The Relationship between Diet and Mortality of Cancer and Non-communicable Disease in Japan

Objective: To evaluate the effects of dietary factors on cancer and non-communicable diseases. Methods: A correlation analysis between the consumption of various indicator food and mortality rates of cancer or non-communicable diseases was conducted by collecting secondary data from national nutrition surveys in Japan. Results: The consumption of cereal foods, plant energy and plant protein showed a significant negative correlation with mortality of cancer, heart diseases and diabetes; negatively related to the lung cancer and colon cancer in both sexes; a strong negative correlation with mortality of rectum cancer, liver cancer and prostate cancer in males, and of breast cancer in females; and a significant positive correlation with the stomach cancer in both sexes. The consumption of animal foods, animal energy, animal protein and fat showed a strong positive correlation with cancer, heart diseases and diabetes; a positive relations to lung cancer and colon cancer in both sexes, and rectum cancer, liver cancer and prostate cancer in males and breast cancer in females. On the contrary, a strong negative correlation was found in stomach cancer in both sexes; and esophagus cancer, liver cancer and uterus cancer in females. The consumption of vegetables and fruits showed a weak negative correlation with stomach cancer. Conclusion : The results suggest that diet not only plays a significant role in increasing the risks of some kinds of cancer or non-communicable diseases but also has a preventive effect. It is very important that dietary balance should be emphasized to prevent cancer and non-com-municable diseases.

The roles of the proteasome pathway in signal transduction and neurodegenerative diseases

There are two degradation systems in mammalian cells, autophagy/lysosomal pathway and ubiquitin-proteasome pathway. Proteasome is consist of multiple protein subunits and plays important roles in degradation of short-lived cellular proteins. Recent studies reveal that proteasomal degradation system is also involved in signal transduction and regulation of various cellular functions. Dysfunction or dysregulation of proteasomal function may thus be an important pathogenic mechanism in certain neurological disorders. This paper reviews the biological functions of proteasome in signal transduction and its potential roles in neurodegenerative diseases.

Wnt signaling in disease and in development

The highly conserved Wnt secreted proteins are critical mediators of cell-to-cell signaling during development of animals. Recent biochemical and genetic analyses have led to significant insight into understanding how Wnt signals work. The catalogue of Wnt signaling components has exploded. We now realize that multiple extracellular, cytoplasmic, and nuclear components modulate Wnt signaling. Moreover, receptor-ligand specificity and multiple feedback loops determine Wnt signaling outputs. It is also clear that Wnt signals are required for adult tissue maintenance. Perturbations in Wnt signaling cause human degenerative diseases as well as cancer.

Neurogenic bowel dysfunction in patients with spinal cord injury, myelomeningocele, multiple sclerosis and Parkinson’s disease

Exciting new features have been described concerning neurogenic bowel dysfunction,including interactions between the central nervous system,the enteric nervous system,axonal injury,neuronal loss,neurotransmission of noxious and non-noxious stimuli,and the fields of gastroenterology and neurology.Patients with spinal cord injury,myelomeningocele,multiple sclerosis and Parkinson's disease present with serious upper and lower bowel dysfunctions characterized by constipation,incontinence,gastrointestinal motor dysfunction and altered visceral sensitivity.Spinal cord injury is associated with severe autonomic dysfunction,and bowel dysfunction is a major physical and psychological burden for these patients.An adult myelomeningocele patient commonly has multiple problems reflecting the multisystemic nature of the disease.Multiple sclerosis is a neurodegenerative disorder in which axonal injury,neuronal loss,and atrophy of the central nervous system can lead to permanent neurological damage and clinical disability.Parkinson's disease is a multisystem disorder involving dopaminergic,noradrenergic,serotoninergic and cholinergic systems,characterizedby motor and non-motor symptoms.Parkinson's disease affects several neuronal structures outside the substantia nigra,among which is the enteric nervous system.Recent reports have shown that the lesions in the enteric nervous system occur in very early stages of the disease,even before the involvement of the central nervous system.This has led to the postulation that the enteric nervous system could be critical in the pathophysiology of Parkinson's disease,as it could represent the point of entry for a putative environmental factor to initiate the pathological process.This review covers the data related to the etiology,epidemiology,clinical expression,pathophysiology,genetic aspects,gastrointestinal motor dysfunction,visceral sensitivity,management,prevention and prognosis of neurogenic bowel dysfunction patients with these neurological diseases.Embryological,morphological and experimental studies on animal models and humans are also taken into account.

