Biological Reactivity Research Articles

The interactive effect of family conflict history and physiological reactivity on different forms of aggression in young women

Evidence indicates that patterns of biological reactivity underlie different forms of aggression, but greater precision is needed in research targeting biopsychosocial processes that underlie such differences. This study investigated how sympathetic and parasympathetic nervous system (SNS and PNS) responses to social stress were associated with multiple forms of aggression in an ethnically-diverse sample of young adult females; it further examined whether early life exposure to family conflict moderated these relationships. In the context of high levels of family conflict history, greater SNS activation during a social conflict task was associated with more direct proactive aggression and increasing RSA was associated with more direct reactive aggression. Greater SNS activation during the task was associated with more direct reactive aggression regardless of family conflict history. Our findings affirm the need to capture the contributions of multiple physiological systems simultaneously and the importance of considering family history in the study of aggression.

Biological Stress Reactivity and Introspective Sensitivity: An Exploratory Study.

Reaction to stressful events has an impact on several cognitive processes. High levels of stress can be detrimental to working memory, attention and decision-making. Here, we investigated whether individuals’ reactivity to stress is related to their introspective sensitivity (i.e., how well individuals monitor their own cognitive processes). To this aim, 27 participants (16 women, mean 20 years old) were exposed to a psychosocial stress protocol (trier social stress test, TSST), where individuals were asked to simulate a job interview and perform arithmetic calculations in front of a panel of experts. The salivary cortisol concentration, which is considered a hormonal index of stress reactivity, was collected during the TSST through the enzyme immunoassay DRG cortisol ELISA kit. Based on literature recommendations, we classified participants as responders and non-responders to the TSST. In a second session, through a visual search paradigm, we evaluated the introspective sensitivity of the participants. We evaluated how these individuals (i) monitor their own performance (through a confidence estimation), (ii) monitor their own attentional shifts (through a subjective number of scanned items estimation, SNSI), and (iii) monitor their own response times (through an introspective response time estimation, iRT). We found that individuals with lower biological reactivity to stress are more accurate in estimating their SNSI (p = 0.033) and iRT (p = 0.002), and in evaluating their own performance (p = 0.038) through their confidence. We argue that the effect of stress on introspection is not limited to a particular type of introspective evaluation, but rather consists of a general alteration of the introspective mechanism.

Structural, spectral, biological and antioxidant analyses of baicalin and ıts vanadium complexes: a dft study

Molecular simulation analyses of baicalin and its vanadium complexes were done at B3LYP/6-31+G(d) and B3LYP/ANL2DZ levels, respectively. The conformer analyses were performed for baicalin and the most stable one is determined at OPLS3e method by using Maestro 11.9 program. Structural and spectral analyses of the baicalin – vanadium complex is performed in gas phase and water. Potential energy distribution (PED) analyses were done to evaluate the infrared (IR) spectra. 1H- and 13C-NMR spectra of V (IV) complex are analyzed. Finally, biological reactivity of related compounds is compared with that of cisplatin by using quantum chemical descriptors (QCD). Antioxidant properties of related structures are compared with each other by using same QCDs. According to QCD rankings, antioxidant activity of baicalin is increased with the complexing of studied ligand.

Urbanicity, biological stress system functioning and mental health in adolescents.

Growing up in an urban area has been associated with an increased chance of mental health problems in adults, but less is known about this association in adolescents. We examined whether current urbanicity was associated with mental health problems directly and indirectly via biological stress system functioning. Participants (n = 323) were adolescents from the Dutch general population. Measures included home and laboratory assessments of autonomic nervous system and hypothalamic-pituitary-adrenal axis functioning, neighborhood-level urbanicity and socioeconomic status, and mother- and adolescent self-reported mental health problems. Structural equation models showed that urbanicity was not associated with mental health problems directly. Urbanicity was associated with acute autonomic nervous system and hypothalamic-pituitary-adrenal axis reactivity such that adolescents who lived in more urban areas showed blunted biological stress reactivity. Furthermore, there was some evidence for an indirect effect of urbanicity on mother-reported behavioral problems via acute autonomic nervous system reactivity. Urbanicity was not associated with overall autonomic nervous system and hypothalamic-pituitary-adrenal axis reactivity or basal hypothalamic-pituitary-adrenal axis functioning. Although we observed some evidence for associations between urbanicity, biological stress reactivity and mental health problems, most of the tested associations were not statistically significant. Measures of long-term biological stress system functioning may be more relevant to the study of broader environmental factors such as urbanicity.

