Effects of dragon’s blood resin and its component loureirin B on tetrodotoxin-sensitive voltage-gated sodium currents in rat dorsal root ganglion neurons

Using whole-cell patch clamp technique on the membrane of freshly isolated dorsal root ganglion (DRG) neurons, the effects of dragon’s blood resin and its important component loureirin B on tetrodotoxin-sensitive (TTX-S) voltage-gated sodium currents were observed. The results show that both blood resin and loureirin B could suppress TTX-S voltage-gated sodium currents in a dose-dependent way. The peak current amplitudes and the steady-state activation and inactivation curves are also made to shift by 0.05% blood resin and 0.2 mmol/L loureirin B. These results demonstrate that the effects of blood resin on TTX-S sodium current may contribute to loureirin B in blood resin. Perhaps the analgesic effect of blood resin is caused partly by loureirin B directly interfering with the nociceptive transmission of primary sensory neurons.     

Selenium supplementation on plasma glutathione peroxidase activity in patients with end-stage chronic renal failure

Patients with chronic renal failure (CRF) usually have a lower than healthy level of selenium (Se) in whole blood and plasma. Plasma glutathione peroxidase (GSH-Px) is synthesized mostly in the kidney. In CRF patients, activity of this enzyme is significantly reduced and its reduction increases with the progress of the disease. The aim of the study was to evaluate the effect of Se supplementation to CRF patients at various stages of the disease on Se concentration in blood components and on plasma GSH-Px activity. The study group comprised 53 CRF patients at various stages of the disease supplemented with Se (200 μg/d for 3 mo as Se-enriched yeast, containing about 70% l-selenomethionine [SeMet]). The control group consisted of 20 healthy subjects. The Se concentration in blood components was measured spectrofluorometrically with 2,3-diaminonaphthalene as a complexing reagent. GSH-Px activity in red cell hemolysates and plasma was assayed by the coupled method with tert-butyl hydroperoxide as a substrate. The Se concentration in whole blood and plasma of CRF patients is significantly lower as compared with healthy subjects, but similar at all stages of the disease. In the patients’ plasma, total protein and albumin levels are also significantly lower than in healthy subjects. Plasma GSH-Px activity in patients is extremely low, and contrary to Se concentration, it decreases linearly with the increasing stage of the illness. Se-supplied patients show an increased Se concentration in all blood components and at all disease stages, whereas plasma GSH-Px activity is enhanced only at the incipient stage of the disease. Se supply has no effect on plasma GSH-Px activity in uremic patients at the end stage of the disease. Total plasma protein and albumin levels did not change after Se supplementation. Our data seem to show that in patients with CRF lower total protein and albumin levels in plasma may be the chief cause of the low blood and plasma Se concentrations. GSH-Px activity decreases along with the kidney impairment. At the end stage of the disease, Se supplementation in the form of Se-enriched yeast has no effect on the increase in plasma GSH-Px activity.     

The Involvement of Lipids in Alzheimer's Disease

It has been estimated that Alzheimer＇s disease （AD）, the most common form of dementia, will affect approximately 81 million individuals by 2040. To date, the actual cause and cascade of events in the progression of this disease have not been fully determined. Furthermore, there is currently no definitive blood test or simple diagnostic method for AD. Considerable efforts have been put into proteomic approaches to develop a diagnostic blood test, but to date these efforts have not been successful. More recently, there has been a stronger focus on lipidomic studies in the hope of increasing our understanding of the underlying mechanisms leading to AD and developing an AD blood test. It is well known that the strongest genetic risk factor for AD is the e4 variant of apolipoprotein E （APOE）. Evidence suggests that the ApoE protein, a major lipid transporter, plays a key role in the pathogenesis of AD, and its role in both normal and aberrant lipid metabolism warrants further extensive investigation. Here, we review ApoE-lipid interactions, as well as the roles that lipids may play in the pathogenesis of AD.     

Biomarkers of Alzheimer’s disease in body fluids

Various innovative diagnostic methods for Alzheimer’s disease (AD) have been developed in view of the increasing preva-lence and consequences of later-life dementia. Biomarkers in cerebrospinal fluid (CSF) and blood for AD are primarily based on the detection of components derived from amyloid plaques and neurofibrillary tangles (NFTs). Published reports on CSF and blood biomarkers in AD indicate that although biomarkers in body fluids may be utilized in the clinical diagnosis of AD, there are no specific markers that permit accurate and reliable diagnosis of early-stage AD or the monitoring of disease pro-gression.     

