Volume 25, Issue 2
Development of a Protocol for Virtual Screening of PPARγ Weak Partial Agonists and Their Metabolites: Case Study on Naturally-derived Oleanane Triterpenoids117-132
Merilin Al Sharif, Petko Alov, Vessela Vitcheva, Antonia Diukendjieva, Denitsa Aluani, Virginia Tzankova, Ilza Pajeva
Merilin Al Sharif, Petko Alov, Vessela Vitcheva, Antonia Diukendjieva, Denitsa Aluani, Virginia Tzankova, Ilza Pajeva (2021) Development of a Protocol for Virtual Screening of PPARγ Weak Partial Agonists and Their Metabolites: Case Study on Naturally-derived Oleanane Triterpenoids, Int J Bioautomation, 25 (2), 117-132, doi: 10.7546/ijba.2021.25.2.000792
Abstract: Triterpenoids are well known metabolic syndrome (MetS) modulators. One of the suggested molecular mechanisms of action involves peroxisome proliferator-activated receptor gamma (PPARγ) activation. In this study we aimed to: (i) develop a virtual screening (VS) protocol for PPARγ weak partial agonists, (ii) predict potential metabolic transformations of naturally-derived triterpenoids, and (iii) perform VS of the triterpenoids and their metabolites. The NIH PubMed system was searched for publications about naturally-derived oleanane triterpenoids which are agonists or up-regulators of PPARγ. Structure- and ligand-based methods were combined in the development of the VS protocol. Metabolites were predicted using Meteor Nexus expert system (Lhasa Limited). Two in-house virtual libraries of PPARγ weak partial agonists and naturally-derived triterpenoids with their predicted metabolites were compiled. The pharmacophore-based docking protocol was applied for VS of the collected triterpenoids. Most of the docking poses reproduced the binding mode of caulophyllogenin (a weak partial agonist) in a complex with PPARγ (PDB ID 5F9B). Our results contribute to the mechanistic explanation of the effects of triterpenoids suggesting possible weak partial agonistic activity toward PPARγ. This research can direct further studies on triterpenoids’ role in MetS modulation. The developed protocol can be applied for VS of any PPARγ weak partial agonists.

Keywords: PPARγ, Weak partial agonists, Virtual screening, Triterpenoids, Metabolites, Metabolic syndrome
Molecular and Biochemical Characterization of nifHDK Genes in Klebsiella pneumoniae133-144
F. A. K. Al-Saffar, M. Z. S. Al-Khayyat
F. A. K. Al-Saffar, M. Z. S. Al-Khayyat (2021) Molecular and Biochemical Characterization of nifHDK Genes in Klebsiella pneumoniae, Int J Bioautomation, 25 (2), 133-144, doi: 10.7546/ijba.2021.25.2.000721
Abstract: Nitrogen fixation is carried by an enzyme complex called nitrogenase which consists of two main components, a dinitrogenase that is encoded by nifD and nifK and an iron containing reductase, also called Fe protein which is encoded by nifH. Nitrogen-free medium was used to detect the ability of nitrogen fixation by Klebsiella pneumoniae, then DNA was extracted and overlap extension polymerase chain reaction of nifH, nifD and nifK. To obtain nucleotide sequences of these genes, sequencing of the PCR products was one. The reverse sequence of nifH and the forward sequences of nifD and nifK were converted into amino acids using online translation tool. Homology modeling was carried out using SWISS-MODEL. The modeled amino acids sequences was validated using ERRAT and PROCHECK. The modeled sequences were reliable and of quality higher than 90%. The two subunits of Fe protein were constructed and tertiary structure was predicted together with the binding sites for prosthetic group and ADP molecule in Fe protein. The following amino acids Asp11, Lys13, Asn157, Ser158, Val183, Pro184, Arg185, Asp186, Val189, Gln190 and Glu193 seem to participate in the ADP binding. The complexity of this enzyme makes it difficult to be cloned in plants.

