Basshermansen8454

In diabetic wounds, disruption of various biological mechanisms leads to dysfunction of keratinocytes including impaired migration, adhesion, and proliferation. The function of abnormal keratinocytes can lead to poor diabetic wound healing. Taken together, clarification of molecular and functional disturbances of keratinocyte cells and applying them in diabetic wounds can contribute to enhanced treatment of diabetic wounds. Based on the location of keratinocytes in the epidermis and the central role of keratinocytes in the diabetic wound healing process, applying keratinocytes has great potential for the treatment of diabetic burn wounds.Aging and hypertension are major risk factors for cerebral small vessel disease (CSVD). Anti-hypertensive therapy has achieved effective; however, incomplete results in treating CSVD, suggesting the need for additional treatments. Targeting abnormal inflammatory responses has become a topic of research interest. Small artery remodeling is the main pathological feature of CSVD. Inhibition of the E-prostanoid 3 (EP3) receptor has been shown to attenuate vascular remodeling in peripheral organs; however, little is known about its role in CSVD. Therefore, we investigated whether the deletion of EP3 attenuates the development of CSVD in an animal model-- stroke-prone renovascular hypertensive rat (RHRsp). We found that the cerebral small arteries of RHRsp exhibited increased EP3 expression. Despite no alleviation of hypertension, the deletion of EP3 still attenuated the cerebral small artery remodeling of RHRsp, as evidenced by reduced overexpression of extracellular matrix (ECM) in the vessel. In vitro experiments indicated that EP3 deletion regulated the expression of ECM by downregulating TGF-β1/Smad signaling. Furthermore, the Morris water maze test and magnetic resonance test demonstrated that EP3 knockout attenuated cognitive impairment of the RHRsp, possibly through increased cerebral blood flow. Together, our results indicate that the deletion of EP3 attenuates vascular remodeling and vascular cognitive impairment induced by hypertension, and blockade of the EP3 receptor may be a promising strategy for the treatment of CSVD.Accelerated senescence is triggered by key mediators of arrhythmogenic substrates and contributes to atrial fibrillation (AF). We sought to understand senescence in AF and the extent to which it aggravates the AF process. Twenty-six AF patients undergoing open-heart surgery were included, and 12 patients with sinus rhythm served as controls. Another cohort included 120 consecutive persistent AF patients with valvular heart diseases. HL-1 atrial myocytes were tachypaced (TP) to simulate experimental AF. Compared with sinus rhythm, left atrial appendages (LAAs) with AF presented a significantly increased positive area of cellular senescence, with upregulated expression of p16, p21 and p53. Next, p21 mRNA was increased in patients with AF recurrence compared with that in patients without recurrence. In multivariate analysis, p21 (OR 2.97; 95% CI 1.65-5.34; P less then 0.001) was a significant independent predictor of AF early recurrence. Interestingly, TP induced HL-1 atrial myocyte senescence in vitro, accompanied by a marked increase in the senescence-associated secretory phenotype (SASP) and altered the expression of sarcoplasmic reticulum (SR)-related proteins. Suppression of p21 by siRNA reduced TP induced cell senescence and IL-1β, IL-6 elevation, and partly changed SR-related proteins expression. Moreover, we show that the level of γH2AX, a marker of DNA damage, was higher in AF patients than in sinus rhythm controls. Similarly, an increase in γH2AX levels was observed following TP. selleckchem AF underlies cardiomyocyte senescence and contributes to deleterious atrial remodeling during disease progression. This finding may help facilitate the search for new therapeutic approaches for antiaging therapy for AF.The clinical relevance of IL-1β in chronic inflammation underlying atherosclerosis has been reinforced by recent evidence associating pharmacological inhibition of the cytokine with lower cardiovascular risk. Previously, we have demonstrated a direct involvement of IL-1β in endothelial senescence. Therefore, this can be a key mechanism contributing to the sterile inflammatory milieu associated with aging, termed inflammaging. In the present study, we have evaluated whether a positive feedback of IL-1β in the NLRP3 inflammasome via NF-κB could promote human endothelial senescence in vitro and murine endothelial dysfunction in vivo. Our results indicate that the NLRP3 inflammasome is pivotal in mediating the detrimental effects of IL-1β, showing that auto-activation is a crucial feature boosting endothelial cell senescence in vitro, which is paralleled by vascular dysfunction in vivo. Hence, the inhibitor of NLRP3 inflammasome assembly, MCC 950, was able to disrupt the aforementioned positive loop, thus alleviating inflammation, cell senescence and vascular dysfunction. Besides, we explored alternative NLRP3 inflammasome inhibitory agents such as the RAS heptapeptide Ang-(1-7) and the anti-aging protein klotho, both of which demonstrated protective effects in vitro and in vivo. Altogether, our results highlight a fundamental role for the hereby described NLRP3 inflammasome/IL-1β positive feedback loop in stress-induced inflammaging and the associated vascular dysfunction, additionally providing evidence of a potential therapeutic use of MCC 950, Ang-(1-7) and recombinant klotho to block this loop and its deleterious effects.Diabetes impacts on brain metabolism, structure, and function. Alterations in brain metabolism have been observed in obesity and diabetes models induced by exposure to diets rich in saturated fat and/or sugar and have been linked to memory impairment. However, it remains to be determined