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FKN Facilitates HK-2 Cell EMT and Tubulointerstitial Lesions via the Wnt/ β-Catenin Pathway in a Murine Model of Lupus Nephritis
In this study, we therefore examined whether FKN could stimulate the process of EMT, NF-kB, TGFβ, CCL22, F4/80, inflammation, and tubulointerstitial fibrosis in a murine model of LN. We also determined whether FKN was involved in the EMT process of Wnt/β-catenin-expressing HK-2 cells. Mechanistically, we ascertained, for the first time, whether FKN up-regulated EMT-related gene signatures (e.g., vimentin, α-SMA), and hence, renal tubulointerstitial fibrogenesis, and the role of the Wnt/β-catenin signaling pathway in this process. Materials and Methods Cell Culture, Stable Infection, and Gr...
Source: Frontiers in Immunology - April 29, 2019 Category: Allergy & Immunology Source Type: research

Human CAR NK Cells: A New Non-viral Method Allowing High Efficient Transfection and Strong Tumor Cell Killing
In conclusion, the method of NK cell transfection described in our present study is highly efficient, does not require expensive dedicated structures necessary for viral transduction and avoids possible risks associated with the use of viral vectors. Importantly, it may be applied to NK cells or NK-92 cell line, greatly improving their anti-tumor activity and providing a new NK cell-based platform for new protocols of adoptive immuno-therapy of cancer. Ethics Statement The Ethical Committee of IRCCS Bambino Gesù Pediatric Hospital approved the study (825/2014). Author Contributions TI designed and performed res...
Source: Frontiers in Immunology - April 29, 2019 Category: Allergy & Immunology Source Type: research

Engineered Extracellular Vesicles From Human Periodontal-Ligament Stem Cells Increase VEGF/VEGFR2 Expression During Bone Regeneration
Conclusion In conclusion our results evidenced that 3D-COL/hPDLSCs/PEI-EVs may be an efficacious strategy to induce bone regeneration and vascularization of bone defects, thanks to its capacity to increase the levels of VEGF. Ethics Statement The study was performed in accordance with the guidelines of the Helsinki Declaration (2013). The written approval for the human periodontal ligament collection performed in this study has been obtained from the Medical Ethics Committee at the Medical School, “G. d’Annunzio” University of Chieti–Pescara, Chieti, Italy (n°266/17.04.14, Principal in...
Source: Frontiers in Physiology - April 29, 2019 Category: Physiology Source Type: research

The JAK/STAT Pathway in Skeletal Muscle Pathophysiology
Conclusion and Perspectives The IL-6/JAK/STAT signaling cascade plays a dominant role in skeletal muscle pathophysiology. IL-6 autocrine, paracrine, and endocrine functions assign to its downstream effectors pivotal importance in skeletal muscle-wasting-associated diseases and other multiple system diseases where muscle acts in communication with other organs. Targeting the components of the JAK/STAT pathway recently emerged as a strategic approach for the treatment of inflammatory diseases and human cancer. This review highlights the opposite outcomes on muscle biology caused by the amount of local and systemic release ...
Source: Frontiers in Physiology - April 29, 2019 Category: Physiology Source Type: research

Inhibition of SMYD2 Sensitized Cisplatin to Resistant Cells in NSCLC Through Activating p53 Pathway
In conclusion, the present study elucidated that the activity of SMYD2 in NSCLC may affect the cell sensitivity to chemotherapeutic agents, especially to CDDP. The elevated SMYD2 mediated CDDP resistance and malignant phenotype in NSCLC, indicating that SMYD2 may be a useful biomarker of CDDP resistance in NSCLC. Inhibition of SMYD2 contributes to the methylation-related activation of p53 and thus results in cell apoptosis. Furthermore, combination treatment with CDDP and an SMYD2 inhibitor had a synergistically antitumor effects in a xenograft model in vivo. Given that SMYD2 has reversible effects and is a targetable prot...
Source: Frontiers in Oncology - April 25, 2019 Category: Cancer & Oncology Source Type: research

Gene Therapy Leaves a Vicious Cycle
Reena Goswami1, Gayatri Subramanian2, Liliya Silayeva1, Isabelle Newkirk1, Deborah Doctor1, Karan Chawla2, Saurabh Chattopadhyay2, Dhyan Chandra3, Nageswararao Chilukuri1 and Venkaiah Betapudi1,4* 1Neuroscience Branch, Research Division, United States Army Medical Research Institute of Chemical Defense, Aberdeen, MD, United States 2Department of Medical Microbiology and Immunology, University of Toledo College of Medicine and Life Sciences, Toledo, OH, United States 3Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States 4Department of Physiology and Biophysics, Case Western Reserve University, Clev...
Source: Frontiers in Oncology - April 23, 2019 Category: Cancer & Oncology Source Type: research

