Biological Receptors Research Articles

Mechanisms of oxide copper nanoparticles toxicity to microorganisms and ammonia-oxidizing bacteria and recommendations for future study

In recent years, the biological toxicity of oxide copper nanoparticles (CuO NPs) to microorganisms has received some attentions. The toxicity mechanism of CuO NPs can be concluded as follows: (1) CuO NPs facilitate more rapid dissolution of ions than equivalent bulk material, which potentially leading to increased toxicity of CuO NPs; (2) CuO NPs can generate reactive oxygen species (ROS), and potentially disturb the functioning of protein, enzymes and DNA; (3) CuO NPs have high capacity to adsorb biomolecules and interact with biological receptors, they can reach sub-cellular locations leading to potentially higher localized concentrations of ions once those particles start to dissolve or degrade in situ. Ammonia-oxidizing bacteria (AOB) are the main functional bacteria for biological nitrogen removal in the environment. It has been reported that CuO NPs can change the community structures of AOB, however, the toxicity mechanism of CuO NPs to AOB in cytological level is rarely reported. This review aims to evaluate the current understanding of CuO NPs toxicity to microorganisms, as well as to provide a set of pointers and guidelines for future studies to access the toxicity mechanism of CuO NPs to AOB.

Carbohydrates: Potential Sweet Tools Against Cancer.

Cancer, one of the most devastating degenerative diseases nowadays, is one of the main targets in Medicinal Chemistry and Pharmaceutical industry. Due to the significant increase in the incidence of cancer within world population, together with the complexity of such disease, featured with a multifactorial nature, access to new drugs targeting different biological targets connected to cancer is highly necessary. Among the vast arsenal of compounds exhibiting antitumor activities, this review will cover the use of carbohydrate derivatives as privileged scaffolds. Their hydrophilic nature, together with their capacity of establishing selective interactions with biological receptors located on cell surface, involved in cell-to-cell communication processes, has allowed the development of an ample number of new templates useful in cancer treatment. Their intrinsic water solubility has allowed their use as of pro-drug carriers for accessing more efficiently the pharmaceutical targets. The preparation of glycoconjugates in which the carbohydrate is tethered to a pharmacophore has also allowed a better permeation of the drug through cellular membranes, in which selective interactions with the carbohydrate motifs are involved. In this context, the design of multivalent structures (e.g. gold nanoparticles) has been demonstrated to enhance crucial interactions with biological receptors like lectins, glycoproteins that can be involved in cancer progression. Moreover, the modification of the carbohydrate structural motif, by incorporation of metal complexes, or by replacing their endocyclic oxygen, or carbon atoms with heteroatoms has led to new antitumor agents. Such diversity of sugar-based templates with relevant antitumor activity will be covered in this review.

Modeling the conformational preference, spectroscopic properties, UV light harvesting efficiency, biological receptor inhibitory ability and other physico-chemical properties of five imidazole derivatives using quantum mechanical and molecular mechanics tools

Five imidazole derivatives, 1-boc-imidazole (B1), 1-(trifluoroacetyl)imidazole (B2), 1-(2-hydroxyethyl)imidazole (B3), 1-(aminopropyl)imidazole (B4) and 1-ethylimidazole (B5) were analyzed for the structural, nonlinear optical, electronic and biological properties. The functional nature of the compounds were analyzed using vibrational spectra and Raman spectra and was compared with the scaled, simulated spectra obtained using the density functional theory using appropriate functional and basis set with diffused orbitals and are found to be close agreement. Relaxed potential energy scan predicts the stable conformers. Analysis of the outermost molecular orbitals gave their energy difference, aiding in the forecasting stability and other electronic properties. Time dependent density functional theory was used to analyze the electron excitation and de-excitation dynamics of these molecules and to predict the use of these molecules as effective UV photo sensitizers. This work further discusses in detail, the natural bond orbital (NBO) studies for intra molecular stabilization factors, molecular electrostatic potential (MEP) and hyperpolarizability calculations. Further molecular docking studies were conducted for the compounds with Glucanendo-1,6-beta-glucosidase and Protein-glutamatemethylesterase to predict their utility as potential inhibitors.

