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Rolf Teschke
Alcoholic liver disease is the result of cascade events, which clinically first lead to alcoholic fatty liver, and then mostly via alcoholic steatohepatitis or alcoholic hepatitis potentially to cirrhosis and hepatocellular carcinoma. Pathogenetic events are linked to the metabolism of ethanol and acetaldehyde as its first oxidation product generated via hepatic alcohol dehydrogenase (ADH) and the microsomal ethanol-oxidizing system (MEOS), which depends on cytochrome P450 2E1 (CYP 2E1), and is inducible by chronic alcohol use...
November 12, 2018: Biomedicines
Marta Martinez-Lage, Pilar Puig-Serra, Pablo Menendez, Raul Torres-Ruiz, Sandra Rodriguez-Perales
Cancer is the second leading cause of death globally and remains a major economic and social burden. Although our understanding of cancer at the molecular level continues to improve, more effort is needed to develop new therapeutic tools and approaches exploiting these advances. Because of its high efficiency and accuracy, the CRISPR-Cas9 genome editing technique has recently emerged as a potentially powerful tool in the arsenal of cancer therapy. Among its many applications, CRISPR-Cas9 has shown an unprecedented clinical potential to discover novel targets for cancer therapy and to dissect chemical-genetic interactions, providing insight into how tumours respond to drug treatment...
November 12, 2018: Biomedicines
Christopher J LaRocca, Susanne G Warner
Oncolytic viruses have emerged as a novel class of anti-cancer therapeutics with one virus already receiving United States Food and Drug Administration (FDA) approval (talimogene laherparepvec) and many others undergoing testing in clinical trials. These viruses have direct lytic effects on tumor cells as well as immunomodulatory functions to increase inflammatory cell infiltrates in the tumor microenvironment. Despite all of the advances in cancer care, pancreatic cancer remains a highly lethal malignancy...
November 5, 2018: Biomedicines
Verónica Rodilla, Silvia Fre
The hierarchical relationships between stem cells, lineage-committed progenitors, and differentiated cells remain unclear in several tissues, due to a high degree of cell plasticity, allowing cells to switch between different cell states. The mouse mammary gland, similarly to other tissues such as the prostate, the sweat gland, and the respiratory tract airways, consists of an epithelium exclusively maintained by unipotent progenitors throughout adulthood. Such unipotent progenitors, however, retain a remarkable cellular plasticity, as they can revert to multipotency during epithelial regeneration as well as upon oncogene activation...
November 1, 2018: Biomedicines
Ihor Atabiekov, Elie Hobeika, Ujala Sheikh, Abdeljabar El Andaloussi, Ayman Al-Hendy
Premature ovarian insufficiency (POI) is a highly prevalent disorder, characterized by the development of menopause before the age of 40. Most cases are idiopathic; however, in some women the cause of this condition (e.g.; anticancer treatment, genetic disorders, and enzymatic defects) could be identified. Although hormone-replacement therapy, the principal therapeutic approach for POI, helps alleviate the related symptoms, this does not effectively solve the issue of fertility. Assisted reproductive techniques also lack efficacy in these women...
November 1, 2018: Biomedicines
Eike-Benjamin Braune, Anita Seshire, Urban Lendahl
Breast cancer is the second leading cause of cancer deaths among women in the world. Treatment has been improved and, in combination with early detection, this has resulted in reduced mortality rates. Further improvement in therapy development is however warranted. This will be particularly important for certain sub-classes of breast cancer, such as triple-negative breast cancer, where currently no specific therapies are available. An important therapy development focus emerges from the notion that dysregulation of two major signaling pathways, Notch and Wnt signaling, are major drivers for breast cancer development...
November 1, 2018: Biomedicines
Masahiro Hata, Yoku Hayakawa, Kazuhiko Koike
Several stem cell markers within the gastrointestinal epithelium have been identified in mice. One of the best characterized is Lgr5 (leucine-rich repeat-containing G-protein coupled receptor 5) and evidence suggests that Lgr5 + cells in the gut are the origin of gastrointestinal cancers. Reserve or facultative stem or progenitor cells with the ability to convert to Lgr5 + cells following injury have also been identified. Unlike the intestine, where Lgr5 + cells at the crypt base act as active stem cells, the stomach may contain unique stem cell populations, since gastric Lgr5 + cells seem to behave as a reserve rather than active stem cells, both in the corpus and in the antral glands...