A Novel Regulator of Preadipocyte Differentiation, Transcription Factor TCF21, Functions Partially Through Promoting LPL Expression
Discussion Excessive fat deposition in chickens can result in many undesirable consequences within the poultry industry, including reduced feeding efficiency (Zhou et al., 2006) and decreased reproductive performance (Walzem and Chen, 2014). Thus, broiler breeders urgently require a more thorough understanding of the molecular mechanism governing chicken adipogenesis. We previously found that broilers from lean and fat lines exhibit clear differences in reproductive performance (Zhang et al., 2018). In addition, TCF21 was found to be related to testis growth and development in these broilers (Zhang et al., 2017). In mice ...
Source: Frontiers in Physiology - April 22, 2019 Category: Physiology Source Type: research

FGF21 as Modulator of Metabolism in Health and Disease
In conclusion, FGF21 belongs to a promising class of cytokines that are induced in response to stress and that can be used as a drug, drug target, or through a biomarker, depending on the physio-pathological context. All these findings will become clear when FGF21 will be used as a therapeutic molecule, exploiting the beneficial effects of FGF21 for treating metabolic disease or when it will be blocked to ameliorate disease progression and the onset of disease. Author Contributions CT and MS wrote the manuscript. VR contributed to the discussion. Funding This work was supported from the AFM-Telethon (19524), Italian Mi...
Source: Frontiers in Physiology - April 16, 2019 Category: Physiology Source Type: research

Sanguinarine Induces Apoptosis Pathway in Multiple Myeloma Cell Lines via Inhibition of the JaK2/STAT3 Signaling
In this study, we aimed to investigate the potential anti-proliferative and pro-apoptotic activities of SNG in a panel of MM cell lines (U266, IM9, MM1S, and RPMI-8226). SNG treatment of MM cells resulted in a dose-dependent decrease in cell viability through mitochondrial membrane potential loss and activation of caspase 3, 9, and cleavage of PARP. Pre-treatment of MM cells with a universal caspase inhibitor, Z-VAD-FMK, prevented SNG mediated loss of cell viability, apoptosis, and caspase activation, confirming that SNG-mediated apoptosis is caspase-dependent. The SNG-mediated apoptosis appears to be resulted from suppres...
Source: Frontiers in Oncology - April 16, 2019 Category: Cancer & Oncology Source Type: research

Non-canonical Notch Signaling Regulates Actin Remodeling in Cell Migration by Activating PI3K/AKT/Cdc42 Pathway
In conclusion, our research results indicate that DAPT activates PI3K/AKT/Cdc42 signaling by non-canonical Notch pathway, and the activated Cdc42 promotes the filopodia formation and inhibits lamellipodia assembly, resulting in reduced migration of breast cancer cells. The results imply that non-canonical Notch signaling may play a very important role in the rapid response of cells to the extracellular signals. Author Contributions LG, JD, and LL designed the study and wrote and revised the manuscript. LL and LZ performed most of the experiments and data analysis. SZ, X-YZ, P-XM, Y-DM, Y-YW, YC, S-JT, and Y-JZ assisted i...
Source: Frontiers in Pharmacology - April 15, 2019 Category: Drugs & Pharmacology Source Type: research

Autophagy Is a Defense Mechanism Inhibiting Invasion and Inflammation During High-Virulent Haemophilus parasuis Infection in PK-15 Cells
In this study, we sought to investigate whether SH0165 (serovar 5, high-virulent strain) and HN0001 (serovar 6, non-virulent strain) infection induces autophagy and the specific role of autophagy in bacterial invasion and inflammation during H. parasuis infection. Moreover, we explored the mechanism underlying autophagy regulated inflammation through inflammatory signaling cascades during H. parasuis infection. This observation could provide useful information for further understanding the role of autophagy in H. parasuis infection and improve our knowledge of new strategies against this pathogen. Materials and Methods B...
Source: Frontiers in cellular and infection microbiology - April 15, 2019 Category: Microbiology Source Type: research

The Functions of Non-coding RNAs in rRNA Regulation
Qi Yan1, Chengming Zhu1, Shouhong Guang1,2* and Xuezhu Feng1* 1Hefei National Laboratory for Physical Sciences at the Microscale, School of Life Sciences, University of Science and Technology of China, Hefei, China 2CAS Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Hefei, China Ribosomes are ribonucleoprotein machines that decode the genetic information embedded in mRNAs into polypeptides. Ribosome biogenesis is tightly coordinated and controlled from the transcription of pre-rRNAs to the assembly of ribosomes. Defects or disorders in rRNA production result in a number of human ri...
Source: Frontiers in Genetics - April 4, 2019 Category: Genetics & Stem Cells Source Type: research