Article
Endocrinology & Metabolism
Chao Gu, Quan Zhou, Xiayu Hu, Xiaoyang Ge, Mingzhuang Hou, Wenhao Wang, Hao Liu, Qin Shi, Yong Xu, Xuesong Zhu, Huilin Yang, Xi Chen, Tao Liu, Fan He
Summary: Osteoporotic bone defects are a severe complication of osteoporosis. This study found that melatonin has the potential to enhance the repair of osteoporotic bone defects by restoring the mitochondrial function of bone marrow-derived mesenchymal stem cells (BMMSCs). In vitro experiments showed that melatonin improved the mitochondrial function of BMMSCs and reduced the level of mitochondrial superoxide. In animal experiments, silk fibroin scaffolds loaded with melatonin partially restored the mitochondrial energy metabolism and osteogenic differentiation of BMMSCs.
JOURNAL OF PINEAL RESEARCH
(2023)
Article
Pharmacology & Pharmacy
Mo Chen, Yan Zhang, Hongqian Wang, Hao Yang, Wen Yin, Saihong Xu, Tao Jiang, Mansi Wang, Feixiang Wu, Weifeng Yu
Summary: This study demonstrates that the NET inhibitor nisoxetine plays a protective role in BDL-induced vascular hyporeactivity in rats by increasing α1-adrenoceptor activation. This research suggests a potential therapeutic target for cardiovascular complications in patients with obstructive jaundice.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Orthopedics
Richard N. Puzzitiello, Jeremy Dubin, Mariano E. Menendez, Michael A. Moverman, Nicholas R. Pagani, Justin Drager, Matthew J. Salzler
Summary: Most respondents believed that stem cell therapies have convincing evidence to support their use for orthopaedic conditions, with 65% stating that these therapies are approved and regulated by the FDA. About 75% of respondents believed that stem cells can stop the progression of arthritis or damaged tendons and relieve pain, while over half believe that stem cells can cure arthritis.
ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY
(2021)
Article
Oncology
Fang Wang, Inge Oudaert, Chenggong Tu, Anke Maes, Arne Van Der Vreken, Philip Vlummens, Elke De Bruyne, Kim De Veirman, Yanmeng Wang, Rong Fan, Ann Massie, Karin Vanderkerken, Peng Shang, Eline Menu
Summary: Multiple myeloma cells obtain proliferative signals from the bone marrow microenvironment through exosomal crosstalk. This study reveals that the expression of system Xc(-) is increased in both bone marrow stromal cells and multiple myeloma cells, which is associated with bortezomib resistance. Glutamate released by system Xc(-) enhances exosome secretion, and the inhibitor of system Xc(-) can reduce bone marrow stromal cell-induced bortezomib resistance and enhance the anti-tumor effects of bortezomib on multiple myeloma cells.
Article
Cell Biology
Annamaria Aprile, Laura Raggi, Simona Bolamperti, Isabella Villa, Mariangela Storto, Gaia Morello, Sarah Marktel, Claudio Tripodo, Maria Domenica Cappellini, Irene Motta, Alessandro Rubinacci, Giuliana Ferrari
Summary: Clinical evidence suggests a relationship between blood and bone, but the underlying mechanism is not fully understood. A study using beta-thalassemia as a model found that increased fibroblast growth factor 23 (FGF23) levels in patients and mice with beta-thalassemia were induced by erythropoietin via ERK1/2 and STAT5 pathways. Inhibiting FGF23 signaling with carboxyl-terminal FGF23 peptide rescued bone defects and restored hematopoietic stem cell function in mice with beta-thalassemia. FGF23 may serve as a molecular link connecting anemia, bone, and the hematopoietic stem cell niche.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Cell Biology
Annamaria Aprile, Laura Raggi, Simona Bolamperti, Isabella Villa, Mariangela Storto, Gaia Morello, Sarah Marktel, Claudio Tripodo, Maria Domenica Cappellini, Irene Motta, Alessandro Rubinacci, Giuliana Ferrari
Summary: This study demonstrates the overproduction of fibroblast growth factor 23 (FGF23) in patients and mice with beta-thalassemia, and shows that inhibition of FGF23 signaling is a safe and effective therapeutic strategy to rescue bone defects and restore hematopoietic stem cell function. FGF23 may serve as a molecular link connecting anemia, bone, and the HSC niche.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Urology & Nephrology
Giedre Martus, Karin Bergling, Javier de Arteaga, Carl M. Oberg
Summary: In this study, SGLT2 inhibition with Empagliflozin was found to increase urinary glucose excretion and lower plasma glucose levels during peritoneal dialysis in rats, without affecting sodium or water transport across the peritoneal barrier.