Zn concentration in thyroid tissue and whole blood of women with different diseases of thyroid

The Zn concentration in thyroid tissue and whole blood of patients with Graves’ disease, thyroid cancer, and nodular goiter disease was determined using the total-reflection X-ray fluorescence method. The dependence of obtained concentrations on the clinical stage of the examined disease, histopathological grading, and kind of analyzed material (thyroid tissue and blood) was studied. The determined concentration of Zn was the lowest in the thyroid tissue of patients with thyroid cancer (23.1 μg/g) and it was the highest in the case of Graves’ disease (41.7 μg/g), whereas in the blood samples, the reverse results were found (7.1 μg/g and 4.8 μg/g, respectively). The physical basis of the method used, the experimental setup, and the procedure of sample preparation are described.     

Delayed information induces oscillations in a dynamical model for infectious disease

During disease outbreak,it has been observed that information about the disease prevalence induces the individuafs behavioral changes.This information is usually assumed to be generated by the density of infective individuals and active mass media.The delay in reporting of these infective individuals may have its impact on generated information.Hence,to study the impact of delay on information generation,and therefore on the disease dynamics,a delay differential equation model is proposed and analyzed.The dynamics of information with delay effect is also modeled by a separate rate equation.Model analysis is performed and a unique infected equilibrium is obtained when the basic reproduction number(R0)is greater than one,whereas the disease free equilibrium always exists.When R0<1,the disease free equilibrium is found to be locally stable independent of delay effect.The unique infected equilibrium is found to be locally stable till delay reaches a threshold value.The global stability of the unique infected equilibrium is also established under some parametric conditions by constructing a suitable Lyapunov function.The occurrence of Hopf bifurcation is observed when the delay in information crosses the threshold value.Analytically,the direction and stability of bifurcating periodic solutions is established.Further,we observed the occurrence of Hopf-Hopf bifurcation at two different delays.At first delay threshold,the endemic equilibrium loses its st ability and produces periodic oscillations via Hopf bifurcation.It further regains its stability at second delay threshold via another Hopf bifurcation.Hence,the delay effect on information shows possibility of stability switches.Numerical experiments are carried out to support the obtained analytical results.Our study infers that the disease will show persistent oscillations if there is a significant time lag in reporting of infective after the disease outbreak.Thus,the delay in dissemination of information shows rich and complex dynamics in the model and provides important insights.We also observe numerically that the saturation in information plays a significant role on stability of infected equilibrium in presence of delay.     

HIV and HCV： from Co-infection to Epidemiology, Transmission, Pathogenesis, and Treatment

Human immunodeficiency virus (HIV) is the infectious agent causing acquired immu-nodeficiency syndrome (AIDS),a deadliest scourge of human society. Hepatitis C virus (HCV) is a major causative agent of chronic liver disease and infects an estimated 170 million people worldwide,resulting in a serious public health burden. Due to shared routes of transmission,co-infection with HIV and HCV has become common among individuals who had high risks of blood exposures. Among hemophiliacs the co-infection rate accounts for 85%; while among injection drug users (IDU) the rate can be as high as 90%. HIV can accelerate the progression of HCV-related liver disease,particularly when immunodeficiency has developed. Although the effect of HCV on HIV infection is controversial,most studies showed an increase in mortality due to liver disease. HCV may act as a direct cofactor to fasten the progression of AIDS and decrease the tolerance of highly active antiretroviral therapy (HARRT). Conversely,HAART-related hepatotoxicity may enhance the progression of liver fibrosis. Due to above complications,co-infection with HCV and HIV-1 has imposed a critical challenge in the management of these patients. In this review,we focus on the epidemiology and transmission of HIV and HCV,the impact of the two viruses on each other,and their treatment.     

