Article
Biochemistry & Molecular Biology
Frederic V. Schwabe, Lotta Happonen, Sofie Ekestubbe, Ariane Neumann
Summary: This study investigated the effects of LL-37 and LTF on blood-derived CD14(+) monocytes and found that these HDPs can induce the release of TNF alpha, nucleosomes, and monocyte ETs. The formation of ETs by LL-37 is dependent on SOCE, MAPK, and ERK1/2, while the release of ETs by LTF is not affected by any inhibitors used in this study.
Article
Immunology
Hao Yu, Ying Feng, Wenjing Du, Meng Zhao, Honghong Jia, Zhe Wei, ShuLin Yan, Zhongchao Han, Leisheng Zhang, Zongjin Li, Zhibo Han
Summary: UC-MSCs products show therapeutic potential in a CCl4-induced ACLF mouse model by reducing liver injury and improving survival rate. The study also reveals that UC-MSCs exhibit preferable homing and delayed attenuation in the damaged liver tissue. These findings provide new references for pharmacology and pharmacokinetics assessments in ACLF.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Review
Biology
Zahra Chinipardaz, Jessica M. Zhong, Shuying Yang
Summary: The goal of regenerative therapy is to restore the structure and function of lost tissues in medicine and dentistry. Challenges such as oxygen and nutrition delivery and infection risk exist. LL-37, a peptide found only in humans, has been shown to play an essential role in neovascularization, stem cell migration and differentiation, and host immune response modulation. It also possesses functions in wound healing, angiogenesis, cell differentiation, and apoptosis modulation.
Article
Chemistry, Medicinal
Yumeng Kang, Chuanxi Zhang, Yang He, Ziyan Zhang, Heliang Liu, Zhongqiu Wei, Jie Yang
Summary: This study investigated the effects of thalidomide on the later stage of inflammation and early stage of fibrosis in rosacea. A long-term induction model was constructed in BALB/c male mice, and the results showed that thalidomide could regulate inflammatory infiltration, collagen deposition, and fibrosis-related processes in rosacea.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2022)
Article
Cell Biology
Pijus K. Barman, Juliana E. Shin, Sloan A. Lewis, Seokjo Kang, Di Wu, Yizhou Wang, Xiaoming Yang, Prakash S. Nagarkatti, Mitzi Nagarkatti, Ilhem Messaoudi, Berenice A. Benayoun, Helen S. Goodridge
Summary: Aging is associated with increased monocyte production as well as altered function, with classical monocytes in old mice showing higher expression of DCMo signature genes. This leads to increased production of moDC in old mice. Additionally, higher expression of Aw112010 in old monocytes may be linked to elevated MHCII expression, indicating a potential mechanism for altered monocyte function during aging.
Article
Nanoscience & Nanotechnology
Shue Jin, Renli Yang, Chen Hu, Shiqi Xiao, Yi Zuo, Yi Man, Yubao Li, Jidong Li
Summary: This study demonstrated a practical biosafety strategy by combining plant polyphenols and LL-37 peptides to modify the fiber surface, resulting in a fibrous scaffold with antimicrobial activity, immunoregulation, and vascularized bone regeneration. In vitro and in vivo experiments confirmed the effectiveness of the modified scaffold in promoting cell migration, differentiation, angiogenesis, and antiinflammatory effects. The fibrous scaffold modified by LL-37 peptide through TA grafting shows significant potential for guided bone regeneration applications.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Article
Engineering, Biomedical
Ting Pan, Wenjing Song, Hongbao Xin, Haiyue Yu, He Wang, Dandan Ma, Xiaodong Cao, Yingjun Wang
Summary: Bone defects pose a major threat to human health and the demand for bone tissue regeneration is increasing worldwide. This study highlights the importance of finding a balance between the degradation behavior of scaffolds and the release profile of miRNA for successful bone repair. The findings provide valuable insights for designing bioactive scaffolds for tissue regeneration.
