Modulation of the Astrocyte-Neuron Lactate Shuttle System contributes to Neuroprotective action of Fibroblast Growth Factor 21

Modulation of the Astrocyte-Neuron Lactate Shuttle System contributes to Neuroprotective action of Fibroblast Growth Factor 21

A point of view given Alzheimer’s disease (AD) as “type 3 diabetes” focuses on the central role of dysfunctional metabolism of cerebral energy in AD. The growth factor for hormonal fibroblasts 21 (FGF21) is a crucial regulator of energy metabolism; However, our understanding of the therapeutic potential and the mechanisms underlying the effect of the FGF21 on the neurodegeneration of advertising is far from complete.

Methods: To further elucidate the effect of FGF21 on AD-related neurodegeneration, we used transgenic mice APP / PS1 to evaluate the effects of the FGF21 on memory malfunction, the pathology of the amyloid plate and L ‘Pathological hyperphosphorylation of Tau. We have also established an in vitro system to imitate astrocyte-neuron communication and an in vivo model of acute injury. On the basis of in vivo and in vitro models, we analyzed the neuroprotective actions of FGF21 and channels relating to astrocyte-neuron communication and focused on the lactate astrocyte-neuron shuttle system.

Results: Here, we note that FGF21 can improve the neurodegeneration of an Alzheimer in transgenic mice app / ps1. We have detected defects in the lactate astrocyte-neuron shuttle system in AD vivo and in vitro models and identified FGF21 as a neuroprotective molecule that can save these deficits. The administration of FGF21 can attenuate the memory malfunction, the pathology of the amyloid plate and the pathological hythesis Tau, and the function of FGF21 in neurodegeneration is partly mediated by the monocarboxylate carriers (MCTs). In vivo, it is also suggested that FGF21 acts centrally in mice to effect on neurodegeneration and energy metabolism through its SCTM regulation.

Conclusions: These results suggest that the FGF21 modifies the metabolic parameters to mediate its neuroprotective functions. The modulation of the lactate astrocyte-neuron lactate shuttle system can be one of the most effective strategies for FGF21 in Alzheimer’s degeneration and helps to improve metabolic defects in the brain and cytotoxicity induced by the amyloid. Our conclusions provide information on the mechanisms underlying FGF21 on neurodegeneration and the metabolism of cerebral energy and suggest that FGF21 can have a therapeutic value in the treatment of advertising and other neurodegenerative diseases.

Therapeutic photobiomodulation improves the growth factor and the cytokine secretion profile in human type 2 diabetic fibroblasts

Cicatrization of altered wounds is a common complication of sweet diabetes (DM) and the underlying mechanism of this disability is still unclear. Fibroblast, as the main reconstructed cell, secretes critical growth factors and cytokine contributing to the healing of wounds. It is well known that DM modifies the behavior of these cells and photobiomodulation therapy (PBMT) compensates for certain deficiencies in diabetic fibroblasts.

As a result, the purpose of this study was to demonstrate the impact of diabetes and the role of PBMT by low-level laser irradiation on the secret profile of human diabetic fibroblasts. Primary human dermal fibers of normal donors and diabetics  were harvested. For PBMT, the DHDFs were irradiated with a 632.8 nm helium laser, wavelength and energy density of 0.5 J / cm2, as a laser-treated groupThen, certain cellular behaviors and a secretory profiling matrix for 60 growth factors / cytokines were studied in LT-DHDFS, and then compared to those of the controls.

The data showed that the PBMT could compensate for these deficiencies in DHDFs in terms of viability, proliferation and migration. In addition, taking into account our new conclusions, these 20 growth factors / cytokines involved in cell proliferation, the immune system regulation and cellular cell communication routes, which have decreased considerably in the DHDF compared to HDF, The PBMT could compensate seven in the LT-DHDFS compared to DHDFS.

 Modulation of the Astrocyte-Neuron Lactate Shuttle System contributes to Neuroprotective action of Fibroblast Growth Factor 21
Modulation of the Astrocyte-Neuron Lactate Shuttle System contributes to Neuroprotective action of Fibroblast Growth Factor 21

The growth factor of the connective tissue produced by fibroblasts associated with cancer is correlated with a bad prognosis in a malignant pleural mesothelioma

Malignant mesothelioma is an aggressive neoplasm for which effective treatments are lacking. We often encounter cases of mesothelioma with a deep clever reaction, suggesting the involvement of fibroblasts associated with cancer (CAFS) in the progression of mesothelioma. While the roles of CAF have been widely studied in other tumors and have hoped that the cancer stroma contains heterogeneous caf populations, their roles in mesothelioma remain unknown.

We have previously shown that the conjunctive tissue growth factor (CTGF), a secreted protein, is produced by mesothelioma cells and fibroblasts and promotes invasion of in vitro mesothelioma cells. In this study, we examined the clinical relevance of CAFS in mesothelioma. Use of the surgical specimens of malignantly pleural mesothelioma, we evaluated the clinicopathological significance of the expression of α-smooth muscle actin (αsma), the most widely used marker of CAFs, the expression of the CTGF and the Extent of fibrosis by immunohistochemistry and masson coloration elastication.

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We also analyzed the expression of the paralague of the stroach cells and the mesenchymate fibroblast, a recently reported CAF marker which labels cancer cafs and differs from the positive coffees of αsma, by hybridization in situ. The extent of fibrosis and the expression of the CTGF in mesothelioma cells are not correlated with the patient’s prognosis. However, the expression of αsma and the CTGF, but not Meflin, in CAF correlated with a bad prognosis. The data suggest that CTGF + CAF are involved in the progression of mesothelioma and represent a potential molecular target for mesothelioma therapy.

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