Lutein and cataract: from bench to bedside

Cataract is one of the most important leading causes of blindness in the world. Extensive research showed that oxidative stress may play an important role in the initiation and progression of a cataract and other age-related eye diseases. Extra-generation of reactive oxygen and nitrogen species in the eye tissue has been shown as one of the most important risk factors for cataracts and other age-related eye diseases. With respect to this, it can be hypothesized that dietary antioxidants may be useful in the prevention and/or mitigation of cataract. Lutein is an important xanthophyll which is widely found in different vegetables such as spinach, kale and carrots as well as some other foods such as eggs. Lutein is concentrated in the macula and suppresses the oxidative stress in the eye tissues. A plethora of literature has shown that increased lutein consumption has a close correlation with reduction in the incidence of cataract. Despite this general information, there is a negligible number of review articles considering the beneficial effects of lutein on cataracts and age-related eye diseases. The present review is aimed at discussing the role of oxidative stress in the initiation and progression of a cataract and the possible beneficial effects of lutein in maintaining retinal health and fighting cataract. We also provide a perspective on the chemistry, sources, bioavailability and safety of lutein.     

Mesenchymal stem cells: From bench to bedside

Human mesenchymal stem cells (hMSCs) have tremendous promise for use in a variety of clinical applications. The ability of these cells to self-renew and differentiate into multiple tissues makes them an attractive cell source for a new generation of cell-based regenerative therapies. Encouraging results from clinical trials have also generated growing enthusiasm regarding MSC therapy and related treatment, but gaps remain in understanding MSC tissue repair mechanisms and in clinical strategies for efficient cell delivery and consistent therapeutic outcomes. For these reasons, discoveries from basic research and their implementation in clinical trials are essential to advance MSC therapy from the laboratory bench to the patient's bedside.     

Curcumin as a natural regulator of monocyte chemoattractant protein-1

Monocyte chemoattractant/chemotactic protein-1 (MCP-1), a member of the CC chemokine family, is one of the key chemokines that regulate migration and tissue infiltration of monocytes/macrophages. Its role in the pathophysiology of several inflammatory diseases has been widely recognized, thus making MCP-1 a possible target for anti-inflammatory treatments. Curcumin (diferuloylmethane) is a natural polyphenol derived from the rhizomes of Curcuma Longa L. (turmeric). Anti-inflammatory action underlies numerous pharmacological effects of curcumin in the control and prevention of several diseases. The purpose of this review is to evaluate the effects of curcumin on the regulation of MCP-1 as a key mediator of chemotaxis and inflammation, and the biological consequences thereof. In vitro studies have shown that curcumin can decrease MCP-1 production in various cell lines. Animal studies have also revealed that curcumin can attenuate MCP-1 expression and improve a range of inflammatory diseases through multiple molecular targets and mechanisms of action. There is limited data from human clinical trials showing the decreasing effect of curcumin on MCP-1 concentrations and improvement of the course of inflammatory diseases. Most of the in vitro and animal studies confirm that curcumin exert its MCP-1-lowering and anti-inflammatory effects by down-regulating the mitogen-activated protein kinase (MAPK) and NF-κB signaling pathway. As yet, there is limited data from human clinical trials showing the effect of curcumin on MCP-1 levels and improvement of the course of inflammatory diseases. More evidence, especially from human studies, is needed to better assess the effects of curcumin on circulating MCP-1 in different human diseases and the role of this modulatory effect in the putative anti-inflammatory properties of curcumin.     

From bench to bedside: stealth of enteroinvasive pathogens

Bacterial enteric infections are often associated with diarrhoea or vomiting, which are clinical presentations commonly referred to as gastroenteritis. However, some enteric pathogens, including typhoidal Salmonella serotypes, Brucella species and enteropathogenic Yersinia species are associated with a clinical syndrome that is characterized by abdominal pain and/or fever and is distinct from acute gastroenteritis. Recent insights into molecular mechanisms of the host-pathogen interaction show that these enteric pathogens share important characteristics that explain why the initial host responses associated with these agents more closely resemble host responses to viral or parasitic infections. Host responses contribute to the clinical presentation of disease and improved understanding of these responses in the laboratory is beginning to bridge the gap between bench and bedside.     

Disentangling the therapeutic tactics in GBM: From bench to bedside and beyond

Glioblastoma multiforme (GBM) is one of the most common and malignant form of adult brain tumor with a high mortality rate and dismal prognosis. The present standard treatment comprising surgical resection followed by radiation and chemotherapy using temozolomide can broaden patient's survival to some extent. However, the advantages are not palliative due to the development of resistance to the drug and tumor recurrence following the multimodal treatment approaches due to both intra- and intertumoral heterogeneity of GBM. One of the major contributors to temozolomide resistance is O⁶-methylguanine-DNA methyltransferase. Furthermore, deficiency of mismatch repair, base excision repair, and cytoprotective autophagy adds to temozolomide obstruction. Rising proof additionally showed that a small population of cells displaying certain stem cell markers, known as glioma stem cells, adds on to the resistance and tumor progression. Collectively, these findings necessitate the discovery of novel therapeutic avenues for treating glioblastoma. As of late, after understanding the pathophysiology and biology of GBM, some novel therapeutic discoveries, such as drug repurposing, targeted molecules, immunotherapies, antimitotic therapies, and microRNAs, have been developed as new potential treatments for glioblastoma. To help illustrate, “what are the mechanisms of resistance to temozolomide” and “what kind of alternative therapeutics can be suggested” with this fatal disease, a detailed history of these has been discussed in this review article, all with a hope to develop an effective treatment strategy for GBM.     

