Biological Actions Research Articles

Multiplexed no-wash cellular imaging using BenzoTag, an evolved self-labeling protein.

Self-labeling proteins are powerful tools for exploring biology as they enable the precise cellular localization of a synthetic molecule, often a fluorescent dye. HaloTag7 is the most popular self-labeling protein due to its broad utility, its bio-orthogonality, and the simplicity of its chloroalkane ligand. However, reaction rates of HaloTag7 with different chloroalkane-containing substrates are highly variable and rates are only very fast for rhodamine-based dyes. This is a major limitation for the HaloTag system because fast labeling rates are critical for live-cell assays. Here, we use yeast surface display to produce a HaloTag variant, BenzoTag, with improved performance with a fluorogenic benzothiadiazole dye. Molecular evolution improved conjugation kinetics and increased the signal from the dye-protein complex, allowing for robust, no-wash fluorescence labeling in live cells. The new BenzoTag-benzothiadiazole system has improved performance compared to the best existing HaloTag7-silicon rhodamine system, including saturation of intracellular enzyme in under 100 seconds and robust labeling at dye concentrations as low as 7 nM. The BenzoTag system was also found to be sufficiently orthogonal to the HaloTag7-silicon rhodamine system to enable multiplexed no-wash labeling in live cells. The BenzoTag system will be immediately useful for a large variety of cell-based assays monitoring biological processes and drug action in real time.

Estimation of gammaaminobutyric acid intake from the human diet

Gamma-aminobutyric acid (GABA) is an endogenous bioactive compound with essential properties for the normal functioning of the human nervous system. As a potent neurotransmitter, it plays an important role in modulating synaptic transmission by exerting phasic inhibition of neurons. This and other effects of GABA provide the phenomenon of neural tissue plasticity underlying learning, memory, maturation and repair of neural tissue after damage. It also has a wide range of biological actions, including antihypertensive, anti-diabetic, antioxidant, and anti-inflammatory. In this regard, GABA is increasingly used in the composition of food for special dietary uses and dietary supplements. However, its adequate intake levels have not yet been assessed and its dietary intake has not been characterized. The aim of the review was to estimate the level of GABA intake under balanced consumption of foods, corresponding to rational norms that meet modern requirements of a healthy diet. Material and methods. The existing literature on the problem in recent years was reviewed using the databases RISC, CyberLeninka, Pubmed, and ResearchGate. Results. Based on the analysis of scientific literature, we evaluated the content of GABA in the average daily diet, compiled on the basis of the rational norms of food consumption that meet modern requirements for healthy nutrition (Order of the Ministry of Healthcare of the Russian Federation dated August 19, 2016. No. 614). The balanced diet can provide about 740 mg of GABA per day, mainly due to vegetables (potatoes - 419 mg/day, beet - 49 mg/day, pumpkin - 41 mg/day), fruits (apple - 15 mg/day, grapes - 3.8 mg/day), as well as low-fat dairy products (92 mg/day). Conclusion. The presented data may be useful in assessing the adequacy of enrichment of foods for special dietary uses and dietary supplements with GABA.

Biological action of melatonin on target receptors in breast cancer.

Biological action of melatonin on target receptors in breast cancer.

Synthesis and evaluation of linearly fused thiadiazolocoumarins as prospects with broad-spectrum bioactivity