Keywords: Nitrogenase, Nitrogen fixation, Homology modeling
Soft Sensor Model Based on IBA-LSSVM for Photosynthetic Bacteria Fermentation Process145-158
Khalil Ur Rehman, Xiang Lin Zhu, Bo Wang, Muhammad Shahzad, Hussain Ahmad, Muhammad Abubakar, Muhammad Ajmal
Khalil Ur Rehman, Xiang Lin Zhu, Bo Wang, Muhammad Shahzad, Hussain Ahmad, Muhammad Abubakar, Muhammad Ajmal (2021) Soft Sensor Model Based on IBA-LSSVM for Photosynthetic Bacteria Fermentation Process, Int J Bioautomation, 25 (2), 145-158, doi: 10.7546/ijba.2021.25.2.000783
Abstract: It is difficult to measure the key biological process variables of photosynthetic bacteria fermentation in real-time, and offline measurement has a large time lag and cannot meet the needs of real-time optimization control. In this paper, a soft sensor model based on least square support vector machine with an improved bat algorithm (IBA-LSSVM) was proposed. The velocity equation of the bat algorithm (BA) was improved and the random variation operation in differential evolution algorithm was introduced into BA algorithm. Thus, the diversity of the population can be increased, and the global and local searching ability of the BA algorithm can be enhanced. Furthermore, the IBA-LSSVM soft sensor model was established for the living cell concentration and compared with BA-LSSVM soft sensor model. Finally, the simulation results show that the improved model was the better learning ability and prediction performance than BA-LSSVM, the measurement error is 0.1358. The improved model could provide accurate guidance for the photosynthetic bacteria fermentation control optimization. This model has certain practical value.

Keywords: Process variables, Improved bat algorithm, Least squares support vector machine, Soft sensor model, Photosynthetic bacteria fermentation
Radioprotective Effect of Curcumin on DNA Double Strand Breaks in Human Blood Lymphocytes after in vitro γ-Irradiation159-168
Nora Kostova, Albena Staynova, Ljubomira Popova-Hadjiiska, Dimka Georgieva, Ilonka Ivanova, Rositsa Hristova
Nora Kostova, Albena Staynova, Ljubomira Popova-Hadjiiska, Dimka Georgieva, Ilonka Ivanova, Rositsa Hristova (2021) Radioprotective Effect of Curcumin on DNA Double Strand Breaks in Human Blood Lymphocytes after in vitro γ-Irradiation, Int J Bioautomation, 25 (2), 159-168, doi: 10.7546/ijba.2021.25.2.000794
Abstract: Curcumin is a component of natural spice Curcuma longa. It is known that this polyphenol has been shown to exhibit anti-inflammatory, anticancer, antiviral, antioxidant and antibacterial activities. The mechanism of curcumin effectiveness on both healthy and cancer tissues is still unclear. Aims: In vitro assessment of curcumin effect on both double-strand breaks and chromosomal translocations frequency, after γ-irradiation. Methods: Human peripheral blood samples were pre-treated with different concentrations of curcumin (0.5 µg/ml; 10 µg/ml; 20 µg/ml and 100 µg/ml). Thereafter they were exposed to 60Co γ-rays using various irradiation doses (0.05 Gy; 0.5 Gy; 1 Gy and 2 Gy). Both γ H2AX/53BP1 foci assay and FISH analysis were used to evaluate DNA double-strand breaks and translocation frequencies. Results: Curcumin pre-treatment exhibited significant lower γ-H2AX/53BP1 foci appearance and reduced translocations frequency in irradiated compared to untreated lymphocytes. At 1 Gy irradiation and 10 µg/ml curcumin, the reduction of total translocations frequency was 42%. We found that at 2 Gy irradiation, the most protective concentration was 0.5 µg/ml curcumin. In this case, translocations declined almost twofold compared to curcumin non-treated cells. Conclusion: The present in vitro study demonstrates that curcumin reduces both γ-H2AX/53BP1 foci and translocations occurrence in peripheral blood lymphocytes, after γ-irradiation.

