Photochemical stability of lipoic acid and its impact on skin ageing

It is well known that α-lipoic acid (LA) functions as an essential co-factor of the mitochondrial multi-enzyme complex and thus plays an important role in energy metabolism. Currently, it is attracting attention as a nutritional supplement because of its unique antioxidant properties and broad spectra of cellular functions. Skin protection from photodamage and ageing is one of the functional applications of LA. Medical and cosmetic application has been widely realized in the world. However, LA has a unique structure bearing a distorted five membered 1, 2-dithiolane ring, making it quite vulnerable to UV radiation. The present article briefly reviews skin ageing from the viewpoint of oxidative stress and sun exposure and analyses the photochemical properties of LA. It also discusses the effect of LA to cellular signalling and its adequate applications to treat skin ageing caused by oxidation. Data presented in this review suggest that LA is a powerful anti-ageing agent under the appropriate usage.     

Hyper-adhesion: A Unique Property of Desmosomes

Abstract

Hyper-adhesion is a unique, strongly adhesive form of desmosomal adhesion that functions to maintain tissue integrity. In this short review, we define hyper-adhesion, summarise the evidence for it in culture and in vivo, discuss its role in development, wound healing, and skin disease, and speculate about its molecular and cellular basis.     

丝素蛋白材料在皮肤创伤愈合中的研究进展

摘要：丝素蛋白是一种天然的高分子纤维蛋白,其结构的特殊性决定了较好的机械性能,再因其优良的生物相容性、降解产物无毒等特点,被广泛用于各种材料的研究。通过各种化学修饰和负载生长因子等,使丝素蛋白在体内外具有促进成纤维细胞增殖分化的作用,拥有诱导创面愈合的功能,同时其可部分降解,具有缓释性能好,柔韧性强,透气以及透水等较好的理化性质不但在皮肤组织工程学中的广泛的应用,并且在敷料领域的研究也显示了其治疗烧烫伤、创伤达到抑制疤痕、促进伤口快速愈合的治疗效果。总之,通过改良丝素蛋白材料的加工方法,通过化学修饰、其他物质复合等手段得到适合于皮肤修复的具有优良性能的各种材料,是具有很大潜力的极具临床价值的皮肤修复材料。本文旨在综述国内及国外学者的各种关于丝素蛋白生物材料治疗皮肤损伤的研究最新进展。     

Adiponectin receptor agonist AdipoRon blocks skin inflamm‐ageing by regulating mitochondrial dynamics

IntroductionSkin is susceptible to senescence‐associated secretory phenotype (SASP) and inflamm‐ageing partly owing to the degeneration of mitochondria. AdipoRon (AR) has protective effects on mitochondria in metabolic diseases such as diabetes. We explored the role of AR on mitochondria damage induced by skin inflamm‐ageing and its underlying mechanism.MethodsWestern blot, immunofluorescence and TUNEL staining were used to detect inflammatory factors and apoptosis during skin ageing. Transmission electron microscopy, ATP determination kit, CellLight Mitochondria GFP (Mito‐GFP), mitochondrial stress test, MitoSOX and JC‐1 staining were used to detect mitochondrial changes. Western blot was applied to explore the underlying mechanism. Flow cytometry, scratch test, Sulforhodamine B assay and wound healing test were used to detect the effects of AR on cell apoptosis, migration and proliferation.ResultsAR attenuated inflammatory factors and apoptosis that increased in aged skin, and improved mitochondrial morphology and function. This process at least partly depended on the suppression of dynamin‐related protein 1 (Drp1)‐mediated excessive mitochondrial division. More specifically, AR up‐regulated the phosphorylation of Drp1 at Serine 637 by activating AMP‐activated protein kinase (AMPK), thereby inhibiting the mitochondrial translocation of Drp1. Moreover, AR reduced mitochondrial fragmentation and the production of superoxide, preserved the membrane potential and permeability of mitochondria and accelerated wound healing in aged skin.ConclusionAR rescues the mitochondria in aged skin by suppressing its excessive division mediated by Drp1.     

