Retinoblastoma: from bench to bedside

Retinoblastoma (Rb) is the most common primary ocular malignancy of children and is caused by a mutation in the gene RB1. Approximately 40% of cases are associated with one or more constitutional mutations, and are therefore heritable, whereas the other 60% are sporadic. Rb is exclusively found in young children. In some cases, Rb tumours metastasise to extraocular organs including bone, lung and brain. Although there is no effective treatment for metastatic disease, non-metastatic cases can be cured by removal of the eye(enucleation). Newer treatment strategies emphasise salvaging the affected eye whenever possible. Animal models of Rb have been developed with xenograft and transgenic techniques. Each model has both strengths and weaknesses for exploring the mechanisms of disease development and progression and the efficacy of new treatment strategies.     

Human serum albumin: from bench to bedside

Human serum albumin (HSA), the most abundant protein in plasma, is a monomeric multi-domain macromolecule, representing the main determinant of plasma oncotic pressure and the main modulator of fluid distribution between body compartments. HSA displays an extraordinary ligand binding capacity, providing a depot and carrier for many endogenous and exogenous compounds. Indeed, HSA represents the main carrier for fatty acids, affects pharmacokinetics of many drugs, provides the metabolic modification of some ligands, renders potential toxins harmless, accounts for most of the anti-oxidant capacity of human plasma, and displays (pseudo-)enzymatic properties. HSA is a valuable biomarker of many diseases, including cancer, rheumatoid arthritis, ischemia, post-menopausal obesity, severe acute graft-versus-host disease, and diseases that need monitoring of the glycemic control. Moreover, HSA is widely used clinically to treat several diseases, including hypovolemia, shock, burns, surgical blood loss, trauma, hemorrhage, cardiopulmonary bypass, acute respiratory distress syndrome, hemodialysis, acute liver failure, chronic liver disease, nutrition support, resuscitation, and hypoalbuminemia. Recently, biotechnological applications of HSA, including implantable biomaterials, surgical adhesives and sealants, biochromatography, ligand trapping, and fusion proteins, have been reported. Here, genetic, biochemical, biomedical, and biotechnological aspects of HSA are reviewed.     

Advances in infection and immunity: from bench to bedside

This report summarizes recent advances on host-pathogen interactions, innate and adaptive responses to infection, as well as novel strategies for the control of infectious diseases.     

Antioxidants and cataract

Abstract

The major causes for cataract formation are free radicals, and these free radicals are neutralized by the presence of endogenous antioxidants in the eye. Using xenobiotics, it has been confirmed that free radicals mediate the formation of cataract. Two cataract model-selenite model and the diabetic cataract model-have been developed to study the pathophysiology of cataract formation due to free radicals and the role of antioxidants during the process of cataractogenesis. This review focuses on natural compounds with antioxidant properties that could actually be applied as an interventional strategy on a large scale and are also relatively inexpensive. A brief overview of plants with antioxidant properties that in addition possess potential anti-cataract properties has been discussed. In addition to plants, three natural compounds (curcumin, vitamin C and vitamin E), on which a lot of data exist showing anti-cataract and antioxidant activities, have also been discussed. These antioxidants can be supplemented in the diet for a better defence against free radicals. Studies on vitamin C and vitamin E have proved that they are capable of preventing lipid peroxidation, thereby preventing the generation of free radicals, but their efficacy as anti-cataract agent is questionable. Unlike vitamins C and E, curcumin is well established as an anti-cataract agent, but the issue of curcumin bioavailability is yet to be addressed. Nanotechnology proves to be a promising area in increasing the curcumin bioavailability, but still a lot more research needs to be done before the use of curcumin as an effective anti-cataract agent for humans.     

Curcumin,a component of golden spice: From bedside to bench and back

Although the history of the golden spice turmeric (Curcuma longa) goes back thousands of years, it is only within the past century that we learned about the chemistry of its active component, curcumin. More than 6000 articles published within the past two decades have discussed the molecular basis for the antioxidant, anti-inflammatory, antibacterial, antiviral, antifungal, and anticancer activities assigned to this nutraceutical. Over sixty five clinical trials conducted on this molecules, have shed light on the role of curcumin in various chronic conditions, including autoimmune, cardiovascular, neurological, and psychological diseases, as well as diabetes and cancer. The current review provides an overview of the history, chemistry, analogs, and mechanism of action of curcumin.     

