Review
Biochemistry & Molecular Biology
Marco Cippitelli, Helena Stabile, Andrea Kosta, Sara Petillo, Lorenzo Lucantonio, Angela Gismondi, Angela Santoni, Cinzia Fionda
Summary: Nuclear factor-kappa B (NF-kappa B) transcription factors are crucial in the pathogenesis of multiple myeloma (MM). The activation of canonical and noncanonical NF-kappa B pathways, triggered by mutations or the production of cytokines and growth factors, supports the survival, proliferation, and chemoresistance of malignant plasma cells. NF-kappa B also affects the activity of noncancerous cells, including mesenchymal stromal cells (MSCs), which play a critical role in disease progression and the interplay between MSCs and MM cells. This review aims to analyze the role of NF-kappa B in MM, focusing on NF-kappa B-dependent mechanisms in tumor cells, MSCs, and their crosstalk.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Zilu Zhang, Chenjing Ye, Jia Liu, Wenbin Xu, Chao Wu, Qing Yu, Xiaoguang Xu, Xinyi Zeng, Huizi Jin, Yingli Wu, Hua Yan
Summary: JaponiconeA (JA) is a natural product with potent anti-tumor effects against multiple myeloma, inhibiting cell proliferation, inducing apoptosis, and cell cycle arrest. In vitro and in vivo experiments showed synergistic effects of JA in combination with bortezomib and enhanced anti-tumor effects in drug-resistant cells.
CANCER BIOLOGY & MEDICINE
(2022)
Article
Oncology
Zsolt Matula, Gabor Mikala, Szilvia Lukacsi, Janos Matko, Tamas Kovacs, Eva Monostori, Ferenc Uher, Istvan Valyi-Nagy
Summary: Mitochondrial transfer plays a crucial role in drug resistance acquisition in multiple myeloma, with bi-directional transfer occurring through tunneling nanotubes and partial cell fusion, especially under the influence of chemotherapeutic drugs. By influencing tumor metabolism and using oxidative phosphorylation inhibitors alongside chemotherapy, the supportive effect of stromal cells can be effectively avoided in myeloma cells.
Article
Biochemistry & Molecular Biology
Shuo-Yu Wang, Yin-Hwa Shih, Tzong-Ming Shieh, Yu-Hsin Tseng
Summary: This study investigated the mechanisms of cytarabine resistance in acute myeloid leukemia (AML) and suggested the potential application of proteasome inhibitors in relapsed or refractory leukemia patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Oncology
Patricia Maiso, Pedro Mogollon, Enrique M. Ocio, Mercedes Garayoa
Summary: Multiple myeloma is a cancer of plasma cells that accumulate in the bone marrow, and the interaction between mesenchymal stromal cells and myeloma cells appears to play a crucial role in the progression of the disease. Structural and functional differences between mesenchymal stromal cells from healthy donors and myeloma patients have been identified, suggesting a significant contribution to the pathophysiology of multiple myeloma.
Article
Oncology
Jing Chen, Shiyu Wang, Bart Blokhuis, Rob Ruijtenbeek, Johan Garssen, Frank Redegeld
Summary: This study demonstrates that omega-3 polyunsaturated fatty acids DHA/EPA and the proteasome inhibitor bortezomib can induce necroptosis in human multiple myeloma cells independent of RIPK3. It also shows that phosphorylation of MLKL is not essential for necroptosis induction in these cells. Furthermore, it reveals that activated caspase-3/8/10 triggers proteolytic cleavage of MLKL, and mutation of Asp140Ala in MLKL blocks this cleavage.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Masanobu Tsubaki, Tomoya Takeda, Takuya Matsuda, Shiori Seki, Yoshika Tomonari, Shoutaro Koizumi, Miki Nagatakiya, Mai Katsuyama, Yuuta Yamamoto, Katsumasa Tsurushima, Toshihiko Ishizaka, Shozo Nishida
Summary: This study reveals different mechanisms of resistance to bortezomib and ixazomib in multiple myeloma cell lines, with high expression levels of SGK1 and NF-kappa B p65 associated with low sensitivity to bortezomib and poor prognosis. Combining bortezomib and ixazomib with SGK1 or NF-kappa B inhibitors may enhance their efficacy in multiple myeloma treatment.
