The brown dog tick (Rhipicephalus sanguineus) is the most prevalent tick in the world and a well-recognized vector of many pathogens affecting dogs and occasionally humans. Pathogens exploit tick ...salivary molecules for their survival and multiplication in the vector and transmission to and establishment in the hosts. Tick saliva contains various non-proteinaceous substances and secreted proteins that are differentially produced during feeding and comprise of inhibitors of blood congealing and platelet aggregation, vasodilatory and immunomodulatory substances, and compounds preventing itch and pain. One of these proteins is Evasin-1, which has a high binding affinity to certain types of chemokines. The binding of Evasin-1 to chemokines prevents the detection and immune response of the host to R. sanguineus, which may result in the successful transmission of pathogens. In this study, we screened potential Evasin-1 inhibitor based on the pharmacophore model derived from the binding site residues. Hit ligands were further screened via molecular docking and virtual ADMET prediction, which resulted in ZINC8856727 as the top ligand (binding affinity: -9.1 kcal/mol). Molecular dynamics simulation studies, coupled with MM-GBSA calculations and principal component analysis revealed that ZINC8856727 plays a vital role in the stability of Evasin-1. We recommend continuing the study by developing a formulation that serves as a potential medicine aid immune response during R. sanguineus infestation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Flax (
L.) is an important oil seed crop that is mostly cultivated in temperate climates. In addition to many commercial applications, flax is also used as a fibrous species or for livestock feed ...(animal fodder). For the last 40 years, flax has been used as a phytoremediation tool for the remediation of different heavy metals, particularly for phytoextraction when cultivated on metal contaminated soils. Among different fibrous crops (hemp, jute, ramie, and kenaf), flax represents the most economically important species and the majority of studies on metal contaminated soil for the phytoextraction of heavy metals have been conducted using flax. Therefore, a comprehensive review is needed for a better understanding of the phytoremediation potential of flax when grown in metal contaminated soil. This review describes the existing studies related to the phytoremediation potential of flax in different mediums such as soil and water. After phytoremediation, flax has the potential to be used for additional purposes such as linseed oil, fiber, and important livestock feed. This review also describes the phytoremediation potential of flax when grown in metal contaminated soil. Furthermore, techniques and methods to increase plant growth and biomass are also discussed in this work. However, future research is needed for a better understanding of the physiology, biochemistry, anatomy, and molecular biology of flax for increasing its pollutant removal efficiency.
Improving growth and productivity of plants that are vulnerable to environmental stresses, such as heavy metals, is of significant importance for meeting global food and energy demands. Because heavy ...metal toxicity not only causes impaired plant growth, it has also posed many concerns related to human well-being, so mitigation of heavy metal pollution is a necessary priority for a cleaner environment and healthier world. Hydrogen sulfide (H
S), a gaseous signaling molecule, is involved in metal-related oxidative stress mitigation and increased stress tolerance in plants. It performs multifunctional roles in plant growth regulation while reducing the adverse effects of abiotic stress. Most effective function of H
S in plants is to eliminate metal-related oxidative toxicity by regulating several key physiobiochemical processes. Soil pollution by heavy metals presents significant environmental challenge due to the absence of vegetation cover and the resulting depletion of key soil functions. However, the use of stress alleviators, such as H
S, along with suitable crop plants, has considerable potential for an effective management of these contaminated soils. Overall, the present review examines the imperative role of exogenous application of different H
S donors in reducing HMs toxicity, by promoting plant growth, stabilizing their physiobiochemical processes, and upregulating antioxidative metabolic activities. In addition, crosstalk of different growth regulators with endogenous H
S and their contribution to the mitigation of metal phytotoxicity have also been explored.
Synergy is defined as an interaction of some substances that cooperate to give rise to the combined effect greater than the sum of their individual effects. It is a natural strategy that has evolved ...by nature to more efficacy with low cost.
This study is designed to evaluate the chemopreventive effect of a combined drug sample which is prepared by mixing an equal portion of stigmasterol and palmatine isolated from
and
respectively at a concentration of 100 mg/kg and 200 mg/kg body weight during the whole concentration.
At the end of the study, it was found that this combined drug sample decreased the number of tumors and their size. This drug significantly reduced the serum level of glutamate pyruvate transaminase, alkaline phosphatase, glutamate oxalate transaminase, and bilirubin and enhanced the level of oxidative enzyme level of glutathione, superoxide dismutase, and catalase, and inhibit the level of lipid peroxides.
The result suggests that combined drug samples exhibit a chemopreventive effect which is better than the effect of individual drugs (stigmasterol and palmatine).
