New insights into liver stem cells

Hepatic progenitor cells are bi-potential stem cells residing in human and animal livers that are able to differentiate towards the hepatocytic and the cholangiocytic lineages. In adult livers, hepatic progenitor cells are quiescent stem cells with a low proliferating rate, representing a reserve compartment that is activated only when the mature epithelial cells of the liver are continuously damaged or inhibited in their replication, or in cases of severe cell loss.Hepatic progenitor cell activation has been described in various acute and chronic liver diseases. Their niche is composed by numerous cells such as Hepatic Stellate Cells, endothelial cells, hepatocytes, cholangiocytes, Kupffer cells, pit cells and inflammatory cells. All these cells, numerous hormones and growth factors could interact and cross-talk with progenitor cells influencing their proliferative and differentiative processes. Hepatic progenitor cells and their niche could represent, in the near future, a target for therapeutic approaches to liver disease based on cell-specific drug delivery systems.Isolation and transplantation of hepatic progenitor cells could represent a new approach for therapy of end-stage chronic liver diseases, as they offer many advantages to transplantation of mature hepatocytes. The possibility of applying stem cell therapy to liver diseases will represent a major goal in this field.     

Recent insights into hepatic cancer stem cells

It has been suggested that the development of hepatocellular carcinoma (HCC) is related to the existence of cancer stem cells (CSCs) or tumor-initiating cells. Although CSCs populations may be recognized by use of stem cell markers and/or their functional capacities, their profiles might be diverse, because of the heterogeneity of HCC among individuals. Recent studies indicate that activation of CSCs is related to dysregulation of crucial molecular signaling pathways able to alter the intrinsic properties of normal stem cells. This short review describes the latest evidence of the presence of CSCs, alteration of several developmental and oncogenic pathways, CSC-related microRNAs, and drug resistance in HCC. This information may aid the development of potential novel therapy targeting CSCs in HCC.     

New insights into haematopoietic stem cell transplantation for patients with haemoglobinopathies

Tumour lysis syndrome (TLS) describes the metabolic derangements that occur with tumour breakdown following the initiation of cytotoxic therapy. TLS results from the rapid destruction of malignant cells and the abrupt release of intracellular ions, nucleic acids, proteins and their metabolites into the extracellular space. These metabolites can overwhelm the body's normal homeostatic mechanisms and cause hyperuricaemia, hyperkalaemia, hyperphosphaetemia, hypocalcaemia and uraemia. TLS can lead to acute renal failure and can be life-threatening. Early recognition of patients at risk and initiation of therapy for TLS is essential. There is a high incidence of TLS in tumours with high proliferative rates and tumour burden such as acute lymphoblastic leukaemia and Burkitt's lymphoma. The mainstays of TLS prophylaxis and treatment include aggressive hydration and diuresis, control of hyperuricaemia with allopurinol prophylaxis and rasburicase treatment, and vigilant monitoring of electrolyte abnormalities. Urine alkalinization remains controversial. Unfortunately, there have been few comprehensive reviews on this important subject. In this review, we describe the incidence, pathophysiological mechanisms of TLS and risk factors for its development. We summarise recent advances in the management of TLS and provide a new classification system and recommendations for prophylaxis and/or treatment based on this classification scheme.     

New insights into thyroid hormone function and modulation of reproduction in goldfish

A number of studies have provided evidence for a link between thyroid hormones and physiological or pathophysiological conditions associated with reproduction. Most of the information available is based on clinical observations in human or research in mammals. There are also a number of studies in non-mammalian species, primarily investigating thyroid and reproductive endocrinology in isolation. The findings demonstrate that hyperthyroidism or hypothyroidism are associated with altered fertility due to changes in the levels and activities of hormones of the brain-pituitary-gonadal axis. There appears to be a consistent pattern based on a number of studies in mammalian and non-mammalian species, linking thyroid with reproduction. Results obtained in goldfish suggest that increased levels of thyroid hormones may reduce overall reproductive function. Since thyroid hormones influence metabolism and are known to stimulate growth in most species, it is likely that increased thyroid hormone levels may divert energy from reproduction and promote somatotropic functions. This is particularly important in oviparous species such as fish since energy investment in females during reproductive season is very significant, and increasing thyroid hormone levels after ovulation may be a contributing factor in promoting growth response. Thyroid hormones will likely work in concert with other hormones to influence reproduction in fish and other vertebrates.     

