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International Journal of Molecular Sciences

Patrick Frank Ottensmeyer, Markus Witzler, Margit Schulze, Edda Tobiasch
The need for bone grafts is high, due to age-related diseases, such as tumor resections, but also accidents, risky sports, and military conflicts. The gold standard for bone grafting is the use of autografts from the iliac crest, but the limited amount of accessible material demands new sources of bone replacement. The use of mesenchymal stem cells or their descendant cells, namely osteoblast, the bone-building cells and endothelial cells for angiogenesis, combined with artificial scaffolds, is a new approach...
November 14, 2018: International Journal of Molecular Sciences
Dorina Coricovac, Claudia Farcas, Cristian Nica, Iulia Pinzaru, Sebastian Simu, Dana Stoian, Codruta Soica, Maria Proks, Stefana Avram, Dan Navolan, Catalin Dumitru, Ramona Amina Popovici, Cristina Adriana Dehelean
The link between melanoma development and the use of oral combined contraceptives is not fully elucidated, and the data concerning this issue are scarce and controversial. In the present study, we show that the components of oral contraceptives, ethinylestradiol (EE), levonorgestrel (LNG), and their combination (EE + LNG) ± UVB (ultraviolet B radiation) induced differential effects on healthy (human keratinocytes, fibroblasts, and primary epidermal melanocytes, and murine epidermis cells) and melanoma cells (human-A375 and murine-B164A5), as follows: (i) at low doses (1 µM), the hormones were devoid of significant toxicity on healthy cells, but in melanoma cells, they triggered cell death via apoptosis; (ii) higher doses (10 µM) were associated with cytotoxicity in all cells, the most affected being the melanoma cells; (iii) UVB irradiation proved to be toxic for all types of cells; (iv) UVB irradiation + hormonal stimulation led to a synergistic cytotoxicity in the case of human melanoma cells-A375 and improved viability rates of healthy and B164A5 cells...
November 14, 2018: International Journal of Molecular Sciences
Andrés D Klein, Juan Esteban Oyarzún, Cristian Cortez, Silvana Zanlungo
Niemann⁻Pick type C (NPC) disease is a rare neurovisceral cholesterol storage disorder that arises from loss of function mutations in the NPC1 or NPC2 genes. Soon after birth, some patients present with an aggressive hepatosplenomegaly and cholestatic signs. Histopathologically, the liver presents with large numbers of foam cells; however, their role in disease pathogenesis has not been explored in depth. Here, we studied the consequences of gadolinium chloride (GdCl₃) treatment, a well-known Kupffer/foam cell inhibitor, at late stages of NPC liver disease and compared it with NPC1 genetic rescue in hepatocytes in vivo...
November 14, 2018: International Journal of Molecular Sciences
Mercedes Garcia-Gil, Marcella Camici, Simone Allegrini, Rossana Pesi, Edoardo Petrotto, Maria Grazia Tozzi
The growing evidence of the involvement of purine compounds in signaling, of nucleotide imbalance in tumorigenesis, the discovery of purinosome and its regulation, cast new light on purine metabolism, indicating that well known biochemical pathways may still surprise. Adenosine deaminase is important not only to preserve functionality of immune system but also to ensure a correct development and function of central nervous system, probably because its activity regulates the extracellular concentration of adenosine and therefore its function in brain...
November 14, 2018: International Journal of Molecular Sciences
Kiran Javed, Qi Cheng, Adam J Carroll, Thy T Truong, Stefan Bröer
Recent studies have established that dietary protein restriction improves metabolic health and glucose homeostasis. SLC6A19 (B⁰AT1) is the major neutral amino acid transporter in the intestine and carries out the bulk of amino acid absorption from the diet. Mice lacking SLC6A19 show signs of protein restriction, have improved glucose tolerance, and are protected from diet-induced obesity. Pharmacological blockage of this transporter could be used to induce protein restriction and to treat metabolic diseases such as type 2 diabetes...
November 14, 2018: International Journal of Molecular Sciences
Sakura Matsuta, Aki Nishiyama, Genki Chaya, Takafumi Itoh, Kotaro Miura, Yukimoto Iwasaki
Heterotrimeric G proteins are the molecule switch that transmits information from external signals to intracellular target proteins in mammals and yeast cells. In higher plants, heterotrimeric G proteins regulate plant architecture. Rice harbors one canonical α subunit gene ( RGA1 ), four extra-large GTP-binding protein genes (XLGs), one canonical β-subunit gene ( RGB1 ), and five γ-subunit genes (tentatively designated RGG1 , RGG2 , RGG3 / GS3 / Mi / OsGGC1 , RGG4 / DEP1 / DN1 / qPE9-1 / OsGGC3 , and RGG5 / OsGGC2 ) as components of the heterotrimeric G protein complex...
