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1.
Giulia Bernardini Gemma Leone Lia Millucci Marco Consumi Daniela Braconi Ottavia Spiga Silvia Galderisi Barbara Marzocchi Cecilia Viti Giovanna Giorgetti Pietro Lupetti Agnese Magnani Annalisa Santucci 《Journal of cellular physiology》2019,234(5):6696-6708
Alkaptonuria (AKU) is a disease caused by a deficient homogentisate 1,2-dioxygenase activity leading to systemic accumulation of homogentisic acid (HGA), that forms a melanin-like polymer that progressively deposits onto connective tissues causing a pigmentation called “ochronosis” and tissue degeneration. The effects of AKU and ochronotic pigment on the biomechanical properties of articular cartilage need further investigation. To this aim, AKU cartilage was studied using thermal (thermogravimetry and differential scanning calorimetry) and rheological analysis. We found that AKU cartilage had a doubled mesopore radius compared to healthy cartilage. Since the mesoporous structure is the main responsible for maintaining a correct hydrostatic pressure and tissue homoeostasis, drastic changes of thermal and rheological parameters were found in AKU. In particular, AKU tissue lost its capability to enhance chondrocytes metabolism (decreased heat capacity) and hence the production of proteoglycans. A drastic increase in stiffness and decrease in dissipative and lubricant role ensued in AKU cartilage. Multiphoton and scanning electron microscopies revealed destruction of cell–matrix microstructure and disruption of the superficial layer. Such observations on AKU specimens were confirmed in HGA-treated healthy cartilage, indicating that HGA is the toxic responsible of morphological and mechanical alterations of cartilage in AKU. 相似文献
2.
Paola Quaranta Sara Antonini Saturnino Spiga Benedetta Mazzanti Michele Curcio Giovanna Mulas Marco Diana Pasquina Marzola Franco Mosca Biancamaria Longoni 《PloS one》2014,9(4)
Graft vascularization is a crucial step to obtain stable normoglycemia in pancreatic islet transplantation. Endothelial progenitor cells (EPCs) contribute to neoangiogenesis and to the revascularization process during ischaemic events and play a key role in the response to pancreatic islet injury. In this work we co-transplanted EPCs and islets in the portal vein of chemically-induced diabetic rats to restore islet vascularization and to improve graft survival. Syngenic islets were transplanted, either alone or with EPCs derived from green fluorescent protein (GFP) transgenic rats, into the portal vein of streptozotocin-induced diabetic rats. Blood glucose levels were monitored and intraperitoneal glucose tolerance tests were performed. Real time-PCR was carried out to evaluate the gene expression of angiogenic factors. Diabetic-induced rats showed long-lasting (6 months) normoglycemia upon co-transplantation of syngenic islets and EPCs. After 3–5 days from transplantation, hyperglycaemic levels dropped to normal values and lasted unmodified as long as they were checked. Further, glucose tolerance tests revealed the animals'' ability to produce insulin on-demand as indexed by a prompt response in blood glucose clearance. Graft neovascularization was evaluated by immunohistochemistry: for the first time the measure of endothelial thickness revealed a donor-EPC-related neovascularization supporting viable islets up to six months after transplant. Our results highlight the importance of a newly formed viable vascular network together with pancreatic islets to provide de novo adequate supply in order to obtain enduring normoglycemia and prevent diabetes-related long-term health hazards. 相似文献
3.
Asma Torche Hayet Benhizia Riccardo Rosselli Ottavia Romoli Marina Zanardo Enrico Baldan Sara Alberghini Alessandra Tondello Barbara Baldan Amar Benguedouar Andrea Squartini Yacine Benhizia 《Annals of microbiology》2014,64(3):1065-1071
The root nodules of two wild legume species endemic to Algeria, Hedysarum naudinianum and He. perrauderianum, were investigated with regard to their anatomy and histology, and the identity of the associated bacteria. Both plants were found to form root nodules with regular features and well infected by rod-shaped bacteria. The culturable fraction of bacteria that could be obtained from surface-sterilized nodules included a prevailing presence of Enterobacteriaceae having 100 % 16S rDNA sequence identity with both Enterobacter cloacae and E. ludwigii. In H. perrauderianum, this taxon was the sole cultured isolate, while from H. naudinianum we also found Bacillus, Lactobacillus, Staphylococcus, Rothia, and isolates that were 100 % identical to Corynebacterium pseudodiphthericum, which is known to be an agent of respiratory and cardiac infections in humans. Whereas no culturable rhizobia and alike could be obtained on plates, PCR-based culture-independent approaches revealed in both plants the presence of a Mesorhizobium sp., which in H. perrauderianum was identical to isolates nodulating other legumes from Africa, European Mediterranean countries, and Asia, while in H. naudinianum it bore a single nucleotide polymorphism which is so far unique for any observed mesorhizobia. Data from the microsymbionts appear to suggest interesting clues to interpret the evolutionary ecology of their host plants. 相似文献
4.
