Hongwei Ma , Dunquan Xu , Yaqiong Wu , Yongtao Ma , Zhichao Li
{"title":"To decipher the hypoxic pulmonary hypertension: Vascular heterogeneity and the hypothesis of hypoxic responsive threshold","authors":"Hongwei Ma , Dunquan Xu , Yaqiong Wu , Yongtao Ma , Zhichao Li","doi":"10.1016/j.jmhi.2015.01.002","DOIUrl":"10.1016/j.jmhi.2015.01.002","url":null,"abstract":"<div><p>Pulmonary hypertension (PH) is a complex and multi-factorial chronic disease characterized by progressively increased pulmonary vascular resistance and vascular remodeling, and it has been recognized as ‘the cancer of cardiovascular diseases’ because of its high morbidity and mortality. Pathophysiological changes of pulmonary arteries, which implicate endothelial dysfunction, smooth muscle cell proliferation, and increased vasoconstriction, decrease the lumen area of the pulmonary microvasculature, optimizing the pulmonary ventilation/perfusion ratio as well as causing fixed elevation of pulmonary resistance. Among various types of PH, hypoxic pulmonary hypertension (HPH) which occurs in patients with cardiopulmonary disease or in residents at high altitude has aroused great interest in researchers. Intriguingly, synchronously exposed to the hypoxic circumstances, the peripheral vessels make responses different from pulmonary arteries, which, besides the effects exerted by nervus and the microenvironment (involving the inflammatory mediators, angiotensin II and other ingredients), has always been expounded as the vascular heterogeneity. Nevertheless, nobody has articulated such heterogeneity and its mechanism to date. Based on our prior experiments, we propound the hypothesis of hypoxic responsive threshold (HRT) for the first time, which means that once the partial pressure of oxygen diminishes to certain degree, vessel in different tissues reacts via the reactive oxygen species (ROS)–potassium channels (K<sub>v</sub>)–hypoxia inducible factors (HIF) triangle, resulting in hypoxic vasoconstriction and vascular remodeling. HRT, varying according to different parts of the body, has close relationship with normoxic condition of the vessels. Physiological oxygen-rich milieu determines higher pulmonary vascular HRT, which explains why the pulmonary arterioles are more susceptible to hypoxia.</p></div>","PeriodicalId":100803,"journal":{"name":"Journal of Medical Hypotheses and Ideas","volume":"9 1","pages":"Pages 29-37"},"PeriodicalIF":0.0,"publicationDate":"2015-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.jmhi.2015.01.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86517359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Near-IR absorbing quantum dots might be usable for growth factor-based differentiation of stem cells","authors":"Hassan Niknejad , Masoumeh Mirmasoumi , Behzad Torabi , Nafiseh Deheshkar-Farahani","doi":"10.1016/j.jmhi.2015.01.003","DOIUrl":"10.1016/j.jmhi.2015.01.003","url":null,"abstract":"<div><p>For stem cell therapy of degenerative diseases, it is necessary to differentiate stem cells into the specific lineage. There are several growth factors which have been used for differentiation of stem cells. Some growth factors can dose-dependently induce differentiation of stem cells so that the increase of growth factor concentration results in production of the higher level of differentiated cells. However, due to the toxicity of some differentiation factors (e.g. retinoic acid), the lower dose of growth factors for the specific lineage differentiation of stem cells is desirable. This paper suggests a new approach in the field of controlled growth factor delivery system using semiconductor nanocrystals; known as quantum dots (QDs). This system contains polymeric microencapsulated growth factor which is conjugated to near infrared (NIR) absorbing QDs. The control release of growth factors from microcapsules in the culture plates can be achieved by irradiation. To modulate growth factor release in response to stem cells needs for differentiation, the intensity and period of irradiation will be controlled. Our hypothesis is based on the fact that QDs can absorb NIR energy and by excitation of electrons and then vibrational relaxation of them become heated when they were irradiated and then release growth factors. We believe that controlled growth factors delivery through the suggested system is an effective method to reduce the amount of growth factors required for differentiation of stem cells.