The current population of Colombia has a genetic heterogeneity resulting from different migrations from other continents and within the country. In addition, there are small groups in their territory that have remained isolated and therefore have a different genetic pool in relation to that of the neighbouring urban populations. This population stratification must be considered in forensic analysis, being more complex for markers with marked intercontinental differentiation. In this study, population differentiation in Colombian admixed, native, and Afro-descendant populations was evaluated for a group of 38 indels described for forensic use. Allelic frequencies and parameters of forensic relevance were determined in each of the groups defined based on population differentiation analyses. In addition to the differences found between population groups, the results show that the set of 38 indels analysed could be useful in studies of individual identification in Colombia. The exclusion power presented by this set of markers suggests the need for joint use with other markers, being able to complement the STRs in paternity cases. High levels of both power of discrimination and exclusion were found when complementing the 38 HID-indels with a second multiplex, for a total of 83 indels.
Impaired redox homeostasis is a hallmark of end-stage renal disease (ESRD). Oxidative stress is one of the major risk factors associated with increased cardiovascular complications and mortality in this group. Both increased free radical production and reduced antioxidant activity play role in systemic oxidative stress in these patients. Genetic polymorphisms in genes encoding antioxidative enzymes such as glutathione transferases (GST), superoxide dismutase 2 or glutathione peroxidase 1 influence susceptibility towards chronic kidney disease as well as oxidative phenotype and mortality. Thus, individuals with a homozygous deletion of GSTM1 gene have shorter overall and cardiovascular-specific survival in ESRD. Biomarkers of oxidative stress including advanced oxidation protein products, malondialdehyde and cell adhesion molecules (soluble vascular cell adhesion molecule-1 and soluble intercellular adhesion molecule-1) also demonstrated a significant predictive role in terms of overall and cardiovascular survival in ESRD. Very recently a new approach towards testing proteomic biomarkers of endothelial dysfunction in the uremic milieu has been applied. Namely, biomarkers of oxidative stress and expression of a panel of inflammatory markers were studied in human umbilical vein endothelial cells (HUVECs) incubated in uremic serum. Incubation in uremic serum resulted in changes in the expression of a series of arteriosclerosis and atherosclerosis biomarkers including retinol-binding protein 4, regulated on activation, normal T cell expressed and secreted (RANTES), C-reactive protein, angiogenin, dickkopf-1 and platelet factor 4. The biomarker signature consisting of genomic and proteomic biomarkers could enable better monitoring of cardiovascular risk in ESRD patients and stratification into appropriate treatment groups.
Stress, poses a huge problem in today’s era when our lives have paced up and we are hooked up all the time. It can lead to a spectrum of health problems. Computer aided artificial intelligence systems for diagnosis of stress would enable a more objective and consistent diagnosis and decisions. Several parameters like Body temperature, Blood Pressure, muscle tension and stiffness, and heart rate are clear indicators and can be used by sensors to collect data about an individual and predict his stress levels. This stress creates pernicious effects particularly for employees and business owners. When workers hear artificial intelligence, robotizing the workplace doesn’t lend any relaxation, rather creates a sense of insecurity of losing job. Ironically, AI tools may do the opposite, making the workplace more human and keeping work stress at bay. In today’s workplace, AI tools are gaining traction. Chatbots and messaging interfaces for tasks like customer support, and client follow-up, can effectively cut out the unnecessary workload and reduce the burden. Automated repetitive tasks that employees do daily leave no room for them to relax. Rather, it drains out the energy and leads to stress. AI can automate for them thus enabling the employees to harness their intellect and skill set for building emotional intelligence, and social interactions which AI can never automate. AI enabled wearable devices, can analyse, and monitor behaviour and emotions. This can identify employees battling with stress. AI-led workplace stress management can play a significant role in diagnosis and cure of stress This will be key to workplace stress management, as you strive towards building a happy, productive, and future-ready workforce.
