations within immunological epitope containing regions of influenza A virus can impair the established immune response between influenza strains and could impact rational vaccine design. Here Grant et al. examine the presence, structural impact and ... ...

Abstract	Mutations within immunological epitope containing regions of influenza A virus can impair the established immune response between influenza strains and could impact rational vaccine design. Here Grant et al. examine the presence, structural impact and cross reactivity of two human immunodominant influenza epitope variants.
Keywords	Science ; Q
Language	English
Publishing date	2018-12-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Inhibition of proanthocyanidin A2 on porcine reproductive and respiratory syndrome virus replication in vitro.

Mingxin Zhang / Qianqian Wu / Yao Chen / Mubing Duan / Ge Tian / Xianbo Deng / Yankuo Sun / Tong Zhou / Guihong Zhang / Weisan Chen / Jianxin Chen

PLoS ONE, Vol 13, Iss 2, p e

2018 Volume 0193309

Abstract: Porcine reproductive and respiratory syndrome virus (PRRSV) is a widely prevalent and endemic swine pathogen that causes significant economic losses for the global pig industry annually. Currently, the most prevalent strategy for PRRSV control remains ... ...

Abstract	Porcine reproductive and respiratory syndrome virus (PRRSV) is a widely prevalent and endemic swine pathogen that causes significant economic losses for the global pig industry annually. Currently, the most prevalent strategy for PRRSV control remains the prevention of virus transmission, with highly effective therapeutic agents and vaccines still lacking. Proanthocyanidin A2 (PA2) belongs to the family of tea polyphenols, which have been reported to exhibit a range of biological activities including anti-oxidative, cardio-protective, anti-tumoural, anti-bacterial, anti-viral, and anti-inflammatory effects in vitro as well as in vivo. Here, we demonstrate that PA2 exhibits potent anti-viral activity against PRRSV infection in Marc-145 cells. Similar inhibitory effects were also found in porcine alveolar macrophages, the primary target cell type of PRRSV infection in pigs in vivo. For traditional type II PRRSV CH-1a strain and high pathogenic GD-XH strain and GD-HD strain, PA2 exhibited broad-spectrum and comparable inhibitory activities in vitro with EC50 ranging from 2.2 to 3.2 μg/ml. Treatment of PRRSV-infected Marc-145 cells with PA2 significantly inhibited viral RNA synthesis, viral protein expression and progeny virus production in a dose-dependent manner. In addition, PA2 treatment reduced gene expressions of cytokines (TNF-α, IFN-α, IL-1β and IL-6) induced by PRRSV infection in PAMs. Mechanistically, PA2 inhibited PRRSV replication by targeting multiple pathways including blockade of viral entry and progeny virus release. Altogether, our findings suggest that PA2 has the potential to serve as a novel prophylactic and therapeutic strategies against PRRSV infection.
Keywords	Medicine ; R ; Science ; Q
Subject code	570
Language	English
Publishing date	2018-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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