Various pharmacological properties of coumarins brought them under light among the heterocyclics. Also, coumarin derivatives still approve of their importance in the medical field as a valuable building block to elicit further derivatives with diverse, potent, and interesting biological activities. Moreover, the numerous biological actions of thiadiazole-based compounds contribute to the notion of this unique synthesis of linearly fused thiadiazolocoumarins using the molecular hybridization method. This work reported the novel synthesis of seven linearly fused thiadiazolocoumarins, including Precursor N-III and TDA1-TDA6. These derivatives were characterized by their physicochemical properties and through spectrophotometric tools, including FTIR, 1H NMR, and 13C NMR. Also, their pharmacokinetics were predicted using computer-based studies by the SwissADME and PreADMET programs. Furthermore, the derivatives were checked for several biological activities, including anticancer, biosafety, anti-oxidative stress, anti-inflammatory, antimicrobial, normal flora safety, and antidiabetic activities. According to the results, TDA3 showed the greatest anticancer activity against the examined cancer cell lines, with the highest cellular biosafety. TDA3 and TDA4 showed higher anti-oxidative stress activity than the other derivatives. All the prepared derivatives showed significant inflammation-inhibitory activity toward the LOX-5 enzyme while showing poor activity towards COX enzymes. According to antimicrobial activity, TDA4 exhibited the greatest anti-gram-negative activity and also showed the best safety toward the examined normal flora. TDA1 exhibited promising activity against anaerobic bacteria, while Precursor N-III, TDA3, and TDA4 showed significant antifungal activity. Finally, TDA1 demonstrated moderate antidiabetic activity, which was the greatest activity among the other derivatives. The authors concluded from the gathered results that the linearly fused thiadiazolocoumarins represent key structures for developing compounds with versatile bioactivities.

Synthesis, crystal structure, thermal stability and biological study of bis{(2-methoxy-6-[(E)-(propylimino)methyl]phenolato}nickel(II) complex

A Schiff base complex of nickel, bis{(2-methoxy-6-[(E)-(propylimino)methyl]phenolato}nickel(II) was synthesised by condensing bis(2-hydroxy-3-methoxybenzaldehyde) nickel (II) and n-propylamine in methanolic medium. Single crystal X-ray diffraction analysis of the complex revealed it to possess planar geometry with a monoclinic crystal system. The non-isothermal TG/DTA runs on this complex in a high purity (99.99 %) nitrogen environment at atmospheric pressure confirmed the absence of any coordinated water. A sharp endotherm in its DTA shows a melting temperature range of 168–171 °C. It is thermally stable up to 243 °C and decomposes in two steps, yielding NiO and carbon as residue. In addition to the methoxy group (-OCH3), infrared analysis (IR) confirmed the presence of the characteristic azomethine group (-CN-) which is also responsible for the biological action. It was further analysed by elemental analyser (C, H, N), 1H and 13C NMR as well as mass spectrometry. It showed considerable antibacterial activity towards Escherichia coli and Staphylococcus aureus when the concentration exceeds 200 μg/ml. The antifungal study shows significant inhibition with the antifungal drug imidazole as a positive control (PC). Small values of MIC, MBC/MIC indicate a lesser quantity of complex is required to inhibit the growth of micro-organisms.

Dietary Polyphenols against Oxidative Stress in Head and Neck Cancer: What's New, What's Next.

Head and neck cancers (HNC) are a worldwide health problem, accounting for over 5% of all types of cancers. Their varied nature makes it sometimes difficult to find clear explanations for the molecular mechanisms that underline their onset and development. While chemio- and radiotherapy are clearly not to be dismissed, we cannot undervalue the effect that polyphenols - especially dietary polyphenols - can have in helping us to cope with this medical emergency. By influencing several different proteins involved in numerous different metabolic pathways, polyphenols can have a broad spectrum of biological action and can hopefully act synergistically to tackle down head and neck cancer. Moreover, being natural molecules, polyphenols does not present any side effects and can even enhance drugs efficacy, making our clinical therapy against head and neck cancer more and more effective. Certainly, oxidative stress plays an important role, altering several molecular pathways, lowering the body's defenses, and ultimately helping to create a microenvironment conducive to the appearance and development of the tumor. In this regard, the regular and constant intake of foods rich in polyphenols can help counteract the onset of oxidative stress, improving the health of the general population. In this review, we highlight the role of polyphenols in managing oxidative stress, with such positive effects that they can be considered new tools to use in our anti-head and neck cancer strategy.