The deadliest recent pandemic outbreak of COVID-19 disease has severely damaged the socio-economic health of the people globally. Due to unavailability of any effective vaccine or treatment the human ...beings are still struggling to overcome the pandemic condition. In an attempt to discover anti-COVID molecule, we used in-silico approach and reported 160 natural polyphenols to identify the most promising druggable HITs that can further used for drug discovery process. The co-crystallized structure COVID protease enzyme (PDB id 6LU7) was used. HTVS, MD simulation, binding energy calculations and in-silico ADME calculation were done and analyzed. Depending upon the scores three compounds galangin, nalsudaldain and rhamnezine were identified and the docking score were found to be −7.704, −6.51, −4.212 respectively. These docked complexes were further subjected to MD simulation runs over a 100 ns time and the RMSD and RMSF values were determined. The RMSD values of three compounds were found to be 2.9 Å, 7.6 Å & 9.5 Å respectively and the lowest RMSF values suggested the steady stability of ligand–protein complexes. The binding free energies (ΔG) of compounds with protein were found to be −49.8, −56.45, −62.87 kJ/mole. Moreover, in-silico ADME calculations indicated the drug likeliness properties of these molecules. By considering all these in-silico results the identified HITs would be the most probable anti-COVID drug molecules that can be further taken in wet lab and can act as lead for development of newer inhibitor of COVID-19 main protease enzyme.
Within the family Fabaceae , the genus Glycine is composed of two subgenera annuals (2n=40) and perennials. This life strategy transition may have differentially affected the evolution of various ...gene families. Its cultivated species G. max has high level of susceptibility to major pathogens including viruses, bacteria and fungi. Understanding nucleotide-binding domain leucine-rich repeat ( NLR ) genes evolution in soybean is of paramount importance due to their central role in plant immunity and their potential in improving disease resistance in soybean cultivars. In this study, we investigated the significance of this annual-perennial transition on the macroevolution of NLR genes in the genus Glycine . Our results reveal a remarkable distinction between annual species such as Glycine max and Glycine soja , which exhibit an expanded NLR ome compared to perennial species ( G. cyrtoloba, G. stenophita, G. dolichocarpa, G. falcata, G. syndetika, G. latifolia and G. tomentella ). Our evolutionary timescale analysis pinpoints recent accelerated gene duplication events for this expansion, which occurred between 0.1 and 0.5 million years ago, driven predominantly by lineage-specific and terminal duplications. In contrast, perennials initially experienced significant contraction during the diploidisation phase following the Glycine -specific whole-genome duplication event (~10 million years ago). Despite the reduction in the NLR ome, perennial lineages exhibit a unique and highly diversified repertoire of NLR genes with limited interspecies synteny. The investigation of gene gain and loss ratios revealed that this diversification resulted from the birth of novel genes following individual speciation events. Among perennials, G. latifolia , a well-known resistance resource, has the highest ratio of these novel genes in the tertiary gene pool. Our study suggests evolutionary mechanisms, including recombination and transposition, as potential drivers for the emergence of these novel genes. This study also provides evidence for the unbalanced expansion of the NLR ome in the D t subgenome compared with the A t subgenome in the young allopolyploid G. dolichocarpa . To the best of our knowledge, this is the first study to investigate the effect of annuality and perenniality life transition on the evolution of NLR genes in the genus Glycine to identify its genomics resources for improving the resistance of soybean crop with global importance on the economy and food security.
Hydrogen cyanamide (Dormex) is a plant growth regulator that is classified as a highly toxic poison. There are no definite investigations to help in its diagnosis and follow-up. This study aimed to ...investigate the role of hypoxia-inducible factor-1α (HIF-1α) in the diagnosis, prediction, and follow-up of Dormex-intoxicated patients. Sixty subjects were equally divided into two groups: group A, the control group, and group B, the Dormex group. Clinical and laboratory evaluations, including arterial blood gases (ABG), prothrombin concentration (PC), the international normalized ratio (INR), a complete blood count (CBC), and HIF-1α, were done on admission. CBC and HIF-1α were repeated for group B 24 and 48 h after admission to track abnormalities. Group B also had brain computed tomography (CT). Patients with abnormal CT scans were referred for brain magnetic resonance imaging (MRI). Significant differences in levels of HB, WBCs, and platelets were also detected in group B up to 48 h after admission, as white blood cells (WBCs) rose with time and hemoglobin (HB) and platelets diminished. The results described a highly significant difference in HIF-1α between the groups, and it depended on the clinical condition; therefore, it can be used in the prediction and follow-up of patients up to 24 h after admission.
•Hypoxia inducible factor-1α level ≥ 2.75 IU is an indicator of severe Dormex poisoning.•HIF-1α is beneficial for patient follow up in the first 24 h.•HIF-1α can differentiate the presence of Dormex toxicity in doubted cases.•Platelet measurements decline and WBCs rise even if the first readings are normal in Dormex toxicity.
