Prediction of anticancer peptides derived from the true lectins of Phoenix dactylifera and their synergetic effect with mitotane.

Background and aims: Cancer continues to be a significant source of both illness and death on a global scale, traditional medicinal plants continue to serve as a fundamental resource of natural bioactive compounds as an alternative source of remedies. Although there have been numerous studies on the therapeutic role of Phoenix dactylifera, the study of the role of peptides has not been thoroughly investigated. This study aimed to investigate the anticancer activity of lectin peptides from P. dactylifera using in silico and in vivo analysis. Methods: Different computational tools were used to extract and predict anticancer peptides from the true lectins of P. dactylifera. Nine peptides that are bioactive substances have been investigated for their anticancer activity against MCF-7 and T47D (two forms of breast cancer). To counteract the unfavorable effects of mitotane, the most potent peptides (U3 and U7) were combined with it and assessed for anticancer activity against MCF-7 and HepG2. Results: In silico analysis revealed that nine peptides were predicted with anticancer activity. In cell lines, the lowest IC50 values were measured in U3 and U7 against MCF-7 and T47D cells. U3 or U7 in combination with mitotane demonstrated the lowest IC50 against MCF-7 and HepG2. The maximum level of cell proliferation inhibition was 22% when U3 (500 µg/mL) and 25 µg/mL mitotane were combined, compared to 41% when 25 µg/mL mitotane was used alone. When mitotane and U3 or U7 were combined, it was shown that these bioactive substances worked synergistically with mitotane to lessen its negative effects. The combination of peptides and mitotane could be regarded as an efficient chemotherapeutic medication having these bioactive properties for treating a variety of tumors while enhancing the reduction of side effects.

Multi-targeted therapeutic potential of stigmasterol from the Euphorbia ammak plant in treating lung and breast cancer.

Cancer is the most prevalent disease globally, which presents a significant challenge to the healthcare industry, with breast and lung cancer being predominant malignancies. This study used RNA-seq data from the TCGA database to identify potential biomarkers for lung and breast cancer. Tumor Necrosis Factor (TNFAIP8) and Sulfite Oxidase (SUOX) showed significant expression variation and were selected for further study using structure-based drug discovery (SBDD). Compounds derived from the Euphorbia ammak plant were selected for in-silico study with both TNFAIP8 and SUOX. Stigmasterol had the greatest binding scores (normalized scores of -8.53 kcal/mol and -9.69 kcal/mol) with both proteins, indicating strong stability in their binding pockets throughout the molecular dynamics' simulation. Although Stigmasterol first changed its initial conformation (RMSD = 0.5 nm with the starting conformation) in SUOX, it eventually reached a stable conformation (RMSD of 1.5 nm). The compound on TNFAIP8 showed a persistent shape (RMSD of 0.35 nm), indicating strong protein stability. The binding free energy of the complex was calculated using the MM/GBSA technique; TNFAIP8 had a ΔGTOTAL of -24.98 kcal/mol, with TYR160 being the most significant residue, contributing -2.52 kcal/mol. On the other hand, the SUOX complex had a binding free energy of -16.87 kcal/mol, with LEU151 being the primary contributor (-1.17 kcal/mol). Analysis of the complexes' free energy landscape unveiled several states with minimum free energy, indicating robust interactions between the protein and ligand. In its conclusion, this work emphasises the favourable ability of Stigmasterol to bind with prospective targets for lung and breast cancer, indicating the need for more experimental study.

Intrinsic factors behind long COVID: IV. Hypothetical roles of the SARS-CoV-2 nucleocapsid protein and its liquid-liquid phase separation.

When the SARS-CoV-2 virus infects humans, it leads to a condition called COVID-19 that has a wide spectrum of clinical manifestations, from no symptoms to acute respiratory distress syndrome. The virus initiates damage by attaching to the ACE-2 protein on the surface of endothelial cells that line the blood vessels and using these cells as hosts for replication. Reactive oxygen species levels are increased during viral replication, which leads to oxidative stress. About three-fifths (~60%) of the people who get infected with the virus eradicate it from their body after 28 days and recover their normal activity. However, a large fraction (~40%) of the people who are infected with the virus suffer from various symptoms (anosmia and/or ageusia, fatigue, cough, myalgia, cognitive impairment, insomnia, dyspnea, and tachycardia) beyond 12 weeks and are diagnosed with a syndrome called long COVID. Long-term clinical studies in a group of people who contracted SARS-CoV-2 have been contrasted with a noninfected matched group of people. A subset of infected people can be distinguished by a set of cytokine markers to have persistent, low-grade inflammation and often self-report two or more bothersome symptoms. No medication can alleviate their symptoms efficiently. Coronavirus nucleocapsid proteins have been investigated extensively as potential drug targets due to their key roles in virus replication, among which is their ability to bind their respective genomic RNAs for incorporation into emerging virions. This review highlights basic studies of the nucleocapsid protein and its ability to undergo liquid-liquid phase separation. We hypothesize that this ability of the nucleocapsid protein for phase separation may contribute to long COVID. This hypothesis unlocks new investigation angles and could potentially open novel avenues for a better understanding of long COVID and treating this condition.