BIOACTIVE MATERIALS
(2022)
Article
Virology
Niloofar Khairkhah, Azam Bolhassani, Farzad Rajaei, Reza Najafipour
Summary: Human papillomavirus (HPV) type 16 is the most common sexually transmitted virus associated with cervical cancer. In this study, optimal gRNA sequences targeting HPV16 E5, E6, E7, and p97 promoter for CRISPR/Cas9-mediated genome editing were designed. The E6 + E7-treated group showed the best treatment efficacy, with a high percentage of cleaved caspase-3 positive cells (45.75%) and a low mitotic index of 2-3. Additionally, the potential of LL-37 peptide to overcome the CRISPR/Cas9 delivery challenge was demonstrated for the first time. Overall, the study suggests that CRISPR/Cas9-mediated gene editing is an effective, specific, and nontoxic treatment for pre-existing tumors, and the future of precise gene therapy in cancer patients is very promising.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Article
Immunology
Maria Faas, Natacha Ipseiz, Jochen Ackermann, Stephan Culemann, Anika Grueneboom, Fenja Schroeder, Tobias Rothe, Carina Scholtysek, Martin Eberhardt, Martin Boettcher, Philipp Kirchner, Cornelia Stoll, Arif Ekici, Maximilian Fuchs, Meik Kunz, Benno Weigmann, Stefan Wirtz, Roland Lang, Joerg Hofmann, Julio Vera, David Voehringer, Alessandro Michelucci, Dimitrios Mougiakakos, Stefan Uderhardt, Georg Schett, Gerhard Kroenke
Summary: Uncoupling protein-2 and the transcription factor GATA3 were found to regulate the differentiation of AAMs in response to IL-33, leading to their polarization. IL-33 induced metabolic rewiring in macrophages, which subsequently triggered GATA3-mediated AAM polarization.
Article
Multidisciplinary Sciences
Christopher S. Wilson, Emilee M. Hoopes, Alexander C. Falk, Daniel J. Moore
Summary: The immune system of healthy individuals is capable of regulating autoimmunity. However, in Type 1 Diabetes (T1D), natural IgM is unable to perform its normal immunoregulatory function. Treating diabetic mice with IgM from healthy donors or an IgM-enriched preparation called Pentaglobin can reverse the disease and boost protective immunity.
SCIENTIFIC REPORTS
(2022)
Article
Engineering, Biomedical
Mingchao Jin, Juli Zhu, Zhipeng Meng, Xuesheng Jiang, Zhuo Chen, Juntao Xu, Hongliang Gao, Junkun Zhu, Fengfeng Wu
Summary: In this study, a functional MoS2/PDA-LL-37 coating was prepared on TiO2 nanotubes surface. The coating showed enhanced antibacterial and osteogenic activity under near-infrared laser irradiation.
BIOMEDICAL MATERIALS
(2022)
Article
Immunology
Anna-Lena Unterweger, Alena Ruescher, Marietta Seuss, Paula Winkelmann, Florian Beigel, Leandra Koletzko, Simone Breiteneicher, Matthias Siebeck, Roswitha Gropp, Attila Aszodi
Summary: The combined approach of patient immune-profiling and a mouse model based on NSG reconstituted with PBMC from CD patients partially reflects the human disease, showing an immune-remodeling phenotype with increased collagen deposition, elevated levels of specific immune cells, and inflammatory markers. This model provides a platform for studying fibrosis development in CD.
IMMUNITY INFLAMMATION AND DISEASE
(2021)
Article
Physiology
Jianwei Liang, Jianjun Chen, Zhan Ye, Dandan Bao
Summary: LL-37 exerts a protective role in regulating bone loss and abnormal bone metabolism in rats with osteoporosis by activating the Wnt/B-catenin pathway.
PHYSIOLOGICAL RESEARCH
(2022)
Article
Cell Biology
Jessika Appelt, Serafeim Tsitsilonis, Ellen Otto, Denise Jahn, Paul Koehli, Anke Baranowsky, Shan Jiang, Melanie Fuchs, Christian H. Bucher, Georg N. Duda, Karl-Heinz Frosch, Johannes Keller
Summary: Despite the crucial role of osteoclast-to-osteoblast coupling in normal bone turnover, it appears to have limited relevance in bone healing, as shown in the study with CTR-deficient mice. Accelerated bone regeneration was not observed in the CTR-deficient mice, indicating that the specific involvement of the CTR-S1P axis may not significantly impact bone repair.
