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Genes & Diseases

Trevor E Angell, Le Min, Tad J Wieczorek, F Stephen Hodi
Blockade of immune checkpoint molecules to reverse cancer-induced immune suppression can improve anti-tumor immune responses in cancer patients. Monoclonal antibodies targeting two such molecules, Programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte associated protein 4 (CTLA-4) have shown clinical benefit in the treatment of advanced malignancies, including metastatic melanoma. Adverse effects of these immune checkpoint inhibitors include immune-related adverse events (irAE) and the inducing of new autoimmunity, of which one of the most common is autoimmune thyroiditis...
March 2018: Genes & Diseases
Elliot S Bishop, Sami Mostafa, Mikhail Pakvasa, Hue H Luu, Michael J Lee, Jennifer Moriatis Wolf, Guillermo A Ameer, Tong-Chuan He, Russell R Reid
Advances in three-dimensional (3D) printing have increased feasibility towards the synthesis of living tissues. Known as 3D bioprinting, this technology involves the precise layering of cells, biologic scaffolds, and growth factors with the goal of creating bioidentical tissue for a variety of uses. Early successes have demonstrated distinct advantages over conventional tissue engineering strategies. Not surprisingly, there are current challenges to address before 3D bioprinting becomes clinically relevant...
December 2017: Genes & Diseases
Chen Zhao, Wei Jiang, Nian Zhou, Junyi Liao, Mingming Yang, Ning Hu, Xi Liang, Wei Xu, Hong Chen, Wei Liu, Lewis L Shi, Leonardo Oliveira, Jennifer Moriatis Wolf, Sherwin Ho, Aravind Athiviraham, H M Tsai, Tong-Chuan He, Wei Huang
Cartilage injuries caused by arthritis or trauma pose formidable challenges for effective clinical management due to the limited intrinsic proliferative capability of chondrocytes. Autologous stem cell-based therapies and transgene-enhanced cartilage tissue engineering may open new avenues for the treatment of cartilage injuries. Bone morphogenetic protein 2 (BMP2) induces effective chondrogenesis of mesenchymal stem cells (MSCs) and can thus be explored as a potential therapeutic agent for cartilage defect repair...
December 2017: Genes & Diseases
Mikhail Pakvasa, Alex Alverdy, Sami Mostafa, Eric Wang, Lucy Fu, Alexander Li, Leonardo Oliveira, Aravind Athiviraham, Michael J Lee, Jennifer Moriatis Wolf, Tong-Chuan He, Guillermo A Ameer, Russell R Reid
Bone tissue regeneration holds the potential to solve both osteoporosis and large skeletal defects, two problems associated with significant morbidity. The differentiation of mesenchymal stem cells into the osteogenic lineage requires a specific microenvironment and certain osteogenic growth factors. Neural EGF Like-Like molecule 1 (NELL-1) is a secreted glycoprotein that has proven, both in vitro and in vivo , to be a potent osteo-inductive factor. Furthermore, it has been shown to repress adipogenic differentiation and inflammation...
September 2017: Genes & Diseases
Jinlong Jian, Aubryanna Hettinghouse, Chuan-Ju Liu
Multifunctional factor progranulin (PGRN) plays an important role in lysosomes, and its mutations and insufficiency are associated with lysosomal storage diseases, including neuronal ceroid lipofuscinosis and Gaucher disease (GD). The first breakthrough in understanding the molecular mechanisms of PGRN as regulator of lysosomal storage diseases came unexpectedly while investigating the role of PGRN in inflammation. Challenged PGRN null mice displayed typical features of GD. In addition, GRN gene variants were identified in GD patients and the serum levels of PGRN were significantly lower in GD patients...
September 2017: Genes & Diseases
Cody S Lee, Elliot S Bishop, Ruyi Zhang, Xinyi Yu, Evan M Farina, Shujuan Yan, Chen Zhao, Zongyue Zheng, Yi Shu, Xingye Wu, Jiayan Lei, Yasha Li, Wenwen Zhang, Chao Yang, Ke Wu, Ying Wu, Sherwin Ho, Aravind Athiviraham, Michael J Lee, Jennifer Moriatis Wolf, Russell R Reid, Tong-Chuan He
With rapid advances in understanding molecular pathogenesis of human diseases in the era of genome sciences and systems biology, it is anticipated that increasing numbers of therapeutic genes or targets will become available for targeted therapies. Despite numerous setbacks, efficacious gene and/or cell-based therapies still hold the great promise to revolutionize the clinical management of human diseases. It is wildly recognized that poor gene delivery is the limiting factor for most in vivo gene therapies...
