Murine models of colorectal cancer

Colorectal cancer is one of the most prevalent cancers of humans. To experimentally investigate this common disease, numerous murine models have been established. These models accurately recapitulate the molecular and pathologic characteristics of human colorectal cancers, including activation of the myelocytomatosis oncogene (MYC), which has recently been suggested to be a key mediator of colorectal cancer development. This review focuses on the variety of murine models of human colorectal cancer that are available to the research community and on their use to identify common and distinct characteristics of colorectal cancer.     

人体肠道乳杆菌的最新研究进展

乳杆菌是健康人体肠道的重要菌群之一,它与肠道微生态系统的调节和代谢、免疫的调控密切相关。大多数乳杆菌对人类健康有积极作用,其中一部分已被归为益生菌。一直以来,乳杆菌在人体中的存在状态和作用机制都是肠道微生态领域的研究重点。本文总结了人体肠道乳杆菌在种类、数量和功能方面的最新进展,值得注意的是,基于现代分子生物学技术的研究发现乳杆菌在人体肠道菌群中所占的数量比例相当小。虽然在数量上不占优势,但在对宿主生理功能的影响和代谢过程的调节上有不可替代的作用。此外本文还讨论了该领域仍需研究的内容,为人们进一步探索提供一些帮助。     

The metastatic process: history, models and recent advances

The onset of metastasis is a critical event in the natural history of cancer, and is generally associated with a poor clinical outcome. Mechanistically, the metastatic process is made of several steps that are biologically distinct and now rather well characterized. Several explanatory models have been proposed: selective models (clonal selection), adaptive models (initial oncogenesis), involvement of tumor "stem" cells, epithelial-mesenchymal transition… The next progresses are expected to come from the characterization of circulating and disseminated tumor cells, which are two recently opened windows on the metastatic process in patients.     

乳腺癌组织及肠道微生态研究进展

乳腺癌是全球女性患病率及病死率最高的恶性肿瘤,对生命健康造成极大威胁。微生物群被认为是人体“第二基因组”,在维护人类健康中扮演着重要角色,其结构及功能紊乱与疾病发生发展密切相关。随着高通量测序等生物技术的发展,诸多研究揭示了微生物群与乳腺癌关系密切,微生物群可能通过影响雌激素代谢、干预细胞增殖与凋亡、调节免疫及炎症等途径影响乳腺癌的发生发展,并可能影响乳腺癌对化疗及免疫治疗的反应。本文就乳腺癌组织微生态与肠道微生态研究概况展开综述,并提出预防和治疗乳腺癌的新策略。

     

Peroxisome biogenesis: recent advances

In recent years, it has become evident that peroxisomes form part of the endomembrane system. Peroxisomes can form from the ER via a maturation process and they can multiply by growth and division, whereby the ER provides membrane for growth and ongoing fission (Figure 1). Until very recently, it was widely accepted that most peroxisomal membrane proteins (PMPs) insert directly into peroxisomes, whereas a small subset of PMPs traffic via the ER. In this minireview, we focus mainly on PMP biogenesis, and highlight recent advances in peroxisomal matrix protein import, fission and segregation in yeast.     

Hepatitis vaccines: recent advances

Despite the availability of hepatitis A vaccines that might provide protection for decades, hepatitis B vaccines that provides protection for at least 15 years and the recent introduction of a combined hepatitis A and B vaccine, these infections continue to spread in both the developed and developing world. Hepatitis A vaccine coverage has been limited to high-risk groups: such a selective immunisation policy is unlikely to have a major impact. If adequate immunogenicity in infants is confirmed, dosing schedules can be improved and the costs of vaccination reduced, universal paediatric immunisation with combined hepatitis A and B products is likely to result in the eventual eradication of these infections. In the interim, novel hepatitis A vaccines are being investigated and additional studies on hepatitis A vaccine immunogenicity in infants are in progress. Worldwide use of hepatitis B vaccines for the newborn, young children and high-risk groups should control this infection and obviate the need for a vaccine against hepatitis D. Newer hepatitis B vaccines that may reduce the likelihood of non-responsiveness and have immunotherapeutic value are under study. A recombinant hepatitis E vaccine for use in endemic regions is currently in clinical trials. The development of an effective hepatitis C vaccine has been agonisingly slow and many impediments have been recognised. These include the lack of a susceptible small animal, a high degree of hepatitis C virus (HCV) genomic diversity and failure to produce high quantities of HCV in tissue culture. The development of a novel HCV replicon system may be a major breakthrough. Nonetheless, it may still be exceedingly difficult to produce a vaccine that uniformly provides sterilising immunity; the possibility of developing a hepatitis C vaccine that can prevent chronic infection is an exciting concept that requires further investigation. Advances in recombinant technology, the use of novel genetic (DNA-based) vaccines, expression of hepatitis antigens in plants and improved adjuvants also hold considerable promise.     

