Article
Immunology
Jing Xun, Siying Zhou, Zongjing Lv, Botao Wang, Hai Luo, Lanqiu Zhang, Lei Yang, Aimin Zhang, Xueliang Wu, Zhenyu Wang, Ximo Wang, Xiangyang Yu, Qi Zhang
Summary: It has been reported that colitis is a risk factor for colorectal cancer. Intervening in intestinal inflammation and early tumorigenesis is crucial in controlling the incidence and mortality of colorectal cancer. Natural active products from traditional Chinese medicine, such as Dioscin, have shown promising progress in disease prevention. Dioscin was found to inhibit the initiation and tumorigenesis of colitis-associated colon cancer, including reducing colonic inflammation, improving intestinal barrier function, and decreasing tumor burden. Furthermore, Dioscin also demonstrated immunoregulatory effects by modulating macrophage phenotype and inhibiting monocytic myeloid-derived suppressor cells in mice.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Food Science & Technology
Yaozhong Hu, Jiaxin Gu, Jing Lin, Yi Wang, Feier Yang, Jia Yin, Zhenting Yu, Sihao Wu, Huan Lv, Xuemeng Ji, Shuo Wang
Summary: The intervention of EGCG on macrophage polarization was found to promote M2 polarization and inhibit M1 polarization, particularly in liver, colon, spleen, and brain.
JOURNAL OF FUNCTIONAL FOODS
(2021)
Review
Immunology
Maorun Zhang, Xiaoping Li, Qi Zhang, Jiahua Yang, Gang Liu
Summary: Colitis-associated colorectal cancer (CAC) is a severe complication of ulcerative colitis (UC), characterized by multiple lesions, worse pathological type, and poor prognosis. Macrophages, as innate immune cells, play a crucial role in both inflammatory response and tumor immunity. Enhanced macrophage infiltration in UC leads to the production of inflammatory cytokines, promoting UC tumorigenesis. Macrophage polarization into M1 has an anti-tumor effect, while M2 polarization promotes tumor growth. Targeting macrophages has shown effectiveness in preventing and treating CAC.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Yong Cao, Yan Lin, Yan Sun, Weiyu Liu, Yichuan Shao, Changqing Zheng
Summary: The study demonstrated that 4-HPR may be a potent anti-UC agent that works by regulating macrophage polarization via PPAR gamma.
Article
Biochemistry & Molecular Biology
Iva Vukelic, Suncica Buljevic, Lara Baticic, Karmela Barisic, Barbara Franovic, Dijana Detel
Summary: Deficiency of CD26 regulates macrophage polarization towards the anti-inflammatory M2 phenotype in UC, primarily driven by STAT6/STAT3 signaling pathways and the reduction of proinflammatory STAT1.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Xin Zheng, Qi Jiang, Mingshun Han, Fenfen Ye, Mingchang Wang, Ying Qiu, Jialu Wang, Minxia Gao, Fajian Hou, Hongyan Wang
Summary: Macrophages are versatile cells that can be activated by different stimuli to differentiate into distinct subsets. FBXO38, a protein identified in this study, was found to promote immunosuppressive function in macrophages without affecting other macrophage functions. Further investigation revealed that deletion of FBXO38 in macrophages can block tumor development and protect against colitis.
CELLULAR & MOLECULAR IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Min Zhu, Xiaotao Wu, Jun Sun, Zhou Zhou, Mingzhu Kang, Yiwei Hu, Liping Teng
Summary: This study aimed to evaluate the immunoregulatory effects of NDesulfated reacetylated derivative of heparin (NDeSAcH) on macrophage polarization. The findings indicated that NDeSAcH could effectively promote the release of nitric oxide (NO), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) in RAW264.7 cells compared to heparin. NDeSAcH also significantly inhibited the production of NO, IL-6, and TNF-alpha in LPS-induced RAW264.7 cells, while suppressing the secretion of transforming growth factor-beta (TGF-beta) in M2 macrophages. These results suggest that NDeSAcH may be a promising candidate for modulating macrophage polarization and treating inflammation-related diseases.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Biochemistry & Molecular Biology
Min Liu, Hanyu Rao, Jing Liu, Xiaoxue Li, Wenxin Feng, Liming Gui, Huayuan Tang, Jin Xu, Wei-Qiang Gao, Li Li
Summary: The study revealed that SETD2 regulates oxidative stress to attenuate colonic inflammation and tumorigenesis in mice. Depletion of Setd2 leads to excess ROS production, disrupting barrier integrity and causing inflammatory damage. These findings highlight the important role of SETD2 in maintaining intestinal epithelial homeostasis.