Etiology for Degenerative Disc Disease

Degenerative disc disease is a multifaceted progressive irreversible condition and an inevitable part of aging,which has been found to be a contributing factor for low back pain and might cause radiculopathy,myelopathy,spinal stenosis,degenerative spondylolisthesis,and herniations.Its etiology is complex and multifactorial.Although genetics influence more dominant,the occupational and mechanical influences still persist as a major risk factor.This review emphasizes up-to-date knowledge regarding etiology of disc degeneration with special consideration on occupational,lifestyle factors,and genetic polymorphisms.

Impact of miRNAs on cardiovascular aging

Aging is a multidimensional process that leads to an increased risk of developing severe diseases, such as cancer and cardiovascular, neurodegenerative, and immunological diseases. Recently, small non-coding RNAs known as microRNAs （miRNAs） have been shown to regulate gene expression, which contributes to many physiological and pathophysiological processes in humans. Increasing evidence suggests that changes in miRNA expression profiles contribute to cellular senescence, aging and aging-related diseases. However, only a few miRNAs whose functions have been elucidated have been associated with aging and/or aging-related diseases. This article reviews the currently available findings regarding the roles of aging-related miRNAs, with a focus on cardiac and cardiovascular aging.

Aortic valve stenosis： treatments options in elderly high-risk patients

In the last decades, a trend towards a worldwide aging has been reported and diseases which are common in the elderly people would have important implications in clinical practice. Aortic stenosis （AS） is perhaps the most common and most often cause of sudden death among valvular heart diseases. Its prevalence is low among adults aged 〈 60 years, but increases to almost 10% in adults ≥ 80 years.[2] Since the degenerative calcific disease represents the lead- ing cause of AS in developed countries, the improved understanding on its pathogenesis （atherosclerotic processes and/or skeleton key） may offer potentially new targets for preventing and inhibiting AS development and progres- sion.[3] Patients with AS are generally asymptomatic for a prolonged period and the development of symptoms is a critical point in the natural history. Indeed, the prognosis changes dramatically with the onset of symptoms of angina,

Targeting voltage-gated sodium channels for treatment for chronic visceral pain

Voltage-gated sodium channels (VGSCs) play a fundamental role in controlling cellular excitability,and their abnormal activity is related to several pathological processes,including cardiac arrhythmias,epilepsy,neurodegenerative diseases,spasticity and chronic pain.In particular,chronic visceral pain,the central symptom of functional gastrointestinal disorders such as irritable bowel syndrome,is a serious clinical problem that affects a high percentage of the world population.In spite of intense research efforts and after the dedicated decade of pain control and research,there are not many options to treat chronic pain conditions.However,there is a wealth of evidence emerging to give hope that a more refined approach may be achievable.By using electronic databases,available data on structural and functional properties of VGSCs in chronic pain,particularly functional gastrointestinal hypersensitivity,were reviewed.We summarize the involvement and molecular bases of action of VGSCs in the pathophysiology of several organic and functionalgastrointestinal disorders.We also describe the efficacy of VGSC blockers in the treatment of these neurological diseases,and outline future developments that may extend the therapeutic use of compounds that target VGSCs.Overall,clinical and experimental data indicate that isoform-specific blockers of these channels or targeting of their modulators may provide effective and novel approaches for visceral pain therapy.

