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Article: HCMV-IE2 promotes atherosclerosis by inhibiting vascular smooth muscle cells' pyroptosis.

Ma, Guixin / Yu, Zhongjie / Nan, Fulong / Zhang, Xianjuan / Jiang, Shasha / Wang, Yunyang / Wang, Bin

2023 Volume 14, Page(s) 1177391

Abstract: Atherosclerosis is still the main cause of death in developed and developing countries. Vascular smooth muscle cells (VSMCs) death disorder is a key pathogens of atherosclerosis. During the early stage of human cytomegalovirus (HCMV) infection, immediate ...

Abstract	Atherosclerosis is still the main cause of death in developed and developing countries. Vascular smooth muscle cells (VSMCs) death disorder is a key pathogens of atherosclerosis. During the early stage of human cytomegalovirus (HCMV) infection, immediate early protein 2 (IE2) is critical in regulating its host cell death to ensure HCMV replication. Abnormal cell death induced by HCMV infection contributes to the development of numerous diseases, including atherosclerosis. Hitherto, the underlying mechanism of HCMV involved in the progression of atherosclerosis is still unclear. In this study, the infection models
Language	English
Publishing date	2023-05-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587354-4
ISSN	1664-302X
ISSN	1664-302X
DOI	10.3389/fmicb.2023.1177391
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Article: Analysis of the mRNA export protein ZC3H11A in HCMV infection and pan-cancer.

Li, Jiawen / Song, Min / Liu, Zhen / Nan, Fulong / Wang, Bin / Qian, Dongmeng / Hu, Ming

Frontiers in microbiology

2023 Volume 14, Page(s) 1296725

Abstract: Background: We have previously reported that human cytomegalovirus (HCMV) infection could promote the progression of glioma. Here we discovered a stress-induced nuclear protein ZC3H11A (ZC3) through high-throughput sequencing after HCMV infection, which ...

Abstract	Background: We have previously reported that human cytomegalovirus (HCMV) infection could promote the progression of glioma. Here we discovered a stress-induced nuclear protein ZC3H11A (ZC3) through high-throughput sequencing after HCMV infection, which has been reported recently by our research group in regulating mRNA export under stress conditions. And also, a thorough analysis of ZC3 in pan-cancer and the omics data of ZC3 are yet to be conducted. Methods: The transcriptomes of glioma cells after HCMV infection were assessed by RNA sequencing. ZC3 mRNA and protein level following HCMV infection were validated and measured by qRT-PCR and Western-blot. The RNA sequencing and protein expression information of ZC3 across pan-cancer were analyzed and visualized by R packages. The localization of ZC3 protein was assessed by IHC images from HPA. The ZC3 proteomics and transcriptomics data in different cancers were extracted through the CPTAC data portal, and comparisons were conducted with a Python script. The genetic alteration, survival prognosis, immune infiltration analysis of ZC3 in pan-cancer were analyzed by cBioPortal, TCGA, and TIMER2 databases. The protein interaction networks were revealed by STRING, GEPIA2 and TCGA. Results: Genes in mRNA processing pathways were upregulated after HCMV infection and ZC3 expression in mRNA and protein level was validated. We also discovered that the status of ZC3 were generally at high levels in cancers, although varied among different cancer types. ZC3 protein in tumor cells localized to the nuclear whereas in normal cells it was mainly found in cytoplasmic/membranous. However, from ZC3 proteomics and transcriptomics data in some cancer types, the increase in ZC3 protein was not accompanied by a significant elevation in mRNA level. Additionally, our analysis indicated that elevated ZC3 expression was primarily linked to a negative prognosis in majority cancers but still varied depending on the cancer types. Our annotation analysis suggested that ZC3-related proteins are mainly involved in mRNA processing clusters. Conclusion: We demonstrated that ZC3 significantly impacted by HCMV infection in gliomas. Furthermore, we identified a set of genes exhibiting analogous expression patterns to ZC3H11A in TCGA pan-cancer cohorts, implying a potential functional role for ZC3H11A in mRNA processing. Our study provided valuable insights into the role of a new mRNA export protein ZC3 in HCMV infection and pan-cancer progression. These results lay the foundation for our next research on the regulatory mechanism of ZC3 in virus-infected tumors.
Language	English
Publishing date	2023-11-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587354-4
ISSN	1664-302X
ISSN	1664-302X
DOI	10.3389/fmicb.2023.1296725
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Article: Human Cytomegalovirus Induced Aberrant Expression of Non-coding RNAs.