Article
Chemistry, Multidisciplinary
Liyuan Zheng, Disheng Zhou, Feier Ju, Zixuan Liu, Chenzhi Yan, Zhaoxia Dong, Shuna Chen, Lizhi Deng, Szehoi Chan, Junjie Deng, Xingding Zhang
Summary: A method called oscillating fluid flow (OFF) loading is reported, which enables osteocytes to specifically initiate bone formation without triggering bone resorption. After OFF loading, osteocytes produce multiple soluble mediators that consistently induce robust osteoblastic differentiation and proliferation, while inhibiting osteoclast generation and activity under unloading or pathological conditions. Mechanistic studies reveal that increased glycolysis and activation of the ERK1/2 and Wnt/beta-catenin pathways are the major contributors to the osteoinduction functions induced by osteocytes. Furthermore, an osteocyte lysate-based hydrogel is designed to establish a reservoir of active osteocytes for sustained delivery of bioactive proteins, resulting in accelerated healing by regulating endogenous osteoblast/osteoclast homeostasis.
Article
Multidisciplinary Sciences
Zhifang Zhang, Jinong Feng, Allen Mao, Keith Le, Deirdre La Placa, Xiwei Wu, Jeffrey Longmate, Claudia Marek, R. Paul St Amand, Susan L. Neuhausen, John E. Shively
Article
Immunology
Zhifang Zhang, Deirdre La Placa, Tung Nguyen, Maciej Kujawski, Keith Le, Lin Li, John E. Shively
Article
Cell Biology
Chunyan Zhang, Chanyu Yue, Andreas Herrmann, Jieun Song, Colt Egelston, Tianyi Wang, Zhifang Zhang, Wenzhao Li, Heehyoung Lee, Maryam Aftabizadeh, Yi Jia Li, Peter P. Lee, Stephen Forman, George Somlo, Peiguo Chu, Laura Kruper, Joanne Mortimer, Dave S. B. Hoon, Wendong Huang, Saul Priceman, Hua Yu
Article
Surgery
Yanghee Woo, Zhifang Zhang, Annie Yang, Shyambabu Chaurasiya, Anthony K. Park, Jianming Lu, Sang-In Kim, Susanne G. Warner, Daniel Von Hoff, Yuman Fong
JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
(2020)
Article
Oncology
Shyambabu Chaurasiya, Annie Yang, Seonah Kang, Jianming Lu, Sang-In Kim, Anthony K. Park, Venkatesh Sivanandam, Zhifang Zhang, Yanghee Woo, Susanne G. Warner, Yuman Fong
Article
Oncology
Sang-In Kim, Anthony K. Park, Shyambabu Chaurasiya, Seonah Kang, Jianming Lu, Annie Yang, Venkatesh Sivanandam, Zhifang Zhang, Yanghee Woo, Saul J. Priceman, Yuman Fong, Susanne G. Warner
Summary: The study found that CF33 oncolytic virus has good efficacy against colon cancer and can increase the infiltration of lymphocytes and macrophages in tumors. CF33 infection can upregulate PD-L1 expression on tumor cells and promote an increase in active CD8(+) T cells. Furthermore, combination treatment of CF33 derivatives with anti-PD-L1 resulted in durable tumor regression and long-term survival.
MOLECULAR CANCER THERAPEUTICS
(2021)
Article
Biotechnology & Applied Microbiology
Zhifang Zhang, Annie Yang, Shyambabu Chaurasiya, Anthony K. Park, Jianming Lu, Sang-In Kim, Susanne G. Warner, Yate-Ching Yuan, Zheng Liu, Haiyong Han, Daniel Von Hoff, Yuman Fong, Yanghee Woo
Summary: The study demonstrates that genetically modified oncolytic viruses can significantly upregulate PD-L1 expression in PDAC, and virus-delivered anti-PD-L1 antibodies can enhance anti-tumor immune killing in PDAC.
