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Article ; Online: Murine model of eosinophilic chronic rhinosinusitis with nasal polyposis inducing neuroinflammation and olfactory dysfunction.

Huang, Wei-Hao / Hung, Yu-Wen / Hung, Wei / Lan, Ming-Ying / Yeh, Chien-Fu

The Journal of allergy and clinical immunology

2024

Abstract: Background: Chronic rhinosinusitis (CRS) is a common inflammatory condition affecting the nasal and paranasal sinus mucosa, often accompanied by olfactory dysfunction. Eosinophilic CRS with nasal polyps (ECRSwNP) is a subtype of CRS characterized by ... ...

Abstract	Background: Chronic rhinosinusitis (CRS) is a common inflammatory condition affecting the nasal and paranasal sinus mucosa, often accompanied by olfactory dysfunction. Eosinophilic CRS with nasal polyps (ECRSwNP) is a subtype of CRS characterized by eosinophilic infiltration. Animal models for ECRSwNP with olfactory dysfunction are necessary for exploring potential therapeutic strategies. Objective: The aim of this study was to establish a mouse model of ECRSwNP combined with olfactory dysfunction in a shorter time frame using intranasal ovalbumin and Aspergillus protease (AP) administration. The efficacy of the model was validated by evaluating sinonasal inflammation, cytokine levels, olfactory function, and neuroinflammation in the olfactory bulb. Methods: Male BALB/c mice were intranasally administered ovalbumin and AP for 6 and 12 weeks to induce ECRSwNP. The resultant ECRSwNP mouse model underwent histologic assessment, cytokine analysis of nasal lavage fluid, olfactory behavioral tests, and gene expression profiling to identify neuroinflammatory markers within the olfactory bulb. Results: The developed mouse model exhibited substantial eosinophil infiltration, increased levels of inflammatory cytokines in nasal lavage fluid, and confirmed olfactory dysfunction through behavioral assays. Furthermore, olfactory bulb inflammation and reduced mature olfactory sensory neurons were observed in the model. Conclusion: This study successfully established a validated mouse model of ECRSwNP with olfactory dysfunction within a remarkably short span of 6 weeks, providing a valuable tool for investigating the pathogenesis and potential therapies for this condition. The model offers an efficient approach for future research in CRS with nasal polyps and olfactory dysfunction.
Language	English
Publishing date	2024-03-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	121011-7
ISSN	1097-6825 ; 1085-8725 ; 0091-6749
ISSN (online)	1097-6825 ; 1085-8725
ISSN	0091-6749
DOI	10.1016/j.jaci.2024.02.021
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Article ; Online: Correction to: Vertebral artery stenosis predicts cerebrovascular diseases following radiotherapy for nasopharyngeal carcinoma.

Yeh, Chien-Fu / Chin, Yu-Ching / Hung, Wei / Huang, Pin-I / Lan, Ming-Ying

Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer

2023 Volume 31, Issue 8, Page(s) 456

Language	English
Publishing date	2023-07-10
Publishing country	Germany
Document type	Published Erratum
ZDB-ID	1134446-5
ISSN	1433-7339 ; 0941-4355
ISSN (online)	1433-7339
ISSN	0941-4355
DOI	10.1007/s00520-023-07924-y
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Zs.A 3697: Show issues

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Article: Distinct Age-Specific Effects on Olfactory Associative Learning in C57BL/6 Substrains.

Chen, Hung-Lun / Chen, Chien-Fu F / Huang, Han-Bin

Frontiers in behavioral neuroscience

2022 Volume 16, Page(s) 808978

Abstract: C57BL/6 is the most widely used mouse strain in the laboratories. Two substrains of C57BL/6, C57BL/6J (B6J), and C57BL/6N (B6N) are well-known backgrounds for genetic modification and have been shown difference in quite a few tests, including open field ... ...