Luise Ehlers Karen Bannert Sarah Rohde Peggy Berlin Johannes Reiner Mats Wiese Julia Doller Markus M. Lerch Ali A. Aghdassi Fatuma Meyer Luzia Valentini Ottavia Agrifoglio Cornelia C. Metges Georg Lamprecht Robert Jaster 《Journal of cellular and molecular medicine》2020,24(15):8304-8314
Muscle wasting represents a constant pathological feature of common chronic gastrointestinal diseases, including liver cirrhosis (LC), inflammatory bowel diseases (IBD), chronic pancreatitis (CP) and pancreatic cancer (PC), and is associated with increased morbidity and mortality. Recent clinical and experimental studies point to the existence of a gut‐skeletal muscle axis that is constituted by specific gut‐derived mediators which activate pro‐ and anti‐sarcopenic signalling pathways in skeletal muscle cells. A pathophysiological link between both organs is also provided by low‐grade systemic inflammation. Animal models of LC, IBD, CP and PC represent an important resource for mechanistic and preclinical studies on disease‐associated muscle wasting. They are also required to test and validate specific anti‐sarcopenic therapies prior to clinical application. In this article, we review frequently used rodent models of muscle wasting in the context of chronic gastrointestinal diseases, survey their specific advantages and limitations and discuss possibilities for further research activities in the field. We conclude that animal models of LC‐, IBD‐ and PC‐associated sarcopenia are an essential supplement to clinical studies because they may provide additional mechanistic insights and help to identify molecular targets for therapeutic interventions in humans. 相似文献
5.
New Treatment of Medullary and Papillary Human Thyroid Cancer: Biological Effects of Hyaluronic Acid Hydrogel Loaded With Quercetin Alone or in Combination to an Inhibitor of Aurora Kinase 下载免费PDF全文
6.
Ferretti A Boschi E Stefani A Spiga S Romanelli M Lemmi M Giovannetti A Longoni B Mosca F 《Life sciences》2003,73(15):1985-1994
The angiogenesis and reinnervation were studied in a porcine model of human skin equivalent (SE) graft and the relationship between the two processes was investigated. Confocal laser scanning microscopy was used to monitor, during the healing process, the pattern of vascularization and reinnervation at different time points. The SE was obtained by co-culturing fibroblasts and keratinocytes on a collagen-glycosaminoglycan-chitosan biopolymer and grafted on dorsal wounds generated by full-thickness resection in 25/30 Kg Large white pigs. Frozen sections were obtained from biopsies performed in autograft and xenograft, then were immunolabeled by using the endothelial marker lectin Lactifolia and with the neuronal marker gene product PGP9.5. Cajal staining was also used to visualize the nerve fibers. The results show that the vascularization precedes the innervation process. These data are consistent with the view that the development of nervous tissue is driven by nutritional and trophic factors provided by the vascular system. The arborization of the two systems observed during the third week from the graft might play a key role in maintaining the healing process and the graft survival. 相似文献
7.
Summary A 2-year-old girl had a de novo duplication in the long arm of one chromosome 7 and an increased level of the enzyme -glucuronidase in cultured fibroblasts. The phenotype of the girl partly overlaps those of two presumptive syndromes due to secondary partial trisomies 7q. The ratio of the enzyme activity was 1.43 to the controls, and 1.37 to her parent's values. We could not define the abnormality but suggest two alternatives: either the patient is trisomic for region q112 to q22 or for the region q22 to q34. If the second alternative is correct the locus for -glucuronidase is possibly assigned to band 7q22. 相似文献
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Jones P Altamura S Chakravarty PK Cecchetti O De Francesco R Gallinari P Ingenito R Meinke PT Petrocchi A Rowley M Scarpelli R Serafini S Steinkühler C 《Bioorganic & medicinal chemistry letters》2006,16(23):5948-5952
Histone deacetylase (HDAC) inhibitors offer a promising strategy for cancer therapy and the first generation HDAC inhibitors are currently in clinical trials. A structurally novel series of HDAC inhibitors based on the natural cyclic tetrapeptide Apicidin is described. Selected screening of the sample collection looking for L-2-amino-8-oxodecanoic acid (L-Aoda) derivatives identified a small acyclic lead molecule 1 with the unusual ketone zinc binding group. SAR studies around this lead resulted in optimization to potent, low molecular weight, selective, non-hydroxamic acid HDAC inhibitors, equipotent to current clinical candidates. 相似文献
10.
Beverdam A Merlo GR Paleari L Mantero S Genova F Barbieri O Janvier P Levi G 《Genesis (New York, N.Y. : 2000)》2002,34(4):221-227
In modern vertebrates upper and lower jaws are morphologically different. Both develop from the mandibular arch, which is colonized mostly by Hox-free neural crest cells. Here we show that simultaneous inactivation of the murine homeobox genes Dlx5 and Dlx6 results in the transformation of the lower jaw into an upper jaw and in symmetry of the snout. This is the first homeotic-like transformation found in this Hox-free region after gene inactivation. A suggestive parallel comes from the paleontological record, which shows that in primitive vertebrates both jaws are essentially mirror images of each other. Our finding supports the notion that Dlx genes are homeotic genes associated with morphological novelty in the vertebrate lineage. 相似文献