INTERRELATION OF BIOLOGICAL ACTIVITY AND CALCULATED PARAMETERS OF NITRILSILANES AND NITRILSILOXANES

The processes of oil production, transport, refining are time-bound, which is fraught with sludge and storage, which is the cause of microbiological corrosion. The geometric, electronic and energy parameters of previously synthesized organosilicon nitriles and the manifestation of their antimicrobial activity are studied, and some regularities of their physicochemical properties are established. It was found that heteroatomic compounds containing silicon atoms in their composition have a high and effective fungicidal activity, inhibiting the growth of fungi and plants, as well as minimal toxicity. It has been established that the effect of the studied compounds can last up to several weeks, in contrast to the currently used drugs of biological action during the storage and transportation of petroleum oils. The results of the physicochemical parameters of a number of nitrilesilanes and nitrilesiloxanes calculated by the DFT method with the B3LYP/6-31G(d,p) functional are presented. The studied compounds are highly reactive, and in this work the biological activities of a number of organosilicon nitriles have been experimentally established. Based on the calculated and experimental data obtained, the relationship between the energies of the boundary molecular orbitals (depending on the electronic structure) and the antimicrobial properties of the presented nitrile silanes and nitrile siloxanes were established. It has been shown that a number of studied organosilicon compounds, especially nitrile siloxanes, are superior in bactericidal activity to the biocide sodium pentachlorophenolate. When compiling a 3D function graph, the average deviation of the results of mathematical calculations from the results of a biological experiment was a maximum of 23%. It has been established that the most effective of the given compounds of a number of organosilicon nitrile silanes and nitrile siloxanes can be widely used in industry and can be recommended as biocidal additives for lubricating oils and other lubricating and cutting fluids and materials.

Long-term effectiveness and sustainability of EHC remediation in carbon tetrachloride-contaminated groundwater: Mechanistic understanding and practical applications

The presence of carbon tetrachloride in groundwater raises concerns for human health and the environment. Thus, there is an urgent need for a faster and more efficient groundwater remediation method. Our study found that the EHC remedial agent can achieve promising pilot remediation results quickly, as demonstrated in laboratory tests. During the pilot test, the contaminated groundwater was subjected to injection with the EHC remedial agent using in-situ high-pressure rotary jet technology. It was observed that indicators such as alkalinity and SO42− can signify the occurrence of biological reduction, with the presence of ZVI significantly shortening the beginning time of biological action within the EHC. The pilot test results reveal that the initial four days following the injection of the EHC witnessed only chemical reduction, with chemical and biological reduction coexisting from day 4 to day 45. Post the 45-day mark, the removal of contaminants solely relied on biological reduction. While chemical reduction displayed a rapid rate but limited duration, insufficient for ensuring long-term effectiveness in the remediation process, bioremediation offered sustained efficacy for continuous contaminant reduction. These findings signify a more eco-friendly and efficient approach to groundwater remediation, offering both human health and environmental benefits.

Expression of Relaxin Family Peptide Receptors 1 and 3 in the Ovarian Follicle of Japanese Quail.

In our previous studies, we demonstrated that the primary source of relaxin 3 (RLN3) in Japanese quail is ovarian granulosa cells. Although several relaxin family peptide (RXFP) receptors have been sequenced, the intricacies of these receptors in avian species remain insufficiently clarified. Therefore, we assessed the expression of RXFP receptors, RXFP1 and 3, in Japanese quail. Using RT-PCR, we found that both RXFP1 and 3 were ubiquitously expressed. The expression level of RXFP1 is significantly higher in the ovarian theca layer, indicating that it is the primary receptor for RLN3 in the ovary. During follicular development, there was an elevation in thecal RXFP1 expression, but it declined after the luteinizing hormone (LH) surge. We found that the protease activity of the 60 kDa band increased after the LH surge, suggesting the involvement of RLN3 signaling in ovulation. These results suggest a paracrine role of RLN3, involving its binding with RXFP1 in ovarian theca cells. This interaction may elicit biological actions, potentially initiating ovulation after the LH surge.