Is alpha-lipoic acid a scavenger of reactive oxygen species in vivo? Evidence for its initiation of stress signaling pathways that promote endogenous antioxidant capacity

The chemical reduction and oxidation (redox) properties of alpha-lipoic acid (LA) suggest that it may have potent antioxidant potential. A significant number of studies now show that LA and its reduced form, dihydrolipoic acid (DHLA), directly scavenge reactive oxygen species (ROS) and reactive nitrogen species (RNS) species and protect cells against a host of insults where oxidative stress is part of the underlying etiology. However, owing to its limited and transient accumulation in tissues following oral intake, the efficacy of nonprotein-bound LA to function as a physiological antioxidant has been questioned. Herein, we review the evidence that the micronutrient functions of LA may be more as an effector of important cellular stress response pathways that ultimately influence endogenous cellular antioxidant levels and reduce proinflammatory mechanisms. This would promote a sustained improvement in cellular resistance to pathologies where oxidative stress is involved, which would not be forthcoming if LA solely acted as a transient ROS scavenger.     

Guest Editorial

Abstract

It is time that we consider applications of the properties of lipid molecules for other than building grocery bags for carrying therapeutic drugs from the pharmacy to sick cells. Lipids have other functions in the cell besides being components of bilayer-based membranes that separate cellular components. Aside from their role as barriers to diffusion, membranes serve to organize a good deal of cellular chemistry. They also provide lipid molecules that serve to regulate key elements of this chemistry. A great deal of lipid research now focuses on issues related to drug delivery via liposomes. Much of this is published in The Journal of Liposome Research. Is it not time that we “greasers” and this journal point towards lipids as the drugs as well as the drug carriers? The purpose of this brief comment is to review the role of lipids (especially PS) as regulators of cellular chemistry, with special emphasis being placed on the role of PS in regulating blood coagulation.     

Fibroblast subpopulations: a developmental approach of skin physiology and ageing

Skin is an organ whose function is far beyond a physical barrier between the inside and the outside of the body. Skin as the whole organism is subjected to ageing which concerns skin mostly in its dermal and deepest component which is also its matricial component. The dermis is a tissue rich in matricial elements and poor in cellular content and it is generally admitted that modifications occurring in the matrix are those which mostly contribute to skin ageing, by altering its biomechanical properties. Therefore it is common to address questions related to skin ageing by considering alterations in matrix molecules like collagen. Actually the dermis is a complex tissue both matricial and cellular and is divided between a superficial dermis close to epidermis and a deep dermis much thicker and histologically different. Several years ago we have undertaken investigations related to fibroblasts which are the cells responsible for the formation and maintenance of the dermis, aiming at isolation, culture and characterization of the fibroblasts from the superficial dermis also called papillary dermis and fibroblasts from the deep dermis also called reticular dermis. We were able to show that these fibroblasts in classical culture on plastic exhibit very different morphologies associated with different secretion properties and we have confirmed and expanded such observations revealing different phenotypes by incorporating these cells in reconstructed skin which allows the reproduction of a three-dimensional architecture recalling skin in vivo especially after grafting onto the nude mouse. We also raise the question of how these two dermal regions appear during the formation of the dermis and the question of their fate during ageing. Progress in solving these questions would certainly appear to be very useful for a better understanding of skin physiology and ageing and would hopefully provide new strategies in anti-ageing research.     

微流控芯片在心肌细胞功能研究中的应用

心肌细胞是心脏结构和功能的基本单位,约占心脏细胞总数的三分之一,是心脏发育、生理病理研究的重点对象,然而传统的在体和体外研究技术存在诸多困难,无法实现细胞微环境的有效控制和生理功能的实时动态监测,制约着心肌细胞功能研究的快速发展。近年来迅速发展的微加工技术,尤其是微流控芯片技术为心肌细胞功能研究提供了便利。微流控芯片技术具有微米尺度的细胞及其微环境的时空控制功能,有效提高了体外细胞研究的组织相关性,是心肌细胞生理功能和力学特性研究的重要工具,如实时监测单个心肌细胞的代谢活性、表征细胞的电生理特性和力学特性、研究细胞微环境和力学微环境对心肌细胞形态和功能的影响。本文从前述几个方面对微流控芯片在心肌细胞生理功能研究中的应用进行综述和对其应用前景进行了展望。     