Recent advances in cancer research: mouse models of tumorigenesis

Over the past 20 years, cancer research has gained major insights into the complexity of tumor development, in particular into the molecular mechanisms that underlie the progressive transformation of normal cells into highly malignant derivatives. It is estimated that the transformation of a normal cell to a malignant tumor cell is dependent upon a small number of genetic alterations, estimated to be within the range of four to seven rate-limiting events. Critical events in the evolution of neoplastic disease include the loss of proliferative control, the failure to undergo programmed cell death (apoptosis), the onset of neoangiogenesis, tissue remodeling, invasion of tumor cells into surrounding tissue and, finally, metastatic dissemination of tumor cells to distant organs. In patients, the molecular analysis of these multiple steps is hampered by the unavailability of tumor biopsies from all tumor stages. In contrast, mouse models of tumorigenesis allow the reproducible isolation of all tumor stages, including normal tissue, which are then amenable to pathological, genetic and biochemical analyses and, hence, have been instrumental in investigating cancer-related genes and their role in carcinogenesis. In this review, we discuss mouse tumor models that have contributed substantially to the identification and characterization of novel tumor pathways. In particular, we focus on transgenic and knockout mouse models that closely mimic human cancer and thus can be used as model systems for cancer research.     

Murine mutants in the study of systemic iron metabolism and its disorders: an update on recent advances

Many past and recent advances in the field of iron metabolism have relied upon the use of mouse models of disease. These models have arisen spontaneously in breeder colonies or have been engineered for global or conditional ablation or overexpression of select genes. Full phenotypic characterization of these models typically involves maintenance on iron-loaded or -deficient diets, treatment with oxidative or hemolytic agents, breeding to other mutant lines or other stresses. In this review, we focus on systemic iron biology and the contributions that mouse model-based studies have made to the field. We have divided the field into three broad areas of research: dietary iron absorption, regulation of hepcidin expression and cellular iron metabolism. For each area, we begin with an overview of the current understanding of key molecular and cellular determinants then discuss recent advances. Finally, we conclude with brief comments on prospects for future study. This article is part of a Special Issue entitled: Cell Biology of Metals.     

Aerobic granular sludge: recent advances

Aerobic granulation, a novel environmental biotechnological process, was increasingly drawing interest of researchers engaging in work in the area of biological wastewater treatment. Developed about one decade ago, it was exciting research work that explored beyond the limits of aerobic wastewater treatment such as treatment of high strength organic wastewaters, bioremediation of toxic aromatic pollutants including phenol, toluene, pyridine and textile dyes, removal of nitrogen, phosphate, sulphate and nuclear waste and adsorption of heavy metals. Despite this intensive research the mechanisms responsible for aerobic granulation and the strategy to expedite the formation of granular sludge, and effects of different operational and environmental factors have not yet been clearly described. This paper provides an up-to-date review on recent research development in aerobic biogranulation technology and applications in treating toxic industrial and municipal wastewaters. Factors affecting granulation, granule characterization, granulation hypotheses, effects of different operational parameters on aerobic granulation, response of aerobic granules to different environmental conditions, their applications in bioremediations, and possible future trends were delineated. The review attempts to shed light on the fundamental understanding in aerobic granulation by newly employed confocal laser scanning microscopic techniques and microscopic observations of granules.     

Downstream processing of proteins: recent advances

This review on the downstream processing of proteins describes innovations that have occurred in the field since 1983. Several areas have seen particularly high levels of achievement, and are accorded expanded coverage relative to our previous review [1]. As an example, the increasing integration of downstream operations with upstream technologies, such as molecular biology and fermentation, has led to the development of some very powerful processes. The degree to which organizations understand that there needs to be one unified process, rather than the independent steps of cloning, fermentation and recovery, seems directly related to the ultimate speed and success of the development effort.