Abstract	C57BL/6 is the most widely used mouse strain in the laboratories. Two substrains of C57BL/6, C57BL/6J (B6J), and C57BL/6N (B6N) are well-known backgrounds for genetic modification and have been shown difference in quite a few tests, including open field test, rotarod test, and Morris water maze. However, difference between these two substrains in olfaction-dependent behaviors remains unknown. Here, we used olfactory two-alternative choice task, which is modified to have two training stages, to evaluate animals' ability in instrumental learning and olfactory association. In the first (rule learning) stage, the mice were trained to use the operant chamber to collect water rewards. An odor cue was provided in the procedure, with no indication about reward locations. In the following (discrimination learning) stage, two odor cues were provided, with each indicating a specific water port. The animals were rewarded upon correct port choices following cue deliveries. We found that during young adulthood (7-10 weeks old), proportionally more B6J than B6N mice were able to pass rule learning (58.3% vs. 29.2%) and ultimately acquire this task (54.2% vs. 25%), with the two substrains showing similar pass rates in discrimination learning (92.9% vs. 85.7%). Surprisingly, at a more mature age (17 weeks old), this substrain difference disappeared. Mature B6N mice had a significant improvement in pass percentages of rule learning and overall task, whereas similar improvement was not observed in the B6J counterparts. Instead, mature B6J mice had an improved speed in rule learning and overall task. We further examined behavioral patterns of 8-week-old B6J and B6N mice in the olfactory habituation or dishabituation test. We observed normal olfactory habituation from subjects of both substrains, with the B6J mice exhibiting stronger investigative responses to newly presented odorants. These results reveal for the first time that B6J and B6N mice are different in acquisition processes of a behavioral task that requires instrumental learning and olfactory association, and that maturation appears to employ different effects on these two substrains during these processes. Furthermore, young adult B6J and B6N mice might be similar in olfactory habituation but different in the olfactory aspects of novelty seeking.
Language	English
Publishing date	2022-02-02
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2452960-6
ISSN	1662-5153
ISSN	1662-5153
DOI	10.3389/fnbeh.2022.808978
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Article ; Online: Profiling of VEGF Receptors and Immune Checkpoints in Recurrent Respiratory Papillomatosis.

Lam, Brandon / Miller, Jonas / Kung, Yu Jui / Wu, T C / Hung, Chien-Fu / Roden, Richard B S / Best, Simon R

The Laryngoscope

2024

Abstract: Objectives: Recurrent respiratory papillomatosis (RRP) is caused by human papilloma virus (HPV) infection of the aerodigestive tract that significantly impacts quality-of-life including the ability to communicate and breathe. Treatment was traditionally ...

Abstract	Objectives: Recurrent respiratory papillomatosis (RRP) is caused by human papilloma virus (HPV) infection of the aerodigestive tract that significantly impacts quality-of-life including the ability to communicate and breathe. Treatment was traditionally limited to serial ablative procedures in the O.R. with possible local adjuvant therapy, but new systemic therapies, such as Vascular endothelial growth factor (VEGF) inhibitors, are showing significant promise. This study aims to determine whether rationale exists for combination therapeutic approaches using VEGF inhibitors and/or immune checkpoint blockade. Methods: Using fresh specimens from the O.R., we performed flow cytometry on papilloma, normal adjacent tissue, and blood. Papilloma and surrounding tissue were examined for expression of PD-L1, PD-L2, Galectin-9, VEGFR2, and VEGFR3. CD8+ and CD4+ T cells were assayed for expression of PD-1, TIGIT, LAG3, and TIM3. Results: Our data shows that papilloma tissue exhibits significantly higher levels of PD-L1 and PD-L2 compared to adjacent tissue. Elevated levels of the VEGF receptor VEGFR3 were also observed in papilloma tissue. When examining T cells within the papilloma, elevated PD-1 and TIGIT expression was observed on CD8+ T cells, while levels of PD-1, TIGIT, and TIM3 were elevated on CD4+ T cells compared to PBMCs. Heterogenous marker expression was observed between individuals. Conclusions: Our analysis shows that RRP tissue shows elevated levels of multiple immune check point targets and VEGFR3, with varied patterns unique to each papilloma patient. Some of these immune checkpoint markers already have novel immunotherapies available or in development, providing molecular rationale to offer these systemic treatments to selected patients affected by RRP alongside VEGF inhibitors. Laryngoscope, 2024.
Language	English
Publishing date	2024-01-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	80180-x
ISSN	1531-4995 ; 0023-852X
ISSN (online)	1531-4995
ISSN	0023-852X
DOI	10.1002/lary.31253
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Article: Congenital Heart Diseases Impair Female Fertility.