Alleviation of carbendazim toxicity effect by Moringa oleifera oil and Linum usitatissimum L. oil on testes of male rats: Physiological, histological and in silico study.

Carbendazim (CBZ) is a widely used fungicide that is used to control the unwanted growth of fungi on fruits and vegetables. Sixty male rats were divided into six groups, each having ten. Group one served as control, animals belonging to group two were exposed to CBZ in the measure of 200 mg/kg body weight (BW). In the third and fourth groups, rats were administered 800 mg/kg BW of Moringa oleifera (moringa oil) and Linum usitatissimum L. (flaxseed oil), plus CBZ with the same dose given to group two. Groups five and six were administered with moringa and flaxseed oils respectively for six weeks. A marked decline was seen in oxidative stress markers, reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and a rise in malondialdehyde (MDA) level in group two with severe histological disruptions. Moringa oil and flaxseed oil were used to alleviate these changes. In addition, a biocomputational molecular docking analysis of three proteins found in male rats was performed. In relation to CBZ (CID:10584007) the screened proteins namely testis-expressed protein (TX101_RAT), EPPI_RAT, and glutathione peroxidase 5 (GPX5_RAT) were docked, and their docking score were obtained (-5.9 kcal/mol), (-5.8 kcal/mol) and (-5.6 kcal/mol) respectively. By examining these interactions in 2D and 3D structures, a detailed understanding of the unique and specific binding affinity, hydrogen bonds, hydrophobic interactions, ionic bonds, and water bonds were obtained. Structure-based virtual screening (SBVS) molecular docking analysis showed that protein interaction with CBZ causes reproductive complications in protein expression and functions by hampering their normal function and blocking active sites.

Overview of the SARS-CoV-2 nucleocapsid protein.

Since the emergence of SARS-CoV in 2003, researchers worldwide have been toiling away at deciphering this virus's biological intricacies. In line with other known coronaviruses, the nucleocapsid (N) protein is an important structural component of SARS-CoV. As a result, much emphasis has been placed on characterizing this protein. Independent research conducted by a variety of laboratories has clearly demonstrated the primary function of this protein, which is to encapsidate the viral genome. Furthermore, various accounts indicate that this particular protein disrupts diverse intracellular pathways. Such observations imply its vital role in regulating the virus as well. The opening segment of this review will expound upon these distinct characteristics succinctly exhibited by the N protein. Additionally, it has been suggested that the N protein possesses diagnostic and vaccine capabilities when dealing with SARS-CoV. In light of this fact, we will be reviewing some recent headway in the use cases for N protein toward clinical purposes within this article's concluding segments. This forward movement pertains to both developments of COVID-19-oriented therapeutic targets as well as diagnostic measures. The strides made by medical researchers offer encouragement, knowing they are heading toward a brighter future combating global pandemic situations such as these.

Effect of iron nanoparticles and conventional sources of Fe on growth, physiology and nutrient accumulation in wheat plants grown on normal and salt-affected soils.

Salt stress is becoming a serious problem for the global environment and agricultural sector. Different sources of iron (Fe) can provide an eco-friendly solution to remediate salt-affected soils. The Fe nanoparticles (FeNPs) and conventional sources of Fe (iron-ethylene diamine tetra acetic acid; Fe-EDTA; and iron sulfate; FeSO4) were used to evaluate their effects on wheat crop grown in normal and salt-affected soils. Application of FeNPs (25 mg/kg) on normal soil increased the dry weights of wheat roots, shoots, and grains by 46%, 59%, and 77%, respectively. In salt-affected soil, FeNPs increased the dry weights of wheat roots, shoots, and grains by 65%, 78%, and 61%, respectively. The application of FeSO4 and Fe-EDTA increased the growth parameters of wheat in both normal and salt-affected soils compared to the respective controls. The photosynthetic parameters, including chlorophyll a (50%), chlorophyll b (67%), carotenoids (62%), and total chlorophyll contents (50%), were increased with the application of FeNPs under salt stress. The FeNPs increased plant-essential nutrients like iron, zinc, calcium, magnesium, and potassium in both normal and salt-affected soils. The experiment revealed that the application of Fe plays a significant role in enhancing the growth of wheat on alkaline normal and salt-affected soils. Maximum growth response was recorded with FeNPs than other Fe sources. The future must be focused on long term field experiments to economize the application of FeNPs on a large scale for commercialization.