细菌纤维素在生物医学材料中应用的研究进展

细菌纤维素是一种天然的生物高聚物,具有生物活性、生物可降解性、生物适应性,具有独特的物理、化学和机械性能,例如高的结晶度、高的持水性、超细纳米纤维网络、高抗张强度和弹性模量等,因而成为近来国际上新型生物医学材料的研究热点。本文概括了细菌纤维素的性质、研究历史以及在生物医学材料上的应用,重点阐述了细菌纤维素在组织工程支架、人工血管、人工皮肤和治疗皮肤损伤方面的应用以及当前研究现状。     

An enriched polyphenolic extract obtained from the by-product of Rosa damascena hydrodistillation activates antioxidant and proteostatic modules

BackgroundProlonged maintenance of proteome stability and functionality (proteostasis) is of emerging significance in aging retardation and healthspan.PurposeAn enriched polyphenolic extract obtained from the hydrodistillation of rose petals was tested for its capacity to activate the proteostasis network modules, and thus modulate health- and/or lifespan at the cellular and whole organism level.MethodsThe aqueous extract that remained after the hydrodistillation of Rosa damascena petals, was processed with a polystyrene-FPX66 adsorption resin and sequentially fractionated by FCPC. NMR and UHPLC-HRMS analyses revealed the presence of 28 metabolites, mainly glycosides of kaempferol and quercetin.ResultsThe extract showed high in vitro antioxidant activity and was not toxic in normal human skin fibroblasts, while it promoted the upregulation of NRF2-induced antioxidant genes and main proteostatic modules. Consistently, supplementation of this extract in Drosophila flies’ culture medium induced a cncC/NRF2-mediated upregulation of antioxidant and proteostatic modules. Prolonged administration of the extract in flies’ culture medium was not toxic and did not affect food intake rate or fecundity; also, it delayed the age-related decline of stress tolerance and locomotion performance (neuromuscular functionality) and dose-dependently extended flies’ lifespan.ConclusionOur findings indicate that the enriched polyphenolic extract obtained from the residue of R. damascena hydrodistillation activates cytoprotective cellular modules that, likely, contribute to its potential anti-aging properties.     

Discoidin domain receptors: Microenvironment sensors that promote cellular migration and invasion

ABSTRACT

Extracellular matrix (ECM) provides cells scaffolding for cell migration and microenvironment for various cellular functions. Collagens are major ECM components in tissue and discoidin domain receptors (DDRs) are receptor tyrosine kinases (RTK) that recognise fibrillar collagens. Unlike other RTK, their ligands are solid ECM the that are abundantly present in the pericellular environment in various tissue, and thus its activation and regulations are unique amongst RTK family. It is emerging that DDRs may be the sensors that monitor and detects changes in ECM microenvironment and determines the cellular fates upon tissue injuries. In this mini-review, recent findings on the role of DDRs as microenvironment sensor and their roles in cell migration and invasion are discussed.     

NAD+ metabolism and oxidative stress: the golden nucleotide on a crown of thorns

Abstract

In the twentieth century, NAD⁺ research generated multiple discoveries. Identification of the important role of NAD⁺ as a cofactor in cellular respiration and energy production was followed by discoveries of numerous NAD⁺ biosynthesis pathways. In recent years, NAD⁺ has been shown to play a unique role in DNA repair and protein deacetylation. As discussed in this review, there are close interactions between oxidative stress and immune activation, energy metabolism, and cell viability in neurodegenerative disorders and ageing. Profound interactions with regard to oxidative stress and NAD⁺ have been highlighted in the present work. This review emphasizes the pivotal role of NAD⁺ in the regulation of DNA repair, stress resistance, and cell death, suggesting that NAD⁺ synthesis through the kynurenine pathway and/or salvage pathway is an attractive target for therapeutic intervention in age-associated degenerative disorders. NAD⁺ precursors have been shown to slow down ageing and extend lifespan in yeasts, and protect severed axons from degeneration in animal models neurodegenerative diseases.     