Chien, Shao-Ju / Lin, Ying-Jui / Lo, Mao-Hung / Huang, Chien-Fu / Yang, Yao-Hsu

Frontiers in pediatrics

2021 Volume 9, Page(s) 687276

Abstract: Background: ...

Abstract	Background:
Language	English
Publishing date	2021-07-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2711999-3
ISSN	2296-2360
ISSN	2296-2360
DOI	10.3389/fped.2021.687276
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Article ; Online: Interleukin 2-Based Fusion Proteins for the Treatment of Cancer.

MacDonald, Alana / Wu, T-C / Hung, Chien-Fu

Journal of immunology research

2021 Volume 2021, Page(s) 7855808

Abstract: Interleukin 2 (IL-2) plays a fundamental role in both immune activation and tolerance and has revolutionized the field of cancer immunotherapy since its discovery. The ability of IL-2 to mediate tumor regression in preclinical and clinical settings led ... ...

Abstract	Interleukin 2 (IL-2) plays a fundamental role in both immune activation and tolerance and has revolutionized the field of cancer immunotherapy since its discovery. The ability of IL-2 to mediate tumor regression in preclinical and clinical settings led to FDA approval for its use in the treatment of metastatic renal cell carcinoma and metastatic melanoma in the 1990s. Although modest success is observed in the clinic, cancer patients receiving IL-2 therapy experience a wide array of side effects ranging from flu-like symptoms to life-threatening conditions such as vascular leak syndrome. Over the past three decades, efforts have focused on circumventing IL-2-related toxicities by engineering methods to localize IL-2 to the tumor or secondary lymphoid tissue, preferentially activate CD8
MeSH term(s)	Animals ; CD8-Positive T-Lymphocytes/immunology ; Humans ; Interleukin-2/immunology ; Killer Cells, Natural/immunology ; Neoplasms/immunology ; Neoplasms/therapy ; Recombinant Fusion Proteins/immunology
Chemical Substances	Interleukin-2 ; Recombinant Fusion Proteins
Language	English
Publishing date	2021-11-08
Publishing country	Egypt
Document type	Journal Article ; Review
ZDB-ID	2817541-4
ISSN	2314-7156 ; 2314-7156
ISSN (online)	2314-7156
ISSN	2314-7156
DOI	10.1155/2021/7855808
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Article ; Online: Virus-like particle vaccine displaying an external, membrane adjacent MUC16 epitope elicits ovarian cancer-reactive antibodies.

Tu, Hsin-Fang / Wong, Margaret / Tseng, Ssu-Hsueh / Ingavat, Nattha / Olczak, Pola / Notarte, Kin Israel / Hung, Chien-Fu / Roden, Richard B S

Journal of ovarian research

2024 Volume 17, Issue 1, Page(s) 19

Abstract: Background: MUC16 is a heavily glycosylated cell surface mucin cleaved in the tumor microenvironment to shed CA125. CA125 is a serum biomarker expressed by > 95% of non-mucinous advanced stage epithelial ovarian cancers. MUC16/CA125 contributes to the ... ...