Article
Multidisciplinary Sciences
Antonio Garcia-Gomez, Tianlu Li, Carlos de la Calle-Fabregat, Javier Rodriguez-Ubreva, Laura Ciudad, Francesc Catala-Moll, Gerard Godoy-Tena, Montserrat Martin-Sanchez, Laura San-Segundo, Sandra Muntion, Xabier Morales, Carlos Ortiz-de-Solorzano, Julen Oyarzabal, Edurne San Jose-Eneriz, Manel Esteller, Xabier Agirre, Felipe Prosper, Mercedes Garayoa, Esteban Ballestar
Summary: Research has shown that mesenchymal stromal cells (MSCs) isolated from the bone marrow of multiple myeloma patients exhibit altered DNA methylation patterns, and treatment with a methyltransferase inhibitor can reverse MM-associated bone loss and reduce tumor burden in MM murine models.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Cuicui Wu
Summary: The study investigated the synergistic effect of beta-catenin inhibitors, ICG-001 and pyrvinium (PP), with BTZ in treating BTZ-resistant MM cells. Results showed that these inhibitors not only increased apoptosis but also sensitized BTZ-resistant MM cells to BTZ, indicating their potential therapeutic application in MM.
Article
Biochemistry & Molecular Biology
Zsolt Matula, Ferenc Uher, Istvan Valyi-Nagy, Gabor Mikala
Summary: Belantamab mafodotin (belamaf) is an afucosylated monoclonal antibody that targets B cell maturation antigen (BCMA) and can eliminate myeloma cells through multiple mechanisms. However, primary myeloma cells can exhibit widely varying levels of BCMA expression, and low expression is associated with high resistance to belamaf. Additionally, we found that increasing concentrations of belamaf can lead to enhanced incorporation of mitochondria from bone marrow stromal cells, resulting in increased resistance to belamaf, similar to other medications like carfilzomib or venetoclax. The observed resistance to belamaf suggests the need for combination therapies to overcome the risk of antigen escape.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Nanoscience & Nanotechnology
You-Ren Ji, Ching-Chia Cheng, An-Li Lee, Jonathan Chang-Cheng Shieh, Hsin-Ju Wu, Abel Po-Hao Huang, Yi-Hua Hsu, Tai-Horng Young
Summary: The novel polycation PAG induced apoptosis in GBM cells, while the commonly used polycation PAH induced necrosis. PAG coating limited the proliferation of GBM8901 cells and induced apoptotic cell death via the NF-kappa B pathway by the regulation of TGF-beta. These findings suggest that PAG has potential in suppressing cancer cell proliferation and promoting neural viability.
ACS APPLIED MATERIALS & INTERFACES
(2021)
Article
Biochemistry & Molecular Biology
Anna Staskiewicz, Erica Wong, Michael Tucker, Riya Farhin, Jonathan Park, Rana Saade, Tina Alkhazali, Tu Dang, Xinyu Wang
Summary: Multiple myeloma (MM) is a cancer characterized by bone lesions, hypercalcemia, anemia, and renal failure. Bortezomib (BTZ) is a common treatment for MM, but can be toxic at high doses. Resveratrol (RES), a compound found in grapes, inhibits MM cell growth. This study identified a synergistic combination of BTZ and a RES derivative that decreased MM cell viability by inducing apoptosis and oxidative stress.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Xiaowen Ge, Yiqun Du, Jianfeng Chen, Na Zhu, Jiamei Yao, Xin Zhang, Na Wang, Yujing Sun, Feng Gao, Weiguo Hu, Yingyong Hou
Summary: The study showed that herbal drugs (curcumin and perillyl alcohol) specifically inhibit NF-κB, increasing the sensitivity of resistant cells to rituximab. The activation of NF-κB and CREB is highly correlated with CD59 expression in B-NHL tissues.
FRONTIERS IN ONCOLOGY
(2021)
Article
Hematology
Manjun Li, Melissa K. Bennett, John Toubia, Victoria S. Pope, Melinda N. Tea, Sarah Tamang, Michael S. Samuel, Paul H. Anderson, Briony L. Gliddon, Jason A. Powell, Stuart M. Pitson
Summary: This article describes the development of a mouse model of bortezomib-resistant multiple myeloma for the evaluation of new therapeutic approaches.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Cell Biology
Nicholas Nikesitch, Patricia Rebeiro, Lye Lin Ho, Srinivasa Pothula, Xin Maggie Wang, Tiffany Khong, Hazel Quek, Andrew Spencer, Cheok Soon Lee, Tara L. Roberts, Silvia C. W. Ling
Summary: The study found that the upregulation of CMA in Bz-resistant MM cells and the inhibition of CMA can sensitize the resistant cells to Bz. The protein levels of LAMP2A, the rate-limiting factor of the CMA pathway, were significantly increased in MM patients resistant to Bz and in the Bz-resistant cell line model. Inhibition of CMA sensitizes Bz-resistant cells to Bz and the combination of CMA inhibition and Bz had a more cytotoxic effect on myeloma cells than Bz alone.