Enhanced flow sensing with interfacial microstructures

Biological flow receptors show astonishing performance and are used as models for the design of novel flow sensors. However, the functional importance of interfacial microstructures is seldom discussed in previous review papers. Herein, this review summarises the underlying biomechanical principles in the biological flow receptors and describes the recent progress in bio-inspired flow sensors, in which the underlying sensing-enhancement mechanisms are emphasised.

An Alternative Approach to Computational Peptidology Based on Conceptual DFT and Empirical Bioactivity Scores

This work presents the results of a study of the global and local chemical reactivity of the antineoplastic Elisidepsin and Plitidepsin marine drugs based on the calculation of descriptors coming from Conceptual DFT for their consideration as a tool to explain the molecular interactions, and as a useful complement to those approximations based on Molecular Docking. The knowledge of the values of the global and local descriptors of the molecular reactivity of the Elisidepsin and Plitidepsin molecules obtained through our proposed methodology could be useful in the development of new drugs based on these compound or some analogs relying in the chemical interaction between these peptides and their biological receptors of protein kind. It can be concluded that the Conceptual DFT approximation to the global and local chemical reactivity based on the descriptors can provide interesting information for the consideration of both molecules a potential drugs. This is complemented with a study on AGEs inhibition by comparison with the usual molecular systems considered for that task. Finally, the bioactivity scores for Elisidepsin and Plitidepsin are predicted by considering similarity searches of compounds with structures that can be compared to those that are being studied whose pharmacological properties are well known.

Long non-coding RNA expression profiling of macrophage line RAW264.7 infected by Mycobacterium tuberculosis

ABSTRACT Long non-coding RNAs (lncRNAs) have been implicated in regulation of biological processes. The role of lncRNAs in macrophages in response to Mycobacterium tuberculosis infection has not been explored. We used high throughput lncRNA microarray analysis to detect differentially expressed lncRNAs and mRNAs in RAW264.7 macrophages with or without M. tuberculosis infection. Quantitative real-time PCR (qRT-PCR) was used to verify the microarray results. Bioinformatics analysis (GO and KEGG) were used to explore the function of significantly dysregulated genes. Microarray results indicated that 1,487 lncRNAs (791 up and 696 down) and 910 mRNAs (536 up and 374 down) were expressed differentially in RAW264.7 macrophages with M. tuberculosis infection compared to controls. GO and pathway analysis revealed that up-regulated mRNAs were involved in immune response, immune system process, system development or TNF signaling pathway, and antigen processing and presentation. To the contrary, down-regulated mRNAs participated in system development, regulation of biological processes and peroxisome proliferator-activated receptor (PPAR) signaling pathway. qRT-PCR results of 10 lncRNAs and mRNAs were consistent with the microarray data. M. tuberculosis infection of macrophages caused enhanced expression of lncRNA AK151345 in a time- and dose-dependent manner. We determined comprehensive expression profiles of differentially expressed lncRNAs in RAW264.7 macrophages infected by M. tuberculosis.

The epidemic of 2019-novel-coronavirus (2019-nCoV) pneumonia and insights for emerging infectious diseases in the future

At the end of December 2019, a novel coronavirus, 2019-nCoV, caused an outbreak of pneumonia spreading from Wuhan, Hubei province, to the whole country of China, which has posed great threats to public health and attracted enormous attention around the world. To date, there are no clinically approved vaccines or antiviral drugs available for these human coronavirus infections. Intensive research on the novel emerging human infectious coronaviruses is urgently needed to elucidate their route of transmission and pathogenic mechanisms, and to identify potential drug targets, which would promote the development of effective preventive and therapeutic countermeasures. Herein, we describe the epidemic and etiological characteristics of 2019-nCoV, discuss its essential biological features, including tropism and receptor usage, summarize approaches for disease prevention and treatment, and speculate on the transmission route of 2019-nCoV.

