Correlation of circulating CD133+ progenitor subclasses with a mild phenotype in Duchenne muscular dystrophy patients

Background

Various prognostic serum and cellular markers have been identified for many diseases, such as cardiovascular diseases and tumor pathologies. Here we assessed whether the levels of certain stem cells may predict the progression of Duchenne muscular dystrophy (DMD).

Methods and Findings

The levels of several subpopulations of circulating stem cells expressing the CD133 antigen were determined by flow cytometry in 70 DMD patients. The correlation between the levels and clinical status was assessed by statistical analysis. The median (±SD) age of the population was 10.66±3.81 (range 3 to 20 years). The levels of CD133+CXCR4+CD34- stem cells were significantly higher in DMD patients compared to healthy controls (mean±standard deviation: 17.38±1.38 vs. 11.0±1.70; P = 0.03) with a tendency towards decreased levels in older patients. Moreover, the levels of this subpopulation of cells correlated with the clinical condition. In a subgroup of 19 DMD patients after 24 months of follow-up, increased levels of CD133+CXCR4+CD34- cells was shown to be associated with a phenotype characterised by slower disease progression. The circulating CD133+CXCR4+CD34- cells in patients from different ages did not exhibit significant differences in their myogenic and endothelial in vitro differentiation capacity.

Conclusions

Our results suggest that levels of CD133+CXCR4+CD34- could function as a new prognostic clinical marker for the progression of DMD.     

Leech responses to tissue transplantation

The aim of the present work is to describe histologically, histochemically and immunocytochemically, the sequence of events that lead to first and second set rejection of allo- or xenograft in leeches. Graft responses of leeches are comparable and are described following specific steps: inflammatory phase, rejection phase and granulation tissue formation (including re-epithelialisation, angiogenesis and fibroplasia).The responses to first and second graft in first set graft rejection as well as to the first transplant in second set graft experiments are identical and in the time span of a week all grafts are destroyed and disappear. In the second set graft rejection experiments the responses against the second transplant are markedly accelerated. The second graft shows massive structural alterations and it is rapidly rejected, within 3-4 days.Our results permit to highlight that in leeches there is a specific responsiveness of immune system similar to those described in highly divergent phyla.     

Resveratrol treatment reduces cardiac progenitor cell dysfunction and prevents morpho-functional ventricular remodeling in type-1 diabetic rats

Emerging evidence suggests that both adult cardiac cell and the cardiac stem/progenitor cell (CSPC) compartments are involved in the patho-physiology of diabetic cardiomyopathy (DCM). We evaluated whether early administration of Resveratrol, a natural antioxidant polyphenolic compound, in addition to improving cardiomyocyte function, exerts a protective role on (i) the progenitor cell pool, and (ii) the myocardial environment and its impact on CSPCs, positively interfering with the onset of DCM phenotype. Adult Wistar rats (n?=?128) with streptozotocin-induced type-1 diabetes were either untreated (D group; n?=?54) or subjected to administration of trans-Resveratrol (i.p. injection: 2.5 mg/Kg/day; DR group; n?=?64). Twenty-five rats constituted the control group (C). After 1, 3 or 8 weeks of hyperglycemia, we evaluated cardiac hemodynamic performance, and cardiomyocyte contractile properties and intracellular calcium dynamics. Myocardial remodeling and tissue inflammation were also assessed by morphometry, immunohistochemistry and immunoblotting. Eventually, the impact of the diabetic "milieu" on CSPC turnover was analyzed in co-cultures of healthy CSPCs and cardiomyocytes isolated from D and DR diabetic hearts. In untreated animals, cardiac function was maintained during the first 3 weeks of hyperglycemia, although a definite ventricular remodeling was already present, mainly characterized by a marked loss of CSPCs and adult cardiac cells. Relevant signs of ventricular dysfunction appeared after 8 weeks of diabetes, and included: 1) a significant reduction in ±dP/dt in comparison with C group, 2) a prolongation of isovolumic contraction/relaxation times, 3) an impaired contraction of isolated cardiomyocytes associated with altered intracellular calcium dynamics. Resveratrol administration reduced atrial CSPC loss, succeeded in preserving the functional abilities of CSPCs and mature cardiac cells, improved cardiac environment by reducing inflammatory state and decreased unfavorable ventricular remodeling of the diabetic heart, leading to a marked recovery of ventricular function. These findings indicate that RSV can constitute an adjuvant therapeutic option in DCM prevention.     

Antibacterial photodynamic therapy in dermatology.

