Fibrin glue displays promising in vitro characteristics as a potential carrier of adipose progenitor cells for tissue regeneration

Adipose‐derived multipotent stem/progenitor cells (ASPCs) were shown to be ideal candidates for cell‐based regenerative therapies. Yet, despite their huge potential, successful clinical applications are still rare. It was suggested that the efficacy of ASPCs at the recipient site depends on the vehicle of cell delivery. In this study, for preparation of a murine critical‐size nerve defect model, we assessed the commercially available fibrin gel (ARTISS) as a potential cell carrier. In a thorough in vitro analysis, we investigated cell–fibrin interactions and analyzed the distribution and the long‐term behavior of ASPCs cultivated in fibrin gel under normoxic and hypoxic conditions. ASPCs attached to the surface of a thin fibrin layer (two‐dimensional condition) and spread with the abundant formation of actin stress fibers. Cells cultured within a fibrin matrix (three‐dimensional condition) displayed a uniform distribution and formed interconnected networks while exhibiting strong cell–matrix interactions. Using time‐lapse analysis, cells were found to migrate out of the gel and subsequently proliferated robustly both under hypoxic and normoxic conditions. During 14 days of culture in fibrin gel, ASPCs showed high viability, metabolic, and remodeling activities. At the end of the culture period, the fibrin matrix was degraded entirely accompanied by an upregulation of matrix metalloproteinases. In conclusion, fibrin gel stands out as a valuable biomaterial for delivering vital and active cells to damaged tissues. As a direct proof, ASPCs carried in a fibrin matrix will be evaluated in a murine critically sized peripheral nerve repair model.     

Protein pathway activation mapping of colorectal metastatic progression reveals metastasis-specific network alterations

The mechanism by which tissue microecology influences invasion and metastasis is largely unknown. Recent studies have indicated differences in the molecular architecture of the metastatic lesion compared to the primary tumor, however, systemic analysis of the alterations within the activated protein signaling network has not been described. Using laser capture microdissection, protein microarray technology, and a unique specimen collection of 34 matched primary colorectal cancers (CRC) and synchronous hepatic metastasis, the quantitative measurement of the total and activated/phosphorylated levels of 86 key signaling proteins was performed. Activation of the EGFR–PDGFR-cKIT network, in addition to PI3K/AKT pathway, was found uniquely activated in the hepatic metastatic lesions compared to the matched primary tumors. If validated in larger study sets, these findings may have potential clinical relevance since many of these activated signaling proteins are current targets for molecularly targeted therapeutics. Thus, these findings could lead to liver metastasis specific molecular therapies for CRC.     

Parathormone,vitamin D and the risk of atrial fibrillation in older adults: A prospective study

Background & aimsVitamin D and parathormone (PTH) have been associated with cardiovascular outcomes, but their impact on atrial fibrillation (AF) onset is still unclear. We explored the influence of serum 25-hydroxyvitamin D (25[OH]D) and PTH on AF risk in older adults.Methods and resultsData come from 2418 participants enrolled in the Progetto Veneto Anziani study. Serum 25(OH)D and intact PTH were measured using radioimmunoassay and two-site immunoassay, respectively. The associations between 25(OH)D, PTH and adjudicated AF cases over 4-years were explored by Cox regression.Over the follow-up, 134 incident cases of AF were assessed. The incidence rate of the sample was 13.5 (95%CI 11.4–15.9) per 1000 person-years, and was higher among those with high PTH levels (high: 16.4 [95%CI 11.3–24.0] per 1000 person-years), especially when associated to low 25(OH)D (20.3 [95%CI 12.9–32.3] per 1000 person-years). At Cox regression, only high PTH was significantly associated to an increased risk of AF (HR = 1.90, 95%CI 1.27–2.84). A marginal significant interaction (p = 0.06) was found between 25[OH]D and PTH concentrations in influencing AF risk. When exploring the risk of AF for combined categories of 25(OH)D and PTH, we found that those with high PTH and low 25(OH)D levels had an AF risk twice as high as that of people with normal values (HR = 2.09, 95%CI 1.28–3.42).ConclusionThe risk of AF may be increased by high PTH levels, especially when associated with 25(OH)D deficiency. The identification and treatment of high PTH or vitamin D deficiency may thus contribute to lower the risk of AF.     

Interactions between fascicles and tendinous tissues in gastrocnemius medialis and vastus lateralis during drop landing

Animal tendons have been shown to act as shock absorbers to protect muscle fascicles from exercise‐induced damage during landing tasks. Meanwhile, the contribution of tendinous tissues to damping activities such as landing has been less explored in humans. The aim of this study was to analyze in vivo fascicle‐tendon interactions during drop landing to better understand their role in energy dissipation. Ultrafast ultrasound images of the gastrocnemius medialis (GM) and vastus lateralis (VL), lower limb electromyographic activity, 2‐D kinematics, and ground reaction forces were collected from twelve participants during single‐ and double‐leg drop landings from various heights. For both muscles, length changes were higher in tendinous tissues than in fascicles, demonstrating their key role in protecting fascicles from rapid active lengthening. Increasing landing height increased lengthening and peak lengthening velocity of VL fascicle and GM architectural gear ratio, whereas GM fascicle displayed similar length and velocity patterns. Single‐leg landing lengthens the tendinous tissues of GM and, to a greater degree, VL muscles, without affecting the fascicles. These findings demonstrate the adjustment in fascicle‐tendon interactions to withstand mechanical demand through the tendon buffer action and fascicle rotation. The higher VL fascicle contribution to negative work as the drop height increases would suggest muscle‐specific damping responses during drop landing. This can originate from the distal‐to‐proximal sequence of joint kinetics, from differences in muscle and tendon functions (one‐ and two‐joint muscles), architectural and morphological properties (eg, tendon stiffness), as well as from the muscle activity of the GM and VL muscles.     

Etanercept provides a more physiological approach in the treatment of psoriasis

Psoriasis is a common chronic inflammatory disease affecting the skin and joints. Moderate to severe psoriasis is traditionally treated with systemic treatments, which can be effective but are often associated with relevant adverse effects, even when administered intermittently or rotationally. Biologic therapies may provide high and consistent efficacy over time, long-term safety, and simple administration schedules compared with nonbiologic therapies, and can be used in patients intolerant and/or resistant to these therapies. TNF-antagonists have a definite advantage over other biologic agents (e.g., T-cell targeting drugs) in the early and late manifestations of joint involvement. TNF-antagonists are a class of drugs with distinct pharmacokinetic and pharmacodynamic properties, and different safety profiles. Etanercept provides a more "physiological" mechanism of action compared to anti-TNF antibodies. Etanercept has less dramatic effects on TNF homeostasis although it has been proved to be highly effective in blocking psoriatic joint erosions. It maintains stable efficacy over time on skin psoriasis, also when used intermittently. Moreover, etanercept has been shown to be not immunogenic, and it only slightly increases the risk of granulomatous infections compared to anti-TNF antibodies. According to the "physiologic" paradigm of selection among TNF-antagonists linked to more or less physiologic mechanism of action, etanercept appears to be the anti-TNF of choice for treating most patients with moderate to severe plaque psoriasis and psoriatic arthritis, possibly even at an early stage.