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Sinclair Hayes opublikował 1 rok, 3 miesiące temu
Mesenchymal stem cells (MSCs) have been identified within dental pulp tissues of exfoliated deciduous (SHEDs) and permanent (DPSCs) teeth. Although differences in their proliferative and differentiation properties were revealed, variability in SHEDs and DPSCs responsiveness to growth factors and cytokines have not been studied before. Here, we investigated the influence of interleukin-17 (IL-17) and basic fibroblast growth factor (bFGF) on stemness features of SHEDs and DPSCs by analyzing their proliferation, clonogenicity, cell cycle progression, pluripotency markers expression and differentiation after 7-day treatment. Results indicated that IL-17 and bFGF differently affected SHEDs and DPSCs proliferation and clonogenicity, since bFGF increased proliferative and clonogenic potential of both cell types, while IL-17 similarly affected SHEDs, exerting no effects on adult counterparts DPSCs. In addition, both factors stimulated NANOG, OCT4, and SOX2 pluripotency markers expression in SHEDs and DPSCs showing diverse intracellular expression patterns dependent on MSCs type. As for the differentiation capacity, both factors displayed comparable effects on SHEDs and DPSCs, including stimulatory effect of IL-17 on early osteogenesis in contrast to the strong inhibitory effect showed for bFGF, while having no impact on SHEDs and DPSCs chondrogenesis. Moreover, bFGF combined with IL-17 reduced CD90 and stimulated CD73 expression on both types of MSCs, whereas each factor induced IL-6 expression indicating its’ role in IL-17/bFGF-modulated properties of SHEDs and DPSCs. All these data demonstrated that dental pulp MSCs from primary and permanent teeth exert intrinsic features, providing novel evidence on how IL-17 and bFGF affect stem cell properties important for regeneration of dental pulp at different ages.Circulating free light chains (FLCs), considered biomarkers of B cell activity, are frequently elevated in patients affected by systemic inflammatory autoimmune diseases. As the systemic sclerosis (SSc) clinical course can be variable, this study is aimed at evaluating FLCs levels in affected individuals as biomarkers of disease activity. We assessed FLC levels in serum and urine of 72 SSc patients and 30 healthy controls (HC). Results were analyzed in comparison with overall clinical and laboratory findings, disease activity index (DAI) and disease severity scale (DSS). SSc patients displayed increased levels of κ and λ FLC in serum significantly higher than HC (p = 0.0001) alongside the mean values of free κ/λ ratio and κ + λ sum (p = 0.0001). SSc patients showed increased free κ in urine with a κ/λ higher than HC (p = 0.0001). SSc patients with increased κ + λ in serum showed that erythro-sedimentation rate (p = 0.034), C-reactive protein (p = 0.003), DAI (p = 0.024) and DSS (p = 0.015) were higher if compared to SSc patients with normal levels of FLC. A positive linear correlation was found between serum levels of free κ and DAI (r = 0.29, p = 0.014). In addition, SSc patients with increased free κ in urine had higher DAI (p = 0.048) than SSc patients with normal κ levels. Our results strengthen the role of serum FLC as useful biomarker in clinical practice to early diagnosis and monitor disease activity, showing for the first time that also urine FLC levels correlated with disease activity in SSc patients.Cadmium (Cd) exposure can impair the traits of aquatic animals associated with reproduction. In natural lakes Cd is typically detected at concentrations below 0.001 mg l-1 . The authors investigated the impact of ultra-acute Cd exposure on sperm motility in European whitefish (Coregonus lavaretus). They activated sperm with water containing various nominal concentrations of Cd and recorded sperm motility parameters. Only the highest Cd concentration (500 mg l-1 ) was associated with decreased sperm swimming velocity and increases in both the percentage of static cells and curvature of the sperm swimming trajectory. The results indicate that environmentally realistic concentrations of Cd during the sperm motility activation are not critically harmful to male C. lavaretus fertilization potential.Meta-analyses of correlation coefficients are an important technique to integrate results from many cross-sectional and longitudinal research designs. Uncertainty in pooled estimates is typically assessed with the help of confidence intervals, which can double as hypothesis tests for two-sided hypotheses about the underlying correlation. A standard approach to construct confidence intervals for the main effect is the Hedges-Olkin-Vevea Fisher-z (HOVz) approach, which is based on the Fisher-z transformation. Results from previous studies (Field, 2005, Psychol. Meth., 10, 444; Hafdahl and Williams, 2009, Psychol. Meth., 14, 24), however, indicate that in random-effects models the performance of the HOVz confidence interval can be unsatisfactory. To this end, we propose improvements of the HOVz approach, which are based on enhanced variance estimators for the main effect estimate. In order to study the coverage of the new confidence intervals in both fixed- and random-effects meta-analysis models, we perform an extensive simulation study, comparing them to established approaches. Data were generated via a truncated normal and beta distribution model. The results show that our newly proposed confidence intervals based on a Knapp-Hartung-type variance estimator or robust heteroscedasticity consistent sandwich estimators in combination with the integral z-to-r transformation (Hafdahl, 2009, Br. J. Math. Stat. Psychol., 62, 233) provide more accurate coverage than existing approaches in most scenarios, especially in the more appropriate beta distribution simulation model.The IL-7/IL-7R pathway plays a vital role in the immune system, especially in the