Cross-talk elimination in determination of gross α and gross β activities using a low-background α/β gas-flow proportional counter / 中国辐射卫生

Objective To explore cross-talk elimination method in the determination of gross α and gross β activities using a low-background α/β gas-flow proportional counter. Methods A CLB-104 low-background α/β gas-flow proportional counter was used in this study. First, the α threshold was increased to eliminate the cross-talk counting caused by β particles in the α channel. Then, the α-β anticoincidence threshold was reduced to eliminate the cross-talk counting induced by low-energy α particles in the β channel, and β counts were corrected to eliminate the counts induced by internal convention electrons in the β channel. Finally, gross α and gross β activities of non-saline water samples with different activity levels were determined and compared with gross α and gross β activities of the same samples determined on a BH1227 low-background α/β solid scintillation counter, in order to verify effectiveness of the cross-talk elimination method. Results By eliminating the cross-talk counts of β particles in the α channel and the cross-talk counts of α particles in the β channel, and deducting the counts of internal convention electrons in the β channel, the gross α and gross β activities of the same samples determined by CLB-104 were consistent with the values determined by BH1227. Conclusion Cross-talk counts induced by low-energy α particles or β particles can be eliminated by threshold adjustment, and the counts caused by internal convention electrons in the β channel can be eliminated by correction.

Triple-negative breast cancer cells respond to T cells severely at the alternative splicing layer

BACKGROUND: Cross talk of tumor­immune cells at the gene expression level has been an area of intense research. However, it is largely unknown at the alternative splicing level which has been found to play important roles in the tumor­immune microenvironment. RESULTS: Here, we re-exploited one transcriptomic dataset to gain insight into tumor­immune interactions from the point of AS level. Our results showed that the AS profiles of triple-negative breast cancer cells co-cultured with activated T cells were significantly changed but not Estrogen receptor positive cells. We further suggested that the alteration in AS profiles in triple-negative breast cancer cells was largely caused by activated T cells rather than paracrine factors from activated T cells. Biological pathway analyses showed that translation initiation and tRNA aminoacylation pathways were most disturbed with T cell treatment. We also established an approach largely based on the AS factor­AS events associations and identified LSM7, an alternative splicing factor, may be responsible for the major altered events. CONCLUSIONS: Our study reveals the notable differences of response to T cells among breast cancer types which may facilitate the development or improvement of tumor immunotherapy.

Neurogenic stress cardiomyopathy: What do we need to know

The interaction between the heart and brain is complex and integral to the maintenance of normal cardiovascular function. Even in the absence of coronary disease, acute neuronal injury can induce a variety of cardiac changes. Recent neuroimaging data revealed a network including the insular cortex, anterior cingulate gyrus, and amygdala playing a crucial role in the regulation of central autonomic nervous system. Damage in these areas has been associated with arrhythmia, myocardial injury, higher plasma levels of brain natriuretic peptide, catecholamines, and glucose. Some patients after brain injury may die due to occult cardiac damage and functional impairment in the acute phase. Heart failure adversely influences acute stroke mortality. Troponin and NT-proBNP are elevated in acute brain injury patients, in response to the activated renin–angiotensin–aldosterone system and other neurohumoral changes, as a protective mechanism for sympathoinhibitory activity. Such patients have been shown to be associated with higher short- and long-term mortality. While thrombolysis, neuroprotection, and other measures, alone or in combination, may limit the cerebral damage, attention should also be directed toward the myocardial protection. Early administration of cardioprotective medication aimed at reducing increased sympathetic tone may have a role in myocardial protection in stroke patients. For a full understanding of the brain–heart control, the consequences of disruption of this control, the true incidence of cardiac effects of stroke, and the evidence-based treatment options further research are needed.