Responses of two strawberry cultivars to NaCl-induced salt stress under the influence of ZnO nanoparticles.

Salinity stress is one of the most serious impacts of climate changes on agriculture production, especially in salt sensitive crop plants, like strawberry. Currently, the utilization of nanomolecules in agriculture is thought to be a useful strategy to compact abiotic and biotic stresses. This study aimed to investigate the effect of zinc oxide nanoparticles (ZnO-NPs) on the in vitro growth, ions uptake, biochemical and anatomical responses of two strawberry cvs (Camarosa and Sweet Charlie) under NaCl-induced salt stress. A 2x3x3 factorial experiment was conducted, with three levels of ZnO-NPs (0, 15 and 30 mg 1-l) and three levels of NaCl-induced salt stress (0, 35 and 70 mM). The results showed that increased levels of NaCl in the medium had led to decrease in shoot fresh weight and proliferative potential. The cv Camarosa was found to be relatively more tolerant to salt stress. Additionally, salt stress leads to an accumulation of toxic ions (Na + and Cl-), as well as a decrease in K + uptake. However, application of ZnO-NPs at a concentration of 15 mg 1-l was found to alleviate these effects by increasing or stabilizing growth traits, decreasing the accumulation of toxic ions and the Na+/K + ratio, and increasing K + uptake. Additionally, this treatment led to elevated levels of catalase (CAT), peroxidase (POD) and proline content. The positive impacts of ZnO-NPs application were reflected on the leaf anatomical features, being better adapted to salt stress. The study highlighted the efficiency of utilizing tissue culture technique in screening of strawberry cultivars for salinity tolerance under the influence of NPs.

Arabica coffee and olive oils mitigate malathion-induced nephrotoxicity in rat: In silico, immunohistochemical and biochemical evaluation.

Malathion (MAL) is an organophosphate insecticide that disrupts the body's antioxidant system; it is one of the earliest organophosphate insecticides extensively used as dust, emulsion, and vapor control a wide variety of insect pests under different conditions. This experimentation aims to evaluate the influence of Arabica coffee oil and olive oil on MAL-induced nephrotoxicity in male rat. 6 sets bearing the same number of animals were applied to this experiment. Each set comprised 10 rats. The first set of rats was used as the control group; rats in the second set were exposed to MAL measured at 100 mg/kg body weight for 7 weeks. Animals in the third and fourth set were treated with 400 mg/kg body weight of Arabica coffee oil and olive oil, and 100 mg/kg body weight of MAL. The fifth, together with the sixth set, were fed with a similar proportion of Arabica coffee oil and olive oil as administered to the third set of rats. After the experimental duration, rats of group 2 showed severe biochemical alterations, including significant increases of creatinine, uric acids, and urea nitrogen (BUN), resulting in marked decreases in serum albumin values and total protein (TP). Severe histopathological and immunohistochemical alterations of kidney tissues were observed in exposed MAL-intoxicated rats. Administration of these oils reduced the detected biochemical, histopathological modifications caused by MAL intoxication. Two active ingredients in Arabica coffee oil (oleic acid) and olive oil (hydroxytyrosol) showed good cyclooxygenase-2 (COX 2) interaction. Moreover, oleic acid from coffee oil and olive oil exhibited impressive association with xanthine oxidase (XO). The current finding showed that coffee oil and olive oil could be appraised as possible and a likely deterrence component against nephrotoxicity brought about by MAL.

In vitro evaluation of some high yield potato (Solanum tuberosum L.) cultivars under imposition of salinity at the cellular and organ levels.

Salinity and drought stress, which combines a lack of water and sodium toxicity, are more of the problems faced by plants and agricultural crops in newly reclaimed lands. Therefore, the direction of our research is to produce salinity-tolerant plants to increase the productivity of crops under conditions of salt stress. Potato callus was studied using different concentrations of NaCl (0.0, 50, 75, 100, 125, 150 and 200 mM). Shoot induction was obtained from callus treated with MS medium containing 4.0 and 5.0 mg l-1 TDZ + 0.5 mg l-1 GA3 with NaCl up to 125 mM and 150 mM for Rosetta and Victoria, respectively. When plantlets were cultured on MS medium containing 3.0 mg l-1 kinetin and 1.0 mg l-1paclobutrazol (PBZ) with 80 or 90 g l-1 sucrose after two months gave a good microtuber per explant of Rosetta and Victoria cultivar which gave number of microtuber/plantlet (1.85) and (2.40) when plantlets treated with 125 mM and 150 mM NaCl of Rosetta and Victoria cultivar, respectively. In general, the results were shown in each treatment of NaCl and that amounts of proline at 125 and 150 mMNaCl were significantly more than 0.0, 50, 75 and 100 mM NaCl. This result is related to the role of proline in the osmotic adjustment of a higher concentration of salinity. The results showed that the amounts of sodium increased with increasing the salt concentration, but the amount of potassium decreased and also increased the Na+/K+ ratio with increasing the salt concentration. This research is important for in vitro potato plant regeneration, which requires optimization before genetic transformation can be achieved.