DNA sequencing: bench to bedside and beyond

Fifteen years elapsed between the discovery of the double helix (1953) and the first DNA sequencing (1968). Modern DNA sequencing began in 1977, with development of the chemical method of Maxam and Gilbert and the dideoxy method of Sanger, Nicklen and Coulson, and with the first complete DNA sequence (phage ϕX174), which demonstrated that sequence could give profound insights into genetic organization. Incremental improvements allowed sequencing of molecules >200 kb (human cytomegalovirus) leading to an avalanche of data that demanded computational analysis and spawned the field of bioinformatics. The US Human Genome Project spurred sequencing activity. By 1992 the first ‘sequencing factory’ was established, and others soon followed. The first complete cellular genome sequences, from bacteria, appeared in 1995 and other eubacterial, archaebacterial and eukaryotic genomes were soon sequenced. Competition between the public Human Genome Project and Celera Genomics produced working drafts of the human genome sequence, published in 2001, but refinement and analysis of the human genome sequence will continue for the foreseeable future. New ‘massively parallel’ sequencing methods are greatly increasing sequencing capacity, but further innovations are needed to achieve the ‘thousand dollar genome’ that many feel is prerequisite to personalized genomic medicine. These advances will also allow new approaches to a variety of problems in biology, evolution and the environment.     

Oxidative physiology is weakly associated with pigmentation in birds

The mechanistic link between avian oxidative physiology and plumage coloration has attracted considerable attention in past decades. Hence, multiple proximal hypotheses were proposed to explain how oxidative state might covary with the production of melanin and carotenoid pigments. Some hypotheses underscore that these pigments (or their precursors, e.g., glutathione) have antioxidant capacities or function as molecules storing the toxic excess of intracellular compounds, while others highlight that these pigments can act as pro‐oxidants under specific conditions. Most studies addressing these associations are at the intraspecific level, while phylogenetic comparative studies are still scarce, though needed to assess the generality of these associations. Here, we tested whether plumage and bare part coloration were related to oxidative physiology at an interspecific level by measuring five oxidative physiology markers (three nonenzymatic antioxidants and two markers of lipid peroxidative damage) in 1387 individuals of 104 European bird species sampled during the breeding season, and by scoring plumage eumelanin, pheomelanin, and carotenoid content for each sex and species. Only the plasma level of reactive oxygen metabolites was related to melanin coloration, being positively associated with eumelanin score and negatively with pheomelanin score. Thus, our results do not support the role of antioxidant glutathione in driving variation in melanin synthesis across species. Furthermore, the carotenoid scores of feathers and bare parts were unrelated to the measured oxidative physiology parameters, further suggesting that the marked differences in pigmentation across birds does not influence their oxidative state.     

The molecular basis of erectile dysfunction: from bench to bedside

Erectile dysfunction is a common problem affecting many men across all age groups. Its etiology is multifactorial. Hormonal, vascular, neurogenic, lifestyle, and psychological entities have all been implicated as causative agents. The molecular basis underlying its etiology and progression is complex and still challenges researchers in the field. Nonetheless, newly discovered common pathways and targets of its pathogenesis have opened a new era for both prevention and active treatment of the disease. This review describes some of the known molecular mechanisms contributing to erectile dysfunction and discusses the future of gene therapy for the disease.     

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.     

Mitochondrial gene therapy: The tortuous path from bench to bedside

The association of mitochondrial dysfunction with a variety of human diseases and disabilities has been documented. Mitochondrial gene therapy (MGT) seeks to correct the genetic defect in mitochondrial DNA. For successful MGT, an appreciation of the nature of the dysfunction and of the complexities of mitochondrial disease is necessary. This review summarizes the current status of various MGT protocols described in the literature. Although there are many technical difficulties to be overcome, there are indications that some of them will find clinical applications in the near future.     

Pro-inflammatory cytokines in acute coronary syndromes: from bench to bedside

Cytokines are produced in a variety of tissues and regulate the expression of a number of inflammatory molecules, leading to destabilization and finally rupture of vulnerable atheromatic plaques. They also participate in the pathophysiology of acute coronary syndromes (ACS) by direct effects on myocardial contractility and apoptosis. At a clinical level, circulating cytokines have a prognostic role since they are useful markers predicting future coronary events in patients with advanced atherosclerosis and in patients after ACS.     

