Link N as a therapeutic agent for discogenic pain.

Neurotrophins (NTs) are the major contributors of sensory axonal sprouting, neural survival, regulation of nociceptive sensory neurons, inflammatory hyperalgesia, and neuropathic pain. Intervertebral disc (IVD) cells constitutively express NTs. Their expression is upregulated by proinflammatory cytokines present in the IVD during degeneration, which can promote peripheral nerve ingrowth and hyperinnervation, leading to discogenic pain.

Natriuretic peptide receptor-C activation attenuates angiotensin II-induced enhanced oxidative stress and hyperproliferation of aortic vascular smooth muscle cells.

We showed previously that natriuretic peptide receptor-C (NPR-C) agonist, C-ANP, attenuated the enhanced expression of Giα proteins in vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) through the inhibition of enhanced oxidative stress. Since the enhanced levels of endogenous angiotensin II (Ang II) contribute to the overexpression of Giα proteins and augmented oxidative stress in VSMC from SHR, the present study was undertaken to investigate if C-ANP could also attenuate angiotensin II (Ang II)-induced oxidative stress and associated signaling. Ang II treatment of aortic VSMC augmented the levels of superoxide anion (O), NADPH oxidase activity, and the expression of NADPH oxidase subunits and C-ANP treatment attenuated all these to control levels.

Naproxen induces type X collagen expression in human bone-marrow-derived mesenchymal stem cells through the upregulation of 5-lipoxygenase.

Several studies have shown that type X collagen (COL X), a marker of late-stage chondrocyte hypertrophy, is expressed in mesenchymal stem cells (MSCs) from osteoarthritis (OA) patients. We recently found that Naproxen, but not other nonsteroidal anti-inflammatory drugs (NSAIDs) (Ibuprofen, Celebrex, Diclofenac), can induce type X collagen gene (COL10A1) expression in bone-marrow-derived MSCs from healthy and OA donors. In this study we determined the effect of Naproxen on COL X protein expression and investigated the intracellular signaling pathways that mediate Naproxen-induced COL10A1 expression in normal and OA hMSCs.

Antidiabetic compounds from Sarracenia purpurea used traditionally by the Eeyou Istchee Cree First Nation.

Through ethnobotanical surveys, the CIHR Team in Aboriginal Antidiabetic Medicines identified 17 boreal forest plants stemming from the pharmacopeia of the Cree First Nations of Eeyou Istchee (James Bay region of Northern Quebec) that were used traditionally against diabetes symptoms. The leaves of Sarracenia purpurea (pitcher plant), one of the identified Cree plants, exhibited marked antidiabetic activity in vitro by stimulating glucose uptake in C2C12 mouse muscle cells and by reducing glucose production in H4IIE rat liver cells. Fractionation guided by glucose uptake in C2C12 cells resulted in the isolation of 11 compounds from this plant extract, including a new phenolic glycoside, flavonoid glycosides, and iridoids.

Knockdown of natriuretic peptide receptor-A enhances receptor C expression and signalling in vascular smooth muscle cells.

Aims: Natriuretic peptide receptor-A (NPR-A) knockout mice exhibited an increased blood pressure that may also be attributed to the up-regulation of NPR-C and associated signalling; however, the interaction between the two receptors has not been investigated. In the present study, we investigated the effect of knockdown of NPR-A using NPR-A antisense (AS) on the expression of NPR-C and adenylyl cyclase (AC) signalling in A10 vascular smooth muscle cells (VSMC).

Methods And Results: The receptor and G protein expression was determined by western blotting, and AC activity was determined by measuring [(32)P]cAMP formation from [α-(32)P]ATP.

The constitutive expression of type x collagen in mesenchymal stem cells from osteoarthritis patients is reproduced in a rabbit model of osteoarthritis.

The expression of type X collagen (COL X), a late-stage chondrocyte hypertrophy marker in human mesenchymal stem cells (MSCs) from osteoarthritis (OA) patients poses a major setback to current cartilage and intervertebral disc tissue engineering efforts. However, it is not yet clear whether COL X is expressed by all human bone marrow stem cells or if it is related to age, gender, site, disease status, or drug therapy. In the current study, we report that COL X expression is upregulated in MSCs from rabbits in a surgical instability model of OA (anterior cruciate ligament transection (ACLT)) when compared to control rabbit MSCs.

The In Vivo Antidiabetic Activity of Nigella sativa Is Mediated through Activation of the AMPK Pathway and Increased Muscle Glut4 Content.

The antidiabetic effect of N. sativa seed ethanol extract (NSE) was assessed in Meriones shawi after development of diabetes. Meriones shawi were divided randomly into four groups: normal control, diabetic control, diabetic treated with NSE (2 g eq plant/kg) or with metformin (300 mg/kg) positive control, both administered by daily intragastric gavage for 4 weeks.

Bioassay-guided isolation of the antidiabetic principle from Sorbus decora (Rosaceae) used traditionally by the Eeyou Istchee Cree First Nations.

Bioassay-guided fractionation of a crude extract (80% EtOH in H(2)O) of stem bark of Sorbus decora led the isolation of three new pentacycle triterpenes (compounds 1-3). The structures of 1-3 were established on the basis of spectroscopic methods (IR, HREIMS, 1D and 2D NMR) as 23,28-dihydroxyursan-12-ene-3β-caffeate, 23,28-dihydroxylupan-20(29)-ene-3β-caffeate, and 3β,23,28-trihydroxy-12-ursene, respectively. Compound 2 significantly enhanced glucose uptake in C2C12 cells, but compounds 1 and 3 did not.

Hydro-ethanolic extract of cashew tree (Anacardium occidentale) nut and its principal compound, anacardic acid, stimulate glucose uptake in C2C12 muscle cells.

Scope: Products of cashew tree (Anacardium occidentale) are used in traditional medicine for various ailments, including diabetes.

Methods And Results: The anti-diabetic properties of cashew plant parts were studied using differentiated C2C12 myoblasts (myotubes) and rat liver mitochondria. Hydroethanolic extract of cashew seed (CSE) and its active component, anacardic acid (AA), stimulated glucose transport into C2C12 myotubes in a concentration-dependent manner.

Mitochondrial acetylcarnitine provides acetyl groups for nuclear histone acetylation.

Dynamic acetylation and deacetylation of nuclear histones is essential for regulating the access of chromosomal DNA to transcriptional machinery. The source of acetyl-CoA for histone acetylation in mammalian cell nuclei is not clearly known. We show that acetylcarnitine formed in mitochondria, is transported into cytosol by carnitine/acylcarnitine translocase, and then enters nucleus, where it is converted to acetyl-CoA by a nuclear carnitine acetyltransferase and becomes a source of acetyl groups for histone acetylation.