Ternary Co(II), Ni(II) and Cu(II) complexes containing dipyridophenazine and saccharin: Structures, reactivity, binding interactions with biomolecules and DNA damage activity

Herein, we report physiochemical aspects, crystal structures, biological reactivity and interaction, DNA damage activity and preliminary antimicrobial properties of three metal complexes, [Co/Ni(dppz)2(sac)(H2O)]ClO4 [Co(II), 1; Ni(II), 2] and [Cu(dppz)2(sac)]ClO4 (3), where dppz is dipyrido[3,2-a:2′,3′-c]phenazine as potential photosensitizer and DNA intercalator and sac is artificial sweetener saccharin (o-sulfobenzimide). The solid-state structural analysis revealed that the bivalent metal centre is in distorted octahedral [MN5(OH2); M = Co(II) (1), M = Ni(II) (2)] and square pyramidal [MN5; M = Cu(II) (3)] geometries arising from N,N donor-dppz and saccharinate (sac) ligands. The complexes showed redox responses with characteristic metal and ligand (dppz) redox couples. The reactivity and speciation of complexes were studied with glutathione (GSH) and sodium L(+) ascorbate (asc) from UV–vis, fluorescence and ESI-MS analyses. The complexes exhibit high binding affinity (K ~ 105–107 M−1) to human serum albumin (HSA) with a preferential binding affinity towards tryptophan (Trp-214) residue. The fluorescence resonance energy transfer (FRET) analysis showed an efficient energy transfer to the complexes. The monocationic complexes strongly bind CT-DNA (Kb ~ 105–106 M−1) by intercalation from planar dppz and stabilized from the electrostatic interactions resulting in unwinding and loss of helicity of DNA double helix. The complexes 1–3 damage supercoiled pUC19 DNA efficiently upon photo-irradiation at UV-A light (λ = 365 nm) to its nicked circular form via generation of hydroxyl radical (OH) and singlet oxygen (1O2) mediated pathways. The hydrolytic DNA cleavage activity of Cu-complex 3 induced by OH radicals and enhanced multifold in the presence of asc, GSH and light indicate involvement of a possible photoredox mechanism. All the complexes show moderate to good anti-microbial activity against Gram-positive Staphylococcus aureus bacterium. The studies showed the active and distinct role of transition metals and ligands for their biological activity.

Emotional Processing Coping Methods and Biomarkers of Stress in Young Adult Testicular Cancer Survivors.

Coping through emotional processing (EP) with cancer-related circumstances can take several forms, including methods thought to be constructive (e.g., planning, meaning making) and unconstructive (e.g., rumination). These forms can have differential relationships with experiences of stress. Associations of coping through constructive and unconstructive EP in expressive writing with salivary stress biomarkers were examined among young adult testicular cancer survivors. Constructive processing was significantly associated with less overall daily cortisol output and smaller salivary alpha-amylase awakening response; unconstructive processing was also associated with lower daily cortisol output. These preliminary results from this exploratory study inform future research associating emotion-regulation coping and biological stress reactivity.

Biological activity of typical chernozemic soil under different systems of main tillage and crops fertilisation of a short crop rotation