Modulation of dragon’s blood on tetrodotoxin-resistant sodium currents in dorsal root ganglion neurons and identification of its material basis for efficacy

To clarify the modulation of dragon's blood on the tetrodotoxin-resistant (TTX-R) sodium currents in dorsal root ganglion (DRG) neurons and explore its corresponding material basis for the efficacy, using whole-cell patch clamp technique, the effects of dragon's blood and the combined effects of three components (cochinchinenin A, cochinchinenin B, and loureirin B) extracted from dragon's blood on the TTX-R sodium currents in acute-isolated DRG neurons of rats were observed. According to the operational definition of material basis for the efficacy of TCM established, the material basis of the modulation on the TTX-R sodium currents in DRG neurons of dragon's blood was judged from the experimental results. The drug interaction equation of Greco et al. was used to assess the interaction of the three components extracted from dragon's blood. This investigation demonstrated that dragon's blood suppressed the peak TTX-R sodium currents in a dose-dependent way and affected the activations of TTX-R sodium currents. The effects of the combination of cochinchinenin A, cochinchinenin B, and loureirin B were in good agreement with those of dragon's blood. Although the three components used alone could modulate TTX-R sodium currents, the concentrations of the three components used alone were respectively higher than those used in combination when the inhibition rates on the TTX-R sodium currents of them used alone and in combination were the same. The combined effects of the three components were synergistic. These results suggested that the interference with pain messages caused by the modulation of dragon's blood on TTX-R sodium currents in DRG neurons may explain some of the analgesic effect of dragon's blood and the corresponding material basis for the efficacy is the combination of cochinchinenin A, cochinchinenin B, and loureirin B.     

Modulation of dragon's blood on tetrodotoxin-resistant sodium currents in dorsal root ganglion neurons and identification of its material basis for efficacy

To clarify the modulation of dragon's blood on the tetrodotoxin-resistant (TTX-R) sodium currents in dorsal root ganglion (DRG) neurons and explore its corresponding material basis for the efficacy, using whole-cell patch clamp technique, the effects of dragon's blood and the combined effects of three components (cochinchinenin A, cochinchinenin B, and loureirin B) extracted from dragon's blood on the TTX-R sodium currents in acute-isolated DRG neurons of rats were observed. According to the operational definition of material basis for the efficacy of TCM established, the material basis of the modulation on the TTX-R sodium currents in DRG neurons of dragon's blood was judged from the experimental results. The drug interaction equation of Greco et al. was used to assess the interaction of the three components extracted from dragon's blood. This investigation demonstrated that dragon's blood suppressed the peak TTX-R sodium currents in a dose-dependent way and affected the activations of TTX-R sodium currents. The effects of the combination of cochinchinenin A, cochinchinenin B, and loureirin B were in good agreement with those of dragon's blood. Although the three components used alone could modulate TTX-R sodium currents, the concentrations of the three components used alone were respectively higher than those used in combination when the inhibition rates on the TTX-R sodium currents of them used alone and in combination were the same. The combined effects of the three components were synergistic. These results suggested that the interference with pain messages caused by the modulation of dragon's blood on TTX-R sodium currents in DRG neurons may explain some of the analgesic effect of dragon's blood and the corresponding material basis for the efficacy is the combination of cochinchinenin A, cochinchinenin B, and loureirin B.     

蛇与人微循环血流健康长寿初探

<正>一、蛇与人微循环血流-健康-亚健康-疾病发生、发展、转归生命科学基础临床探索。Basic clinical exploration of life science on the relationship between snake and the occurrence,development,transfer of human microcirculatory blood flow-health-sub-health-disease.二、微循环血流不畅是引起疾病,有碍健康,促进衰老损寿的早期主要原因。Obstruction of microcirculatory blood flow is the main reason,which will cause disease,harm the human body,promote senescence and reduce life in the early stage.     

Resin foraging dynamics in Varroa destructor-infested hives: a case of medication of kin?

t Social insects have evolved colony behavioral, physiological, and organiza. tional adaptations (social immunity) to reduce the risks of parasitization and/or disease transmission. The collection of resin from various plants and its use in the hive as propolis is a clear example of behavioral defense. For Apis mellifera, an increased propolis content in the hive may correspond to variations in the microbial load of the colony and to a downregulation of an individual bee's immune response. However, many aspects of such antimicrobial mechanism still need to be clarified. Assuming that bacterial and fungal infection mechanisms differ from the action of a parasite, we studied the resin collection dynamics in Varroa destructor-infested honeybee colonies. Comparative experiments involving hives with different mite infestation levels were conducted in order to assess the amount of resin collected and propolis quality within the hive, over a 2-year period (2014 and 2015). Our study demonstrates that when A. mellifera colonies are under stress because of Varroa infestation, an increase in the number of resin foragers is recorded, even if a general intensification of the foraging activity is not observed. A reduction in the total polyphenolic content in propolis produced in infested versus uninfested hives was also noticed. Considering that different propolis types show varying levels of inhibition against a variety of honey bee pathogens in vitro, it would be very important to study the effects against Varroa of two diverse types of propolis: from Varroa-free and from Varroa-infested hives.     