Ruiz & Pav is known as "matico" and belongs to the Piperaceae family, and in Peru it is traditionally used as an infusion or decoction to ameliorate wound healings or ulcers. In this study, the aim ...was to investigate the volatile components, the antioxidant profile, and the phytotoxic activity of the essential oil (EO) of
from Peru. To identify the phytoconstituents, the EO was injected into a Gas Chromatography-Mass Spectrometry (GC-MS) to obtain the chemical profile of the volatile components, followed by the antioxidant activity carried out by the reaction with three organic radicals (2,2-diphenyl-1-picrylhydrazyl (DPPH); 2,2'-azinobis-(3-ethylbenzothiazoline)-6- sulfonic acid (ABTS); ferric reducing/antioxidant power (FRAP)). Finally, the phytotoxic capabilities of the EO were tested on two model plants,
seeds and
bulbs. As a result, the analysis identified α-phellandrene as its main volatile chemical at 38.18%, followed by β-myrcene (29.48%) and β-phellandrene (21.88%). Regarding the antioxidant profile, the half inhibitory concentration (IC
) in DPPH was 160.12 ± 0.30 µg/mL, for ABTS it was 138.10 ± 0.06 µg/mL and finally in FRAP it was 450.10 ± 0.05 µg/mL. The phytotoxic activity demonstrated that the EO had high activity at 5% and 10% against
seed germination, the inhibition of root length, and hypocotyl length. Additionally, in
bulbs, the inhibition root length was obtained at 10%, both comparable to glyphosate, which was used as a positive control. The molecular docking on 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) revealed that α-phellandrene had -5.8 kcal/mol, being near to glyphosate at -6.3 kcal/mol. The conclusion shows that the EO of
presented antioxidant and phytotoxic activity and might be useful as a bioherbicide in the future.
Lung cancer is considered as one of the most serious disease worldwide. The progress of drug carriers based on nonmaterial, which selectively hold chemotherapeutic agents to cancer cells, has become ...a major focus in biomedical research. This study aimed to evaluate the growth inhibition and apoptosis induction of the human lung cancer cells (A-549) by Q-loaded SBA-15 conjugate system. Mesoporous silica nanoparticles (SBA-15) as host materials for transporting therapeutics medicaments were fabricated for targeted drug delivery toward lung cancer. With the objective of increasing bioavailability and aqueous solubility of flavonoids, SBA-15 was successfully loaded with the quercetin (Q)—a major flavonoid and characterized with the help of Fourier-transform infrared spectroscopy (FTIR) and transmission electron microscopy (TEM). The biological investigation on A549 cell line confirmed that the efficacy of Q-SBA-15 is much higher than only Q. Moreover, the apoptotic pathway of synthesized Q-SBA-15 NPs examined that the Q-SBA-15–mediated apoptosis via PI3K/AKT/mTOR signaling pathway. Thus, the newly conjugated Q-SBA-15 system improved the apoptotic fate through caspase-mediated apoptosis via PI3K/AKT/mTOR signaling pathway and hence, it can be potentially employed as an anticancer agent for lung cancer.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Antibiotic resistance is one of the major growing concerns for public health. Conventional antibiotics act on a few predefined targets and, with time, several bacteria have developed resistance ...against a large number of antibiotics. The WHO has suggested that antibiotic resistance is at a crisis stage and identification of new antibiotics and targets could be the only approach to bridge the gap. Filamentous Temperature Sensitive-Mutant Z (Fts-Z) is one of the promising and less explored antibiotic targets. It is a highly conserved protein and plays a key role in bacterial cell division by introducing a cytokinetic Z-ring formation. In the present article, the potential of over 165 cyanobacterial compounds with reported antibiotic activity against the catalytic core domain in the Fts-Z protein of the
was studied. The identified cyanobacterial compounds were screened using the GLIDE module of Maestro v-2019-2 followed by 100-ns molecular dynamics (MD) simulation. Ranking of the potential compound was performed using dock score and MMGBSA based free energy. The study reported that the docking score of aphanorphine (-6.010 Kcalmol
) and alpha-dimorphecolic acid (ADMA) (-6.574 Kcalmol
) showed significant role with respect to the reported potential inhibitor PC190723 (-4.135 Kcalmol
). A 100 ns MD simulation infers that Fts-Z ADMA complex has a stable conformation throughout the progress of the simulation. Both the compounds, i.e., ADMA and Aphanorphine, were further considered for In-vitro validation by performing anti-bacterial studies against
by agar well diffusion method. The results obtained through In-vitro studies confirm that ADMA, a small molecule of cyanobacterial origin, is a potential compound with an antibacterial activity that may act by inhibiting the novel target Fts-Z and could be a great drug candidate for antibiotic development.
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