ATAD3, a vital membrane bound mitochondrial ATPase involved in tumor progression

ATAD3 (ATPase family AAA Domain-containing protein 3) is a mitochondrial membrane bound ATPase whose function has not yet been discovered but its role is essential for embryonic development. The ATAD3 gene has existed since the pluri-cellular organisms with specialized tissues and has remained unique until vertebrates. In primates and human, two other genes have appeared (called ATAD3B and ATAD3C versus ATAD3A the ancestral gene). ATAD3 knock-down in different non-transformed cell lines is associated with drastic changes in the mitochondrial network, inhibition of proliferation and modification of the functional interactions between mitochondria and endoplasmic reticulum. However, the analysis of the cellular properties of ATAD3A and ATAD3B in different human cancer cell lines shows on the contrary that they can present anti-proliferative and chemoresistant properties. ATAD3 may therefore be implicated in an unknown but essential and growth-linked mitochondrial function existing since pluri-cellular organization and involved in tumorigenesis.     

Cyclin-dependent kinase inhibitor p21<Superscript>Waf1</Superscript>: Contemporary view on its role in senescence and oncogenesis

p21^Waf1 was identified as a protein suppressing cyclin E/A-CDK2 activity and was originally considered as a negative regulator of the cell cycle and a tumor suppressor. It is now considered that p21^Waf1 has alternative functions, and the view of its role in cellular processes has begun to change. At present, p21^Waf1 is known to be involved in regulation of fundamental cellular programs: cell proliferation, differentiation, migration, senescence, and apoptosis. In fact, it not only exhibits antioncogenic, but also oncogenic properties. This review provides a contemporary understanding of the functions of p21^Waf1 depending on its intracellular localization. On one hand, when in the nucleus, it serves as a negative cell cycle regulator and tumor suppressor, in particular by participating in the launch of a senescence program. On the other hand, when p21^Waf1 is localized in the cytoplasm, it acts as an oncogene by regulating migration, apoptosis, and proliferation.     

Microbial β-Glucosidases: Cloning,Properties, and Applications

ABSTRACT:?

β-Glucosidases constitute a major group among glycosylhydrolase enzymes. Out of the 82 families classified under glycosylhydrolase category, these belong to family 1 and family 3 and catalyze the selective cleavage of glucosidic bonds. This function is pivotal in many crucial biological pathways, such as degradation of structural and storage polysaccharides, cellular signaling, oncogenesis, host-pathogen interactions, as well as in a number of biotechnological applications. In recent years, interest in these enzymes has gained momentum owing to their biosynthetic abilities. The enzymes exhibit utility in syntheses of diverse oligosaccharides, glycoconjugates, alkyl- and amino-glucosides. Attempts are being made to understand the structure-function relationship of these versatile biocatalysts. Earlier reviews described the sources and properties of microbial β-glucosidases, yeast β-glucosidases, thermostable fungal β-glucosidase, and the physiological functions, characteristics, and catalytic action of native β-glucosidases from various plant, animal, and microbial sources. Recent efforts have been directed towards molecular cloning, sequencing, mutagenesis, and crystallography of the enzymes. The aim of the present article is to describe the sources and properties of recombinant β-glucosidases, their classification schemes based on similarity at the structural and molecular levels, elucidation of structure-function relationships, directed evolution of existing enzymes toward enhanced thermostability, substrate range, biosynthetic properties, and applications.     

Signaling pathways of prohibitin and its role in diseases

Abstract

Prohibitin (PHB), appearing to be a negative regulator of cell proliferation and to be a tumor suppressor, has been connected to diverse cellular functions including cell cycle control, senescence, apoptosis and the regulation of mitochondrial activities. It is a growth regulatory gene that has pleiotropic functions in the nucleus, mitochondria and cytoplasmic compartments. However, in different tissues/cells, the expression of PHB was different, such as that it was increased in most of the cancers, but its expression was reduced in kidney diseases. Signaling pathways might be very important in the pathogenesis of diseases. This review was performed to provide a relatively complete signaling pathways flowchart for PHB to the investigators who were interested in the roles of PHB in the pathogenesis of diseases. Here, we review the signal transduction pathways of PHB and its role in the pathogenesis of diseases.     