The New Trends in Physiological and Pathological Actions of Ghrelin (Brain-Heart Axis) on the Heart and Cardiovascular System

Background: Ghrelin increased significantly the Left Ventriculus Eject Fraction and end-systolic volume after 30 minutes of intra-venous injection and without alterations heart rate and blood pressure. Ghrelin was discovered in 1999 as an only one 28 amino acid peptides (with octanoyl serine group) located on the short arm of chromosome 3 (position 3p25-26) having six exons, two are noncoding and four introns and encodes a 511 bp mRNA. Ghrelin is synthesized by the endocrine X/A-like cells located from the gastric fundus mucosa through the whole mucosa of the medium right vertical side of the stomach until to the 1 inch before anatomical pylorus. These cells are responsible to produced 80% of the whole ghrelin produced in the human body. Furthermore, other place of this production occurs at the hypothalamus, the pituitary, second portion of duodenum, pancreas, heart and other tissues. Bibliographic references also demonstrate the importance of ghrelin’s action in the main cardiovascular activities. Related to cardiovascular activities, ghrelin plays multitudinous beneficial and thereby help during cardiovascular diseases. Several studies demonstrated that ghrelin cause an anti-inflammatory activity by the inhibition of proinflammatory cytokines which can diminish inflammatory diseases in the heart, pericardium and specific innervations, for instance, vagus nerve and inhibited sympathetic nerves. Outcomes of this review emphasize these important actions of ghrelin. Methods: A systematic review of ghrelin activities over the heart and cardiovascular system with the inclusion of papers in review involved the physiological and physio pathological activities of ghrelin in vivo and in vitro studies. Results: Ghrelin is a natural tide with the growth hormone secretagogue (GHS) receptor (GHS-R) which cloned in 1996. The processes which generate this peptide and ghrelin-related peptides are transcriptional, translational and posttranslational. Homo and heterodimers of GHS-R and other yet unidentified receptors mediate the biological actions of acyl ghrelin and desacyl ghrelin. However, the main biological functions of ghrelin involve the secretion of growth hormone, stimulation of appetite and food intake at the hypothalamus, modulate acid secretion and motility, endocrine and exocrine pancreas secretion, blockaded insulin activity, heart functions and cardiovascular responses and other. Conclusion: One of the main occurrences in acute heart infarction is an increase activation of cardiac sympathetic nerve activity (CSNA) which is one of the causes of chronic cardiac dysfunction (CCD). Ghrelin is an effective for obtain a better cardiac function and by the suppression of renal sympathetic nerve activity which also have an important benefit to the acute myocardial infarction. Therefore, the physiological effects of ghrelin are very important to the body homeostasis even in the grave heart and cardiovascular diseases and in the immunological system.

Polymeric Vehicles for Nucleic Acid Delivery: Enhancing the Therapeutic Efficacy and Cellular Uptake.

Therapeutic gene delivery may be facilitated by the use of polymeric carriers. When combined with nucleic acids to form nanoparticles or polyplexes, a variety of polymers may shield the cargo from in vivo breakdown and clearance while also making it easier for it to enter intracellular compartments. Polymer synthesis design choices result in a wide variety of compounds and vehicle compositions. Depending on the application, these characteristics may be changed to provide enhanced endosomal escape, longer-lasting distribution, or stronger connection with nucleic acid cargo and cells. Here, we outline current methods for delivering genes in preclinical and clinical settings using polymers. Significant therapeutic outcomes have previously been attained using genetic material- delivering polymer vehicles in both in-vitro and animal models. When combined with nucleic acids to form nanoparticles or polyplexes, a variety of polymers may shield the cargo from in vivo breakdown and clearance while also making it easier for it to enter intracellular compartments. Many innovative diagnoses for nucleic acids have been investigated and put through clinical assessment in the past 20 years. Polymer-based carriers have additional delivery issues due to their changes in method and place of biological action, as well as variances in biophysical characteristics. We cover recent custom polymeric carrier architectures that were tuned for nucleic acid payloads such genomemodifying nucleic acids, siRNA, microRNA, and plasmid DNA. In conclusion, the development of polymeric carriers for gene delivery holds promise for therapeutic applications. Through careful design and optimization, these carriers can overcome various challenges associated with nucleic acid delivery, offering new avenues for treating a wide range of diseases.