Article
Virology
Xingyu Gong, Tianyi Ma, Qiaoya Zhang, Yanhong Wang, Chengchuang Song, Min Lai, Chunlei Zhang, Xingtang Fang, Xi Chen
Summary: Porcine reproductive and respiratory syndrome virus (PRRSV) is a major infectious disease in pigs that leads to significant economic losses. This study reveals that PRRSV modulates the polarization of macrophages from M1 to M2 by upregulating the secretion of CD83 induced by monocyte-derived dendritic cells (MoDCs). The inhibition of M1 macrophages and enhancement of M2 macrophages by PRRSV can be counteracted by neutralizing sCD83 or by mutating the sCD83-related amino acid site in PRRSV.
Article
Immunology
Lianlian Tian, Jun-Long Zhao, Jian-Qin Kang, Shi-bo Guo, Nini Zhang, Lei Shang, Ya-Long Zhang, Jian Zhang, Xun Jiang, Yan Lin
Summary: Inflammatory bowel disease (IBD) is characterized by chronic and relapsing intestinal inflammation, with a lack of safe and effective medicine. Studies have shown that Astragaloside IV (AS-IV) extracted from traditional Chinese medicine can alleviate experimental colitis symptoms by modulating macrophage phenotype transition, potentially offering a new approach for IBD treatment.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Pharmacology & Pharmacy
Qi Lv, Yao Xing, Yijun Liu, Qingzhu Chen, Jingyi Xu, Lihong Hu, Yinan Zhang
Summary: Our study demonstrates that didymin can alleviate clinical symptoms of colitis in mice by modulating macrophage phenotypes. Mechanistic studies reveal that didymin induces the conversion of pro-inflammatory M1-like macrophages to anti-inflammatory M2-like macrophages through enhancing fatty acid oxidation.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Immunology
Xiaoya Wang, Hai Zhang, Rui Guo, Xiaomin Li, Haixin Liu, Zhenyu Wang, Qian Du, Dewen Tong, Yong Huang
Summary: miR-223 plays a crucial role in modulating macrophage polarization balance during sepsis, by targeting Nfat5 and Rasa1 to control IL-4-mediated M2-type polarization. miR-223 deletion increases clinical scores and mortality in septic mice, indicating its important regulatory function in sepsis.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Baisui Feng, Lingzhi Xu, Shuo Song, Huazhen Liu, Yan Li, Suqin Hu, Qing Shu, Jiangqi Liu, Zhiqiang Liu, Haiqiong Yu, Pingchang Yang
Summary: The impaired immune regulatory function of M4 cells obtained from UC patient colon lavage fluid (CLF) was characterized in this study. M4s were the most abundant cellular components in CLF (21.3 4.0%). The M2 M4s (M2 cells) from the ulcerative colitis (UC) group showed weaker immune suppressive function and lower abundance. High levels of endoplasmic reticulum (ER) stress associated molecules were detected in UC M2 cells. XBP1 promoted the expression of Rnf20 in M2 cells. Rnf20 reduced PD-L1 abundance in UC M2 cells and impaired the immune suppressive ability. Inhibition of Rnf20 restored the immune regulating capacity of M2 cells and suppressed experimental colitis.
Article
Plant Sciences
Jun Li, Ming Li, Ke Ye, Qixin Jiang, Mi Wang, Xiaodong Wen, Jie Yang
Summary: Xian-He-Cao-Chang-Yan formula (XHCF) is a formula containing six Chinese herbs that has been used to improve symptoms of ulcerative colitis (UC). The study found that XHCF could improve UC by modulating macrophage polarization and metabolic reprogramming.
JOURNAL OF ETHNOPHARMACOLOGY
(2021)
Article
Cell Biology
Beilei Liang, Haicheng Wang, Di Wu, Zuolin Wang
Summary: After dental implantation, M phi s dynamically adapt their phenotypes and play a key role in coordinating interactions with bone cells. While M1 and M2 M phi s have different functions in bone remodelling, it is important to control immune strategies within proper ranges for optimal tissue engineering implants.
JOURNAL OF LEUKOCYTE BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Pirkka-Pekka Laurila, Peiling Luan, Martin Wohlwend, Nadege Zanou, Barbara Crisol, Tanes Imamura de Lima, Ludger J. E. Goeminne, Hector Gallart-Ayala, Minho Shong, Julijana Ivanisevic, Nicolas Place, Johan Auwerx
Summary: Inhibition of sphingolipid synthesis, targeting multiple pathogenic pathways, shows promise as a potential treatment for muscular dystrophies.