Yu, Zhongjie / Wang, Jing / Nan, Fulong / Shi, Wenyi / Zhang, Xianjuan / Jiang, Shasha / Wang, Bin

Frontiers in microbiology

2022 Volume 13, Page(s) 918213

Abstract: Human cytomegalovirus (HCMV) is a β-herpesvirus whose genome consists of double stranded linear DNA. HCMV genome can generate non-coding RNAs (ncRNAs) through transcription in its host cells. Besides that, HCMV infection also changes the ncRNAs ... ...

Abstract	Human cytomegalovirus (HCMV) is a β-herpesvirus whose genome consists of double stranded linear DNA. HCMV genome can generate non-coding RNAs (ncRNAs) through transcription in its host cells. Besides that, HCMV infection also changes the ncRNAs expression profile of the host cells. ncRNAs play a key role in maintaining the normal physiological activity of cells, and the disorder of ncRNAs expression has numerous adverse effects on cells. However, until now, the relationship between ncRNAs and HCMV-induced adverse effects are not summarized in detail. This review aims to give a systematic summary of the role of HCMV infection in ncRNAs expression while providing insights into the molecular mechanism of unnormal cellular events caused by ncRNAs disorder. ncRNAs disorder induced by HCMV infection is highly associated with cell proliferation, apoptosis, tumorigenesis, and immune regulation, as well as the development of cardiovascular diseases, and the potential role of biomarker. We summarize the studies on HCMV associated ncRNAs disorder and suggest innovative strategies for eliminating the adverse effects caused by HCMV infection.
Language	English
Publishing date	2022-06-13
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2587354-4
ISSN	1664-302X
ISSN	1664-302X
DOI	10.3389/fmicb.2022.918213
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Article ; Online: CRM197-conjugated peptides vaccine of HCMV pp65 and gH induce maturation of DC and effective viral-specific T cell responses.

Zhang, Shuyun / Nan, Fulong / Jiang, Shasha / Zhou, Xiaoqiong / Niu, Delei / Li, Jun / Wang, Hui / Zhang, Xueming / Zhang, Xianjuan / Wang, Bin

Virulence

2023 Volume 14, Issue 1, Page(s) 2169488

Abstract: Human cytomegalovirus (HCMV) infection is prevalent worldwide, and there is currently no licenced HCMV vaccine to control it. Therefore, developing an effective HCMV vaccine is a significant priority. Because of their excellent immunogenicity, the ... ...