Abstract P5-06-10: Validation of prognostic stage and anatomic stage in the American joint committee on cancer 8th edition for inflammatory breast cancer

Abstract Background: The American Joint Committee on Cancer (AJCC) recently updated its breast cancer staging system to incorporate biological factors, including estrogen and progesterone receptor (ER, PR), and HER2 status, in the new “prognostic stage” in addition to the traditional TNM anatomic stage. For the clinical anatomic staging, IBCs are classified at T4d; N0-2 as IIIB; and N3 as IIIC. For the clinical prognostic staging, ER+/PR+/HER2+/grade1-2 staged as IIIA; ER+/PR-/HER2-/grade3, ER-/PR+/HER2-/grade3, and all triple-negative cancers staged as IIIC; and all others as IIIB. We undertook this study to validate the clinical prognostic and anatomic stages for inflammatory breast cancer (IBC), an aggressive subgroup. The prognostic staging system, which was developed using non-IBC data, has not been validated in IBC. Methods: We established two cohorts of IBC patients diagnosed without distant metastasis: (1) patients treated at MD Anderson Cancer Center between 1989 and 2017 (MDA-cohort) and (2) patients registered in the SEER database between 2010 and 2015 (SEER-cohort). Survival endpoints including overall survival (OS), and disease-free survival (DFS) were calculated by the Kaplan-Meier method. Breast cancer-specific survival (BCSS) was calculated by the competing risk analysis. The log-rank test was used to compare differences in endpoints between staging groups. The Harrell concordance index (C index) was used to quantify staging models’ predictive performance. A higher C index indicates a better predictive performance. Results: We studied 885 patients in the MDA cohort and 338 in the SEER cohort. In the MDA cohort, the prognostic stage upstaged 248 patients (28%) and downstaged 146 (16%) comparing with the anatomic stage. The prognostic stage showed significant predictive power for BCSS, OS, and DFS (all P<0.0001), although the anatomic stage did not. The C index was significantly higher in the prognostic stage than the anatomic stage for BCSS (0.643 vs. 0.526, P<0.0001), OS (0.641 vs. 0.533, P<0.0001) and DFS (0.599 vs. 0.494, P<0.0001). In the SEER cohort, the prognostic stage upstaged 117 patients (27%) and downstaged 73 (17%). The survival differences between staging groups were more prominent with prognostic stage than with anatomic stage. The C index was significantly higher in the prognostic stage than the anatomic stage for BCSS (0.685 vs. 0.550, P=0.0028) and OS (0.681 vs. 0.557, P=0.0008). In both cohorts, prognostic stage IIIA patients had the best survival rates with the 5-year BCSS of 83% in the MDA cohort and 100% in the SEER cohort. Conclusions: The prognostic stage incorporating biological factors provided more accurate prognostication for IBC patients than the anatomic stage. Our results show that the 8th edition AJCC prognostic staging system is optimal for prognostification in IBC. Citation Format: Kumiko Kida, Kenneth R Hess, Bora Lim, Toshiaki Iwase, Sudpreeda Chainitikun, Maryanne E Sapon, Vicente Valero, Anthony Lucci, Carisa Le-Petross, Wendy A Woodward, Savitri Krishnamurthy, Gabriel N Hortobagyi, Debu Tripathy, Naoto T Ueno. Validation of prognostic stage and anatomic stage in the American joint committee on cancer 8th edition for inflammatory breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-06-10.

Image-based effective feature generation for protein structural class and ligand binding prediction.

Proteins are the building blocks of all cells in both human and all living creatures of the world. Most of the work in the living organism is performed by proteins. Proteins are polymers of amino acid monomers which are biomolecules or macromolecules. The tertiary structure of protein represents the three-dimensional shape of a protein. The functions, classification and binding sites are governed by the protein’s tertiary structure. If two protein structures are alike, then the two proteins can be of the same kind implying similar structural class and ligand binding properties. In this paper, we have used the protein tertiary structure to generate effective features for applications in structural similarity to detect structural class and ligand binding. Firstly, we have analyzed the effectiveness of a group of image-based features to predict the structural class of a protein. These features are derived from the image generated by the distance matrix of the tertiary structure of a given protein. They include local binary pattern (LBP) histogram, Gabor filtered LBP histogram, separate row multiplication matrix with uniform LBP histogram, neighbor block subtraction matrix with uniform LBP histogram and atom bond. Separate row multiplication matrix and neighbor block subtraction matrix filters, as well as atom bond, are our novels. The experiments were done on a standard benchmark dataset. We have demonstrated the effectiveness of these features over a large variety of supervised machine learning algorithms. Experiments suggest support vector machines is the best performing classifier on the selected dataset using the set of features. We believe the excellent performance of Hybrid LBP in terms of accuracy would motivate the researchers and practitioners to use it to identify protein structural class. To facilitate that, a classification model using Hybrid LBP is readily available for use at http://brl.uiu.ac.bd/PL/. Protein-ligand binding is accountable for managing the tasks of biological receptors that help to cure diseases and many more. Therefore, binding prediction between protein and ligand is important for understanding a protein’s activity or to accelerate docking computations in virtual screening-based drug design. Protein-ligand binding prediction requires three-dimensional tertiary structure of the target protein to be searched for ligand binding. In this paper, we have proposed a supervised learning algorithm for predicting protein-ligand binding, which is a similarity-based clustering approach using the same set of features. Our algorithm works better than the most popular and widely used machine learning algorithms.