The influence of four main tillage systems and four fertilization systems on biological reactivity of a plow layer of typical chernozemic soil under agrophytocenosis of five crops was investigated during four year research (2016–2019) of the stationary field grain row crop rotation. Loss of mass of flax linen in a plow layer of soil during two months of the study characterizing the intensity of cellulose-decomposing microorganisms under beard, beardless, differential and disc tillage made correspondingly 24.5; 22.7; 23.4 and 23.3 % – for soybeans; 16.3; 15.7; 15.9 and 16.2 % for winter wheat, 24.1; 22.8; 24.7 and 22.6 % – for sunflowers, 27.7; 24.1; 25.1 and 23.7 % – for spring barley, 21.9; 19.9; 22.4 and 19.0 % – for corn. Steady surface and beardless tillage strengthen the differentiation of a plow layer according to the intensity indices of flax linen decomposing while the beard one tillage decreases. The most heterogenic plow layer was observed under beardless tillage; it was a bit lower under disk tillage in a crop rotation. The intensity of flax linen decomposing on the top of a plow layer (0–10 cm) is the highest under beardless tillage and the lowest under beard tillage, while in the bottom (20–30 cm) of a plow layer an inverse relation can be observed. The intensity of carbon dioxide production by the soil under soybeans, winter wheat and spring barley is the highest under beard tillage and the lowest it is for soybeans under beardless and differential tillage, for winter wheat, sunflowers and spring barley under beardless tillage and for corn under disc tillage. For sunflowers and corn this index is higher under differential rather than under beard tillage in a crop rotation. The biological reactivity of a plow layer of a typical chornozemic soil increases as the fertilizers application rates increase. Crop rotation productivity is almost at the same level under beard and beard-beardless tillage in a crop rotation. Systematic beardless and surface disc tillage decreases this index significantly. Key words: soil, crop, crop rotation, tillage, fertilizers, flax linen, carbon dioxide, plow layer, heterogeneity.

Importance of refractory ligands and their photodegradation for iron oceanic inventories and cycling

Iron is an essential micronutrient that limits primary production in up to 40% of the surface ocean and influences carbon dioxide uptake and climate change. Dissolved iron is mostly associated with loosely characterised organic molecules, called ligands, which define key aspects of the iron cycle such as its residence time, distribution and bioavailability to plankton. Models based on in situ ligand distributions and the behaviour of purified compounds include long-lived ligands in the deep ocean, bioreactive ligands in the surface ocean and photochemical processes as important components of the iron cycle. Herein, we further characterise biologically refractory ligands in dissolved organic matter (DOM) from the deep ocean and labile ligands in DOM from the surface ocean, and their photochemical and biological reactivities. Experimental results indicated that photodegradation of upwelled refractory iron-binding ligands can fuel iron remineralisation and its association with labile organic ligands, thus enhancing iron bioavailability in surface waters. These observations better elucidate the roles of biologically refractory and labile molecules and global overturning circulation in the ocean iron cycle, with implications for the initiation and sustainment of biological activity in iron-limited regions and the residence time of iron in the ocean.

Age, Physical Activity Motivation and Perceived Stress in Minority Girls.

Background:Physical activity in childhood and adolescence helps support physical and emotional health.Purpose:The study aimed to investigate if age was related to motivation for physical activity in minority girls, and whether the relationship may be potentially mediated by psychological or physiological stress.Methods:This cross-sectional observational study recruited Latino and African American girls ages 8 – 12 years (n = 79) in Tanner stage 1 or 2 via purposive sampling. Intrinsic motivation and perceived stress were measured by self-report survey; morning salivary cortisol samples were taken to calculate cortisol awakening response to estimate biological stress reactivity.Results:Increased age was related to higher intrinsic motivation to engage in physical activity. Lower perceived stress and lower awakening cortisol response were associated with higher intrinsic motivation. Bootstrapped mediation results indicated perceived stress may be a pathway through which age impacts intrinsic motivation for physical activity.Conclusion:While motivation to engage in physical activity may increase with age, perceived stress may dampen this motivation, resulting in decreased physical activity. Interventions to help increase pre-adolescent girls’ engagement in active behaviors may benefit from reducing children’s perceptions of stress.

