Pseudomonas putida Metallothionein: Structural Analysis and Implications of Sustainable Heavy Metal Detoxification in Madinah.

Heavy metals, specifically cadmium (Cd) and lead (Pb), contaminating water bodies of Madinah (Saudi Arabia), is a significant environmental concern that necessitates prompt action. Madinah is exposed to toxic metals from multiple sources, such as tobacco, fresh and canned foods, and industrial activities. This influx of toxic metals presents potential hazards to both human health and the surrounding environment. The aim of this study is to explore the viability of utilizing metallothionein from Pseudomonas putida (P. putida) as a method of bioremediation to mitigate the deleterious effects of pollution attributable to Pb and Cd. The use of various computational approaches, such as physicochemical assessments, structural modeling, molecular docking, and protein-protein interaction investigations, has enabled us to successfully identify the exceptional metal-binding properties that metallothionein displays in P. putida. The identification of specific amino acid residues, namely GLU30 and GLN21, is crucial in understanding their pivotal role in facilitating the coordination of lead and cadmium. In addition, post-translational modifications present opportunities for augmenting the capacity to bind metals, thereby creating possibilities for focused engineering. The intricate web of interactions among proteins serves to emphasize the protein's participation in essential cellular mechanisms, thereby emphasizing its potential contributions to detoxification pathways. The present study establishes a strong basis for forthcoming experimental inquiries, offering potential novel approaches in bioremediation to tackle the issue of heavy metal contamination. Metallothionein from P. putida presents a highly encouraging potential as a viable remedy for environmental remediation, as it is capable of proficiently alleviating the detrimental consequences related to heavy metal pollution.

Galangal-Cinnamon Spice Mixture Blocks the Coronavirus Infection Pathway through Inhibition of SARS-CoV-2 MPro, Three HCoV-229E Targets; Quantum-Chemical Calculations Support In Vitro Evaluation.

Natural products such as domestic herbal drugs which are easily accessible and cost-effective can be used as a complementary treatment in mild and moderate COVID-19 cases. This study aimed to detect and describe the efficiency of phenolics detected in the galangal-cinnamon mixture in the inhibition of SARS-CoV-2's different protein targets. The potential antiviral effect of galangal-cinnamon aqueous extract (GCAE) against Low Pathogenic HCoV-229E was assessed using cytopathic effect inhibition assay and the crystal violet method. Low Pathogenic HCoV-229E was used as it is safer for in vitro laboratory experimentation and due to the conformation and the binding pockets similarity between HCoV-229E and SARS-CoV-2 MPro. The GCAE showed a significant antiviral effect against HCoV-229E (IC50 15.083 µg/mL). Twelve phenolic compounds were detected in the extract with ellagic, cinnamic, and gallic acids being the major identified phenolic acids, while rutin was the major identified flavonoid glycoside. Quantum-chemical calculations were made to find molecular properties using the DFT/B3LYP method with 6-311++G(2d,2p) basis set. Quantum-chemical values such as EHOMO, ELUMO, energy gap, ionization potential, chemical hardness, softness, and electronegativity values were calculated and discussed. Phenolic compounds detected by HPLC-DAD-UV in the GCAE were docked into the active site of 3 HCoV-229E targets (PDB IDs. 2ZU2, 6U7G, 7VN9, and 6WTT) to find the potential inhibitors that block the Coronavirus infection pathways from quantum and docking data for these compounds. There are good adaptations between the theoretical and experimental results showing that rutin has the highest activity against Low Pathogenic HCoV-229E in the GCAE extract.

An In Silico Bioremediation Study to Identify Essential Residues of Metallothionein Enhancing the Bioaccumulation of Heavy Metals in Pseudomonas aeruginosa.

Microorganisms are ubiquitously present in the environment and exert significant influence on numerous natural phenomena. The soil and groundwater systems, precipitation, and effluent outfalls from factories, refineries, and waste treatment facilities are all sources of heavy metal contamination. For example, Madinah, Saudi Arabia, has alarmingly high levels of lead and cadmium. The non-essential minerals cadmium (Cd) and lead (Pb) have been linked to damage to vital organs. Bioremediation is an essential component in the process of cleaning up polluted soil and water where biological agents such as bacteria are used to remove the contaminants. It is demonstrated that Pseudomonas aeruginosa (P. aeruginosa) isolated from activated sludge was able to remove Cd and Pb from water. The protein sequence of metallothionein from P. aeruginosa was retrieved to explore it for physicoparameters, orthologs, domain, family, motifs, and conserved residues. The homology structure was generated, and models were validated. Docking of the best model with the heavy metals was carried out to inspect the intramolecular interactions. The target protein was found to belong to the "metallothionein_pro" family, containing six motifs, and showed a close orthologous relationship with other heavy metal-resistant bacteria. The best model was generated by Phyre2. In this study, three key residues of metallothionein were identified that participate in heavy metal (Pb and Cd) binding, viz., Ala33, Ser34, and Glu59. In addition, the study provides an essential basis to explore protein engineering for the optimum use of metallothionein protein to reduce/remove heavy metals from the environment.

Biochemical and histopathological studies of the PTU-induced hypothyroid rat kidney with reference to the ameliorating role of folic acid.

Thyroid hormones (THs) are essential for growth and development of the kidney. Also TH influences glomerular filtration and tubular functions. Hypothyroidism negative influences kidney function indirectly by affecting the cardiovascular system and the renal blood flow, and directly by affecting glomerular filtration, tubular functions and the structure of the kidney. The purpose of this study was to evaluate changes in biochemical markers, oxidative stress parameter and histological changes in kidney of hypothyroid rats before and after treatment with folic acid. Hypothyroidism was induced for 6 weeks by the administration of propylthiouracil in drinking water. Urea and creatinine were measured to evaluate the changes in kidney function. Also malondialdehyde, nitrite, nitrate and other oxidative stress parameter were measured in serum and kidney tissue as indicators of oxidative damage. Kidney function and oxidative stress parameters in hypothyroid rats were significantly changed compared to those in control rats. Treatment with folic acid helps in improving the adverse effect of hypothyroidism; the histological study also confirms this finding.