In 1983 one of the most active development areas was chromatography, especially affinity chromatography. This is still true today, and this topic has been expanded to include biospecific adsorptions that would not traditionally be classified as chromatography. With more proteins being developed for human administration, there has been an increased emphasis on all aspects of process hygiene. In addition, there has been much discussion about the impact of regulatory demands on the design and development of the manufacturing processes. Therefore, a section has been added which covers several of the regulatory issues that have been raised for products of the new biotechnology. Finally, as some of the early process development achievements are now beginning to bear fruit in the form of patents, we have increased our citation of this area of the literature.     

Fluorescence imaging in vivo: recent advances

In vivo fluorescence imaging uses a sensitive camera to detect fluorescence emission from fluorophores in whole-body living small animals. To overcome the photon attenuation in living tissue, fluorophores with long emission at the near-infrared (NIR) region are generally preferred, including widely used small indocarbocyanine dyes. The list of NIR probes continues to grow with the recent addition of fluorescent organic, inorganic and biological nanoparticles. Recent advances in imaging strategies and reporter techniques for in vivo fluorescence imaging include novel approaches to improve the specificity and affinity of the probes and to modulate and amplify the signal at target sites for enhanced sensitivity. Further emerging developments are aiming to achieve high-resolution, multimodality and lifetime-based in vivo fluorescence imaging.     

Polyamines and abiotic stress: recent advances

Summary. In this review we will concentrate in the results published the last years regarding the involvement of polyamines in the plant responses to abiotic stresses, most remarkably on salt and drought stress. We will also turn to other types of abiotic stresses, less studied in relation to polyamine metabolism, such as mineral deficiencies, chilling, wounding, heavy metals, UV, ozone and paraquat, where polyamine metabolism is also modified. There is a great amount of data demonstrating that under many types of abiotic stresses, an accumulation of the three main polyamines putrescine, spermidine and spermine does occur. However, there are still many doubts concerning the role that polyamines play in stress tolerance. Several environmental challenges (osmotic stress, salinity, ozone, UV) are shown to induce ADC activity more than ODC. The rise in Put is mainly attributed to the increase in ADC activity as a consequence of the activation of ADC genes and their mRNA levels. On the other hand, free radicals are now accepted as important mediators of tissue injury and cell death. The polycationic nature of polyamines, positively charged at physiological pH, has attracted the attention of researchers and has led to the hypothesis that polyamines could affect physiological systems by binding to anionic sites, such as those associated with nucleic acids and membrane phospholipids. These amines, involved with the control of numerous cellular functions, including free radical scavenger and antioxidant activity, have been found to confer protection from abiotic stresses but their mode of action is not fully understood yet. In this review, we will also summarize information about the involvement of polyamines as antioxidants against the potential abiotic stress-derived oxidative damage. Authors’ address: Dr. María Patricia Benavides, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, Buenos Aires 1113, Argentina     

Thyroglobulin structure and function: recent advances

Thyroglobulin is a large-size iodoglycoprotein specific to thyroid tissue and is the substrate for the synthesis of thyroid hormones, thyroxine and 3,5,3'-triiodothyronine. Recent studies, which greatly benefited from recombinant DNA methodologies, improved the knowledge of several structural features of this dimeric protein and permitted insights into some structure-function relationships. Analysis-function of the primary structure of the human thyroglobulin monomer revealed several main characteristics: 1) 3 types of internal homologies; 2) extensive homology with the bovine thyroglobulin monomer and known partial sequences in the thyroglobulins of other mammalian species; 3) significant homologies with 2 other non-thyroid proteins (acetylcholinesterase and the invariant chain of the Ia class II histocompatibility antigen); 4) a terminal localization of the hormonogenic sites at both ends of the monomer. Current studies aim at determining conformational characteristics, understanding the molecular mechanisms of thyroid hormone formation and unraveling those interactions which in the thyroid cell and the thyroid follicle will permit this large pro-hormone to synthesize and release a few small thyroid hormone molecules. A more precise knowledge of this molecule in higher vertebrates and during evolution would impart valuable information concerning thyroid pathology, since thyroglobulin has been implicated in some genetic and in autoimmune thyroid diseases.     

Dientamoebiasis: clinical importance and recent advances

Dientamoeba fragilis, an unusual single-celled parasite that was described first in 1918, is found worldwide in the gastrointestinal tract of humans. D. fragilis has emerged from obscurity recently because it is now recognized as a common cause of chronic diarrhoea and is treatable with drugs. Recent molecular studies have described D. fragilis as having two genotypes. Diagnostic tests, based on conventional and real-time PCR, have been developed that will provide a rapid, sensitive and specific diagnosis of D. fragilis. These tests will also aid the elucidation of the host distribution and the life cycle of this pathogen.