Derivatives of pyridine and thiazole hybrid: Synthesis, DFT, biological evaluation via antimicrobial and DNA cleavage activity

A novel series of the 2-pyridine substituted 3a-e and 4-pyridine substituted 4a-e thiazole derivatives were synthesized, characterized, and evaluated for the biological activity. Crystallographic parameters and inter- and intramolecular interactions of 3a and 3c single crystals were examined through XRD analysis. The chemical reactivity potentials of the compounds were evaluated, by comparing with a theoretical approach based on DFT. The biological activity properties of synthesized compounds were determined by antimicrobial activity with Gram positive, Gram negative, Yeast via minimal inhibitory concentration (MIC) method and DNA cleavage activity studies. The most obvious findings to emerge from this study are that on the basis of both biological activity and chemical reactivity 4-pyridine thiazole hybrid compounds 4a-e showed more potent activity than 3a-e. In general, the antimicrobial activity of synthesized compounds follows the Bacillus cereus > Staphylococcus aureus > Candida albicans > Escherichia coli > Pseudomonas aeruginosa. The most potent compound 4c (MIC values 0.02 mM) exhibited antimicrobial activity against Staphylococcus aureus and Bacillus cereus. Furthermore, this compound has a good electrophilicity index value (4.56 eV).

Chemical and Biological Characteristics of Ethanolic Extract of Tussilago farfara L. Flowers: Composition, Antimicrobial and Antioxidant Activities

Tussilago farfara L. (Asteraceae) has a wide spectrum of biological reactivity, widely used in herbal medicine and has the potential for use in the agricultural sector. The ethanolic extract was obtained by maceration of freshly harvested flowers, followed by filtration of the extract and concentration with the help of a rotary evaporator. The chemical composition of ethanolic extract of Tussilago farfara L. was studied with the help of gas chromatography/mass spectrometry (GC/MS) method. It was found that the ethanolic extract of Tussilago farfara L. had antimicrobial reactivity against human pathogens and phytopathogens (bacteria and fungi). The values of the minimal inhibiting, bactericidal and fungicidal concentrations varied in the range of 2500-5000 μg/mL. The phytopathogenic fungus Alternaria solani St108 was the most sensitive to the components of ethanolic extract of Tussilago farfara L. Moderate antioxidant properties of ethanolic extract of Tussilago farfara L. at concentrations of 0.001 mg/mL and higher were revealed with the help of chemiluminescence analysis.

DAILY SOCIAL INTERACTIONS AND BIOLOGICAL STRESS REACTIVITY: ARE THERE AGE DIFFERENCES?

Older people experience fewer negative social interactions and report less anger and stress when faced with interpersonal tensions. Little is known, however, about age differences in biological responses to social interactions. We evaluated how salivary DHEA-S, a key indicator of stress reactivity, is associated with daily positive and negative social interactions among midlife and older adults. Participants were drawn from the Daily Health, Stress, and Relationship Study, which includes 93 adults age 40 to 95 who completed 14 days of daily diary interviews and provided saliva samples on four of those days. Multilevel models showed that people had higher DHEA-S on days in which they reported more positive interactions. Older respondents were less reactive to negative interactions relative to younger respondents. These findings indicate that positive social interactions may benefit biological stress reactivity regardless of age, whereas older adults are more resilient to the adverse effects of negative social interactions.

Oxidative Potential Versus Biological Effects: A Review on the Relevance of Cell-Free/Abiotic Assays as Predictors of Toxicity from Airborne Particulate Matter

Background and Objectives: The oxidative potential (OP) of particulate matter (PM) in cell-free/abiotic systems have been suggested as a possible measure of their biological reactivity and a relevant exposure metric for ambient air PM in epidemiological studies. The present review examined whether the OP of particles correlate with their biological effects, to determine the relevance of these cell-free assays as predictors of particle toxicity. Methods: PubMed, Google Scholar and Web of Science databases were searched to identify relevant studies published up to May 2019. The main inclusion criteria used for the selection of studies were that they should contain (1) multiple PM types or samples, (2) assessment of oxidative potential in cell-free systems and (3) assessment of biological effects in cells, animals or humans. Results: In total, 50 independent studies were identified assessing both OP and biological effects of ambient air PM or combustion particles such as diesel exhaust and wood smoke particles: 32 in vitro or in vivo studies exploring effects in cells or animals, and 18 clinical or epidemiological studies exploring effects in humans. Of these, 29 studies assessed the association between OP and biological effects by statistical analysis: 10 studies reported that at least one OP measure was statistically significantly associated with all endpoints examined, 12 studies reported that at least one OP measure was significantly associated with at least one effect outcome, while seven studies reported no significant correlation/association between any OP measures and any biological effects. The overall assessment revealed considerable variability in reported association between individual OP assays and specific outcomes, but evidence of positive association between intracellular ROS, oxidative damage and antioxidant response in vitro, and between OP assessed by the dithiothreitol (DDT) assay and asthma/wheeze in humans. There was little support for consistent association between OP and any other outcome assessed, either due to repeated lack of statistical association, variability in reported findings or limited numbers of available studies. Conclusions: Current assays for OP in cell-free/abiotic systems appear to have limited value in predicting PM toxicity. Clarifying the underlying causes may be important for further advancement in the field.