Article
Multidisciplinary Sciences
Arwen W. Gao, Gaby El Alam, Amelia Lalou, Terytty Yang Li, Marte Molenaars, Yunyun Zhu, Katherine A. Overmyer, Evgenia Shishkova, Kevin Hof, Maroun Bou Sleiman, Riekelt H. Houtkooper, Joshua J. Coon, Johan Auwerx
Summary: The mitochondrial unfolded protein response (UPRmt) is a potential pharmacological target for aging and age-related diseases. Through an integrative analysis of omics datasets, researchers found that activation of UPRmt through doxycycline (Dox) prolonged the lifespan of genetically divergent worm strains. The study revealed shared and strain-specific mechanisms of the beneficial effects of Dox-induced UPRmt on lifespan, involving impacts on mitochondria, defense response, and lipid metabolism.
Article
Biochemistry & Molecular Biology
Andrea Sanchez-Navarro, Miguel Angel Martinez-Rojas, Adrian Albarran-Godinez, Rosalba Perez-Villalva, Johan Auwerx, Abigail de la Cruz, Lilia G. Noriega, Florencia Rosetti, Norma A. Bobadilla
Summary: Sirt7 deficiency protects mice from acute kidney injury by reducing albuminuria and tubular damage markers, as well as decreasing inflammation. This suggests that Sirt7 plays a critical role in promoting renal damage and inflammation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Laia Morato, Simone Astori, Ioannis Zalachoras, Joao Rodrigues, Sriparna Ghosal, Wei Huang, Isabelle Guillot de Suduiraut, Jocelyn Grosse, Olivia Zanoletti, Lei Cao, Johan Auwerx, Carmen Sandi
Summary: Puberty stress can lead to changes in adiposity and social behavior, and the reduced levels of NAMPT in fat tissue contribute to lifelong reductions in sociability induced by stress. Impairments in the NAD(+)/SIRT1 pathway in the nucleus accumbens are implicated in sociability deficits. Normalization of NAMPT levels or treatment with NAD(+) boosters can prevent impairments in sociability and neuronal excitability in the accumbens.
Article
Gastroenterology & Hepatology
Kassem Makki, Harald Brolin, Natalia Petersen, Marcus Henricsson, Dan Ploug Christensen, Muhammad Tanweer Khan, Annika Wahlstrom, Per-Olof Bergh, Valentina Tremaroli, Kristina Schoonjans, Hanns-Ulrich Marschall, Fredrik Backhed
Summary: The study demonstrates that oligofructose, a soluble dietary fiber, improves host metabolism by modulating bacterial transformation of bile acids in mice fed a western-style diet.
Article
Gastroenterology & Hepatology
Nadia Bresciani, Hadrien Demagny, Vera Lemos, Francesca Pontanari, Xiaoxu Li, Yu Sun, Hao Li, Alessia Perino, Johan Auwerx, Kristina Schoonjans
Summary: Here, we highlight the significance of a locus containing a liver-specific gene encoding a mitochondrial transport protein called SLC25A47. We demonstrate that mice with genetic disruption of the Slc25a47 locus fail to maintain mitochondrial homeostasis, leading to diverse liver abnormalities and profound physiological consequences.
JOURNAL OF HEPATOLOGY
(2022)
Article
Cell Biology
Terytty Yang Li, Arwen W. Gao, Xiaoxu Li, Hao Li, Yasmine J. Liu, Amelia Lalou, Nagammal Neelagandan, Felix Naef, Kristina Schoonjans, Johan Auwerx
Summary: Stressed mitochondria activate the mitochondrial unfolded protein response (UPRmt) to improve organismal health. A study found that increased ATFS-1 translation, mediated by v-ATPase/TORC1, plays an essential role in UPRmt activation and mild mitochondrial stress-induced longevity.
JOURNAL OF CELL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Woo Kyung Lee Doolittle, Sunmi Park, Seul Gi Lee, Seonhyang Jeong, Gibbeum Lee, Dongryeol Ryu, Kristina Schoonjans, Johan Auwerx, Jandee Lee, Young Suk Jo
Summary: This study identified a mechanism linking mitochondrial stress response (MSR) with thyroid cancer progression and revealed a novel pathway regulating tumor growth signaling. The findings suggest that MSR could serve as a predictive marker for assessing the aggressiveness of thyroid cancer and as a promising therapeutic target.