Abstract	Background: MUC16 is a heavily glycosylated cell surface mucin cleaved in the tumor microenvironment to shed CA125. CA125 is a serum biomarker expressed by > 95% of non-mucinous advanced stage epithelial ovarian cancers. MUC16/CA125 contributes to the evasion of anti-tumor immunity, peritoneal spread and promotes carcinogenesis; consequently, it has been targeted with antibody-based passive and active immunotherapy. However, vaccination against this self-antigen likely requires breaking B cell tolerance and may trigger autoimmune disease. Display of self-antigens on virus-like particles (VLPs), including those produced with human papillomavirus (HPV) L1, can efficiently break B cell tolerance. Results: A 20 aa juxta-membrane peptide of the murine MUC16 (mMUC16) or human MUC16 (hMUC16) ectodomain was displayed either via genetic insertion into an immunodominant loop of HPV16 L1-VLPs between residues 136/137, or by chemical coupling using malemide to cysteine sulfhydryl groups on their surface. Female mice were vaccinated intramuscularly three times with either DNA expressing L1-MUC16 fusions via electroporation, or with alum-formulated VLP chemically-coupled to MUC16 peptides. Both regimens were well tolerated, and elicited MUC16-specific serum IgG, although titers were higher in mice vaccinated with MUC16-coupled VLP on alum as compared to L1-MUC16 DNA vaccination. Antibody responses to mMUC16-targeted vaccination cross-reacted with hMUC16 peptide, and vice versa; both were reactive with the surface of CA125+ OVCAR3 cells, but not SKOV3 that lack detectable CA125 expression. Interestingly, vaccination of mice with mMUC16 peptide mixed with VLP and alum elicited mMUC16-specific IgG, implying VLPs provide robust T help and that coupling may not be required to break tolerance to this epitope. Conclusion: Vaccination with VLP displaying the 20 aa juxta-membrane MUC16 ectodomain, which includes the membrane proximal cleavage site, is likely to be well tolerated and induce IgG targeting ovarian cancer cells, even after CA125 is shed.
MeSH term(s)	Humans ; Female ; Animals ; Mice ; Ovarian Neoplasms/genetics ; Vaccines, Virus-Like Particle ; Epitopes ; Apoptosis ; Cell Line, Tumor ; Peptides ; Immunoglobulin G ; DNA ; CA-125 Antigen/genetics ; Tumor Microenvironment ; Membrane Proteins/genetics ; Alum Compounds
Chemical Substances	aluminum sulfate (34S289N54E) ; Vaccines, Virus-Like Particle ; Epitopes ; Peptides ; Immunoglobulin G ; DNA (9007-49-2) ; CA-125 Antigen ; MUC16 protein, human ; Membrane Proteins ; Alum Compounds
Language	English
Publishing date	2024-01-16
Publishing country	England
Document type	Journal Article
ZDB-ID	2455679-8
ISSN	1757-2215 ; 1757-2215
ISSN (online)	1757-2215
ISSN	1757-2215
DOI	10.1186/s13048-023-01325-9
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Article ; Online: Lipopolysaccharide-Initiated Rhinosinusitis Causes Neuroinflammation and Olfactory Dysfunction in Mice.

Yeh, Chien-Fu / Huang, Wei-Hao / Lan, Ming-Ying / Hung, Wei

American journal of rhinology & allergy

2022 Volume 37, Issue 3, Page(s) 298–306

Abstract: Background: Olfactory dysfunction is a common disease and it may be caused by sinonasal inflammation, toxin inhalation, or neurological disorders. After sinonasal inflammation, if both olfactory neuroinflammation and olfactory dysfunction occur still ... ...

Abstract	Background: Olfactory dysfunction is a common disease and it may be caused by sinonasal inflammation, toxin inhalation, or neurological disorders. After sinonasal inflammation, if both olfactory neuroinflammation and olfactory dysfunction occur still under investigation. Objective: This study aimed to investigate whether neuroinflammation and olfactory dysfunction occur after lipopolysaccharide (LPS)-initiated rhinosinusitis. Methods: Adult C57BL/6 mice were intranasally administered with LPS for 3 weeks. The olfactory function was evaluated with a buried food test. The inflammatory status of sinonasal cavity and olfactory bulb was evaluated with histology and biochemistry. Results: After 3-week LPS treatment, mice developed olfactory dysfunction, sinonasal cavity, and olfactory bulb inflammation. LPS-treated mice had greater sinonasal mucosal thickness. Besides, pro-inflammatory interleukin-6, the number of goblet cells and neutrophils in the sinonasal cavity was increased after LPS administration. The olfactory sensory neurons in the olfactory epithelium and the olfactory bulb were decreased, and the olfactory function was impaired by LPS administration. Inflammatory cytokines such as interferon-γ and tumor necrosis factor-α were increased in the olfactory bulb. Conclusion: This study showed that LPS-initiated rhinosinusitis caused olfactory neuroinflammation and olfactory dysfunction in mice.
MeSH term(s)	Mice ; Animals ; Lipopolysaccharides ; Neuroinflammatory Diseases ; Mice, Inbred C57BL ; Sinusitis/pathology ; Inflammation/pathology ; Olfactory Bulb/pathology ; Olfaction Disorders/chemically induced ; Olfaction Disorders/pathology
Chemical Substances	Lipopolysaccharides
Language	English
Publishing date	2022-11-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	2482804-X
ISSN	1945-8932 ; 1945-8924
ISSN (online)	1945-8932
ISSN	1945-8924
DOI	10.1177/19458924221140965
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Zs.A 2542: Show issues

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Article ; Online: Dietary supplementation of fermented lemon peel enhances lysozyme activity and susceptibility to Photobacterium damselae for orange-spotted grouper, Epinephelus coioides.

