1,724,317 research outputs found
A Novel CD147 Inhibitor, SP-8356, Attenuates Pathological Fibrosis in Alkali-Burned Rat Cornea
No full textThe corneal fibrotic responses to corneal damage often lead to severe corneal opacification thereby resulting in severe visual impairment or even blindness. The persistence of corneal opacity depends heavily on the activity of corneal myofibroblast. Myofibroblasts are opaque and synthesize a disorganized extracellular matrix (ECM) and thus promoting opacification. Cluster of differentiation 147 (CD147), a member of the immunoglobulin superfamily, is known to play important roles in the differentiation process from fibroblast to myofibroblast in damaged cornea and may therefore be an effective target for treatment of corneal opacity. Here, we examined the therapeutic efficacy of novel CD147 inhibiting verbenone derivative SP-8356 ((1S,5R)-4-(3,4-dihydroxy-5-methoxystyryl)-6,6-dimethylbicyclo[3.1.1]hept-3-en-2-one) on corneal fibrosis. Topical SP-8356 significantly reduced corneal haze and fibrosis in the alkali-burned cornea. In detail, SP-8356 inhibited both alpha-smooth muscle actin (α-SMA) expressing myofibroblast and its ECM-related products, such as matrix-metalloproteinase-9 and collagen type III and IV. Similar to SP-8356, topical corticosteroid (prednisolone acetate, PA) also reduced the ECM-related products and opacification. However, prednisolone acetate failed to decrease the population of α-SMA-positive corneal myofibroblast. In conclusion, SP-8356 is capable enough to prevent corneal haze by preventing pathological fibrosis after severe corneal damage. Therefore, SP-8356 could be a potentially promising therapeutic drug for corneal fibrosis
Metabolism and Pharmacokinetics of SP-8356, a Novel (1S)-(−)-Verbenone Derivative, in Rats and Dogs and Its Implications in Humans
No full text(1S,5R)-4-((E)-3,4-dihydroxy-5-methoxystryryl)-6,6-dimethylbicylco[3.1.1]hept-3-en-2-one (SP-8356) is a novel (1S)-(−)-verbenone derivative that is currently in preclinical development for the treatment of ischemic stroke and atherosclerosis. This report aimed at characterization of the metabolism and pharmacokinetic properties of SP-8356. Following intravenous dose in rats and dogs, plasma concentrations of SP-8356 declined rapidly with high clearance (CL) and short half-life; after oral administration in both species, its plasma levels were below the quantitation limit. Fourteen circulating metabolites, formed by mono-oxygenation, demethylation, glucuronidation, catechol O-methylation, sulfation and oxidation (bioactivation) followed by glutathione (GSH) conjugation, were tentatively identified in both species. Urinary excretion of SP-8356 appeared to be minimal in rats, compared to its metabolites. GSH conjugate of SP-8356 was also formed during incubation with rat liver S9 fraction consistent with oxidative bioactivation; this bioactivation was almost completely inhibited by the cofactors for glucuronidation, sulfation and methylation, indicating that it may be abolished by competing metabolic reactions in the body. The human pharmacokinetics of SP-8356 was predicted to be similar to that of the animals based on the current in vitro metabolic stability results. In summary, rapid phase II metabolism appears to be mainly responsible for its suboptimal pharmacokinetics, such as high CL and low oral absorption. Because of competing metabolic reactions, potential safety risks related to SP-8356 bioactivation may be low
Linked collectors and determiners for: CAS Mammalogy (MAM).
No full textNatural history specimen data linked to collectors and determiners held within, "CAS Mammalogy (MAM)". Claims or attributions were made on Bionomia by volunteer Scribes, <a href="http://bionomia.net/dataset/6ce7290f-47f6-4046-8356-371f5b6749df">https://bionomia.net/dataset/6ce7290f-47f6-4046-8356-371f5b6749df</a> using specimen data from the dataset aggregated by the Global Biodiversity Information Facility, <a href="https://gbif.org/dataset/6ce7290f-47f6-4046-8356-371f5b6749df">https://gbif.org/dataset/6ce7290f-47f6-4046-8356-371f5b6749df</a>. Formatted as a Frictionless Data package
Linked collectors and determiners for: CAS Mammalogy (MAM).