Od Nobelove nagrade za fiziologiju do nove trenažne i takmičarske paradigme sportskog plivanja

Nitric-monoxide is recognized as a molecule with a very simple structure, considered for a long time as an extremely toxic substance. Yet, due to the possibility of endogenous biosynthesis and the variety of biological actions it possesses, today it is considered as paracrine substance of exceptional pharmacological, physiological and pathophysiological interest. Bearing in mind the numerous negative ecological and health effects that it has on the human environment on a daily basis, extremely large initial efforts have been made for decades to suppress it to a certain extent.. However, the discoveries that, in the eighties of the last century, led to new scientific advances in the fields of chemistry, physiology and medicine, led to a stunning conclusion-that the survival of the most dominant species on Earth mostly depends on its (bio)synthesis. Depending on the concentration, it performs a dual role in the vasculature, since in lower concentrations it has the function of an extremely powerful vasodilator, while in the case of high concentrations it performs the role of cytotoxin and cytostatic, thereby contributing to the body's defense against parasitic infections and tumors. Maintaining its availability in the endothelium is crucial for the normal functioning of the cardiovascular system. The Nobel Prize, which was awarded in 1998. for the discovery of the signaling role of nitric oxide in the human body, opened up a series of specific questions, which primarily relate to the place and role of this molecule in various biochemical processes that constantly occur in the human body under different conditions. Accordingly, the theoretical and empirical issues of the role of nitric oxide in swimming, training, and the general health of swimmers (athletes) in water are the subject of this paper.

Advancing Sensitivity in Guided-Wave Surface Plasmon Resonance Sensor through Integration of 2D BlueP/MoS2 Hybrid Layers.

The surface plasmon resonance (SPR) signal, generated from the Kretschmann configuration, has been developed as an effective detection technology in chemical and biological sensors. The sensitivity of SPR signals to changes in the surrounding media makes it a valuable tool, as even a slight variation in refractive index can cause a significant change in SPR signals, such as phase, intensity, and resonance angle. However, the detection of ultralow changes in refractive index, which occur in chemical reactions or biological actions, remains a challenge for conventional SPR sensors due to their limited sensitivity. To overcome this limitation, we theoretically propose a novel guided-wave SPR (GWSPR) configuration coated with a few-layer blue phosphorene (blueP)/MoS2 hybrid structure. This configuration aims to enhance the electric field and subsequently achieve a significant improvement in sensitivity. The results of our study demonstrate that the proposed blueP/MoS2-based GWSPR sensor exhibits a high sensitivity of 290°/RIU, which represents an impressive enhancement of approximately 82.4% compared to the conventional Au-based SPR sensor. This advancement addresses the challenge of detecting ultralow changes in refractive index and offers significant potential for enhancing the performance of chemical and biological sensors.

A Review on 1,2,3 - Triazole & Piperazine Derivatives with Various Biological Activities

The largest family of organic molecules in organic chemistry are heterocyclic compounds. A heterocyclic compound is created when an oxygen, nitrogen, sulphur, or atom of a similar element is included in place of a carbon atom. Heterocyclic compounds play a crucial role in daily living. It has a wide scope of uses in agrochemicals and medicinal chemistry. One of a pair of chemical compounds known as triazoles and Piperazine, with the molecular formula C2H3N3 and C5H5N. A fundamental aromatic heterocyclic scaffold is 1,2,3-triazole and piperazine. Because of its structural characteristics, these moiety’s are valuable in material science and due to its extensive application in chemistry, these can also be synthesized from readily available compounds. This literature review sheds light on the fact that 1,2,3-triazole and piperazine of hetero compounds are profoundly receptive and are known to possess potent diverse activities like, analgesic, anti-HIV, antimalarial, antiviral, anti-inflammatory, anticancer, antibacterial, antifungal, anthelmintic, and so forth. In conclusion numerous biological actions of the Piperazine and 1,2,3-Triazole derivatives of heterocyclic compounds were detailed and reviewed in this review. Keywords: 1,2,3 - Triazole; Biological activities; Piperazine; Anticancer Activity

5-Oxo-ETE/OXER1: A Link between Tumor Cells and Macrophages Leading to Regulation of Migration.

