Current Issue : July - September Volume : 2018 Issue Number : 3 Articles : 5 Articles
Background&Aims;. Identifying NAFLD patients at risk of progression is crucial to orient medical care and resources.We aimed to\nverify if the effects determined by different single nucleotide polymorphisms (SNPs) could add up tomultiply the risk ofNAFLDand\nNASH-cirrhosis. Methods.Three study populations, that is, patients diagnosed with NASH-cirrhosis or with noncirrhotic NAFLD\nand healthy controls, were enrolled. PNPLA3 rs738409, TM6SF2 rs58542926, KLF6 rs3750861, SOD2 rs4880, and LPIN1 rs13412852\nwere genotyped. Results. One hundred and seven NASH-cirrhotics, 93 noncirrhotic NAFLD, and 90 controls were enrolled. At\nleast one difference in allele frequency between groups was significant, or nearly significant, for the PNPLA3, TM6SF2, and KLF6\nvariants (...
Casiopeinas are a group of copper-based antineoplastic molecules designed as a less toxic and more therapeutic alternative to\ncisplatin or Doxorubicin; however, there is scarce evidence about their toxic effects on the whole heart and cardiomyocytes.\nGiven this, rat hearts were perfused with Casiopeinas or Doxorubicin and the effects on mechanical performance, energetics,\nand mitochondrial function were measured. As well, the effects of Casiopeinas-triggered cell death were explored in isolated\ncardiomyocytes. Casiopeinas III-Ea, II-gly, and III-ia induced a progressive and sustained inhibition of heart contractile function\nthat was dose- and time-dependent with an IC50 of 1.3 �± 0.2, 5.5 �± 0.5, and 10 �± 0.7 �¼M, correspondingly. Myocardial oxygen\nconsumption was not modified at their respective IC50, although ATP levels were significantly reduced, indicating energy\nimpairment. Isolated mitochondria from Casiopeinas-treated hearts showed a significant loss of membrane potential and\nreduction of mitochondrial Ca2+ retention capacity. Interestingly, Cyclosporine A inhibited Casiopeinas-induced mitochondrial\nCa2+ release, which suggests the involvement of the mitochondrial permeability transition pore opening. In addition,\nCasiopeinas reduced the viability of cardiomyocytes and stimulated the activation of caspases 3, 7, and 9, demonstrating a cell\ndeath mitochondrial-dependent mechanism. Finally, the early perfusion of Cyclosporine A in isolated hearts decreased\nCasiopeinas-induced dysfunction with reduction of their toxic effect. Our results suggest that heart cardiotoxicity of Casiopeinas\nis similar to that of Doxorubicin, involving heart mitochondrial dysfunction, loss of membrane potential, changes in energetic\nmetabolites, and apoptosis triggered by mitochondrial permeability....
Vaccination is one of the most successful immunology applications that has considerably\nimproved human health. The DNA vaccine is a new vaccine being developed since the early 1990s.\nAlthough the DNA vaccine is promising, no human DNA vaccine has been approved to date.\nThe main problem facing DNA vaccine efficacy is the lack of a DNA vaccine delivery system. Several\nstudies explored this limitation. One of the best DNA vaccine delivery systems uses a live bacterial\nvector as the carrier. The live bacterial vector induces a robust immune response due to its natural\ncharacteristics that are recognized by the immune system. Moreover, the route of administration\nused by the live bacterial vector is through the mucosal route that beneficially induces both mucosal\nand systemic immune responses. The mucosal route is not invasive, making the vaccine easy to\nadminister, increasing the patient�s acceptance. Lactic acid bacterium is one of the most promising\nbacteria used as a live bacterial vector. However, some other attenuated pathogenic bacteria, such as\nSalmonella spp. and Shigella spp., have been used as DNA vaccine carriers. Numerous studies showed\nthat live bacterial vectors are a promising candidate to deliver DNA vaccines....
Bone tissue regeneration was closely associated with osteogenesis and angiogenesis. The harmonious regulation of osteogenetic and\nangiogenic growth factors would enhance bone regeneration, while the imbalance of that would lead to local excessive bone\nformation or vascular mass due to exogenous delivery. Therefore, microRNA is believed to regulate multiple metabolism\nprogress through endogenous signaling pathways on the gene level. In this work, we identified microRNA 378 as a positive\nregulator of osteogenesis and angiogenesis simultaneously and also observed an increase of microRNA 378 than control in\nhuman bone marrow mesenchymal stem cells (hBMMSCs) after osteoblast induction. Besides, osteogenetic and angiogenic gene\nexpression increased simultaneously after overexpression of microRNA 378. Moreover, alizarin red staining and alkaline\nphosphatase (ALP) staining enhanced, and secretion of vascular endothelial growth factor (VEGF) increased. In this way, we\nbelieved miR378 was an ideal target to osteogenesis-angiogenesis coupling for bone regeneration, which provides a potential tool\nfor the gene therapy of bone regeneration....
The human skin fulfills important barrier, sensory, and immune functionsââ?¬â?all of which contribute significantly to health and\norganism integrity. Widespread skin damage requires immediate treatment and coverage because massive skin loss fosters the\ninvasion of pathogens, causes critical fluid loss, and may ultimately lead to death. Since the skin is a highly immunocompetent\norgan, autologous transplants are the only viable approach to permanently close a widespread skin wound. Despite the\ndevelopment of tissue-saving autologous transplantation techniques such as mesh and Meek grafts, treatment options for\nextensive skin damage remain severely limited. Yet, the skin is also a rich source of stem and progenitor cells. These cells\npromote wound healing under physiological conditions and are potential sources for tissue engineering approaches aiming to\naugment transplantable tissue by generating cultured epidermal autografts (CEAs). Here, we review autologous tissue\nengineering strategies as well as transplantation products based on skin-derived stem cells. We further provide an overview of\nclinical trial activities in the field and discuss relevant translational and clinical challenges associated with the use of these products....
Loading....