No full textNatural history specimen data linked to collectors and determiners held within, "CAS Mammalogy (MAM)". Claims or attributions were made on Bionomia by volunteer Scribes, <a href="http://bionomia.net/dataset/6ce7290f-47f6-4046-8356-371f5b6749df">https://bionomia.net/dataset/6ce7290f-47f6-4046-8356-371f5b6749df</a> using specimen data from the dataset aggregated by the Global Biodiversity Information Facility, <a href="https://gbif.org/dataset/6ce7290f-47f6-4046-8356-371f5b6749df">https://gbif.org/dataset/6ce7290f-47f6-4046-8356-371f5b6749df</a>. Formatted as a Frictionless Data package
SP-8356, a Novel Inhibitor of CD147-Cyclophilin A Interactions, Reduces Plaque Progression and Stabilizes Vulnerable Plaques in apoE-Deficient Mice
No full textInteractions between CD147 and cyclophilin A (CypA) promote plaque rupture that causes atherosclerosis-related cardiovascular events, such as myocardial infarction and stroke. Here, we investigated whether SP-8356 ((1S,5R)-4-(3,4-dihydroxy-5-methoxystyryl)-6,6-dimethylbicyclo[3.1.1]hept-3-en-2-one), a novel drug, can exert therapeutic effects against plaque progression and instability through disruption of CD147-CypA interactions in apolipoprotein E-deficient (ApoE KO) mice. Immunocytochemistry and immunoprecipitation analyses were performed to assess the effects of SP-8356 on CD147-CypA interactions. Advanced plaques were induced in ApoE KO mice via partial ligation of the right carotid artery coupled with an atherogenic diet, and SP-8356 (50 mg/kg) orally administrated daily one day after carotid artery ligation for three weeks. The anti-atherosclerotic effect of SP-8356 was assessed using histological and molecular approaches. SP-8356 interfered with CD147-CypA interactions and attenuated matrix metalloproteinase-9 activation. Moreover, SP-8356 induced a decreased in atherosclerotic plaque size in ApoE KO mice and stabilized plaque vulnerability by reducing the necrotic lipid core, suppressing macrophage infiltration, and enhancing fibrous cap thickness through increasing the content of vascular smooth muscle cells. SP-8356 exerts remarkable anti-atherosclerotic effects by suppressing plaque development and improving plaque stability through inhibiting CD147-CypA interactions. Our novel findings support the potential utility of SP-8356 as a therapeutic agent for atherosclerotic plaque
The Therapeutic Effects of SP-8356, a Verbenone Derivative, with Multimodal Cytoprotective Mechanisms in an Ischemic Stroke Rat Model
No full textAn ischemic cerebral stroke results from the interruption of blood flow to the brain, triggering rapid and complex cascades of excitotoxicity, oxidative stress, and inflammation. Current reperfusion therapies, including intravenous thrombolysis and mechanical thrombectomy, cause further brain injury due to reperfusion-induced cytotoxicity. To date, novel cytoprotective therapies that could address these challenges have yet to be developed, likely due to the limitations of targeting a single pathologic mechanism. To address these unmet clinical needs, we investigated a synthetic verbenone derivative, SP-8356, as a potential multi-target cytoprotective agent for acute ischemic strokes. In transient middle cerebral artery occlusion (MCAO) rats, SP-8356 significantly reduced brain infarct and edema volumes while improving acute neurological deficits in a dose-dependent manner. Furthermore, SP-8356 improved long-term outcomes, particularly by reducing mortality. These potent cytoprotective effects of SP-8356 were achieved by suppressing the excessive production of free radicals and pro-inflammatory cytokines, reducing the infiltration of inflammatory cells, and mitigating increases in blood–brain barrier permeability. Additional research is needed to determine whether co-administration of SP-8356 can extend the therapeutic time window of reperfusion therapies by mitigating ischemia/reperfusion injury
SP-8356 (A Verbenone Derivative) Inhibits Proliferation, Suppresses Cell Migration and Invasion and Decreases Tumor Growth of Osteosarcoma: Role of PGC-1α/TFAM and AMPK-Activation