PF439 EXPLORING THE THERAPEUTIC POTENTIAL OF T‐CELL‐RECEPTOR REDIRECTED CD3+ NATURAL KILLER CELLS FOR ADOPTIVE CELLULAR THERAPY TO ACUTE MYELOID LEUKEMIA

Background:Adoptive cellular therapy (ACT) with redirected T cells expressing a chimeric antigen receptor (CAR) or transgenic T‐cell‐receptor (tTCR) has revolutionized cellular immunotherapy to hematological neoplasia, in particular to acute lymphoid leukemia, and also shows great promise as therapy for solid tumors. While CARs can only detect fully cell surface expressed target structures, TCR‐mediated recognition is not limited to surface antigens, but covers processed tumor neoantigens derived from the whole proteome. However, mispairing of transgenic and endogenous TCRs and restriction to patient‐derived, autologous T lymphocytes with variable “fitness” and T cell subsets due to individual health conditions and age of the patient exemplify the current limitations encountered in TCR‐redirected ACT. The natural killer (NK) cell line NK92 elicits lytic activity comparable to T cells, has been approved by the FDA for ACT and shown not to cause graft‐vs‐host disease. Since NK cell redirection is currently limited to CARs, NK92 cells engineered to express a CD3/TCR or CD3/CD8/TCR complex might evolve as an attractive, standardized cellular source for off‐the‐shelf TCR‐based ACT.Aims:Thus, the goal of this study was to explore NK92‐CD3+ and NK92‐CD3+CD8+ variants redirected to acute myeloid leukemia (AML) by expression of different AML‐reactive TCRs for antileukemic immunity in vitro and in vivo.Methods:NK92 cells expressing the γδεζ‐chains of the CD3 complex (NK92CD3+) were kindly provided by Dr. C. Wölfel (III. Dept. of Medicine) and further genetically engineered to express different human CD8 isoforms. Upon retroviral transfer (RT) of 3 different codon‐optimized and murinized TCRs obtained from AML‐specific CD8+CTL clones into NK92‐CD3+cells TCR expression was examined by flow cytometry (FC). NK92CD3+TCR+as well as NK92CD3+CD8+TCR+cells (together referred to as NK92TCR+) were enriched using antibiotic selection and immunomagnetic cell sorting (MACS®). Biological reactivity of redirected NK92TCR+cells to patient‐derived (primary) AML blasts was tested in vitro by IFN‐γ ELISPOT and 51Cr‐release assays. Comparable expression‐profiling of checkpoint molecules on NK92 and NK92TCR+cells such as e.g. CD80/86, PD1/PDL1, NKG2A, TIM3, TIGIT and HLA‐E was performed by FC. A patient‐derived AML‐xenograft (PDX) model in NSG mice has been already established.Results:Following RT and enrichment >80% of NK92‐CD3+cells expressed a given TCR, and >90% of NK92CD3+CD8+TCR+cells could be obtained. Upon coculture with different primary AML samples and corresponding EBV‐LCL blasts as controls NK92CD3+TCR+ elicited TCR dependent IFN–γ release and exhibited cytolytic activity to some but not all AML samples. CD8 coexpression slightly increased reactivity as measured by IFN‐γ release. Interestingly, as TCR‐redirected NK92 antileukemic responses appeared to be inhibited to some but not all AML samples we found high expression of HLA‐E on these AML blasts and of NGK2A on NK92TCR+ cells. Current blocking studies to examine whether a HLA‐E/NKG2A interaction might impair NK92TCR+ mediated AML reactivity are ongoing and will be presented. Moreover, first preliminary in vivo experiments of adoptively transferred NK92TCR+ cells into a NSG‐AML PDX model indicated biological activity but further studies are in progress to evaluate this point in more detail.Summary/Conclusion:These studies demonstrate that the established and FDA approved NK92 cell line can be redirected to elicit TCR‐mediated antitumoral immunity to AML. NK92TCR+ cells might thus represent a promising universal tool for an ‘off‐the‐shelf’ ACT product