Advances in bioinformatics and high-throughput sequencing technologies have significantly increased our capability to explore the human microbiome. 16S ribosomal RNA (rRNA) is sequenced to understand the taxonomic composition of the human microbiome. In this study, bioinformatics analysis of 16S rRNA sequenced data from diseased (Crohn’s Colitis (CC) or Ulcerative Colitis (UC)) and adjacent healthy colon samples was performed by using Quantitative Insights Into Microbial Ecology (QIIME). Further, considering the race-specific information for these samples, a comparison of colon microbiome differences between African-Americans and Caucasians was performed. As a result, two hundred-eight different bacterial species were characterized. However, only fifty-three bacteria were described at the species level. The fraction of non-detrimental bacteria in diseased CC and UC samples was different from adjacent healthy colon samples. Additionally, the microbiome of diseased samples was dominated by oral bacteria belonging to the Phyla Firmicutes (Streptococcus, Staphylococcus, Peptostreptococcus) and Fusobacteria (Fusobacterium). The results also showed differences in the microbiome between African-Americans and Caucasians, indicating potential research focus on health disparities.
Inflammation is a vital part of the immune system’s response to injury and infection. Chronic inflammation and low grade inflammation has been linked to certain diseases such as heart disease, stroke and obesity, and may also lead to autoimmune disorders, such as rheumatoid arthritis (RA) and lupus (SLE). Researchers are still working to understand the implications of chronic inflammation on the body and the mechanisms involved in the process as well as monitoring outcome of drug treatment. Advances in high-throughput molecular technologies have increased investigations into the utility of transcriptomic, proteomic and metabolomic approaches as diagnostic tools for precision medicine [1,2]. Basic blood tests include readily detectable inflammatory markers and central autoantibodies, however, now deep analysis allow more clinical insight biofluids by proteomic profiling of plasma/ serum, extracellular vesicles and global autoantibody profiling. We present recent concepts and present studies investigating inflammatory diseases as well as low grade inflammatory diseases in different biofluids from plasma to synovial fluid and CSF accessing causalities leading to inflammation and pain in autoimmune diseases. High density protein array with more than 1600 antigen spots now allow subtyping of common autoimmune diseases including RA and SLE demonstrating new proteomic profiling of native autoantigens from patient biofluids [3,4]. Prediction of treatment outcome in low grade inflammatory diseases including obesity may be assessed by proteomic and multiplex analysis [5]. Label-free quantitative shotgun proteomics now enable individualized profiling of subjects providing biomarkers indicative of diagnosis and treatment efficacy. Translational biofluid profiling between systemic and local sites of inflammation e.g. plasma enables biomarker analysis and in-depth insight into disease pathology [6,7].
Many Gram-negative bacteria have been implicated in ocular infections causing severe vision impairment. The aim of this study is to list the virulence factors of the main gram-negative ocular pathogens. Data were extracted from PubMed and Google Scholar. Virulence factors of N. gonorrhoeae: pili, opacity proteins, lipooligosaccharide, sialylation, outer membrane porin PorB, IgA extracellular proteases, reduction modifiable protein. Virulence factors of Pseudomonas aeruginosa: Slime-glycolipoprotein, flagella, type IV pili, Quorum Sensing in biofilms. Virulence factors of Chlamydia trachomatis: The inoculation of the bacterium triggers an outburst of inflammatory response in the conjunctiva. The result is the replacement of the loose Type I stromal collagen of the area by compact Type V collagen that leads to trachomatous scarring of conjunctiva and severe vision impairment. Virulence factors of Bartonella Species: Bartonella targets and enters in the CD34+ cells, mainly erythrocytes and endothelial cells, where it survives in a vacuole protected from host defense mechanisms. The first step of pathogenesis is proinflammatory and autocrine activation and proliferation of the endothelial cell, which leads to inhibition of apoptosis. The second step is paracrine activation of macrophages and epithelial cells. Other virulence factors are the outer membrane proteins, TFSS transport systems, and the LPS which is atypical. It is a weak stimulus and antagonizes Toll Like Receptor 4. Gram negative bacteria provoke direct tissue damage and interact mainly with components of the innate immunity. The outcome of the battle is abolishment of the blood-ocular barrier and enhanced recruitment of inflammatory cells. For biofilm forming bacteria like P. aeruginosa, comprehension of their communication, survival and attack of host tissues is always a challenge. The enlightenment of the mechanisms of infection caused by these pathogens is crucial in diagnosis and treatment as they remain major causes of vision impairment.