PERITONEAL DIALYSIS INTERNATIONAL
(2021)
Article
Chemistry, Multidisciplinary
Qixin Chen, Jiaying Li, Feng Han, Qingchen Meng, Huan Wang, Qiang Wei, Zexi Li, Feifei Li, En Xie, Xiaoyan Qin, Song Chen, Weishan Wang, Chaoyong Liu, Bin Li, Fengxuan Han
Summary: Bone repair in patients with osteoporosis is challenging due to abnormal inflammation and high level of ROS. This study developed a composite hydrogel containing MnO2-coated calcium phosphate microspheres to eliminate ROS, regulate immune response, and promote bone repair. The multi-pronged approach holds great promise for treating osteoporotic bone defects.
ADVANCED FUNCTIONAL MATERIALS
(2022)
Review
Cell Biology
Thomas Bessy, Tomer Itkin, Diana Passaro
Summary: The bone marrow tissue is essential for adult hematopoiesis. Recent research has focused on bioengineering BM tissues, with particular emphasis on the vascular system. While the vasculature has traditionally been overlooked, studies have underscored its crucial role in tissue development and hematopoiesis. Future clinical perspectives include the adoptive transfer of vascularized BM-niche grafts to support hematopoiesis in patients.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Long Chen, Wei Luo, Yuanzheng Wang, Xiongbo Song, Senlei Li, Jun Wu, Li Sun
Summary: This study demonstrates that glycosylation modification enhances the directional homing ability of BMSCs to bone defect sites by enabling them to express high levels of sLe(X) antigen. Results show that glycosylation-modified BMSCs can improve the repair of bone defects in mice.
JOURNAL OF NANOBIOTECHNOLOGY
(2021)
Article
Cell & Tissue Engineering
Liang Chen, Ri-Yan Zhang, Jun Xie, Jia-Yi Yang, Kang-Hao Fang, Chen-Xuan Hong, Rong-Bo Yang, Najeeb Bsoul, Lei Yang
Summary: The study found that catalpol can enhance the osteogenic ability of bone marrow mesenchymal stem cells and promote BMSC-mediated angiogenesis by activating the JAK2/STAT3 signaling pathway. This suggests that catalpol may be an ideal therapeutic agent for the clinical treatment of osteoporotic bone fractures.
STEM CELL RESEARCH & THERAPY
(2021)
Article
Biochemistry & Molecular Biology
Runze Jin, Hanshu Zhang, Chujiao Lin, Jinqiang Guo, Weiguo Zou, Zhi Chen, Huan Liu
Summary: Inhibition of miR338 can rescue the dwarfism phenotype caused by Runx2 mutation in a mouse model, suggesting that miR338 may be a potential therapeutic target for cleidocranial dysplasia.
EXPERIMENTAL AND MOLECULAR MEDICINE
(2023)
Article
Biotechnology & Applied Microbiology
Xiongbo Song, Xin Wang, Lin Guo, Tao Li, Yang Huang, Junjun Yang, Zhexiong Tang, Zhenlan Fu, Liu Yang, Guangxing Chen, Cheng Chen, Xiaoyuan Gong
Summary: The study demonstrates that the embedding of Ept in hydrogel can enhance the therapeutic efficacy of BMS, promoting cartilage repair through regulating catabolic and anabolic dynamics in adjacent chondrocytes and enhancing BMSCs chondrogenesis.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Endocrinology & Metabolism
Huajie Dai, Longyi Zheng, Zheng Zhu, Xin Geng, Tianzhichao Hou, Qi Wang, Yijie Zhu, Hong Lin, Shuangyuan Wang, Ruizhi Zheng, Zhiyun Zhao, Mian Li, Jieli Lu, Yu Xu, Tiange Wang, Jianmin Liu, Guang Ning, Weiqing Wang, Yufang Bi, Jie Zheng, Min Xu
Summary: This study aimed to evaluate the causal effect of SGLT2 inhibition on BMD, osteoporosis, and fracture risk using genetics. The results showed little evidence of association between genetically proxied SGLT2 inhibition and BMD, osteoporosis, or most types of fracture. Only a nominal significance was found for fracture of the lower leg and shoulder and upper arm. This study does not support an effect of genetically proxied SGLT2 inhibition on fracture risk.