whether brain dysfunction induced by obesogenic diets results from permanent brain alterations. We tested the hypothesis that an obesogenic diet (high-fat and high-sucrose diet; HFHSD) causes reversible changes in hippocampus and cortex metabolism and alterations in behavior. Mice were exposed to HFHSD for 24 weeks or for 16 weeks followed by 8 weeks of diet normalization. Development of the metabolic syndrome, changes in behavior, and brain metabolite profiles by magnetic resonance spectroscopy (MRS) were assessed longitudinally. Control mice were fed an ingredient-matched low-fat and low-sugar diet. Mice fed the HFHSD developed obesity, glucose intolerance and insulin resistance, with a more severe phenotype in male than female mice. Relative to controls, both male and female HFHSD-fed mice showed increased anxiety-like behavior, impaired memory in object recognition tasks, but preserved working spatial memory as evaluated by spontaneous alternation in a Y-maze. Alterations in the metabolite profiles were observed both in the hippocampus and cortex but were more distinct in the hippocampus. HFHSD-induced metabolic changes included altered levels of lactate, glutamate, GABA, glutathione, taurine, N-acetylaspartate, total creatine and total choline. Notably, HFHSD-induced metabolic syndrome, anxiety, memory impairment, and brain metabolic alterations recovered upon diet normalization for 8 weeks. In conclusion, cortical and hippocampal derangements induced by long-term HFHSD consumption are reversible rather than being the result of permanent tissue damage.Blood vessels are one of the most essential organs, which nourish all tissues in our body. Once there are intravascular plaques or vascular occlusion, other organs and circulatory systems will not work properly. Therefore, it is necessary to detect abnormal blood vessels by intravascular imaging technologies for subsequent vascular treatment. The emergence of lasers and fiber optics promotes the development of intravascular imaging and treatment. Laser imaging techniques can obtain deep vascular images owing to light scattering and absorption properties. Moreover, photothermal and photomechanical effects of laser make it possible to treat vascular diseases accurately. In this review, we present the research progress and applications of laser techniques in intravascular imaging and treatment. Firstly, we introduce intravascular optical coherent tomography and intravascular photoacoustic imaging, which can obtain various information of plaques. Multimodal intravascular imaging techniques provide more information about intravascular plaques, which have an essential influence on intravascular imaging. Secondly, two laser techniques including laser angioplasty and endovenous laser ablation are discussed for the treatment of arterial and venous diseases, respectively. Finally, the outlook of laser techniques in blood vessels, as well as the integration of laser imaging and treatment are prospected in the section of discussions.Ceramide is a core molecule of sphingolipid metabolism that causes selective insulin resistance and dyslipidemia. Research on its involvement in cardiovascular diseases has grown rapidly. In resting cells, ceramide levels are extremely low, while they rapidly accumulate upon encountering external stimuli. Recently, the regulation of ceramide levels under pathological conditions, including myocardial infarction, hypertension, and atherosclerosis, has drawn great attention. Increased ceramide levels are strongly associated with adverse cardiovascular risks and events while inhibiting the synthesis of ceramide or accelerating its degradation improves a variety of cardiovascular diseases. In this article, we summarize the role of ceramide in cardiovascular disease, investigate the possible application of ceramide as a new diagnostic biomarker and a therapeutic target for cardiovascular disorders, and highlight the remaining problems.Epilepsy is a serious neurological disorder characterized by abnormal, recurrent, and synchronous discharges in the brain. Long-term recurrent seizure attacks can cause serious damage to brain function, which is usually observed in patients with temporal lobe epilepsy. Controlling seizure attacks is vital for the treatment and prognosis of epilepsy. Animal models, such as the kindling model, which was the most widely used model in the past, allow the understanding of the potential epileptogenic mechanisms and selection of antiepileptic drugs. In recent years, various animal models of epilepsy have been established to mimic different seizure types, without clear merits and demerits. Accordingly, this review provides a summary of the views mentioned above, aiming to provide a reference for animal model selection.Owing to the global exponential increase in population ageing, there is an urgent unmet need to develop reliable strategies to slow down and delay the ageing process. Age-related neurodegenerative diseases are among the main causes of morbidity and mortality in our contemporary society and represent a major socio-economic burden. There are several controversial factors that are thought to play a causal role in brain ageing which are continuously being examined in experimental models. Among them are oxidative stress and brain inflammation which are empirical to brain ageing. Although some candidate drugs have been developed which reduce the ageing phenotype, their clinical translation is limited. There are several strategies currently in development to improve brain ageing. These include strategies such as caloric restriction, ketogenic diet, promotion of cellular nicotinamide adenine dinucleotide (NAD+) levels, removal of senescent cells, 'young blood' transfusions, enhancement of adult neurogenesis, stem cell therapy, vascular risk reduction, and non-pharmacological lifestyle strategies.