A panel of monoclonal antibodies against the prion protein proves that there is no prion protein in human pancreatic ductal epithelial cells

Prion diseases are a group of neurodegenerative diseases that are fatal. The study of these unique diseases in China is hampered by a lack of resources. Amongst the most important resources for biological study are monoclonal antibodies. Here, we characterize a panel of monoclonal antibodies specific for cellular prion protein by enzyme-linked immunosorbent assay(ELISA), immunofluorescent staining, flow cytometry, and western blotting. We identify several antibodies that can be used for specific applications and we demonstrate that there is no prion protein expression in human pancreatic ductal epithelial cells(HPDC).

The complex role of physical exercise and reactive oxygen species on brain

Reactive oxygen species （ROS） are continuously generated during aerobic metabolism and at moderate level. They play a role in redox signaling, but in significant concentration they cause oxidative damage and neurodegeneration. Because of the enhanced sensitivity of brain to ROS, it is especially important to maintain the normal redox state in different types of neuron cells. In last decade it became clear that regular exercise beneficially affects brain function, and can play an important preventive and therapeutic role in stroke, Alzheimer, and Parkinson diseases. The effects of exercise appear to be very complex and could include neurogenesis via neurotrophic factors, increased capillariszation, decreased oxidative damage, and increased proteolyfic degradation by proteasome and neprilysin. Data from our and other laboratories indicate that exercise-induced modulation of ROS levels plays a role in the protein content and expression of brain-derived neurotrophic factor, tyrosinerelated kinase B （TrkB）, and cAMP response element binding protein, resulting in better function and increased neurogenesis. Therefore, it appears that exercise-induced modulation of the redox state is an important means, by which exercise benefits brain function, increases the resistance against oxidative stress, facilitates recovery from oxidative stress, and attenuates age-associated decline in cognition.

Globular adiponectin induces differentiation and fusion of skeletal muscle cells

The growing interest in skeletal muscle regeneration is associated with the opening of new therapeutic strategies for muscle injury after trauma, as well as several muscular degenerative pathologies, including dystrophies, muscu- lar atrophy, and cachexia. Studies focused on the ability of extracellular factors to promote myogenesis are therefore highly promising. We now report that an adipocyte-derived factor, globular adiponectin （gAd）, is able to induce mus- cle gene expression and cell differentiation, gAd, besides its well-known ability to regulate several metabolic func- tions in muscle, including glucose uptake and consumption and fatty acid catabolism, is able to block cell cycle entry of myoblasts, to induce the expression of specific skeletal muscle markers such as myosin heavy chain or caveolin-3, as well as to provoke cell fusion into multinucleated syncytia and, finally, muscle fibre formation, gAd exerts its pro- differentiative activity through redox-dependent activation of p38, Akt and 5＇-AMP-activated protein kinase path- ways. Interestingly, differentiating myoblasts are autocrine for adiponectin, and the mimicking of pro-inflammatory settings or exposure to oxidative stress strongly increases the production of the hormone from differentiating cells. These data suggest a novel function of adiponectin, directly coordinating the myogenic differentiation program and serving an autocrine function during skeletal myogenesis.

Polyglutamine toxicity in non-neuronal cells

The neurodegenerative polyglutamine diseases are caused various disease proteins. Although these mutant proteins are by an expansion of unstable polyglutamine repeats in expressed ubiquitously in neuronal and non-neuronal cells, they cause selective degeneration of specific neuronal populations. Recently, increasing evidence shows that polyglutamine disease proteins also affect non-neuronal cells. However, it remains unclear how the expression of polyglutamine proteins in non-neuronal cells contributes to the course of the polyglutamine diseases. Here, we discuss recent findings about the expression of mutant polyglutamine proteins in non-neuronal cells and their influence on neurological symptoms. Understanding the contribution of non-neuronal polyglutamine proteins to disease progres- sion will help elucidate disease mechanisms and also help in the development of new treatment options.