Full text linkObjective: Osteosarcoma (OS) is an uncommon sarcoma with osteoid formation in conjunction with malignantmesenchymal cells on histological examination. SP-8356 has been reported to exhibit anti-cancer properties in humancancers. However the impact of SP-8356 on OS is largely unknown. The metabolic pathways are coordinated by AMPactivatedprotein kinase (AMPK), which maintains a balance between the supply and demand of nutrients and energy.This study aimed to investigate effect of SP-8356 on proliferation and apoptosis of OS cells and tumor growth in mice.Furthermore, involvement of PGC-1α/TFAM and AMPK-activation was studied.Materials and Methods: In the experimental study, Saos-2 and MG63 cells were cultured with SP-8356 for 24hours and analysed for cellular proliferation using MTT assay. DNA fragmentation was studied using ELISA basedkit. Furthermore, transwell chambers assay was used to determine cell migration and cell invasion. Targeted proteinexpression levels were assessed using western blotting. For in vivo studies, mice (5-6 weeks old) were implanted witheither Saos-2 or MG63 cells on dorsal surface subcutaneously and they were administered with SP-8356 (10 mg/kg)for two weeks prior to bone tumor induction.Results: We found that SP-8356 exerted anti-proliferative effects on Saos-2 and MG63 cells. Furthermore, SP-8356treatment significantly restricted migration and invasion of Saos-2 and MG63 cells. Compared to the control, SP-8356significantly reduced apoptotic cell death, while it increased PGC-1α and TFAM expressions. Without affecting bodyweight, SP-8356 significantly reduced tumor development in mice, as compared to the control group.Conclusion: SP-8356 was found to inhibit proliferation, suppressed cells migration and invasion and decreased OStumor growth. Furthermore, SP-8356 was found to act through PGC-1α/TFAM and AMPK activations. SP-8356 can betherefore used as therapeutic agent for OS treatment
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Measuring the poverty impact of ACIAR projects: a broad framework
Full text linkThis report sets out some broad ideas about how poverty evaluation could be conducted for ACIAR research projects. As with good benefit–cost analysis, there are good practices that need to be observed when undertaking poverty analysis. While poverty is a broad concept, and can be addressed through many means, these need to be grounded in some common understanding of the economics of poverty. This report is concerned mostly with quantitative evaluation, in the same sense that current ACIAR project evaluations are quantitative. That is, it is concerned with saying something about the order of magnitude of the effects of the project. Of course, qualitative analysis is important, and in most cases is a prelude to quantification — there is little point quantifying if you don’t understand what you are talking about. Quantification, however, provides a discipline and focus for qualitative speculation and provides an important extra dimension when comparing the effects of different projects. When quantifying, there are many sensible approaches that could be adopted. We will focus here on approaches that are broadly consistent with the current approaches to benefit–cost analysis and that could readily be used to augment those approaches. The report begins by reviewing some basic notions of poverty (Chapter 2) and then goes on (Chapter 3) to discuss in principle the ways that agricultural research could influence poverty. Chapter 4 explains, with the use of some examples, a range of analytical approaches that could be taken, and Chapter 5 draws some specific implications for ACIAR.poverty evaluation, benefit-cost analysis, poverty analysis, economics of poverty, quantitative evaluation, analytical, Agribusiness, Agricultural and Food Policy, Crop Production/Industries, Farm Management, Food Consumption/Nutrition/Food Safety, Food Security and Poverty, International Development, Livestock Production/Industries, Production Economics,
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