What have we learned about the kallikrein-kinin and renin-angiotensin systems in neurological disorders?

The kallikrein-kinin system(KKS) is an intricate endogenous pathway involved in several physiological and pathological cascades in the brain. Due to the pathological effects of kinins in blood vessels and tissues, their formation and degradation are tightly controlled. Their components have been related to several central nervous system diseases such as stroke, Alzheimer's disease, Parkinson's disease, multiple sclerosis, epilepsy and others. Bradykinin and its receptors(B1R and B2R) may have a role in the pathophysiology of certain central nervous system diseases. It has been suggested that kinin B1R is up-regulated in pathological conditions and has a neurodegenerative pattern, while kinin B2R is constitutive and can act as a neuroprotective factor in many neurological conditions. The renin angiotensin system(RAS) is an important blood pressure regulator and controls both sodium and water intake. AngⅡ is a potent vasoconstrictor molecule and angiotensin converting enzyme is the major enzyme responsible for its release. AngⅡ acts mainly on the AT1 receptor, with involvement in several systemic and neurological disorders. Brain RAS has been associated with physiological pathways, but is also associated with brain disorders. This review describes topics relating to the involvement of both systems in several forms of brain dysfunction and indicates components of the KKS and RAS that have been used as targets in several pharmacological approaches.     

Cytoskeletal changes in diseases of the nervous system

The neuronal cytoskeleton not only provides the structural backbone of neurons, but also plays a fundamental role in maintaining neuronal functions. Dysregulation of neuronal architecture is evident in both injury and diseases of the central nervous system. These changes often result in the disruption of protein trafficking, loss of synapses and the death of neurons, ultimately impacting on signal transmission and manifesting in the disease phenotype. Furthermore, mutations in cytoskeletal proteins have been implicated in numerous diseases and, in some cases, identified as the cause of the disease, highlighting the critical role of the cytoskeleton in disease pathology. This review focuses on the role of cytoskeletal proteins in the pathology of mental disorders, neurodegenerative diseases and motor function deficits. In particular, we illustrate how cytoskeletal proteins can be directly linked to disease pathology and progression.     

Identification of a NF-кB site in the negative regulatory element (ε-NRAII) of human ε-globin gene and its binding protein NF-кB p50 in the nuclei of K562 cells

INTRODUCTIONThe human P-like globin genes are arranged as acluster of five genes(e, Gry, Ary, 8 and P) in the orderof their temporal expression. The human embryonicE-globin gene is expressed in the blood island of theembryonic yolk sac and is silenced completely at 6~8w of gestation in the fetal liverI11. Studies on trans-genic mice suggested that the regulation of 5-globingene expression is autonomous. The activating andsilencing of 5-globin gene expression rely on distallocus control …     

The progress of abnormal expression of Lutheran blood group glycoprotein in cancers

Lutheran blood group glycoprotein (Lu-gp) is a specific α5 laminin receptor that is linked by binding to its receptor in the basement membrane matrix. Although the biological function of Lu-gp is unknown, its special affinity with laminin in the chain suggests that it plays an important role in human development and physiological processes. As the interaction between Lu-gp and laminin is further investigated, their expression may be found to play an important role in tumor invasion and metastasis. Laminin receptors help cells adhere, receive and conduct extracellular information into cells, mainly through MAPK pathways, including ERKs, p38MAPK, etc., affecting the degradation of the extracellular matrix and enhancing tumor cell infiltration and metastasis. Present researches in cancers mainly focus on aspects relating to laminin, but largely do not pay attention to the Lutheran blood group antigen, basal cell adhesion molecule. This paper focuses on the abnormal expression of the laminin receptor, that is, the Lutheran blood group antigen, in cancers, which is of great significance to the mechanism of cancer invasion and metastasis, and for finding effective treatment methods for cancers.     