Electromagnetic Pollution and Human Health

The electromagnetic fields surrounding the electric and communication installations are blamed not only for cancerigenic effects, but also for negative influences on the natural electrophysiological phenomena and ＂accused＂ of causing some degenerative diseases of the nervous system, genetic modifications with hereditary effects, mental and behavioural disturbances. This research aimed to highlight that Directive 2008 / 46 / EC had a series of positive aspects as well as drawbacks. Directive 2008 / 46 / EC of the European Parliament and of the Council amending Directive 2004 / 40 / EC on the minimum health and safety requirements regarding the exposure of workers to the risks arising from physical agents （electromagnetic fields） is criticized because these norms should regard not only the category of those working in different domains, but also the large category of consumers （of cell phones, microwave ovens, computers, etc.）.

Hepatitis B virus prevalence and transmission risk factors in inflammatory bowel disease patients at Clementino Fraga Filho university hospital

AIM: To evaluate the prevalence of hepatitis B virus (HBV) infection in inflammatory bowel disease (IBD) patients that followed up in our hospital and try to identify the possible risk factors involved in this infection transmission. METHODS: This was a cross-sectional study for which 176 patients were selected according to their arrival for the medical interview. All these patients had already IBD diagnosis. The patient was interviewed and a questionnaire was filled out. RESULTS: In the group of 176 patients whom we examined, we found that 17% (30) were anti-HBc positive. Out of 30 patients with positive anti-HBc, 2.3% (4) had positive HBsAg and negative HBV-DNA. In an attempt to identify the possible HBV infection transmission risk factors in IBD patients, it was observed that 117 patients had been submitted to some kind of surgical procedure, but only 24 patients had positive anti-HBc (P = 0.085). It was also observed that surgery to treat IBD complications was not a risk factor for HBV infection transmission, since we did not get a statically significant P value. However, IBDpatients that have been submitted to surgery to treat IBD complications received more blood transfusions then patients submitted to other surgical interventions (P = 0.015). CONCLUSION: There was a high incidence of positive anti-HBc (17%) and positive HBsAg (2.3%) in IBD patient when compared with the overall population (7.9%).

Comparative Alternative Medicinal （CAM） Properties in Camel Milk for Treatment of Epidemic Diseases

This communication brings scientific evidence to explain the basis for efficacy of camel milk, especially on diseases where the immune system is compromised. Camels （Camelu sdromedarius） have very small and active antibodies, nanaobodies. Their special properties are being used by the USA Department of Homeland Security as bio-receptors to determine which substance could be used in a biological warfare attack. The antibodies are part of the ＂protective proteins＂ in camel milk. These include potent antibacterial, antiviral and antifungal properties. Camel milk antibodies are, in fact, ＂nanobodies＂. They are not destroyed in their passage through the stomach. These nanobodies are responsible for data concerning the use of camel milk in autoimmune diseases. Various diseases treated with camel milk are presented, as is the mode of action. The effect of pasteurization on activity of camel milk is presented as a way to overcome the need for heat. This is accomplished by presenting ＂pathogen-free＂ camel milk. The antibodies are part of the ＂protective proteins＂ in camel milk. These include potent antibacterial, antiviral and antifungal properties. The effect of pasteurization on activity of camel milk is presented as a way to overcome the need for heat. This is accomplished by presenting ＂pathogen-free＂ camel milk.

Development of a Zebrafish Model for Rapid Drug Screening against Alzheimer＇s Disease

Alzheimer＇s disease, the leading cause of dementia in the elderly, is a complex neurodegenerative disorder which leads to a progressive decline in cognitive functions. A rapid screening model is highly demanded for identification and evaluation of novel anti-Alzheimer＇s disease drugs from a large numbers of compounds. Until now, numerous studies utilized zebrafish model for drug discovery. Since aluminum can induce a similar biological activity in zebrafish as in Alzheimer patients, in this study, we developed a novel animal model using 3 to 5 day post-fertilization larval zebrafish by optimizing the doses and duration of aluminum chloride exposure. Six anti-Alzheimer＇s disease drugs with a variety of mechanisms were tested to validate the newly developed zebrafish model. Importantly, Rivastigmine, ThT, Flurbiprofen and AM-117 could increase the value of Dyskinesia Recovery Rate by 53.4-64%, 169.4-200%, 54.5-96% and 70.9-121%, respectively. Rivastigmine, Memantine, ThT, Flurbiprofen, Rosiglitazone and AM-117 improved the value of Response Efficiency by 86.6-175.1%, 28.2-66.6%, 127.2-236.5%, 118.3-323.7%, 26.6-140.8% and 70.2-161.4%, respectively. Our results suggest that the zebrafish model developed in this study could be a useful tool for high throughput screening of potential novel anti-Alzheimer＇s disease leading compounds targeting acetylcholinesterase, N-methyl-D-aspartic acid receptor, γ-secretase, peroxisome proliferator-activated receptor-γand amyloid-β.