June 2017: Genes & Diseases
Hannah Brechka, Raj R Bhanvadia, Calvin VanOpstall, Donald J Vander Griend
The recent and exciting discovery of germline HOXB13 mutations in familial prostate cancer has brought HOX signaling to the forefront of prostate cancer research. An enhanced understanding of HOX signaling, and the co-factors regulating HOX protein specificity and transcriptional regulation, has the high potential to elucidate novel approaches to prevent, diagnose, stage, and treat prostate cancer. Toward our understanding of HOX biology in prostate development and prostate cancer, basic research in developmental model systems as well as other tumor sites provides a mechanistic framework to inform future studies in prostate biology...
June 2017: Genes & Diseases
Le Min
Immune checkpoint inhibition against advance malignancies was named breakthrough discovery by the science magazine in 2013. In numerous clinical studies, monoclonal antibodies against the immune checkpoints, CTLA4, PD1 and PD1 ligand PDL1 have shown promising tumor response in different type of metastatic malignancies. The adverse events are autoimmune-related. The endocrine disorders, hypothysitis and thyroiditis are among the most common side effects associated with immune checkpoint inhibition treatment...
December 2016: Genes & Diseases
Fugui Zhang, Jinglin Song, Hongmei Zhang, Enyi Huang, Dongzhe Song, Viktor Tollemar, Jing Wang, Jinhua Wang, Maryam Mohammed, Qiang Wei, Jiaming Fan, Junyi Liao, Yulong Zou, Feng Liu, Xue Hu, Xiangyang Qu, Liqun Chen, Xinyi Yu, Hue H Luu, Michael J Lee, Tong-Chuan He, Ping Ji
Tooth is a complex hard tissue organ and consists of multiple cell types that are regulated by important signaling pathways such as Wnt and BMP signaling. Serious injuries and/or loss of tooth or periodontal tissues may significantly impact aesthetic appearance, essential oral functions and the quality of life. Regenerative dentistry holds great promise in treating oral/dental disorders. The past decade has witnessed a rapid expansion of our understanding of the biological features of dental stem cells, along with the signaling mechanisms governing stem cell self-renewal and differentiation...
December 2016: Genes & Diseases
Qiang Wei, Junyi Liao, Xinyi Yu, Eric J Wang, Claire Wang, Hue H Luu, Rex C Haydon, Michael J Lee, Tong-Chuan He
While CRISPR/Cas9-mediated genome editing technology has been experiencing a rapid transformation during the past few years, a recent report on NgAgo-mediated single-stranded DNA-guided genome editing may offer an attractive alternative for genome manipulation. While it's too early to predict whether NgAgo will be able to compete with or be superior to CRISPR/Cas9, the scientific community is anxiously waiting for further optimization and broader applications of the NgAgo genome editing technology.
September 2016: Genes & Diseases
Yi Feng, Brian Egan, Jinxi Wang
Low back pain (LBP) is a major cause of disability and imposes huge economic burdens on human society worldwide. Among many factors responsible for LBP, intervertebral disc degeneration (IDD) is the most common disorder and is a target for intervention. The etiology of IDD is complex and its mechanism is still not completely understood. Many factors such as aging, spine deformities and diseases, spine injuries, and genetic factors are involved in the pathogenesis of IDD. In this review, we will focus on the recent advances in studies on the most promising and extensively examined genetic factors associated with IDD in humans...
September 2016: Genes & Diseases
Jun Sun, Ikuko Kato
Although genes contribute to colorectal cancer, the gut microbiota are an important player. Accumulating evidence suggests that chronic infection and the ensuing inflammation contributes to tumor initiation and tumor progression. A variety of bacterial species and tumor-promoting virulence mechanisms have been investigated. Significant advances have been made in understanding the composition and functional capabilities of the gut microbiota and its roles in cancer. In the current review, we discuss the novel roles of microbiota in the progression of colon cancer...
June 2016: Genes & Diseases
Jing Wang, Qiang Wei, Xin Wang, Shengli Tang, Hao Liu, Fugui Zhang, Maryam K Mohammed, Jiayi Huang, Dan Guo, Minpeng Lu, Feng Liu, Jianxiang Liu, Chao Ma, Xue Hu, Rex C Haydon, Tong-Chuan He, Hue H Luu
Two recent studies provide intriguing evidence that challenges the role of the epithelial-mesenchymal transition (EMT) as a critical mediator of cancer metastasis, while revealing an unexpected role in cancer drug resistance.(1,2) While these findings may not settle the EMT's role in metastasis, these studies suggest that targeting the EMT may inhibit both cancer metastasis and chemoresistance.