Brain aging is a complex multifactorial process characterized by gradual and continuous loss of neuronal functions. It is hypothesized that at the basis of brain aging as well as age-related diseases, there is an impairment of the antioxidant defense system leading to an increase of oxidative stress. In this study, two different biological aspects involved in brain aging and neurodegeneration have been investigated: oxidative stress and iron accumulation damage. In primary mouse astrocytes, the stimulation with 50 μM lipoic acid (LA) and 100 nM vitamin D (vitD) was first investigated in a time-course study to determine the dosages to be used in combination and then in a permeability test using an in vitro blood-brain barrier. In a second set of experiments, the role of oxidative stress was investigated pretreating astrocytes with 200μM H2O2 for 30min. The ability of vitD and LA alone and combined together to prevent or repair the damage caused by oxidative stress was investigated after 24 h of stimulation by the MTT test, mitochondrial membrane potential measurement, and Western blot analysis. To induce neurodegeneration, cells were pretreated with 300 μM catalytic iron for 6 days and then treated with vitD and LA alone and combined for additional 6 days to investigate the protection exerted by combination, analyzing viability, ROS production, iron concentration, and activation of intracellular pathways. In our study, the combination of LA and vitD showed beneficial effects on viability of astrocytes, since the substances are able to cross the brain barrier. In addition, combined LA and vitD attenuated the H2O2-induced apoptosis through the mitochondrial-mediated pathway. The combination was also able to counteract the adverse conditions caused by iron, preventing its accumulation. All these data support the hypothesis of the synergistic and cooperative activity exerted by LA and vitD in astrocytes indicating a possible new strategy to slow down aging.
UV radiation contained in sunlight, as well as used in phototherapies, causes oxidative modifications to cellular components and biomolecules in cells forming various layers of human skin. These changes to a great extent concern on proteins involved in the metabolism and cytoprotection of skin fibroblasts and keratinocytes. As a result, occurred modifications can contribute to the disruption of cell function and the development of skin disorders. Therefore, there is still a need for highly active cytoprotective compounds with antioxidant properties. However, only the description of the exact changes induced by UV, as well as the mechanism of action of individual cytoprotective compounds would allow for the selection of an appropriate and safe method of skin cell protection. The proteomic approach, showing not only the profile of expressed proteins in experimental cells, but also the structures, conformations, localizations and interactions between these molecules, ensures complex look at this issue. Examples of compounds with a protective effect are known natural antioxidants: ascorbic acid, known as a vitamin C; polyphenol – rutin; and phytocannabinoid – cannabidiol. All of these compounds significantly affect the proteomic profile of skin cells, but according to the differences in their structure, they act in a various pathways. However, the proteomic analysis clearly indicate how mentioned compounds protects skin cells against UV induced upregulation of proteins involved in the proinflammatory signaling, DNA reorganization/expression, catalytic processes, antioxidant pathways and apoptosis, and downregulation of proteins with binding activity. Moreover, ascorbic acid, rutin as well as cannabidiol protect proteins against modifications by lipid peroxidation products and carboxymethylation/carboxyethylation, what is important in the level of their activity as well as signal transduction. Analysis of the data obtained through proteomic approach may create a potentially effective protective system against skin damages caused by UV radiation, taking into account various aspects of this factor action.
