The potential for dietary factors to prevent or treat osteoarthritis

Osteoarthritis (OA) is a degenerative joint disease for which there are no disease-modifying drugs. It is a leading cause of disability in the UK. Increasing age and obesity are both major risk factors for OA and the health and economic burden of this disease will increase in the future. Focusing on compounds from the habitual diet that may prevent the onset or slow the progression of OA is a strategy that has been under-investigated to date. An approach that relies on dietary modification is clearly attractive in terms of risk/benefit and more likely to be implementable at the population level. However, before undertaking a full clinical trial to examine potential efficacy, detailed molecular studies are required in order to optimise the design. This review focuses on potential dietary factors that may reduce the risk or progression of OA, including micronutrients, fatty acids, flavonoids and other phytochemicals. It therefore ignores data coming from classical inflammatory arthritides and nutraceuticals such as glucosamine and chondroitin. In conclusion, diet offers a route by which the health of the joint can be protected and OA incidence or progression decreased. In a chronic disease, with risk factors increasing in the population and with no pharmaceutical cure, an understanding of this will be crucial

Sulforaphane represses matrix-degrading proteases and protects cartilage from destruction in vitro and in vivo:Sulforaphane is protective in the articular Joint

Sulforaphane (SFN) has been reported to regulate signaling pathways relevant to chronic diseases. The aim of this study was to investigate the impact of SFN treatment on signaling pathways in chondrocytes and to determine whether sulforaphane could block cartilage destruction in osteoarthritis

Distinct regulation of cytosolic phospholipase A(2) phosphorylation, translocation, proteolysis and activation by tumour necrosis factor-receptor subtypes

The hormonally regulated Ca2+-dependent enzyme, cytosolic phospholipase A(2), (cPLA(2)) is activated by a range of inflammatory stimuli. Tumour necrosis factor-alpha (TNF) is one of the first known Stimuli for cPLA, but it is not known whether both TNF receptor subtypes are involved in activating the lipase. In the present study, we show for the first time that both type 1 55 kDa TNFR (TNFR1) and type 11 75 kDa TNFR (TNFR2) stimulate cPLA(2) enzyme, but with distinct signalling mechanisms. TNFR I activates mitogen-activated protein kinase (MAPK) and p38MAPK. TNFR1 then phosphorylates and activates cPLA(2) in a MAPK-dependent fashion. Furthermore, TNFR1 causes the translocation and caspase-dependent proteolysis of cPLA, as part of its activation profile. TNFR2, on the other hand, does not cause the phosphorylation of cPLA(2) as it does not activate MAPK or p38MAPK, but instead activates cPLA(2) by causing its translocation to plasma membrane and perinuclear subcellular regions. TNFR2 activation causes a delayed, slight increase in [Ca2+](i) of < 50 nM that may contribute towards the translocation and activation of cPLA(2). Therefore both TNF receptor subtypes play a role in cPLA(2) activation, but by means of separate signal-transduction pathways

Biomarkers of Postsurgical Outcome in Dupuytren Disease

We hypothesised that the measurement of circulating collagen-degrading matrix metalloproteinases (MMPs) would be predictive of postsurgical outcome after fasciectomy for Dupuytren disease (DD), measured through total extension deficit (TED). Assay of MMP-1, MMP-13 and MMP-14 in the plasma of DD patients showed poor correlation with change in TED after surgery. However, MMP-14 levels correlated with preoperative TED. In order to extend this study, we also measured the transcriptome in tissue samples from DD patients and showed that expression of specific genes correlated with preoperative and postoperative TED. These methodologies demonstrate the use of the approach in uncovering biomarkers which both illuminate the mechanism of the disease and have clinical utility

Phase 2 of the Norwich COVID-19 testing initiative: An evaluation

University campuses have experienced widespread transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The virus is particularly prevalent in the student-age population and more likely to be asymptomatic

Replacement of the Alpha variant of SARS-CoV-2 by the Delta variant in Lebanon between April and June 2021

The COVID-19 pandemic continues to expand globally, with case numbers rising in many areas of the world, including the Eastern Mediterranean Region. Lebanon experienced its largest wave of COVID-19 infections from January to April 2021. Limited genomic surveillance was undertaken, with just 26 SARS-CoV-2 genomes available for this period, nine of which were from travellers from Lebanon detected by other countries. Additional genome sequencing is thus needed to allow surveillance of variants in circulation. In total, 905 SARS-CoV-2 genomes were sequenced using the ARTIC protocol. The genomes were derived from SARS-CoV-2-positive samples, selected retrospectively from the sentinel COVID-19 surveillance network, to capture diversity of location, sampling time, sex, nationality and age. Although 16 PANGO lineages were circulating in Lebanon in January 2021, by February there were just four, with the Alpha variant accounting for 97 % of samples. In the following 2 months, all samples contained the Alpha variant. However, this had changed dramatically by June and July 2021, when all samples belonged to the Delta variant. This study documents a ten-fold increase in the number of SARS-CoV-2 genomes available from Lebanon. The Alpha variant, first detected in the UK, rapidly swept through Lebanon, causing the country's largest wave to date, which peaked in January 2021. The Alpha variant was introduced to Lebanon multiple times despite travel restrictions, but the source of these introductions remains uncertain. The Delta variant was detected in Gambia in travellers from Lebanon in mid-May, suggesting community transmission in Lebanon several weeks before this variant was detected in the country. Prospective sequencing in June/July 2021 showed that the Delta variant had completely replaced the Alpha variant in under 6 weeks