Predicting pathway cross-talks in ankylosing spondylitis through investigating the interactions among pathways

Given that the pathogenesis of ankylosing spondylitis (AS) remains unclear, the aim of this study was to detect the potentially functional pathway cross-talk in AS to further reveal the pathogenesis of this disease. Using microarray profile of AS and biological pathways as study objects, Monte Carlo cross-validation method was used to identify the significant pathway cross-talks. In the process of Monte Carlo cross-validation, all steps were iterated 50 times. For each run, detection of differentially expressed genes (DEGs) between two groups was conducted. The extraction of the potential disrupted pathways enriched by DEGs was then implemented. Subsequently, we established a discriminating score (DS) for each pathway pair according to the distribution of gene expression levels. After that, we utilized random forest (RF) classification model to screen out the top 10 paired pathways with the highest area under the curve (AUCs), which was computed using 10-fold cross-validation approach. After 50 bootstrap, the best pairs of pathways were identified. According to their AUC values, the pair of pathways, antigen presentation pathway and fMLP signaling in neutrophils, achieved the best AUC value of 1.000, which indicated that this pathway cross-talk could distinguish AS patients from normal subjects. Moreover, the paired pathways of SAPK/JNK signaling and mitochondrial dysfunction were involved in 5 bootstraps. Two paired pathways (antigen presentation pathway and fMLP signaling in neutrophil, as well as SAPK/JNK signaling and mitochondrial dysfunction) can accurately distinguish AS and control samples. These paired pathways may be helpful to identify patients with AS for early intervention.

Comprehensive regulation effect of traditional Chinese medicine on proliferation and differentiation of neural stem cells / 中国中药杂志

Since the discovery of neural stem cells(NSCs) in embryonic and adult mammalian central nervous systems, new approaches for proliferation and differentiation of NSCs have been put forward. One of the approaches to promote the clinical application of NSCs is to search effective methods to regulate the proliferation and differentiation. This problem is urgently to be solved in the medical field. Previous studies have shown that traditional Chinese medicine could promote the proliferation and differentiation of NSCs by regulating the relevant signaling pathway in vivo and in vitro. Domestic and foreign literatures for regulating the proliferation and differentiation of neural stem cells in recent 10 years and the reports for their target and signaling pathways were analyzed in this paper. Traditional Chinese medicine could regulate the proliferation and differentiation of NSCs through signaling pathways of Notch, PI3K/Akt, Wnt/β-catenin and GFs. However, studies about NSCs and traditional Chinese medicine should be further deepened; the mechanism of multiple targets and the comprehensive regulation function of traditional Chinese medicine should be clarified.

Insulation of cross-talk between signalingpathways-inspiration for innovative drug design / 中国药理学通报

Cross-talk of intracellular signaling pathways that share common components (hubs) is organized in form of a bow-tie network topology.Signaling cross-talk is functionally pleiotropic for target genes regulation, resulting in functional redundancy, synergism and antagonism, which should be precisely controlled to prevent signaling 'leaking' or 'spillover'.Thus, the biological system has evolved multiple insulating mechanisms to achieve stimulus-specific response that maintains intracellular homeostasis.The insulation mechanism of signaling cross-talk suggests: (1) the functional duality of cross-talk molecules that determine cell fate requires selectively targeting dysregulated cross-talk molecules while protecting the normal ones from off-target or unintended effects, and we propose them as the targetable cross-talk molecules;(2) cross-talk molecules are usually carried on the macromolecular complex as their functional platforms, thus the structural plasticity of conformational changes at the interaction surface of cross-talk molecules asks for intensive work on the relationship study between drug binding and biological activity, which we propose as the accessible cross-talk molecules.Therefore, signaling cross-talk and its insulation mechanism play instructive leading roles in resolving the bottlenecks of current drug R&D and improve the clinical outcome.