Background: A tumor microenvironment is a complicated multicellular system comprised of tumor cells, immune cells and blood vessels. Blood vessels are the barriers for drug tissue penetration. Effectively treating a cancer requires drug delivery systems to overcome biological barriers present in tumor microenvironments (TMEs). Methods: We designed a drug delivery system made of bacterial (Escherichia coli) double layer membrane-derived nanovesicles (DMVs) with the expression of RGD peptides and endogenous targeting ligands of bacteria. The physical and biological characteristics of DMVs were assessed by cryogenic transmission electron microscopy, western blotting, flow cytometry and confocal microscopy. Doxorubicin (DOX) was loaded in DMVs via a pH gradient driven drug loading method. Therapeutical effects of DOX-loaded DMVs were studied in a melanoma xenograft mouse model. Results:In vitro and in vivo experiments showed that DMVs can target neutrophils and monocytes that mediated the transport of DMVs across blood vessel barriers and they can also directly target tumor vasculature and tumor cells, resulting in enhanced delivery of therapeutics to TMEs. Furthermore, we developed a remote drug loading approach to efficiently encapsulate DOX inside DMVs, and the drug loading was 12% (w/w). In the B16-F10 melanoma mouse model, we showed that DOX-RGD-DMVs significantly inhibited the tumor growth compared to several controls. Conclusion: Our studies reveal that DMVs are a powerful tool to simultaneously target multiple cells in TMEs, thus increasing drug delivery for improved cancer therapies.
Despite the advances in synthetic chemistry and ligand binding assay technologies, the time and cost of synthesizing and testing thousands of compounds is prohibitive. Herein, will be presented deepScaffOpt algorithm for highly accurate, 1-sec fast, 2D-ligand based binding affinity prediction with minimal human input. deepScaffOpt employs artificial intelligence to build “on the fly” a receptor-specific Meta-Predictor that combines the output of multiple deep neural networks, which are engineered from feature vectors (“warheads”) carrying information only about 2D chemical structure. The arsenal of deepScaffOpt comprises warheads suitable for a wide range of molecules, including macrocycles, covalent inhibitors, peptidomimetics, even small fragments. deepScaffOpt’s automated scoring protocol achieved top performance in D3R Grand Challenges 2017 & 2018, and could predict free energies significantly closer to the experimental ones than Free Energy Perturbations (FEP). Unlike structure-based methods, deepScaffOpt can work well in the absence of receptor structure, and can be easily adapted for virtual screening of large chemical libraries to discover new diverse hit compounds, as well as off-target prediction and drug repurposing. However, in the absence of training samples, one must resort to first principles. Therefore, we develop in parallel semiempirical quantum mechanical (SQM) free energy methods [2]. We have demonstrated the superiority of SQM scoring protocols in native pose recognition and hit identification over the most widely used docking scoring functions on a variety of systems where binding was dominated by Enthalpy. A new SQM-based ligand conformational Entropy descriptor was recently introduced, which can be coupled both with physics based and machine learning methods for superior performance. In the case studies that will be shown in this presentation, Enthalpy alone failed to explain inhibitory activity, but SQMscoring enhanced with the Entropy descriptor reversed the situation. Analogous effects were observed when the Entropy descriptor was incorporated into deepScaffOpt’s warheads.
On behalf of Allied Academies delighted to welcome you all to the 4th International Conference and Expo on Proteomics, Genomics and Molecular Medicine, programmed in the month of February 26-27, 2021, in Vienna, Austria. Proteomics 2021 Congress Organized under the theme “World of opportunities and Evolution in Proteomics and Molecular Medicine” Now a few days, most proteomics, bioinformatics, mass spectrometry, statistical science, and restorative informatics territories have experienced enormous advancements driven by analytical methods and new work. Furthermore, these studies continue to be an active research field with growing applications and new difficulties in developing. Proteomics Congress 2021 seeks special and top-notch contributions in the fields of Proteomics Research, Mass Spectrometry, Protein Expression and Analysis, Bioinformatics, Computational Molecular Biology , Biochemistry and Biophysics, Glycobiology, Genetics and Genomics, Structural Biology, Structural Bioinformatics, Cardiac Proteomics, Proteomics and Bioinformatics Advances and associated zoos Proteomics and Bioinformatics give analysts the ability to calculate physiological effects and scan for troubled sedate reactions. Link future specialists and achieve great understanding of the mutagenic human changeability and successful atomic drug treatment. It contributes interdisciplinary stage and significant recognition for Poster Initiator, speakers to exhibit and discuss the latest trends, creation and handy challenges faced and arrangements in this field. We’re sure your experience and motivation will help us achieve our goals. To explore the field of proteomics and molecular medicine and some of the tools we may want to offer you, it would be perfect if you enjoy a walk with us in Vienna.