Heart is the Target Organ of Endogenous Cardiac Natriuretic Peptides.

This study aimed to evaluate whether the heart is the target organ of endogenous atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in patients with heart failure (HF) with reduced ejection fraction (HFrEF).We measured the plasma levels of cyclic guanosine monophosphate (cGMP), which is a second messenger of ANP and BNP, in the aortic root (AO) and coronary sinus (CS) in 237 patients with HFrEF. Plasma levels of cGMP were significantly higher in the CS than those in the AO in 237 patients with HFrEF (10.0 ± 4.5 versus 10.5 ± 4.3 pmoL/mL, P < 0.0001) and were significantly higher in the CS than those in the AO (8.0 ± 3.6 versus 8.9 ± 3.8 pmoL/mL, P < 0.0001) in mild HF patients (New York Heart Association (NYHA) II, n = 114), but there was no difference in plasma cGMP between the AO and the CS (11.9 ± 4.4 versus 11.9 ± 4.3 pmoL/mL, NS) in severe HF patients (NYHA III-IV, n = 123). In mild HF patients, log (ANP + BNP) in the AO was an independent predictor of (CS-AO) cGMP among hemodynamics and nitrate therapy. There was a significant correlation between log [(CS-AO) ANP + (CS-AO) BNP] and (CS-AO) cGMP (r = 0.455, P < 0.0001) in mild HF patients.These findings indicate that cGMP is produced from the failing heart and that the heart is the target organ of endogenous ANP and BNP in patients with HFrEF. In severe HF patients, cGMP production may be attenuated because of the downregulation of biological receptors and/or increased cGMP degradation in the failing heart.

IMMUNE AND GENETIC STATUS OF WOMEN WITH REPRODUCTIVE DISORDERS IN THE CONDTIONS OF EXPOSED CONTAMINATION OF BIOLOGICAL MEDIA WITH PHENOLS

Introduction. A Hormon-like agent such as phenol is able both to integrate into the work of hypothalamus-pituitary-ovary system and trigger a cascade of responses that leads to the development of the immune, hormonal and endocrine systems disorder. Material and methods. The study included 181 woman who permanently live in the area with contamination with phenol in air above standard level. All women are comparable in age, material status and ethnicity. Immunological and hormonal indices were determined by enzyme immunoassay, genetic markers were detected by polymerase chain reaction. Statistical data processing was carried out with the soffware Statistica 10.0, using parametric and non-parametric methods. Results. Between the study groups there were obtained significant differences in following markers: thyroid-stimulating hormone, serotonin, interleukin 6, interleukin 10, estradiol. The dependence of appearance of unfavorable reproductive effects on the presence of polymorphic allele’s was determined: A allele of a gene SULT1A1, G allele of a gene PER2, C allele of a gene SIRT1. Correlation models are defined: thyroid-stimulating hormone and phenol, serotonin and phenol, thyroid-stimulating hormone and cresol, serotonin and cresol, estradiol and cresol. Conclusion. All found markers (increased concentration of phenol in biological media, gene polymorphism, altered protein and receptor expression) create special conditions for the course of the miscarriage pathology.

Advances in aptasensor technology.

Aptasensors form a class of biosensors that function on the basis of a biological recognition. An aptasensor is advantageous because it incorporates a unique biologic recognition element, i.e., an aptamer, coupled to a transducer to convert a biological interaction to readable signals that can be easily processed and reported. In such biosensors, the specificity of aptamers is comparable to and sometimes even better than that of antibodies. Using the SELEX technique, aptamers with high specificity and affinity to various targets can be isolated from large pools of different oligonucleotides. Nowadays, new modifications of the SELEX technique and, as a result, easy generation and synthesis of aptamers have led to the wide application of these materials as biological receptors in biosensors. In this regard, aptamers promise a bright future. In the present research a brief account is initially provided of the recent developments in aptasensors for various targets. Then, immobilization methods, design strategies, current limitations and future directions are discussed for aptasensors.