inflammatory response. Monocytes/macrophages (osteoclast precursors) have been recently recognized as important participants in the osteoclastogenesis of rheumatoid arthritis (RA) patients. Here, we aimed to investigate the therapeutic potential of IL-7/IL-7R pathway in RA and to determine whether it could restrain osteoclastogenic functions and therefore ameliorate RA. Firstly, collagen-induced arthritis (CIA) mice were administered with IL-7Rα-target antibodies to assess their therapeutic effect on arthritis. We found that blockade of the IL-7/IL-7R pathway protected CIA mice from bone destruction in addition to inducing inflammatory remission, by altering the RANKL/RANK/OPG ratio and consequently decreasing osteoclast formation. To explore the effect and mechanism of this pathway, bone marrow cells were induced to osteoclasts and treated with IL-7, a STAT5 inhibitor or supernatants from T cells. The results showed that the IL-7/IL-7R pathway played a direct inhibitory role in osteoclast differentiation via STAT5 signalling pathway in a RANKL-induced manner. We applied flow cytometry to analyse the effect of IL-7 on T-cell RANKL expression and found that IL-7/IL-7R pathway had an indirect role in the osteoclast differentiation process by enhancing the RANKL expression on T cells. In conclusion, the IL-7/IL-7R pathway exhibited a dual effect on osteoclastogenesis of CIA mice by interacting with osteoimmunology processes and could be a novel therapeutic target for autoimmune diseases such as RA.The identification of gunshot residue (GSR) on wounds enables the differentiation of entry and exit wounds. Unfortunately, studies analyzing GSR on degraded bodies have been poorly documented, and no data exist regarding GSR detection after stagnant water immersion. The aim of this preliminary experimental study was to detect GSR on wounds altered in stagnant water, using scanning electron microscopy coupled with energy-dispersive X (SEM-EDX) and inductively coupled plasma mass spectrometry (ICP-MS). Shots were performed on sheep limbs with a 22LR at a distance of 20 cm. The limbs were then submerged in stagnant water and analyzed on days 0, 6, and 14. SEM-EDX was performed on previously dehydrated wounds. For ICP-MS analysis, the wounds were rubbed with a cotton swab that was then analyzed. In the SEM studies, a higher number of particles were detected in entry wounds compared to exit wounds under every set of experimental conditions. Unfortunately, SEM-EDX failed to detect GSR particles, even on day 0. ICP-MS enabled the detection of Pb, Sb, and Ba at every stage with higher quantities on entry than in exit. These elements remained detectable following limb immersion. ICP-MS enabled differentiate entry from exit wounds, even after immersion in stagnant water. Nevertheless, when manually swabbing the wounds, quantities of matter collected is highly variable. ICP-MS is a more suitable technique than SEM-EDX for GSR identification of wounds after decomposition in stagnant water; however, standardization is needed.
The aim of this review was to interrogate the evidence base for treatment of keratomalacia in dogs and cats, through examination of the applicable literature.
Studies were screened for evidence to answer the following question Which of the treatment options for keratomalacia in dogs and cats offers the best chance of globe survival, the fastest time to resolution with globe survival, and the best visual outcome. The search utilised the PubMed (http//www.pubmed.gov/) and ISI Web of Science (http//wok.mimas.ac.uk/) databases. Databases were searched using the following terms (keratomalacia OR corneal melt OR corneal malacia) AND (dog OR canine OR canid OR cat OR feline OR felid) AND (treatment OR outcome OR morbidity OR complications). Studies were assessed by one author (CH) and excluded if they related to less than three keratomalacia cases, experimental treatments, in vitro studies, or did not provide information regarding outcome. Studies were classified to a level of evidence according to the system described by the Oxford Centre for EvidenceBased Medicine.
Eighteen (18) studies were identified as providing information to answer the proposed question, one as level 3, 10 as level 4 and seven as level 5 evidence. Only one study compared two treatments, the remaining were prospective or retrospective case series of a single treatment intervention. Study design was highly variable with respect to population size, followup and outcome assessment, making direct comparison difficult, and metaanalysis was not applied.
Overall, the evidence for improved outcome of one proposed treatment over another proposed treatment for keratomalacia in dogs and/or cats is very weak.
Overall, the evidence for improved outcome of one proposed treatment over another proposed treatment for keratomalacia in dogs and/or cats is very weak.Inflammation and immune dysfunction have been increasingly recognized as crucial mechanisms in atherogenesis. Modifications in cell lipid metabolism, plasma dyslipidaemia and particularly low high-density lipoprotein (HDL) levels occur both in atherosclerosis and in autoimmune rheumatic diseases (which are strongly associated with an increased risk of atherosclerosis), suggesting the presence of a crucial link. HDL, the plasma lipoprotein responsible for reverse cholesterol transport, is known for its several protective effects in the context of atherosclerosis. Among these, HDL immunomodulatory effects are possibly the less understood. Through the efflux of cholesterol from plasma cell membranes with the consequent disruption of lipid rafts and the interaction with the cholesterol transporters present in the plasma membrane, HDL affects both the innate and adaptive immune responses. Animal and human studies have demonstrated a predominance of HDL anti-inflammatory effects, despite some pro-inflammatory actions having also been reported.