JOURNAL OF BONE AND MINERAL RESEARCH
(2023)
Article
Chemistry, Medicinal
Ravinder Reddy Gaddam, Karishma Dhuri, Young-Rae Kim, Julia S. Jacobs, Vikas Kumar, Qiuxia Li, Kaikobad Irani, Raman Bahal, Ajit Vikram
Summary: Research has developed a miR-122 inhibitor based on gamma PNA technology, which effectively rescues vascular endothelial dysfunction in mice fed a high-fat diet. Comprehensive safety analysis reveals that the inhibitor is non-toxic in vivo, showing potential for clinical applications.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Cardiac & Cardiovascular Systems
Andrea Cignarella, Gian Paolo Fadini, Chiara Bolego, Lucia Trevisi, Carlotta Boscaro, Viola Sanga, Teresa Maria Seccia, Antonio Rosato, Gian Paolo Rossi, Matthias Barton
Summary: This review discusses the challenges clinicians face in angiogenesis inhibitor therapy, including the need to consider sex differences in clinical efficacy and safety, and proposes future research directions.
CARDIOVASCULAR RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Mattia Albiero, Marianna D'Anna, Benedetta Maria Bonora, Gaia Zuccolotto, Antonio Rosato, Marco Giorgio, Elisabetta Iori, Angelo Avogaro, Gian Paolo Fadini
Summary: For the first time, this study explores the hematopoietic and nonhematopoietic roles of p66Shc in regulating HSPC traffic and ischemic responses. Hematopoietic deletion of p66Shc is sufficient to rescue HSPC mobilization and homing in diabetes after ischemia and improves blood flow recovery. Inhibiting p66Shc in blood cells may be a novel strategy to counter PAD in diabetes.
ANTIOXIDANTS & REDOX SIGNALING
(2022)
Article
Biochemistry & Molecular Biology
Shafeeq A. Mohammed, Mattia Albiero, Samuele Ambrosini, Era Gorica, Gergely Karsai, Carlo M. Caravaggi, Stefano Masi, Giovanni G. Camici, Florian A. Wenzl, Vincenzo Calderone, Paolo Madeddu, Sebastiano Sciarretta, Christian M. Matter, Gaia Spinetti, Thomas F. Luscher, Frank Ruschitzka, Sarah Costantino, Gian Paolo Fadini, Francesco Paneni
Summary: The study shows that APA can restore angiogenic response in experimental diabetes by improving limb vascularization and perfusion through preventing detrimental changes in the THBS1/VEGFA axis. This sets the stage for clinical trials testing APA in the treatment of diabetic PAD.
ANTIOXIDANTS & REDOX SIGNALING
(2022)
Review
Endocrinology & Metabolism
Gian Paolo Fadini, Stefano Del Prato, Angelo Avogaro, Anna Solini
Summary: With the increasing global population aging and prevalence of type 2 diabetes, prevention of diabetic complications remains a major challenge. SGLT2 inhibitors have been proven to reduce DKD progression and improve cardiovascular outcomes, but critical challenges such as channelling bias and database heterogeneity need to be addressed in research studies.
DIABETES OBESITY & METABOLISM
(2022)
Article
Endocrinology & Metabolism
Mattia Albiero, Stefano Ciciliot, Anna Rodella, Ludovica Migliozzi, Francesco Ivan Amendolagine, Carlotta Boscaro, Gaia Zuccolotto, Antonio Rosato, Gian Paolo Fadini
Summary: Innate immune cells infiltrate and spread inflammatory signals in growing adipose tissue, leading to glucose intolerance and insulin resistance in distant tissues. Oncostatin M (OSM), a cytokine, is debated for its role in the metabolic consequences of overfeeding. Through this study, it was found that OSM is required during obesity development, as its concentrations are dynamically regulated during a high-fat diet. Osm(-/-) mice showed glucose intolerance, impaired muscle glucose uptake, and worsened liver inflammation and damage, demonstrating the importance of OSM in adapting to overfeeding.