November 14, 2018: International Journal of Molecular Sciences
Federica Papaccio, Carminia Maria Della Corte, Giuseppe Viscardi, Raimondo Di Liello, Giovanna Esposito, Francesca Sparano, Fortunato Ciardiello, Floriana Morgillo
An overactivation of hepatocyte growth factor (HGF)/mesenchymal-epithelial transition factor (MET) axis promotes tumorigenesis and tumor progression in various cancer types. Research data recently evidenced that HGF/MET signaling is also involved also in the immune response, mainly modulating dendritic cells functions. In general, the pathway seems to play an immunosuppressive role, thus hypothesizing that it could constitute a mechanism of primary and acquired resistance to cancer immunotherapy. Recently, some approaches are being developed, including drug design and cell therapy to combine MET and programmed cell death receptor-1 (PD-1)/programmed cell death receptor-ligand 1 (PD-L1) inhibition...
November 14, 2018: International Journal of Molecular Sciences
Ian Simon Olivier, Ramón Cacabelos, Vinogran Naidoo
Neurocognitive impairments associated with human immunodeficiency virus (HIV) infection remain a considerable health issue for almost half the people living with HIV, despite progress in HIV treatment through combination antiretroviral therapy (cART). The pathogenesis and risk factors of HIV-associated neurocognitive disorder (HAND) are still incompletely understood. This is partly due to the complexity of HAND diagnostics, as phenotypes present with high variability and change over time. Our current understanding is that HIV enters the central nervous system (CNS) during infection, persisting and replicating in resident immune and supporting cells, with the subsequent host immune response and inflammation likely adding to the development of HAND...
November 14, 2018: International Journal of Molecular Sciences
Hong Yang, Ningya Zhang, Emmanuel U Okoro, Zhongmao Guo
Passage of apolipoprotein B-containing lipoproteins (apoB-LPs), i.e., triglyceride-rich lipoproteins (TRLs), intermediate-density lipoproteins (IDLs), and low-density lipoproteins (LDLs), through the endothelial monolayer occurs in normal and atherosclerotic arteries. Among these lipoproteins, TRLs and IDLs are apoE-rich apoB-LPs (E/B-LPs). Recycling of TRL-associated apoE has been shown to form apoE-carrying high-density lipoprotein (HDL)-like (HDLE ) particles in many types of cells. The current report studied the formation of HDLE particles by transcytosis of apoB-LPs through mouse aortic endothelial cells (MAECs)...
November 14, 2018: International Journal of Molecular Sciences
Aki Nishiyama, Sakura Matsuta, Genki Chaya, Takafumi Itoh, Kotaro Miura, Yukimoto Iwasaki
Heterotrimeric G proteins are important molecules for regulating plant architecture and transmitting external signals to intracellular target proteins in higher plants and mammals. The rice genome contains one canonical α subunit gene ( RGA1 ), four extra-large GTP-binding protein genes (XLGs), one canonical β subunit gene (RGB1 ), and five γ subunit genes (tentatively named RGG1 , RGG2 , RGG3/GS3/Mi/OsGGC1 , RGG4/DEP1/DN1/OsGGC3 , and RGG5/OsGGC2 ). RGG1 encodes the canonical γ subunit; RGG2 encodes the plant-specific type of γ subunit with additional amino acid residues at the N-terminus; and the remaining three γ subunit genes encode the atypical γ subunits with cysteine abundance at the C-terminus...
November 14, 2018: International Journal of Molecular Sciences
Greg Clark, Stanley J Roux
Among the most recently discovered chemical regulators of plant growth and development are extracellular nucleotides, especially extracellular ATP (eATP) and extracellular ADP (eADP). Plant cells release ATP into their extracellular matrix under a variety of different circumstances, and this eATP can then function as an agonist that binds to a specific receptor and induces signaling changes, the earliest of which is an increase in the concentration of cytosolic calcium ([Ca2+ ]cyt ). This initial change is then amplified into downstream-signaling changes that include increased levels of reactive oxygen species and nitric oxide, which ultimately lead to major changes in the growth rate, defense responses, and leaf stomatal apertures of plants...
November 14, 2018: International Journal of Molecular Sciences
Irene Del Molino Del Barrio, Georgina C Wilkins, Annette Meeson, Simi Ali, John A Kirby
Upon binding with the chemokine CXCL12, the chemokine receptor CXCR4 has been shown to promote breast cancer progression. This process, however, can be affected by the expression of the atypical chemokine receptor ACKR3. Given ACKR3's ability to form heterodimers with CXCR4, we investigated how dual expression of both receptors differed from their lone expression in terms of their signalling pathways. We created single and double CXCR4 and/or ACKR3 Chinese hamster ovary (CHO) cell transfectants. ERK and Akt phosphorylation after CXCL12 stimulation was assessed and correlated with receptor internalization...
November 14, 2018: International Journal of Molecular Sciences
Claudia Rossi, Ilaria Cicalini, Mirco Zucchelli, Maria di Ioia, Marco Onofrj, Luca Federici, Piero Del Boccio, Damiana Pieragostino
Multiple sclerosis (MuS) is an autoimmune disease of the central nervous system characterized by neuroinflammation, neurodegeneration, and degradation of the myelin sheath. Epidemiological studies have shown that the female gender is more susceptible than the male gender to MuS development, with a female-to-male ratio of 2:1. Despite this high onset, women have a better prognosis than men, and the frequency of the relapsing phase decreases during pregnancy, while it increases soon after birth. Therefore, it is interesting to investigate hormonal fluctuations during pregnancy and whether they correlate with metabolic signatures...
