Journal of Medical Hypotheses and Ideas最新文献

Basically flavonoids are naturally occurring phenolic compounds that are distributed in plants. They contain wide range of biological activity and lot of research has been carried out on their potential role in treating diabetes and other diseases. Most importantly the flavonoids and their related natural compounds are known to encompass antidiabetic potential, demonstrated in various animal models. Such beneficial flavonoids are less utilized on account of its deprived solubility, decreased bioavailability; first pass metabolism and intestinal degradation. However, flavonoids are capable of improving, stabilizing and long sustaining the insulin secretion, human islets and pancreatic cell respectively. In this article we propose, remarkable antidiabetic activity of flavonoids as well as few approaches on nanoparticulate systems in diabetes induced animal models. The proposed nanoparticulate system of flavonoids is projected to improve the solubility, bioavailability, by passing the first pass metabolism and decreasing susceptibility to intestinal environment as compared to pure flavonoid isolates. Further, this hypothesis exemplifies to enhance the efficacy of flavonoids in a novel way of antidiabetic treatment.

The annual incidence of thyroid cancer worldwide is alarming. Despite current various treatments such as surgical resection, radioiodine therapy and chemotherapy/radiotherapy, thyroid carcinoma remains a lethal cancer. Assuredly, the operative and new treatment strategies are necessary to control this malignancy. Gene therapy is regarded as one of the most reliable novel therapeutic methods for hopeless cases of thyroid cancer and those who do not respond to the prevalent treatments. Accumulated evidence suggests that interleukin-24 (IL-24), also known as melanoma differentiation-associated gene-7, has very important roles in regulation of cell differentiation, cell growth and apoptosis, and it is also a promising anticancer agent. Here, we propose that it could be advantageous to evaluate the anti-tumoural effect of IL-24 in a mouse xenograft model of thyroid cancer.

Negative pressure drainage (NPD) technology is required to extract chyme from the gastric cavity of the patient suffering from stomach disease in order to observe the mucosal condition of the gastric cavity clearly and to avoid being misdiagnosed in gastroscopy. However, there are problems, such as insufficient vacuum and easy clogging, in the current NPD devices. To deal with these problems, by applying the principle of hydraulic check valve, a novel device, convenient to extract chyme from gastric cavity, is discussed in this article, which will meet the clinical demand. The proposed new device has the advantages of enough vacuum degree, smooth drainage without backflow and blockage, and has a better application prospect as compared to existing devices.

Radiotherapy is one of the most important methods for the treatment of breast cancer. There is great interest in identifying factors that help to predict patient response to radiotherapy. MicroRNAs (miRNAs) are a class of small RNA molecules that regulate gene expression at the post-transcriptional level and play a key role in cellular responses to ionising radiation. Several regulatory proteins participate in breast tumour cell radiosensitivity and there are crosstalks between miRNAs and these proteins at multiple levels. By analysing the relationships between miRNAs and these proteins, we concluded that radioresistant and radiosensitive breast cancer patients might have different patterns of some specific miRNAs. MiRNAs are present in body fluids in a remarkably stable form and can easily be detected and quantified by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). It seems that profiling circulating miRNAs have the potential to be used for the prediction of radiotherapy outcome in breast cancer.

Tuberculosis (TB) is a growing unsolved health concern, as it is the main infectious cause of death in the globe. The ability of the pathogen to develop into a dormant state is the main obstacle in overcoming the disease. It seems that the development of compounds that can target latent TB is the key to eradicate this pathogen. In this regard, many researchers started to search for novel compounds that could inhibit the activity of molecules involved in the resuscitation of latent bacilli. The discovery of an extremely potent anti-dormancy factor, a resuscitation-promoting factor (Rpf) from Micrococcus luteus, shifted the idea towards developing potent inhibitors of Rpfs to establish latent TB and avoid reactivation of the sleeping pathogen. However, besides the advantages of this approach over the application of annoying long-term regimes of toxic antibiotics, such approaches that rely on silencing latent TB have many drawbacks that may question their application in human research. The major drawback of the current approaches is that they hide the latent TB rather than treating/eradicating it. Here, we propose a novel cost-effective approach that could effectively eradicate both active and latent TB in a short period of time without having any risk of reactivation.