Abstract	Human cytomegalovirus (HCMV) infection is prevalent worldwide, and there is currently no licenced HCMV vaccine to control it. Therefore, developing an effective HCMV vaccine is a significant priority. Because of their excellent immunogenicity, the crucial components of HCMV, phosphoprotein 65 (pp65) and glycoproteins H (gH) are potential target proteins for HCMV vaccine design. In this study, we predicted and screened the dominant antigenic epitopes of B and T cells from pp65 and gH conjugated with the carrier protein cross-reacting material 197 (CRM197) to form three peptide-CRM197 vaccines (pp65-CRM197, gH-CRM197, and pp65-CRM197+gH-CRM197). Furthermore, the immunogenicity of the peptide-CRM197 vaccines and their effects on dendritic cells (DCs) were explored. The results showed that three peptide-CRM197 vaccines could induce maturation of DCs through the p38 MAPK signalling pathway and promote the release of proinflammatory factors, such as TNF-α and interleukin (IL) -6. Meanwhile, the peptide-CRM197 vaccines could effectively activate T cell and humoral immunity, which were far better than the inactivated HCMV vaccine. In conclusion, we constructed three peptide-CRM197 vaccines, which could induce multiple immune effects, providing a novel approach for HCMV vaccine design.
MeSH term(s)	Humans ; Cytomegalovirus/genetics ; Cytomegalovirus Vaccines ; Glycoproteins ; Peptides ; T-Lymphocytes
Chemical Substances	CRM197 (non-toxic variant of diphtheria toxin) (08VC9WC084) ; Cytomegalovirus Vaccines ; Glycoproteins ; Peptides ; cytomegalovirus matrix protein 65kDa
Language	English
Publishing date	2023-02-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2657572-3
ISSN	2150-5608 ; 2150-5594
ISSN (online)	2150-5608
ISSN	2150-5594
DOI	10.1080/21505594.2023.2169488
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Article ; Online: Gut microbiota induces hepatic steatosis by modulating the T cells balance in high fructose diet mice.

Zhou, Xiaoqiong / Zhang, Xianjuan / Niu, Delei / Zhang, Shuyun / Wang, Hui / Zhang, Xueming / Nan, Fulong / Jiang, Shasha / Wang, Bin

Scientific reports

2023 Volume 13, Issue 1, Page(s) 6701

Abstract: Metabolic diseases are often associated with high fructose (HF) consumption. HF has also been found to alter the gut microbiota, which then favors the development of nonalcoholic fatty liver disease. However, the mechanisms underlying of the gut ... ...

Abstract	Metabolic diseases are often associated with high fructose (HF) consumption. HF has also been found to alter the gut microbiota, which then favors the development of nonalcoholic fatty liver disease. However, the mechanisms underlying of the gut microbiota on this metabolic disturbance are yet to be determined. Thus, in this study, we further explored the effect the gut microbiota concerning the T cells balance in an HF diet mouse model. We fed mice 60% fructose-enriched diet for 12 weeks. At 4 weeks, HF diet did not affect the liver, but it caused injury to the intestine and adipose tissues. After 12 weeks, the lipid droplet aggregation was markedly increased in the liver of HF-fed mice. Further analysis of the gut microbial composition showed that HF decreased the Bacteroidetes/Firmicutes ratio and increased the levels of Blautia, Lachnoclostridium, and Oscillibacter. In addition, HF can increase the expression of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) in the serum. T helper type 1 cells were significantly increased, and regulatory T(Treg) cells were markedly decreased in the mesenteric lymph nodes of the HF-fed mice. Furthermore, fecal microbiota transplantation alleviates systemic metabolic disorder by maintaining liver and intestinal immune homeostasis. Overall, our data indicated that intestinal structure injury and intestinal inflammation might be early, and liver inflammation and hepatic steatosis may be a subsequent effect following HF diets. Gut microbiota disorders impairing the intestinal barrier function and triggering immune homeostasis imbalance may be an importantly responsible for long-term HF diets induced hepatic steatosis.
MeSH term(s)	Mice ; Animals ; Gastrointestinal Microbiome ; Fructose/metabolism ; Liver/metabolism ; Diet ; Non-alcoholic Fatty Liver Disease/metabolism ; Inflammation/metabolism ; Diet, High-Fat ; Mice, Inbred C57BL
Chemical Substances	Fructose (30237-26-4)
Language	English
Publishing date	2023-04-24
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-33806-8
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Article ; Online: HCMV IE1/IE1mut Therapeutic Vaccine Induces Tumor Regression via Intratumoral Tertiary Lymphoid Structure Formation and Peripheral Immunity Activation in Glioblastoma Multiforme.