Photodynamic therapy (PDT) appears to be endowed with several favourable features for the treatment of localized microbial infections, especially after the advent of cationic photosensitising agents (phenothiazines, meso-substituted porphyrins, polylysine-bound chlorins) which properly interact with the outer wall at the surface of several types of bacterial and yeast cells, increase their permeability, and allow significant amounts of photosensitizer to be accumulated at the level of the cytoplasmic membrane. These photosensitisers are characterized by a broad spectrum of activity, being effective toward both wild strain and antibiotic-resistant gram-positive and gram-negative bacteria and yeasts. In general, extensive eradication of pathogens can be achieved under mild irradiation conditions, such as short incubation times and low fluence-rates, which guarantees a high degree of selectivity in comparison with the main constituents of host tissues, such as keratinocytes and fibroblasts. Moreover, the photosensitised inactivation of microorganisms is typically a multi-target process; as a consequence, the selection of photoresistant microbial strains is very unlikely and has not been experimentally observed so far. Possible initial targets of antimicrobial PDT applications include periodontal diseases, impetigo, atopic dermatitis, acne vulgaris, infected wounds, and superinfected posriatic plaques.     

"Contractile interstitial cells" in pulmonary alveolar septa: a possible regulator of ventilation-perfusion ratio? Ultrastructural, immunofluorescence, and in vitro studies

In the lungs of healthy rats, humans, lambs, and monkeys, about 50% of the alveolar interstitial cells—resembling fibroblasts—contain bundles of fibrils measuring 30–80 Å in diameter. Immunofluorescence studies on frozen sections of rat lung demonstrate that many interstitial cells bind sera containing antiactin antibodies. On account of these two sets of findings and our additional in vitro studies suggesting alveolar tissue contraction due to hypoxia or epinephrine, we postulate that the alveolar septa contain contractile cells different from that of smooth muscle. For these cells we propose the name of "contractile interstitial cells." Such cells lie within the thick portion of the air-blood barrier and around the pre- or postcapillary vessels. Hence it is possible that they play a role in the autoregulation of ventilation/perfusion (V/Q) ratio, particularly in hypoxic pulmonary hypertension. These findings, demonstrating a contractile system other than bronchial and arterial smooth muscle, suggest that the alveolus should no more be conceived as a passive "organ."     

Priority invasive alien plants in the Tuscan Archipelago (Italy): comparing the EPPO prioritization scheme with the Australian WRA

For the first time, we tested the European and Mediterranean Plant Protection Organization (EPPO) prioritization process (EPP) on 212 alien plant species thriving in the Tuscan Archipelago, Central Italy. We compared the results of the EPPO procedure with those of the Australian Weed Risk Assessment (A-WRA) system. The two methods were also tested against the categorization performed at the national and local level by a panel of experts. Our results suggest that both methods accurately predict the invasiveness of species already present in the Tuscan Archipelago. However, the total numbers of species included in the highest risk categories by the two methods differed greatly, with the EPPO prioritization process including fewer species in the highest risk class. The two methods differed in the ability to correctly detect the invasive species, with the A-WRA method being more conservative, but at cost of more species in the highest risk class. Using Generalized Linear Models, we showed that both methods suffer from some degree of dependence from one or more of the tested explanatory variables (life span, year of first record). The results suggest that the choice of a risk assessment method should be driven by the main aim of the assessment, i.e., distinguishing between a more predictive tool (A-WRA) and a prioritization tool (EPP) for already introduced species.     

Novel evolutionary insights on the interactions of the Holosporales (Alphaproteobacteria) with eukaryotic hosts from comparative genomics

Holosporales are an alphaproteobacterial order engaging in obligate and complex associations with eukaryotes, in particular protists. The functional and evolutionary features of those interactions are still largely undisclosed. Here, we sequenced the genomes of two members of the species Bealeia paramacronuclearis (Holosporales, Holosporaceae) intracellularly associated with the ciliate protist Paramecium, which resulted in high correspondence. Consistent with the short-branched early-divergent phylogenetic position, Bealeia presents a larger functional repertoire than other Holosporaceae, comparable to those of other Holosporales families, particularly for energy metabolism and motility. Our analyses indicate that different Holosporales likely experienced at least partly autonomous genome reduction and adaptation to host interactions, for example regarding dependence on host biotin driven by multiple independent horizontal acquisitions of transporters. Among Alphaproteobacteria, this is reminiscent of the convergently evolved Rickettsiales, which however appear more diverse, possibly due to a probably more ancient origin. We identified in Bealeia and other Holosporales the plasmid-encoded putative genetic determinants of R-bodies, which may be involved in a killer trait towards symbiont-free hosts. While it is not clear whether these genes are ancestral or recently horizontally acquired, an intriguing and peculiar role of R-bodies is suggested in the evolution of the interactions of multiple Holosporales with their hosts.