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    • GDC-0623 synthesis COPD is almost unheard of in individuals

    2023-02-07

    COPD is almost unheard of in individuals less than 40 years of age (even among heavy smokers), 1 in 10 lifetime never-smokers and 1 in 3 develop COPD by age 75 [26], unquestionably, COPD is an age-related disorder. This notion of accelerated ageing of COPD is supported by animal models, which demonstrate premature appearance of emphysematous lungs in mice, which have genetically altered age-related pathways (eg, Klotho mice) [27]. Unlike apoptotic cells, senescent GDC-0623 synthesis remain metabolically active and display a senescence-associated secretory phenotype characterised by the production of proinflammatory cytokines [28]. GDF is one very interesting age-related protein that may modulate senescence. GDF11 as a member of the TGFβ superfamily of cytokines, could be secreted by a diseased lung and acts on skeletal muscle and induces the activation of ubiquitin-proteasome system, leading to protein degradation [29,30]. GDF11 was localized in mesenchymal cells within the airway walls and airway epithelial cells [31], because of this, we recruited the mesenchymal cells for our study. And in the present study, we found that both the protein level of GDF11 in plasma and cells from COPD patients were all decreased, when compared with both the NC-smoker group and NC-no-smoker group. And the effect of GDF11 on cell senescent needs to be further explored in our next study. Scholar found that smoking has been identified as the dominant cause for COPD in both men and women [32]. Our study demonstrated that the smoke from lit cigarette could make mice into COPD. Moreover, CSE, the cigarette smoke extract, decreased the expression of CSE at a time and concentration-dependent manner, which was consistent with the previous study, that placement of human lung fibroblasts to CSE decreased GDF11 production, as well as increased expression of p21, p53 and the senescence-associated β-galactosidase (SA-β-gal) [31]. The central role of pulmonary inflammation in the pathogenesis of COPD is well established [33,34]. Previous studies demonstrated that the PI3K/AKT pathway was crucial for macrophage migration [35] and that PI3Kγ−/− mice showed reduced neutrophil and macrophage chemotaxis to inflammatory stimuli [36], indicating that the PI3K pathway played an important role in promoting inflammation, and might be involved in the occurrence of COPD [20,37]. Studies have demonstrated that hyperactivation of the PI3K/AKT signaling pathway is a hallmark of the majority of sporadic human cancers [38,39]. Paradoxically, chronic activation of this pathway in nontransformed cells promotes senescence, which acts as a significant barrier to malignant progression [40,41]. The current study showed that the knockdown of GDF11 could activate AKT signaling. According to this, we speculate that in mesenchymal cells AKT-induced senescence occurs very rapidly without a hyperproliferative phase and without DNA damage, which will be proved in our further study.
    Introduction Sensory and motor signals to and from the brain and spinal cord can be disrupted by peripheral nerve injury, causing a loss of sensations, and even paralysis, in the innervated area of injured nerve [1]. In recent years, many studies have demonstrated the protective effect of herbal extracts on diverse neurological disorders, suggesting as therapeutic and preventative agents. Curcumin is the main active component of turmeric, a yellow compound originally isolated from the plant Curcuma longa L. [2]. Curcumin is associated with anti-inflammatory, anti-oxidant, anti-viral, anti-cancer, and anti-bacterial activities and over 100 clinical studies have been carried out with curcumin [3]. Although therapeutic role of curcumin against Parkinson’s Disease has been well documented [4], therapeutic evaluation of curcumin in other neurological conditions is significantly limited. However, several studies have attempted to elucidate the neuroprotective effect of curcumin in different rat models focusing on various molecular networks. Improved functional recovery was observed along with curcumin treatment after sciatic nerve crush injury in diabetic rats via significant enhancement of axonal regeneration [5]. A comparative analysis of therapeutic effect of propolis, curcumin, and methylprednisolone on crush injuries of the sciatic nerve showed that curcumin and propolis, two traditional drugs, had a positive effect on nerve crush injuries [6]. It was also proved by another study that curcumin has a protective effect on the dorsal root ganglion (DRG) and sciatic nerve in rats after crush [7]. Underlying mechanism of this effect was investigated by another functional experiment which revealed that curcumin could ameliorate the chronic constrictive injury-induced neuropathic pain through inhibiting CX3CR1 expression by the activation of NF-κB p65 in spinal cord and (DRG) [8]. Despite of the great efforts abovementioned literatures have displayed, underlying molecular mechanism in therapeutic effect of curcumin still remains unclear.