Alpha‐fetoprotein accelerates the progression of hepatocellular carcinoma by promoting Bcl‐2 gene expression through an RA‐RAR signalling pathway

Previous studies have found that alpha‐fetoprotein (AFP) can promote the proliferation of hepatoma cells and accelerate the progression of hepatocellular carcinoma (HCC). However, the exact mechanism of action remains unclear. Recent bioinformatics studies have predicted the possible interaction between AFP and retinoic acid receptors (RARs). Thus, the purpose of this study was to investigate the molecular mechanism through which AFP promotes tumour cell proliferation by interfering with the RA‐RAR signal pathway. Our data indicated that AFP could significantly promote the proliferation and weaken ATRA‐induced apoptosis of hepatoma cells. Besides, cytoplasmic AFP interacts with RAR, disrupting its entrance into the nucleus, which in turn affects the expression of the Bcl‐2 gene. In addition, knockdown of AFP in HepG2 cells was synchronously associated with an incremental increase of RAR binding to DNA, as well as down‐regulation of Bcl‐2; the opposite effect was observed in AFP gene‐transfected HLE cells. Moreover, a similar effect of AFP was detected in tumour tissues with high serum AFP, but not in adjacent non‐cancerous liver tissues, or HCC tissues with low serum AFP levels. These results indicate that AFP acts as signalling molecule and prevents RAR from entering into the nucleus by interacting with RAR, thereby promoting the expression of Bcl‐2. Our data reveal a novel mechanism through which AFP regulates Bcl‐2 expression and further suggest that AFP may be used as a novel target for treating HCC.     

Deoxycytidylate deaminase activity in non-stimulated and phytohemagglutinin-stimulated human lymphocytes,and in leukemic cells

Deoxycytidylate deaminase isolated from normal human lymphocytes and from mononuclear leucocytes from patients with acute lymphoblastic leukemia, chronic lymphocytic leukemia and acute monocytic leukemia has been characterized in regard to the substrate, dAMP and the allosteric regulators dCTP and dTTP. The enzymes exhibited sigmoidal initial velocity versus dCMP concentration whereas in the presence of the activator, dCTP, Michaelis-Menten kinetics were obtained.At saturating substrate concentrations dTTP acted as an allosteric inhibitor of the enzyme isolated from non-stimulated as well as from stimulated lymphocytes. However, the enzymes isolated from the leukemic cells had lost the allosteric regulation by dTTP.At low substrate concentrations the competitive inhibitor, dAMP, activated all the enzymes. This activation was abolished in the presence of dCTP which indicates that dAMP might be involved in the regulation of dCMP deaminase activity and thus influence the dCTP and dTTP pools under physiological conditions.Abbreviations dCMP deaminase deoxycytidylate deaminase - PHA Phytohemagglutinin - ALL acute lymphoblastic leukemia - CLL chronic lymphocytic leukemia - AMOL acute monocytic leukemia - WBC white blood cells     

GsCML27, a Gene Encoding a Calcium-Binding Ef-Hand Protein from Glycine soja,Plays Differential Roles in Plant Responses to Bicarbonate,Salt and Osmotic Stresses

Calcium, as the most widely accepted messenger, plays an important role in plant stress responses through calcium-dependent signaling pathways. The calmodulin-like family genes (CMLs) encode Ca²⁺ sensors and function in signaling transduction in response to environmental stimuli. However, until now, the function of plant CML proteins, especially soybean CMLs, is largely unknown. Here, we isolated a Glycine soja CML protein GsCML27, with four conserved EF-hands domains, and identified it as a calcium-binding protein through far-UV CD spectroscopy. We further found that expression of GsCML27 was induced by bicarbonate, salt and osmotic stresses. Interestingly, ectopic expression of GsCML27 in Arabidopsis enhanced plant tolerance to bicarbonate stress, but decreased the salt and osmotic tolerance during the seed germination and early growth stages. Furthermore, we found that ectopic expression of GsCML27 decreases salt tolerance through modifying both the cellular ionic (Na⁺, K⁺) content and the osmotic stress regulation. GsCML27 ectopic expression also decreased the expression levels of osmotic stress-responsive genes. Moreover, we also showed that GsCML27 localized in the whole cell, including cytoplasm, plasma membrane and nucleus in Arabidopsis protoplasts and onion epidermal cells, and displayed high expression in roots and embryos. Together, these data present evidence that GsCML27 as a Ca²⁺-binding EF-hand protein plays a role in plant responses to bicarbonate, salt and osmotic stresses.     

Body Image Change in Obese and Overweight Persons Enrolled in Weight Loss Intervention Programs: A Systematic Review and Meta-Analysis

To report the results of a systematic review and meta-analysis examining whether weight loss interventions improve body image in obese/overweight individuals. Medline, Current Contents, and the Cochrane database were searched to identify studies involving obese/overweight adults who were enrolled in weight loss interventions in which body image was quantitatively assessed. Outcomes assessed were changes in body shape concern, body size dissatisfaction, and body satisfaction (intervention vs comparator/control group). Seven studies were included in the systematic review (4 in the meta-analysis). All but 1 study involved female participants only. The type of weight loss intervention varied between studies as did the type of control/comparator group. In 3 studies, there was no significant difference in body image outcomes, whereas in 4 studies, improvement in body image was significantly more pronounced in the intervention vs the control/comparator group. Meta-analysis revealed that improvements in body shape concern (standardized difference: -0.52; 95% confidence interval [CI]: -1.04 to 0.00), body size dissatisfaction (standardized difference: -0.66; 95% CI: -0.88 to -0.45), and body satisfaction (standardized difference: 0.74; 95% CI: 0.09 to 1.38) significantly favored the intervention over the comparator/control group (P<0.05). The results of this systematic review/meta-analysis lend support to the notion that weight loss interventions may improve body image. This is a noteworthy finding that has clear clinical applicability because body image affects psychological well-being and the ability of an individual to maintain weight loss. Future research should determine which weigh loss interventions are associated with optimal improvements in body image and maintenance of weight loss.     

Specific neuronal expression of human NGF receptors in the basal forebrain and cerebellum of transgenic mice

Transgenic mice carrying multiple copies of the human NGF receptor gene have been generated. Using a monoclonal antibody specific for the human receptor, we have detected specific expression in cholinergic neurons in the basal forebrain and Purkinje cells in the cerebellum during the postnatal period. Expression in the PNS was exemplified by immunostaining of sympathetic and sensory neurons during an early embryonic age. Transection of the sciatic nerve in transgenic animals resulted in induction of human NGF receptors, indicating that the inserted gene can be appropriately regulated. These transgenic mice will provide an opportunity to study the elements regulating the NGF receptor. Furthermore, the ability to obtain specific expression in transgenic mice will permit directed expression of heterologous genes in discrete cells important in the cholinergic septal-hippocampal pathway and the PNS.     

Experimental infection in a human subject by a possibly undescribed species of Taenia in Taiwan

A cysticercus of a possibly undescribed species of Taenia which occurs commonly in Taiwan aborigines was used to establish an experimental infection in a human volunteer. Symptomatic effects attributed to the infection included diarrhoea, upper abdominal pain, and increase or loss of appetite over a four-month period. After an expelled proglottid was observed 122 days post-exposure, eggs and proglottids were found continuously until the patient was treated with anthelmintics. Antibody titres measured by enzyme-linked immunosorbent assay and levels of eosinophilia seemed to correlate with symptoms. Haematological analyses revealed an abnormal lipid metabolism during the entire symptomatic period.