Zhuo, Li-Chao / Chen, Chien-Fu / Lin, Yu-Hung

Fish & shellfish immunology

2021 Volume 117, Page(s) 248–252

Abstract: The waste recycling of lemon peel, as a functional feed additive in aquafeed was evaluated by estimating the effects of fermented lemon peel (FLP) supplementation in diet on growth performance, innate immune responses, and susceptibility to ... ...

Abstract	The waste recycling of lemon peel, as a functional feed additive in aquafeed was evaluated by estimating the effects of fermented lemon peel (FLP) supplementation in diet on growth performance, innate immune responses, and susceptibility to Photobacterium damselae of grouper, Epinephelus coioides. A basal diet was added FLP at 0%, 1%, 3%, and 5%. Four tested diets were each fed to juvenile grouper (initial weight: 15.89 ± 0.10 g, triplicate groups) in a recirculation rearing system for eight weeks. Fish fed diets with 0%-3% FLP exhibited higher (p < 0.05) final weight, weight gain, and feed efficiency than fish fed the 5% FLP-diet. After challenge test, fish fed the 3% FLP-diet appeared the lowest mortality, followed by fish fed the 1% FLP-diet, and lowest in fish fed 0% and 5% FLP-diets. Plasma lysozyme activities were higher in fish fed diets with FLP than in fish fed the FLP-free control diet before challenge test. After challenge, fish fed diets with 1% and 3% FLP showed highest lysozyme activities, followed by fish fed the diet with 5% FLP, and lowest in fish fed the control diet. Hepatic malondialdehyde content was higher in fish fed the control diet than in fish fed diets with 1%-3% FLP. Results found that diets supplemented with 1%-3% fermented lemon peel can enhance lysozyme activity and resistance to pathogen P. damselae of grouper.
MeSH term(s)	Animals ; Citrus ; Dietary Supplements ; Disease Susceptibility ; Fermentation ; Fish Diseases/immunology ; Fruit ; Gram-Negative Bacterial Infections/immunology ; Gram-Negative Bacterial Infections/veterinary ; Liver/immunology ; Malondialdehyde/immunology ; Muramidase/blood ; Muramidase/immunology ; Perciformes/blood ; Perciformes/immunology ; Perciformes/microbiology ; Photobacterium
Chemical Substances	Malondialdehyde (4Y8F71G49Q) ; Muramidase (EC 3.2.1.17)
Language	English
Publishing date	2021-08-19
Publishing country	England
Document type	Journal Article ; Randomized Controlled Trial, Veterinary
ZDB-ID	1067738-0
ISSN	1095-9947 ; 1050-4648
ISSN (online)	1095-9947
ISSN	1050-4648
DOI	10.1016/j.fsi.2021.08.015
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Article: STAT1-Deficient HPV E6/E7-Associated Cancers Maintain Host Immunocompetency against Therapeutic Intervention.

Lim, Ling / Hu, Ming-Hung / Fan, Darrell / Tu, Hsin-Fang / Tsai, Ya-Chea / Cheng, Michelle / Wang, Suyang / Chang, Chih-Long / Wu, Tzyy-Choou / Hung, Chien-Fu

Vaccines

2024 Volume 12, Issue 4

Abstract: Human papillomavirus (HPV) remains a global health concern because it contributes to the initiation of various HPV-associated cancers such as anal, cervical, oropharyngeal, penile, vaginal, and vulvar cancer. In HPV-associated cancers, oncogenesis begins ...

Abstract	Human papillomavirus (HPV) remains a global health concern because it contributes to the initiation of various HPV-associated cancers such as anal, cervical, oropharyngeal, penile, vaginal, and vulvar cancer. In HPV-associated cancers, oncogenesis begins with an HPV infection, which is linked to the activation of the Janus protein tyrosine kinase (JAK)/STAT signaling pathway. Various STAT signaling pathways, such as STAT3 activation, have been well documented for their tumorigenic role, yet the role of STAT1 in tumor formation remains unclear. In the current study, STAT1
Language	English
Publishing date	2024-04-17
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2703319-3
ISSN	2076-393X
ISSN	2076-393X
DOI	10.3390/vaccines12040430
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