Keywords: Curcumin, γ-irradiation, γ-H2AX/53BP1 foci, Translocations
Impact Assessment of the Wastewater Treatment Plants’ Discharges on Maritsa River169-182
Tony Venelinov, Galina Yotova, Veronika Mihaylova, Svetlana Lazarova, Stefan Tsakovski
Tony Venelinov, Galina Yotova, Veronika Mihaylova, Svetlana Lazarova, Stefan Tsakovski (2021) Impact Assessment of the Wastewater Treatment Plants’ Discharges on Maritsa River, Int J Bioautomation, 25 (2), 169-182, doi: 10.7546/ijba.2021.25.2.000823
Abstract: Data analysis of wastewater samples at the outlets of wastewater treatment plants (WWTPs) of Pazardzhik, Plovdiv and Svilengrad, which discharge into the Maritsa River is presented. Total monthly loads for 2017 at the outlets are calculated using the monthly averages for the concentrations of chemical oxygen demand, biochemical oxygen demand, total phosphorus and total nitrogen (TN) and the monthly averages for the flow rates. The contributions of the WWTPs to the total river loads emphasize that the impact of WWTPs of Pazardzhik and Plovdiv is significantly greater than WWTP of Svilengrad. Additionally, river water samples were collected before and after the discharge points of the WWTPs in August 2018 and analyzed for water quality parameters listed in Directive 75/440/EEC. Comparison between the river concentrations before the outlet of WWPT - Pazardzhik and after the last sampling point (the outlet of WWTP - Svilengrad) indicates an increase for all the studied parameters, except for Al and Cu. Based on the results obtained for TN, the category of the surface water is significantly deteriorated after discharge of the WWTP - Plovdiv. Wastewater effect on the river surface water is also estimated by using a battery of ecotoxicological tests. The results are presented and compared by the classical approach using categorization based on water quality indicators.

Keywords: Surface water, Maritsa, Physicochemical parameters, Trace elements, Ecotoxicity, Wastewater treatment plant
Comparison of ECG Baseline Wander Removal Techniques and Improvement Based on Moving Average of Wavelet Approximation Coefficients183-204
Mounaim Aqil, Atman Jbari, Abdennasser Bourouhou
Mounaim Aqil, Atman Jbari, Abdennasser Bourouhou (2021) Comparison of ECG Baseline Wander Removal Techniques and Improvement Based on Moving Average of Wavelet Approximation Coefficients, Int J Bioautomation, 25 (2), 183-204, doi: 10.7546/ijba.2021.25.2.000770
Abstract: The baseline wander is among the artifacts that corrupt the ECG signal. This noise can affect some signal features, in particular the ST segment, which is an important marker for the diagnosis of ischemia. This paper presents a study on the effectiveness of several methods and techniques for suppressing the baseline wonder (BW) from the ECG signals. As a result, a new technique called moving average of wavelet approximation coefficients (DWT-MAV) is proposed. The techniques concerned are the moving average, the approximation of the baseline by polynomial fitting, the Savitzky-Golay filtering, and the discrete wavelet transform (DWT). The comparison of this techniques is performed using the main criteria for assessing the BW denoising quality criteria such mean square error (MSE), percent root mean square difference (PRD) and correlation coefficient (COR). In this paper, three other criteria of comparison are proposed namely the number of samples of the ECG signal, the baseline frequency variation and the time processing. Two of these new indices are related to possible real time ECG denoising. To improve the quality of BW suppression including the new indices, a new method is proposed. This technique is a combination of the DWT and the moving average methods. This new technique performs the best compromise in terms of MSE, PRD, coefficient correlation and the time processing. The simulations were performed on ECG recording from MIT-BIH database with synthetic and real baselines.

Keywords: ECG signal, Baseline wander, Discrete wavelet analysis, Mean square error, Percent root mean square difference, Baseline removal techniques


Sponsored by National Science Fund of Bulgaria, Grant No KP-06-NP/2/12, 2020

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