Interleukin 39: a new member of interleukin 12 family.

Interleukin (IL)-12 family member is a heterodimer glycoprotein, composed of two covalently linked subunits, α and β chains. The α subunit consists of IL-23p19, IL-27p28, and IL-12p35, and the β subunit includes IL-12p40 and Epstein-Barr virus-induced gene (Ebi3). IL-39 is a new heterodimeric IL-12 family member composed of IL-23p19 and Ebi3 subunits. IL-39 is secreted by lipopolysaccharide-stimulated B cells. Other immune cells, such as dendritic cells and macrophages, express IL-39 mRNA. In lupus-like mice, GL7+B cells and CD138+plasma cells are highly activated and widely expressed, promoting high expression of IL-39. IL-39 mediates inflammatory responses through binding to a heterodimer of IL-23R/gp130 receptor and activation of signal transducer and activator of transcription (STAT)1/STAT3 signal molecules. The serum levels of IL-39 were significantly increased in patients with acute coronary syndrome compared with patients with normal coronary arteries. This review discusses the biological characteristics, receptor, and signal pathway as well as biological activity of IL-39 and its potential role in inflammation and other diseases.

A chiral trick to map protein ligandability.

Biological receptors distinguish between S- and R-enantiomers and these subtle differences in chirality can lead to vastly different protein affinities. Now, a proteomics approach has been developed that capitalizes on chirality to map enantiomeric probe pairs and provides a rapid and global view of protein ligandability within the cell.

Design of the trinitrotoluene biosensor using polydiacetylene conjugated with peptide receptors coated on GR-FETs with colorimetric response

PurposeSmart biosensors that can perform sensitive and selective monitoring of target analytes are tremendously valuable for trinitrotoluene (TNT) explosive detection. In this research, the pre-developed sensor was integrated with biological receptors in which they enhanced the sensitivity of the sensor. This is due to conjugated polydiacetylene onto a peptide-based molecular recognition element (Trp-His-Trp) for TNT molecules in graphene field-effect transistors (GR-FETs) as biosensor that is capable of responding to the presence of a TNT target with a colorimetric response. The authors confirmed the efficacy of the receptor while being attached to polydiacetylene (PDA) by observing the binding ability between the Trp-His-Trp and TNT to alter the electronic band structure of the PDA conjugated backbones. The purpose of this paper is to demonstrate a modular system capable of transducing small-molecule TNT binding into a detectable signal. The details of the real-time and selective TNT biosensor have been reported.Design/methodology/approachFollowing an introduction, this paper describes the way of fabrication GR-FETs with conventional photolithography techniques and the other processes, which is functionalized by the TNT peptide receptors. The authors first determined the essential TNT recognition elements from UV-visible spectrophotometry spectroscopy for PDA sensor unit fabrication. In particular, the blue percentage and the chromic response were used to characterize the polymerization parameter of the conjugatedpbackbone. A continuous-flow trace vapor source of nitroaromatics (two, four, six-TNT) was designed and evaluated in terms of temperature dependence. The TNT concentration was measured by liquid/gas extraction in acetonitrile using bubbling sequence. The sensor test is performed using a four-point probe and semiconductor analyzer. Finally, brief conclusions are drawn.FindingsBecause of their unique optical and stimuli-response properties, the polydiacetylene and peptide-based platforms have been explored as an alternative to complex mechanical and electrical sensing systems. Therefore, the authors have used GR-FETs with biological receptor-PDAs as a biosensor for achieving high sensitivity and selectivity that can detect explosive substances such as TNT. The transport property changed compared to that of the field-effect transistors made by intrinsic graphene, that is, the Dirac point position moved from positive Vg to negative Vg, indicating the transition of graphene fromp-type ton-type after annealing in TNT, and when the device was tested from RT, the response of the device was found to increase linearly with increasing concentrations. Average shifting rate of the Dirac peak was obtained as 0.1-0.3 V/ppm. The resulting sensors exhibited at the limit ppm sensitivity toward TNT in real-time, with excellent selectivity over various similar aromatic compounds. The biological receptor coating may be useful for the development of sensitive and selective micro and nanoelectronic sensor devices for various other target analytes.Originality/valueThe detection of illegally transported explosives has become important as the global rise in terrorism subsequent to the events of September 11, 2001, and is at the forefront of current analytical problems. It is essential that a detection method has the selectivity to distinguish among compounds in a mixture of explosives. So, the authors are reporting a potential solution with the designing and manufacturing of electrochemical biosensor using polydiacetylene conjugated with peptide receptors coated on GR-FETs with the colorimetric response for real-time detection of TNT explosives specifically.