November 14, 2018: International Journal of Molecular Sciences
Mykolas Bendorius, Chrystelle Po, Sylviane Muller, Hélène Jeltsch-David
It took decades to arrive at the general consensus dismissing the notion that the immune system is independent of the central nervous system. In the case of uncontrolled systemic inflammation, the relationship between the two systems is thrown off balance and results in cognitive and emotional impairment. It is specifically true for autoimmune pathologies where the central nervous system is affected as a result of systemic inflammation. Along with boosting circulating cytokine levels, systemic inflammation can lead to aberrant brain-resident immune cell activation, leakage of the blood⁻brain barrier, and the production of circulating antibodies that cross-react with brain antigens...
November 13, 2018: International Journal of Molecular Sciences
Yan Wang, Yanquan Fei, Lirui Liu, Yunhua Xiao, Yilin Pang, Jinhe Kang, Zheng Wang
Increasing evidence suggests that the gut microbiota plays vital roles in metabolic diseases. Polygonatum odoratum extract alleviates hyperglycemia and hyperlipidemia, but the underlying mechanism remains unclear. This study investigated the effects of P. odoratum polysaccharides (POPs) on high-fat diet (HFD)-induced obesity in rats and whether these effects were related to modulation of gut microbiota. POP treatment attenuated weight gain, fat accumulation, epididymal adipocyte size, liver triglycerides, and total liver cholesterol content in HFD-fed rats...
November 13, 2018: International Journal of Molecular Sciences
Takenobu Katagiri, Sho Tsukamoto, Yutaka Nakachi, Mai Kuratani
Bone is a unique organ because it can be experimentally induced in soft tissues by implanting a single growth factor, bone morphogenetic protein (BMP). Heterotopic bone-inducing activity was found in demineralized bone matrix in 1965. The characterization of this activity in bone enabled the purification and molecular cloning of BMPs and showed that they are members of the transforming growth factor-β (TGF-β) superfamily. Assay systems developed for this bone-inducing activity revealed the molecular mechanisms of the intracellular signaling of members of the superfamily, including BMPs...
November 13, 2018: International Journal of Molecular Sciences
Rafael Delgado-Ruiz, Georgios Romanos
Implant surface characteristics, as well as physical and mechanical properties, are responsible for the positive interaction between the dental implant, the bone and the surrounding soft tissues. Unfortunately, the dental implant surface does not remain unaltered and changes over time during the life of the implant. If changes occur at the implant surface, mucositis and peri-implantitis processes could be initiated; implant osseointegration might be disrupted and bone resorption phenomena (osteolysis) may lead to implant loss...
November 13, 2018: International Journal of Molecular Sciences
Hui-Ching Wang, Wen-Chun Hung, Li-Tzong Chen, Mei-Ren Pan
Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with a 5-year survival rate of approximately 8%. More than 80% of patients are diagnosed at an unresectable stage due to metastases or local extension. Immune system reactivation in patients by immunotherapy may eliminate tumor cells and is a new strategy for cancer treatment. The anti-CTLA-4 antibody ipilimumab and anti-PD-1 antibodies pembrolizumab and nivolumab have been approved for cancer therapy in different countries. However, the results of immunotherapy on PDAC are unsatisfactory...
November 13, 2018: International Journal of Molecular Sciences
Michelangelo Paci, Simona Casini, Milena Bellin, Jari Hyttinen, Stefano Severi
Loss-of-function long QT (LQT) mutations inducing LQT1 and LQT2 syndromes have been successfully translated to human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) used as disease-specific models. However, their in vitro investigation mainly relies on experiments using small numbers of cells. This is especially critical when working with cells as heterogeneous as hiPSC-CMs. We aim (i) to investigate in silico the ionic mechanisms underlying LQT1 and LQT2 hiPSC-CM phenotypic variability, and (ii) to enable massive in silico drug tests on mutant hiPSC-CMs...
November 13, 2018: International Journal of Molecular Sciences
Yu Xia, Tiantian Xu, Mingqi Zhao, Liang Hua, Yi Chen, Changbing Wang, Ying Tang, Bing Zhu
Cancer-specific drug delivery represents an attractive approach to preventing undesirable side effects and increasing the accumulation of the drug in tumors. The surface modification of selenium nanoparticles (SeNPs) with targeting moieties thus represents an effective strategy for cancer therapy. In this study, SeNPs were modified with folic acid (FA), whose receptors were overexpressed on the surface of cancer cells, including human cervical carcinoma HeLa cells, to fabricate tumor-targeting delivery carrier FA-SeNPs nanoparticles...
November 13, 2018: International Journal of Molecular Sciences
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