Genetic, environmental factors, dysregulation of immune system, intestinal microbes and oxidative stress are the most important factors that play the role in the pathogenesis of inflammatory bowel disease (IBD). Current treatments do not always result in complete remission and usually accompanied with several adverse effects. Recent studies showed that nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α) and oxidative stress play the pivotal role in the induction of inflammation. Butyrate, l-Carnitine, and probiotics have the potential to control inflammation by reduction of main inflammatory cytokines, including NF-κB and TNF-α. They also stimulate antioxidant enzymes and inhibit IκB kinase (IKK). Regarding the beneficial effects of these three compounds in inflammation via several mechanisms, we hypothesize that the mixture of these compounds would be synergistically effective in reduction of inflammation and alleviation of IBD. Further experimental investigations are needed, to evaluate the hypothesis.

Over the past half-century, biomaterials have been used in orthopaedic surgery world widely, but orthopaedic implant-associated infections (OIAIs) are still a puzzle for orthopaedic surgeons, which may result in prolonged hospitalisation, poor functional status and high costs. The presence of implants increases the risk of microbial infection; moreover, the formation of bacterial biofilm leads to a higher resistance to antibiotics and local immune response. In such cases, conventional systemic delivery of drugs seems to be fairly inefficient and out-dated. Owing to this, debridement and/or removing the implant always become the only solution. Hence, it needs a simple, minimally invasive and effective therapy to eradicate the problem. There are abundant evidences showing that extracorporeal shock wave therapy (ESWT) has favourable effects on stimulating callus formation, inducing angiogenesis, promoting osteogenesis and relieving pain. Studies also indicated that ESWs have a significant bactericidal effect on bacterial strains of bone- and implant-associated infections. Therefore, a hypothesis proposed herein is that ESWT may well be an effective adjuvant treatment for OIAI by controlling infection, inducing bone regeneration and promoting re-osseointegration.

Effective pharmacological treatments for drug abuse and addiction have not yet been identified. Evidences show that vitamin D may be involved in neurodevelopment and may have a neuroprotective effect on dopaminergic pathways in the adult brain. The fact that vitamin D increases the levels of tyrosine hydroxylase expression implies that vitamin D could modulate dopaminergic processes. Drugs of abuse act through different mechanisms of action and on different locations in the brain reward system; however, all of them share a final action in which they increase dopamine levels in the reward pathway. Vitamin D-treated animals showed significant attenuated methamphetamine-induced reductions in dopamine and metabolites when compared to control, indicating that vitamin D provides protection for the dopaminergic system against the depleting effects of methamphetamine. In this article, it is speculated that vitamin D would be an effective treatment approach for drug abuse and addiction, if we consider that vitamin D would provide protection for the dopaminergic system against dopamine-depleting effects of drugs, as it did for methamphetamine. This hypothesis can provide a new direction towards a new treatment approach for drug abuse and addiction, as we have no pharmacological treatments at our disposal at the present moment, although several issues need further investigation.

Osteoporosis is a common disease characterised by low bone density and brittle bone due to osteoblast–osteoclast uncoupling. The cellular and molecular mechanisms responsible for osteoblast–osteoclast coupling lead to the identification of novel therapeutic targets. The increasing evidence for a role for Eph–ephrin signalling in biological processes, including cell–cell interactions, cell morphology, cell migration, angiogenesis, cancer and bone homeostasis, identifies new molecular pathways and potentially novel therapeutic targets for the treatment of diseases. Recent studies suggest that the interactions between Eph and ephrin play critical roles in bone cell differentiation and patterning by exerting dimorphic effects on osteoblast and osteoclast differentiation, resulting in the intriguing coupling of bone resorption and bone formation. These findings suggest that interventions targeting osteoblast–osteoclast coupling by the regulation of the Eph–ephrin bidirectional signalling according to its biological effects, which results in inhibiting osteoclastic resorption and promoting osteoblastic formation, may be a promising approach for osteoporosis prevention and treatment in the near future.

Prolonged exposure to an opioid induces hyperalgesia and tolerance, which negatively affect pain management in turn and significantly hamper the application of opioids. A growing body of evidence has demonstrated that glial activation contributes to the development of these two side effects. Recent studies have demonstrated that morphine, binding to an accessory protein of Toll-like receptor 4 (TLR4), activates microglia and produces neuroinflammation in a manner parallel to lipopolysaccharide. Meanwhile, lipopolysaccharide activates microglia through TLR4/caspase signalling. Therefore, we hypothesise that morphine may activate microglia through TLR4/caspase signalling and that caspase inhibitors may attenuate opioid-induced hyperalgesia and tolerance via inhibiting microglial activation and neuroinflammation.