Squamous cell cancer of the rectum

Squamous cell carcinoma of the rectum is a rare malignancy.It appears to be associated with chronic inflammatory conditions and infections.The clear association seen between Human Papilloma Virus and various squamous cancers has not been firmly established for the squamous cell cancer of the rectum. The presentation is nonspecific and patients tend to present with advanced stage disease.Diagnosis relies on endoscopic examination with biopsy of the lesion.Distinction from squamous cell cancer of the anus can be difficult,but can be facilitated by immunohistochemical staining for cytokeratins.Staging of the cancer with endoscopic ultrasound and computed tomography provides essential information on prognosis and can guide therapy.At present,surgery remains the main therapeutic option;however recent advances have made chemoradiation a valuable therapeutic addition. Squamous cell carcinoma of the rectum is a distinct entity and it is of crucial importance for the practicing Gastroenterologist to be thoroughly familiar with this disease.Compared to adenocarcinoma of the rectum and squamous cell cancer of the anal canal,squamous cell carcinoma of the rectum has different epidemiology, etiology,pathogenesis,and prognosis but,most importantly,requires a different therapeutic approach. This review will examine and summarize the available information regarding this disease from the perspective of the practicing gastroenterologist.

Hemorrhagic Fever with Renal Syndrome Associated with Acute Pancreatitis

Hemorrhagic fever with renal syndrome (HFRS) is a systemic infectious disease caused by Hantaviruses and characterized by fevers, bleeding tendencies, gastrointestinal symptoms and renal failure. It encompasses a broad spectrum of clinical presentations, ranging from unapparent or mild illnesses to fulminant hemorrhagic processes. Among the various complications of HFRS, acute pancreatitis is a rare find. In this report, based on clinical data, laboratory and radiologic examination findings, we describe a clinical case, with HFRS from Dobrava virus, associated with acute pancreatitis. The patient was successfully treated by supportive management. Clinicians should be alert to the possibility of HFRS when examining patients with epidemiological data and symptoms of acute pancreatitis.

Association of hepatitis C virus infection and diabetes

Epidemiologic studies have suggested a relation between hepatitis C virus (HCV) infection and diabetes mellitus. HCV infection is emerging as a metabolic disease, and diabetes mellitus as a risk factor for HCV infection. However, some data on the prevalence of antibodies to HCV in patients with diabetes are conflicting. These seroprevalence data should be interpreted with caution. Some potential bias may occur in those clinic-based studies that target a specif ic disease group. In this letter we explain some reasons for these conflicting studies.

PrP 106-126 Altered PrP mRNA Gene Expression in Mouse Microglia BV-2 Cells

Prion diseases are infectious and fatal neurodegenerative diseases.The pathogenic agent is an abnormal prion protein aggregate.Microglial activation in the centre nervous system is a characteristic feature of prion disease.In this study,we examined the effect of PrP 106-126 on PrP mRNA gene expression in Mouse microglia cells BV-2 by real-time quantitative PCR.PrP mRNA expression level was found to be significantly increased after 18 h exposure of BV-2 cells to PrP 106-126,with 3-fold increase after 18 h and 4.5-fold increase after 24 h and BV-2 cells proliferating occurred correspondingly.Our results provide the first in vitro evidence of the increase of PrP mRNA levels in microglial cells exposed to PrP 106-126,and indicate that microglial cells might play a critical role in prion pathogenesis.