Polymeric Nanogels as Versatile Nanoplatforms for Biomedical Applications

Nanomaterials have found extensive biomedical applications in the past few years because of their small size, low molecular weight, larger surface area, enhanced biological, and chemical reactivity. Among these nanomaterials, nanogels (NGs) are promising drug delivery systems and are composed of cross-linked polymeric nanoparticles ranging from 100 to 200 nm. NGs represent an innovative zone of research with speedy developments taking place on a daily basis. An incredible amount of focus is placed on the fabrication of NGs with novel polymers to achieve better control over the drug release. This review article covers a number of aspects of NGs including their types, associated pros and cons, and methods of preparation along with technical and economical superiority and therapeutic efficacy over each other. The last part of review summarizes the applications of NGs in the drug delivery and treatment of various diseases including brain disease, cardiovascular diseases, oxidative stress, diabetes, cancer therapy, tissue engineering, gene therapy, inflammatory disorders, pain management, ophthalmic and autoimmune diseases, and their future challenges. NGs appear to be an outstanding nominee for drug delivery systems, and further study is required to explore their interactions at the cellular and molecular levels.

Investigations of structural, spectral and electronic properties of enrofloxacin and boron complexes via quantum chemical calculation and molecular docking.

Quantum chemical analyses were performed over enrofloxacin and boron complexes. The most stable isomer of enrofloxacin was examined at M062X/6-31+G(d) level in gas phase. Structural and spectral characterizations of enrofloxacin and its complexes were performed at same level of theory. MEP maps of studied compound were calculated via ESP charges analyses. Some quantum chemical descriptors (QCDs) were calculated to determine the non-linear optical (NLO) and biological reactivity of studied molecules. Furthermore, molecular docking calculations between boron complexes and a protein (ID: 2ITN and 2ITV) were done. ADME analyses were done in the determination of the best drug candidate. As a result, complex (3) was found as the best in the NLO applications and it was found that complex (1) and (3) have similar biological reactivity in lung cancer treatment.

Small-Molecule-Based Fluorescent Sensors for Selective Detection of Reactive Oxygen Species in Biological Systems.

Reactive oxygen species (ROS) encompass a collection of intricately linked chemical entities characterized by individually distinct physicochemical properties and biological reactivities. Although excessive ROS generation is well known to underpin disease development, it has become increasingly evident that ROS also play central roles in redox regulation and normal physiology. A major challenge in uncovering the relevant biological mechanisms and deconvoluting the apparently paradoxical roles of distinct ROS in human health and disease lies in the selective and sensitive detection of these transient species in the complex biological milieu. Small-molecule-based fluorescent sensors enable molecular imaging of ROS with great spatial and temporal resolution and have thus been appreciated as excellent tools for aiding discoveries in modern redox biology. We review a selection of state-of-the-art sensors with demonstrated utility in biological systems. By providing a systematic overview based on underlying chemical sensing mechanisms, we wish to highlight the strengths and weaknesses in prior sensor works and propose some guiding principles for the development of future probes.

The inflammatory cytokine TNF-α regulates the biological behavior of rat nucleus pulposus mesenchymal stem cells through the NF-κB signaling pathway in vitro.