Initial practice on cross-talk tests for MRI scanners / 中国医学影像技术

Objective To detect the cross-talk RF signal interference of three MRI scanners,in order to deepen the understanding of cross-talk RF signal interference.Methods Three different GE magnetic resonance imaging scanners (GE 1.5T HDi,installation time:2012;GE 3.0T HD,installation time:2006;GE 3.0T 750W,installation time:2016) were tested.The axial T1-weighted sequence was used to scan ACR phantom.Slice gaps with 5.0 mm,1.0 mm,0.5 mm and 0 were performed,respectively.SNR values were also recorded.Based on the results,the percentage change charts of SNR with slice gaps were made.Test standard was set as SNR decreased less than 20 ％ when the slice gap reduced from 5 mm to 0.Results When slice gap was reduced from 5 mm to 0,SNRs for three scanners decreased by 18.16 ％,23.57％ and 10.75％,respectively.Both the results of cross-talk obtained with GE 1.5T HDi and GE 3.0T 750W scanner met the test standard,while the result obtained with GE 3.0T HD (used for more than 10 years) was below the standard.Conclusion The cross-talk RF signal interference still exists for three MRI scanners.The test result of the scanner used for the longest time is unqualified.The quality control test of cross-talk should be done in the daily work.

Comprehensive regulation of traditional Chinese medicine on proliferation and differentiation of neural stem cells / 中国药理学与毒理学杂志

Since the diccovery of neural stem cells (NSCs) in the embryonic and adult mammalian central nerous system, it provided novel ideas forneurogenesis as the potential of proliferation and differentiation of NSCs. One of the ways to promote the clinical application of neural stem cells (NSCs) is searching effective methods which regulate the proliferation and differentiation.This is also a problem urgently to be solved in medical field. Plenty of earlier studies have shown that traditional chinese medicine can promote the proliferation and differentiation of NSCs by regulating the related signaling pathway in vivo and in vitro. The reports of Chinese and foreign literatures on regulating the proliferation and differentiation of neural stem cells in recent ten years and their target and signaling pathways is analyzed in this review.The traditional chinese medicine regulate proliferation and differentiation of NSCs by the signaling pathways of Notch,PI3K/Akt, Wnt/β- catenin, and GFs. And, those signaling pathways have cross- talk in the regulation progress. Moreover, some traditional Chinese medicine, such as astragalus,has a variety of active ingredients to regulate proliferation and differentiation of NSCs through different signaling pathways. However, to accelerate the clinical application of neural stem cells, the studies aboutthe proliferation and differentiation of NSCs and Chinese medicine should be further deepened, the mechanism of multiple targets and the comprehensive regulation function of traditional Chinese medicine should be clarified.

Skin Pigmentation and Pigmentary Disorders: Focus on Epidermal/Dermal Cross-Talk

Variation in human skin and hair color is the most notable aspect of human variability and several studies in evolution, genetics and developmental biology contributed to explain the mechanisms underlying human skin pigmentation, which is responsible for differences in skin color across the world's populations. Despite skin pigmentation is primarily related to melanocytes functionality, the surrounding keratinocytes and extracellular matrix proteins and fibroblasts in the underlying dermal compartment actively contribute to cutaneous homeostasis. Many autocrine/paracrine secreted factors and cell adhesion mechanisms involving both epidermal and dermal constituents determine constitutive skin pigmentation and, whenever deregulated, the occurrence of pigmentary disorders. In particular, an increased expression of such mediators and their specific receptors frequently lead to hyperpigmentary conditions, such as in melasma and in solar lentigo, whereas a defect in their expression/release is related to hypopigmented disorders, as seen in vitiligo. All these interactions underline the relevant role of pigmentation on human evolution and biology.

Genes Regulating Maternal Recognition of Pregnancy in Domestic Animals: an Update

ABSTRACT Early embryonic mortality is one of the main sources of reproductive wastages and major constraints for full exploitation of the production potential of livestock. The survivality of embryo during early embryonic life is mostly dependent on the efficiency with which the maternal recognition of pregnancy (MRP) is established. Maternal recognition of pregnancy involves molecular dialogue between the trophoblast of conceptus and uterine endometrium. Embryonic development to the blastocyst stage and uterine differentiation to the receptive environment are crucial for successful establishment of the embryo-uterine cross-talk that leads to the initiation and progression of successful implantation. Unravelling the complex intricate molecular and cellular dialogues between the conceptus and uterine environment will facilitate development of strategies to augment early embryo survivality.