</p></div>","PeriodicalId":100803,"journal":{"name":"Journal of Medical Hypotheses and Ideas","volume":"9 1","pages":"Pages 24-28"},"PeriodicalIF":0.0,"publicationDate":"2015-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.jmhi.2015.01.003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76492909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The progression of cancer and metastasis formation: An epigenetic hypothesis","authors":"R. Alelú-Paz","doi":"10.1016/j.jmhi.2015.01.001","DOIUrl":"10.1016/j.jmhi.2015.01.001","url":null,"abstract":"<div><p>The molecular mechanisms of tumor metastasis remain largely unknown and undefined. A recent model suggests that a minor population of cells (cancer stem cells) is programmed to preferentially metastasize to specific organs based on their gene expression patterns. These cells have the ability to generate tumors after implantation into animal hosts, to self-renew and give rise to non-stem cells. In this paper I hypothesize that epigenetic mechanisms could play an important role in tumor metastasis through the reorganization of the bivalent chromatin marks in cancer stem cells in three phases: 1) the reprogramming of epigenetic marks in differentiation master regulator genes responsible for the differentiation to one particular lineage 2) the resolution of these bivalent chromatin marks forces cells to develop the necessary mechanisms to migrate to a new niche and 3) the epigenetic activation of the tissue-specific genes associated with the specific target organ and, simultaneously, the repression of genes associated with alternative developmental pathways.</p></div>","PeriodicalId":100803,"journal":{"name":"Journal of Medical Hypotheses and Ideas","volume":"9 1","pages":"Pages 20-23"},"PeriodicalIF":0.0,"publicationDate":"2015-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.jmhi.2015.01.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80346524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Blocking IRES-mediated translation pathway as a new method to treat Alzheimer’s disease","authors":"Q.Y. Liu","doi":"10.1016/j.jmhi.2014.05.001","DOIUrl":"10.1016/j.jmhi.2014.05.001","url":null,"abstract":"<div><p>Scientists theorized that β-amyloid (Aβ) plaques and tau tangles are involved in the development of Alzheimer’s disease (AD), and amyloid precursor protein (APP) produces Aβ to trigger the disease process. However, the normal synaptic function of APP itself is not fully understood. Several findings cast APP as a potential key player in learning and memory under normal condition. Nevertheless, the regular operation of APP will be disrupted by abnormal accumulation of Aβ under cellular pathological conditions. Herein, there is a hypothesis that AD could be treated by attenuating APP synthesis during cellular pathophysiological stress. In virtue of a previous study, it was speculated that cells could not decrease APP synthesis via self-protection maybe because APP is synthesized via internal ribosome entry segment (IRES)-mediated translation. Consequently, the blockage of this translation might be a new inoffensive and high-level specificity treatment.</p></div>","PeriodicalId":100803,"journal":{"name":"Journal of Medical Hypotheses and Ideas","volume":"9 1","pages":"Pages 57-60"},"PeriodicalIF":0.0,"publicationDate":"2015-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.jmhi.2014.05.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90649647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ravinder Jerath , Molly W. Crawford , Vernon A. Barnes
{"title":"Functional representation of vision within the mind: A visual consciousness model based in 3D default space","authors":"Ravinder Jerath , Molly W. Crawford , Vernon A. Barnes","doi":"10.1016/j.jmhi.2015.02.001","DOIUrl":"10.1016/j.jmhi.2015.02.001","url":null,"abstract":"<div><p>The human eyes and brain, which have finite boundaries, create a “virtual” space within our central nervous system that interprets and perceives a space that appears boundless and infinite. Using insights from studies on the visual system, we propose a novel fast processing mechanism involving the eyes, visual pathways, and cortex where external vision is imperceptibly processed in our brain in real time creating an internal representation of external space that appears as an external view. We introduce the existence of a three-dimension default space consisting of intrapersonal body space that serves as the framework where visual and non-visual sensory information is sensed and experienced. We propose that the thalamus integrates processed information from corticothalamic feedback loops and fills-in the neural component of 3D default space with an internal visual representation of external space, leading to the experience of visual consciousness. This visual space inherently evades perception so we have introduced three easy clinical tests that can assist in experiencing this visual space. We also review visual neuroanatomical pathways, binocular vision, neurological disorders, and visual phenomenon to elucidate how the representation of external visible space is recreated within the mind.</p></div>","PeriodicalId":100803,"journal":{"name":"Journal of Medical Hypotheses and Ideas","volume":"9 1","pages":"Pages 45-56"},"PeriodicalIF":0.0,"publicationDate":"2015-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.jmhi.2015.02.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82934614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chang-Kui Liu , Cai-xia Jing , Xin-Ying Tan , Juan Xu , Min Hu