October 31, 2018: Biomedicines
Klaas W Decoene, Willem Vannecke, Toby Passioura, Hiroaki Suga, Annemieke Madder
Flexible in vitro translation (FIT) was used as a screening method to uncover a new methodology for peptide constraining based on the attack of a nucleophilic side-chain functionality onto an oxidized furylalanine side chain. A set of template peptides, each containing furylalanine as furan-modified amino acid and a nucleophilic residue (Cys, His, Lys, Arg, Ser, or Tyr), was produced through FIT. The translation mixtures were treated with N -bromosuccinimide (NBS) to achieve selective furan oxidation and subsequent MALDI analysis demonstrated Lys and Ser as promising residues for cyclisation...
October 30, 2018: Biomedicines
Stéphane Turcotte, Katia Mellal, Ramesh Chingle, Mukandila Mulumba, Samy Omri, Lylia Dif-Yaiche, Sylvain Chemtob, Huy Ong, William D Lubell
Modulation of the cluster of differentiation-36 receptor (CD36) has proven promising for dampening pro-inflammatory macrophage signaling. For example, azapeptides (e.g., 1 and 2 ) bind CD36 selectively with high affinity, mitigate Toll-like receptor (TLR) agonist-induced overproduction of nitric oxide (NO), and reduce pro-inflammatory cytokine and chemokine production in macrophages. Moreover, semicarbazides 1 and 2 inhibit microvascular sprouting mediated through CD36 in the choroid explant. Seeking a selective CD36 modulator that mediated inflammation without influencing neovascularization, a set of azasulfurylpeptides (e...
October 22, 2018: Biomedicines
Claudia Cobos, Paramjit S Bansal, Linda Jones, Phurpa Wangchuk, David Wilson, Alex Loukas, Norelle L Daly
Inflammatory bowel diseases are a set of complex and debilitating diseases, for which there is no satisfactory treatment. Peptides as small as three amino acids have been shown to have anti-inflammatory activity in mouse models of colitis, but they are likely to be unstable, limiting their development as drug leads. Here, we have grafted a tripeptide from the annexin A1 protein into linaclotide, a 14-amino-acid peptide with three disulfide bonds, which is currently in clinical use for patients with chronic constipation or irritable bowel syndrome...
October 6, 2018: Biomedicines
Mohamed Ismail, Sara Ibrahim, Azza El-Amir, Amira M El-Rafei, Nageh K Allam, Ahmed Abdellatif
Innovative drug-delivery systems offer a unique approach to effectively provide therapeutic drug dose over the needed time to achieve better tissue protection and enhanced recovery. The hypothesis of the current study was to test the antioxidant and anti-inflammatory effects of genistein and nanofibers on the spinal cord tissue following experimental spinal cord injury (SCI). Rats were treated post SCI with genistein that is loaded on chitosan/polyvinyl alcohol (CS/PVA) nanofibers as an implantable drug-delivery system...
October 4, 2018: Biomedicines
Linda J Popplewell
No abstract text is available yet for this article.
September 27, 2018: Biomedicines
Daria S Chulpanova, Valeriya V Solovyeva, Kristina V Kitaeva, Stephen P Dunham, Svetlana F Khaiboullina, Albert A Rizvanov
Recombinant viruses are novel therapeutic agents that can be utilized for treatment of various diseases, including cancers. Recombinant viruses can be engineered to express foreign transgenes and have a broad tropism allowing gene expression in a wide range of host cells. They can be selected or designed for specific therapeutic goals; for example, recombinant viruses could be used to stimulate host immune response against tumor-specific antigens and therefore overcome the ability of the tumor to evade the host's immune surveillance...
September 25, 2018: Biomedicines
Abdeljabar El Andaloussi, Prosper Igboeli, Amero Amer, Ayman Al-Hendy
Cancer treatment with specific chemotherapeutic agents has been well documented to have an adverse impact on female fertility leading to premature ovarian failure (POF). The objective of this study is to investigate if chemotherapeutic induced POF can be reversed by the infusion of autologous nucleated peripheral blood cells (PBMC). To reach our goal, mice were treated with a single intraperitoneal injections of busulfan and cyclophosphamide to induce POF. This was followed by transfusion of PBMC. The ovarian morphology and functional parameters were monitored by radioimmunoassay, real-time PCR, immunofluorescence and immunohistochemistry analysis...