New insights into the immunoregulatory functions of mast cells

Mast cells, which are preferentially located in connective tissues and epithelial layers, are now recognized as effector cells that participate in innate and acquired immunity. Upon activation with various secretagogues, mast cells release a large number of mediators stored in their secretory granules which consist of inflammatory mediators, cytokines, proteoglycans and neutral proteases. In addition to soluble mediators, mast cell granules have recently been shown to harbour small vesicles with immunoregulatory properties. Isolated exosomes have been shown to activate B and T lymphocytes and act as potent adjuvants for specific antibody responses in vivo. In this article I will discuss the mechanisms by which mast cells fulfill immunoregulatory functions that may be beneficial for the host.     

New insights into autoimmune liver diseases.

Autoinflammatory liver disease represents an important aspect of global hepatological practice. The three principal disease divisions recognized are autoimmune hepatitis, primary sclerosing cholangitis and primary biliary cirrhosis. Largely, but not exclusively, these diseases are considered to be autoimmune in origin. Increased recognition of outlier and overlap syndromes, changes in presentation and natural history, as well as the increased awareness of IgG4-associated sclerosing cholangitis, all highlight the limitations of the classic terminology. New insights continue to improve the care given to patients, and have arisen from carefully conducted clinical studies, therapeutic trials, as well as genetic and laboratory investigations. The challenges remain to treat patients before liver injury becomes permanent and to prevent the development of organ failure.     

New insights into functions of erythroid proteins in nonerythroid cells

This article presents new insights into potential roles that three erythrocyte cytoskeletal proteins, protein 4.1, ankyrin, and spectrin, may play in nonerythroid nucleated cells. Each of these proteins is encoded by several closely related genes characterized by complex alternative splicing of their pre-mRNA, thus resulting in the cellular expression of a broad repertoire of isoforms that can adopt tissue- and cell-specific distribution. This could account for the presence of skeletal networks in intracellular organelles such as lysosomes, the Golgi apparatus, or the nucleus. In addition to providing structural support to cell membranes, these cytoskeletal proteins regulate the functions of various transmembrane proteins they interact with, in particular ion channels, as well as the activity of membrane-bound enzymes. Thus, they appear to be key players in major unsuspected cell functions such as protein sorting, dynamics of nuclear architecture during mitosis, or regulation of signal transduction pathways.     

New insights into glucose regulation

This review article describes the regulation of glucose homeostasis in subjects with and without diabetes based on the emergence of new information and discusses modes of action, attributes, and limitations of current diabetes therapies. In normal physiology, glucose homeostasis is tightly controlled by the interaction of pancreatic and gut hormones. Since the 1920s, diabetes has been viewed as a disease caused by deficient secretion of insulin, resulting in reduced glucose uptake and subsequent hyperglycemia. The discovery in the 1950s of the pancreatic hormone glucagon, which opposes insulin by increasing glucose appearance in the circulation, resulted in a bihormonal model of glucose homeostasis. More recently, with the discovery of the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) in the 1970s and the pancreatic hormone amylin in the 1980s, it is now understood that several organs and hormones play roles in maintaining glucose homeostasis. Therapies for diabetes have focused on compensation for deficient insulin action through stimulation of insulin secretion, administration of insulin itself, reduction of peripheral insulin resistance, or decreased glucose absorption from the intestine. The discoveries of amylin and GLP-1 have furthered our understanding of the abnormalities involved in diabetes, enabling the development of additional therapeutic options.     

甲状腺干细胞的研究进展

甲状腺干细胞是一类具有自我复制能力及具有向甲状腺细胞分化潜能的未分化细胞.近年来,关于甲状腺干细胞的研究日益成熟,已经成功地从胚胎干细胞、甲状腺成体干细胞和骨髓干细胞诱导分化出甲状腺滤泡细胞,这类细胞能够表达甲状腺特征性基因,并具有摄碘功能.甲状腺干细胞的研究为临床甲状腺疾病的治疗,特别是甲状腺干细胞移植奠定了基础.     

New insights into pneumococcal disease

Streptococcus pneumoniae (pneumococcus) remains a common cause of disease and death throughout the world. Despite considerable research into various aspects of this infection, there still remain a number of unresolved issues, as well as considerable ongoing controversies, particularly with regard to its optimal management. Among the risk factors for pneumococcal pneumonia, cigarette smoking has been shown to play a major role, more recently among HIV-infected individuals. Considerable recent research has focused on determining the role of the various protein virulence factors in disease pathogenesis. Among the ongoing controversies has been an appreciation of the true impact of antimicrobial resistance on the outcome of pneumococcal infections, as well an understanding of the role of combination antibiotic therapy in the more severely ill hospitalized cases. An important advance in the prevention of pneumococcal infections has been the introduction of the pneumococcal protein conjugate vaccine.