Article
Hematology
C. B. Webb, S. G. Yates, R. Sarode, J. Kim
Summary: Therapeutic plasma exchange (TPE) may be considered as an adjunct treatment for patients with acute complications of sickle cell disease (SCD) that progress to multiple organ dysfunction syndrome (MODS), especially in cases where there is no significant improvement following red cell exchange (RBCx).
Article
Oncology
Jenna L. L. Hansen, Mark B. B. Juckett, Mikayla A. A. Foster, Meredith E. E. Rumble, Keayra E. E. Morris, Peiman Hematti, Erin S. S. Costanzo
Summary: This study comprehensively evaluated physical and psychological function among individuals with cGVHD and investigated the relationships between disease severity and psychological and physical function, as well as patterns of function by disease site. The results showed that patients with cGVHD in the skin and GI tract had the most severe symptoms, including mood disturbance, fatigue, and pain. These findings suggest that patients with more severe cGVHD and those with cGVHD manifesting in specific sites are at risk for poorer psychological and physical outcomes and may benefit from proactive interventions to optimize function.
JOURNAL OF CANCER SURVIVORSHIP
(2023)
Review
Biochemistry & Molecular Biology
Jiankai Fang, Wangwang Chen, Pengbo Hou, Zhanhong Liu, Muqiu Zuo, Shisong Liu, Chao Feng, Yuyi Han, Peishan Li, Yufang Shi, Changshun Shao
Summary: Nicotinamide adenine dinucleotide (NAD(+)) is an essential molecule in energy metabolism, and it also plays a role in immune response and inflammatory diseases. This review explores the biochemistry of NAD(+) and its impact on the immune system, as well as the potential of NAD(+) research in developing therapeutics for inflammatory diseases, including COVID-19.
CELL AND BIOSCIENCE
(2023)
Article
Green & Sustainable Science & Technology
Yufang Shi, Tianlun Zhang, Yufeng Jiang
Summary: As an emerging economic form, the digital economy plays a crucial role in promoting high-quality economic development, resolving regional development incoherence, and improving the level of urban resilience. This paper analyzes the impact of the digital economy on urban resilience using various models, and finds that the development of the digital economy has a positive impact on improving urban resilience. The digital economy also has positive spatial spillover effects on urban resilience, and technological innovation acts as a mediator in this relationship.
Article
Multidisciplinary Sciences
Nicholas J. Hess, David P. Turicek, Jeremiah Riendeau, Sean J. McIlwain, Emmanuel Contreras Guzman, Kalyan Nadiminti, Amy Hudson, Natalie S. Callander, Melissa C. Skala, Jenny E. Gumperz, Peiman Hematti, Christian M. Capitini
Summary: An important aspect of allogeneic hematopoietic cell transplantations is finding a way to prevent graft-versus-host disease (GVHD) while still maintaining the graft-versus-leukemia (GVL) activity of donor T cells. In an observational clinical study, a specific type of T cell called CD4+/CD8+ double-positive T cell (DPT) was identified in recipients of allo-HCT, and its presence was found to be predictive of severe GVHD. Further experiments using a transplant model revealed that DPTs develop from antigen-stimulated CD8 T cells and exhibit distinct characteristics from single-positive CD4 and CD8 T cells. These findings highlight the role of DPTs in GVHD pathology.
Article
Biology
Crystal C. C. Uwazie, Tyler U. U. Faircloth, Rhett N. N. Parr, Yenamala U. U. Reddy, Peiman Hematti, Devi Rajan, Raghavan Chinnadurai
Summary: In this study, the researchers investigated the effects of human bone-marrow-derived MSCs on peripheral blood dendritic cell responses. They found that plasmacytoid dendritic cells were not significantly affected by MSCs, but myeloid dendritic cells showed increased maturation. The study also identified the secretory factors associated with MSC-mediated upregulation of myeloid dendritic cell maturation. These findings suggest that circulating dendritic cell subsets may serve as potency biomarkers in MSC therapy.
Article
Biochemistry & Molecular Biology
Zhanhong Liu, Pengbo Hou, Jiankai Fang, Jingyu Zhu, Juanmin Zha, Rui Liu, Yayun Ding, Muqiu Zuo, Peishan Li, Lijuan Cao, Chao Feng, Gerry Melino, Changshun Shao, Yufang Shi
Summary: Chemotherapy resistance in breast cancer can be induced by mesenchymal stromal cells (MSCs) through reducing the intratumoral accumulation of doxorubicin. This resistance is mediated by hyaluronan (HA), a major extracellular matrix (ECM) product of MSCs, which can bind with doxorubicin and inhibit its entry into breast cancer cells. High levels of HA in the serum are positively associated with chemoresistance in breast cancer patients.