CD3-specific antibody-induced active tolerance: from bench to bedside

Although they were used initially as non-specific immunosuppressants in transplantation, CD3-specific monoclonal antibodies have elicited renewed interest owing to their capacity to induce immune tolerance. In mouse models of autoimmune diabetes, CD3-specific antibodies induce stable disease remission by restoring tolerance to pancreatic beta-cells. This phenomenon was extended recently to the clinic--preservation of beta-cell function in recently diagnosed patients with diabetes was achieved by short-term administration of a CD3-specific antibody. CD3-specific antibodies arrest ongoing disease by rapidly clearing pathogenic T cells from the target. Subsequently, they promote long-term T-cell-mediated active tolerance. Recent data indicate that transforming growth factor-beta-dependent CD4+CD25+ regulatory T cells might have a central role in this effect.     

Dendritic cells: On the move from bench to bedside.

As dendritic cells increasingly become the adjuvant of choice in new approaches to cancer immunotherapy, a degree of protocol standardization is required to aid future large-scale clinical trials.     

Free radicals in the 1900's: from in vitro to in vivo

Remarkable progress has been achieved in the past 100 years in the field of free radical chemistry, biology and medicine since the discovery of free radicals in 1900. Free radical-mediated processes play a major role in the present industrial chemistry, but they also cause deleterious effects on rubber, plastics, oil products and foods. The importance of free radicals in vivo has been recognized increasingly from both positive and negative sides. Free radicals play an important role in phagocytosis, the production of some biologically essential compounds and possibly cell signaling. At the same time, they may cause oxidative modification of biological molecules, which leads to oxidative damage and eventually to various diseases, cancer and aging. The role and beneficial effects of antioxidants against such oxidative stress support this view. Furthermore, novel issues have been continuously found in this fascinating and yet controversial field of free radicals in biology. In this short article, the past work, present problems and future perspectives of free radicals in life science will be briefly discussed.     

Abiotic stress modifies the synthesis of alpha‐tocopherol and beta‐carotene in phytoplankton species

We performed laboratory experiments to investi‐gate whether the synthesis of the antioxidants α‐tocopherol (vitamin E) and β‐carotene in phytoplankton depends on changes in abiotic factors. Cultures of Nodularia spumigena, Phaeodactylum tricornutum, Skeletonema costatum, Dunaliella tertiolecta, Prorocentrum cordatum, and Rhodomonas salina were incubated at different tempe‐ratures, photon flux densities and salinities for 48 h. We found that abiotic stress, within natural ecological ranges, affects the synthesis of the two antioxidants in different ways in different species. In most cases antioxidant production was stimulated by increased abiotic stress. In P. tricornutum KAC 37 and D. tertiolecta SCCAP K‐0591, both good producers of this compound, α‐tocopherol accumulation was negatively affected by environmentally induced higher photosystem II efficiency (F_v/F_m). On the other hand, β‐carotene accumulation was positively affected by higher F_v/F_m in N. spumigena KAC 7, P. tricornutum KAC 37, D. tertiolecta SCCAP K‐0591 and R. salina SCCAP K‐0294. These different patterns in the synthesis of the two compounds may be explained by their different locations and functions in the cell. While α‐tocopherol is heavily involved in the protection of prevention of lipid peroxidation in membranes, β‐carotene performs immediate photo‐oxidative protection in the antennae complex of photosystem II. Overall, our results suggest a high variability in the antioxidant pool of natural aquatic ecosystems, which can be subject to short‐term temperature, photon flux density and salinity fluctuations. The antioxidant levels in natural phytoplankton communities depend on species composition, the physiological condition of the species, and their respective strategies to deal with reactive oxygen species. Since α‐tocopherol and β‐carotene, as well as many other nonenzymatic antioxidants, are exclusively produced by photo‐synthetic organisms, and are required by higher trophic levels through dietary intake, regime shifts in the phytoplankton as a result of large‐scale environmental changes, such as climate change, may have serious consequences for aquatic food webs.     

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.