Article
Multidisciplinary Sciences
Maroun Bou Sleiman, Suheeta Roy, Arwen W. Gao, Marie C. Sadler, Giacomo V. G. von Alvensleben, Hao Li, Saunak Sen, David E. Harrison, James F. Nelson, Randy Strong, Richard A. Miller, Zoltan Kutalik, Robert W. Williams, Johan Auwerx
Summary: This study provides insights into the determinants of health, disease, and aging by examining DNA variants that affect life span. The researchers identified sex-specific genetic effects on life span and gene expression, and validated several genes as conserved longevity genes. The findings underscore the importance of early access to nutrients and early growth for longevity.
Article
Multidisciplinary Sciences
Julianna D. Zeidler, Claudia C. S. Chini, Karina S. Kanamori, Sonu Kashyap, Jair M. Espindola-Netto, Katie Thompson, Gina Warner, Fernanda S. Cabral, Thais R. Peclat, Lilian Sales Gomez, Sierra A. Lopez, Miles K. Wandersee, Renee A. Schoon, Kimberly Reid, Keir Menzies, Felipe Beckedorff, Joel M. Reid, Sebastian Brachs, Ralph G. Meyer, Mirella L. Meyer-Ficca, Eduardo Nunes Chini
Summary: It has been found that dietary vitamin B-3 can partially regulate the levels of NAM and its derived metabolites in plasma, but not in tissues. The synthesis of NAD from tryptophan and the enzyme CD38 play a major role in the production of plasma and tissue NAM.
Review
Biochemistry & Molecular Biology
Fahmida Jahan, Goutham Vasam, Alex E. Green, Shannon A. Bainbridge, Keir J. Menzies
Summary: The placenta plays a crucial role in pregnancy, regulating various aspects such as adaptation to pregnancy, maternal-fetal exchange, and fetal development. Placental dysfunction, particularly in the case of preeclampsia, can lead to adverse pregnancy outcomes. This review examines the evidence of placental mitochondrial dysfunction in preeclampsia and discusses the potential of targeting mitochondria for therapeutic interventions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Giorgia Benegiamo, Giacomo V. G. von Alvensleben, Sandra Rodriguez-Lopez, Ludger J. E. Goeminne, Alexis M. Bachmann, Jean-David Morel, Ellen Broeckx, Jing Ying Ma, Vinicius Carreira, Sameh A. Youssef, Nabil Azhar, Dermot F. Reilly, Katharine D'Aquino, Shannon Mullican, Maroun Bou-Sleiman, Johan Auwerx
Summary: Mice from different genetic backgrounds have diverse responses to metabolic challenges. PWK/PhJ mice show significant mitochondrial dysfunction and progress to fibrotic NASH similar to human NASH, making them a novel NASH mouse model.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Article
Biology
Ece Yildiz, Gaby El Alam, Alessia Perino, Antoine Jalil, Pierre-Damien Denechaud, Katharina Huber, Lluis Fajas, Johan Auwerx, Giovanni Sorrentino, Kristina Schoonjans
Summary: During severe or chronic hepatic injury, biliary epithelial cells (BECs) can rapidly accumulate lipids and undergo metabolic rewiring, leading to their conversion into reactive progenitor cells. This process, driven by the activation of E2F transcription factors, plays a crucial role in the early stages of non-alcoholic fatty liver disease (NAFLD) and provides insights into the connection between lipid metabolism, stemness, and regeneration.
Article
Cell Biology
Terytty Yang Li, Qi Wang, Arwen W. Gao, Xiaoxu Li, Yu Sun, Adrienne Mottis, Minho Shong, Johan Auwerx
Summary: Lysosomal acidification through v-ATPase is crucial for the transcriptional activation of the mitochondrial unfolded protein response (UPRmt). The activation of lysosomes by v-ATPase stimulates mTORC1, which then phosphorylates the transcription factor ATF4, leading to the activation of the UPRmt and mitochondrial function resilience.
Article
Medicine, Research & Experimental
Yu Sun, Hadrien Demagny, Adrien Faure, Francesca Pontanari, Antoine Jalil, Nadia Bresciani, Ece Yildiz, Melanie Korbelius, Alessia Perino, Kristina Schoonjans
Summary: The enzyme asparagine synthetase (ASNS) is responsible for the de novo synthesis of the nonessential amino acid asparagine. The expression of ASNS in pericentral hepatocytes, specialized liver cells in xenobiotic detoxification, is significantly increased in models of acute liver injury. Mice with hepatocyte-specific Asns deletion are more susceptible to pericentral liver damage, which can be reversed by intravenous administration of asparagine. The upregulation of ASNS in response to stress is mediated by the nuclear receptor, liver receptor homolog 1 (LRH-1; NR5A2) through an ATF4-independent, noncanonical pathway.
JOURNAL OF CLINICAL INVESTIGATION
(2023)