The Altered Expression of Perineuronal Net Elements During Neural Differentiation

Background Perineuronal nets (PNNs), which are localized around neurons during development, are specialized forms of neural extracellular matrix with neuroprotective and plasticity-regulating roles. Hyaluronan and proteoglycan link protein 1 (HAPLN1), tenascin-R (TNR) and aggrecan (ACAN) are key elements of PNNs. In diseases characterized by neuritogenesis defects, the expression of these proteins is known to be downregulated, suggesting that PNNs may have a role in neural differentiation. Methods In this study, the mRNA and protein levels of HAPLN1, TNR and ACAN were determined and compared at specific time points of neural differentiation. We used PC12 cells as the in vitro model because they reflect this developmental process. Results On day 7, the HAPLN1 mRNA level showed a 2.9-fold increase compared to the non-differentiated state. However, the cellular HAPLN1 protein level showed a decrease, indicating that the protein may have roles in neural differentiation, and may be secreted during the early period of differentiation. By contrast, TNR mRNA and protein levels remained unchanged, and the amount of cellular ACAN protein showed a 3.7-fold increase at day 7. These results suggest that ACAN may be secreted after day 7, possibly due to its large amount of post-translational modifications. Conclusions Our results provide preliminary data on the expression of PNN elements during neural differentiation. Further investigations will be performed on the role of these elements in neurological disease models.PubMedWoSScopu

C-Reactive Protein Levels and Vitamin D Receptor Polymorphisms as Markers in Predicting Cachectic Syndrome in Cancer Patients

BACKGROUND AND OBJECTIVE: In patients with advanced cancer, cachexia correlates with low performance status and poor quality of life. In addition, cachexia may be associated with reduced response to chemoradiotherapy and a poor prognosis in cancer patients. Nearly all forms of cachexia are closely associated with chronic inflammation and elevated levels of inflammatory and pro-inflammatory circulating factors, including C-reactive protein (CRP), which is considered a valid laboratory and clinical marker. Among the different pathways involved in the production of inflammatory cytokines and chemokines, the vitamin D-vitamin D receptor (VDR) axis plays a fundamental role. In this study, we explore the possible association between CRP and key factors pertaining to the vitamin D axis--in particular, VDR gene polymorphisms--in cancer patients with cachexia. Although certain tumor types are more commonly associated with cachexia, even within the same tumor type there are significant differences in the extent and duration of cachexia. Such variations may be due to polymorphisms of the VDR gene that could lead to cachexia-prone genotypes or to cachexia-resistant genotypes. Identification of such genotypes could be very helpful in the management of cancer patients. METHODS: Forty-three cancer patients were recruited by the Nutritional Unit of the Prato Hospital. Data on age, gender, type of cancer, stage of cancer, and nutritional assessment, as well as transferrin, ferritin, albumin, and CRP levels, were collected. Genomic DNA was extracted from peripheral blood leukocytes and amplified by polymerase chain reaction. BsmI, ApaI, TaqI, and FokI polymorphisms of the VDR gene were investigated using the respective restriction enzymes. For the different VDR polymorphisms, the absence or presence of the restriction sites were designated with capital or small letters, respectively. For example, for the BsmI polymorphism, the presence of the undigested fragment identified the B allele, whereas the presence of the digested fragment identified the b allele. RESULTS: Cancer patients with cachexia have higher CRP levels compared with non-cachectic cancer patients, independently from the genotype. In cachectic patients, the presence of specific VDR BsmI and TaqI alleles was associated with higher CRP levels. In particular, the VDR b and T alleles were more frequent in cachectic cancer patients with elevated CRP levels than in cachectic patients with normal CRP levels. CONCLUSION: From these results, we hypothesize that there is an association between BsmI and TaqI VDR gene polymorphisms and the cachectic syndrome. In particular, we propose that in cancer patients, the concomitance of b and T alleles with elevated CRP levels may represent an early clinical predictor for the development of a more aggressive form of cachexia

Prevalence of Psoriatic Arthritis in Patients with Psoriasis: A Systematic Review and Meta-Analysis of Observational and Clinical Studies

BACKGROUND: Wide-ranging prevalence estimates of psoriatic arthritis (PsA) in patients with psoriasis have been reported. OBJECTIVES: To assess the prevalence and incidence of PsA in patients with psoriasis. METHODS: Two authors independently searched 3 databases for studies reporting on the prevalence or incidence of PsA in patients with psoriasis. A proportion meta-analysis was performed to calculate the pooled proportion estimates of PsA in patients with psoriasis. RESULTS: A total of 266 studies examining 976,408 patients with psoriasis were included. Overall, the pooled proportion (95% confidence interval [CI]) of PsA among patients with psoriasis was 19.7% (95% CI, 18.5%-20.9%). In children and adolescents (\u3c18 years of age), the pooled prevalence was 3.3% (95% CI, 2.1%-4.9%). The PsA prevalence was 22.7% (95% CI, 20.6%-25.0%) in European patients with psoriasis, 21.5% (95% CI, 15.4%-28.2%) in South American patients with psoriasis, 19.5% (95% CI, 17.1%-22.1%) in North American patients with psoriasis, 15.5% (95% CI, 0.009%-51.5%) in African patients with psoriasis, and 14.0% (95% CI, 95% CI, 11.7%-16.3%) in Asian patients with psoriasis. The prevalence of PsA was 23.8% (95% CI, 20.1%-27.6%) in studies in which the Classification Criteria for Psoriatic Arthritis were applied. The incidence of PsA among patients with psoriasis ranged from 0.27 to 2.7 per 100 person-years. LIMITATIONS: Between-study heterogeneity may have affected the estimates. CONCLUSIONS: We found that 1 in 4 patients with psoriasis have PsA. With the growing recognition of the Classification Criteria for Psoriatic Arthritis, more homogenous and comparable prevalence estimates are expected to be reported