Synthesis of Chalcone Derivatives: Inducing Apoptosis of HepG2 Cells via Regulating Reactive Oxygen Species and Mitochondrial Pathway.

Chalcone derivatives, as a hot research field, exhibit a variety of physiological bioactivities and target multiple biological receptors. Based on the skeleton of (E)-1,3-diphenyl-2-propene-1-one, 14 chalcone derivatives were designed and synthesized, and evaluated as the antitumor candidates agents against four human cancer cell lines (A549, Hela, HepG2, and HL-60) as well as one normal cell line (WI-38). Among the title compounds, compound a14 showed better inhibitory activity against HepG2 cells (IC50 = 38.33 µM) and had relatively weak cytotoxicity towards normal cells WI-38 (IC50 = 121.29 µM). In this study, apoptosis, cycle arrest, assessment of reactive oxygen species (ROS) level, and measurement of mitochondrial membrane potential were adopted to explore the inhibitory mechanism of a14 towards HepG2. Compound a14 could effectively block the division of HepG2 cell lines in the G2/M phase and robustly induced generation of ROS, demonstrating that the generation of ROS induced by a14 was the main reason for resulting in the apoptosis of HepG2 cells. Moreover, the mitochondrial membrane potential (MMP) of HepG2 cells treated with a14 was significantly decreased, which was closely related to the enhanced ROS level. Furthermore, based on Western blot experiment, cell apoptosis induced by a14 also involved the expression of B-cell lymphoma-2 (Bcl-2) family and Caspase 3 protein. In summary, compound a14 could contribute to the apoptosis of HepG2 cells through regulating ROS-mitochondrial pathway, which provides valuable hints for the discovery of novel anti-tumor drug candidates.

SUPPRESSION OF GHRELIN SIGNALING EXACERBATES ULCERATIVE COLITIS IN OLDER MICE

The aging process is characterized by increased chronic low-grade inflammation, aka inflamm-aging, which offend is accompanied by ‘leaky gut’ syndrome. Inflamm-aging is a highly significant risk factor for both morbidity and mortality in the older adult population (>65 years of age). In addition, there is a growing prevalence of inflammatory bowel disease (IBD), a chronic inflammatory condition of the gastrointestinal tract in the older adult population. The pathogenesis of late-onset IBD is suggested to be more complex compared with younger IBD patients; the causes determining the age of IBD onset remain unexplained. Ghrelin is a 28-amino-acid peptide hormone mainly produced by X/A-like cells of the stomach, with well-characterized functions in growth hormone secretion, food intake, adiposity and insulin resistance. Ghrelin’s biological relevant receptor is Growth Hormone Secretagogue Receptor (GHS-R). Ghrelin and ghrelin mimetics have been considered viable candidates for treating cachexia, sarcopenia, and gastrointestinal disorders. As expected, we observed that the expression of tight junction proteins in colon mucosal layer decreases with age. When challenged with dextran sulfate sodium (DSS) to induce experimental ulcerative colitis, 18-months old male C57BL/6 mice exhibited exacerbated disease activity scores compared to young male mice (5-months), showing worsened pathology such as rectal bleeding and difficulty in defecation. DSS-induced colitis was exacerbated in both ghrelin-deficient (Ghrl-/-) and ghrelin receptor-deficient (Ghsr-/-) mice. Together, these data suggest endogenous ghrelin signaling contributes to susceptibility to colitis, and ghrelin signaling pathway may present a novel target for prevention and treatment of leaky gut syndrome in aging.

