Stable sulforaphane protects against gait anomalies and modifies bone microarchitecture in the spontaneous STR/Ort model of osteoarthritis

Osteoarthritis (OA), affecting joints and bone, causes physical gait disability with huge socio-economic burden; treatment remains palliative. Roles for antioxidants in protecting against such chronic disorders have been examined previously. Sulforaphane is a naturally occurring antioxidant. Herein, we explore whether SFX-01®, a stable synthetic form of sulforaphane, modifies gait, bone architecture and slows/reverses articular cartilage destruction in a spontaneous OA model in STR/Ort mice. Sixteen mice (n = 8/group) were orally treated for 3 months with either 100 mg/kg SFX-01® or vehicle. Gait was recorded, tibiae were microCT scanned and analysed. OA lesion severity was graded histologically. The effect of SFX-01® on bone turnover markers in vivo was complemented by in vitro bone formation and resorption assays. Analysis revealed development of OA-related gait asymmetry in vehicle-treated STR/Ort mice, which did not emerge in SFX-01®-treated mice. We found significant improvements in trabecular and cortical bone. Despite these marked improvements, we found that histologically-graded OA severity in articular cartilage was unmodified in treated mice. These changes are also reflected in anabolic and anti-catabolic actions of SFX-01® treatment as reflected by alteration in serum markers as well as changes in primary osteoblast and osteoclast-like cells in vitro. We report that SFX-01® improves bone microarchitecture in vivo, produces corresponding changes in bone cell behaviour in vitro and leads to greater symmetry in gait, without marked effects on cartilage lesion severity in STR/Ort osteoarthritic mice. Our findings support both osteotrophic roles and novel beneficial gait effects for SFX-01® in this model of spontaneous OA

Identification and Expression of the Family of Classical Protein-Tyrosine Phosphatases in Zebrafish

Protein-tyrosine phosphatases (PTPs) have an important role in cell survival, differentiation, proliferation, migration and other cellular processes in conjunction with protein-tyrosine kinases. Still relatively little is known about the function of PTPs in vivo. We set out to systematically identify all classical PTPs in the zebrafish genome and characterize their expression patterns during zebrafish development. We identified 48 PTP genes in the zebrafish genome by BLASTing of human PTP sequences. We verified all in silico hits by sequencing and established the spatio-temporal expression patterns of all PTPs by in situ hybridization of zebrafish embryos at six distinct developmental stages. The zebrafish genome encodes 48 PTP genes. 14 human orthologs are duplicated in the zebrafish genome and 3 human orthologs were not identified. Based on sequence conservation, most zebrafish orthologues of human PTP genes were readily assigned. Interestingly, the duplicated form of ptpn23, a catalytically inactive PTP, has lost its PTP domain, indicating that PTP activity is not required for its function, or that ptpn23b has lost its PTP domain in the course of evolution. All 48 PTPs are expressed in zebrafish embryos. Most PTPs are maternally provided and are broadly expressed early on. PTP expression becomes progressively restricted during development. Interestingly, some duplicated genes retained their expression pattern, whereas expression of other duplicated genes was distinct or even mutually exclusive, suggesting that the function of the latter PTPs has diverged. In conclusion, we have identified all members of the family of classical PTPs in the zebrafish genome and established their expression patterns. This is the first time the expression patterns of all members of the large family of PTP genes have been established in a vertebrate. Our results provide the first step towards elucidation of the function of the family of classical PTPs

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Hamstrings anterior cruciate ligament reconstruction with and without platelet rich fibrin matrix

Anterior cruciate ligament (ACL) rupture is the most common complete ligamentous injury in the knee. Many studies explored ACL graft integration and maturation, but only a few assessed the application of platelet rich fibrin matrix (PRFM) as augmentation for ACL reconstruction. The main aim of this study was to test the PRFM augmentation in terms of graft-bone integration and knee stability. The secondary aim was to investigate patient-reported functional status.Prospective evaluation has been done in two consecutive series of patients who underwent ACL reconstruction with semitendinosus and gracilis (STG) grafts: 14 patients were operated with PRFM augmentation and 14 patients without PRFM augmentation. Objective clinical evaluation (Rolimeter) and MRI evaluation were performed at 1 year from surgery. Subjective evaluation (IKDC) was performed pre-operatively and at 6 months, 1 and 2 years from surgery.A statistically significant difference was not detected between the two groups in terms of MRI and objective clinical evaluation, although PRFM-augmented patients showed a statistically significant higher clinical improvement.The procedure described for PRFM augmentation in ACL STG reconstruction does not improve radiologic graft integration and knee stability after 1 year and should not be used by clinicians to this purpose. However, it may result in a short-term improvement of patient-reported knee function, and future research should focus on further developing PRP treatment to optimize ACL clinical outcome. LEVEL OF EVIDENCE: III

QUANDO DEFINIRE È FAR FINIRE IL MONDO IN UNA SCATOLA. PER UNA POSSIBILE ORIGINE DEL COSIDDETTO MASCHILE NON MARCATO

Scopo di questo contributo è la misurazione degli effetti della formalizzazione metalinguistica sulla percezione dei generi – a cascata linguistico e culturalmente costruito, nel senso di gender – nella società parlante italiana. Più precisamente, ciò che si ambisce a fare, nel piccolo di questa riflessione, è ipotizzare che alla base del cosiddetto maschile inclusivo e della sua successiva normatizzazione e normalizzazione possa aver agito quell’operazione di codifica metalinguistica resasi necessaria per preservare il latino in una società per la quale la latinitas era sentita come necessaria a preservare il senso di appartenenza a un mondo ambito