Almeidaschmitt6690

This review produces a current and comprehensive understanding of integrative and systematic mechanisms for the use of TCMs for anti-obesity. We also advocate taking advantage of TCMs as another therapy for interventions on obesity-related diseases, as well as stressing the fact that more is needed to be done, scientifically, to determine the active compounds and modes of action of the TCMs.Autophagy is the major catabolic pathway involved in removing and recycling damaged macromolecules and organelles and several evidences suggest that dysfunctions of this pathway contribute to the onset and progression of central and peripheral neurodegenerative diseases. Diabetic retinopathy (DR) is a serious complication of diabetes mellitus representing the main preventable cause of acquired blindness worldwide. DR has traditionally been considered as a microvascular disease, however this concept has evolved and neurodegeneration and neuroinflammation have emerged as important determinants in the pathogenesis and evolution of the retinal pathology. Here we review the role of autophagy in experimental models of DR and explore the potential of this pathway as a target for alternative therapeutic approaches.In 2004, the US FDA approved Rufinamide, an anti-epileptic drug under the brand name Banzel®. In 2015, Banzel® received approval for its use in pediatric patients (ages 1-4 years). Rufinamide shows low oral bioavailability due to a low dissolution rate resulting in less of the drug reaching the brain. This has led to the high dose and dosing frequency of Rufinamide. In this work, using the principle of design of experiments (DoE), we have formulated Rufinamide-loaded chitosan nanoparticles and suspended them in a solution of a thermoresponsive polymer-tamarind seed xyloglucan to form a nasal in situ gel for direct nose to brain delivery of Rufinamide. The nanoparticles were characterized for particle size, entrapment efficiency, zeta potential, and physical stability. The in situ gel formulations were characterized for rheological properties, stability, and in vivo plasma and brain pharmacokinetics. Pharmacokinetic parameters were computed for aqueous suspension of nanoparticles and in situ gelling formulation for nanoparticles and compared with the pharmacokinetic parameters of an aqueous suspension of plain Rufinamide. The percentage of direct transport efficiency (% DTE) and direct transport percentage (%DTP) values were calculated for all the formulations. The optimized nanoparticle formulation showed a size of 180 ± 1.5 nm, a zeta potential of 38.3 ± 1.5 mV, entrapment efficiency of 75 ± 2.0%, and drug loading of 11 ± 0.3%. The in situ gelling formulation of nanoparticles showed a solution to the gel transition temperature of 32°C. The %DTE values for aqueous suspension of nanoparticles and in situ gelling formulation for nanoparticles were 988.5 and 1177.3 and the %DTP values were 86.06 and 91.5 respectively.Multiple sclerosis is a chronic inflammatory and neurodegenerative disease of the central nervous system. The current treatment of Multiple sclerosis is based on anti-inflammatory disease-modifying treatments, which can not regenerate myelin and eventually neurons. So, we need new approaches for axonal protection and remyelination. Amniotic epithelial stem cells amniotic epithelial cells, as a neuroprotective and neurogenic agent, are a proper source in tissue engineering and regenerative medicine. Due to differentiation capability and secretion of growth factors, AECs can be a candidate for the treatment of MS. MK-2206 cell line Moreover, sphingosine-1-phosphate (S1P) receptor modulators were recently approved by FDA for MS. Ponesimod is an S1P receptor-1 modulator that acts selectively as an anti-inflammatory agent and provides a suitable microenvironment for the function of the other neuroprotective agents. In this study, due to the characteristics of AECs, they are considered a treatment option in MS. The conditioned medium of AECs concurrently with ponesimod was used to evaluate the viability of the oligodendrocyte cell line after induction of cell death by cuprizone. Cell viability after treatment by conditioned medium and ponesimod was increased compared to untreated groups. Also, the results showed that combination therapy with CM and ponesimod had a synergistic anti-apoptotic effect on oligodendrocyte cells. The combination treatment with CM and ponesimod reduced the expression of caspase-3, caspase-8, Bax, and Annexin V proteins and increased the relative BCL-2/Bax ratio, indicating inhibition of apoptosis as a possible mechanism of action. Based on these promising results, combination therapy with amniotic stem cells and ponesimode could be a proper alternative for multiple sclerosis treatment.Following brain injury or in neurodegenerative diseases, astrocytes become reactive and may suffer pathological remodeling, features of which are the loss of their homeostatic functions and a pro-inflammatory gain of function that facilitates neurodegeneration. Pharmacological intervention to modulate this astroglial response and neuroinflammation is an interesting new therapeutic research strategy, but it still requires a deeper understanding of the underlying cellular and molecular mechanisms of the phenomenon. Based on the known microglial-astroglial interaction, the prominent role of the nuclear factor kappa B (NF-κB) pathway in mediating astroglial pathological pro-inflammatory gain of function, and its ability to recruit chromatin-remodeling enzymes, we first explored the microglial role in the initiation of astroglial pro-inflammatory conversion and then monitored the progression of epigenetic changes in the astrocytic chromatin. Different configurations of primary glial culture were used to modulate mroglia-derived cues. These results open a new avenue in the study of potential pharmacological interventions that modify the initiation and stabilization of astroglial pathological remodeling, which would be useful in acute and chronic CNS injury. Epigenetic changes represent a plausible pharmacological target to interfere with the stabilization of the pathological astroglial phenotype.