RNA-based gene therapy for the treatment and prevention of HIV: from bench to bedside

Gene therapy is considered a feasible approach for the treatment and prevention of HIV/AIDS. Targeting both viral genes and host dependency factors can interfere with the viral lifecycle and prevent viral replication. A number of approaches have been taken to target these genes, including ribozymes, aptamers, and RNAi based therapies. A number of these therapies are now beginning to make their way into clinical trials and providing proof of principle that gene therapy is a safe and realistic option for treating HIV. Here, we focus on those therapies that have progressed along the pipeline to preclinical and clinical testing.     

IL-1β in atherosclerotic vascular calcification: From bench to bedside

Atherosclerotic vascular calcification contributes to increased risk of death in patients with cardiovascular diseases. Assessing the type and severity of inflammation is crucial in the treatment of numerous cardiovascular conditions. IL-1β, a potent proinflammatory cytokine, plays diverse roles in the pathogenesis of atherosclerotic vascular calcification. Several large-scale, population cohort trials have shown that the incidence of cardiovascular events is clinically reduced by the administration of anti-IL-1β therapy. Anti-IL-1β therapy might reduce the incidence of cardiovascular events by affecting atherosclerotic vascular calcification, but the mechanism underlying this effect remains unclear. In this review, we summarize current knowledge on the role of IL-1β in atherosclerotic vascular calcification, and describe the latest results reported in clinical trials evaluating anti-IL-1β therapies for the treatment of cardiovascular diseases. This review will aid in improving current understanding of the pathophysiological roles of IL-1β and mechanisms underlying its activity.     

Neural stem cells, adult neurogenesis, and galectin-1: from bench to bedside

Neural stem cells (NSCs) in the adult brain have been a consistent focus of biomedical research largely because of their potential clinical application. To fully exploit this potential, the molecular mechanisms that regulate NSCs must be clarified. Several lines of evidence show that a multifunctional protein, Galectin-1, is expressed and has a functional role in a subset of adult NSCs. Researchers, including our group, have explored the physiological role of Galectin-1 in NSCs and its application in the treatment of animal models of neurological disorders such as brain ischemia and spinal cord injury. Here, we summarize what is currently known regarding the role of Galectin-1 in adult NSCs. Furthermore, we discuss current issues in researching the role of Galectin-1 in adult NSCs under both physiological and pathological conditions.     

Tissue engineering for full-thickness burns: a dermal substitute from bench to bedside

Our aim was to obtain a viable and easily available dermal substitute (DS) for the definitive coverage of full-thickness burns. A DS composed of a collagen-glycosaminoglycan-chitosan dermal matrix (DM) colonized with foreskin fibroblasts (FF) is described. FF-colonized DS were compared to the DM seeded with adult dermal fibroblasts (DF). FF-colonized DS expressed more fibrillin and tropoelastin than that with DF. Reconstructed skin obtained with both FF- and DF-colonized DS similarly expressed laminin-5 and collagen VII at the dermal-epidermal junction. Both FF- and DF-colonized DS produced cutaneous wound healing mediators in a dose-dependent manner in the presence of platelet lysate. After freeze-thawing, the FF-colonized DS were recovered in culture and retained their ability to produce vascular endothelial growth factor. Grafting of DS into nude rats achieved a complete healing of a dermal-epidermal lesion with a good epidermalization.     

Curcumin and cyclopalladated complexes: a recipe for bifunctional biomaterials

The first examples of binuclear and mononuclear ortho-palladated complexes based on a functionalized 2-phenylquinoline ligand have been synthesized and fully characterized. Conjugating cyclopalladated fragments to curcumin family biologically active beta-diketones gives in one single molecule two different functionalities. The structural variations based on the curcuminoid structure have been tested for their in vitro cytotoxic activity. The activity of complexes comprised of a cyclopalladated fragment conjugated to functionalized bioactive ligands, represents the potential of organometallic systems in generating new bifunctional biomaterials.     

无绿藻的研究进展:从基础到临床

无绿藻是一种直径约3 ～ 30 μm的单细胞生物,广泛存在于自然界和动物体表及体内,属于条件致病性真菌.目前主要通过直接镜检、真菌培养、组织病理学检查及分子生物学等手段对无绿藻进行鉴定.现已发现无绿藻属包括五个种,其中对人有致病性的仅为中型无绿藻基因型2、小型无绿藻和P.blaschkeae,其致病机制可能与外伤和免疫力低下有关.随着研究的深入,越来越多的无绿藻病被临床确诊.根据不同的类型及其临床表现,对无绿藻病的治疗也有所区别.为了提高对无绿藻这一条件真菌及其致病性的认识,该文对其生物学特性、鉴定方法、致病性、临床表现等研究进展做一简要综述.