September 15, 2018: Biomedicines
Shannon J Kelly, Anjali Hirani, Vishal Shahidadpury, Aum Solanki, Kathleen Halasz, Sheeba Varghese Gupta, Brian Madow, Vijaykumar Sutariya
Age-related macular degeneration (AMD) is one of the leading causes of blindness in the United States, affecting approximately 11 million patients. AMD is caused primarily by an upregulation of vascular endothelial growth factor (VEGF). In recent years, aflibercept injections have been used to combat VEGF. However, this treatment requires frequent intravitreal injections, leading to low patient compliance and several adverse side effects including scarring, increased intraocular pressure, and retinal detachment...
September 11, 2018: Biomedicines
Bahare Salehi, Abhay Prakash Mishra, Manisha Nigam, Bilge Sener, Mehtap Kilic, Mehdi Sharifi-Rad, Patrick Valere Tsouh Fokou, Natália Martins, Javad Sharifi-Rad
Resveratrol (3,5,4'-trihydroxy-trans-stilbene) belongs to polyphenols' stilbenoids group, possessing two phenol rings linked to each other by an ethylene bridge. This natural polyphenol has been detected in more than 70 plant species, especially in grapes' skin and seeds, and was found in discrete amounts in red wines and various human foods. It is a phytoalexin that acts against pathogens, including bacteria and fungi. As a natural food ingredient, numerous studies have demonstrated that resveratrol possesses a very high antioxidant potential...
September 9, 2018: Biomedicines
Volker Herzig, Aline Dantas de Araujo, Kathryn P Greenwood, Yanni K-Y Chin, Monique J Windley, Youmie Chong, Markus Muttenthaler, Mehdi Mobli, Neil Audsley, Graham M Nicholson, Paul F Alewood, Glenn F King
Spider venoms are a rich source of insecticidal peptide toxins. Their development as bioinsecticides has, however, been hampered due to concerns about potential lack of stability and oral bioactivity. We therefore systematically evaluated several synthetic strategies to increase the stability and oral potency of the potent insecticidal spider-venom peptide ω-HXTX-Hv1a (Hv1a). Selective chemical replacement of disulfide bridges with diselenide bonds and N- to C-terminal cyclization were anticipated to improve Hv1a resistance to proteolytic digestion, and thereby its activity when delivered orally...
August 28, 2018: Biomedicines
Shaker A Mousa, Gennadi V Glinsky, Hung-Yun Lin, Osnat Ashur-Fabian, Aleck Hercbergs, Kelly A Keating, Paul J Davis
Acting at a cell surface receptor on the extracellular domain of integrin αvβ3, thyroid hormone analogues regulate downstream the expression of a large panel of genes relevant to cancer cell proliferation, to cancer cell survival pathways, and to tumor-linked angiogenesis. Because αvβ3 is involved in the cancer cell metastatic process, we examine here the possibility that thyroid hormone as l-thyroxine (T4) and the thyroid hormone antagonist, tetraiodothyroacetic acid (tetrac), may respectively promote and inhibit metastasis...
August 22, 2018: Biomedicines
Samuel Marques, Teresa Trevisan, Carlos Maia, Andrea Breuer, Robert W Owen
Advanced glycation end products (AGEs) represent a set of molecules that contribute directly to the initiation and aggravation of diseases associated with ageing. AGEs are produced by the reaction between reducing sugars (or α-dicarbonyl compounds), proteins, and amino acid residues. Previous in vitro methods using non-enzymatic procedures described in the literature require an incubation period of 1⁻3 weeks to generate AGEs. In this study, the reaction time for the formation of AGEs (48 and 3 h) was significantly reduced by adaptation of methods previously described in the literature and coupling them to the free radical generation system termed hypoxanthine/xanthine oxidase assay...
August 15, 2018: Biomedicines
Jiajia Zhang, Shafat Quadri, Christopher L Wolfgang, Lei Zheng
Biomarkers refer to a plethora of biological characteristics that can be quantified to facilitate cancer diagnosis, forecast the prognosis of disease, and predict a response to treatment. The identification of objective biomarkers is among the most crucial steps in the realization of individualized cancer care. Several tumor biomarkers for gastrointestinal malignancies have been applied in the clinical setting to help differentiate between cancer and other conditions, facilitate patient selection for targeted therapies, and to monitor treatment response and recurrence...
August 13, 2018: Biomedicines
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