{"title":"Using three-dimensional porous internal titanium scaffold or allogenic bone scaffold for tissue-engineering condyle as a novel reconstruction of mandibular condylar defects","authors":"Chang-Kui Liu , Cai-xia Jing , Xin-Ying Tan , Juan Xu , Min Hu","doi":"10.1016/j.jmhi.2013.11.003","DOIUrl":"10.1016/j.jmhi.2013.11.003","url":null,"abstract":"<div><p>Mandibular destruction resulting from tumours, trauma, congenital, ankylosis and other reasons leads to disturbed masticatory function. The ideal goal would be to reconstruct a condyle that is similar to the original. However, each of the condylar reconstruction approaches in current has specific shortcomings. Tissue engineering can provide a method to overcome these difficulties. A tissue-engineered mandibular condyle composed of bone and cartilage has been reported, but the strength and shape of the scaffolds used cannot meet the requirement of the clinical use. Freeze-dried allogenic condylar bone is biocompatible, bioresorbable of low antigenicity and provides the morphology for the condyle similar to the original. It is a good scaffold material for tissue engineering. The three-dimensional porous internal titanium scaffold is also biocompatible; it can be easily made into the shape that we need. The two scaffolds have sufficient mechanical strength before no bone formation. Hence, we hypothesise using a three-dimensional porous titanium scaffold or an allogenic bone scaffold combined with osteogenic, chondrogenic material and bone marrow stromal stem cells <em>in vivo</em> tissue engineering to repair condylar defects. This article discusses the hypotheses.</p></div>","PeriodicalId":100803,"journal":{"name":"Journal of Medical Hypotheses and Ideas","volume":"8 2","pages":"Pages 69-73"},"PeriodicalIF":0.0,"publicationDate":"2014-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.jmhi.2013.11.003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73615538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Faheem Maqbool , Haji Bahadar , Mohammad Abdollahi
{"title":"Science for the benefits of all: The way from idea to product","authors":"Faheem Maqbool , Haji Bahadar , Mohammad Abdollahi","doi":"10.1016/j.jmhi.2014.02.002","DOIUrl":"10.1016/j.jmhi.2014.02.002","url":null,"abstract":"<div><p>Science is a knowledge based on hypotheses, observations, and experiments. From its very beginning science has served the humanity and will continue to do so until the needs of human being are fulfilled. History is rich of many scientists who have contributed to different fields of science free of politics, religion, cast, and region. Every human being must have the right to use science and technology for beneficial purposes. Mutual coordination between academia and industries is extremely important for the growth of science. The spread of ideas is only possible with publication and distribution of information to all in the world. Unpublished new ideas will remain hidden. With no doubt, many of publications and products get the spirit from the very first ideas. It is necessary that all scientists share their ideas, opening new opportunities for others to work in the various aspects. We are of the view that, to find a solution to our problems or satisfy human needs, it is important to ponder new ways in science, generate new ideas and share with others, so the concept of “science for the benefits of all” remain alive forever.</p></div>","PeriodicalId":100803,"journal":{"name":"Journal of Medical Hypotheses and Ideas","volume":"8 2","pages":"Pages 74-77"},"PeriodicalIF":0.0,"publicationDate":"2014-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.jmhi.2014.02.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81158785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Combination of IMOD™ and Arbidol to increase their immunomodulatory effects as a novel medicine to prevent and cure influenza and some other infectious diseases","authors":"Mahmoud Arastoo , Hamid Reza Khorram Khorshid , Ramin Radmanesh , Farhad Gharibdoust","doi":"10.1016/j.jmhi.2014.02.001","DOIUrl":"10.1016/j.jmhi.2014.02.001","url":null,"abstract":"<div><p>Viral diseases such as influenza, which are easily transferable from person to person or even country to country, pose one of the biggest threats to health today. Viruses such as avian influenza viruses (N1H5 and H9N1) have been reported to spread in the present decade and, very recently, the novel coronavirus that has caused many life-threatening illnesses and deaths all around the world has received much attention.