Chronic inflammation is an important factor in the development of cancer. Macrophages found in tumors, known as tumor associated macrophages (TAMs), are key players in this process, promoting tumor growth through humoral and cellular mechanisms. 5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE), an arachidonic acid metabolite, has been described to possess a potent chemoattractant activity for human white blood cells (WBCs). The biological actions of 5-oxo-ETE are mediated through the GPCR 5-oxo-6E,8Z,11Z,14Z-eicosatetraenoic acid receptor (OXER1). In addition, we have previously reported OXER1 as one of the membrane androgen receptors with testosterone antagonizing 5-oxo-ETE's actions. OXER1 is highly expressed in inflammatory cells and many normal and cancer tissues and cells, including prostate and breast cancer, promoting cancer cell survival. In the present study we investigate the expression and role of OXER1 in WBCs, THP-1 monocytes, and THP-1 derived macrophages, as well as its possible role in the interaction between macrophages and cancer cells (DU-145 and T47D). We report that OXER1 is differentially expressed between WBCs and macrophages and that receptor expression is modified by LPS treatment. Our results show that testosterone and 5-oxo-ETE can act in an antagonistic way affecting Ca2+ movements, migration, and cytokines' expression in immune-related cells, in a differentiation-dependent manner. Finally, we report that 5-oxo-ETE, through OXER1, can attract macrophages to the tumor site while tumor cells' OXER1 activation in DU-145 prostate and T47D breast cancer cells, by macrophages, induces actin cytoskeletal changes and increases their migration.

An updated review on Phytochemical constituent and pharmacological properties of Moringa oleifera Lam

Moringa oleifera is a widely distributed plant of the Moringaceae family. Nearly, every portion of this tree has extraordinary qualities for food, medicine, or other industrial uses. This study is to gather an overview of global research, pharmacological activity, phytochemical and medicinal updates of M. oleifera, and give insight into its industrial and phytopharmaceutical uses to aid exploration. Moringa species have long been recognized for their antioxidant, anti-inflammatory, anticancer, and anti-hyperglycaemic properties. Most of their biological action is due to their high presence of flavonoids, glucosides, and glucosinolates. Furthermore, after analyzing the current M. oleifera research, we conclude that the majority of current research focuses on the plant's leaves and seeds, and the most concerned feature of M. oleifera is focused on its therapeutic potential. Yet more research is required to understand the molecular processes underlying its many features.

Comprehensive Study of Chalcone Derivatives

Chalcones are flavonoid molecules that exist naturally and are essentially plant substances. These are the chemical compounds that have demonstrated a variety of intriguing biological actions with therapeutic potential against a variety of ailments. Anthranilic acid and orthophenylene diamine combine to produce benzimidazole. Additionally, the benzimidazole acetylated product goes via Claisen-Schmidt condensation with aryl aldehyde to create the respective chalcones. Due to phenolic groups and the existence of α, β unsaturated carbonyl groups, naturally occurring chalcones are polyhydroxylated in the aryl ring and exhibit a variety of biological activities, including antioxidant, antibacterial, antiinflammatory, and anticancer properties. Being natural precursors, chalcones are intermediates that are crucial for the synthesis of flavones. This review article emphasizes on the informative aspects, methods of synthesis, biological activities and applications of Chalcones.