Article
Endocrinology & Metabolism
Alessandra Giannella, Esmeralda Castelblanco, Carlo Federico Zambon, Daniela Basso, Marta Hernandez, Emilio Ortega, Nuria Alonso, Didac Mauricio, Angelo Avogaro, Giulio Ceolotto, Saula Vigili de Kreutzenberg
Summary: This study analyzed the miRNA expression profile in patients with type 1 diabetes who had either carotid calcified or fibrous plaque. The results showed that miR-503-5p, let-7d-5p, miR-106b-3p, and miR-93-5p were significantly upregulated in patients with calcified plaque, while miR-10a-5p was downregulated. These findings provide new insights into the pathophysiology of plaque formation.
Editorial Material
Cardiac & Cardiovascular Systems
Gian Paolo Fadini, Mario Luca Morieri
EUROPEAN HEART JOURNAL
(2023)
Article
Endocrinology & Metabolism
M. L. Morieri, I. Raz, A. Consoli, M. Rigato, A. Lapolla, F. Broglio, E. Bonora, A. Avogaro, G. P. Fadini
Summary: This study compared the effectiveness of dapagliflozin to DPP-4 inhibitors in achieving individualized HbA1c targets and extra-glycaemic endpoints in elderly patients with type 2 diabetes. The results showed that patients initiating dapagliflozin had a lower likelihood of reaching individualized HbA1c targets compared to those initiating DPP-4 inhibitors. However, they experienced greater improvements in body weight and blood pressure.
JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION
(2023)
Article
Endocrinology & Metabolism
B. M. Bonora, R. Cappellari, M. Albiero, L. Prevedello, M. Foletto, R. Vettor, A. Avogaro, G. P. Fadini
Summary: This study examined adipose tissue-derived stem cells (ASCs) in individuals with metabolic syndrome traits and found that these cells can enter the systemic circulation and establish ectopic adipose depots, leading to insulin resistance. This phenomenon, previously observed in mice, has been confirmed in humans, highlighting the importance of further investigation.
JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION
(2023)
Article
Endocrinology & Metabolism
Mauro Rigato, Gian Paolo Fadini, Angelo Avogaro
Summary: This study aimed to assess the safety of SGLT2 inhibitors (SGLT2is) in elderly patients with type 2 diabetes. A meta-analysis of randomized controlled trials (RCTs) showed that SGLT2is were well tolerated in the elderly, but older patients were underrepresented in clinical trials.
DIABETES OBESITY & METABOLISM
(2023)
Review
Endocrinology & Metabolism
Jonathan Golledge, Shivshankar Thanigaimani, Kristen S. Barratt, Gian Paolo Fadini
Summary: Diabetes is a major risk factor for ischaemic foot disease, which can lead to severe complications such as tissue loss and amputation. Current treatment options focus on revascularisation, but there are limitations in both surgical eligibility and success rates. Recent research in animal models and clinical trials have identified potential novel medical targets for ischaemia, aiming to improve wound healing and enhance blood supply recovery. However, translating these findings to human patients remains challenging due to limitations in clinically relevant animal models. Promising results have been reported in small clinical trials with certain therapies, but further research and larger clinical trials are needed to determine their broader applicability.
DIABETES-METABOLISM RESEARCH AND REVIEWS
(2023)
Article
Endocrinology & Metabolism
Benedetta Maria Bonora, Mario Luca Morieri, Marella Marassi, Roberta Cappellari, Angelo Avogaro, Gian Paolo Fadini
Summary: This study aimed to investigate whether measuring circulating levels of haematopoietic stem/progenitor cells (HSPCs) can improve the prediction of long-term kidney outcomes in individuals with type 2 diabetes. The results showed that HSPC levels are associated with worsening kidney function and can enhance the identification of adverse kidney outcomes in individuals with type 2 diabetes.