Diffusive Molecular Communication in a Biological Spherical Environment With Partially Absorbing Boundary

Diffusive molecular communication (DMC) is envisioned as a promising approach to help realize healthcare applications within bounded biological environments. In this paper, a DMC system within a biological spherical environment (BSE) is considered, inspired by bounded biological sphere-like structures throughout the body. As a biological environment, it is assumed that the inner surface of the sphere’s boundary is fully covered by biological receptors that may irreversibly react with hitting molecules. Moreover, information molecules diffusing in the sphere may undergo a degradation reaction and be transformed to another molecule type. Concentration Green’s function (CGF) of diffusion inside this environment is analytically obtained in terms of a convergent infinite series. By employing the obtained CGF, the information channel between transmitter and transparent receiver of DMC in this environment is characterized. Interestingly, it is revealed that the information channel is reciprocal, i.e., interchanging the position of receiver and transmitter does not change the information channel. Results indicate that the conventional simplifying assumption that the environment is unbounded may lead to an inaccurate characterization in such biological environments.

Épidémiologie des cancers du sein

The breast is the leading cancer site in women throughout the world. That said, breast cancer incidence varies widely, ranging from 27/100,0002 (Central-East Asia and Africa) to 85-94/100,0002 (Australia, North America and Western Europe). Its frequency in France is among the highest in Europe. While in most countries, its incidence has been increasing for more than 40years, in a few other countries (USA, Canada, Australia, France…), it has been decreasing since 2000-2005. Possibly due to a substantial reduction of hormone-based treatments at menopause, the decrease may be transient. It is also the leading cause of female cancer deaths in almost all countries, with the exception of the most economically developed, in which it is currently second to lung cancer. That much said, for thirty years in highly industrialized countries such as France, breast cancer mortality has been declining. Taken together, early diagnosis and improved treatment explain this success. In France, 5-year survival and 10-year survival approximate 88% and 78% respectively; these rates are among the most elevated in Western Europe. Excess mortality due to breast cancer is consequently low (<5%) but variable according to age, and maximal during the first two years of follow-up. Several thousand epidemiological studies on risk factors for breast cancer have been carried out worldwide; it is difficult to draw up an overall assessment, especially insofar as the identified factors interact and vary according to whether the cancers occur before or after menopause and depending on their histological, biological (receptors) or molecular characteristics. Moreover, their prevalence varies in time and from one region to another. For the majority of these factors, the level of relative risk is≤2. Genetic particularities: presence of proliferative mastopathy, a first child after 35years of age and thoracic irradiation are the sole factors entailing relative risk from 2to 5 (comparatively speaking, the risk levels associated with tobacco consumption reach values from 10to 20, and in some cases even higher). However, exposure to risk factors≤2may be relatively frequent and consequently favorable to development of a substantial number of breast cancers. Estimation (based on degree of risk and frequency of exposure) of the proportion of risk attributable to a given factor facilitates decision-making aimed at determining the most effective primary prevention actions. Taking into consideration the identified factors pertaining to post-menopausal cancers, only 35% [23to 45%] of the attributable proportions could be reduced by primary prevention. In view of achieving this level of reduction, it is possible to put forward the following recommendations: for the women themselves: have a first child before the age of 30, breastfeed for several months, engage in sufficiently intense and regular physical activity, avoid or reduce excess weight after turning thirty, avoid exposure to active or passive smoking, limit alcohol consumption; for their physicians: do not prescribe pointless thoracic irradiations (unnecessary mammography in particular) or unjustified hormonal treatments. *persons/years.

Bioavailability and ecotoxicity of metals in aquatic systems: critical levels of pollution

The bioavailability and ecotoxicity of metals depending on the geochemical factors of the aquatic environment are considered. For the most metals free ions have the greatest penetration with the exception of some mercury organometallic complexes it has been shown. The models for assessing the danger of pollution of the aquatic environment with metals based on thermodynamic calculations of free ions concentration, the ability of biological receptors to bind them and the toxicological properties of metals, are analyzed. The main mechanisms of penetration and elimination of metals and the cytotoxicity of non-essential elements are considered. A new method for determining critical levels of polymetallic water pollution based on measurements of the complexing ability of waters components and establishing dose-effect relationships between integral indicators of polymetallic water pollution and indicators of ecosystem “health” of ecosystems based on research in the Kola North are presented.