Advances on receptor tyrosine kinase inhibitors taking c-Met as anti-tumor target / 中国药科大学学报

@#c-Met receptor tyrosine kinase plays an important role in signaling pathways including cell proliferation, metabolism as well as tumorigenic growth, migration and angiogenesis. c-Met has emerged as an attractive target for cancer therapy. Moreover, the interactive cross-talk between c-Met signaling and several other signaling pathways underlies a key effect for resistance of anti-cancer drugs. Thus, multi-target inhibitors become a new approach to cancer therapy. This paper introduces the c-Met signaling pathway and the resistance of kinase inhibitors caused by the cross-talk between c-Met and other membrane receptors and then will reviews the progress of single-target and multi-target c-Met inhibitors.

Medical education in India: Time to encourage cross-talk between different streams.

Currently, India recognizes fi ve different healthcare systems, collectively known as AYUSH (Ayurveda, Yoga, Unani, Siddha, Homeopathy), along with the conventional biomedicine. These systems have their own institutionalized structure for monitoring medical education and practice. However, because of the ‘parallel’ kind of policy model that is followed in India, there is no formal provision for any cross-talk between the professionals belonging to these different streams. This situation has not only given rise to mutual misgivings among these professionals regarding the strengths and weaknesses of each other, but also has led to a poor appreciation of the historical and socio-cultural connections these streams share with the community at large. To tackle these issues and to promote adequate participation of biomedicine experts in AYUSH-related research projects, ‘introduction of an AYUSH module in the current curriculum of MBBS (Bachelor of Medicine and Bachelor of Surgery) program’ has been proposed in this communication along with a possible roadmap for its implementation. It is also suggested that the experts in biomedicine be engaged for training AYUSH graduates in their respective specialties so that quality AYUSH education may be ensured.

Specific Protein Markers for Stem Cell Cross-Talk with Neighboring Cells in the Environment

A stem cell interacts with the neighboring cells in its environment. To maintain a living organism's metabolism, either cell-cell or cell-environment interactions may be significant. Usually, these cells communicate with each other through biological signaling by interactive behaviors of primary proteins or complementary chemicals. The signaling intermediates offer the stem cell's functionality on its metabolism. With the rapid advent of omics technologies, various specific markers by which stem cells cooperate with their surroundings have been discovered and established. In this article, we review several stem cell markers used to communicate with either cancer or immune cells in the human body.

Effect of PPARγ and glucocorticoid receptor on hepatic glucose metabolism / 中华内分泌代谢杂志

HepG2 cells were incubated with dexamethasone,glucocorticoid receptor (GR) antagonist RU486,and pioglitazone for 24 or 48 h.Glucose concentration in culture medium was detected.The results showed that 10 μmol/L RU486 blocked the surge of glucose concentration by 48 h of dexamethasone treatment and the glucose concentration in RU486 + pioglitazone group was higher than pioglitazone group( P＜0.05 ),suggesting that the cross talk between PPARγ and GR may exist in hepatic glucose metabolism.

Mesangial cell-derived tumor necrosis factor α up-regulates the expression of tubular liver type fatty acid binding-protein and its renoprotective role in IgA nephropathy / 中华肾脏病杂志