Yang, Xiaoli / Jiang, Shasha / Liu, Fengjun / Li, Zonghui / Liu, Wenxuan / Zhang, Xianjuan / Nan, Fulong / Li, Jun / Yu, Meng / Wang, Yunyang / Wang, Bin

Molecular neurobiology

2024

Abstract: Glioblastoma multiforme (GBM), a highly malignant invasive brain tumor, is associated with poor prognosis and survival and lacks an effective cure. High expression of the human cytomegalovirus (HCMV) immediate early protein 1 (IE1) in GBM tissues is ... ...

Abstract	Glioblastoma multiforme (GBM), a highly malignant invasive brain tumor, is associated with poor prognosis and survival and lacks an effective cure. High expression of the human cytomegalovirus (HCMV) immediate early protein 1 (IE1) in GBM tissues is strongly associated with their malignant progression, presenting a novel target for therapeutic strategies. Here, the bioluminescence imaging technology revealed remarkable tumor shrinkage and improved survival rates in a mouse glioma model treated with HCMV IE1/IE1mut vaccine. In addition, immunofluorescence data demonstrated that the treated group exhibited significantly more and larger tertiary lymphoid structures (TLSs) than the untreated group. The presence of TLS was associated with enhanced T cell infiltration, and a large number of proliferating T cells were found in the treated group. Furthermore, the flow cytometry results showed that in the treatment group, cytotoxic T lymphocytes exhibited partial polarization toward effector memory T cells and were activated to play a lethal role in the peripheral immunological organs. Furthermore, a substantial proportion of B cells in the draining lymph nodes expressed CD40 and CD86. Surprisingly, quantitative polymerase chain reaction indicated that a high expression of cytokines, including chemokines in brain tumors and immune tissues, induced the differentiation, development, and chemokine migration of immune cells in the treated group. Our study data demonstrate that IE1 or IE1mut vaccination has a favorable effect in glioma mice models. This study holds substantial implications for identifying new and effective therapeutic targets within GBM.
Language	English
Publishing date	2024-01-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	645020-9
ISSN	1559-1182 ; 0893-7648
ISSN (online)	1559-1182
ISSN	0893-7648
DOI	10.1007/s12035-024-03937-8
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Article ; Online: 4-Octyl Itaconate Treatment Inhibits Mitochondrial Dysfunction and ER stress via Stimulating SIRT1 Expression in vitro and Attenuates Osteoarthritis Process in Murine DMM Model in vivo

Yu, Ziping / Zhang, Zhao / Zhang, Xuancheng / Bao, Junduo / Li, Hualin / Yu, Jiapei / Shi, Ning / Nan, Fulong / Cao, Liang / Li, Chenghui / Wang, Wei

Journal of Functional Foods. , p.105450-

2023 , Page(s) 105450–

Abstract: Osteoarthritis (OA), a degenerative disease, has many pathological factors, including oxidative stress (OS), endoplasmic reticulum (ER) stress, apoptosis, and extracellular matrix (ECM) degeneration. OS regulates the pathological progression of OA via ... ...

Abstract	Osteoarthritis (OA), a degenerative disease, has many pathological factors, including oxidative stress (OS), endoplasmic reticulum (ER) stress, apoptosis, and extracellular matrix (ECM) degeneration. OS regulates the pathological progression of OA via mitochondrial dysfunction, and ER stress and by modulating the derivation and elimination of reactive oxygen species (ROS). Though. 4-octyl itaconate (4-OI) is known for its effects on the treatment of various diseases, how it affects OA and its underlying mechanism still needs to be elucidated. Therefore, it is necessary to explore the effects of 4-OI both in vivo and in vitro. In our study, we used H₂O₂, which can accumulate ROS, OS and ER stress, to imitate the OA model in vitro. Using western blot, real-time quantitative reverse transcription polymerase chain reaction and immunofluorescence staining, we found that 125 μM 4-OI can inhibit apoptosis, ECM degeneration, mitochondrial dysfunction, ER stress and abundant accumulation of ROS in chondrocytes. We also showed that 4-OI can activate the Sirtuin1 gene (SIRT1). We used a SIRT1 inhibitor EX527 to identify the relationships among these pathological factors, and it showed that the 4-OI-mediated effect was achieved by promoting the SIRT1. In vivo, the bilateral medial meniscus was resected to establish the destabilization of the medial meniscus model wherein intraperitoneal injections of 2% and 5% 4-OI postponed the progression of OA. Collectively, this study confirmed that 4-OI can potentially impede the progression of OA by promoting the expression of SIRT1.
Keywords	Western blotting ; apoptosis ; chondrocytes ; endoplasmic reticulum ; extracellular matrix ; fluorescent antibody technique ; genes ; mice ; mitochondria ; models ; osteoarthritis ; oxidative stress ; reactive oxygen species ; reverse transcriptase polymerase chain reaction ; mitochondrial dysfunction ; 4-Octyl Itaconate
Language	English
Publishing place	Elsevier Ltd
Document type	Article ; Online
Note	Pre-press version ; Use and reproduction
ZDB-ID	2511964-3
ISSN	1756-4646
ISSN	1756-4646
DOI	10.1016/j.jff.2023.105450
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Polygalacin D inhibits the growth of hepatocellular carcinoma cells through BNIP3L-mediated mitophagy and endogenous apoptosis pathways