Drug chemistry and medicinal chemistry in the field at the intersection of chemistry, commonly organic chemistry and pharmacology and various other biological Specialities. Drug chemistry is aimed to invent new A drug that is a chemical substance, typically of known structure, which when administered to a living organism, produces a biological effect. As a part of this Drug Design 2020 Conference aims to innovation, Researches in new drug discovery. Drug Design is the field to find remedies and discover new medicine by chemical formulation applied to chemical synthesis in organic chemistry. By produce new drugs and medication to improve health and wellness to the people.
Medicinal plants produce important secondary metabolites such as flavonoids, tannins, saponins, alkaloids and many other compounds. These compounds are considered to be the chief plant constituent, because of their important role as antibacterial, anti-inflammatory and antioxidants agents. The aim of this study was to determine and characterize the phytochemicals present in water and methanol extracts of the roots of Asparagus nelsii, and conduct antioxidant tests of the extracts. Roots of A. nelsii were collected from Othika village in the Omusati Region and crude extracts were obtained with solvent extraction by reflux for 3 hours. Different screening methods from literature were employed to detect the phytochemicals present in the extracts. Characterization of the compounds was done using GCMS and the data was compared to the NIST library database for compound identification. Antioxidant test was conducted using the hydrogen peroxide scavenging essay with different concentrations of crude extracts. The phytochemicals present in the root extracts were determined to be flavonoids, saponins, tannins and phenolic compounds. One of the compounds that were successfully identified from the database by comparison of MS spectral data was Phenol-2methoxy-4-(1-propenyl). The water extract exhibited the highest antioxidant potential at a concentration of 110 μg/ml, and also exhibited higher higher antioxidant capacity compared to methanol extract. The results of this study show that the water and methanol extracts of A. nelsii can be used as accessible source of natural antioxidants.
The IOCB Prague was incorporated in 1953 as a part of the Czech Academy of Sciences. Already in early seventies first drugs developed by IOCB Prague scientists entered market. These drugs were commercialized through collaboration with local pharmaceutical company SPOFA and later with company Ferring. Great success of the research of prof. Antonin Holý brought antiviral drugs which were commercialized in collaboration with KU Leuven and US company Gilead Sciences. These drugs represent one of the main pillars in the treatment of HIV and HBV patients. Over last decade we have signed several license agreements with pharmaceutical companies and currently there are more than 10 projects in a preclinical development running at the IOCB Prague.
The identification of novel small and active molecules for the treatment of leishmaniases constitutes a research priority. Here, we expand on previous in silico investigations and virtual screens of small molecules targeting the Leishmania infantum initiation factor 4A (LieIF) as a potential drug target. LieIF belongs to the DEAD-box family of RNA helicases. DEAD-box proteins contain a highly conserved core structure with a dumbbell shape containing two, linked domains with structural homology to that of recombinant protein A (RecA). This core structure confers an ATP-dependent RNA-binding affinity, an RNA-dependent ATPase activity and an ATP-dependent RNA unwinding activity. We used the ATPase activity to establish a colorimetric assay in microtiter plates to screen for molecules that inhibit LieIF. We screened hundreds molecules previously identified by virtual screenings for their ability to bind to sites on LieIF that were important for the enzymatic activity. We discovered an interesting inhibitor: 6-α/β-aminocholestanol with an IC50 value of 150 ± 15 μM for 1 μM of LieIF. This compound also inhibits the RNA helicase activity of LieIF. The helicase assays and the ATPase competition experiments with the individual RecA-like domains and other proteins indicate that there are multiple binding sites on LieIF, and that the primary binding site is on domain 1 involving conserved RNA-binding motifs. Two out of ten identified chemical analogues of 6-α/β-aminocholestanol (6-α-aminocholestanol and 6-ketocholestanol) showed inhibitor effects on the ATPase activity of LieIF. Similar inhibitor effects were observed with mammalian eIF4A, but with different reaction profiles. All three molecules showed an anti-leishmanial activity against the promastigotes and the amastigotes of L. infantum parasites, and they showed non-significant toxicity toward macrophages. This study constitutes a first step towards the validation of LieIF as a drug target. It demonstrates biochemical differences between the Leishmania and mammalian eIF4A proteins, most notably in ATPase assays that show that rocaglamide affects the two proteins differently. To conclude, this work delivers a promising leishmanicidal molecule: 6- aminocholestanol with IC50 value lower than 1 μM on intracellular amastigotes, with little toxicity and with a selectivity index higher than 20. The 6-aminocholestanol constitutes a promising anti-Leishmania molecule that deserves further investigation.