March 2016: Genes & Diseases
Baozhong Zhao, Lei Qiang, Joy Joseph, Balaraman Kalyanaraman, Benoit Viollet, Yu-Ying He
Autophagy is a cellular self-eating process essential for stress response and maintaining tissue homeostasis by lysosomal degradation of unwanted or damaged proteins and organelles. Here, we show that cells with defective mitochondria induce autophagy to promote cell survival through activating the AMPK pathway. Loss of mitochondrial complex III protein cytochrome b activates the AMPK signaling and induced autophagy. Inhibiting mitochondria energetics by mitochondria-targeted agents activates the AMPK signaling and induced autophagy...
March 2016: Genes & Diseases
Hua Geng, Xiao-Di Tan
Precise and dynamic regulation of gene expression is a key feature of immunity. In recent years, rapid advances in transcriptome profiling analysis have led to recognize long non-coding RNAs (lncRNAs) as an additional layer of gene regulation context. In the immune system, lncRNAs are found to be widely expressed in immune cells including monocytes, macrophages, dendritic cells (DCs), neutrophils, T cells and B cells during their development, differentiation and activation. However, the functional importance of immune-related lncRNAs is just emerging to be characterized...
March 2016: Genes & Diseases
Viktor Tollemar, Zach J Collier, Maryam K Mohammed, Michael J Lee, Guillermo A Ameer, Russell R Reid
Current reconstructive approaches to large craniofacial skeletal defects are often complicated and challenging. Critical-sized defects are unable to heal via natural regenerative processes and require surgical intervention, traditionally involving autologous bone (mainly in the form of nonvascularized grafts) or alloplasts. Autologous bone grafts remain the gold standard of care in spite of the associated risk of donor site morbidity. Tissue engineering approaches represent a promising alternative that would serve to facilitate bone regeneration even in large craniofacial skeletal defects...
March 2016: Genes & Diseases
Saint-Aaron L Morris, Suyun Huang
Many cancers have similar aberrations in various signaling cascades with crucial roles in cellular proliferation, differentiation, and morphogenesis. Dysregulation of signal cascades that play integral roles during early cellular development is well known to be a central feature of many malignancies. One such signaling cascade is the Wnt/β-catenin pathway, which has a profound effect on stem cell proliferation, migration, and differentiation. This pathway is dysregulated in numerous cell types, underscoring its global oncogenetic potential...
March 2016: Genes & Diseases
Maryam K Mohammed, Connie Shao, Jing Wang, Qiang Wei, Xin Wang, Zachary Collier, Shengli Tang, Hao Liu, Fugui Zhang, Jiayi Huang, Dan Guo, Minpeng Lu, Feng Liu, Jianxiang Liu, Chao Ma, Lewis L Shi, Aravind Athiviraham, Tong-Chuan He, Michael J Lee
Wnt signaling transduces evolutionarily conserved pathways which play important roles in initiating and regulating a diverse range of cellular activities, including cell proliferation, calcium homeostasis, and cell polarity. The role of Wnt signaling in control of cell proliferation and stem cell self-renewal is primarily carried out through the canonical pathway, which is the best characterized among the multiple Wnt signaling branches. The past 10 years has seen a rapid expansion in our understanding of the complexity of this pathway, as many new components of Wnt signaling have been identified and linked to signaling regulation, stem cell functions, and adult tissue homeostasis...
March 2016: Genes & Diseases
Maryam K Mohammed, Connie Shao, Hue H Luu, Rex C Haydon
No abstract text is available yet for this article.
December 2015: Genes & Diseases
Leonid V Kapilevich, Tatyana A Kironenko, Anna N Zaharova, Yuri V Kotelevtsev, Nickolai O Dulin, Sergei N Orlov
During the last two decades numerous research teams demonstrated that skeletal muscles function as an exercise-dependent endocrine organ secreting dozens of myokines. Variety of physiological and pathophysiological implications of skeletal muscle myokines secretion has been described; however, upstream signals and sensing mechanisms underlying this phenomenon remain poorly understood. It is well documented that in skeletal muscles intensive exercise triggers dissipation of transmembrane gradient of monovalent cations caused by permanent activation of voltage-gated Na+ and K+ channels...
December 2015: Genes & Diseases
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