In situ structural biology using in-cell NMR

BackgroundAccumulating evidence from the experimental and computational studies indicated that the functional properties of proteins are different between in vitro and living cells, raising the necessity to examine the protein structure under the native intracellular milieu. To gain structural information of the proteins inside the living cells at an atomic resolution, in-cell NMR method has been developed for the past two decades.Scope of reviewIn this review, we will overview the recent progress in the methodological developments and the biological applications of in-cell NMR, and discuss the advances and challenges in this filed.Major conclusionsA number of methods were developed to enrich the isotope-labeled proteins inside the cells, enabling the in-cell NMR observation of bacterial cells as well as eukaryotic cells. In-cell NMR has been applied to various biological systems, including de novo structure determinations, protein/protein or protein/drug interactions, and monitoring of chemical reactions exerted by the endogenous enzymes. The bioreactor system, in which the cells in the NMR tube are perfused by fresh culture medium, enabled the long-term in-cell NMR measurements, and the real-time observations of intracellular responses upon external stimuli.General significanceIn-cell NMR has become a unique technology for its ability to obtain the function-related structural information of the target proteins under the physiological or pathological cellular environments, which cannot be reconstituted in vitro.     

The in vitro effects of cigarette smoke on fatty acid metabolism are partially counteracted by simvastatin

BackgroundStatins enhance the synthesis of long-chain polyunsaturated fatty acids (LC-PUFAs) from their precursors both in vitro and in vivo. In particular, an increased conversion of linoleic acid (LA) and of alpha-linolenic acid to their derivatives is observed in cultured cells. On the contrary, cigarette smoke (CS) negatively and dose-dependently affects the LC-PUFA production.AimTo evaluate the effects of CS alone or with simvastatin, on [1-¹⁴C] LA metabolism in THP-1 cells.ResultsCS inhibits LA conversion; after co-incubation, simvastatin nullifies the effects of CS, maintaining LA conversion comparable to controls. However, at the highest CS concentration, simvastatin is unable to counteract the effects of CS. Changes of LA conversion reflect the modulation of desaturase activities by simvastatin and CS.ConclusionCS decreases PUFA conversion and its effects are modulated by the opposite effect of statins. It can be speculated that statin treatments in smoking patients may provide some beneficial effects on PUFA metabolism in addition to lowering cholesterol levels.     

Nanodiamonds for bioapplications–specific targeting strategies

BackgroundNanodiamonds (NDs) provide a unique multitasking system for drug delivery and fluorescent imaging in biological environments. Owing to their quantum properties, NDs are expected to be employed as multifunctional probes in the future for the accurate visualization of biophysical parameters such as temperature and magnetic fields. However, the use of NDs for the selective targeting of the biomolecules of interest within a complicated biological system remains a challenge. One of the most promising solutions is the appropriate surface design of NDs based on organic chemistry and biochemistry. The engineered NDs have high biocompatibility and dispersibility in a biological environment and hence undergo cellular uptake through specific pathways.Scope of reviewThis review focuses on the selective targeting of NDs for biomedical and biophysical applications from the viewpoint of ND surface functionalizations and modifications. These pretreatments make possible the specific targeting of biomolecules of interest on or in a cell by NDs via a designed biochemical route.Major conclusionsThe surface of NDs is covalently or noncovalently modified with silica, polymers, or biomolecules to reshape them, control their size, and enhance the colloidal stability and biomolecular selectivity toward the biomolecules of interest. Electroporation, chemical treatment, injection, or endocytosis are the methods generally adopted to introduce NDs into living cells. The pathway, efficiency, and the cell viability depend on the selected method.General significanceIn the biomedical field, the surface modification facilitates specific delivery of a drug, leading to a higher therapeutic efficacy. In biophysical applications, the surface modification paves the way for the accurate measurement of physical parameters to gain a better understanding of various cell functions.     

Rapid culture of human keratinocytes in an autologous,feeder-free system with a novel growth medium

Background aimsThe ability to culture human keratinocytes is beneficial in the treatment of skin injury and disease, as well as for testing chemicals in vitro as a substitute for animal testing.ResultsWe have identified a novel culture medium for the rapid growth of keratinocytes from human skin. “Kelch's medium” supports keratinocyte growth that is as rapid as in the classical Rheinwald and Green method, but without the need for cholera toxin or xenogeneic feeder cells. It enables keratinocytes to out-compete co-cultured autologous fibroblasts so that separation of the epidermis from the dermis is no longer required before keratinocyte culture. Enzymatic digests of whole human skin can therefore be used to generate parallel cultures of autologous keratinocytes, fibroblasts and melanocytes simply by using different cell culture media.ConclusionsThis new keratinocyte medium and the simplified manufacturing procedures it enables are likely to be beneficial in skin engineering, especially for clinical applications.