Objective To explore the mechanism of up-regulation of tubular liver-type fatty acid binding-protein (L-FABP) in IgA nephropathy (IgAN) and its renoprotective role.Methods Murine mesangial cells (MCs) from primary cell culture were cultured with aggregated IgA (AIgA) (10 to 250 mg/L) for 48 hours. The supernatant after culture was collected as AIgA-MC medium. Murine proximal tubular cell line (mProx) stably expressing human L-FABP (hL-FABP) by transfection (mProx-L) were cultured with AIgA, AIgA-MC medium and /or neutralizing anti-TNF-α antibody and recombinant murine TNF-α, respectively. AIgA-MC medium (AIgA final concentration was 25 mg/L) was cultured with mProx and mProx-L cells. The mRNA expressions of hL-FABP and MCP-1 of the cells were detected by real-time PCR. The protein expressions of hL-FABP and 4-HNE of the cells were detected by Western blotting. Results (1) The hL-FABP mRNA and protein expression stimulated by AIgA-MC medium was significantly higher as compared to AIgA (P＜0.01). (2) Pre-incubation of neutralizing anti-TNF-α antibody (final concentration was 1 and 5 mg/L) with mProx-L cells could significantly suppress the up-regulation of hL-FABP protein expression induced by AlgA-MC medium (P＜0.05 and P＜0.01).(3) Recombinant murine TNF-α (final concentration was 50 and 250 ng/L) also induced a significant up-regulation of hL-FABP expression (P＜0.01). (4) After the stimulation of AIgA-MC medium, both 4-HNE protein expression and MCP-1 mRNA expression were significantly suppressed in mProx-L cells compared to those of mProx cells (P ＜0.05 and P＜0.01). Conclusion Mesangial cell-derived TNF-α can induce up-regulation of tubular L-FABP expression. Overexpression of tubular L-FABP may lessen the progression of IgAN by reducing oxidative stress and inflammatory mediators.

NF-κB relative signal pathway and pancreatic cancer / 国际外科学杂志

Pancreatic cancer is one of the most malignant diseases.With the development of biology,its pathogenesis has become more and more clear.There are a lot of signal pathway aberrant in pancreatic cancer cell including Notch signal pathway,k-ras signal pathway,hedghog signal pathway,NF-κB signal pathway and so on.Because of the widespread of NF-κB signal pathway aberration in pancreatic cancer cell,we think that NF-κB play a key role in the various kinds of aberrant signal pathways.So the NF-κB relative sighal pathways in pancreatic cancer are reviewed in this atticle.

Cross-talk between Integrin and SMAD Signal Pathway in Articular Chondrocyte / 대한정형외과연구학회지

PURPOSE: Identifying the signal cross-talk between integrin signaling cascade and TGF-beta 1 signaling cascade in articular chondrocytes. MATERIALS AND METHODS: To analyze integrin or TGF-beta 1 mediated signaling pathways from extracellular stimuli, type II collagen was coated on the cell culture plate and TGF-beta 1 was added to cell culture media. Chondrocytes were cultured in the conditioned media with each or both stimuli. Altered activation of signaling proteins detected with western blot technique. RESULTS: More rapid attachment of cells was observed in the type II collagen coated group than non-coated group. The phosphorylated SMAD 2 and 3 were expressed in the type II collagen coated group and synergistically up-regulated phosphorylation in the co-treated group. The phosphorylated FAK at tyrosine 925 was activated by TGF-beta 1 treatment and synergistically up-regulated by both stimuli. But there was no meaningfully changed phosphorylation of extracellular signal regulated protein kinase (ERK) 1/2 and p38, as known downstream molecules of FAK cascade. CONCLUSION: This result means that SMAD 2, SMAD 3 and tyrosine 925 of FAK are involved in this signal cross-talking in articular chondrocytes.

KAMPO Medicine for the Self-Medication Age / 日本東洋医学雑誌

Kampo medicines, boiling water extracts of several kinds of herbal medicines, has been widely used for the clinical treatments in Japan. This medicine was created in China and brought to Japan via Korean peninsula at 5th century and has followed an independent course of development in Japan. But a modern scientific knowledge on Kampo medicines are still lacking, so this precious properties are slighted by modern medical treatment.<br>Last twenty five years, we have investigated the Kampo medicine chemically and pharmacologically to change this situation. In this paper, few topics will be discussed as shown bellow.<br>1) Difference between Kampo medicines and modern western medicines<br>2) Structural transformation of ingredients of crude drug<br>3) What is Kampo medicines based on components<br>4) Biological evaluation of some Kampo medicines<br>a. Effects of Sho-saiko-to toward the expression of P450mRNA<br>b. Effects of some Kampo formula toward the AD models<br>c. Effects of some Kampo formula toward the rheumatic models