NAN, Fulong / NAN, Wenlong / YU, Zhongjie / Wang, Hui / CUI, Xiaoni / JIANG, Shasha / ZHANG, Xianjuan / Li, Jun / WANG, Zhifei / Zhang, Shuyun / Wang, Bin / Li, Yiquan

Chinese Journal of Natural Medicines. 2023 May, v. 21, no. 5 p.346-358

2023

Abstract: Platycodon grandiflorum (Jacq.) A. DC. is a famous medicinal plant commonly used in East Asia. Triterpene saponins isolated from P. grandiflorum are the main biologically active compounds, among which polygalacin D (PGD) has been reported to be an anti- ... ...

Abstract	Platycodon grandiflorum (Jacq.) A. DC. is a famous medicinal plant commonly used in East Asia. Triterpene saponins isolated from P. grandiflorum are the main biologically active compounds, among which polygalacin D (PGD) has been reported to be an anti-tumor agent. However, its anti-tumor mechanism against hepatocellular carcinoma is unknown. This study aimed to explore the inhibitory effect of PGD in hepatocellular carcinoma cells and related mechanisms of action. We found that PGD exerted significant inhibitory effect on hepatocellular carcinoma cells through apoptosis and autophagy. Analysis of the expression of apoptosis-related proteins and autophagy-related proteins revealed that this phenomenon was attributed to the mitochondrial apoptosis and mitophagy pathways. Subsequently, using specific inhibitors, we found that apoptosis and autophagy had mutually reinforcing effects. In addition, further analysis of autophagy showed that PGD induced mitophagy by increasing BCL2 interacting protein 3 like (BNIP3L) levels.In vivo experiments demonstrated that PGD significantly inhibited tumor growth and increased the levels of apoptosis and autophagy in tumors. Overall, our findings showed that PGD induced cell death of hepatocellular carcinoma cells primarily through mitochondrial apoptosis and mitophagy pathways. Therefore, PGD can be used as an apoptosis and autophagy agonist in the research and development of antitumor agents.
Keywords	Platycodon grandiflorus ; agonists ; antineoplastic agents ; apoptosis ; hepatoma ; medicinal plants ; mitochondria ; mitophagy ; research and development ; triterpenoid saponins ; East Asia ; Platycodon grandiflorum ; Autophagy ; Hepatocellular carcinoma ; Polygalacin D
Language	English
Dates of publication	2023-05
Size	p. 346-358.
Publishing place	Elsevier B.V.
Document type	Article ; Online
ZDB-ID	2192577-X
ISSN	1875-5364 ; 2095-6975 ; 1672-3651
ISSN (online)	1875-5364
ISSN	2095-6975 ; 1672-3651
DOI	10.1016/S1875-5364(23)60452-2
Database	NAL-Catalogue (AGRICOLA)