Рецензія на монографію «Сучасні радіаційно-ядерні загрози: навчальний посібник»

The study guide "Modern Radiation-Nuclear Threats" examines issues of radiation-nuclear threats at the current stage of human development (characteristics of the phenomenon of radioactivity and ionizing radiation, descriptions of nuclear warheads, damage factors of a nuclear explosion, radiation terrorism and radiation weapons, radiation-nuclear accidents at nuclear power plants etc). Features of the biological action of ionizing radiation (primary and secondary radiobiological effects, stochastic and deterministic effects, chronic radiation sickness) are described. Data are provided on the prospects for the development of nuclear energy in Ukraine. Modern technical means for assessing the degree of radiation-nuclear threat were considered separately: military dosimetric devices, dosimetric devices of the State Emergency Service and devices used in atomic energy were characterized. Issues of interdepartmental cooperation in the field of prevention and response to radiation and nuclear threats in Ukraine were considered. The study guide is intended for students, intern doctors and students of higher medical educational institutions of Ukraine and post-graduate medical education institutions. The study guide is drawn up in accordance with the requirements of the Program for the Training of Citizens of Ukraine under the Program for the Training of Reserve Officers of the Medical Service, the module "Military Toxicology, Radiology and Medical Protection" for applicants of the first (bachelor's) level of knowledge 22 "Health Care" in the specialties "Medical business", "Dentistry", "Pediatrics", "Pharmacy" and the second (master's) level of knowledge 22 "Health care" for military accounting specialties "Medical business", "Dentistry", "Pharmacy".

Dual Effect of Carnosine on ROS Formation in Rat Cultured Cortical Astrocytes.

Carnosine is composed of β-alanine and L-histidine and is considered to be an important neuroprotective agent with antioxidant, metal chelating, and antisenescence properties. However, children with serum carnosinase deficiency present increased circulating carnosine and severe neurological symptoms. We here investigated the in vitro effects of carnosine on redox and mitochondrial parameters in cultured cortical astrocytes from neonatal rats. Carnosine did not alter mitochondrial content or mitochondrial membrane potential. On the other hand, carnosine increased mitochondrial superoxide anion formation, levels of thiobarbituric acid reactive substances and oxidation of 2',7'-dichlorofluorescin diacetate (DCF-DA), indicating that carnosine per se acts as a pro-oxidant agent. Nonetheless, carnosine prevented DCF-DA oxidation induced by H2O2 in cultured cortical astrocytes. Since alterations on mitochondrial membrane potential are not likely to be involved in these effects of carnosine, the involvement of N-Methyl-D-aspartate (NMDA) receptors in the pro-oxidant actions of carnosine was investigated. MK-801, an antagonist of NMDA receptors, prevented DCF-DA oxidation induced by carnosine in cultured cortical astrocytes. Astrocyte reactivity induced by carnosine was also prevented by the coincubation with MK-801. The present study shows for the very first time the pro-oxidant effects of carnosine per se in astrocytes. The data raise awareness on the importance of a better understanding of the biological actions of carnosine, a nutraceutical otherwise widely reported as devoid of side effects.

Structural and Functional Analysis of Crucial Protein Complex in Basal Cell Skin Carcinoma via Network Construction

 Background: The basal-cell carcinoma (BCC) as one of the most common type of skin cancers reported to have an increasing trend during past years. Molecular approaches can be useful to advance diagnosis and treatment goals in this cancer.Materials and Methods: In this sense, one of the recent popular investigations, protein-protein interaction network analysis (PPI), was applied in this study to better facilitate molecular view of BCC.  Cytoscape v3.6.0 and its plug-ins analyzed and explored the topological and annotation features of the constructed network. Result: Among TP53, EGFR, AKT1, ERBB2, HRAS, and CCND1 as central agents of the network, five of them were also present in the first prominent cluster of the network in which considered for further analysis. It is suggested that there are significant related biological processes, actions, and expression changes for this highlighted cluster that may be related to BCC risk.  Conclusion: Therefore, the studied complex of proteins may worth considering for clinical studies and therapeutic interventions after validating by related tests. What is more, among these genes, EBBR2 has more to offer and consequently with additional values.  [GMJ.2018;7:e1271]