Bioscience hypotheses最新文献

Aldo-keto reductase family 1 B10 (AKR1B10, also designated aldose reductase-like-1, ARL-1) is a novel protein identified from human hepatocellular carcinoma (HCC). This protein belongs to aldo-keto reductase superfamily, a group of proteins implicated in intracellular detoxification, cell carcinogenesis, and cancer therapeutics. AKR1B10 is primarily expressed in the colon and small intestine with low levels in the liver, thymus, prostate, and testis but overexpressed in the liver and lung cancer, making it a potential cancer diagnostic and/or prognostic marker. AKR1B10 could reduce retinals to retinols eliminating intracellular retinoic acid, a signaling molecule regulating cell proliferation and differentiation. AKR1B10 may impact the carcinogenesis process through controlling retinoic acid signaling.

Chronic myeloid leukemia is a myeloproliferative disease, characterized by the presence of the Philadelphia chromosome, which results from the reciprocal chromosomal translocation t(9;22)(q34;q11). Tyrosine kinase inhibitors like imatinib mesylate are selective inhibitors of the BCR–ABL tyrosine kinase, produces high rates of major cytogenetic responses in chronic myeloid leukemia cases. After the imatinib mesylate therapy, some chromosomal abnormalities including trisomy 8, monosomy 7 and nullisomy Y had been reported more frequently. The selective inhibition of tyrosine kinase with imatinib mesylate treatment may cause the proliferation of Philadelphia negative type cell clones. The occurrence of different chromosomal abnormalities including trisomy 8, monosomy 7 and nullisomy Y may have been occurred as a result of an additional chromosomal instability in imatinib mesylate therapy in chronic myeloid leukemia patients. A feedback mechanism due to imatinib mesylate therapy may cause the proliferation of a different Ph-negative stem cell clone with or without chromosomal abnormalities. In the imatinib mesylate treated chronic myeloid leukemia cases, a dosage effect of a gene or an imprinting factor may be the reason of the chromosomal abnormalities. Also a duplication of a mutated/rearranged gene may cause the chromosomal abnormalities due to chromosomal instability. So, we need to clarify these mechanisms in alternative pathways, affected in CML progression.

An effort was made to design a hypothetical system of gene regulation that would allow for precise and reproducible development of a single eukaryote cell into a multi-cell/clone/tissue organism through internal guidance alone, without external cues or environmental coordinates. The concept was constrained only by chemical feasibility. The result is not consistent with biology as currently interpreted, but it has some interesting features and it is consistent with accepted biological facts. The hypothesis is based on a Master Development Program (i.e., DNA sequences protected by the heterochromatin) that is transcribed into Generation-Specific Control Keys that consist of nuclear messenger RNAs that regulate high-level transcription factor genes (e.g., Hox genes). The execution and evolution of this hypothetical mechanism are discussed as are its implications for evolution and development.

B-cell chronic lymphocytic leukemia (B-CLL) affects women and men with different frequency: men show a more than double as high risk to acquire this disease than women. The reason for this sex-related difference is unknown. It is proposed here that menstruation confers advantages to women in two ways: i) early stage B-CLL cells and/or their potential precursors are partially removed from the body with menstrual bleeding which includes shedding of endometrial tissue; and ii) during degradation of the remaining endometrial tissue an immune response against B-CLL is triggered. The regular reduction of potential B-CLL cells throughout pre-menopausal life as well as the immunization against B-CLL would enable the female organism to better control outbreak and course of the disease. Both processes depend on specific binding of the leukemic cells to the endometrial tissue. CD23 expressed on the surface of B-CLL cells is suggested to mediate binding to the vitronectin receptor/CD47 expressed on endometrium. The menstrual inflammatory process includes danger signals that might facilitate initiation of an anti-leukemia immune response. Menstrual immunization might explain sex-related differences in clinical features of other malignancies as well and might therefore have broad implications for the development of individualized therapies.

There are many CNS disorders with imbalance of dopamine in brain. Cimetidine adversely increases serum level of the prolactin and leads to activate feedback control to decrease prolactin release and intensifies synthesis and secretion of dopamine. Thus, cimetidine can be critical in CNS disorders.

Fibrogenesis is a frequent pathogenesis in the processes of many diseases from the initial-stage to the end-stage. Unfortunately, mechanisms of fibrogenesis are complex and not fully understood by now. Recently, researches have proved that oxidative stress participates in the process of fibrosis. Some studies suggest that PTEN, a tumor suppressor, is down-regulated in fibrosis, and it will be a new agent for fighting against fibrogenesis. DJ-1, an oncogene product, has been identified as a protein with various functions in cellular transformation, oxidative stress response and transcriptional regulation, and it is considered as a negative regulator of PTEN in tumor. DJ-1 is also observed overexpression in hepatic fibrosis, but the specific effects of it are obscure. We hypothesize that DJ-1 is a double-edged sword in fibrogenesis: DJ-1 may hamper oxidative damage; overexpression of DJ-1 possibly promote fibrogenesis through depressing the expression of PTEN and activating PI3K/Akt pathway subsequently.

Neurotrophins (NTs) family was first discovered in nervous system and it regulates the proliferation and differentiation of many neural cell types in the peripheral and central nervous system.

Due to their perineural invasive characters, certain part of malignant tumor cases was first diagnosed because of nerve paralysis or idiopathic neuralgia caused by perineural invasion. For this reason, the study on the association between NTs and perineural invasion of malignant tumor aroused the attention of many researchers. Increasing evidence indicates that NTs and their receptors, Trks, play important roles in malignant cells, especially the exhibiting perineural invasive phenotype. It was suggested that NTs produced by neural tissue can act as a chemotactic factor, and tumor cells in which the overexpression of Trks' exists seem to be selected to invade the perineural space. Except for contributing to perineural invasion of malignant tumor, accumulated evidence proved NTs now also significantly associated with the metastasis of malignant tumor. Overexpression of NTs or Trks often correlated with the tumorigenesis, angiogenesis and anoikis resistance in these malignancies, contributing significantly to the metastasis and poor prognosis.

In summary, besides its role in development and function of nervous system, NTs also play an important role in the perineural invasion and metastasis of malignant tumor. Considering the role that NTs played in malignant tumor, we believe that further studies between NTs and malignant tumor are necessary. Research on the role of NTs pathway might allow advancements in this field.

The geomagnetic field is typically about 50 μT (range 20–90 μT). Geomagnetic activity generally decreases by about 4% for the seven days leading up to a full moon, and increases by about 4% after the full moon, lasting for seven days. Animals can clearly detect the changes in magnetic field intensity that occur at full moon, as it has been shown that variations of just a few tens of nT are adequate to form a useful magnetic ‘map’. We think that moonlight increases the sensitivity of animals' magnetoreception because the radical pair model predicts that magnetoreception is light dependent. In fact, there have been some reports of changes in the sensitivity of magnetoreception with lunar phase. We propose a hypothesis that animals respond to the full moon because of changes in geomagnetic fields, and that the sensitivity of animals' magnetoreception increases at this time.

Non-alcoholic fatty liver disease (NAFLD) is and will continue to be a major liver health issue worldwide in the coming decades. There are no leading drug candidates at this point, although there are several promising concepts in drug development. Recent studies have proposed a possible role of intestinal bacterial overgrowth in the development of non-alcoholic steatohepatitis, thus indicated probiotics maybe a potential specific liver drug for NAFLD in the future.