Bioscience hypotheses最新文献

Parkinson's disease is a neurodegenerative disorder associated with cell loss from the substantia nigra pars compacta (SNc). The dopaminergic cells of the SNc project to the striatum where the loss of dopaminergic tone is thought to be the main cause of Parkinsonism symptoms. Animal models have shown that striatal tissue content of dopamine declines proportionally to cell death in the SNc but the extracellular concentration of dopamine (EDA) in the striatum remains near normal until more than 85% of SNc neurons have died. We investigate various explanations for the remarkable homeostasis of EDA with a mathematical model that has recently been constructed for dopamine synthesis, release, and reuptake, which includes the effects of the autoreceptors. We provide evidence and explanations for the passive stabilization hypothesis and show that the autoreceptors enhance stabilization of EDA only when fewer than 25% of the SNc cells remain.

Chemotherapy is the best method yet for the treatment of advanced cancers, but resistance to chemotherapy limits its therapeutic effect. This has prompted the development of many new approaches for the treatment of cancer. The most important and established is the epidermal growth factor receptor (EGFR) targeted therapy. Since alterations in the expression of gene and activity of the pathway may affect the sensitivity of cancer cells to conventional chemotherapy, it has evoked combination of EGFR targeted drugs and chemotherapy. In fact, EGFR targeted drugs have shown activity in combination with conventional antitumor treatments in preclinical and clinical trials. But there are a significant part of patients in clinical trials demonstrating an unfavourable response. Facing this dilemma, more research is needed to clarify the exact molecular mechanism of the interaction. Nuclear factor erythroid-2-related factor 2 (Nrf2) is a key transcription factor for cell defense mechanisms that regulates the expression of electrophile and xenobiotic detoxification enzymes and drug efflux pump proteins. Moreover, Nrf2 can enhance resistance of cancer cells to chemotherapeutic drugs. And, it is clear that some upstream pathways of Nrf2 are the downstream of EGFR pathway. These significant conditions support the hypothesis that EGFR-Nrf2 pathway plays a role in cancer cell's chemoresistance. Attempts to confirm this hypothesis will provide new evidence in the treatment of combination of EGFR targeted drugs and chemotherapy and the development of new ways of combination of targeted therapy and chemotherapy.

The consensual basis for selecting research topics works for incremental innovation, but is the enemy of radical breakthroughs. Consensual processes, from the ‘European Year of Creativity and Innovation’ to peer review, should be supplemented by the leadership of those with the courage to back the extremes. Such leadership requires support from the very top of scientific management and funding, in academia and industry.

Cancer stem cells are regarded as the hurdle of cancer therapy at least partially due to their intrinsic resistance to therapy. To this end, chemotherapy is widely used for enrichment of cancer stem cells. In contrast to the dogma, we hypothesized that besides enrichment, cancer stem cells could also be induced by chemotherapy in those regions without sufficient drug delivery. Due to the imbalance of the angiogenesis and insufficient blood supply in certain regions of the tumor mass, chemotherapy delivery is compromised in these regions. The insufficient drug delivery in turn transforms the bulk cancer cells to stem cells rather than kill them through NFkappaB-HIF, NFkappaB-Wnt and other signals. Detection of the induction of cancer stem cells from the chemotherapy treated non-stem cancer cells would shed light on our hypothesis, which in turn would broad our understanding of clinical cancer chemotherapy.

Hemangioma is the most common benign vascular tumor in infants and children with unknown etiology and pathogenesis. It is characterized by rapid proliferation followed by a slow involution phase. Histological analyses of infantile hemangioma (IH) in the early proliferating phase have generated a number of developmental theories suggesting an embryonic or primitive cell origin. We here hypothesize the IH may originate from multipotential stem cells. Further investigations of these hemangioma-initiating cells may improve our understanding of their function and possibly lead to novel therapeutic modalities for hemangiomas.

Stature is the most often used anthropometric measure in the nutritional, growth and development, anthropological and forensic oriented studies. Its estimate is considered to be an important assessment in the identification of unknown human remains and its medico-legal significance is obvious in forensic examinations. Diurnal variation in stature is a biological norm in the human body and its effects can be reflected in the reliability of height data in these studies. We hypothesize that the extent of diurnal variation is more in children as compared to adults in a population.

In recent years, researchers have expressed an ongoing interest in developing RNA interference (RNAi) technology for therapeutic gene suppression in various diseases. Preclinical studies in animal models and cultured cell studies indicated that RNAi technology was an effective experimental tool against a variety of ocular diseases, and some small interference RNA (siRNA) drugs have been entered into clinical trials in Stage I and Stage II. However, in these studies siRNAs were delivered into ocular tissues via either systemic or subconjunctival/intravitreous injection, which is invasive and harmful if repeated. Based on this evidence, we hypothesize that topical application of siRNA eye drops may be a safe and effective therapeutic option in ocular surface diseases with temporary changes of gene expression. Furthermore, siRNA eye drops targeting different genes may simultaneously treat several ocular surface diseases.

Peripheral nerve injury and repair is a complex and dynamic process including the outgrowth of newborn axons, the selecting targeting of regenerating axons and their remyelination. The whole process is finely modulated and affected by various regeneration-associated factors and other molecules cooperating with them. The emphasis of current studies aims to improve nerve repair and functional recovery by coordinating the activity of each member involved in the teamwork of nerve regeneration. The neural cells are highly polarized, most of which develop various subcellular compartments including the cell body and processes, respectively participating in the consecutive synthesis and delivery of genes and proteins. Some RNAs synthesized at perikaryon are selectively transported to the distal end and translated into proteins locally. Some proteins choose the way to the distal part of the growing process and play biological functions there. Changes of the microenvironment could induce intracellular biosynthesis at the nucleus and processes thereby to impact the network between cells. Although the route of the specific trafficking of genes and proteins is only partly revealed, it is a feasible means to facilitate negotiation between the nucleus and the distal reaches in this way to assist nerve repair. Electrical stimulation as a convenient technique was applied extensively to clinical therapies on nervous diseases and proved to produce marked effects. But the underlying mechanism of electrical stimulation on nerve injury and repair is poorly understood. We speculate that electrical stimulation therapies take part in nerve degeneration and regeneration not only by stimulating the neural cells to synthesize regeneration-associated genes and proteins, but also by accelerating their transport and promote the localized genes translation at the lesion site.

The last decade has witnessed the emergence of several new viral infectious agents, most notably avian influenza H5N1, SARS and West Nile Virus. The emergence of these agents is heavily associated with zonotic animal hosts, as well as migratory pathways of infected bird vectors. The environmental survival and persistence of nucleic acid associated with these viral agents may be important for both the detection as well as the occurrence of related diseases. Our hypothesis suggests that nucleic acid from such emerging viruses may enter into a virus-parasite surrogate relationship to aid in viral persistence. We suggest that Cryptosporidium and other gastrointestinal parasites, including Giardia, could be a) a reservoir of genetic material and a environment where assortment between that genetic variation can occur and, b) a source of zoonoses through infection of the ‘target’ animal (including humans). One example which illustrates this may be the uptake dsRNA from rotavirus into cryptosporidial oocysts, as this parasite has previously been shown to contain dsRNA viral-like particles. The importance of such a surrogate relationship is discussed and its implications for human and animal health highlighted.