Making a steady sedate definition could be a challenging errand in numerous occasions with regard to compatibility considers. The compatibility ponder between Croscarmellose (an excipient) and Amlodipine Besylate is considered amid the steady detailing sedate advancement of Amlodipine Besylate and is talked about in this introduction. Drug-excipient interaction between essential amine drug substances and Croscarmellose sodium is depicted in several writing sources and affirmed tentatively in our laboratory. The impact of soluble soil cation that included to the test dissolvable within the frame of Calcium acetic acid derivation salt was found and considered in our research facility to decrease such interaction and progress the recuperation of the sedate substance amid test planning for assay assurance by turned around stage HPLC. The interaction instrument and assurance of ideal concentration of Calcium Acetic acid derivation within the test dissolvable was decided. The assurance was based on Amlodipine Besylate test sampleplanning, within the nearness of Croscarmellose Na for accomplishing the total recuperation of Amlodipine Besylate from the test lattices. Unintended physicochemical interaction of an excipient with a medicate substance in a dose shape can result within the complication or official of the medicate, coming about in moderate and/or fragmented sedate discharge in a disintegration medium. It is imperative to evaluate the hazard whether such intuitive would decrease verbal bioavailability of a sedate from its dose shape. This chapter portrays the advancement of a technique to evaluate the bio relevance of the medicate discharge effect of drug-excipient official intuitive employing a model compound, brivanib aluminate. This technique was created employing a combination of modeling and reenactment devices as well as test information created in vitro and in vivo. In expansion, common application of this rule and strategy to other medicate substances and official affinities of drugs with excipients as a work of measurements is portrayed.
The journal aims to publish the most complete and reliable source of information on the advanced and very latest research topics related to the recent advancements in Proteomics for cancer research, Quantitative proteomics, Translational Research, Biomarker identification, Metabolomics, Biomolecular \u0026 Analytical Mass Spectrometry, Bioinformatics Tools and Bioinformatics Databases.
Development of novel drug delivery has been a growing interest among the researchers. The novel drug delivery usually aims for maximal drug bioavailability, tissue targeting, controlled release kinetics, minimal immune response, ease of administration, and the effective delivery of traditionally difficult drugs such as lipophiles, amphiphiles and biomolecules. Colloidal drug carriers are one of the most acceptable approach to attain the goals of the novel drug delivery system. Colloidal drug carriers include vesicular drug carriers and microparticulate drug carriers, which successfully prolong the existence of the drug in systemic circulation and lower the toxicity. A number of colloidal drug carriers such as liposomes, niosomes, pharmacosomes, virosomes, immunoliposomes, microparticles, nanoparticles, albumin microspheres have been developed, however, these carriers still have some draw-backs. To combat these drawbacks, Solid Lipid Nanoparticles (SLN) were introduced as a new class of colloidal drug carries. In this work, an overview about the definition, advantages, selection of ingredients and formulation techniques of the SLN is presented.
We are pleased to welcome you to the European Summit on Personalized Medicine and Pharmacogenomics after the successful completion of the series of Euro Personalized Medicine Congress. The congress is scheduled to take place in the beautiful city of Frankfurt, Germany, on May 28-29, 2020. This Euro Personalized Medicine 2020 conference will provide you with an exemplary research experience and huge ideas.