Quantitative assessment of acute kidney injury by noninvasive arterial spin labeling perfusion MRI:a pilot study

The kidneys are essential for maintaining homeostasis,are responsible for the reabsorption of water,glucose and amino acids,and filter the blood by removing waste.Acute kidney injury(AKI) is a syndrome characterized by the rapid loss of renal excretory function and the accumulation of end metabolic products of urea and creatinine.AKI is associated with the later development of chronic kidney disease and end-stage kidney disease,and may eventually be fatal.Early diagnosis of AKI and assessments of the effects of treatment,however,are challenging.The pathophysiological mechanism of AKI is thought to be the imbalance between oxygen supply and demand in the kidneys.We have assessed the ability of arterial spin labeling(ASL) perfusion magnetic resonance imaging(MRI),without the administration of contrast media,to quantify renal blood flow(RBF) non-invasively.We found that RBF was significantly lower in AKI patients than in healthy volunteers.These results suggest that ASL perfusion MRI,a noninvasive measurement of RBF,may be useful in the early diagnosis of AKI.     

Effects of Three Commonly-used Diuretics on the Urinary Proteome

bstract Biomarker is the measurable change associated with a physiological or pathophysiological process. Unlike blood which has mechanisms to keep the internal environment homeostatic,rine is more likely to reflect changes of the body. As a result, urine is likely to be a better biomarker ource than blood. However, since the urinary proteome is affected by many factors, including iuretics, careful evaluation of those effects is necessary if urinary proteomics is used for biomarker iscovery. Here, we evaluated the effects of three commonly-used diuretics(furosemide, F; hydrochlorothiazide,H; and spirolactone, S) on the urinary proteome in rats. Urine samples were collected before and after intragastric administration of diuretics at therapeutic doses and the roteomes were analyzed using label-free liquid chromatography–tandem mass spectrometry LC–MS/MS). Based on the criteria of P 6 0.05, a fold change P2, a spectral count P5, and false ositive rate(FDR) 61%, 14 proteins(seven for F, five for H, and two for S) were identified by rogenesis LC–MS. The human orthologs of most of these 14 proteins are stable in the healthy uman urinary proteome, and ten of them are reported as disease biomarkers. Thus, our results uggest that the effects of diuretics deserve more attention in future urinary protein biomarker tudies. Moreover, the distinct effects of diuretics on the urinary proteome may provide clues to     

Chronic pancreatitis, pancreatic adenocarcinoma and the black box in-between

Pancreatic cancer is a challenging disease for patients, doctors and researchers who for decades have searched for a cure for this deadly malignancy. Although existing mouse models of pancreatic cancer have shed light on the mechanistic basis of the neoplastic conversion of the pancreas, their impact in terms of offering new diagnostics and therapeutic modalities remains limited. Chronic pancreatitis is an inflammatory disease of the pancreas that is associated with a gradual damage of the organ and an increased risk of developing neoplastic lesions. In this review, we propose that detailed studies of chronic inflammatory processes in the pancreas will provide insights into the evolution of pancreatic cancer. This information may prove useful in the design of effective therapeutic strategies to battle the disease.     

Overview and countermeasures of cancer burden in China

Cancer is one of the leading causes of human death worldwide. Treatment of cancer exhausts significant medical resources, and the morbidity and mortality caused by cancer is a huge social burden. Cancer has therefore become a serious economic and social problem shared globally. As an increasingly prevalent disease in China, cancer is a huge challenge for the country’s healthcare system. Based on recent data published in the Journal of the National Cancer Center on cancer incidence and mortality ...     

Genetics of Nonalcoholic Fatty Liver Disease:An Overview

Nonalcoholic fatty liver disease(NAFLD) is the most common liver disease in the world today.Its incidence in adults and children is rising rapidly due to the ongoing epidemics of obesity and type 2 diabetes.Hence,it has become a global public health issue.Environmental factors have been found to play a major role in the etiology of NAFLD,especially for genetically susceptible populations. Among these,one of the most important factors is junk food,especially the typical "Western-style" diet rich in simple carbohydrates, saturated fat,and highly processed food materials.Genetic predisposition to NAFLD does occur;however,a precise definition of genetic factors responsible for NAFLD is still lacking.Specific variants of different genes have been shown to present a risk for NAFLD.Genetic studies might be helpful in the management of the disease by developing novel treatment strategies based on individual’s genotype.