Review
Biochemistry & Molecular Biology
Yanan Li, Sara Giovannini, Tingting Wang, Jiankai Fang, Peishan Li, Changshun Shao, Ying Wang, Yufang TOR Ctr, Yufang Shi, Eleonora Candi, Gerry Melino, Francesca Bernassola
Summary: Epithelial tissue homeostasis is closely associated with the self-renewal and differentiation behaviors of epithelial stem cells (ESCs). p63, a well-known marker of ESCs, regulates the transcription of genes involved in cell survival, stem cell self-renewal, migration, differentiation, and epithelial-to-mesenchymal transition. p63 plays a crucial role in normal epithelial development and epithelium-derived cancer pathogenesis.
Review
Cell Biology
Rui Liu, Manuel Scimeca, Qiang Sun, Gerry Melino, Alessandro Mauriello, Changshun Shao, Yufang TOR Ctr, Yufang Shi, Mauro Piacentini, Giuseppe Tisone, Massimiliano Agostini
Summary: Liver regeneration is a complex process involving inflammation, granulation, and tissue remodeling. Hepatic macrophages play a crucial role in orchestrating liver regeneration by transitioning between tolerant and inflammatory phenotypes. Dysfunctional macrophages can exacerbate liver injury and promote fibrosis and cirrhosis, highlighting the need for macrophage-targeting strategies. Metabolic rewiring may offer a potential therapeutic approach to modulate macrophage function and promote liver inflammation management and regeneration.
CELL DEATH & DISEASE
(2023)
Review
Cell & Tissue Engineering
Mengting Zhu, Lijuan Cao, Sonia Melino, Eleonora Candi, Ying Wang, Changshun Shao, Gerry Melino, Yufang Shi, Xiaodong Chen
Summary: This review outlines the role of mesenchymal stem/stromal cells (MSCs) in wound healing and regeneration, with a focus on the central role of neutrophils, macrophages, and T cells in the interaction between MSCs and the immune system. The specific effects of MSC-based therapy on different pathological wound healing are also discussed, along with the translation of scientific advances in MSCs into clinical strategies.
STEM CELLS TRANSLATIONAL MEDICINE
(2023)
Article
Immunology
Jiankai Fang, Pengbo Hou, Shisong Liu, Muqiu Zuo, Zhanhong Liu, Wangwang Chen, Yuyi Han, Yanan Li, Tingting Wang, Chao Feng, Peishan Li, Changshun Shao, Yufang Shi
Summary: Mesenchymal stem/stromal cells (MSCs) have strong immunoregulatory functions and can be used for treating inflammatory disorders. This capacity is not inherent but is activated or 'licensed' by inflammatory cytokines. The mechanism behind this activation is still unclear, but it is suggested that inflammatory cytokines metabolically reprogram MSCs to confer immunoregulatory capacity.
CELLULAR & MOLECULAR IMMUNOLOGY
(2023)
Correction
Immunology
Xue Yang, Qing Li, Wenting Liu, Chen Zong, Lixin Wei, Yufang Shi, Zhipeng Han
CELLULAR & MOLECULAR IMMUNOLOGY
(2023)
Review
Immunology
Xue Yang, Qing Li, Wenting Liu, Chen Zong, Lixin Wei, Yufang Shi, Zhipeng Han
Summary: Hepatic fibrosis/cirrhosis is a complex condition with a significant global health burden. Endogenous and exogenous mesenchymal stromal cells (MSCs) play key roles in its pathogenesis and treatment. Clinical trials have shown the effectiveness of exogenous MSCs in liver cirrhosis, but there are still challenges to be addressed for their future clinical use. This review examines the role of MSCs in hepatic fibrosis/cirrhosis and discusses the standardization of parameters and promotion of MSCs' clinical application.
CELLULAR & MOLECULAR IMMUNOLOGY
(2023)
Review
Chemistry, Multidisciplinary
Haiyue Tu, Haoyu Ren, Junjie Jiang, Changshun Shao, Yufang Shi, Peishan Li
Summary: This review discusses the multifarious neutrophil death pathways and their effects on immune responses and disease progression. Understanding the multifaceted aspects of neutrophil death and the ramifications of immunity is crucial for the development of novel therapeutic methods.
Article
Biology
Angela Cappello, Giulia Tosetti, Artem Smirnov, Carlo Ganini, Xue Yang, Yufang Shi, Ying Wang, Gerry Melino, Francesca Bernassola, Eleonora Candi
Summary: The study demonstrates a direct role of p63 in the metabolic regulation of Head and neck squamous cell carcinoma (HNSCC), with significant clinical effects on the overall survival of cancer patients. The altered expression of p53 family members and specifically of p63 play a pivotal role in the pathogenesis of HNSCC. Physiologically, p63 affects metabolism through the direct transactivation of enzymes and controls the proliferation of epithelial cells.