Predominance of Antioxidants in Some Edible Plant Oils in Ameliorating Oxidative Stress and Testicular Toxicity Induced by Malathion.

Malathion (MAL) is an insecticide that has been linked to reproductive system damage in both humans and animals. In the present investigation, the antitoxic effects of coffee and olive oils on MAL-induced testicular dysfunctions were evaluated. MAL-intoxicated rats were supplemented with coffee and olive oils (400 mg/kg) for 7 weeks. Exposure to MAL resulted in statistically altered antioxidant enzymes and histopathological findings of necrotic seminiferous tubules and spermatogenetic arrest in rats after seven weeks of treatment. The effects of MAL intoxication on physiological and histopathological changes were improved by the use of these oils. Murine double minute 2 (MDM2) was found to interact well with chlorogenic acid and oleuropein, two compounds from coffee and olive oils, respectively. Coffee oil and olive oil were found to be promising therapeutic agents for MAL-induced testicular toxicity and oxidative damage.

Molecular insights into novel environmental strains of Klebsiella quasipneumoniae harboring different antimicrobial-resistance genes.

Introduction: The emergence of bacterial pathogens in environmental hosts represents a major risk to public health. This study aimed at characterizing seven novel environmental strains of K. quasipneumoniae using a genomic approach which was misidentified by phenotypic methods in a previous batch of 27 species thought to be K. pneumoniae. Methods: Whole-genome sequencing was performed using the Illumina platform, and the generated raw reads were de novo assembled. Comparative genomic, resistome, virulome, mobilome, and phylogeny were then investigated using dierent bioinformatics tools. Results: Six strains were identified as K. quasipneumoniae subsp similipneumoniae and one as K. quasipneumoniae subsp. quasipneumoniae. All isolates were resistant to ampicillin, cephalexin, and amoxicillin-clavulanic acid and harbored the fosA, bla OKP types, oqxB, and oqxA genes. One isolate additionally harbored a gene cassettes consisting of bla SHV-1, bla OXA-1, aac(6')-Ib-cr, catB genes. The aminoglycoside-modifying enzyme gene aph(3")-Ia was bracketed by two insertion elements. Plasmid analyses showed that IncFIBK was the most prevalent plasmid, circulating in six isolates, while one isolate exhibited seven different plasmids. The isolates have virulence genes responsible for capsule formation, lipopolysaccharide, iron uptake aerobactin (iutA), salmochelins (iroE, iroN), enterobactin siderophore, adherence, and biofilm formation (mrkA, mrkB, mrkC, mrkD, mrkF, and mrkH). Conclusion: Our study highlights the ecology and transmission of K. quasipneumoniae (which have the ability to disseminate to other environmental sources including animals) outside the clinical setting and the contribution of water, vegetables, and table surfaces as potential reservoirs of farm-to-fork transmission of disease via local markets in Khartoum, Sudan.

Effect of tea (Camellia sinensis) and olive (Olea europaea L.) leaves extracts on male mice exposed to diazinon.

The present study was aimed to evaluate the effects of tea and olive leaves extracts and their combination in male mice intoxicated with a sublethal concentration of diazinon. Exposure of mice to 6.5 mg/kg body weight of diazinon for seven weeks resulted in statistical increases of serum alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, alkaline phosphatase, creatine kinase, creatinine, glucose, triglycerides, and cholesterol, while the value of serum total protein was declined. Treating diazinon-intoxicated mice with tea and olive leaves extracts or their combination significantly attenuated the severe alterations in these hematobiochemical parameters. Moreover, the results indicated that the supplementation with combination of tea and olive leaves extracts led to more attenuation effect against diazinon toxicity. Additionally, these new findings suggest that the effect of tea and olive leaves extracts and their combination against toxicity of diazinon may be due to antioxidant properties of their chemical constituents. Finally, the present study indicated that the extracts of tea and olive leaves and their combination can be considered as promising therapeutic agents against hepatotoxicity, cardiotoxicity, nephrotoxicity, and metabolic disorders induced by diazinon and maybe by other toxicants and pathogenic factors.