90 research outputs found
Gla-rich protein function as an anti-inflammatory agent in monocytes/macrophages: implications for calcification-related chronic inflammatory diseases
Calcification-related chronic inflammatory diseases are multifactorial pathological processes, involving a complex interplay between inflammation and calcification events in a positive feed-back loop driving disease progression. Gla-rich protein (GRP) is a vitamin K dependent protein (VKDP) shown to function as a calcification inhibitor in cardiovascular and articular tissues, and proposed as an anti-inflammatory agent in chondrocytes and synoviocytes, acting as a new crosstalk factor between these two interconnected events in osteoarthritis. However, a possible function of GRP in the immune system has never been studied. Here we focused our investigation in the involvement of GRP in the cell inflammatory response mechanisms, using a combination of freshly isolated human leucocytes and undifferentiated/differentiated THP-1 cell line. Our results demonstrate that VKDPs such as GRP and matrix gla protein (MGP) are synthesized and gamma-carboxylated in the majority of human immune system cells either involved in innate or adaptive immune responses. Stimulation of THP-1 monocytes/macrophages with LPS or hydroxyapatite (HA) up-regulated GRP expression, and treatments with GRP or GRP-coated basic calcium phosphate crystals resulted in the down-regulation of mediators of inflammation and inflammatory cytokines, independently of the protein gamma-carboxylation status. Moreover, overexpression of GRP in THP-1 cells rescued the inflammation induced by LPS and HA, by down-regulation of the proinflammatory cytokines TNF alpha, IL-1 beta and NFkB. Interestingly, GRP was detected at protein and mRNA levels in extracellular vesicles released by macrophages, which may act as vehicles for extracellular trafficking and release. Our data indicate GRP as an endogenous mediator of inflammatory responses acting as an anti-inflammatory agent in monocytes/macrophages. We propose that in a context of chronic inflammation and calcification-related pathologies, GRP might act as a novel molecular mediator linking inflammation and calcification events, with potential therapeutic application.Portuguese Science and Technology Foundation (FCT) [PTDC/SAU-ORG/117266/2010, PTDC/BIM-MEC/1168/2012, UID/Multi/ 04326/2013]; FCT fellowships [SFRH/BPD/70277/2010, SFRH/BD/111824/2015
Vertical Heterophoria and Postural Control in Nonspecific Chronic Low Back Pain
The purpose of this study was to test postural control during quiet standing in
nonspecific chronic low back pain (LBP) subjects with vertical heterophoria (VH)
before and after cancellation of VH; also to compare with healthy subjects with,
and without VH. Fourteen subjects with LBP took part in this study. The postural
performance was measured through the center of pressure displacements with a
force platform while the subjects fixated on a target placed at either 40 or 200
cm, before and after VH cancellation with an appropriate prism. Their postural
performance was compared to that of 14 healthy subjects with VH and 12 without
VH (i.e. vertical orthophoria) studied previously in similar conditions. For LBP
subjects, cancellation of VH with a prism improved postural performance. With
respect to control subjects (with or without VH), the variance of speed of the
center of pressure was higher, suggesting more energy was needed to stabilize
their posture in quiet upright stance. Similarly to controls, LBP subjects
showed higher postural sway when they were looking at a target at a far distance
than at a close distance. The most important finding is that LBP subjects with
VH can improve their performance after prism-cancellation of their VH. We
suggest that VH reflects mild conflict between sensory and motor inputs involved
in postural control i.e. a non optimal integration of the various signals. This
could affect the performance of postural control and perhaps lead to pain.
Nonspecific chronic back pain may results from such prolonged conflict
Behavioural Significance of Cerebellar Modules
A key organisational feature of the cerebellum is its division into a series of cerebellar modules. Each module is defined by its climbing input originating from a well-defined region of the inferior olive, which targets one or more longitudinal zones of Purkinje cells within the cerebellar cortex. In turn, Purkinje cells within each zone project to specific regions of the cerebellar and vestibular nuclei. While much is known about the neuronal wiring of individual cerebellar modules, their behavioural significance remains poorly understood. Here, we briefly review some recent data on the functional role of three different cerebellar modules: the vermal A module, the paravermal C2 module and the lateral D2 module. The available evidence suggests that these modules have some differences in function: the A module is concerned with balance and the postural base for voluntary movements, the C2 module is concerned more with limb control and the D2 module is involved in predicting target motion in visually guided movements. However, these are not likely to be the only functions of these modules and the A and C2 modules are also both concerned with eye and head movements, suggesting that individual cerebellar modules do not necessarily have distinct functions in motor control
A comparison of replicative senescence and doxorubicin-induced premature senescence of vascular smooth muscle cells isolated from human aorta
Extraocular Muscle Damage Associated with Endoscopic Sinus Surgery: An Ophthalmology Perspective
Is Saccadic Lateropulsion in Wallenberg’s Syndrome Caused by a Cerebellar or a Brain-Stem Lesion?
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