CANCER GENE THERAPY
(2022)
Review
Oncology
Shyambabu Chaurasiya, Sang-In Kim, Michael O'Leary, Anthony K. Park, Jianming Lu, Seonah Kang, Zhifang Zhang, Annie Yang, Yanghee Woo, Yuman Fong, Susanne G. Warner
Summary: Oncolytic viruses infect and kill cancer cells, while activating immune cells against tumors. Real-time tracking of viral replication and immune responses is crucial for enhancing treatment effects. Additional modalities to track virus-induced changes in tumor microenvironments are being explored.
MOLECULAR THERAPY-ONCOLYTICS
(2021)
Article
Oncology
Sang-In Kim, Shyambabu Chaurasiya, Venkatesh Sivanandam, Seonah Kang, Anthony K. Park, Jianming Lu, Annie Yang, Zhifang Zhang, Isabella A. Bagdasarian, Yanghee Woo, Joshua T. Morgan, Zhirong Yin, Yuman Fong, Susanne G. Warner
Summary: Pancreatic cancer resistance to immunotherapies is partly due to deficits in tumor-infiltrating immune cells and stromal density. Combination therapies that modify stroma and recruit immune cells are needed. This study found that using Calcipotriol to modify the stroma can enhance oncolytic viroimmunotherapy. The results showed that Calcipotriol decreases fibrosis, increases immune cell infiltration, and reduces T cell exhaustion.
MOLECULAR THERAPY-ONCOLYTICS
(2022)
Article
Endocrinology & Metabolism
Alyssa Thunen, Deirdre La Placa, Zhifang Zhang, John E. Shively
Summary: Recent studies have identified a long non-coding RNA, LIPE-AS1, that plays a potential regulatory role in adipogenesis. This study characterizes a specific isoform of the murine lncRNA, mLas-V3, which shows conservation in genomic organization and tissue expression between mouse and man. Knock down of mLas-V3 led to a decrease in pre-adipocyte cell differentiation and induced apoptosis, suggesting its role in protecting against stress associated with adipogenesis.
Article
Medicine, Research & Experimental
Shyambabu Chaurasiya, Annie Yang, Zhifang Zhang, Jianming Lu, Hannah Valencia, Sang-In Kim, Yanghee Woo, Suanne G. Warner, Tove Olafsen, Yuqi Zhao, Xiwei Wu, Seymour Fein, Linda Cheng, Maria Cheng, Nicholas Ede, Yuman Fong
Summary: CF33-hNIS-anti-PD-L1, an oncolytic chimeric poxvirus encoding two transgenes, showed anti-tumor activity against triple-negative breast cancer models in mice. Preclinical toxicology studies demonstrated no adverse effects and a low risk of transmission. Stability and compatibility tests under clinical scenarios confirmed its suitability for clinical use.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2022)
Article
Oncology
Zhifang Zhang, Annie Yang, Shyambabu Chaurasiya, Anthony K. Park, Sang-In Kim, Jianming Lu, Tove Olafsen, Susanne G. Warner, Yuman Fong, Yanghee Woo
Summary: CF33-hNIS-antiPDL1 has anti-pancreatic adenocarcinoma activity and can infect, detect, and kill peritoneal tumors.
MOLECULAR THERAPY-ONCOLYTICS
(2022)
Article
Endocrinology & Metabolism
Zhifang Zhang, Deirdre La Placa, Gabriel Gugiu, Alyssa Thunen, Keith Le, John E. Shively
Summary: Ceacam1 deficiency in mice leads to obesity and a higher risk of liver cancer. Bone marrow transplantation or introduction of the human CEACAM1 gene can reverse the obesity phenotype.
Article
Oncology
Annie Yang, Zhifang Zhang, Shyambabu Chaurasiya, Anthony K. Park, Audrey Jung, Jianming Lu, Sang-In Kim, Saul Priceman, Yuman Fong, Yanghee Woo
Summary: CF33-OVs demonstrate effective antitumor activity and delivery of functional proteins in gastric cancer peritoneal metastases (GCPM) models when delivered intraperitoneally. These preclinical results will inform the design of future peritoneal-directed therapy in GCPM patients.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Endocrinology & Metabolism
Zhifang Zhang, Keith Le, Deirdre La Placa, Brian Armstrong, Marcia M. Miller, John E. Shively