</p><p>To prevent these highly contagious viral infections, we have proposed the combination of IMOD™ and Arbidol to increase their immunomodulatory effects as a novel medicine to prevent and cure influenza and some other infectious diseases such as hepatitis B and C. On the one hand, IMOD™ within the last few years has been proven to safely and effectively increase the life expectancy for human immunodeficiency virus (HIV)-infected individuals by increasing CD4 lymphocytes. On the other hand, Arbidol, an antiviral agent has been used safely and effectively in the past two decades to prevent and cure all types of influenza and flu. Therefore, the combination of both in a single dosage to further increase CD4 lymphocytes and interferon gamma (IFN-γ) could be a better choice for treatment of viral infections. This proposal tries to provide enough support and background for approval of a randomized clinical trial by a relevant team of investigators.</p></div>","PeriodicalId":100803,"journal":{"name":"Journal of Medical Hypotheses and Ideas","volume":"8 2","pages":"Pages 53-56"},"PeriodicalIF":0.0,"publicationDate":"2014-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.jmhi.2014.02.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79777567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The possible role of peripherally generated cross-reactive IgG in breakdown of the blood–brain barrier and initiation of multiple sclerosis","authors":"Aram Mokarizadeh , Mohammad Abdollahi , Mohammad-Amin Rezvanfar , Mohammad-Reza Rahmani","doi":"10.1016/j.jmhi.2013.11.002","DOIUrl":"10.1016/j.jmhi.2013.11.002","url":null,"abstract":"<div><p>The initiating event in multiple sclerosis (MS) pathogenesis is not known yet. However, in general, breakdown of the blood-brain barrier (BBB) and subsequent infiltration of immune cells into the central nervous system (CNS) has been thought to be the main initiating event. Nonetheless, the mechanism by which the BBB gets disrupted and allows immune cells to infiltrate into the CNS is not fully understood. Evidence indicates that prior to cellular infiltration, over passing peripherally generated cross-reactive immunoglobulin G (IgG) through the transiently permeable BBB during systemic inflammation, hypoxia, hyperthermia, transient hypertension or acute stresses may cause CNS inflammation, BBB breakdown and then initiation of MS disease. Here, we discuss the possible detailed mechanisms that may be involved in cross-reactive IgG-mediated MS autoimmunity.</p></div>","PeriodicalId":100803,"journal":{"name":"Journal of Medical Hypotheses and Ideas","volume":"8 2","pages":"Pages 63-68"},"PeriodicalIF":0.0,"publicationDate":"2014-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.jmhi.2013.11.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80243386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Beta-amyloid exhibits antagonistic effects on alpha 7 nicotinic acetylcholine receptors in orchestrated manner","authors":"Saeed Sadigh-Eteghad , Mahnaz Talebi , Mehdi Farhoudi , Samad E.J. Golzari , Babak Sabermarouf , Javad Mahmoudi","doi":"10.1016/j.jmhi.2014.01.001","DOIUrl":"10.1016/j.jmhi.2014.01.001","url":null,"abstract":"<div><p>Although beta-amyloid (Aβ) has been regarded as the principal toxic factor in the pathogenesis of Alzheimer’s disease (AD), it plays important physiological roles in phenomena such as neuron survival, synaptic plasticity, and memory formation. There are numerous plausible reasons to assume that all of the mentioned pathological and physiological functions of Aβ may be partially mediated via alpha 7 nicotinic acetylcholine receptor (nAChR). Agonistic and antagonistic aspects of Aβ on nAChRs may explain this paradox in peptide–receptor function. It seems that Aβ shows antagonistic effects on α7 nAChR in a dose-dependent manner, and its pathologic function may partially correlate with antagonization of the receptor.</p><p>If this hypothesis is supported, the related mechanisms of neurotoxicity, neuroprotection, memory formation, and AD pathogenesis might be identified. In addition, such knowledge helps make a more valid interpretation of neuron signaling and a better design of AD animal models. In addition, it may provide new insights into AD therapy development via reducing the amount of Aβ and inhibiting peptide aggregation.</p></div>","PeriodicalId":100803,"journal":{"name":"Journal of Medical Hypotheses and Ideas","volume":"8 2","pages":"Pages 49-52"},"PeriodicalIF":0.0,"publicationDate":"2014-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.jmhi.2014.01.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85716516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}