Oxidative stress plays an important role in the development of aging-related diseases by accelerating the lipid peroxidation of polyunsaturated fatty acids in the cell membrane, resulting in the production of aldehydes, such as malondialdehyde and 4-hydroxy-2-nonenal (4-HNE) and other toxic substances. The compound 4-HNE forms adducts with DNA or proteins, disrupting many cell signaling pathways including the regulation of apoptosis signal transduction pathways. The binding of proteins to 4-HNE (4-HNE-protein) acts as an important marker of lipid peroxidation, and its increasing concentration in brain tissues and fluids because of aging, ultimately gives rise to some hallmark disorders, such as neurodegenerative diseases (Alzheimer’s and Parkinson’s diseases), ophthalmic diseases (dry eye, macular degeneration), hearing loss, and cancer. This review aims to describe the physiological origin of 4-HNE, elucidate its toxicity in aging-related diseases, and discuss the detoxifying effect of aldehyde dehydrogenase and glutathione in 4-HNE-driven aging-related diseases.

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BackgroundType VI collagen is supposed to be a regulation factor in adipogenesis. This study aimed to assess the promoting effect of vitamin C (VC) on adipogenic differentiation of preadipocytes as well as its mechanism.MethodsFive sets of different combinations of chemicals were used to inhibit synthesis of type I to VI collagens, blocking ERK1/2 phosphorylation during adipogenesis of 3T3-L1 preadipocytes. Furthermore, to explore whether collagen VI plays a critical role during adipogenesis, specific knockdown of collagen VI was performed by using RNA interference. The morphology and expression patterns of several target factors involved in adipogenesis were assessed at various time points.ResultsA reduction in ERK1/2 phosphorylation and an increase in collagen VI and adipogenic-specific factors, such as C/EBPβ, PPARγ and C/EBPα, were observed after treating adipogenic 3T3-L1 cells with AA2P, a stable derivative of VC. Inhibition of collagen synthesis by ethyl-3, 4-dihydroxybenzoate (EDHB) or by specific knockdown of collagen VI by RNAi could promote ERK1/2 phosphorylation. The ERK1/2 phosphorylation in both cases could be attenuated by AA2P treatment. In addition, the inhibition of ERK1/2 phosphorylation by U0126, a highly selective inhibitor of both MEK1 and MEK2 and a type of MAPK/ERK kinase, up-regulated the expression of collagen VI, while it down-regulated the adipogenic-specific factors.ConclusionAA2P could up-regulate the expression of collagen VI by attenuating ERK1/2 phosphorylation, further up-regulating adipocyte-specific factors, thus finally promoting the adipogenesis of 3T3-L1 preadipocytes.Electronic supplementary materialThe online version of this article (10.1186/s12986-017-0234-y) contains supplementary material, which is available to authorized users.

Neuroinflammatory response is the immune response mechanism of the innate immune system of the central nervous system. Both primary and secondary injury can activate neuroinflammatory response. Among them, the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome plays a key role in the inflammatory response of the central system. Inflammasome is a type of pattern recognition receptor, a cytoplasmic polyprotein complex composed of members of the Nod-like receptor (NLR) family and members of the pyrin and HIN domain (PYHIN) family, which can be affected by a variety of pathogen-related molecular patterns or damage-related molecular patterns are activated. As one of the research hotspots in the field of medical research in recent years, there are increasing researches on immune function abnormalities in the onset of neurological diseases such as depression, AD, ischemic brain injury and cerebral infarction, the NLRP3 inflammasome causes the activated caspase-1 to cleave pre-interleukin-1β and pre-interleukin-18 into mature interleukin-1β and interleukin-18, in turn, a large number of inflammatory factors are produced, which participate in the occurrence and development of the above-mentioned diseases. Targeted inhibition of the activation of inflammasomes can reduce the inflammatory response, promote the survival of nerve cells, and achieve neuroprotective effects. This article reviews NLRP3 inflammasome’s role in neurological diseases and related regulatory mechanisms, which providing references for future research in this field.

Stroke is a leading cause of death and disability world-widely. The incidence rate of stroke has been increasing due to the aging population and lifestyle changes. At present, the only drug approved by the US Food and Drug Administration (FDA) for the treatment of ischemic stroke is tissue plasminogen activator (t-PA), but its clinical application is greatly limited because of its narrow time window and bleeding risk. Natural products have a long history of being used in traditional medicine with good safety, making them an important resource for the development of new drugs. Indeed, some natural products can target a variety of pathophysiological processes related to stroke, including oxidative stress, in lammation and neuronal apoptosis. Therefore, the development of high-e ficiency, lowtoxicity, safe and cheap active substances from natural products is of great significance for improving the treatment alternatives of patients with stroke. This article reviews the neuroprotective e fects of 33 natural compounds by searching recent related literature. Among them, puerarin, pinocembrin, quercetin, epigallocatechin-3-gallate (EGCG), and resveratrol have great potential in the clinical treatment of ischemic stroke. This review will provide a powerful reference for screening natural compounds with potential clinical application value in ischemic stroke or synthesizing new neuroprotective agents with natural compounds as lead compounds.