Nucleus pulposus (NP) mesenchymal stem cells (NPMSCs) are a potential cell source for intervertebral disc (IVD) regeneration; however, little is known about their response to tumor necrosis factor-α (TNF-α), a critical inflammation factor contributing to accelerating IVD degeneration. Accordingly, the aim of this study was to investigate the regulatory effects of TNF-α at high and low concentrations on the biological behaviors of healthy rat NPMSCs, including proliferation, migration, andNP differentiation. In this study, NPMSCs were treated with different concentration of TNF-α (0-200 ng/mL). Then we used annexin V/propidium iodide flow cytometry analysis to detect the apoptosis rate of NPMSCs. Cell Counting Kit-8, Edu assay, and cell cycle test were used to examine the proliferation of NPMSCs. Migration ability of NPMSCs was detected by wound healing assay and transwell migration assay. Pellets method was used to induce NP differentiation of NPMSCs, and immunohistochemical staining, real-time polymerase chain reaction, and Western blot analysis were used to examine the NPC phenotypic genes and proteins. The cells were further treated with the nuclear factor-κB (NF-κB) pathway inhibitor Bay 11-7082 to determine the role of the NF-κB pathway in the mechanism underlying the differentiation process. Results showed that treatment with a high concentration of TNF-α(50-200 ng/mL) could induce apoptosis of NPMSCs, whereas a relatively low TNF-α concentration (0.1-10 ng/mL) promoted the proliferation and migration of NPMSCs, but inhibited their differentiation toward NP cells. Moreover, we identified that the NF-κB signaling pathway is activated during the TNF-α-inhibited differentiation of NPMSCs, and the NF-κB signal inhibitor Bay 11-7082 could partially eliminate the adverse effect of TNF-α on the differentiation of NPMSCs. Therefore, our findings provide important insight into the dynamic biological behavior reactivity of NPMSCs to TNF-α during IVD degeneration process, thus may help us understanding the underlying mechanism of IVD degeneration.

Theoretical investigation of dicarboxamide mono copper (II) and novel transition metal complexes: Structural, chemical reactivity, vibrational and in-silico biological analysis

We are interested to the theoretical investigation of new synthesized dicarboxamide mono copper(II) complex, and other hypothetical one by modifying the transition metal by another one of the same series as (Mn(II), Fe(II), Fe(III), Co(II), Co(III), Cu(II), Ni(II) and Zn(II)). The aim of this study is to predict other stable complexes which can be synthesized and which would have comparable or better biological activity than that obtained experimentally, and predict their synthesis. For this purpose, structural, energetic, spectroscopic (IR, UV–Visible and NMR) properties have been evaluated at the DFT level. The stability of the considered complexes has been studied in the basis of the binding energies. The in-silico biological properties and chemical reactivity descriptors of hypothetical and synthesized compounds have been calculated and discussed.

Discovery of a pathway for terminal-alkyne amino acid biosynthesis.

Living systems can generate an enormous range of cellular functions, from mechanical infrastructure and signalling networks to enzymatic catalysis and information storage, using a notably limited set of chemical functional groups. This observation is especially notable when compared to the breadth of functional groups used as the basis for similar functions in synthetically derived small molecules and materials. The relatively small cross-section between biological and synthetic reactivity space forms the foundation for the development of bioorthogonal chemistry, in which the absence of a pair of reactive functional groups within the cell allows for a selective in situ reaction1-4. However, biologically 'rare' functional groups, such as the fluoro5, chloro6,7, bromo7,8, phosphonate9, enediyne10,11, cyano12, diazo13, alkene14 and alkyne15-17 groups, continue to be discovered in natural products made by plants, fungi and microorganisms, whichoffers a potential route to genetically encode the endogenous biosynthesis of bioorthogonal reagents within living organisms. In particular, the terminal alkyne has found broad utility via the Cu(I)-catalysed azide-alkyne cycloaddition 'click' reaction18. Here we report the discovery and characterization of a unique pathway to produce a terminal alkyne-containing amino acid in the bacterium Streptomyces cattleya. We found that L-lysine undergoes an unexpected reaction sequence that includes halogenation, oxidative C-C bond cleavage and triple bond formation through a putative allene intermediate. This pathway offers the potential for de novo cellular production of halo-, alkene- and alkyne-labelled proteins and natural products from glucose for a variety of downstream applications.