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Zs.A 6113: Show issues

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Article: Cross-species opsonic activity of zebrafish fish-egg lectin on mouse macrophages

Qiao, Hongye / Wang, Yunyang / Zhang, Xianjuan / Lu, Ran / Niu, Junyun / Nan, Fulong / Ke, Dingxin / Zeng, Zhou / Wang, Yashuo / Wang, Bin

Developmental and comparative immunology. 2022 Apr., v. 129

2022

Abstract: Zebrafish Fish-egg lectin (zFEL) has been identified and proved to be a maternal factor with antibacterial and opsonic ability in fishes. In this study, we found that zFEL was capable of enhancing the phagocytosis of the bacteria by macrophages of mouse ( ...

Abstract	Zebrafish Fish-egg lectin (zFEL) has been identified and proved to be a maternal factor with antibacterial and opsonic ability in fishes. In this study, we found that zFEL was capable of enhancing the phagocytosis of the bacteria by macrophages of mouse (RAW264.7 and mouse peritoneal macrophages), suggesting a cross-species function of zFEL in higher animals. Further studies showed that zFEL can active the antigen presentation ability by up-regulating the expression of CD80, CD86 and MHC II. Meanwhile, zFEL also promoted the polarization of macrophages to M1-type, which was confirmed by the increase of cytokines TNF-α and IL-6. The expression of p38 gene was up-regulated in macrophages preincubated with zFEL. Taken together, zFEL appears opsonic function in mammal macrophages and has potential application in immunomodulation.
Keywords	Danio rerio ; antigen presentation ; genes ; immunomodulation ; interleukin-6 ; lectins ; macrophages ; mice ; phagocytosis
Language	English
Dates of publication	2022-04
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	752411-0
ISSN	1879-0089 ; 0145-305X
ISSN (online)	1879-0089
ISSN	0145-305X
DOI	10.1016/j.dci.2021.104332
Database	NAL-Catalogue (AGRICOLA)

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Zs.A 1327: Show issues

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Article: Retrospective investigation of the origin and epidemiology of the dengue outbreak in Yunnan, China from 2017 to 2018.

Cao, Liang / Yu, Ziping / He, Haiqiang / Guo, Xiaofang / Wei, Chun / Zhang, Xuancheng / Bao, Junduo / Li, Chenghui / Zhou, Hongning / Xin, Jialiang / Nan, Fulong

Frontiers in veterinary science

2023 Volume 10, Page(s) 1137392

Abstract: Since 2013, a dengue epidemic has broken out in Yunnan, China and neighboring countries. However, after the COVID-19 pandemic in 2019, the number of dengue cases decreased significantly. In this retrospective study, epidemiological and genetic diversity ... ...

Abstract	Since 2013, a dengue epidemic has broken out in Yunnan, China and neighboring countries. However, after the COVID-19 pandemic in 2019, the number of dengue cases decreased significantly. In this retrospective study, epidemiological and genetic diversity characterizations of dengue viruses (DENV) isolated in Yunnan between 2017 and 2018 were performed. The results showed that the dengue outbreak in Yunnan from 2017 to 2018 was mainly caused by DENV1 (genotype I and genotype V) and DENV2 (Asia I, Asia II, and Cosmopolitan). Furthermore, correlation analysis indicated a significant positive correlation between the number of imported and local cases (correlation coefficient = 0.936). Multiple sequence alignment and phylogenetic divergence analysis revealed that the local isolates are closely related to the isolates from Myanmar and Laos. Interestingly, recombination analysis found that the DENV1 and DENV2 isolates in this study had widespread intra-serotype recombination. Taken together, the results of the epidemiological investigation imply that the dengue outbreak in Yunnan was primarily due to imported cases. This study provides a new reference for further investigations on the prevalence and molecular epidemiology of DENV in Yunnan, China.
Language	English
Publishing date	2023-04-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2834243-4
ISSN	2297-1769
ISSN	2297-1769
DOI	10.3389/fvets.2023.1137392
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